Early Clinical Manifestations Associated with Death from Visceral Leishmaniasis

PubMed Central

de Araújo, Valdelaine Etelvina Miranda; Morais, Maria Helena Franco; Reis, Ilka Afonso; Rabello, Ana; Carneiro, Mariângela

2012-01-01

Background In Brazil, lethality from visceral leishmaniasis (VL) is high and few studies have addressed prognostic factors. This historical cohort study was designed to investigate the prognostic factors for death from VL in Belo Horizonte (Brazil). Methodology The analysis was based on data of the Reportable Disease Information System-SINAN (Brazilian Ministry of Health) relating to the clinical manifestations of the disease. During the study period (2002–2009), the SINAN changed platform from a Windows to a Net-version that differed with respect to some of the parameters collected. Multivariate logistic regression models were performed to identify variables associated with death from VL, and these were included in prognostic score. Principal Findings Model 1 (period 2002–2009; 111 deaths from VL and 777 cured patients) included the variables present in both SINAN versions, whereas Model 2 (period 2007–2009; 49 deaths from VL and 327 cured patients) included variables common to both SINAN versions plus the additional variables included in the Net version. In Model 1, the variables significantly associated with a greater risk of death from VL were weakness (OR 2.9; 95%CI 1.3–6.4), Leishmania-HIV co-infection (OR 2.4; 95%CI 1.2–4.8) and age ≥60 years (OR 2.5; 95%CI 1.5–4.3). In Model 2, the variables were bleeding (OR 3.5; 95%CI 1.2–10.3), other associated infections (OR 3.2; 95%CI 1.3–7.8), jaundice (OR 10.1; 95%CI 3.7–27.2) and age ≥60 years (OR 3.1; 95%CI 1.4–7.1). The prognosis score was developed using the variables associated with death from VL of the latest version of the SINAN (Model 2). The predictive performance of which was evaluated by sensitivity (71.4%), specificity (73.7%), positive and negative predictive values (28.9% and 94.5%) and area under the receiver operating characteristic curve (75.6%). Conclusions Knowledge regarding the factors associated with death from VL may improve clinical management of patients and contribute to lower mortality. PMID:22347514

Phase Misalignment between Suprachiasmatic Neuronal Oscillators Impairs Photic Behavioral Phase Shifts but not Photic Induction of Gene Expression

PubMed Central

Schwartz, Michael D.; Congdon, Seth; de la Iglesia, Horacio O.

2010-01-01

The ability of the circadian pacemaker within the suprachiasmatic nucleus (SCN) to respond to light stimulation in a phase-specific manner constitutes the basis for photic entrainment of circadian rhythms. The neural basis for this phase-specificity is unclear. We asked whether a lack of synchrony between SCN neurons, as reflected in phase misalignment between dorsomedial (dmSCN) and ventrolateral (vlSCN) neuronal oscillators in the rat, would impact the pacemaker’s ability to respond to phase-resetting light pulses. Light pulses delivered at maximal phase-misalignment between the vl-and dmSCN oscillators increased expression of Per1 mRNA, irrespective of the circadian phase of the dmSCN. However, phase shifts of locomotor activity were only observed when the vl-and dmSCN were phase-aligned at the time of stimulation. Our results fit a model in which a vlSCN oscillator phase-gates its own response to light and in turn relays light information to a dmSCN oscillator. This model predicts that the phase misalignment that results from circadian internal desynchronization could preserve the ability of light to induce gene expression within the master circadian clock but impair its ability to induce behavioral phase shifts. PMID:20881133

Crystal structure of a 3B3 variant - A broadly neutralizing HIV-1 scFv antibody

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clark, K. Reed; Walsh, Scott T.R.; NCH)

2009-12-10

We present the crystal structure determination of an anti-HIV-1 gp120 single-chain variable fragment antibody variant, 3B3, at 2.5 {angstrom} resolution. This 3B3 variant was derived from the b12 antibody, using phage display and site-directed mutagenesis of the variable heavy chain (V{sub H}) complementary-determining regions (CDRs). 3B3 exhibits enhanced binding affinity and neutralization activity against several cross-clade primary isolates of HIV-1 by interaction with the recessed CD4-binding site on the gp120 envelope protein. Comparison with the structures of the unbound and bound forms of b12, the 3B3 structure closely resembles these structures with minimal differences with two notable exceptions. First, theremore » is a reorientation of the CDR-H3 of the V{sub H} domain where the primary sequences evolved from b12 to 3B3. The structural changes in CDR-H3 of 3B3, in light of the b12-gp120 complex structure, allow for positioning an additional Trp side chain in the binding interface with gp120. Finally, the second region of structural change involves two peptide bond flips in CDR-L3 of the variable light (VL) domain triggered by a point mutation in CDR-H3 of Q100eY resulting in changes in the intramolecular hydrogen bonding patterning between the VL and VH domains. Thus, the enhanced binding affinities and neutralization capabilities of 3B3 relative to b12 probably result from higher hydrophobic driving potential by burying more aromatic residues at the 3B3-gp120 interface and by indirect stabilization of intramolecular contacts of the core framework residues between the VL and VH domains possibly through more favorable entropic effect through the expulsion of water.« less

Large-scale sequence and structural comparisons of human naive and antigen-experienced antibody repertoires

PubMed Central

DeKosky, Brandon J.; Lungu, Oana I.; Park, Daechan; Johnson, Erik L.; Charab, Wissam; Chrysostomou, Constantine; Kuroda, Daisuke; Ellington, Andrew D.; Ippolito, Gregory C.; Gray, Jeffrey J.; Georgiou, George

2016-01-01

Elucidating how antigen exposure and selection shape the human antibody repertoire is fundamental to our understanding of B-cell immunity. We sequenced the paired heavy- and light-chain variable regions (VH and VL, respectively) from large populations of single B cells combined with computational modeling of antibody structures to evaluate sequence and structural features of human antibody repertoires at unprecedented depth. Analysis of a dataset comprising 55,000 antibody clusters from CD19+CD20+CD27− IgM-naive B cells, >120,000 antibody clusters from CD19+CD20+CD27+ antigen–experienced B cells, and >2,000 RosettaAntibody-predicted structural models across three healthy donors led to a number of key findings: (i) VH and VL gene sequences pair in a combinatorial fashion without detectable pairing restrictions at the population level; (ii) certain VH:VL gene pairs were significantly enriched or depleted in the antigen-experienced repertoire relative to the naive repertoire; (iii) antigen selection increased antibody paratope net charge and solvent-accessible surface area; and (iv) public heavy-chain third complementarity-determining region (CDR-H3) antibodies in the antigen-experienced repertoire showed signs of convergent paired light-chain genetic signatures, including shared light-chain third complementarity-determining region (CDR-L3) amino acid sequences and/or Vκ,λ–Jκ,λ genes. The data reported here address several longstanding questions regarding antibody repertoire selection and development and provide a benchmark for future repertoire-scale analyses of antibody responses to vaccination and disease. PMID:27114511

Cellular internalization mechanism and intracellular trafficking of filamentous M13 phages displaying a cell-penetrating transbody and TAT peptide.

PubMed

Kim, Aeyung; Shin, Tae-Hwan; Shin, Seung-Min; Pham, Chuong D; Choi, Dong-Ki; Kwon, Myung-Hee; Kim, Yong-Sung

2012-01-01

Cellular internalization of bacteriophage by surface-displayed cell penetrating peptides has been reported, though the underlying mechanism remains elusive. Here we describe in detail the internalization mechanism and intracellular trafficking and stability of filamentous M13 phages, the cellular entry of which is mediated by surface-displayed cell-penetrating light chain variable domain 3D8 VL transbody (3D8 VL-M13) or TAT peptide (TAT-M13). Recombinant 3D8 VL-M13 and TAT-M13 phages were efficiently internalized into living mammalian cells via physiologically relevant, energy-dependent endocytosis and were recovered from the cells in their infective form with the yield of 3D8 VL-M13 being higher (0.005 ≈ 0.01%) than that of TAT-M13 (0.001 ≈ 0.005%). Biochemical and genetic studies revealed that 3D8 VL-M13 was internalized principally by caveolae-mediated endocytosis via interaction with heparan sulfate proteoglycans as cell surface receptors, whereas TAT-M13 was internalized by clathrin- and caveolae-mediated endocytosis utilizing chondroitin sulfate proteoglycans as cell surface receptors, suggesting that phage internalization occurs by physiological endocytotic mechanism through specific cell surface receptors rather than non-specific transcytotic pathways. Internalized 3D8 VL-M13 phages routed to the cytosol and remained stable for more than 18 h without further trafficking to other subcellular compartments, whereas TAT-M13 phages routed to several subcellular compartments before being degraded in lysosomes even after 2 h of internalization. Our results suggest that the internalizing mechanism and intracellular trafficking of filamentous M13 bacteriophages largely follow the attributes of the displayed cell-penetrating moiety. Efficient internalization and cytosolic localization of 3D8 VL transbody-displayed phages will provide a useful tool for intracellular delivery of polar macromolecules such as proteins, peptides, and siRNAs.

Cellular Internalization Mechanism and Intracellular Trafficking of Filamentous M13 Phages Displaying a Cell-Penetrating Transbody and TAT Peptide

PubMed Central

Shin, Seung-Min; Pham, Chuong D.; Choi, Dong-Ki; Kwon, Myung-Hee; Kim, Yong-Sung

2012-01-01

Cellular internalization of bacteriophage by surface-displayed cell penetrating peptides has been reported, though the underlying mechanism remains elusive. Here we describe in detail the internalization mechanism and intracellular trafficking and stability of filamentous M13 phages, the cellular entry of which is mediated by surface-displayed cell-penetrating light chain variable domain 3D8 VL transbody (3D8 VL-M13) or TAT peptide (TAT-M13). Recombinant 3D8 VL-M13 and TAT-M13 phages were efficiently internalized into living mammalian cells via physiologically relevant, energy-dependent endocytosis and were recovered from the cells in their infective form with the yield of 3D8 VL-M13 being higher (0.005∼0.01%) than that of TAT-M13 (0.001∼0.005%). Biochemical and genetic studies revealed that 3D8 VL-M13 was internalized principally by caveolae-mediated endocytosis via interaction with heparan sulfate proteoglycans as cell surface receptors, whereas TAT-M13 was internalized by clathrin- and caveolae-mediated endocytosis utilizing chondroitin sulfate proteoglycans as cell surface receptors, suggesting that phage internalization occurs by physiological endocytotic mechanism through specific cell surface receptors rather than non-specific transcytotic pathways. Internalized 3D8 VL-M13 phages routed to the cytosol and remained stable for more than 18 h without further trafficking to other subcellular compartments, whereas TAT-M13 phages routed to several subcellular compartments before being degraded in lysosomes even after 2 h of internalization. Our results suggest that the internalizing mechanism and intracellular trafficking of filamentous M13 bacteriophages largely follow the attributes of the displayed cell-penetrating moiety. Efficient internalization and cytosolic localization of 3D8 VL transbody-displayed phages will provide a useful tool for intracellular delivery of polar macromolecules such as proteins, peptides, and siRNAs. PMID:23251631

Near-visible light and UV photoprotection in the treatment of melasma: a double-blind randomized trial.

PubMed

Castanedo-Cazares, Juan Pablo; Hernandez-Blanco, Diana; Carlos-Ortega, Blanca; Fuentes-Ahumada, Cornelia; Torres-Álvarez, Bertha

2014-02-01

Melasma is an acquired hyperpigmentation on sun-exposed areas. Multiple approaches are used to treat it, but all include broad ultraviolet (UV)-spectrum sunscreens. Visible light (VL) can induce pigmentary changes similar to those caused by UV radiation on darker-skinned patients. To assess the efficacy of sunscreen with broad-spectrum UV protection that contains iron oxide as a VL-absorbing pigment (UV-VL) compared with a regular UV-only broad-spectrum sunscreen for melasma patients exposed to intense solar conditions. Sixty-eight patients with melasma were randomized in two groups to receive either UV-VL sunscreen or UV-only sunscreen, both with sun protection factor ≥ 50, over 8 weeks. All patients received 4% hydroquinone as a depigmenting treatment. At onset and at conclusion of the study, they were assessed by the Melasma Activity and Severity Index (MASI; a subjective scale), colorimetry (L*) and histological analysis of melanin. Sixty-one patients concluded the study. At 8 weeks, the UV-VL group showed 15%, 28% and 4% greater improvements than the UV-only group in MASI scores, colorimetric values and melanin assessments, respectively. UV-VL sunscreen enhances the depigmenting efficacy of hydroquinone compared with UV-only sunscreen in treatment of melasma. These findings suggest a role for VL in melasma pathogenesis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

A comparison of direct versus indirect laryngoscopic visualization during endotracheal intubation of lightly embalmed cadavers utilizing the GlideScope®, Storz Medi Pack Mobile Imaging System™ and the New Storz CMAC™ videolaryngoscope.

PubMed

Boedeker, Ben H; Nicholsal, Thomas A; Carpenter, Jennifer; Singh, Leighton; Bernhagen, Mary A; Murray, W Bosseau; Wadman, Michael C

2011-01-01

Studies indicate that the skills needed to use video laryngoscope systems are easily learned by healthcare providers. This study compared several video laryngoscopic (VL) systems and a direct laryngoscope (DL) view when used by medical residents practicing intubation on cadavers. The video devices used included the Storz Medi Pack Mobile Imaging System™, the Storz CMAC® VL System and the GlideScope®. After Institutional Review Board (IRB) approval, University of Nebraska Medical Center, Department of Emergency Medicine (UNMC EM) residents were recruited and given a brief pre-study informational period. The cadavers were lightly embalmed. The study subjects were asked to perform intubations on two cadavers using both DL and VL while using the three different VL systems. Procedural data was recorded for each attempt and pre and post experience perceptions were collected. N=14. All subjects reported their varied previous intubation experience. The average airway score using DL: for the Storz VL was 1.54 (SD = 0.576) and for the C-MAC was 1.46 (SD = 0.637). Success in intubation of the standard airway using DL was 93% versus a 100% success rate when intubating with indirect VL visualization. Based on our data, we believe that the incorporation of VL into cadaver airway management training provided an improved learning environment for the study residents. In our study, the resident subjects were 93% successful with DL intubation even though 50% had less than 30 intubations. As well, there was a 100% success rate when intubating with indirect VL visualization. In conclusion, the researchers believe this cadaver model incorporated with VL is a powerful tool which may help improve the overall learning curve for orotracheal intubation. 2011.

A Single Mutation at the Sheet Switch Region Results in Conformational Changes Favoring 6 Light-Chain Fibrillogenesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernández-Santoyo, A.; Del Pozo Yauner, L; Fuentes-Silva, D

Systemic amyloid light-chain (LC) amyloidosis is a disease process characterized by the pathological deposition of monoclonal LCs in tissue. All LC subtypes are capable of fibril formation although {lambda} chains, particularly those belonging to the {lambda}6 type, are overrepresented. Here, we report the thermodynamic and in vitro fibrillogenic properties of several mutants of the {lambda}6 protein 6aJL2 in which Pro7 and/or His8 was substituted by Ser or Pro. The H8P and H8S mutants were almost as stable as the wild-type protein and were poorly fibrillogenic. In contrast, the P7S mutation decreased the thermodynamic stability of 6aJL2 and greatly enhanced itsmore » capacity to form amyloid-like fibrils in vitro. The crystal structure of the P7S mutant showed that the substitution induced both local and long-distance effects, such as the rearrangement of the VL (variable region of the light chain)-VL interface. This mutant crystallized in two orthorhombic polymorphs, P2{sub 1}2{sub 1}2{sub 1} and C222{sub 1}. In the latter, a monomer that was not arranged in the typical Bence-Jones dimer was observed for the first time. Crystal-packing analysis of the C222{sub 1} lattice showed the establishment of intermolecular {beta}-{beta} interactions that involved the N-terminus and {beta}-strand B and that these could be relevant in the mechanism of LC fibril formation. Our results strongly suggest that Pro7 is a key residue in the conformation of the N-terminal sheet switch motif and, through long-distance interactions, is also critically involved in the contacts that stabilized the VL interface in {lambda}6 LCs.« less

Amino acid sequence of the Fv region of a human monoclonal IgM (protein WEA) with antibody activity against 3,4-pyruvylated galactose in Klebsiella polysaccharides K30 and K33.

PubMed Central

Goñi, F; Frangione, B

1983-01-01

We have determined the amino acid sequence of the Fv [variable heavy (VH) and variable light (VL)] region of a human monoclonal IgM-kappa with antibody activity against 3,4-pyruvylated galactose, isolated from the plasma of patient WEA with Waldenström macroglobulinemia. The VH region has 114 residues, belongs to subgroup III, and has a very short third complementarity-determining region (CDR3), probably due to a small D segment/or an unusual D-J rearrangement (D, diversity; J, joining). The VL region has 108 residues and belongs to subgroup V kappa I. Compared to other members of the human VHIII and V kappa I families, WEA Fv does not appear to have significant differences within the framework residues but has unique CDRs that might be responsible for the particular antibody activity. Another IgM-kappa (GAL), which has an as-yet-undetermined antibody activity, shares a striking homology in V kappa with WEA, including an identical CDR1. PMID:6410398

The N-terminal strand modulates immunoglobulin light chain fibrillogenesis.

PubMed

del Pozo-Yauner, Luis; Wall, Jonathan S; González Andrade, Martín; Sánchez-López, Rosana; Rodríguez-Ambriz, Sandra L; Pérez Carreón, Julio I; Ochoa-Leyva, Adrián; Fernández-Velasco, D Alejandro

2014-01-10

It has been suggested that the N-terminal strand of the light chain variable domain (V(L)) protects the molecule from aggregation by hindering spurious intermolecular contacts. We evaluated the impact of mutations in the N-terminal strand on the thermodynamic stability and kinetic of fibrillogenesis of the V(L) protein 6aJL2. Mutations in this strand destabilized the protein in a position-dependent manner, accelerating the fibrillogenesis by shortening the lag time; an effect that correlated with the extent of destabilization. In contrast, the effect on the kinetics of fibril elongation, as assessed in seeding experiments was of different nature, as it was not directly dependant on the degree of destabilization. This finding suggests different factors drive the nucleation-dependent and elongation phases of light chain fibrillogenesis. Finally, taking advantage of the dependence of the Trp fluorescence upon environment, four single Trp substitutions were made in the N-terminal strand, and changes in solvent exposure during aggregation were evaluated by acrylamide-quenching. The results suggest that the N-terminal strand is buried in the fibrillar state of 6aJL2 protein. This finding suggest a possible explanation for the modulating effect exerted by the mutations in this strand on the aggregation behavior of 6aJL2 protein. Copyright © 2013 Elsevier Inc. All rights reserved.

Complete erasing of ghost images caused by deeply trapped electrons on computed radiography plates

NASA Astrophysics Data System (ADS)

Ohuchi, H.; Kondo, Y.

2011-03-01

The ghost images, i.e., latent image that is unerasable with visible light (LIunVL) and reappearing image appeared on computed radiography (CR) plates were completely erased by simultaneous exposing them to filtered ultraviolet light and visible light. Three different types of CR plates (Agfa, Kodak, and Fuji) were irradiated with 50 kV X-ray beams in the dose range 8.1 mGy to 8.0 Gy, and then conventionally erased for 2 h with visible light. The remaining LIunVL could be erased by repeating 6 h simultaneous exposures to filtered ultraviolet light and visible light. After the sixth round of exposure, all the LIunVL in the three types of CR plates were erased to the same level as in an unirradiated plate and no latent images reappeared after storage at 0°C for 14 days. The absorption spectra of deep centers were specified using polychromatic ultraviolet light from a deep-ultraviolet lamp. It was found that deep centers showed a dominant peak in the absorption spectra at around 324 nm for the Agfa and Kodak plates, and at around 320 nm for the Fuji plate, in each case followed by a few small peaks. After completely erasing CR plates, these peaks were no longer observed.

Predicting the geographic distribution of Lutzomyia longipalpis (Diptera: Psychodidae) and visceral leishmaniasis in the state of Mato Grosso do Sul, Brazil

PubMed Central

de Almeida, Paulo Silva; Sciamarelli, Alan; Batista, Paulo Mira; Ferreira, Ademar Dimas; Nascimento, João; Raizer, Josué; Andrade, José Dilermando; Gurgel-Gonçalves, Rodrigo

2013-01-01

To understand the geographic distribution of visceral leishmaniasis (VL) in the state of Mato Grosso do Sul (MS), Brazil, both the climatic niches of Lutzomyia longipalpis and VL cases were analysed. Distributional data were obtained from 55 of the 79 counties of MS between 2003-2012. Ecological niche models (ENM) of Lu. longipalpis and VL cases were produced using the maximum entropy algorithm based on eight climatic variables. Lu. longipalpis showed a wide distribution in MS. The highest climatic suitability for Lu. longipalpis was observed in southern MS. Temperature seasonality and annual mean precipitation were the variables that most influenced these models. Two areas of high climatic suitability for the occurrence of VL cases were predicted: one near Aquidauana and another encompassing several municipalities in the southeast region of MS. As expected, a large overlap between the models for Lu. longipalpis and VL cases was detected. Northern and northwestern areas of MS were suitable for the occurrence of cases, but did not show high climatic suitability for Lu. longipalpis . ENM of vectors and human cases provided a greater understanding of the geographic distribution of VL in MS, which can be applied to the development of future surveillance strategies. PMID:24402151

Predicting the geographic distribution of Lutzomyia longipalpis (Diptera: Psychodidae) and visceral leishmaniasis in the state of Mato Grosso do Sul, Brazil.

PubMed

Almeida, Paulo Silva de; Sciamarelli, Alan; Batista, Paulo Mira; Ferreira, Ademar Dimas; Nascimento, João; Raizer, Josué; Andrade Filho, José Dilermando; Gurgel-Gonçalves, Rodrigo

2013-12-01

To understand the geographic distribution of visceral leishmaniasis (VL) in the state of Mato Grosso do Sul (MS), Brazil, both the climatic niches of Lutzomyia longipalpis and VL cases were analysed. Distributional data were obtained from 55 of the 79 counties of MS between 2003-2012. Ecological niche models (ENM) of Lu. longipalpis and VL cases were produced using the maximum entropy algorithm based on eight climatic variables. Lu. longipalpis showed a wide distribution in MS. The highest climatic suitability for Lu. longipalpis was observed in southern MS. Temperature seasonality and annual mean precipitation were the variables that most influenced these models. Two areas of high climatic suitability for the occurrence of VL cases were predicted: one near Aquidauana and another encompassing several municipalities in the southeast region of MS. As expected, a large overlap between the models for Lu. longipalpis and VL cases was detected. Northern and northwestern areas of MS were suitable for the occurrence of cases, but did not show high climatic suitability for Lu. longipalpis. ENM of vectors and human cases provided a greater understanding of the geographic distribution of VL in MS, which can be applied to the development of future surveillance strategies.

Variable responses of two VlMYBA gene promoters to ABA and ACC in Kyoho grape berries.

PubMed

Zhai, Xiawan; Zhang, Yushu; Kai, Wenbin; Liang, Bin; Jiang, Li; Du, Yangwei; Wang, Juan; Sun, Yufei; Leng, Ping

2017-04-01

The VlMYBA subfamily of transcription factors has been known to be the functional regulators in anthocyanin biosynthesis in red grapes. In this study, the expressions of the VlMYBA1-2 and VlMYBA 2 genes, and the responses of the VlMYBA1-2/2 promoters to ABA and ACC treatments in Kyoho grape berries are examined through quantitative real-time PCR analysis and the transient expression assay. The results show that the expressions of VlMYBA1-2/2 increase dramatically after véraison and reach their highest levels when the berries are nearly fully ripe. Exogenous ABA promotes the expressions of VlMYBA1-2/2, whereas the ACC treatment increases the expression of VlMYBA2, however, it has no effect on VlMYBA1-2. The ABA treatment has a faster and stronger effect on berry pigmentation than ACC does. The VlMYBA1-2 promoter sequence contains two ABA response elements (ABRE) but no ethylene response element (ERE), whereas the VlMYBA2 promoter sequence contains two ABRE and one ERE in the upstream region of the start codon. The VlMYBA2 promoter can be activated by both ABA (more effective) and ACC, whereas the VlMYBA1-2 promoter can be activated by ABA only. In sum, ABA can promote the coloring of Kyoho grape by the promotion of VlMYBA1-2/2 transcriptions via activating the response of their promoters to ABA, whereas ethylene only regulates VlMYBA2 through the response activation of its promoter to ACC which partially enhances the coloring. Copyright © 2017 Elsevier GmbH. All rights reserved.

Role of valued living and associations with functional outcome following traumatic brain injury.

PubMed

Pais Hons, Celia; Ponsford, Jennie L; Gould Clin Neuro, Kate R; Wong, Dana

2017-04-19

Valued living (VL) is associated with improved enjoyment and engagement with daily activities despite negative emotional state or ongoing pain. However, the role of VL in recovery following traumatic brain injury (TBI) has yet to be investigated. This study aimed to examine changes in VL over the course of recovery and variables associated with VL. Participants with moderate-to-severe TBI were recruited from a rehabilitation hospital in three cohorts: "Early" (n = 25), "Mid" (n = 9) and "Late" (n = 36) post-TBI. All participants were assessed at time of recruitment and 12 months later. The main measure was the Valued Living Questionnaire. Compared to pre-injury estimates, VL was significantly reduced at 12 months post-injury. Levels of VL remained reduced between 2 and 3 years and increased between 3 and 6 years post-injury. VL was strongly associated with improved functional and psychosocial outcomes. Changes in VL occur over at least 3-5 years post-injury, with 12 months post-TBI a suitable time for intervention given VL remains low over the next 24 to 36 months post injury. Targeted intervention to modify values and/or valued activities to be consistent with post-injury capacity could improve rates of return to pre-injury levels of VL.

In situ modification of cell-culture scaffolds by photocatalysis of visible-light-responsive TiO2 film

NASA Astrophysics Data System (ADS)

Kono, Sho; Furusawa, Kohei; Kurotobi, Atsushi; Hattori, Kohei; Yamamoto, Hideaki; Hirano-Iwata, Ayumi; Tanii, Takashi

2018-02-01

We propose a novel process to modify the cell affinity of scaffolds in a cell-culture environment using the photocatalytic activity of visible-light (VL)-responsive TiO2. The proposed process is the improved version of our previous demonstration in which ultraviolet (UV)-responsive TiO2 was utilized. In that demonstration, we showed that cell-repellent molecules on TiO2 were decomposed and replaced with cell-permissive molecules upon UV exposure in the medium where cells are being cultured. However, UV irradiation involves taking the risk of inducing damage to the cells. In this work, a TiO2 film was sputter-deposited on a quartz coverslip at 640 °C without O2 gas injection to create a rutile structure containing oxygen defects, which is known to exhibit photocatalytic activity upon VL exposure. We show that the cell adhesion site and migration area can be controlled with the photocatalytic activity of the VL-responsive TiO2 film, while the cellular oxidative stress is reduced markedly by the substitution of VL for UV.

Efficient generation of monoclonal antibodies from single rhesus macaque antibody secreting cells.

PubMed

Meng, Weixu; Li, Leike; Xiong, Wei; Fan, Xuejun; Deng, Hui; Bett, Andrew J; Chen, Zhifeng; Tang, Aimin; Cox, Kara S; Joyce, Joseph G; Freed, Daniel C; Thoryk, Elizabeth; Fu, Tong-Ming; Casimiro, Danilo R; Zhang, Ningyan; A Vora, Kalpit; An, Zhiqiang

2015-01-01

Nonhuman primates (NHPs) are used as a preclinical model for vaccine development, and the antibody profiles to experimental vaccines in NHPs can provide critical information for both vaccine design and translation to clinical efficacy. However, an efficient protocol for generating monoclonal antibodies from single antibody secreting cells of NHPs is currently lacking. In this study we established a robust protocol for cloning immunoglobulin (IG) variable domain genes from single rhesus macaque (Macaca mulatta) antibody secreting cells. A sorting strategy was developed using a panel of molecular markers (CD3, CD19, CD20, surface IgG, intracellular IgG, CD27, Ki67 and CD38) to identify the kinetics of B cell response after vaccination. Specific primers for the rhesus macaque IG genes were designed and validated using cDNA isolated from macaque peripheral blood mononuclear cells. Cloning efficiency was averaged at 90% for variable heavy (VH) and light (VL) domains, and 78.5% of the clones (n = 335) were matched VH and VL pairs. Sequence analysis revealed that diverse IGHV subgroups (for VH) and IGKV and IGLV subgroups (for VL) were represented in the cloned antibodies. The protocol was tested in a study using an experimental dengue vaccine candidate. About 26.6% of the monoclonal antibodies cloned from the vaccinated rhesus macaques react with the dengue vaccine antigens. These results validate the protocol for cloning monoclonal antibodies in response to vaccination from single macaque antibody secreting cells, which have general applicability for determining monoclonal antibody profiles in response to other immunogens or vaccine studies of interest in NHPs.

Optimal timing of viral load monitoring during pregnancy to predict viraemia at delivery in HIV-infected women initiating ART in South Africa: a simulation study.

PubMed

Lesosky, Maia; Glass, Tracy; Mukonda, Elton; Hsiao, Nei-Yuan; Abrams, Elaine J; Myer, Landon

2017-11-01

HIV viral load (VL) monitoring is a central tool to evaluate ART effectiveness and transmission risk. There is a global movement to expand VL monitoring following recent recommendations from the World Health Organization (WHO), but there has been little research into VL monitoring in pregnant women. We investigated one important question in this area: when and how frequently VL should be monitored in women initiating ART during pregnancy to predict VL at the time of delivery in a simulated South African population. We developed a mathematical model simulating VL from conception through delivery using VL data from the Maternal and Child Health - Antiretroviral Therapy (MCH-ART) cohort. VL was modelled based on three major compartments: pre-ART VL, viral decay immediately after ART initiation and viral maintenance (including viral suppression and viraemic episodes). Using this simulation, we examined the performance of various VL monitoring schema in predicting elevated VL at delivery. If WHO guidelines for non-pregnant adults were used, the majority of HIV-infected pregnant women (69%) would not receive a VL test during pregnancy. Most models that based VL monitoring in pregnancy on the time elapsed since ART initiation (regardless of gestation) performed poorly (sensitivity <50%); models that based VL measures in pregnancy on the woman's gestation (regardless of time on ART) appeared to perform better overall (sensitivity >60%). Across all permutations, inclusion of pre-ART VL values had a negligible impact on predictive performance (improving test sensitivity and specificity <6%). Performance of VL monitoring in predicting VL at delivery generally improved at later gestations, with the best performing option a single VL measure at 36 weeks' gestation. Development and evaluation of a novel simulation model suggests that strategies to measure VL relative to gestational age may be more useful than strategies relative to duration on ART, in women initiating ART during pregnancy, supporting better integration of maternal and HIV health services. Testing turnaround times require careful consideration, and point-of-care VL testing may be the best approach for measuring VL at delivery. Broadening the scope of this simulation model in the light of current scale up of VL monitoring in high burden countries is important. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Peptide docking of HIV-1 p24 with single chain fragment variable (scFv) by CDOCKER algorithm

NASA Astrophysics Data System (ADS)

Karim, Hana Atiqah Abdul; Tayapiwatana, Chatchai; Nimmanpipug, Piyarat; Zain, Sharifuddin M.; Rahman, Noorsaadah Abdul; Lee, Vannajan Sanghiran

2014-10-01

In search for the important residues that might have involve in the binding interaction between the p24 caspid protein of HIV-1 fragment (MET68 - PRO90) with the single chain fragment variable (scFv) of FAB23.5, modern computational chemistry approach has been conducted and applied. The p24 fragment was initially taken out from the 1AFV protein molecule consisting of both light (VL) and heavy (VH) chains of FAB23.5 as well as the HIV-1 caspid protein. From there, the p24 (antigen) fragment was made to dock back into the protein pocket receptor (antibody) by using the CDOCKER algorithm to conduct the molecular docking process. The score calculated from the CDOCKER gave 15 possible docked poses with various docked ligand's positions, the interaction energy as well as the binding energy. The best docked pose that imitates the original antigen's position was determined and further processed to the In Situ minimization to obtain the residues interaction energy as well as to observe the hydrogen bonds interaction in the protein-peptide complex. Based on the results demonstrated, the specific residues in the complex that have shown immense lower interaction energies in the 5Å vicinity region from the peptide are from the heavy chain (VH:TYR105) and light chain (VL: ASN31, TYR32, and GLU97). Those residues play vital roles in the binding mechanism of Antibody-Antigen (Ab-Ag) complex of p24 with FAB23.5.

Comparing domain interactions within antibody Fabs with kappa and lambda light chains.

PubMed

Toughiri, Raheleh; Wu, Xiufeng; Ruiz, Diana; Huang, Flora; Crissman, John W; Dickey, Mark; Froning, Karen; Conner, Elaine M; Cujec, Thomas P; Demarest, Stephen J

2016-10-01

IgG antibodies are multi-domain proteins with complex inter-domain interactions. Human IgG heavy chains (HCs) associate with light chains (LCs) of the κ or λ isotype to form mature antibodies capable of binding antigen. The HC/LC interaction involves 4 domains: VH and CH1 from the HC and VL and CL from the LC. Human Fabs with κ LCs have been well characterized for their unfolding behaviors and demonstrate a significant level of cooperativity and stabilization when all 4 domains are intact. Very little is known regarding the thermodynamic properties of human Fabs with λ LCs. Here, we dissect the domain contributions to Fab stability for both κ and λ LC-containing Fabs. We find the cooperativity of unfolding between the constant domains, CH1/Cλ, and variable domains, VH/Vλ, within λ LC-containing Fabs is significantly weaker than that of κ LC-containing Fabs. The data suggests there may not be an evolutionary necessity for strong variable/constant domain cooperativity within λ LC-containing Fabs. After investigating the biophysical properties of Fabs with mismatched variable and constant domain subunits (e.g., VH/Vκ paired with CH1/Cλ or T cell receptor Cα/Cβ), the major role of the constant domains for both κ- and λ-containing Fabs may be to reduce the hydrophobic exposure at the VH/VL interface. Even though Fabs with these non-native pairings were thermodynamically less stable, they secreted well from mammalian cells as well behaved monodisperse proteins, which was in contrast to what was observed with the VH/Vκ and VH/Vλ scFvs that secreted as a mixture of monomer and aggregates.

Video Laryngoscopic Techniques Associated with Intubation Success in a Helicopter Emergency Medical Service System.

PubMed

Naito, Hiromichi; Guyette, Francis X; Martin-Gill, Christian; Callaway, Clifton W

2016-01-01

Video laryngoscopy (VL) is a technical adjunct to facilitate endotracheal intubation (ETI). VL also provides objective data for training and quality improvement, allowing evaluation of the technique and airway conditions during ETI. Previous studies of factors associated with ETI success or failure are limited by insufficient nomenclature, individual recall bias and self-report. We tested whether the covariates in prehospital VL recorded data were associated with ETI success. We also measured association between time and clinical variables. Retrospective review was conducted in a non-physician staffed helicopter emergency medical service system. ETI was typically performed using sedation and neuromuscular-blockade under protocolized orders. We obtained process and outcome variables from digitally recorded VL data. Patient characteristics data were also obtained from the emergency medical service record and linked to the VL recorded data. The primary outcome was to identify VL covariates associated with successful ETI attempts. Among 304 VL recorded ETI attempts in 268 patients, ETI succeeded for 244 attempts and failed for 60 attempts (first-pass success rate, 82% and overall success rate, 94%). Laryngoscope blade tip usually moved from a shallow position in the oropharynx to the vallecula. In the multivariable logistic regression analysis, attempt time (p = 0.02; odds ratio [OR] 0.99), Cormack-Lehane view (p < 0.001; OR 0.23), bodily fluids obstructing the view (p = 0.01; OR 0.29), and VL equipment failure (p < 0.001; OR 0.14) were negatively associated with successful attempts. Bodily fluids obstructing the view (p < 0.001; hazard ratio [HR] 0.51), VL equipment failure (p = 0.003; HR 0.42), shallow placement of blade tip within 4 seconds (p < 0.001; HR 0.40), number of forward movements (p < 0.001; HR 0.84), trauma (p = 0.04; HR 0.65), and neurological diagnosis (p = 0.04; HR 0.60) were associated with longer ETI attempt time. Bodily fluids obstructing the view, equipment problems, higher Cormack-Lehane view, and longer ETI attempt time were negatively associated with successful ETI attempts. Initially shallow blade tip position may associate with longer ETI time. VL is useful for measuring and describing multiple factors of ETI and can provide valuable data.

Dissociation between two subgroups of the suprachiasmatic nucleus affected by the number of damped oscillated neurons

NASA Astrophysics Data System (ADS)

Gu, Changgui; Yang, Huijie; Rohling, Jos HT

2017-03-01

In mammals, the main clock located in the suprachiasmatic nucleus (SCN) of the brain synchronizes the body rhythms to the environmental light-dark cycle. The SCN is composed of about 2 ×104 neurons which can be classified into three oscillatory phenotypes: self-sustained oscillators, damped oscillators, and arrhythmic neurons. Exposed to an artificial external light-dark cycle with a period of 22 h instead of 24 h , two subgroups of the SCN can become desynchronized (dissociated). The ventrolateral (VL) subgroup receives photic input and is entrained to the external cycle and a dorsomedial (DM) subgroup oscillates with its endogenous (i.e., free running) period and is synchronized to the external light-dark cycle through coupling from the VL. In the present study, we examined the effects of damped oscillatory neurons on the dissociation between VL and DM under an external 22 h cycle. We found that, with increasing numbers of damped oscillatory neurons located in the VL, the dissociation between the VL and DM emerges, but if these neurons are increasingly present in the DM the dissociation disappears. Hence, the damped oscillatory neurons in different subregions of the SCN play distinct roles in the dissociation between the two subregions of the SCN. This shows that synchrony between SCN subregions is affected by the number of damped oscillatory neurons and the location of these cells. We suggest that more knowledge on the number and the location of these cells may explain why some species do show a dissociation between the subregions and others do not, as the distribution of oscillatory types of neurons offers a plausible and novel candidate mechanism to explain heterogeneity.

Stability engineering of anti-EGFR scFv antibodies by rational design of a lambda-to-kappa swap of the VL framework using a structure-guided approach.

PubMed

Lehmann, Andreas; Wixted, Josephine H F; Shapovalov, Maxim V; Roder, Heinrich; Dunbrack, Roland L; Robinson, Matthew K

2015-01-01

Phage-display technology facilitates rapid selection of antigen-specific single-chain variable fragment (scFv) antibodies from large recombinant libraries. ScFv antibodies, composed of a VH and VL domain, are readily engineered into multimeric formats for the development of diagnostics and targeted therapies. However, the recombinant nature of the selection strategy can result in VH and VL domains with sub-optimal biophysical properties, such as reduced thermodynamic stability and enhanced aggregation propensity, which lead to poor production and limited application. We found that the C10 anti-epidermal growth factor receptor (EGFR) scFv, and its affinity mutant, P2224, exhibit weak production from E. coli. Interestingly, these scFv contain a fusion of lambda3 and lambda1 V-region (LV3 and LV1) genes, most likely the result of a PCR aberration during library construction. To enhance the biophysical properties of these scFvs, we utilized a structure-based approach to replace and redesign the pre-existing framework of the VL domain to one that best pairs with the existing VH. We describe a method to exchange lambda sequences with a more stable kappa3 framework (KV3) within the VL domain that incorporates the original lambda DE-loop. The resulting scFvs, C10KV3_LV1DE and P2224KV3_LV1DE, are more thermodynamically stable and easier to produce from bacterial culture. Additionally, C10KV3_LV1DE and P2224KV3_LV1DE retain binding affinity to EGFR, suggesting that such a dramatic framework swap does not significantly affect scFv binding. We provide here a novel strategy for redesigning the light chain of problematic scFvs to enhance their stability and therapeutic applicability.

Optical radiation in modern medicine

PubMed Central

Sowa, Paweł; Rutkowska-Talipska, Joanna; Rutkowski, Krzysztof; Kosztyła-Hojna, Bożena

2013-01-01

Optical radiation extends between microwaves and X-rays of the electromagnetic radiation and includes ultraviolet (UV), visible light (VL) and infrared (IR) components. The dose of radiation that reaches the skin is influenced by the ozone layer, position of the Sun, latitude, altitude, cloud cover and ground reflections. The photobiological effects of UV, VL and IR bands depend on their wavelength, frequency and mechanism of action. They are modified by the thickness, structure, vasculature and pigmentation of skin's stratum corneum, epidermis and dermis. Following absorption, IR affects the body mainly through transfer of thermal energy to tissues. Visible light and skin interact either thermally or photochemically, whereas UV acts mainly photochemically. Optical radiation in the form of sunlight therapy had been used already in ancient times. Nowadays IR, VL and UV are widely applied in the therapy of allergic, dermatological, cardiovascular, respiratory, rheumatic, neonatal, pediatric and psychiatric disorders. PMID:24278082

Flavonoid biosynthesis-related genes in grape skin are differentially regulated by temperature and light conditions.

PubMed

Azuma, Akifumi; Yakushiji, Hiroshi; Koshita, Yoshiko; Kobayashi, Shozo

2012-10-01

Temperature and light are important environmental factors that affect flavonoid biosynthesis in grape berry skin. However, the interrelationships between temperature and light effects on flavonoid biosynthesis have not been fully elucidated at the molecular level. Here, we investigated the effects of temperature and light conditions on the biosynthesis of flavonoids (anthocyanins and flavonols) and the expression levels of related genes in an in vitro environmental experiment using detached grape berries. Sufficient anthocyanin accumulation in the grape skin was observed under a low temperature (15 °C) plus light treatment, whereas high temperature (35 °C) or dark treatment severely suppressed anthocyanin accumulation. This indicates that the accumulation of anthocyanins is dependent on both low temperature and light. qRT-PCR analysis showed that the responses of three MYB-related genes (VlMYBA1-3, VlMYBA1-2, and VlMYBA2) to temperature and light differed greatly even though the products of all three genes had the ability to regulate anthocyanin biosynthesis pathway genes. Furthermore, the expression levels of other MYB-related genes and many flavonoid biosynthesis pathway genes were regulated independently by temperature and light. We also found that temperature and light conditions affected the anthocyanin composition in the skin through the regulation of flavonoid biosynthesis pathway genes. Our results suggest that low temperature and light have a synergistic effect on the expression of genes in the flavonoid biosynthesis pathway. These findings provide new information about the relationships between environmental factors and flavonoid accumulation in grape berry skin.

The intervening removable affinity tag (iRAT) production system facilitates Fv antibody fragment‐mediated crystallography

PubMed Central

Nomura, Yayoi; Sato, Yumi; Suno, Ryoji; Horita, Shoichiro

2016-01-01

Abstract Fv antibody fragments have been used as co‐crystallization partners in structural biology, particularly in membrane protein crystallography. However, there are inherent technical issues associated with the large‐scale production of soluble, functional Fv fragments through conventional methods in various expression systems. To circumvent these problems, we developed a new method, in which a single synthetic polyprotein consisting of a variable light (VL) domain, an intervening removable affinity tag (iRAT), and a variable heavy (VH) domain is expressed by a Gram‐positive bacterial secretion system. This method ensures stoichiometric expression of VL and VH from the monocistronic construct followed by proper folding and assembly of the two variable domains. The iRAT segment can be removed by a site‐specific protease during the purification process to yield tag‐free Fv fragments suitable for crystallization trials. In vitro refolding step is not required to obtain correctly folded Fv fragments. As a proof of concept, we tested the iRAT‐based production of multiple Fv fragments, including a crystallization chaperone for a mammalian membrane protein as well as FDA‐approved therapeutic antibodies. The resulting Fv fragments were functionally active and crystallized in complex with the target proteins. The iRAT system is a reliable, rapid and broadly applicable means of producing milligram quantities of Fv fragments for structural and biochemical studies. PMID:27595817

Abscisic acid metabolism and anthocyanin synthesis in grape skin are affected by light emitting diode (LED) irradiation at night.

PubMed

Kondo, Satoru; Tomiyama, Hiroyuki; Rodyoung, Abhichartbut; Okawa, Katsuya; Ohara, Hitoshi; Sugaya, Sumiko; Terahara, Norihiko; Hirai, Nobuhiro

2014-06-15

The effects of blue and red light irradiation at night on abscisic acid (ABA) metabolism and anthocyanin synthesis were examined in grape berries. The expressions of VlMYBA1-2, VlMYBA2, UDP-glucose-flavonoid 3-O-glucosyltransferase (VvUFGT), 9-cis-epoxycarotenoid dioxygenase (VvNCED1), and ABA 8'-hydroxylase (VvCYP707A1) were also investigated. Endogenous ABA, its metabolite phaseic acid (PA), and the expressions of VvNCED1 and VvCYP707A1 were highest in red light-emitting diode (LED)-treated skin. In contrast, anthocyanin concentrations were highest in blue LED-treated skin, followed by red LED treatment. However, the expressions of VlMYBA1-2, VlMYBA2, and VvUFGT did not necessarily coincide with anthocyanin concentrations. The quality of coloring may depend on the amount of malvidin-based anthocyanin, which increased toward harvest in blue and red LED-treated skin, unlike in untreated controls. An increase in sugars was also observed in blue and red LED-treated skin. These results suggest that blue LED irradiation at night may be effective in increasing anthocyanin and sugar concentrations in grape berries. However, there is evidence that another factor may influence anthocyanin concentrations in grape berry skin significantly more than endogenous ABA: ABA concentrations were highest in red LED-treated skin, which had lower anthocyanin concentrations than blue LED-treated skin. Copyright © 2014 Elsevier GmbH. All rights reserved.

Analyses of chicken immunoglobulin light chain cDNA clones indicate a few germline V lambda genes and allotypes of the C lambda locus.

PubMed

Parvari, R; Ziv, E; Lentner, F; Tel-Or, S; Burstein, Y; Schechter, I

1987-01-01

cDNA libraries of chicken spleen and Harder gland (a gland enriched with immunocytes) constructed in pBR322 were screened by differential hybridization and by mRNA hybrid-selected translation. Eleven L-chain cDNA clones were identified from which VL probes were prepared and each was annealed with kidney DNA restriction digests. All VL probes revealed the same set of bands, corresponding to about 15 germline VL genes of one subgroup. The nucleotide sequences of six VL clones showed greater than or equal to 85% homology, and the predicted amino acid sequences were identical or nearly identical to the major N-terminal sequence of L-chains in chicken serum. These findings, and the fact that the VL clones were randomly selected from normal lymphoid tissues, strongly indicate that the bulk of chicken L-chains is encoded by a few germline VL genes, probably much less than 15 since many of the VL genes are known to be pseudogenes. Therefore, it is likely that somatic mechanisms operating prior to specific triggering by antigen play a major role in the generation of antibody diversity in chicken. Analysis of the constant region locus (sequencing of CL gene and cDNAs) demonstrate a single CL isotype and suggest the presence of CL allotypes.

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis

PubMed Central

Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha

2018-01-01

ABSTRACT Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation (n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation (n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics (n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. PMID:29386266

Performance of the Xpert HIV-1 Viral Load Assay: a Systematic Review and Meta-analysis.

PubMed

Nash, Madlen; Huddart, Sophie; Badar, Sayema; Baliga, Shrikala; Saravu, Kavitha; Pai, Madhukar

2018-04-01

Viral load (VL) is the preferred treatment-monitoring approach for HIV-positive patients. However, more rapid, near-patient, and low-complexity assays are needed to scale up VL testing. The Xpert HIV-1 VL assay (Cepheid, Sunnyvale, CA) is a new, automated molecular test, and it can leverage the GeneXpert systems that are being used widely for tuberculosis diagnosis. We systematically reviewed the evidence on the performance of this new tool in comparison to established reference standards. A total of 12 articles (13 studies) in which HIV patient VLs were compared between Xpert HIV VL assay and a reference standard VL assay were identified. Study quality was generally high, but substantial variability was observed in the number and type of agreement measures reported. Correlation coefficients between Xpert and reference assays were high, with a pooled Pearson correlation ( n = 8) of 0.94 (95% confidence interval [CI], 0.89, 0.97) and Spearman correlation ( n = 3) of 0.96 (95% CI, 0.86, 0.99). Bland-Altman metrics ( n = 11) all were within 0.35 log copies/ml of perfect agreement. Overall, Xpert HIV-1 VL performed well compared to current reference tests. The minimal training and infrastructure requirements for the Xpert HIV-1 VL assay make it attractive for use in resource-constrained settings, where point-of-care VL testing is most needed. Copyright © 2018 Nash et al.

A global comparative evaluation of commercial immunochromatographic rapid diagnostic tests for visceral leishmaniasis.

PubMed

Cunningham, Jane; Hasker, Epco; Das, Pradeep; El Safi, Sayda; Goto, Hiro; Mondal, Dinesh; Mbuchi, Margaret; Mukhtar, Maowia; Rabello, Ana; Rijal, Suman; Sundar, Shyam; Wasunna, Monique; Adams, Emily; Menten, Joris; Peeling, Rosanna; Boelaert, Marleen

2012-11-15

Poor access to diagnosis stymies control of visceral leishmaniasis (VL). Antibody-detecting rapid diagnostic tests (RDTs) can be performed in peripheral health settings. However, there are many brands available and published reports of variable accuracy. Commercial VL RDTs containing bound rK39 or rKE16 antigen were evaluated using archived human sera from confirmed VL cases (n = 750) and endemic non-VL controls (n = 754) in the Indian subcontinent (ISC), Brazil, and East Africa to assess sensitivity and specificity with 95% confidence intervals. A subset of RDTs were also evaluated after 60 days' heat incubation (37°C, 45°C). Interlot and interobserver variability was assessed. All test brands performed well against ISC panels (sensitivity range, 92.8%-100%; specificity range, 96%-100%); however, sensitivity was lower against Brazil and East African panels (61.5%-91% and 36.8%-87.2%, respectively). Specificity was consistently > 95% in Brazil and ranged between 90.8% and 98% in East Africa. Performance of some products was adversely affected by high temperatures. Agreement between lots and readers was good to excellent (κ > 0.73-0.99). Diagnostic accuracy of VL RDTs varies between the major endemic regions. Many tests performed well and showed good heat stability in the ISC; however, reduced sensitivity against Brazilian and East African panels suggests that in these regions, used alone, several RDTs are inadequate for excluding a VL diagnosis. More research is needed to assess ease of use and to compare performance using whole blood instead of serum and in patients coinfected with human immunodeficiency virus.

Analysis of Vision loss caused by radiation-induced optic neuropathy after particle therapy for head-and-neck and skull-base tumors adjacent to optic nerves.

PubMed

Demizu, Yusuke; Murakami, Masao; Miyawaki, Daisuke; Niwa, Yasue; Akagi, Takashi; Sasaki, Ryohei; Terashima, Kazuki; Suga, Daisaku; Kamae, Isao; Hishikawa, Yoshio

2009-12-01

To assess the incident rates of vision loss (VL; based on counting fingers or more severe) caused by radiation-induced optic neuropathy (RION) after particle therapy for tumors adjacent to optic nerves (ONs), and to evaluate factors that may contribute to VL. From August 2001 to August 2006, 104 patients with head-and-neck or skull-base tumors adjacent to ONs were treated with carbon ion or proton radiotherapy. Among them, 145 ONs of 75 patients were irradiated and followed for greater than 12 months. The incident rate of VL and the prognostic factors for occurrence of VL were evaluated. The late effects of carbon ion and proton beams were compared on the basis of a biologically effective dose at alpha/beta = 3 gray equivalent (GyE(3)). Eight patients (11%) experienced VL resulting from RION. The onset of VL ranged from 17 to 58 months. The median follow-up was 25 months. No significant difference was observed between the carbon ion and proton beam treatment groups. On univariate analysis, age (>60 years), diabetes mellitus, and maximum dose to the ON (>110 GyE(3)) were significant, whereas on multivariate analysis only diabetes mellitus was found to be significant for VL. The time to the onset of VL was highly variable. There was no statistically significant difference between carbon ion and proton beam treatments over the follow-up period. Based on multivariate analysis, diabetes mellitus correlated with the occurrence of VL. A larger study with longer follow-up is warranted.

Transmission Dynamics of Visceral Leishmaniasis in the Indian Subcontinent – A Systematic Literature Review

PubMed Central

Boelaert, Marleen; Matlashewski, Greg; Mondal, Dinesh; Arana, Byron; Kroeger, Axel; Olliaro, Piero

2016-01-01

Background As Bangladesh, India and Nepal progress towards visceral leishmaniasis (VL) elimination, it is important to understand the role of asymptomatic Leishmania infection (ALI), VL treatment relapse and post kala-azar dermal leishmaniasis (PKDL) in transmission. Methodology/ Principal Finding We reviewed evidence systematically on ALI, relapse and PKDL. We searched multiple databases to include studies on burden, risk factors, biomarkers, natural history, and infectiveness of ALI, PKDL and relapse. After screening 292 papers, 98 were included covering the years 1942 through 2016. ALI, PKDL and relapse studies lacked a reference standard and appropriate biomarker. The prevalence of ALI was 4–17-fold that of VL. The risk of ALI was higher in VL case contacts. Most infections remained asymptomatic or resolved spontaneously. The proportion of ALI that progressed to VL disease within a year was 1.5–23%, and was higher amongst those with high antibody titres. The natural history of PKDL showed variability; 3.8–28.6% had no past history of VL treatment. The infectiveness of PKDL was 32–53%. The risk of VL relapse was higher with HIV co-infection. Modelling studies predicted a range of scenarios. One model predicted VL elimination was unlikely in the long term with early diagnosis. Another model estimated that ALI contributed to 82% of the overall transmission, VL to 10% and PKDL to 8%. Another model predicted that VL cases were the main driver for transmission. Different models predicted VL elimination if the sandfly density was reduced by 67% by killing the sandfly or by 79% by reducing their breeding sites, or with 4–6y of optimal IRS or 10y of sub-optimal IRS and only in low endemic setting. Conclusion/ Significance There is a need for xenodiagnostic and longitudinal studies to understand the potential of ALI and PKDL as reservoirs of infection. PMID:27490264

Phlebotomus argentipes seasonal patterns in India and Nepal.

PubMed

Picado, Albert; Das, Murari Lal; Kumar, Vijay; Dinesh, Diwakar S; Rijal, Suman; Singh, Shri P; Das, Pradeep; Coosemans, Marc; Boelaert, Marleen; Davies, Clive

2010-03-01

The current control of Phebotomus argentipes (Annandale and Brunetti), the vector of Leishmania donovani (Laveran and Mesnil), on the Indian subcontinent is base on indoor residual spraying. The efficacy of this method depends, among other factors, on the timing and number of spraying rounds, which depend on the P. argentipes seasonality. To describe P. argentipes' seasonal patterns, six visceral leishmaniasis (VL) endemic villages, three in Muzaffarpur and three in Sunsari districts in India and Nepal, respectively, were selected based on accessibility and VL incidence. Ten houses per cluster with the highest P. argentipes density were monitored monthly for 15-16 mo using Center for Disease Control and Prevention light traps. Minimum and maximum temperature and rainfall data for the months January 2006 through December 2007 were collected from the nearest available weather stations. Backwards stepwise regression was used to generate the minimal adequate model for explaining the monthly variation in P. argentipes populations. The seasonality of P. argentipes is similar in India and Nepal, with two annual density peaks around May and October. Monthly P. argentipes density is positively associated with temperature and negatively associated with rainfall in both study sites. The multivariate climate model explained 57% of the monthly vectorial abundance. Vector control programs against P. argentipes (i.e., indoor residual spraying) should take into account the seasonal described here when implementing and monitoring interventions. Monitoring simple meteorological variables (i.e., temperature, rainfall) may allow prediction of VL epidemics on the Indian subcontinent.

Analysis of Vision Loss Caused by Radiation-Induced Optic Neuropathy After Particle Therapy for Head-and-Neck and Skull-Base Tumors Adjacent to Optic Nerves

DOE Office of Scientific and Technical Information (OSTI.GOV)

Demizu, Yusuke, E-mail: y_demizu@nifty.co; Murakami, Masao; Miyawaki, Daisuke

2009-12-01

Purpose: To assess the incident rates of vision loss (VL; based on counting fingers or more severe) caused by radiation-induced optic neuropathy (RION) after particle therapy for tumors adjacent to optic nerves (ONs), and to evaluate factors that may contribute to VL. Methods and Materials: From August 2001 to August 2006, 104 patients with head-and-neck or skull-base tumors adjacent to ONs were treated with carbon ion or proton radiotherapy. Among them, 145 ONs of 75 patients were irradiated and followed for greater than 12 months. The incident rate of VL and the prognostic factors for occurrence of VL were evaluated.more » The late effects of carbon ion and proton beams were compared on the basis of a biologically effective dose at alpha/beta = 3 gray equivalent (GyE{sub 3}). Results: Eight patients (11%) experienced VL resulting from RION. The onset of VL ranged from 17 to 58 months. The median follow-up was 25 months. No significant difference was observed between the carbon ion and proton beam treatment groups. On univariate analysis, age (>60 years), diabetes mellitus, and maximum dose to the ON (>110 GyE{sub 3}) were significant, whereas on multivariate analysis only diabetes mellitus was found to be significant for VL. Conclusions: The time to the onset of VL was highly variable. There was no statistically significant difference between carbon ion and proton beam treatments over the follow-up period. Based on multivariate analysis, diabetes mellitus correlated with the occurrence of VL. A larger study with longer follow-up is warranted.« less

Brief Report: Declining Baseline Viremia and Escalating Discordant HIV-1 Confirmatory Results Within South Africa's Early Infant Diagnosis Program, 2010-2016.

PubMed

Mazanderani, Ahmad Haeri; Moyo, Faith; Kufa, Tendesayi; Sherman, Gayle G

2018-02-01

To describe baseline HIV-1 RNA viral load (VL) trends within South Africa's Early Infant Diagnosis program 2010-2016, with reference to prevention of mother-to-child transmission guidelines. HIV-1 total nucleic acid polymerase chain reaction (TNA PCR) and RNA VL data from 2010 to 2016 were extracted from the South African National Health Laboratory Service's central data repository. Infants with a positive TNA PCR and subsequent baseline RNA VL taken at age <7 months were included. Descriptive statistics were performed for quantified and lower-than-quantification limit (LQL) results per annum and age in months. Trend analyses were performed using log likelihood ratio tests. Multivariable linear regression was used to model the relationship between RNA VL and predictor variables, whereas logistic regression was used to identify predictors associated with LQL RNA VL results. Among 13,606 infants with a positive HIV-1 TNA PCR linked to a baseline RNA VL, median age of first PCR was 57 days and VL was 98 days. Thirteen thousand one hundred ninety-five (97.0%) infants had a quantified VL and 411 (3.0%) had an LQL result. A significant decline in median VL was observed between 2010 and 2016, from 6.3 log10 (interquartile range: 5.6-6.8) to 5.6 log10 (interquartile range: 4.2-6.5) RNA copies per milliliter, after controlling for age (P < 0.001), with younger age associated with lower VL (P < 0.001). The proportion of infants with a baseline VL <4 Log10 RNA copies per milliliter increased from 5.4% to 21.8%. Subsequent to prevention of mother-to-child transmission Option B implementation in 2013, the proportion of infants with an LQL baseline VL increased from 1.5% to 6.1% (P < 0.001). Between 2010 and 2016, a significant decline in baseline viremia within South Africa's Early Infant Diagnosis program was observed, with loss of detectability among some HIV-infected infants.

Construction and characterization of VL-VH tail-parallel genetically engineered antibodies against staphylococcal enterotoxins.

PubMed

He, Xianzhi; Zhang, Lei; Liu, Pengchong; Liu, Li; Deng, Hui; Huang, Jinhai

2015-03-01

Staphylococcal enterotoxins (SEs) produced by Staphylococcus aureus have increasingly given rise to human health and food safety. Genetically engineered small molecular antibody is a useful tool in immuno-detection and treatment for clinical illness caused by SEs. In this study, we constructed the V(L)-V(H) tail-parallel genetically engineered antibody against SEs by using the repertoire of rearranged germ-line immunoglobulin variable region genes. Total RNA were extracted from six hybridoma cell lines that stably express anti-SEs antibodies. The variable region genes of light chain (V(L)) and heavy chain (V(H)) were cloned by reverse transcription PCR, and their classical murine antibody structure and functional V(D)J gene rearrangement were analyzed. To construct the eukaryotic V(H)-V(L) tail-parallel co-expression vectors based on the "5'-V(H)-ivs-IRES-V(L)-3'" mode, the ivs-IRES fragment and V(L) genes were spliced by two-step overlap extension PCR, and then, the recombined gene fragment and V(H) genes were inserted into the pcDNA3.1(+) expression vector sequentially. And then the constructed eukaryotic expression clones termed as p2C2HILO and p5C12HILO were transfected into baby hamster kidney 21 cell line, respectively. Two clonal cell lines stably expressing V(L)-V(H) tail-parallel antibodies against SEs were obtained, and the antibodies that expressed intracytoplasma were evaluated by enzyme-linked immunosorbent assay, immunofluorescence assay, and flow cytometry. SEs can stimulate the expression of some chemokines and chemokine receptors in porcine IPEC-J2 cells; mRNA transcription level of four chemokines and chemokine receptors can be blocked by the recombinant SE antibody prepared in this study. Our results showed that it is possible to get functional V(L)-V(H) tail-parallel genetically engineered antibodies in same vector using eukaryotic expression system.

Stability-Diversity Tradeoffs Impose Fundamental Constraints on Selection of Synthetic Human VH/VL Single-Domain Antibodies from In Vitro Display Libraries

PubMed Central

Henry, Kevin A.; Kim, Dae Young; Kandalaft, Hiba; Lowden, Michael J.; Yang, Qingling; Schrag, Joseph D.; Hussack, Greg; MacKenzie, C. Roger; Tanha, Jamshid

2017-01-01

Human autonomous VH/VL single-domain antibodies (sdAbs) are attractive therapeutic molecules, but often suffer from suboptimal stability, solubility and affinity for cognate antigens. Most commonly, human sdAbs have been isolated from in vitro display libraries constructed via synthetic randomization of rearranged VH/VL domains. Here, we describe the design and characterization of three novel human VH/VL sdAb libraries through a process of: (i) exhaustive biophysical characterization of 20 potential VH/VL sdAb library scaffolds, including assessment of expression yield, aggregation resistance, thermostability and tolerance to complementarity-determining region (CDR) substitutions; (ii) in vitro randomization of the CDRs of three VH/VL sdAb scaffolds, with tailored amino acid representation designed to promote solubility and expressibility; and (iii) systematic benchmarking of the three VH/VL libraries by panning against five model antigens. We isolated ≥1 antigen-specific human sdAb against four of five targets (13 VHs and 7 VLs in total); these were predominantly monomeric, had antigen-binding affinities ranging from 5 nM to 12 µM (average: 2–3 µM), but had highly variable expression yields (range: 0.1–19 mg/L). Despite our efforts to identify the most stable VH/VL scaffolds, selection of antigen-specific binders from these libraries was unpredictable (overall success rate for all library-target screens: ~53%) with a high attrition rate of sdAbs exhibiting false positive binding by ELISA. By analyzing VH/VL sdAb library sequence composition following selection for monomeric antibody expression (binding to protein A/L followed by amplification in bacterial cells), we found that some VH/VL sdAbs had marked growth advantages over others, and that the amino acid composition of the CDRs of this set of sdAbs was dramatically restricted (bias toward Asp and His and away from aromatic and hydrophobic residues). Thus, CDR sequence clearly dramatically impacts the stability of human autonomous VH/VL immunoglobulin domain folds, and sequence-stability tradeoffs must be taken into account during the design of such libraries. PMID:29375542

Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display.

PubMed

Yuan, Qing; Jordan, Ramon; Brlansky, Ronald H; Istomina, Olga; Hartung, John

2015-10-01

Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Antibody based detection assays are commercially available for X. fastidiosa, and are effective at the species, but not at the subspecies level. We have made a library of scFv antibody fragments directed against X. fastidiosa subsp. pauca strain 9a5c (citrus) by using phage display technology. Antibody gene repertoires were PCR-amplified using 23 primers for the heavy chain variable region (V(H)) and 21 primers for the light chain variable region (V(L)). The V(H) and V(L) were joined by overlap extension PCR, and then the genes of the scFv library were ligated into the phage vector pKM19. The library contained 1.2×10(7) independent clones with full-length scFv inserts. In each of 3cycles of affinity-selection with 9a5c, about 1.0×10(12) phage were used for panning with 4.1×10(6), 7.1×10(6), 2.1×10(7) phage recovered after the first, second and third cycles, respectively. Sixty-six percent of clones from the final library bound X. fastidiosa 9a5c in an ELISA. Some of these scFv antibodies recognized strain 9a5c and did not recognize X. fastidiosa strains that cause Pierce's disease of grapevine. Published by Elsevier B.V.

Susceptibility mapping of visceral leishmaniasis based on fuzzy modelling and group decision-making methods.

PubMed

Rajabi, Mohamadreza; Mansourian, Ali; Bazmani, Ahad

2012-11-01

Visceral leishmaniasis (VL) is a vector-borne disease, highly influenced by environmental factors, which is an increasing public health problem in Iran, especially in the north-western part of the country. A geographical information system was used to extract data and map environmental variables for all villages in the districts of Kalaybar and Ahar in the province of East Azerbaijan. An attempt to predict VL prevalence based on an analytical hierarchy process (AHP) module combined with ordered weighted averaging (OWA) with fuzzy quantifiers indicated that the south-eastern part of Ahar is particularly prone to high VL prevalence. With the main objective to locate the villages most at risk, the opinions of experts and specialists were generalised into a group decision-making process by means of fuzzy weighting methods and induced OWA. The prediction model was applied throughout the entire study area (even where the disease is prevalent and where data already exist). The predicted data were compared with registered VL incidence records in each area. The results suggest that linguistic fuzzy quantifiers, guided by an AHP-OWA model, are capable of predicting susceptive locations for VL prevalence with an accuracy exceeding 80%. The group decision-making process demonstrated that people in 15 villages live under particularly high risk for VL contagion, i.e. villages where the disease is highly prevalent. The findings of this study are relevant for the planning of effective control strategies for VL in northwest Iran.

Myeloma-Derived Light Chain Paired with a Diagnostic Monoclonal Antibody Hinders Immunoassay Performance.

PubMed

Tu, Bailin; Tieman, Bryan; Moore, Jeffrey; Pan, You; Muerhoff, A Scott

2017-06-01

Monoclonal antibodies are widely used as the capture and detection reagents in diagnostic immunoassays. In the past, myeloma fusion partners expressing endogenous heavy and/or light chains were often used to generate hybridoma cell lines. As a result, mixed populations of antibodies were produced that can cause inaccurate test results, poor antibody stability, and significant lot-to-lot variability. We describe one such scenario where the P3U1 (P3X63Ag8U.1) myeloma fusion partner was used in the generation of a hybridoma producing protein induced vitamin K absence/antagonist-II (PIVKA II) antibody. The hybridoma produces three subpopulations of immunoglobulin as determined by ion exchange (IEx) chromatography that exhibit varying degrees of immunoreactivity (0%, 50%, or 100%) to the target antigen as determined by Surface Plasmon Resonance. To produce an antibody with the highest possible sensitivity and specificity, the antigen-specific heavy and light chain variable domains (VH and VL) were cloned from the hybridoma and tethered to murine IgG1 and kappa scaffolds. The resulting recombinant antibody was expressed in Chinese hamster ovary cells and is compatible for use in a diagnostic immunoassay.

Utilizing Remote Sensing to Explore Hydrological and Climatic Factors of Visceral Leishmaniasis in South Sudan

NASA Astrophysics Data System (ADS)

Kruczkiewicz, A.; Sweeney, A.; Reid, C.; Seaman, J.; Abubakar, A.; Ritmeijer, K.; Jensen, K.; Schroeder, R.; McDonald, K. C.; Lessel, J.; Thomson, M. C.; Elnaiem, D.; Ceccato, P.

2014-12-01

Recent epidemics of visceral leishmaniasis (VL) in Sudan and South Sudan (locally known as Kala Azar) have caused an estimated 100,000 deaths and have renewed the impetus for defining the ecological boundaries of this vector borne disease. In the past 30 years outbreaks have occurred cyclically within this country, but recent shifts in endemicity have necessitated a more robust understanding of the drivers of the disease. Previous work (e.g. Gebre-Michael et al., 2004; Ashford & Thomson, 1991; Hoogstraal & Heyneman, 1969) has suggested that the primary biological vector in this region, the female sand fly Phlebotomus orientalis, exhibits sensitivities to environmental and climatic variables. Results of this study showed a relationship between precipitation and inundation during months of the transmission season (April-July) and the number of confirmed cases in the following September-January period. Particular months of the transmission season with below-average precipitation were better indicators of lagged reports of VL than others. During VL epidemics (2009, 2010, 2011) the month of June exhibited below average precipitation. The two largest epidemics (2010, 2011) were associated with years of below average precipitation in the month of April. Inundation during April-July (AMJJ) also exhibited a strong inverse relationship with reported VL cases in the following September- January (SONDJ). This relationship was best explored when comparing the VL case data of a specific medical center to the inundation anomalies. Results are typified by the Lankien Medical Center analysis where below average inundation during April displays an inverse relationship with VL cases in the following SONDJ. Drought may lead to below average inundation, which could allow for soils to maintain their fissures, thus maintaining the sand fly breeding habitat, resulting in a sustained breeding season for the sandflies (Quate, 1964). Above-average precipitation and inundation might have the inverse effect, eliminating their breeding sites within the soil. Land surface temperature (LST) Night, LST Day, and relative humidity did not show a particularly strong relationship with VL. Further research is needed, as these variables are known to exist across strong gradients within the northern states of South Sudan (Quate, 1964).

Predicted Distribution of Visceral Leishmaniasis Vectors (Diptera: Psychodidae; Phlebotominae) in Iran: A Niche Model Study.

PubMed

Hanafi-Bojd, A A; Rassi, Y; Yaghoobi-Ershadi, M R; Haghdoost, A A; Akhavan, A A; Charrahy, Z; Karimi, A

2015-12-01

Visceral leishmaniasis (VL) is an important vector-borne disease in Iran. Till now, Leishmania infantum has been detected from five species of sand flies in the country including Phlebotomus kandelakii, Phlebotomus major s.l., Phlebotomus perfiliewi, Phlebotomus alexandri and Phlebotomus tobbi. Also, Phlebotomus keshishiani was found to be infected with Leishmania parasites. This study aimed at predicting the probable niches and distribution of vectors of visceral leishmaniasis in Iran. Data on spatial distribution studies of sand flies were obtained from Iranian database on sand flies. Sample points were included in data from faunistic studies on sand flies conducted during 1995-2013. MaxEnt software was used to predict the appropriate ecological niches for given species, using climatic and topographical data. Distribution maps were prepared and classified in ArcGIS to find main ecological niches of the vectors and hot spots for VL transmission in Iran. Phlebotomus kandelakii, Ph. major s.l. and Ph. alexandri seem to have played a more important role in VL transmission in Iran, so this study focuses on them. Representations of MaxEnt model for probability of distribution of the studied sand flies showed high contribution of climatological and topographical variables to predict the potential distribution of three vector species. Isothermality was found to be an environmental variable with the highest gain when used in isolation for Ph. kandelakii and Ph. major s.l., while for Ph. alexandri, the most effective variable was precipitation of the coldest quarter. The results of this study present the first prediction on distribution of sand fly vectors of VL in Iran. The predicted distributions were matched with the disease-endemic areas in the country, while it was found that there were some unaffected areas with the potential transmission. More comprehensive studies are recommended on the ecology and vector competence of VL vectors in the country. © 2015 Blackwell Verlag GmbH.

Relationships Between Lower-Body Muscle Structure and, Lower-Body Strength, Explosiveness and Eccentric Leg Stiffness in Adolescent Athletes

PubMed Central

Secomb, Josh L.; Nimphius, Sophia; Farley, Oliver R.L.; Lundgren, Lina E.; Tran, Tai T.; Sheppard, Jeremy M.

2015-01-01

The purpose of the present study was to determine whether any relationships were present between lower-body muscle structure and, lower-body strength, variables measured during a countermovement jump (CMJ) and squat jump (SJ), and eccentric leg stiffness, in adolescent athletes. Thirty junior male (n = 23) and female (n = 7) surfing athletes (14.8 ± 1.7 y; 1.63 ± 0.09 m; 54.8 ± 12.1 kg) undertook lower-body muscle structure assessment with ultrasonography and performed a; CMJ, SJ and an isometric mid-thigh pull (IMTP). In addition, eccentric leg stiffness was calculated from variables of the CMJ and IMTP. Moderate to very large relationships (r = 0.46-0.73) were identified between the thickness of the vastus lateralis (VL) and lateral gastrocnemius (LG) muscles, and VL pennation angle and; peak force (PF) in the CMJ, SJ and IMTP. Additionally, moderate to large relationships (r = 0.37-0.59) were found between eccentric leg stiffness and; VL and LG thickness, VL pennation angle, and LG fascicle length, with a large relationship (r = 0.59) also present with IMTP PF. These results suggest that greater thickness of the VL and LG were related to improved maximal dynamic and isometric strength, likely due to increased hypertrophy of the extensor muscles. Furthermore, this increased thickness was related to greater eccentric leg stiffness, as the associated enhanced lower-body strength likely allowed for greater neuromuscular activation, and hence less compliance, during a stretch-shortening cycle. Key points Greater thickness of the VL and LG muscles were significantly related to an enhanced ability to express higher levels of isometric and dynamic strength, and explosiveness in adolescent athletes. Isometric strength underpinned performance in the CMJ and SJ in these athletes. Greater lower-body isometric strength was significantly related to eccentric leg stiffness, which is potentially the result of greater neuromuscular activation in the muscle-tendon unit. PMID:26664263

Periodization effects during short-term resistance training with equated exercise variables in females.

PubMed

Pelzer, Thiemo; Ullrich, Boris; Pfeiffer, Mark

2017-03-01

During resistance training, volume and load can be altered either gradually (traditional periodization: TP) or with frequent changes between subsequent sessions (daily undulating periodization: DUP). We hypothesized that the periodization model employed would not impact upon training-induced adaptations when exercise variables are equated. Nineteen females (22.0 years, moderate resistance training experience of 27.9 months) performed 6 weeks of knee extensor training with 3 weekly sessions exercising one leg using TP and the contralateral leg using DUP. Training load varied between 40, 60, and 80% of one repetition maximum (1RM). Volume, range of motion, and time under tension were equated for each leg with a biofeedback software. Dynamometry, surface EMG and ultrasonography were used to determine temporal changes of knee extensor maximum voluntary strength (MVC), neural drive of the M. quadriceps femoris (QF) and vastus lateralis (VL) and rectus femoris (RF) muscle architecture. Significant (P < 0.05) gains for isometric (TP 15%, DUP 13%) and isokinetic-concentric (TP 8%, DUP 10%) MVC and knee extensor 1RM (TP 18%, DUP 24%) occurred post training. VL and RF-muscle thickness showed significant (P < 0.05) increases ranging from 12 to 20% for TP and from 13 to 19% for DUP. Furthermore, significant (P < 0.05) increases in VL-pennation angle and VL-fascicle length occurred in both legs while QF EMG remained unchanged. No significant temporal differences were found between both models, displaying similar small to large effect sizes. Periodization is no adaptation trigger during short-term resistance training with equated exercise variables.

Photoinactivation of Escherichia coli by sulfur-doped and nitrogen-fluorine-codoped TiO2 nanoparticles under solar simulated light and visible light irradiation.

PubMed

Pathakoti, Kavitha; Morrow, Shavonda; Han, Changseok; Pelaez, Miguel; He, Xiaojia; Dionysiou, Dionysios D; Hwang, Huey-Min

2013-09-03

Titanium dioxide (TiO2) is one of the most widely used photocatalysts for the degradation of organic contaminants in water and air. Visible light (VL) activated sulfur-doped TiO2 (S-TiO2) and nitrogen-fluorine-codoped TiO2 (N-F-TiO2) were synthesized by sol-gel methods and characterized. Their photoinactivation performance was tested against Escherichia coli under solar simulated light (SSL) and VL irradiation with comparison to commercially available TiO2. Undoped Degussa-Evonik P-25 (P-25) and Sigma-TiO2 showed the highest photocatalytic activity toward E. coli inactivation under SSL irradiation, while S-TiO2 showed a moderate toxicity. After VL irradiation, Sigma-TiO2 showed higher photoinactivation, whereas S-TiO2 and P-25 showed moderate toxicity. Oxidative stress to E. coli occurred via formation of hydroxyl radicals leading to lipid peroxidation as the primary mechanism of bacterial inactivation. Various other biological models, including human keratinocytes (HaCaT), zebrafish liver cells (ZFL), and zebrafish embryos were also used to study the toxicity of TiO2 NPs. In conclusion, N-F-TiO2 did not show any toxicity based on the assay results from all the biological models used in this study, whereas S-TiO2 was toxic to zebrafish embryos under all the test conditions. These findings also demonstrate that the tested TiO2 nanoparticles do not show any adverse effects in HaCaT and ZFL cells.

Spatial correlations of population and ecological factors with distribution of visceral leishmaniasis cases in southwestern Iran.

PubMed

Ghatee, Mohammad Amin; Sharifi, Iraj; Haghdoost, Ali Akbar; Kanannejad, Zahra; Taabody, Zahra; Hatam, Gholamreza; Abdollahipanah, Abbas

2013-09-01

Leishmaniasis as a dynamic disease may be markedly influenced by demographic and ecological factors. A geospatial information system study was developed to determine the distribution of visceral leishmaniasis (VL) cases in relation to population, climatic and environmental factors in Fars province, southwest of Iran. The dwelling addresses of 217 VL patients were obtained from hospital files. A hazard map produced by unifying buffers (5 km) around nomads travel routes (NTR) was developed to survey the effect of close proximity to NTR on the distribution of VL. Mean annual rainfall (MAR), mean annual temperature (MAT), four months temperature mean (T4), elevation, slope and landcover were climatic and environmental factors that have been analysed. Finally, data of dwelling foci were extracted from maps and analysed using logistic regression models. Close proximity to NTR was the most important factor influenced on the disease distribution. Climatic factors were in second rank. Among them, temperature especially T4 is the most effective variable and rainfall was also shown to be another effective climatic agent. Most cases of VL were reported from temperate and semiarid areas in western and central regions while arid condition was a confined factor. The environmental factor of landcovers including urban, dry farm and thin forest regions was revealed as the third rank effective factor. Altitude importance was only shown when its effect was studied independently from other factors. These findings present the distribution of VL in Fars province is influenced by combination of ecological and nomads demographical variables although closeness to NTR and nomads role in distribution and continuance of kala-azar are the most important factors.

[Cloning of VH and VL Gene of Human anti-IL1RAP McAb and Construction of Recombinant Chimeric Receptor].

PubMed

Yin, Ling-Ling; Ruan, Su-Hong; Tian, Yu; Zhao, Kai; Xu, Kai Lin

2015-10-01

To clone the variable region genes of human anti-IL1RAP (IL-1 receptor accessory protein) monoclonal antibodies (McAb) and to construct IL1RAP chimeric antigen receptors (CARs). The VH and VL DNA of IL1RAP single chain antibodies were amplified by RACE and overlap extension PCR from total RNA extracted from 3H6E10 and 10D8A7 hybridoma and ligated into specific IL1RAP single-chain variable fragments (scFv). CD8α transmembrane domain, CD137 intracellular domain, TCR ζ chain, human CD8α signal peptide and scFv-anti-IL1RAP were cloned into plasmid LV-lac. Recombinant lentiviruses were generated by co-transfection of recombinant plasmid LV-lac, pMD2. G, and psPAX2 helper vectors into 293FT packing cells. The VH and VL genes of 2 human anti-IL1RAP McAb were acquired. The 3H6E10 VH and VL genes consisted of 402 bp and 393 bp encoding 134 and 131 aminoacid residues, respectively; 10D8A7 VH and VL genes consisted of 423 bp and 381 bp encoding 141 and 127 amine acid residues, respectively. Recombinant expression vertors LV-3H6E10 scFv-ICD and LV-10D8A7 scFv-ICD (ICD: CD8α transmembrane domain-CD137 intracellular domain-TCR ζ chain) were constructed. The target fragments were demonstrated by sequencing analysis. Recombinant plasmids were transfected into 293FT cells and lentiviral particles were acquired. Human anti-IL1RAP recombinant receptors are constructed successfully and lay a good foundation for the construction of IL1RAP-CAR killer T cell vaccine.

Effect of village-wide use of long-lasting insecticidal nets on visceral Leishmaniasis vectors in India and Nepal: a cluster randomized trial.

PubMed

Picado, Albert; Das, Murari L; Kumar, Vijay; Kesari, Shreekant; Dinesh, Diwakar S; Roy, Lalita; Rijal, Suman; Das, Pradeep; Rowland, Mark; Sundar, Shyam; Coosemans, Marc; Boelaert, Marleen; Davies, Clive R

2010-01-26

Visceral leishmaniasis (VL) control in the Indian subcontinent is currently based on case detection and treatment, and on vector control using indoor residual spraying (IRS). The use of long-lasting insecticidal nets (LN) has been postulated as an alternative or complement to IRS. Here we tested the impact of comprehensive distribution of LN on the density of Phlebotomus argentipes in VL-endemic villages. A cluster-randomized controlled trial with household P. argentipes density as outcome was designed. Twelve clusters from an ongoing LN clinical trial--three intervention and three control clusters in both India and Nepal--were selected on the basis of accessibility and VL incidence. Ten houses per cluster selected on the basis of high pre-intervention P. argentipes density were monitored monthly for 12 months after distribution of LN using CDC light traps (LT) and mouth aspiration methods. Ten cattle sheds per cluster were also monitored by aspiration. A random effect linear regression model showed that the cluster-wide distribution of LNs significantly reduced the P. argentipes density/house by 24.9% (95% CI 1.80%-42.5%) as measured by means of LTs. The ongoing clinical trial, designed to measure the impact of LNs on VL incidence, will confirm whether LNs should be adopted as a control strategy in the regional VL elimination programs. The entomological evidence described here provides some evidence that LNs could be usefully deployed as part of the VL control program. ClinicalTrials.gov CT-2005-015374.

Generation of a mouse scFv library specific for porcine aminopeptidase N using the T7 phage display system.

PubMed

Sun, Dongbo; Shi, Hongyan; Chen, Jianfei; Shi, Da; Zhu, Qinghe; Zhang, Hong; Liu, Shengwang; Wang, Yunfeng; Qiu, Huaji; Feng, Li

2012-06-01

Porcine aminopeptidase N (pAPN) is a common cellular receptor for swine transmissible gastroenteritis virus (TGEV) and porcine epidemic diarrhea virus (PEDV). To investigate single-chain fragment variable (scFv) repertoire against pAPN, the genes encoding the immunoglobulin light chain variable region (VL) and heavy chain variable region (VH) were amplified by reverse transcript polymerase chain reaction (RT-PCR) using a series of degenerate primers from the spleen of BABL/c mice immunized with native pAPN. The VL and VH amplicons were combined randomly by a 12 amino acid flexible linker by splicing by overlap extension PCR (SOE-PCR), which produced the scFv gene repertoire. After ligation of the scFv gene repertoire into the T7Select10-3b vector, a mouse scFv phage library specific for pAPN was produced through in vitro packaging. The primary scFv library against pAPN contained 2.0×10(7) recombinant phage clones, and the titer of the amplified library was 3.6×10(9)pfu/mL. BstNI restriction analysis and DNA sequencing revealed that 28 phage clones from the primary pAPN scFv library showed excellent diversity. The effectiveness of the scFv library against pAPN was verified further by phage ELISA using the recombinant protein of the pAPN C subunit as coating antigen. The construction and evaluation of a murine scFv library against the common receptor pAPN of porcine coronaviruses TGEV and PEDV using the T7 phage display system are described. Copyright © 2012 Elsevier B.V. All rights reserved.

SESOTHO trial ("Switch Either near Suppression Or THOusand") - switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa.

PubMed

Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy Renée; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

2018-02-12

The World Health Organization (WHO) recommends viral load (VL) measurement as the preferred monitoring strategy for HIV-infected individuals on antiretroviral therapy (ART) in resource-limited settings. The new WHO guidelines 2016 continue to define virologic failure as two consecutive VL ≥1000 copies/mL (at least 3 months apart) despite good adherence, triggering switch to second-line therapy. However, the threshold of 1000 copies/mL for defining virologic failure is based on low-quality evidence. Observational studies have shown that individuals with low-level viremia (measurable but below 1000 copies/mL) are at increased risk for accumulation of resistance mutations and subsequent virologic failure. The SESOTHO trial assesses a lower threshold for switch to second-line ART in patients with sustained unsuppressed VL. In this multicenter, parallel-group, open-label, randomized controlled trial conducted in Lesotho, patients on first-line ART with two consecutive unsuppressed VL measurements ≥100 copies/mL, where the second VL is between 100 and 999 copies/mL, will either be switched to second-line ART immediately (intervention group) or not be switched (standard of care, according to WHO guidelines). The primary endpoint is viral resuppression (VL < 50 copies/mL) 9 months after randomization. We will enrol 80 patients, giving us 90% power to detect a difference of 35% in viral resuppression between the groups (assuming two-sided 5% alpha error). For our primary analysis, we will use a modified intention-to-treat set, with those lost to care, death, or crossed over considered failure to resuppress, and using logistic regression models adjusted for the prespecified stratification variables. The SESOTHO trial challenges the current WHO guidelines, assessing an alternative, lower VL threshold for patients with unsuppressed VL on first-line ART. This trial will provide data to inform future WHO guidelines on VL thresholds to recommend switch to second-line ART. ClinicalTrials.gov ( NCT03088241 ), registered May 05, 2017.

Entrainment range of the suprachiasmatic nucleus affected by the difference in the neuronal amplitudes between the light-sensitive and light-insensitive regions.

PubMed

Gu, Changgui; Yang, Huijie; Ruan, Zhongyuan

2017-04-01

Mammals not only can be synchronized to the natural 24-h light-dark cycle, but also to a cycle with a non-24-h period. The range of the period of the external cycle, for which the animals can be entrained to, is called the entrainment range, which differs among species. The entrainment range as a characteristic of the animal is determined by the main circadian clock, i.e., the suprachiasmatic nucleus (SCN) in the brain. The SCN is composed of ∼10000 heterogeneous neurons, which can be divided into two subgroups, i.e., the ventrolateral subgroup (VL) directly receiving the light information from the retina and relaying the information to the dorsomedial subgroup (DM). Among the SCN neurons, the amplitudes are different; however, it is unclear that the amplitude is related to the location of the neurons in experiments. In the present study, we examined the effect of the difference in the neuronal amplitude between the VL and the DM on the entrainment range of the SCN, based on a mathematical model, i.e., the Poincaré model, which is used to describe the circadian clock. We find that the maximal entrainment range is obtained when the difference is equal to a critical point. If the difference of the amplitudes of the VL neurons to the amplitudes of the DM neurons is smaller than a critical point, with the increase of the difference, the entrainment range of the SCN increases, while if the difference is larger than the critical point, the entrainment range decreases with the increase of the difference. Our finding may give a potential explanation for the diversity of the entrainment range among species.

Entrainment range of the suprachiasmatic nucleus affected by the difference in the neuronal amplitudes between the light-sensitive and light-insensitive regions

NASA Astrophysics Data System (ADS)

Gu, Changgui; Yang, Huijie; Ruan, Zhongyuan

2017-04-01

Mammals not only can be synchronized to the natural 24-h light-dark cycle, but also to a cycle with a non-24-h period. The range of the period of the external cycle, for which the animals can be entrained to, is called the entrainment range, which differs among species. The entrainment range as a characteristic of the animal is determined by the main circadian clock, i.e., the suprachiasmatic nucleus (SCN) in the brain. The SCN is composed of ˜10 000 heterogeneous neurons, which can be divided into two subgroups, i.e., the ventrolateral subgroup (VL) directly receiving the light information from the retina and relaying the information to the dorsomedial subgroup (DM). Among the SCN neurons, the amplitudes are different; however, it is unclear that the amplitude is related to the location of the neurons in experiments. In the present study, we examined the effect of the difference in the neuronal amplitude between the VL and the DM on the entrainment range of the SCN, based on a mathematical model, i.e., the Poincaré model, which is used to describe the circadian clock. We find that the maximal entrainment range is obtained when the difference is equal to a critical point. If the difference of the amplitudes of the VL neurons to the amplitudes of the DM neurons is smaller than a critical point, with the increase of the difference, the entrainment range of the SCN increases, while if the difference is larger than the critical point, the entrainment range decreases with the increase of the difference. Our finding may give a potential explanation for the diversity of the entrainment range among species.

Systematic Review of the Performance of HIV Viral Load Technologies on Plasma Samples

PubMed Central

Sollis, Kimberly A.; Smit, Pieter W.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perrins, Jos; Peeling, Rosanna W.

2014-01-01

Background Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring. Methods and Findings A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n = 25), Cobas TaqMan v2.0 (n = 11), Abbott RealTime HIV-1 (n = 23), Versant HIV-1 RNA bDNA 3.0 (n = 15), Versant HIV-1 RNA kPCR 1.0 (n = 2), ExaVir Load v3 (n = 2), and NucliSens EasyQ v2.0 (n = 1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2–26% and 9–70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0–5.1%) and 5.44% (range 1.17–30.00%) across the range of VL counts (2log10–7log10). Conclusions This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL. Prospero registration # CD42013003603. PMID:24558359

Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand

PubMed Central

Ananworanich, Jintanat; Eller, Leigh Anne; Pinyakorn, Suteeraporn; Kroon, Eugene; Sriplenchan, Somchai; Fletcher, James LK; Suttichom, Duanghathai; Bryant, Christopher; Trichavaroj, Rapee; Dawson, Peter; Michael, Nelson; Phanuphak, Nittaya; Robb, Merlin L

2017-01-01

Abstract Introduction: The extent of viral replication during acute HIV infection (AHI) influences HIV disease progression. However, information comparing viral load (VL) kinetics with and without antiretroviral therapy (ART) in AHI is limited. The knowledge gained could inform preventive strategies aimed at reducing VL during AHI and therapeutic strategies to alter the viral kinetics that may enhance the likelihood of achieving HIV remission. Methods: The analysis utilized VL data captured during the first year of HIV infection from two studies in Thailand: the RV217 study (untreated AHI, 30 participants and 412 visits) and the RV254 study (treated AHI, 235 participants and 2803 visits). Fiebig stages were I/II (HIV RNA+, HIV IgM−) and Fiebig III/IV (HIV IgM+, Western blot-/indeterminate). Data were modelled utilizing spline effects within a linear mixed model, with a random intercept and slope to allow for between-subject variability and adjustment for the differences in variability between studies. The number of knots in the quadratic spline basis functions was determined by comparing models with differing numbers of knots via the Akaike Information Criterion. Models were fit using PROC GLIMMIX in SAS v9.3. Results: At enrolment, there were 24 Fiebig I/II and 6 Fiebig III/IV individuals in the untreated group and 137 Fiebig I/II and 98 Fiebig III/IV individuals in the treated group. Overall, the median age was 27.5 years old, most were male (89%), and CRF01_AE was the most common HIV clade (76%). By day 12 (4 days after ART in RV254), the untreated group had a 2.7-fold higher predicted mean VL level compared to those treated (predicted log VL 6.19 for RV217 and 5.76 for RV254, p = 0.05). These differences increased to 135-fold by day 30 (predicted log VL 4.89 for RV217 and 2.76 for RV254) and 1148-fold by day 120 (predicted log VL 4.68 for RV217 and 1.63 for RV254) (p < 0.0001 for both) until both curves were similarly flat at about day 150 (p = 0.17 between days 150 and 160). The VL trajectories were significantly different between Fiebig I/II and Fiebig III/IV participants when comparing the two groups and within the treated group (p < 0.001 for both). Conclusions: Initiating ART in AHI dramatically changed the trajectory of VL very early in the course of infection that could have implications for reducing transmission potential and enhancing responses to future HIV remission strategies. There is an urgency of initiating ART when acute infection is identified. New and inexpensive strategies to engage and test individuals at high risk for HIV as well as immediate treatment access will be needed to improve the treatment of acute infection globally. Clinical Trial Number: NCT00796146 and NCT00796263 PMID:28691436

Viral kinetics in untreated versus treated acute HIV infection in prospective cohort studies in Thailand.

PubMed

Ananworanich, Jintanat; Eller, Leigh Anne; Pinyakorn, Suteeraporn; Kroon, Eugene; Sriplenchan, Somchai; Fletcher, James Lk; Suttichom, Duanghathai; Bryant, Christopher; Trichavaroj, Rapee; Dawson, Peter; Michael, Nelson; Phanuphak, Nittaya; Robb, Merlin L

2017-06-26

The extent of viral replication during acute HIV infection (AHI) influences HIV disease progression. However, information comparing viral load (VL) kinetics with and without antiretroviral therapy (ART) in AHI is limited. The knowledge gained could inform preventive strategies aimed at reducing VL during AHI and therapeutic strategies to alter the viral kinetics that may enhance the likelihood of achieving HIV remission. The analysis utilized VL data captured during the first year of HIV infection from two studies in Thailand: the RV217 study (untreated AHI, 30 participants and 412 visits) and the RV254 study (treated AHI, 235 participants and 2803 visits). Fiebig stages were I/II (HIV RNA+, HIV IgM-) and Fiebig III/IV (HIV IgM+, Western blot-/indeterminate). Data were modelled utilizing spline effects within a linear mixed model, with a random intercept and slope to allow for between-subject variability and adjustment for the differences in variability between studies. The number of knots in the quadratic spline basis functions was determined by comparing models with differing numbers of knots via the Akaike Information Criterion. Models were fit using PROC GLIMMIX in SAS v9.3. At enrolment, there were 24 Fiebig I/II and 6 Fiebig III/IV individuals in the untreated group and 137 Fiebig I/II and 98 Fiebig III/IV individuals in the treated group. Overall, the median age was 27.5 years old, most were male (89%), and CRF01_AE was the most common HIV clade (76%). By day 12 (4 days after ART in RV254), the untreated group had a 2.7-fold higher predicted mean VL level compared to those treated (predicted log VL 6.19 for RV217 and 5.76 for RV254, p  = 0.05). These differences increased to 135-fold by day 30 (predicted log VL 4.89 for RV217 and 2.76 for RV254) and 1148-fold by day 120 (predicted log VL 4.68 for RV217 and 1.63 for RV254) ( p  < 0.0001 for both) until both curves were similarly flat at about day 150 ( p  = 0.17 between days 150 and 160). The VL trajectories were significantly different between Fiebig I/II and Fiebig III/IV participants when comparing the two groups and within the treated group ( p  < 0.001 for both). Initiating ART in AHI dramatically changed the trajectory of VL very early in the course of infection that could have implications for reducing transmission potential and enhancing responses to future HIV remission strategies. There is an urgency of initiating ART when acute infection is identified. New and inexpensive strategies to engage and test individuals at high risk for HIV as well as immediate treatment access will be needed to improve the treatment of acute infection globally. NCT00796146 and NCT00796263.

Stray-light analyses of the multielement telescope for imaging and spectroscopy coronagraph on Solar Orbiter

NASA Astrophysics Data System (ADS)

Sandri, Paolo; Fineschi, Silvano; Romoli, Marco; Taccola, Matteo; Landini, Federico; Da Deppo, Vania; Naletto, Giampiero; Morea, Danilo; Naughton, Denis; Antonucci, Ester

2018-01-01

The modeling of the scattering phenomena for the multielement telescope for imaging and spectroscopy (METIS) coronagraph on board the European Space Agency Solar Orbiter is reported. METIS is an inverted occultation coronagraph including two optical paths: the broadband imaging of the full corona in linearly polarized visible-light (580 to 640 nm) and the narrow-band imaging of the full corona in the ultraviolet Lyman-α (121.6 nm). METIS will have the unique opportunity of observing the solar outer atmosphere as close to the Sun as 0.28 AU and from up to 35 deg out-of-ecliptic. The stray-light simulations performed on the UV and VL channels of the METIS analyzing the contributors of surface microroughness, particulate contamination, cosmetic defects, and diffraction are reported. The results obtained with the nonsequential modality of Zemax OpticStudio are compared with two different approaches: the Monte Carlo ray trace with Advanced Systems Analysis Program (ASAP®) and a semianalytical model. The results obtained with the three independently developed approaches are in considerable agreement and show compliance to the requirement of stray-light level for both the UV and VL channels.

HIV Community Viral Load and Factors Associated With Elevated Viremia Among a Community-Based Sample of Men Who Have Sex With Men in Vancouver, Canada.

PubMed

Moore, David M; Cui, Zishan; Lachowsky, Nathan; Raymond, Henry F; Roth, Eric; Rich, Ashleigh; Sereda, Paul; Howard, Terry; McFarland, Willi; Lal, Allan; Montaner, Julio; Corneil, Trevor; Hogg, Robert S

2016-05-01

We developed estimates of community viral load (VL) and risk factors for unsuppressed VL from a cross-sectional study of men who have sex with men (MSM) in Vancouver, Canada. MSM were recruited from February 25, 2012 to February 28, 2014 using respondent-driven sampling (RDS). Participants completed a computer-assisted self-interview questionnaire and a nurse-administered point-of-care HIV test. For HIV-positive participants, we conducted VL and CD4 cell counts. We used RDS-weighted analysis to obtain population estimates of key variables and multivariable logistic regression to examine factors associated with having a VL of ≥200 copies per milliliter among HIV-positive participants. We recruited 719 participants, of whom 119 (16.6%) were seeds. Our estimate of the population prevalence of HIV was 23.4% [95% confidence interval (CI): 15.8% to 31.0%] after RDS adjustments. We estimated that 18.6% (95% CI: 8.8% to 30.4%) of HIV-positive MSM in Vancouver had a VL of ≥200 copies per milliliter. Having an unsuppressed VL was associated with non-white ethnicity [adjusted odds ratio (AOR) = 4.34; 95% CI: 1.67 to 11.1], an annual income of <$15,000 CAD (AOR = 6.43; 95% CI: 2.08 to 19.9), using gamma-hydroxy butyrate in the previous 6 months (AOR = 4.85; 95% CI: 1.79 to 13.2), unprotected anal intercourse with a known HIV-negative or an unknown serostatus partner (AOR = 3.13; 95% CI: 1.10 to 8.90), and disclosing one's HIV serostatus ≥50% of the time (AOR = 7.04; 95% CI: 1.01 to 49.1). Despite a high prevalence of HIV, we estimated that a small proportion of HIV-positive MSM have undiagnosed HIV and unsuppressed VL. Our results highlight the importance of continued work to address health inequities using a framework based on social determinants of health.

Genetic Predisposition to Self-Curing Infection with the Protozoan Leishmania chagasi: A Genome Wide Scan

PubMed Central

Jeronimo, Selma M. B.; Duggal, Priya; Ettinger, Nicholas A.; Nascimento, Eliana T.; Monteiro, Gloria R.; Cabral, Angela P.; Pontes, Núbia N.; Lacerda, Hênio G.; Queiroz, Paula V.; Maia, Carlos G.; Pearson, Richard D.; Blackwell, Jenefer M.; Beaty, Terri H.; Wilson, Mary E.

2008-01-01

The protozoan Leishmania chagasi can cause disseminated, fatal visceral leishmaniasis (VL) or asymptomatic human infection. We hypothesized that genetic factors contribute to this variable response to infection. A family study was performed in endemic neighborhoods near Natal, northeast Brazil. Subjects were assessed for VL or asymptomatic infection, defined as a positive delayed type hypersensitivity (DTH) skin test response to Leishmania antigen without disease symptoms. A genome scan of 405 microsatellite markers in 1254 subjects was analyzed for regions of linkage. The results indicated loci of potential linkage to DTH response on chromosomes 2, 13, 15 and 19, and a novel region of potential interest for VL on chromosome 9. An understanding of the genetic factors determining whether an individual will develop symptomatic or asymptomatic infection with L. chagasi may illuminate proteins essential for immune protection against this parasitic disease; findings could reveal strategies for immunotherapy or prevention. PMID:17955446

Exploring the Inner Acceleration Region of Solar Wind: A Study Based on Coronagraphic UV and Visible Light Data

NASA Astrophysics Data System (ADS)

Bemporad, A.

2017-09-01

This work combined coronagraphic visible light (VL) and UV data to provide with an unprecedented view of the inner corona where the nascent solar wind is accelerated. The UV (H I Lyα) and VL (polarized brightness) images (reconstructed with SOHO/UVCS, LASCO, and Mauna Loa data) have been analyzed with the Doppler dimming technique to provide for the first time daily 2D images of the radial wind speed between 1 and 6 R ⊙ over 1 month of observations. Results show that both polar and equatorial regions are characterized at the base of the corona by plasma outflows at speeds > 100 km s-1. The plasma is then decelerated within ˜1.5 R ⊙ at the poles and ˜2.0 R ⊙ at the equator, where local minima of the expansion speeds are reached, and gently reaccelerated higher up, reaching speeds typical of fast and slow wind components. The mass flux is highly variable with latitude and time at the equator and more uniform and stable over the poles. The polar flow is asymmetric, with speeds above the south pole lower than those above the north pole. A correlation (anticorrelation) between the wind speed and its density is found below (above) ˜1.8 R ⊙. The 2D distribution of forces responsible for deceleration and reacceleration of solar wind is provided and interpreted in terms of Alfvén waves. These results provide a possible connection between small-scale outflows reported with other instruments at the base of the corona and bulk wind flows measured higher up.

Work-related outcome after acute coronary syndrome: Implications of complex cardiac rehabilitation in occupational medicine.

PubMed

Lamberti, Monica; Ratti, Gennaro; Gerardi, Donato; Capogrosso, Cristina; Ricciardi, Gianfranco; Fulgione, Cosimo; Latte, Salvatore; Tammaro, Paolo; Covino, Gregorio; Nienhaus, Albert; Grazillo, Elpidio Maria; Mallardo, Mario; Capogrosso, Paolo

2016-01-01

Coronary heart disease is frequent in the working-age population. Traditional outcomes, such as mortality and hospital readmission, are useful for evaluating prognosis. Fit-for-work is an emerging outcome with clinical as well as socioeconomic significance. We describe the possible benefit of a cardiac rehabilitation (CR) program for return to work (RTW) after acute coronary syndrome (ACS). We evaluated 204 patients with recent ACS. They were divided into 4 groups on the basis of their occupational work load: very light (VL), light (L), moderate (M), and heavy (H). Work-related outcomes were assessed with the Work Performance Scale (WPS) of the Functional Status Questionnaire and as "days missed from work" (DMW) in the previous 4 weeks. The variables considered for outcomes were percent ejection fraction, functional capacity expressed in metabolic equivalents (METs), and participation or non-participation in the CR program (CR+ and CR-). One hundred thirty (66%) patients took part in the CR program. Total WPS scores for CR+ and CR- subgroups were VL group: 18±4 vs. 14±4 (p < 0.001), L group: 18±3 vs. 14±3 (p < 0.0001), M group: 19±3 vs. 16±3 (p < 0.003), and H group: 20±4 vs. 17±3 (p < 0.006). Fewer DMW were reported by the CR+ group. Non-participation in CR was a consistent cause of poorer work-related outcomes. Our findings indicate that CR and occupational counseling play a very important role in worker recovery and subsequent reintegration in the workplace, in particular among clerical workers. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Systematic Characterization and Comparative Analysis of the Rabbit Immunoglobulin Repertoire

PubMed Central

Lavinder, Jason J.; Hoi, Kam Hon; Reddy, Sai T.; Wine, Yariv; Georgiou, George

2014-01-01

Rabbits have been used extensively as a model system for the elucidation of the mechanism of immunoglobulin diversification and for the production of antibodies. We employed Next Generation Sequencing to analyze Ig germline V and J gene usage, CDR3 length and amino acid composition, and gene conversion frequencies within the functional (transcribed) IgG repertoire of the New Zealand white rabbit (Oryctolagus cuniculus). Several previously unannotated rabbit heavy chain variable (VH) and light chain variable (VL) germline elements were deduced bioinformatically using multidimensional scaling and k-means clustering methods. We estimated the gene conversion frequency in the rabbit at 23% of IgG sequences with a mean gene conversion tract length of 59±36 bp. Sequencing and gene conversion analysis of the chicken, human, and mouse repertoires revealed that gene conversion occurs much more extensively in the chicken (frequency 70%, tract length 79±57 bp), was observed to a small, yet statistically significant extent in humans, but was virtually absent in mice. PMID:24978027

Characterization and screening of IgG binding to the neonatal Fc receptor

PubMed Central

Neuber, Tobias; Frese, Katrin; Jaehrling, Jan; Jäger, Sebastian; Daubert, Daniela; Felderer, Karin; Linnemann, Mechthild; Höhne, Anne; Kaden, Stefan; Kölln, Johanna; Tiller, Thomas; Brocks, Bodo; Ostendorp, Ralf; Pabst, Stefan

2014-01-01

The neonatal Fc receptor (FcRn) protects immunoglobulin G (IgG) from degradation and increases the serum half-life of IgG, thereby contributing to a higher concentration of IgG in the serum. Because altered FcRn binding may result in a reduced or prolonged half-life of IgG molecules, it is advisable to characterize Fc receptor binding of therapeutic antibody lead candidates prior to the start of pre-clinical and clinical studies. In this study, we characterized the interactions between FcRn of different species (human, cynomolgus monkey, mouse and rat) and nine IgG molecules from different species and isotypes with common variable heavy (VH) and variable light chain (VL) domains. Binding was analyzed at acidic and neutral pH using surface plasmon resonance (SPR) and biolayer interferometry (BLI). Furthermore, we transferred the well-accepted, but low throughput SPR-based method for FcRn binding characterization to the BLI-based Octet platform to enable a higher sample throughput allowing the characterization of FcRn binding already during early drug discovery phase. We showed that the BLI-based approach is fit-for-purpose and capable of discriminating between IgG molecules with significant differences in FcRn binding affinities. Using this high-throughput approach we investigated FcRn binding of 36 IgG molecules that represented all VH/VL region combinations available in the fully human, recombinant antibody library Ylanthia®. Our results clearly showed normal FcRn binding profiles for all samples. Hence, the variations among the framework parts, complementarity-determining region (CDR) 1 and CDR2 of the fragment antigen binding (Fab) domain did not significantly change FcRn binding. PMID:24802048

Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.

PubMed

Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J

2000-03-01

MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

American Visceral Leishmaniasis: Factors Associated with Lethality in the State of São Paulo, Brazil

PubMed Central

Madalosso, Geraldine; Fortaleza, Carlos Magno; Ribeiro, Ana Freitas; Cruz, Lisete Lage; Nogueira, Péricles Alves; Lindoso, José Angelo Lauletta

2012-01-01

Objectives. To identify factors associated with death in visceral leishmaniasis (VL) cases. Patients and Methodology. We evaluated prognostic factors for death from VL in São Paulo state, Brazil, from 1999 to 2005. A prognostic study nested in a clinical cohort was carried out by data analysis of 376 medical files. A comparison between VL fatal cases and survivors was performed for clinical, laboratory, and biological features. Association between variables and death was assessed by univariate analysis, and the multiple logistic regression model was used to determine adjusted odds ratio for death, controlling confounding factors. Results. Data analysis identified 53 fatal cases out of 376 patients, between 1999 and 2005 in São Paulo state. Lethality was 14.1% (53/376), being higher in patients older than fifty years. The main causes of death were sepsis, bleeding, liver failure, and cardiotoxicity due to treatment. Variables significantly associated with death were severe anemia, bleeding, heart failure, jaundice, diarrhea, fever for more than sixty days, age older than fifty years, and antibiotic use. Conclusion. Educational health measures are needed for the general population and continuing education programs for health professionals working in the affected areas with the purpose of identifying and treating early cases, thus preventing the disease evolution towards death. PMID:23024661

Using Light to Prepare and Probe an Electron Spin in a Quantum Dot

DTIC Science & Technology

2005-01-01

A. Shabaev, A.L. Efros, D. Park, D. Gershoni, V.L. Korenev , and I.A. Merkulov, “Optical Pumping of the Electronic and Nuclear Spin in Single Charge-tunable Quantum Dots,” Phys. Rev. Lett. 94, 047402 (2005). ´

The Influence of Item Calibration Error on Variable-Length Computerized Adaptive Testing

ERIC Educational Resources Information Center

Patton, Jeffrey M.; Cheng, Ying; Yuan, Ke-Hai; Diao, Qi

2013-01-01

Variable-length computerized adaptive testing (VL-CAT) allows both items and test length to be "tailored" to examinees, thereby achieving the measurement goal (e.g., scoring precision or classification) with as few items as possible. Several popular test termination rules depend on the standard error of the ability estimate, which in turn depends…

Comparison of Ahlstrom grade 226, Munktell TFN, and Whatman 903 filter papers for dried blood spot specimen collection and subsequent HIV-1 load and drug resistance genotyping analysis.

PubMed

Rottinghaus, Erin; Bile, Ebi; Modukanele, Mosetsanagape; Maruping, Maruping; Mine, Madisa; Nkengasong, John; Yang, Chunfu

2013-01-01

Dried blood spots (DBS) collected onto filter paper have eased the difficulty of blood collection in resource-limited settings. Currently, Whatman 903 (W-903) filter paper is the only filter paper that has been used for HIV load and HIV drug resistance (HIVDR) testing. We therefore evaluated two additional commercially available filter papers, Ahlstrom grade 226 (A-226) and Munktell TFN (M-TFN), for viral load (VL) testing and HIVDR genotyping using W-903 filter paper as a comparison group. DBS specimens were generated from 344 adult patients on antiretroviral therapy (ART) in Botswana. The VL was measured with NucliSENS EasyQ HIV-1 v2.0, and genotyping was performed for those specimens with a detectable VL (≥ 2.90 log(10) copies/ml) using an in-house method. Bland-Altman analysis revealed a strong concordance in quantitative VL analysis between W-903 and A-226 (bias = -0.034 ± 0.246 log(10) copies/ml [mean difference ± standard deviation]) and W-903 and M-TFN (bias = -0.028 ± 0.186 log(10) copies/ml) filter papers, while qualitative VL analysis for virological failure determination, defined as a VL of ≥ 3.00 log(10) copies/ml, showed low sensitivities for A-266 (71.54%) and M-TFN (65.71%) filter papers compared to W-903 filter paper. DBS collected on M-TFN filter paper had the highest genotyping efficiency (100%) compared to W-903 and A-226 filter papers (91.7%) and appeared more sensitive in detecting major HIVDR mutations. DBS collected on A-226 and M-TFN filter papers performed similarly to DBS collected on W-903 filter paper for quantitative VL analysis and HIVDR detection. Together, the encouraging genotyping results and the variability observed in determining virological failure from this small pilot study warrant further investigation of A-226 and M-TFN filter papers as specimen collection devices for HIVDR monitoring surveys.

Muscle Activation During Exercise in Severe Acute Hypoxia: Role of Absolute and Relative Intensity

PubMed Central

Torres-Peralta, Rafael; Losa-Reyna, José; González-Izal, Miriam; Perez-Suarez, Ismael; Calle-Herrero, Jaime; Izquierdo, Mikel

2014-01-01

Abstract Torres-Peralta, Rafael, José Losa-Reyna, Miriam González-Izal, Ismael Perez-Suarez, Jaime Calle-Herrero, Mikel Izquierdo, and José A.L. Calbet. Muscle activation during exercise in severe acute hypoxia: Role of absolute and relative intensity. High Alt Med Biol 15:472–482, 2014.—The aim of this study was to determine the influence of severe acute hypoxia on muscle activation during whole body dynamic exercise. Eleven young men performed four incremental cycle ergometer tests to exhaustion breathing normoxic (FIo2=0.21, two tests) or hypoxic gas (FIo2=0.108, two tests). Surface electromyography (EMG) activities of rectus femoris (RF), vastus medialis (VL), vastus lateralis (VL), and biceps femoris (BF) were recorded. The two normoxic and the two hypoxic tests were averaged to reduce EMG variability. Peak Vo2 was 34% lower in hypoxia than in normoxia (p<0.05). The EMG root mean square (RMS) increased with exercise intensity in all muscles (p<0.05), with greater effect in hypoxia than in normoxia in the RF and VM (p<0.05), and a similar trend in VL (p=0.10). At the same relative intensity, the RMS was greater in normoxia than in hypoxia in RF, VL, and BF (p<0.05), with a similar trend in VM (p=0.08). Median frequency increased with exercise intensity (p<0.05), and was higher in hypoxia than in normoxia in VL (p<0.05). Muscle contraction burst duration increased with exercise intensity in VM and VL (p<0.05), without clear effects of FIo2. No significant FIo2 effects on frequency domain indices were observed when compared at the same relative intensity. In conclusion, muscle activation during whole body exercise increases almost linearly with exercise intensity, following a muscle-specific pattern, which is adjusted depending on the FIo2 and the relative intensity of exercise. Both VL and VM are increasingly involved in power output generation with the increase of intensity and the reduction in FIo2. PMID:25225839

Accelerated active case detection of visceral leishmaniasis patients in endemic villages of Bangladesh.

PubMed

Khatun, Jahanara; Huda, M Mamun; Hossain, Md Shakhawat; Presber, Wolfgang; Ghosh, Debashis; Kroeger, Axel; Matlashewski, Greg; Mondal, Dinesh

2014-01-01

The visceral leishmaniasis (VL) elimination program in Bangladesh is in its attack phase. The primary goal of this phase is to decrease the burden of VL as much as possible. Active case detection (ACD) by the fever camp method and an approach using past VL cases in the last 6-12 months have been found useful for detection of VL patients in the community. We aimed to explore the yield of Accelerated Active Case Detection (AACD) of non-self reporting VL as well as the factors that are associated with non-self reporting to hospitals in endemic communities of Bangladesh. Our study was conducted in the Trishal sub-district of Mymensingh, a highly VL endemic region of Bangladesh. We used a two-stage sampling strategy from 12 VL endemic unions of Trishal. Two villages from each union were selected at random. We looked for VL patients who had self-reported to the hospital and were under treatment from these villages. Then we conducted AACD for VL cases in those villages using house-to-house visit. Suspected VL cases were referred to the Trishal hospital where diagnosis and treatment of VL was done following National Guidelines for VL case management. We collected socio-demographic information from patients or a patient guardian using a structured questionnaire. The total number of VL cases was 51. Nineteen of 51 (37.3%) were identified by AACD. Poverty, female gender and poor knowledge about VL were independent factors associated with non self-reporting to the hospital. Our primary finding is that AACD is a useful method for early detection of VL cases that would otherwise go unreported to the hospital in later stage due to poverty, poor knowledge about VL and gender inequity. We recommend that the National VL Program should consider AACD to strengthen its early VL case detection strategy.

Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control

PubMed Central

Egner, Tobias

2013-01-01

Conflict adaptation – a conflict-triggered improvement in the resolution of conflicting stimulus or response representations – has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous functional magnetic resonance imaging (fMRI) studies have localized activation foci associated with conflict resolution to dorsolateral prefrontal cortex (dlPFC). The traditional group-analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach in order to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed, while controlling for individual differences in mean reaction time and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral prefrontal cortex (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ~40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance. PMID:21568631

Right ventrolateral prefrontal cortex mediates individual differences in conflict-driven cognitive control.

PubMed

Egner, Tobias

2011-12-01

Conflict adaptation--a conflict-triggered improvement in the resolution of conflicting stimulus or response representations--has become a widely used probe of cognitive control processes in both healthy and clinical populations. Previous fMRI studies have localized activation foci associated with conflict resolution to dorsolateral PFC (dlPFC). The traditional group analysis approach employed in these studies highlights regions that are, on average, activated during conflict resolution, but does not necessarily reveal areas mediating individual differences in conflict resolution, because between-subject variance is treated as noise. Here, we employed a complementary approach to elucidate the neural bases of variability in the proficiency of conflict-driven cognitive control. We analyzed two independent fMRI data sets of face-word Stroop tasks by using individual variability in the behavioral expression of conflict adaptation as the metric against which brain activation was regressed while controlling for individual differences in mean RT and Stroop interference. Across the two experiments, a replicable neural substrate of individual variation in conflict adaptation was found in ventrolateral PFC (vlPFC), specifically, in the right inferior frontal gyrus, pars orbitalis (BA 47). Unbiased regression estimates showed that variability in activity in this region accounted for ∼ 40% of the variance in behavioral expression of conflict adaptation across subjects, thus documenting a heretofore unsuspected key role for vlPFC in mediating conflict-driven adjustments in cognitive control. We speculate that vlPFC plays a primary role in conflict control that is supplemented by dlPFC recruitment under conditions of suboptimal performance.

Chicken scFvs with an Artificial Cysteine for Site-Directed Conjugation

PubMed Central

Kim, Soohyun; Kim, Hyori; Chung, Junho

2016-01-01

For the site-directed conjugation of chemicals and radioisotopes to the chicken-derived single-chain variable fragment (scFv), we investigated amino acid residues replaceable with cysteine. By replacing each amino acid of the 157 chicken variable region framework residues (FR, 82 residues on VH and 75 on VL) with cysteine, 157 artificial cysteine mutants were generated and characterized. At least 27 residues on VL and 37 on VH could be replaced with cysteine while retaining the binding activity of the original scFv. We prepared three VL (L5, L6 and L7) and two VH (H13 and H16) mutants as scFv-Ckappa fusion proteins and showed that PEG-conjugation to the sulfhydryl group of the artificial cysteine was achievable in all five mutants. Because the charge around the cysteine residue affects the in vivo stability of thiol-maleimide conjugation, we prepared 16 charge-variant artificial cysteine mutants by replacing the flanking residues of H13 with charged amino acids and determined that the binding activity was not affected in any of the mutants except one. We prepared four charge-variant H13 artificial cysteine mutants (RCK, DCE, ECD and ECE) as scFv-Ckappa fusion proteins and confirmed that the reactivity of the sulfhydryl group on cysteine is active and their binding activity is retained after the conjugation process. PMID:26764487

Genetic homogeneity among Leishmania (Leishmania) infantum isolates from dog and human samples in Belo Horizonte Metropolitan Area (BHMA), Minas Gerais, Brazil.

PubMed

da Silva, Thais Almeida Marques; Gomes, Luciana Inácia; Oliveira, Edward; Coura-Vital, Wendel; Silva, Letícia de Azevedo; Pais, Fabiano Sviatopolk-Mirsky; Ker, Henrique Gama; Reis, Alexandre Barbosa; Rabello, Ana; Carneiro, Mariangela

2015-04-15

Certain municipalities in the Belo Horizonte Metropolitan Area (BHMA), Minas Gerais, Brazil, have the highest human visceral leishmaniasis (VL) mortality rates in the country and also demonstrate high canine seropositivity. In Brazil, the etiologic agent of VL is Leishmania (Leishmania) infantum. The aim of this study was to evaluate the intraspecific genetic variability of parasites from humans and from dogs with different clinical forms of VL in five municipalities of BHMA using PCR-RFLP and two target genes: kinetoplast DNA (kDNA) and gp63. In total, 45 samples of DNA extracted from clinical samples (n = 35) or L. infantum culture (n = 10) were evaluated. These samples originated from three groups: adults (with or without Leishmania/HIV co-infection; n = 14), children (n = 18) and dogs (n = 13). The samples were amplified for the kDNA target using the MC1 and MC2 primers (447 bp), while the Sg1 and Sg2 (1330 bp) primers were used for the gp63 glycoprotein target gene. The restriction enzyme patterns of all the samples tested were monomorphic. These findings reveal a high degree of genetic homogeneity for the evaluated gene targets among L. infantum samples isolated from different hosts and representing different clinical forms of VL in the municipalities of BHMA studied.

Visible light responsive sulfated rare earth doped TiO(2)@fumed SiO(2) composites with mesoporosity: enhanced photocatalytic activity for methyl orange degradation.

PubMed

Zhan, Changchao; Chen, Feng; Yang, Jintao; Dai, Daoxing; Cao, Xiaohua; Zhong, Mingqiang

2014-02-28

Visible light (VL) responsive mesoporous sulfated rare earth ions (Nd(3+), La(3+), Y(3+)) incorporated TiO2@fumed SiO2 photocatalysts were prepared by sol-gel method with P123 (EO20PO70EO20) as a template. The resultant samples were characterized by X-ray diffraction (XRD), transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), N2 adsorption-desorption measurements (BET), UV-vis diffuse reflectance spectroscopy, photoluminescence (PL) spectra, Fourier transform infrared spectroscopy (FTIR) and thermal analyses (TG-DTA). In comparison with nondoped sample, RE-doped samples showed not only an increase in the surface areas and pore volumes, but also an inhibition of titania phase transition from anatase to rutile. Photo-degradation results revealed that RE-doped samples could greatly improve the photocatalytic activity, and the experimental degradation rates of methyl orange (MO) were higher than that catalyzed by undoped samples and Degussa P-25, obeyed the order of Nd(3+)>La(3+)>Y(3+). Nd-doped sample expressed the highest photoactivity and the optimal dosage was 0.25mol%, which resulted in MO degradation rates of 99.8% and 90.05% irradiation under UV for 60min and VL (λ>400nm) for 40h, respectively. The enhanced photocatalytic activity could be attributed to the higher specific area, good crystallinity, strong VL absorption and effective separation of photogenerated electron-hole pairs in the catalyst. Copyright © 2014 Elsevier B.V. All rights reserved.

Visceral leishmaniasis in Somalia: A review of epidemiology and access to care.

PubMed

Sunyoto, Temmy; Potet, Julien; Boelaert, Marleen

2017-03-01

Somalia, ravaged by conflict since 1991, has areas endemic for visceral leishmaniasis (VL), a deadly parasitic disease affecting the rural poor, internally displaced, and pastoralists. Very little is known about VL burden in Somalia, where the protracted crisis hampers access to health care. We reviewed evidence about VL epidemiology in Somalia and appraised control options within the context of this fragile state's health system. VL has been reported in Somalia since 1934 and has persisted ever since in foci in the southern parts of the country. The only feasible VL control option is early diagnosis and treatment, currently mostly provided by nonstate actors. The availability of VL care in Somalia is limited and insufficient at best, both in coverage and quality. Precarious security remains a major obstacle to reach VL patients in the endemic areas, and the true VL burden and its impact remain unknown. Locally adjusted, innovative approaches in VL care provision should be explored, without undermining ongoing health system development in Somalia. Ensuring VL care is accessible is a moral imperative, and the limitations of the current VL diagnostic and treatment tools in Somalia and other endemic settings affected by conflict should be overcome.

Visceral leishmaniasis in Somalia: A review of epidemiology and access to care

PubMed Central

Potet, Julien; Boelaert, Marleen

2017-01-01

Somalia, ravaged by conflict since 1991, has areas endemic for visceral leishmaniasis (VL), a deadly parasitic disease affecting the rural poor, internally displaced, and pastoralists. Very little is known about VL burden in Somalia, where the protracted crisis hampers access to health care. We reviewed evidence about VL epidemiology in Somalia and appraised control options within the context of this fragile state’s health system. VL has been reported in Somalia since 1934 and has persisted ever since in foci in the southern parts of the country. The only feasible VL control option is early diagnosis and treatment, currently mostly provided by nonstate actors. The availability of VL care in Somalia is limited and insufficient at best, both in coverage and quality. Precarious security remains a major obstacle to reach VL patients in the endemic areas, and the true VL burden and its impact remain unknown. Locally adjusted, innovative approaches in VL care provision should be explored, without undermining ongoing health system development in Somalia. Ensuring VL care is accessible is a moral imperative, and the limitations of the current VL diagnostic and treatment tools in Somalia and other endemic settings affected by conflict should be overcome. PMID:28278151

Development of anti-bovine IgA single chain variable fragment and its application in diagnosis of foot-and-mouth disease

PubMed Central

Sridevi, N. V.; Shukra, A. M.; Neelakantam, B.; Anilkumar, J.; Madhanmohan, M.; Rajan, S.; Dev Chandran

2014-01-01

Recombinant antibody fragments like single chain variable fragments (scFvs) represent an attractive yet powerful alternative to immunoglobulins and hold great potential in the development of clinical diagnostic/therapeutic reagents. Structurally, scFvs are the smallest antibody fragments capable of retaining the antigen-binding capacity of whole antibodies and are composed of an immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a flexible polypeptide linker. In the present study, we constructed a scFv against bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody against bovine IgA using recombinant DNA technology. The scFv was expressed in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC). The binding activity and specificity of the scFv was established by its non-reactivity toward other classes of immunoglobulins as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement of the scFv indicated that the recombinant antibody fragment had an affinity in picomolar range toward purified IgA. Furthermore, the scFv was used to develop a sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier animals. PMID:24678404

PROPOSED SIMPLE METHOD FOR ELECTROCARDIOGRAM RECORDING IN FREE-RANGING ASIAN ELEPHANTS (ELEPHAS MAXIMUS).

PubMed

Chai, Norin; Pouchelon, Jean Louis; Bouvard, Jonathan; Sillero, Leonor Camacho; Huynh, Minh; Segalini, Vincent; Point, Lisa; Croce, Veronica; Rigaux, Goulven; Highwood, Jack; Chetboul, Valérie

2016-03-01

Electrocardiography represents a relevant diagnostic tool for detecting cardiac disease in animals. Elephants can present various congenital and acquired cardiovascular diseases. However, few electrophysiologic studies have been reported in captive elephants, mainly due to challenging technical difficulties in obtaining good-quality electrocardiogram (ECG) tracings, and no data are currently available for free-ranging Asian elephants (Elephas maximus). The purpose of this pilot prospective study was to evaluate the feasibility of using a simple method for recording ECG tracings in wild, apparently healthy, unsedated Asian elephants (n = 7) in the standing position. Successful six-lead recordings (I, II, III, aVR, aVL, and aVF) were obtained, with the aVL lead providing the best-quality tracings in most animals. Variables measured in the aVL lead included heart rate, amplitudes and duration of the P waves, QRS complexes, T and U waves, and duration of the PR, QT, and QU intervals. A negative deflection following positive P waves, representative of an atrial repolarization wave (Ta wave), was observed for five out of the seven elephants.

Clinical and Mucosal Immune Correlates of HIV-1 Semen Levels in Antiretroviral-Naive Men

PubMed Central

Marsh, Angie K.; Huibner, Sanja; Shahabi, Kamnoosh; Liu, Cindy; Contente, Tania; Nagelkerke, Nico J. D.; Kovacs, Colin; Benko, Erika; Price, Lance; MacDonald, Kelly S.; Kaul, Rupert

2017-01-01

Abstract Background. This study was done to characterize parameters associated with semen human immunodeficiency virus (HIV)-1 ribonucleic acid (RNA) viral load (VL) variability in HIV-infected, therapy-naive men. Methods. Paired blood and semen samples were collected from 30 HIV-infected, therapy-naive men who have sex with men, and 13 participants were observed longitudinally for up to 1 year. Human immunodeficiency virus RNA, bacterial load by 16S RNA, herpesvirus (Epstein-Barr virus and cytomegalovirus [CMV]) shedding, and semen cytokines/chemokines were quantified, and semen T-cell subsets were assessed by multiparameter flow cytometry. Results. Semen HIV RNA was detected at 93% of visits, with >50% of men shedding high levels of virus (defined as >5000 copies/mL). In the baseline cross-sectional analysis, an increased semen HIV VL correlated with local CMV reactivation, the semen bacterial load, and semen inflammatory cytokines, particularly interleukin (IL)-8. T cells in semen were more activated than blood, and there was an increased frequency of Th17 cells and γδ-T-cells. Subsequent prospective analysis demonstrated striking interindividual variability in HIV and CMV shedding patterns, and only semen IL-8 levels and the blood VL were independently associated with semen HIV levels. Conclusions. Several clinical and immune parameters were associated with increased HIV semen levels in antiretroviral therapy-naive men, with induction of local proinflammatory cytokines potentially acting as a common pathway. PMID:28534034

More than the eyes can see: The worrying scenario of canine leishmaniasis in the Brazilian side of the triple border

PubMed Central

Pasquali, Aline Kuhn Sbruzzi; Pozzolo, Eliane Maria; Leandro, André de Souza; Chiyo, Luciana; Baggio, Rafael Antunes; Michaliszyn, Mario Sergio; Silva, Carlos; Cubas, Patrícia Hoerner; Peterlle, Ricardo; Paz, Otacilio Lopes de Souza; Belmonte, Ivana Lucia; Bisetto-Junior, Alceu

2017-01-01

A cross-sectional epidemiological study in the extreme-west of the state of Paraná was carried out to access the prevalence, distribution, and risk variables of canine Visceral Leishmaniases (cVL). This study was conducted in three areas, two cities of far west of Parana state: Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI), and along two transects between these two municipalities. To sample the entire urban area, the cities (FI and STI) were divided into a grid of squares of 400 m2 (patch). Among the 526 patches, 123 in FI, 40 in the transects and 33 in STI were selected according to the ‘worst scenario’ criterion. In the transect areas, in each 0.86 km five dogs from houses were surveyed to leishmaniasis. In each patch, blood of five dogs from houses (and from neighborhood when necessary) in the areas that seemed to be the most appropriate for the proliferation of vector were surveyed. The infection of the dogs by cVL were assessed using two serological tests were used (cELISA and TR-DPP®), and, for those seropositive for both methods, the PCR method were used. Moreover, dogs presenting clinical signs or cutaneous lesions were sampled to PCR. The identification of Leishmania species was confirmed using PCR-RFLP followed by DNA sequencing. Micro, meso and macro scale environmental variables were also surveyed and statistically analyzed. The prevalence rate Leishmania infantum was 23.8% in FI, 4.7% in STI and 9.1% in the transects areas. Among the extrinsic variables analysed, the number of vectors and the presence of infected dogs in neighbouring were positively correlated with the occurrence of infected dogs. Dog size was positively correlated with cVL infection, while the quality of the dog’s nutrition affected cVL negatively. As for cutaneous leishmaniasis (CL), the first registry of dogs infected with L. braziliensis in the region shows that there is potential for transmission in peri-urban areas, since environmental conditions allow the proliferation of vectors capable of transmitting this species of parasite. cVL is widely spread in FI, with high prevalence. This supports the hypothesis that the parasite has been present in the region for longer than previously believed, despite the fact that the presence of leishmaniais in the region has only been recognized recently. It is important to control the population of dogs infected with L. infantum (parasite and non-antibodies) to prevent the spread of the disease to other dogs and also to people in the region. PMID:29232388

More than the eyes can see: The worrying scenario of canine leishmaniasis in the Brazilian side of the triple border.

PubMed

Thomaz Soccol, Vanete; Pasquali, Aline Kuhn Sbruzzi; Pozzolo, Eliane Maria; Leandro, André de Souza; Chiyo, Luciana; Baggio, Rafael Antunes; Michaliszyn, Mario Sergio; Silva, Carlos; Cubas, Patrícia Hoerner; Peterlle, Ricardo; Paz, Otacilio Lopes de Souza; Belmonte, Ivana Lucia; Bisetto-Junior, Alceu

2017-01-01

A cross-sectional epidemiological study in the extreme-west of the state of Paraná was carried out to access the prevalence, distribution, and risk variables of canine Visceral Leishmaniases (cVL). This study was conducted in three areas, two cities of far west of Parana state: Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI), and along two transects between these two municipalities. To sample the entire urban area, the cities (FI and STI) were divided into a grid of squares of 400 m2 (patch). Among the 526 patches, 123 in FI, 40 in the transects and 33 in STI were selected according to the 'worst scenario' criterion. In the transect areas, in each 0.86 km five dogs from houses were surveyed to leishmaniasis. In each patch, blood of five dogs from houses (and from neighborhood when necessary) in the areas that seemed to be the most appropriate for the proliferation of vector were surveyed. The infection of the dogs by cVL were assessed using two serological tests were used (cELISA and TR-DPP®), and, for those seropositive for both methods, the PCR method were used. Moreover, dogs presenting clinical signs or cutaneous lesions were sampled to PCR. The identification of Leishmania species was confirmed using PCR-RFLP followed by DNA sequencing. Micro, meso and macro scale environmental variables were also surveyed and statistically analyzed. The prevalence rate Leishmania infantum was 23.8% in FI, 4.7% in STI and 9.1% in the transects areas. Among the extrinsic variables analysed, the number of vectors and the presence of infected dogs in neighbouring were positively correlated with the occurrence of infected dogs. Dog size was positively correlated with cVL infection, while the quality of the dog's nutrition affected cVL negatively. As for cutaneous leishmaniasis (CL), the first registry of dogs infected with L. braziliensis in the region shows that there is potential for transmission in peri-urban areas, since environmental conditions allow the proliferation of vectors capable of transmitting this species of parasite. cVL is widely spread in FI, with high prevalence. This supports the hypothesis that the parasite has been present in the region for longer than previously believed, despite the fact that the presence of leishmaniais in the region has only been recognized recently. It is important to control the population of dogs infected with L. infantum (parasite and non-antibodies) to prevent the spread of the disease to other dogs and also to people in the region.

Changing demographics of visceral leishmaniasis in northeast Brazil: Lessons for the future

PubMed Central

Lima, Iraci Duarte; Lima, Adila L. M.; Mendes-Aguiar, Carolina de Oliveira; Coutinho, José F. V.; Wilson, Mary E.; Pearson, Richard D.

2018-01-01

Background Visceral leishmaniasis (VL) caused by Leishmania infantum became a disease of urban areas in Brazil in the last 30 years and there has been an increase in asymptomatic L. infantum infection with these areas. Methodology/Principal findings A retrospective study of human VL was performed in the state of Rio Grande do Norte, Brazil, for the period of 1990–2014. The data were divided into five-time periods. For all VL cases, data on sex, age, nutritional status and childhood vaccination were collected. Geographic information system tools and statistical models were used to analyze the dispersion of human VL. The mean annual incidence of VL was 4.6 cases/100,000 inhabitants, with total 3,252 cases reported. The lethality rate was 6.4%. Over time the annual incidence of VL decreased in the 0–4 years (p<0.0001) and 5–9 (p <0.0001) age groups, but increased in ages 20–39 (p<0.001) and >40 years (p<0.0001). VL occurred more often in males (β2 = 2.5; p<0.0001). The decreased incidence of VL in children was associated with improved nutritional status and childhood immunizations including measles, poliomyelitis, BCG, and hepatitis B. Human VL correlated temporally and geographically with canine L. infantum infection (p = 0.002, R2 = 0.438), with rainfall and with Lutzomyia longipalpis density (r = 0.762). Overall, the incidence of VL decreased, while VL-AIDS increased, especially between 2010–2014. VL was more frequently found in areas that lacked urban infrastructure, detected by lack of garbage collection and sewers, whereas HIV infection was associated with higher levels of schooling and evidence of higher socioeconomic status. Conclusion/Significance The demographics of VL in northeastern Brazil have changed. Disease incidence has decreased in children and increased in adults. They were associated with improvements in nutrition, socioeconomic status and immunization rates. Concurrent VL-AIDS poses a serious challenge for the future. PMID:29509765

Cost of Pediatric Visceral Leishmaniasis Care in Morocco.

PubMed

Tachfouti, Nabil; Najdi, Adil; Alonso, Sergi; Sicuri, Elisa; Laamrani El Idrissi, Abderahmane; Nejjari, Chakib; Picado, Albert

2016-01-01

Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients. From March to June 2014 we conducted a survey in eight hospitals treating pediatric VL patients in Morocco. A pro-forma was used to collect demographic, clinical and management data from medical records. We specifically collected data on VL diagnosis and treatment. We also estimated the days of hospitalization and the time to start VL treatment. Costs were estimated by multiplying the use of resources in terms of number of days in hospital, tests performed and drugs provided by the official prices. For patients receiving part of their treatment at Primary Health Centers (PHC) we estimated the cost of administering the Glucantime as outpatient. We calculated the median cost per VL patient. We also estimated the cost of managing a VL case when different treatment strategies were applied: inpatient and outpatient. We obtained data from 127 VL patients. The median total cost per pediatric VL case in Morocco is 520 US$. The cost in hospitals applying an outpatient strategy is significantly lower (307 US$) than hospitals keeping the patients for the whole treatment (636 US$). However the outpatient strategy is not yet recommended as VL treatment for children in the Moroccan guidelines. VL diagnosis and treatment regimens should be standardized following the current guidelines in Morocco.

Cost of Pediatric Visceral Leishmaniasis Care in Morocco

PubMed Central

Alonso, Sergi; Sicuri, Elisa; Laamrani El Idrissi, Abderahmane; Nejjari, Chakib; Picado, Albert

2016-01-01

Background Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated. VL is endemic in Morocco and other countries in North Africa were it mainly affects children from rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow aspirates and serological tests are used to diagnose VL. Glucantime is the first line of treatment. The objective of this study was to report the costs associated to standard clinical management of pediatric VL from the provider perspective in Morocco. As a secondary objective we described the current clinical practices and the epidemiological characteristics of pediatric VL patients. Methods From March to June 2014 we conducted a survey in eight hospitals treating pediatric VL patients in Morocco. A pro-forma was used to collect demographic, clinical and management data from medical records. We specifically collected data on VL diagnosis and treatment. We also estimated the days of hospitalization and the time to start VL treatment. Costs were estimated by multiplying the use of resources in terms of number of days in hospital, tests performed and drugs provided by the official prices. For patients receiving part of their treatment at Primary Health Centers (PHC) we estimated the cost of administering the Glucantime as outpatient. We calculated the median cost per VL patient. We also estimated the cost of managing a VL case when different treatment strategies were applied: inpatient and outpatient. Results We obtained data from 127 VL patients. The median total cost per pediatric VL case in Morocco is 520 US$. The cost in hospitals applying an outpatient strategy is significantly lower (307 US$) than hospitals keeping the patients for the whole treatment (636 US$). However the outpatient strategy is not yet recommended as VL treatment for children in the Moroccan guidelines. VL diagnosis and treatment regimens should be standardized following the current guidelines in Morocco. PMID:27257808

Contribution of different antiretroviral regimens containing zidovudine, lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy.

PubMed

Sripan, Patumrat; Le Coeur, Sophie; Ingsrisawang, Lily; Cressey, Tim R; Bouazza, Naïm; Foissac, Frantz; Ngo-Giang-Huong, Nicole; Traisathit, Patrinee; Srirompotong, Ussanee; Ayudhaya, Orada Patamasingh Na; Puangsombat, Achara; Jungpipun, Jantana; Jittayanun, Kanokwan; Tréluyer, Jean-Marc; Jourdain, Gonzague; Lallemant, Marc; Urien, Saïk

2016-01-01

Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneficial effect of 3TC is crucial for prevention of mother-to-child transmission in women who receive ARVs late and with high pretreatment VL.

A novel Acute Retroviral Syndrome Severity Score predicts the key surrogate markers for HIV-1 disease progression.

PubMed

Braun, Dominique L; Kouyos, Roger; Oberle, Corinna; Grube, Christina; Joos, Beda; Fellay, Jacques; McLaren, Paul J; Kuster, Herbert; Günthard, Huldrych F

2014-01-01

Best long-term practice in primary HIV-1 infection (PHI) remains unknown for the individual. A risk-based scoring system associated with surrogate markers of HIV-1 disease progression could be helpful to stratify patients with PHI at highest risk for HIV-1 disease progression. We prospectively enrolled 290 individuals with well-documented PHI in the Zurich Primary HIV-1 Infection Study, an open-label, non-randomized, observational, single-center study. Patients could choose to undergo early antiretroviral treatment (eART) and stop it after one year of undetectable viremia, to go on with treatment indefinitely, or to defer treatment. For each patient we calculated an a priori defined "Acute Retroviral Syndrome Severity Score" (ARSSS), consisting of clinical and basic laboratory variables, ranging from zero to ten points. We used linear regression models to assess the association between ARSSS and log baseline viral load (VL), baseline CD4+ cell count, and log viral setpoint (sVL) (i.e. VL measured ≥90 days after infection or treatment interruption). Mean ARSSS was 2.89. CD4+ cell count at baseline was negatively correlated with ARSSS (p = 0.03, n = 289), whereas HIV-RNA levels at baseline showed a strong positive correlation with ARSSS (p<0.001, n = 290). In the regression models, a 1-point increase in the score corresponded to a 0.10 log increase in baseline VL and a CD4+ cell count decline of 12/µl, respectively. In patients with PHI and not undergoing eART, higher ARSSS were significantly associated with higher sVL (p = 0.029, n = 64). In contrast, in patients undergoing eART with subsequent structured treatment interruption, no correlation was found between sVL and ARSSS (p = 0.28, n = 40). The ARSSS is a simple clinical score that correlates with the best-validated surrogate markers of HIV-1 disease progression. In regions where ART is not universally available and eART is not standard this score may help identifying patients who will profit the most from early antiretroviral therapy.

Ecological parameters of the (S)-9-methylgermacrene-B population of the Lutzomyia longipalpis complex in a visceral leishmaniasis area in São Paulo state, Brazil.

PubMed

Galvis-Ovallos, Fredy; Casanova, Claudio; Sevá, Anaiá da Paixão; Galati, Eunice Aparecida Bianchi

2017-05-30

Visceral leishmaniasis (VL) is an important public health challenge in Brazil because of the high number of human and canine cases reported annually. Leishmania infantum is the etiological agent of VL and Lutzomyia longipalpis is its main vector. However, evidence suggests that this taxon constitutes a species complex. In Sao Paulo state, there are two populations of Lu. longipalpis, each secreting distinct pheromones, (S)-9-methylgermacrene-B and Cembrene 1; both have been associated with different patterns of VL transmission. The aim of the present study was to investigate the temporal distribution and natural infection of the (S)-9-methylgermacrene-B population of the Lu. longipalpis complex in a highly VL endemic area of Sao Paulo state to obtain information that may contribute to the surveillance of this zoonosis and to the planning of preventive and control measures. The study was carried out in Panorama municipality, Sao Paulo State. Captures were made during 24 months in seven domiciles. The relation between sand fly abundance and climatic variables, temperature and humidity, was analyzed and natural infection by Leishmania spp. in sand fly females was investigated by nested PCR. A total of 4120 sand flies, with predominance of Lu. longipalpis (97.2%) were captured. The highest averages of sand flies/night/trap occurred in the rainy season (November-March) and a positive, significant correlation between sand fly abundance and the temperature and humidity 20 days before the capture days was found. Leishmania infantum DNA was detected in three out of 250 pools of females analyzed, giving an estimated minimum infection rate of 1.2%. The identification of the climatic association between the high abundance of the vector in this highly endemic VL focus constitutes a fundamental point for evaluating future vector and dog control measures and this information increases the data of VL foci in Sao Paulo state that could contribute to the public health authorities in planning prevention and control measures. The identification of natural infection by Le. infantum in Lu. longipalpis specimens reinforces the importance of entomological surveillance activities in this municipality.

Production and characterization of a single-chain variable fragment linked alkaline phosphatase fusion protein for detection of O,O-diethyl organophosphorus pesticides in a one-step enzyme-linked immunosorbent assay

USDA-ARS?s Scientific Manuscript database

A single-chain variable fragment (scFv) and alkaline phosphatase (AP) fusion protein for detection of O, O-diethyl organophosphorus pesticides (OPs) was produced and characterized. The scFv gene was prepared by cloning VL and VH genes from a hybridoma cell secreting monoclonal antibody with broad-s...

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment.

PubMed

Schofield, J T; Barnes, J R; Crisp, D; Haberle, R M; Larsen, S; Magalhães, J A; Murphy, J R; Seiff, A; Wilson, G

1997-12-05

The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24.7 hours). The atmospheric structure and the weather record are similar to those observed by the Viking 1 lander (VL-1) at the same latitude, altitude, and season 21 years ago, but there are differences related to diurnal effects and the surface properties of the landing site. These include a cold nighttime upper atmosphere; atmospheric temperatures that are 10 to 12 degrees kelvin warmer near the surface; light slope-controlled winds; and dust devils, identified by their pressure, wind, and temperature signatures. The results are consistent with the warm, moderately dusty atmosphere seen by VL-1.

Synthesis and polymorphic control for visible light active titania nanoparticles

NASA Astrophysics Data System (ADS)

Kaewgun, Sujaree

Titania (TiO2) is useful for many applications in photocatalysis, antimicrobials, pigment, deodorization, and decomposition of harmful organics and undesirable compounds in the air and waste water under UV irradiation. Among the three phases of TiO2, Rutile, Anatase, and Brookite, studies have been more focused on the anatase and rutile phases. Pure brookite is the most difficult phase to prepare, even under hydrothermal conditions. Predominantly brookite phase TiO2 nanoparticles were prepared by the Water-based Ambient Condition Sol (WACS) process in our laboratory. The objectives of this research were to enhance visible light active (VLA) photocatalytic properties of polymorphic brookite TiO2 by minimizing the lattice defects and narrowing band gap of titania by nitrogen and/or carbon chromophone, and to investigate the deactivation, reusability, and regeneration of the VLA titania in order to design better titania catalysts for organic compound degradation applications. In order to study the influence of hydroxyl content on photocatalytic activities (PCAs) of polymorphic titania nanoparticles, the WACS samples were post-treated by a Solvent-based Ambient Condition Sol (SACS) process in sec-butanol (sec-BuOH). All samples were characterized for phase composition, surface area, hydroxyl contamination, and particle morphology by x-ray diffraction, N2 physisorption, FT-IR, solid state 1H NMR and scanning electron microscopy, and then compared to a commercial titania, Degussa P25. Evaluation of methyl orange (MO) degradation under UV irradiation results showed that the lower lattice hydroxyl content in SACS titania enhanced the PCA. As-prepared titania and SACS samples, which have similar surface areas and crystallinity, were compared in order to prove that the superior PCA came from the reduction in the lattice hydroxyl content. To enhance PCA and VLA properties of WACS, an alternative high boiling point polar solvent, N-methylpyrrolidone (NMP), was utilized in the SACS process at a higher treatment temperature to modify polymorphic titania nanoparticles. This SACS sample was called "SACS-NMP". SACS, using NMP as the solvent, could also extract lattice hydroxyls, and decorate nitrogen on the titania surface. The PCA of SACS-NMP was superior to that of SACS-sec-BuOH. Nitrogen incorporation of SACS-NMP titania was investigated by CHN analysis and x-ray photoelectron spectroscopy (XPS). VL absorbance for all samples was characterized by UV-Vis absorption spectrophotometry. PCA of MO degradation under UV and VL showed that SACS-NMP is a powerful treatment to enhance PCA by minimizing lattice hydroxyls and doping the titania surface with nitrogen. The effect of calcination conditions on SACS-NMP samples was also studied. The calcination conditions, especially the temperature and calcination atmosphere, have an influence on the BET surface area, crystallite size, titania phase content, and PCA under VL irradiation. SACS-NMP samples calcined in air at 200°C for 2 hours showed the best VL activated photocatalytic performance in this research. Additionally, the SACS-NMP sample exhibited superior VL properties to several available reference anatase titania samples. This could be explained as the effective charge separation by the intercrystalline electron transport from brookite to anatase grains complemented by strong VL absorption by the nitrogen species in NMP. The deactivation and regeneration of the VLA titania were investigated and compared to a commercial titania, Kronos VLP7000. PCA of the titania under VL for MO decolorization gradually decreased with increasing testing time and the number of runs. The cause of the deactivation was identified as the deposition of the decomposed MO or the carbonaceous deposit. Among the possible regeneration procedures for used SACS-NMP samples, methanol washing was shown to be the most effective up to ˜80% of the PCA recovery. Accordingly, the SACS-NMP samples could not be completely recovered since a regeneration process would possibly remove some of nitrogen species responsible for the VL properties.

Reactibodies generated by kinetic selection couple chemical reactivity with favorable protein dynamics

PubMed Central

Smirnov, Ivan; Carletti, Eugénie; Kurkova, Inna; Nachon, Florian; Nicolet, Yvain; Mitkevich, Vladimir A.; Débat, Hélène; Avalle, Bérangère; Belogurov, Alexey A.; Kuznetsov, Nikita; Reshetnyak, Andrey; Masson, Patrick; Tonevitsky, Alexander G.; Ponomarenko, Natalia; Makarov, Alexander A.; Friboulet, Alain; Tramontano, Alfonso; Gabibov, Alexander

2011-01-01

Igs offer a versatile template for combinatorial and rational design approaches to the de novo creation of catalytically active proteins. We have used a covalent capture selection strategy to identify biocatalysts from within a human semisynthetic antibody variable fragment library that uses a nucleophilic mechanism. Specific phosphonylation at a single tyrosine within the variable light-chain framework was confirmed in a recombinant IgG construct. High-resolution crystallographic structures of unmodified and phosphonylated Fabs display a 15-Å-deep two-chamber cavity at the interface of variable light (VL) and variable heavy (VH) fragments having a nucleophilic tyrosine at the base of the site. The depth and structure of the pocket are atypical of antibodies in general but can be compared qualitatively with the catalytic site of cholinesterases. A structurally disordered heavy chain complementary determining region 3 loop, constituting a wall of the cleft, is stabilized after covalent modification by hydrogen bonding to the phosphonate tropinol moiety. These features and presteady state kinetics analysis indicate that an induced fit mechanism operates in this reaction. Mutations of residues located in this stabilized loop do not interfere with direct contacts to the organophosphate ligand but can interrogate second shell interactions, because the H3 loop has a conformation adjusted for binding. Kinetic and thermodynamic parameters along with computational docking support the active site model, including plasticity and simple catalytic components. Although relatively uncomplicated, this catalytic machinery displays both stereo- and chemical selectivity. The organophosphate pesticide paraoxon is hydrolyzed by covalent catalysis with rate-limiting dephosphorylation. This reactibody is, therefore, a kinetically selected protein template that has enzyme-like catalytic attributes. PMID:21896761

Fundamental characteristics of the expressed immunoglobulin VH and VL repertoire in different canine breeds in comparison with those of humans and mice.

PubMed

Steiniger, Sebastian C J; Dunkle, William E; Bammert, Gary F; Wilson, Thomas L; Krishnan, Abhiram; Dunham, Steven A; Ippolito, Gregory C; Bainbridge, Graeme

2014-05-01

Complementarity determining regions (CDR) are responsible for binding antigen and provide substantial diversity to the antibody repertoire, with VH CDR3 of the immunoglobulin variable heavy (VH) domain playing a dominant role. In this study, we examined 1200 unique canine VH and 500 unique variable light (VL) sequences of large and small canine breeds derived from peripheral B cells. Unlike the human and murine repertoire, the canine repertoire is heavily dominated by the Canis lupus familiaris IGHV1 subgroup, evolutionarily closest to the human IGHV3 subgroup. Our studies clearly show that the productive canine repertoire of all analyzed breeds shows similarities to both human and mouse; however, there are distinct differences in terms of VH CDR3 length and amino acid paratope composition. In comparison with the human and murine antibody repertoire, canine VH CDR3 regions are shorter in length than the human counterparts, but longer than the murine VH CDR3. Similar to corresponding human and mouse VH CDR3, the amino acids at the base of the VH CDR3 loop are strictly conserved. For identical CDR positions, there were significant changes in chemical paratope composition. Similar to human and mouse repertoires, the neutral amino acids tyrosine, glycine and serine dominate the canine VH CDR3 interval (comprising 35%) although the interval is nonetheless relatively depleted of tyrosine when compared to human and mouse. Furthermore, canine VH CDR3 displays an overrepresentation of the neutral amino acid threonine and the negatively charged aspartic acid while proline content is similar to that in the human repertoire. In general, the canine repertoire shows a bias towards small, negatively charged amino acids. Overall, this analysis suggests that functional canine therapeutic antibodies can be obtained from human and mouse sequences by methods of speciation and affinity maturation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Better management of cow's milk allergy using a very low dose food challenge test: a retrospective study.

PubMed

Okada, Yu; Yanagida, Noriyuki; Sato, Sakura; Ebisawa, Motohiro

2015-07-01

Low dose reactive cow's milk (CM) allergic children are at high risk of persistent CM allergy and a positive oral food challenge (OFC). The present study aimed to evaluate if the results of a very low dose (VL) OFC with these children contributes to better management of CM allergy. We retrospectively reviewed subjects with CM allergy who underwent a VL OFC with 3 mL heated CM and had a previous allergic reaction to <25 mL heated CM in the 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant, and subjects who failed were defined as VL reactive. VL tolerant subjects increased the dose to 25 mL heated CM either during an OFC in our hospital or gradually at home. Of the 83 subjects (median age, 4.3 years; range, 1.0-12.9 years) who were included, 41 (49.4%) were VL tolerant, and 42 (51.6%) were VL reactive. Thirty-nine VL reactive subjects had skin and/or respiratory symptoms during the OFC. Most reactions could be treated with an antihistamine and/or a nebulized β2 agonist. The VL tolerant subjects consumed 3 mL heated CM or 10 g butter. Within the year following the OFC, 18 VL tolerant subjects (45.0%), but none of the VL reactive subjects, were able to consume 25 mL heated CM (p < 0.001). A VL OFC allows the management of some low dose reactive CM allergic children to change from complete avoidance to partial intake of CM. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Consecutive rebounds in plasma viral load are associated with virological failure at 52 weeks among HIV-infected patients.

PubMed

Raboud, Janet M; Rae, Sandra; Woods, Ryan; Harris, Marianne; Montaner, Julio S G

2002-08-16

To describe the characteristics and predictors of transient plasma viral load (pVL) rebounds among patients on stable antiretroviral therapy and to determine the effect of one or more pVL rebounds on virological response at week 52. Individual data were combined from 358 patients from the INCAS, AVANTI-2 and AVANTI-3 studies. Logistic regression models were used to determine the relationship between the magnitude of an increase in pVL and the probability of returning to the lower limit of quantification (LLOQ: 20-50 copies/ml) and to determine the odds of virological success at 52 weeks associated with single and consecutive pVL rebounds. A group of 165 patients achieved a pVL nadir < LLOQ; of these, 85 patients experienced pVL rebounds within 52 weeks. The probability of a pVL rebound was greater among patients who did not adhere to treatment (68% vs 49%; P < 0.05). The probability of reachieving virological suppression after a pVL rebound was not associated with the magnitude of the rebound [odds ratio (OR), 0.86; P = 0.56] but was associated with triple therapy (OR, 2.22; P = 0.06) or non-adherence (OR, 0.40; P = 0.04). The probability of virological success at week 52 was not associated with an isolated pVL rebound but was less likely after detectable pVL at two consecutive visits. An isolated pVL rebound was not associated with virological success at 52 weeks but rebounds at two consecutive visits decreased the probability of later virological success. Given their high risk of short-term virological failure, patients who present with consecutive detectable pVL measurements following complete suppression should be considered ideal candidates for intervention studies.

78 FR 53175 - The Northwestern Mutual Life Insurance Company, et al.;

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-28

...] The Northwestern Mutual Life Insurance Company, et al.; Notice of Application Agency: Securities and... the Act from Section 17(a) of the Act. Applicants: The Northwestern Mutual Life Insurance Company (the... Account B, the ``Annuity Accounts'') and Northwestern Mutual Variable Life Account (``VL Account'') and...

The lost hope of elimination of Kala-azar (visceral leishmaniasis) by 2010 and cyclic occurrence of its outbreak in India, blame falls on vector control practices or co-infection with human immunodeficiency virus or therapeutic modalities?

PubMed

Muniaraj, Mayilsamy

2014-01-01

The Kala-azar/visceral leishmaniasis (VL) turns epidemic form once in every 15 years in the endemic regions of Indian subcontinent. The goal of elimination of Kala-azar from India by 2010 was lost despite paramount efforts taken by the Government of India and World Health Organization and Regional Office for South East Asia. The main objective of this review was to elucidate the possible reason for the failure of Kala-azar elimination program and to suggest possible remedial measures to achieve the goal in future. The annual numbers of VL cases and deaths recorded in India since 1977 were plotted on a graph, to see if the temporal trends could be associated with changes in the vector control practices or co-infection with human immunodeficiency virus (HIV) or therapeutic modalities used against VL. The VL cases flares up whenever the effect of dichlorodiphenyltrichloroethane (DDT) diminished after the withdrawal of spray. The fading effectiveness was clearly correlated with an increasing number of VL cases. Therapeutic modalities were found to be highly correlating with VL mortality not with VL morbidity. The diminishing efficacy of first and second line drugs and the introduction of new drugs and drugs combination were responsible for ups and downs in the VL mortality. The VL mortality is constantly declining since 1993, but cases started increasing from 2003 to 2007 and then recently again from 2010 to 2011. This shows a serious lacuna in the vector control practices applied. The extent of HIV co-infection did not show any correlation with number/trend of VL cases or death over the study period. It is concluded that, by strict vector control practices, the VL cases can be reduced and by applying proper therapeutic strategies, the VL mortality can be reduced. HIV-VL co-infection does not seem to be in a worried stage.

Meta-analysis of two randomized controlled trials comparing combined zidovudine and didanosine therapy with combined zidovudine, didanosine, and nevirapine therapy in patients with HIV. INCAS study team.

PubMed

Raboud, J M; Rae, S; Vella, S; Harrigan, P R; Bucciardini, R; Fragola, V; Ricciardulli, D; Montaner, J S

1999-11-01

To extend the range of CD4 counts in which a plasma viral load nadir (pVL) <20 copies/ml was known to be predictive of the duration of virologic response. To determine whether baseline pVL is predictive of virologic response during the study periods. A meta-analysis was conducted of the original individual patient data from two randomized controlled trials comparing zidovudine (ZDV)/didanosine (ddI) with ZDV/ddI/nevirapine (NVP). In total, 87 patients received ZDV/ddI and 83 received ZDV/ddI/NVP. Study subjects on triple therapy with baseline pVL <100,000 copies/ml were more likely to achieve a pVL <400 copies/ml (odds ratio [OR] = 2.49; p = .02) and <20 copies/ml (OR = 4.76; p = .001) during the trial than those with baseline pVL > 100,000 copies/ml. Among triple therapy patients, the relative risk of virologic failure was higher for patients with higher baseline pVL (rate ratio [RR] = 2.51/log10 copies/ ml; p = .01), after controlling for compliance and pVL nadir. The relative risks of virologic failure associated with pVL nadir <20 copies/ml and between 21 and 400 copies/ml were .04 (p = .0001) and .56 (p = .26), respectively, compared with patients with a pVL nadir >400 copies/ml. We have extended our earlier results that achieving a pVL nadir <20 copies/ml is important for maintaining virologic suppression. In particular, we have demonstrated that a pVL nadir <20 copies/ml is at least fivefold more protective against virologic failure than achieving a pVL nadir between 20 and 400 copies/ml. Baseline pVL is significantly associated with the probability of achieving and sustaining virologic suppression.

Endemic characteristics of infantile visceral leishmaniasis in the People's Republic of China.

PubMed

Fu, Qing; Li, Shi-Zhu; Wu, Wei-Ping; Hou, Yan-Yan; Zhang, Song; Feng, Yu; Zhang, Li-Ping; Tang, Lin-Hua

2013-05-17

Visceral leishmaniasis (VL) was once a severe parasitic disease in China. Thanks to the great efforts of integrated control, VL was eliminated in most epidemic areas, except for certain western provinces (autonomous region) at the end of 1950s. From then on, VL gained less attention and has seemed to spread, especially in the last 15 years. Infants are the most important population threatened by VL. However, there have been few studies on the endemic characteristics of infantile VL in China. Infantile VL cases were collected from the online National Infectious Diseases Reporting System (NIDRS). Statistical description and inference was used to reveal the endemic characteristics in gender, age group, time and regionalism. Spatial analysis was carried out to explore the high risk area for infantile VL in China. A total of 1093 infantile VL cases were reported from 2006 to 2012. There was no statistically significant difference in gender over time. The minimum, maximum and mean age of these cases was 1.1, 35.9 and 13.8 months, respectively. Among them 86.92% were under 2 years of age, and there was a statistically significant difference among age groups over time. An incidence peak appeared in 2008-2009, most cases were distributed in the months September to December, and there was a tail-raising effect in the coming two months of the next year. More than 98% of cases were reported in Xinjiang Uygur Autonomous Region, Gansu Province and Sichuan Province, accounting for 61.02%, 32.75% and 4.57%, respectively. A total of 56 counties reported infantile VL cases, with the cumulative incidence ranging from 0.02 to 24.57%. There were two main zones of high endemicity for infantile VL in China. The monthly incidence clearly coincides with the number of towns where infantile VL cases were reported. Three fatalities were reported during the study period, the case fatality rate was 2.75‰. The endemic situation of infantile VL is serious, and there are several active foci of infantile VL prevalence in China. VL has emerged as a severe threat to infants of endemic regions in China.

Endemic characteristics of infantile visceral leishmaniasis in the People’s Republic of China

PubMed Central

2013-01-01

Background Visceral leishmaniasis (VL) was once a severe parasitic disease in China. Thanks to the great efforts of integrated control, VL was eliminated in most epidemic areas, except for certain western provinces (autonomous region) at the end of 1950s. From then on, VL gained less attention and has seemed to spread, especially in the last 15 years. Infants are the most important population threatened by VL. However, there have been few studies on the endemic characteristics of infantile VL in China. Methods Infantile VL cases were collected from the online National Infectious Diseases Reporting System (NIDRS). Statistical description and inference was used to reveal the endemic characteristics in gender, age group, time and regionalism. Spatial analysis was carried out to explore the high risk area for infantile VL in China. Results A total of 1093 infantile VL cases were reported from 2006 to 2012. There was no statistically significant difference in gender over time. The minimum, maximum and mean age of these cases was 1.1, 35.9 and 13.8 months, respectively. Among them 86.92% were under 2 years of age, and there was a statistically significant difference among age groups over time. An incidence peak appeared in 2008-2009, most cases were distributed in the months September to December, and there was a tail-raising effect in the coming two months of the next year. More than 98% of cases were reported in Xinjiang Uygur Autonomous Region, Gansu Province and Sichuan Province, accounting for 61.02%, 32.75% and 4.57%, respectively. A total of 56 counties reported infantile VL cases, with the cumulative incidence ranging from 0.02 to 24.57%. There were two main zones of high endemicity for infantile VL in China. The monthly incidence clearly coincides with the number of towns where infantile VL cases were reported. Three fatalities were reported during the study period, the case fatality rate was 2.75‰. Conclusions The endemic situation of infantile VL is serious, and there are several active foci of infantile VL prevalence in China. VL has emerged as a severe threat to infants of endemic regions in China. PMID:23680411

Synthesis and characterization of novel plasmonic Ag/AgX-CNTs (X = Cl, Br, I) nanocomposite photocatalysts and synergetic degradation of organic pollutant under visible light.

PubMed

Shi, Huixian; Chen, Jiangyao; Li, Guiying; Nie, Xin; Zhao, Huijun; Wong, Po-Keung; An, Taicheng

2013-08-14

A series of novel well-defined Ag/AgX (X = Cl, Br, I) loaded carbon nanotubes (CNTs) composite photocatalysts (Ag/AgX-CNTs) were fabricated for the first time via a facile ultrasonic assistant deposition-precipitation method at the room temperature (25 ± 1 °C). X-ray diffraction, X-ray photoelectron spectroscopy, nitrogen adsorption-desorption analysis, scanning electron microscopy, and ultraviolet-visible light absorption spectra analysis were used to characterize the structure, morphology, and optical properties of the as-prepared photocatalysts. Results confirmed the existence of the direct interfacial contact between Ag/AgX nanoparticles and CNTs, and Ag/AgX-CNTs nanocomposites exhibit superior absorbance in the visible light (VL) region owing to the surface plasmon resonance (SPR) of Ag nanoparticles. The fabricated composite photocatalysts were employed to remove 2,4,6-tribromophenol (TBP) in aqueous phase. A remarkably enhanced VL photocatalytic degradation efficiency of Ag/AgX-CNTs nanocomposites was observed when compared to that of pure AgX or CNTs. The photocatalytic activity enhancement of Ag/AgX-CNTs was due to the effective electron transfer from photoexcited AgX and plasmon-excited Ag(0) nanoparticles to CNTs. This can effectively decrease the recombination of electron-hole pairs, lead to a prolonged lifetime of the photoholes that promotes the degradation efficiency.

Preparation of carbon nanotubes/BiOBr composites with higher visible light photocatalytic activity

NASA Astrophysics Data System (ADS)

You, Y. J.; Zhang, Y. X.; Li, R. R.; Li, C. H.

2014-12-01

A novel flower-like photocatalyst CNTs/BiOBr was successfully prepared by a facile hydrothermal method. The morphology and the physicochemical properties of the prepared samples were investigated using scanning electron microscopy (SEM), X-ray diffraction (XRD), energy dispersive X-ray spectrometry (EDX), and UV-visible diffuse reflectance spectroscopy (UV-vis DRS). The photocatalytic activity was evaluated by degradation of Rhodamin B (RhB) dye. It was demonstrated that CNTs/BiOBr photocatalyst could effectively photodegrade RhB under visible light (VL) irradiation.

When patients fail UNAIDS' last 90 - the "failure cascade" beyond 90-90-90 in rural Lesotho, Southern Africa: a prospective cohort study.

PubMed

Labhardt, Niklaus Daniel; Ringera, Isaac; Lejone, Thabo Ishmael; Cheleboi, Molisana; Wagner, Sarah; Muhairwe, Josephine; Klimkait, Thomas

2017-07-19

HIV-infected individuals on first-line antiretroviral therapy (ART) in resource-limited settings who do not achieve the last "90" (viral suppression) enter a complex care cascade: enhanced adherence counselling (EAC), repetition of viral load (VL) and switch to second-line ART aiming to achieve resuppression. This study describes the "failure cascade" in patients in Lesotho. Patients aged ≥16 years on first-line ART at 10 facilities in rural Lesotho received a first-time VL in June 2014. Those with VL ≥80 copies/mL were included in a cohort. The care cascade was assessed at four points: attendance of EAC, result of follow-up VL after EAC, switch to second-line in case of sustained unsuppressed VL and outcome 18 months after the initial unsuppressed VL. Multivariate logistic regression was used to assess predictors of being retained in care with viral resuppression at follow-up. Out of 1563 patients who underwent first-time VL, 138 (8.8%) had unsuppressed VL in June 2014. Out of these, 124 (90%) attended EAC and 116 (84%) had follow-up VL (4 died, 2 transferred out, 11 lost, 5 switched to second-line before follow-up VL). Among the 116 with follow-up VL, 36 (31%) achieved resuppression. Out of the 80 with sustained unsuppressed VL, 58 were switched to second-line, the remaining continued first line. At 18 months' follow-up in December 2015, out of the initially 138 with unsuppressed VL, 56 (41%) were in care and virally suppressed, 37 (27%) were in care with unsuppressed VL and the remaining 45 (33%) were lost, dead, transferred to another clinic or without documented VL. Achieving viral resuppression after EAC (adjusted odds ratio (aOR): 5.02; 95% confidence interval: 1.14-22.09; p  = 0.033) and being switched to second-line in case of sustained viremia after EAC (aOR: 7.17; 1.90-27.04; p  = 0.004) were associated with being retained in care and virally suppressed at 18 months of follow-up. Age, gender, education, time on ART and level of VL were not associated. In this study in rural Lesotho, outcomes along the "failure cascade" were poor. To improve outcomes in this vulnerable patient group who fails the last "90", programmes need to focus on timely EAC and switch to second line for cases with continuous viremia despite EAC.

Visceral Leishmaniasis in Ethiopia: An Evolving Disease

PubMed Central

Leta, Samson; Dao, Thi Ha Thanh; Mesele, Frehiwot; Alemayehu, Gezahegn

2014-01-01

Visceral leishmaniasis (also known as kala-azar) is classified as one of the most neglected tropical diseases. It is becoming a growing health problem in Ethiopia, with endemic areas that are continually spreading. The annual burden of visceral leishmaniasis (VL) in Ethiopia is estimated to be between 4,500 and 5,000 cases, and the population at risk is more than 3.2 million. There has been a change in the epidemiology of VL in Ethiopia. Over the last decades, almost all cases and outbreaks of VL were reported from arid and semi-arid parts of the country; however, recent reports indicated the introduction of this disease into the highlands. Migration of labourers to and from endemic areas, climatic and environmental changes, and impaired immunity due to HIV/AIDS and malnutrition resulted in the change of VL epidemiology. HIV spurs the spread of VL by increasing the risk of progression from asymptomatic infection towards full VL. Conversely, VL accelerates the onset of AIDS. In Ethiopia, VL epidemiology remains complex because of the diversity of risk factors involved, and its control is becoming an increasing challenge. This paper reviews the changes in epidemiology of VL in Ethiopia and discusses some of the possible explanations for these changes. The prospects for novel approaches to VL control are discussed, as are the current and future challenges facing Ethiopia's public health development program. PMID:25188253

Discordance of Self-report and Laboratory Measures of HIV Viral Load Among Young Men Who Have Sex with Men and Transgender Women in Chicago: Implications for Epidemiology, Care, and Prevention.

PubMed

Mustanski, Brian; Ryan, Daniel T; Remble, Thomas A; D'Aquila, Richard T; Newcomb, Michael E; Morgan, Ethan

2018-04-10

Suppressing HIV viral load through daily antiretroviral therapy (ART) substantially reduces the risk of HIV transmission, however, the potential population impact of treatment as prevention (TasP) is mitigated due to challenges with sustained care engagement and ART adherence. For an undetectable viral load (VL) to inform decision making about transmission risk, individuals must be able to accurately classify their VL as detectable or undetectable. Participants were 205 HIV-infected young men who have sex with men (YMSM) and transgender women (TGW) from a large cohort study in the Chicago area. Analyses examined correspondence among self-reported undetectable VL, study-specific VL, and most recent medical record VL. Among HIV-positive YMSM/TGW, 54% had an undetectable VL (< 200 copies/mL) via study-specific laboratory testing. Concordance between self-report and medical record VL values was 80% and between self-report and study-specific laboratory testing was 73%; 34% of participants with a detectable study-specific VL self-reported an undetectable VL at last medical visit, and another 28% reported not knowing their VL status. Periods of lapsed viral suppression between medical visits may represent a particular risk for the TasP strategy among YMSM/TGW. Strategies for frequent viral load monitoring, that are not burdensome to patients, may be necessary to optimize TasP.

Better management of wheat allergy using a very low-dose food challenge: A retrospective study.

PubMed

Okada, Yu; Yanagida, Noriyuki; Sato, Sakura; Ebisawa, Motohiro

2016-01-01

Low-dose reactive wheat-allergic children are at a high risk of a positive oral food challenge (OFC). The present study aimed to evaluate whether the results of a very low-dose (VL) OFC would contribute to better wheat allergy management in this population. We retrospectively reviewed wheat-allergic subjects who underwent a VL OFC with 2 g of udon noodles (equivalent to 53 mg of wheat protein) and had a previous allergic reaction to <15 g of udon noodles (equivalent to 400 mg of wheat protein) within 2 years before the OFC. Subjects who passed the OFC were defined as VL tolerant; those who failed were considered VL reactive. In VL tolerant subjects, the dose was increased to 15 g of udon noodles either during an OFC in our hospital or gradually at home. Of the 57 included subjects (median age, 2.9 years; range, 1.0-11.8 years), 32 (56%) were VL tolerant and 25 (44%) were VL reactive. Most reactions during the OFC could be treated with an antihistamine and/or a nebulized β2 agonist. VL tolerant subjects consumed 2 g of udon noodles or a seasoning containing wheat. Within a year after the OFC, 18 VL tolerant subjects (56%), but no VL reactive subjects, were able to consume 15 g of udon noodles (p < 0.001). A VL OFC can shift the management of some low-dose reactive wheat-allergic children from complete avoidance to partial wheat intake. Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Complementary roles for amygdala and periaqueductal gray in temporal-difference fear learning.

PubMed

Cole, Sindy; McNally, Gavan P

2009-01-01

Pavlovian fear conditioning is not a unitary process. At the neurobiological level multiple brain regions and neurotransmitters contribute to fear learning. At the behavioral level many variables contribute to fear learning including the physical salience of the events being learned about, the direction and magnitude of predictive error, and the rate at which these are learned about. These experiments used a serial compound conditioning design to determine the roles of basolateral amygdala (BLA) NMDA receptors and ventrolateral midbrain periaqueductal gray (vlPAG) mu-opioid receptors (MOR) in predictive fear learning. Rats received a three-stage design, which arranged for both positive and negative prediction errors producing bidirectional changes in fear learning within the same subjects during the test stage. Intra-BLA infusion of the NR2B receptor antagonist Ifenprodil prevented all learning. In contrast, intra-vlPAG infusion of the MOR antagonist CTAP enhanced learning in response to positive predictive error but impaired learning in response to negative predictive error--a pattern similar to Hebbian learning and an indication that fear learning had been divorced from predictive error. These findings identify complementary but dissociable roles for amygdala NMDA receptors and vlPAG MOR in temporal-difference predictive fear learning.

When monoclonal antibodies are not monospecific: Hybridomas frequently express additional functional variable regions

PubMed Central

Bradbury, Andrew R. M.; Trinklein, Nathan D.; Wilkinson, Ian C.; Tandon, Atul K.; Anderson, Stephen; Bladen, Catherine L.; Jones, Brittany; Aldred, Shelley Force; Bestagno, Marco; Burrone, Oscar; Maynard, Jennifer; Ferrara, Fortunato; Görnemann, Janina; Glanville, Jacob; Wolf, Philipp; Frenzel, Andre; Wong, Julin; Koh, Xin Yu; Eng, Hui-Yan; Lane, David; Lefranc, Marie-Paule; Clark, Mike

2018-01-01

ABSTRACT Monoclonal antibodies are commonly assumed to be monospecific, but anecdotal studies have reported genetic diversity in antibody heavy chain and light chain genes found within individual hybridomas. As the prevalence of such diversity has never been explored, we analyzed 185 random hybridomas, in a large multicenter dataset. The hybridomas analyzed were not biased towards those with cloning difficulties or known to have additional chains. Of the hybridomas we evaluated, 126 (68.1%) contained no additional productive chains, while the remaining 59 (31.9%) contained one or more additional productive heavy or light chains. The expression of additional chains degraded properties of the antibodies, including specificity, binding signal and/or signal-to-noise ratio, as determined by enzyme-linked immunosorbent assay and immunohistochemistry. The most abundant mRNA transcripts found in a hybridoma cell line did not necessarily encode the antibody chains providing the correct specificity. Consequently, when cloning antibody genes, functional validation of all possible VH and VL combinations is required to identify those with the highest affinity and lowest cross-reactivity. These findings, reflecting the current state of hybridomas used in research, reiterate the importance of using sequence-defined recombinant antibodies for research or diagnostic use. PMID:29485921

Functional and Muscle-Size Effects of Flywheel Resistance Training with Eccentric-Overload in Professional Handball Players.

PubMed

Maroto-Izquierdo, Sergio; García-López, David; de Paz, José A

2017-12-01

The aim of the study was to analyse the effects of 6 week (15 sessions) flywheel resistance training with eccentric-overload (FRTEO) on different functional and anatomical variables in professional handball players. Twenty-nine athletes were recruited and randomly divided into two groups. The experimental group (EXP, n = 15) carried out 15 sessions of FRTEO in the leg-press exercise, with 4 sets of 7 repetitions at a maximum-concentric effort. The control group (CON, n = 14) performed the same number of training sessions including 4 sets of 7 maximum repetitions (7RM) using a weight-stack leg-press machine. The results which were measured included maximal dynamic strength (1RM), muscle power at different submaximal loads (PO), vertical jump height (CMJ and SJ), 20 m sprint time (20 m), T-test time (T-test), and Vastus-Lateralis muscle (VL) thickness. The results of the EXP group showed a substantially better improvement (p < 0.05-0.001) in PO, CMJ, 20 m, T-test and VL, compared to the CON group. Moreover, athletes from the EXP group showed significant improvements concerning all the variables measured: 1RM (ES = 0.72), PO (ES = 0.42 - 0.83), CMJ (ES = 0.61), SJ (ES = 0.54), 20 m (ES = 1.45), T-test (ES = 1.44), and VL (ES = 0.63 - 1.64). Since handball requires repeated short, explosive effort such as accelerations and decelerations during sprints with changes of direction, these results suggest that FRTEO affects functional and anatomical changes in a way which improves performance in well-trained professional handball players.

Lung volume is a determinant of aerosol bolus dispersion.

PubMed

Schulz, Holger; Eder, Gunter; Heyder, Joachim

2003-01-01

The technique of inhaling a small volume element labeled with particles ("aerosol bolus") can be used to assess convective gas mixing in the lung. While a bolus undergoes mixing in the lung, particles are dispersed in an increasing volume of the respired air. However, determining factors of bolus dispersion are not yet completely understood. The present study tested the hypothesis that bolus dispersion is related, among others, to the total volume in which the bolus is allowed to mix--i.e., to the individual lung size. Bolus dispersion was measured in 32 anesthetized, mechanically ventilated dogs with total lung capacities (TLCs) of 1.1-2.5 L. Six-milliliter aerosol boluses were introduced at various preselected time-points during inspiration to probe different volumetric lung depths. Dispersion (SD) was determined by moment analysis of particle concentrations in the expired air. We found linear correlations between SD at a given lung depth and the individual end-inspiratory lung volume (V(L)). The relationship was tightest for boluses inhaled deepest into the lungs: SD(40) = 0.068 V(L) - 1.77, r(2) = 0.59. Normalizing SD to V(L) abolished this dependency and resulted in a considerable reduction of inter-individual variability as compared to the uncorrected measurements. These data indicate that lung size influences measurements of bolus dispersion. It therefore appears reasonable to apply a normalization procedure before interpreting the data. Apart from a reduction in measurement variability, this should help to separate the effects on bolus dispersion of altered lung volumes and altered mixing processes in diseased lungs.

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone; Weissman-Fogel, Irit

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1's role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual's first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and 'SHAM-VL'), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here.

HIV viraemia and mother-to-child transmission risk after antiretroviral therapy initiation in pregnancy in Cape Town, South Africa.

PubMed

Myer, L; Phillips, T K; McIntyre, J A; Hsiao, N-Y; Petro, G; Zerbe, A; Ramjith, J; Bekker, L-G; Abrams, E J

2017-02-01

Maternal HIV viral load (VL) drives mother-to-child HIV transmission (MTCT) risk but there are few data from sub-Saharan Africa, where most MTCT occurs. We investigated VL changes during pregnancy and MTCT following antiretroviral therapy (ART) initiation in Cape Town, South Africa. We conducted a prospective study of HIV-infected women initiating ART within routine antenatal services in a primary care setting. VL measurements were taken before ART initiation and up to three more times within 7 days postpartum. Analyses examined VL changes over time, viral suppression (VS) at delivery, and early MTCT based on polymerase chain reaction (PCR) testing up to 8 weeks of age. A total of 620 ART-eligible HIV-infected pregnant women initiated ART, with 2425 VL measurements by delivery (median gestation at initiation, 20 weeks; median pre-ART VL, 4.0 log 10 HIV-1 RNA copies/mL; median time on ART before delivery, 118 days). At delivery, 91% and 73% of women had VL ≤ 1000 and ≤ 50 copies/mL, respectively. VS was strongly predicted by time on therapy and pre-ART VL. The risk of early MTCT was strongly associated with delivery VL, with risks of 0.25, 2.0 and 8.5% among women with VL < 50, 50-1000 and > 1000 copies/mL at delivery, respectively (P < 0.001). High rates of VS at delivery and low rates of MTCT can be achieved in a routine care setting in sub-Saharan Africa, indicating the effectiveness of currently recommended ART regimens. Women initiating ART late in pregnancy and with high VL appear substantially less likely to achieve VS and require targeted research and programmatic attention. © 2016 British HIV Association.

Serological investigation of visceral Leishmania infection in human and its associated risk factors in Welkait District, Western Tigray, Ethiopia.

PubMed

Bsrat, Abrha; Berhe, Mebrahtu; Gadissa, Endalemaw; Taddele, Habtamu; Tekle, Yohannes; Hagos, Yohannes; Abera, Adugna; G/Micael, Messele; Alemayhu, Tehetna; Gugsa, Getachew; Aseffa, Abraham

2018-02-01

Visceral leishmaniasis (VL) is major neglected public health problem in terms of geographical spread and incidence in Ethiopia. Magnitude, public health impact and dynamics of VL were not well studied in Welkait District, Western Tigray, though the area is known for VL. Hence, this study aimed to determine sero-prevalence of human VL and associated risk factors in Welkait as new foci. A cross sectional study design was employed in this study. Two stage stratified random sampling method was used to select study participants. Hence, a total of 329 human study participants were included for serological survey using ITleish and leishmanin skin tests. Semi structured questionnaire was also used to identify VL associated risk factors. Univariate and multivariate logistic regression statistical methods were used to determine the degree of association. The overall sero-prevalence of human VL in the study area was found to be 8.81%. Statistical significant difference in the prevalence of the disease was found among Sub-districts, sex, re-settlement, sleeping outdoor and dog ownership ( P  < 0.05). Participants who resettled from their original place were found 2 times (AOR = 2.143; 95% CI = 1.02, 14.20) more vulnerable to VL infection. Those who had an experience of sleeping outdoor were found almost 4 times (AOR = 4.29; 95% CI = 1.58, 11.69) more likely to be at risk of acquiring VL infection than those sleep indoor. Furthermore, individuals who owned dogs were 3 times more prone to the VL infection than their counterparts (AOR = 3.37; 95% CI = 1.29, 8.76). Alarming sero-positivity of human VL was recorded from new foci. Hence, it is recommended to improve the VL health services in the study area. The investigation also invites further study on VL dynamics in the study area.

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed Central

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M. Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Background Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Methodology/Principal Findings Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). Conclusion The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study. PMID:26161864

Accounting for False Positive HIV Tests: Is Visceral Leishmaniasis Responsible?

PubMed

Shanks, Leslie; Ritmeijer, Koert; Piriou, Erwan; Siddiqui, M Ruby; Kliescikova, Jarmila; Pearce, Neil; Ariti, Cono; Muluneh, Libsework; Masiga, Johnson; Abebe, Almaz

2015-01-01

Co-infection with HIV and visceral leishmaniasis is an important consideration in treatment of either disease in endemic areas. Diagnosis of HIV in resource-limited settings relies on rapid diagnostic tests used together in an algorithm. A limitation of the HIV diagnostic algorithm is that it is vulnerable to falsely positive reactions due to cross reactivity. It has been postulated that visceral leishmaniasis (VL) infection can increase this risk of false positive HIV results. This cross sectional study compared the risk of false positive HIV results in VL patients with non-VL individuals. Participants were recruited from 2 sites in Ethiopia. The Ethiopian algorithm of a tiebreaker using 3 rapid diagnostic tests (RDTs) was used to test for HIV. The gold standard test was the Western Blot, with indeterminate results resolved by PCR testing. Every RDT screen positive individual was included for testing with the gold standard along with 10% of all negatives. The final analysis included 89 VL and 405 non-VL patients. HIV prevalence was found to be 12.8% (47/ 367) in the VL group compared to 7.9% (200/2526) in the non-VL group. The RDT algorithm in the VL group yielded 47 positives, 4 false positives, and 38 negatives. The same algorithm for those without VL had 200 positives, 14 false positives, and 191 negatives. Specificity and positive predictive value for the group with VL was less than the non-VL group; however, the difference was not found to be significant (p = 0.52 and p = 0.76, respectively). The test algorithm yielded a high number of HIV false positive results. However, we were unable to demonstrate a significant difference between groups with and without VL disease. This suggests that the presence of endemic visceral leishmaniasis alone cannot account for the high number of false positive HIV results in our study.

Permissive and protective factors associated with presence, level, and longitudinal pattern of cervicovaginal HIV shedding.

PubMed

Homans, James; Christensen, Shawna; Stiller, Tracey; Wang, Chia-Hao; Mack, Wendy; Anastos, Kathryn; Minkoff, Howard; Young, Mary; Greenblatt, Ruth; Cohen, Mardge; Strickler, Howard; Karim, Roksana; Spencer, Lashonda Yvette; Operskalski, Eva; Frederick, Toinette; Kovacs, Andrea

2012-05-01

Cervicovaginal HIV level (CV-VL) influences HIV transmission. Plasma viral load (PVL) correlates with CV-VL, but discordance is frequent. We evaluated how PVL, behavioral, immunological, and local factors/conditions individually and collectively correlate with CV-VL. CV-VL was measured in the cervicovaginal lavage fluid (CVL) of 481 HIV-infected women over 976 person-visits in a longitudinal cohort study. We correlated identified factors with CV-VL at individual person-visits and detectable/undetectable PVL strata by univariate and multivariate linear regression and with shedding pattern (never, intermittent, persistent ≥3 shedding visits) in 136 women with ≥3 visits by ordinal logistic regression. Of 959 person-visits, 450 (46.9%) with available PVL were discordant, 435 (45.3%) had detectable PVL with undetectable CV-VL, and 15 (1.6%) had undetectable PVL with detectable CV-VL. Lower CV-VL correlated with highly active antiretroviral therapy (HAART) usage (P = 0.01). Higher CV-VL correlated with higher PVL (P < 0.001), inflammation-associated cellular changes (P = 0.03), cervical ectopy (P = 0.009), exudate (P = 0.005), and trichomoniasis (P = 0.03). In multivariate analysis of the PVL-detectable stratum, increased CV-VL correlated with the same factors and friability (P = 0.05), while with undetectable PVL, decreased CV-VL correlated with HAART use (P = 0.04). In longitudinal analysis, never (40.4%) and intermittent (44.9%) shedding were most frequent. Higher frequency shedders were more likely to have higher initial PVL [odds ratio (OR) = 2.47/log10 increase], herpes simplex virus type 2 seropositivity (OR = 3.21), and alcohol use (OR = 2.20). Although PVL correlates strongly with CV-VL, discordance is frequent. When PVL is detectable, cervicovaginal inflammatory conditions correlate with increased shedding. However, genital shedding is sporadic and not reliably predicted by associated factors. HAART, by reducing PVL, is the most reliable means of reducing cervicovaginal shedding.

The cost-effectiveness of monitoring strategies for antiretroviral therapy of HIV infected patients in resource-limited settings: software tool.

PubMed

Estill, Janne; Salazar-Vizcaya, Luisa; Blaser, Nello; Egger, Matthias; Keiser, Olivia

2015-01-01

The cost-effectiveness of routine viral load (VL) monitoring of HIV-infected patients on antiretroviral therapy (ART) depends on various factors that differ between settings and across time. Low-cost point-of-care (POC) tests for VL are in development and may make routine VL monitoring affordable in resource-limited settings. We developed a software tool to study the cost-effectiveness of switching to second-line ART with different monitoring strategies, and focused on POC-VL monitoring. We used a mathematical model to simulate cohorts of patients from start of ART until death. We modeled 13 strategies (no 2nd-line, clinical, CD4 (with or without targeted VL), POC-VL, and laboratory-based VL monitoring, with different frequencies). We included a scenario with identical failure rates across strategies, and one in which routine VL monitoring reduces the risk of failure. We compared lifetime costs and averted disability-adjusted life-years (DALYs). We calculated incremental cost-effectiveness ratios (ICER). We developed an Excel tool to update the results of the model for varying unit costs and cohort characteristics, and conducted several sensitivity analyses varying the input costs. Introducing 2nd-line ART had an ICER of US$1651-1766/DALY averted. Compared with clinical monitoring, the ICER of CD4 monitoring was US$1896-US$5488/DALY averted and VL monitoring US$951-US$5813/DALY averted. We found no difference between POC- and laboratory-based VL monitoring, except for the highest measurement frequency (every 6 months), where laboratory-based testing was more effective. Targeted VL monitoring was on the cost-effectiveness frontier only if the difference between 1st- and 2nd-line costs remained large, and if we assumed that routine VL monitoring does not prevent failure. Compared with the less expensive strategies, the cost-effectiveness of routine VL monitoring essentially depends on the cost of 2nd-line ART. Our Excel tool is useful for determining optimal monitoring strategies for specific settings, with specific sex-and age-distributions and unit costs.

The Cost-Effectiveness of Monitoring Strategies for Antiretroviral Therapy of HIV Infected Patients in Resource-Limited Settings: Software Tool

PubMed Central

Estill, Janne; Salazar-Vizcaya, Luisa; Blaser, Nello; Egger, Matthias; Keiser, Olivia

2015-01-01

Background The cost-effectiveness of routine viral load (VL) monitoring of HIV-infected patients on antiretroviral therapy (ART) depends on various factors that differ between settings and across time. Low-cost point-of-care (POC) tests for VL are in development and may make routine VL monitoring affordable in resource-limited settings. We developed a software tool to study the cost-effectiveness of switching to second-line ART with different monitoring strategies, and focused on POC-VL monitoring. Methods We used a mathematical model to simulate cohorts of patients from start of ART until death. We modeled 13 strategies (no 2nd-line, clinical, CD4 (with or without targeted VL), POC-VL, and laboratory-based VL monitoring, with different frequencies). We included a scenario with identical failure rates across strategies, and one in which routine VL monitoring reduces the risk of failure. We compared lifetime costs and averted disability-adjusted life-years (DALYs). We calculated incremental cost-effectiveness ratios (ICER). We developed an Excel tool to update the results of the model for varying unit costs and cohort characteristics, and conducted several sensitivity analyses varying the input costs. Results Introducing 2nd-line ART had an ICER of US$1651-1766/DALY averted. Compared with clinical monitoring, the ICER of CD4 monitoring was US$1896-US$5488/DALY averted and VL monitoring US$951-US$5813/DALY averted. We found no difference between POC- and laboratory-based VL monitoring, except for the highest measurement frequency (every 6 months), where laboratory-based testing was more effective. Targeted VL monitoring was on the cost-effectiveness frontier only if the difference between 1st- and 2nd-line costs remained large, and if we assumed that routine VL monitoring does not prevent failure. Conclusion Compared with the less expensive strategies, the cost-effectiveness of routine VL monitoring essentially depends on the cost of 2nd-line ART. Our Excel tool is useful for determining optimal monitoring strategies for specific settings, with specific sex-and age-distributions and unit costs. PMID:25793531

Vitiligo blood transcriptomics provides new insights into disease mechanisms and identifies potential novel therapeutic targets.

PubMed

Dey-Rao, Rama; Sinha, Animesh A

2017-01-28

Significant gaps remain regarding the pathomechanisms underlying the autoimmune response in vitiligo (VL), where the loss of self-tolerance leads to the targeted killing of melanocytes. Specifically, there is incomplete information regarding alterations in the systemic environment that are relevant to the disease state. We undertook a genome-wide profiling approach to examine gene expression in the peripheral blood of VL patients and healthy controls in the context of our previously published VL-skin gene expression profile. We used several in silico bioinformatics-based analyses to provide new insights into disease mechanisms and suggest novel targets for future therapy. Unsupervised clustering methods of the VL-blood dataset demonstrate a "disease-state"-specific set of co-expressed genes. Ontology enrichment analysis of 99 differentially expressed genes (DEGs) uncovers a down-regulated immune/inflammatory response, B-Cell antigen receptor (BCR) pathways, apoptosis and catabolic processes in VL-blood. There is evidence for both type I and II interferon (IFN) playing a role in VL pathogenesis. We used interactome analysis to identify several key blood associated transcriptional factors (TFs) from within (STAT1, STAT6 and NF-kB), as well as "hidden" (CREB1, MYC, IRF4, IRF1, and TP53) from the dataset that potentially affect disease pathogenesis. The TFs overlap with our reported lesional-skin transcriptional circuitry, underscoring their potential importance to the disease. We also identify a shared VL-blood and -skin transcriptional "hot spot" that maps to chromosome 6, and includes three VL-blood dysregulated genes (PSMB8, PSMB9 and TAP1) described as potential VL-associated genetic susceptibility loci. Finally, we provide bioinformatics-based support for prioritizing dysregulated genes in VL-blood or skin as potential therapeutic targets. We examined the VL-blood transcriptome in context with our (previously published) VL-skin transcriptional profile to address a major gap in knowledge regarding the systemic changes underlying skin-specific manifestation of vitiligo. Several transcriptional "hot spots" observed in both environments offer prioritized targets for identifying disease risk genes. Finally, within the transcriptional framework of VL, we identify five novel molecules (STAT1, PRKCD, PTPN6, MYC and FGFR2) that lend themselves to being targeted by drugs for future potential VL-therapy.

View of God as benevolent and forgiving or punishing and judgmental predicts HIV disease progression.

PubMed

Ironson, Gail; Stuetzle, Rick; Ironson, Dale; Balbin, Elizabeth; Kremer, Heidemarie; George, Annie; Schneiderman, Neil; Fletcher, Mary Ann

2011-12-01

This study assessed the predictive relationship between View of God beliefs and change in CD4-cell and Viral Load (VL) in HIV positive people over an extended period. A diverse sample of HIVseropositive participants (N = 101) undergoing comprehensive psychological assessment and blood draws over the course of 4 years completed the View of God Inventory with subscales measuring Positive View (benevolent/forgiving) and Negative View of God (harsh/judgmental/punishing). Adjusting for initial disease status, age, gender, ethnicity, education, and antiretroviral medication (at every 6-month visit), a Positive View of God predicted significantly slower disease-progression (better preservation of CD4-cells, better control of VL), whereas a Negative View of God predicted faster disease-progression over 4 years. Effect sizes were greater than those previously demonstrated for psychosocial variables known to predict HIV-disease-progression, such as depression and coping. Results remained significant even after adjusting for church attendance and psychosocial variables (health behaviors, mood, and coping). These results provide good initial evidence that spiritual beliefs may predict health outcomes.

High-Intensity Cannabis Use And HIV Clinical Outcomes Among HIV-Positive People Who Use Illicit Drugs in Vancouver, Canada

PubMed Central

Lake, Stephanie; Kerr, Thomas; Capler, Rielle; Shoveller, Jeannie; Montaner, Julio; Milloy, M-J

2017-01-01

Background Reforms to the legal status of medical and non-medical cannabis are underway in many jurisdictions, including Canada, as are renewed efforts to scale-up HIV treatment-as-prevention (TasP) initiatives. It has been suggested that high-intensity cannabis use may be associated with sub-optimal HIV treatment outcomes. Thus, using data from a setting with a community-wide treatment-as-prevention (TasP) initiative coinciding with increasing access to medical cannabis, we sought to investigate the possible impact of high-intensity cannabis use on HIV clinical outcomes. Methods Data was derived from the ACCESS study, a prospective cohort of HIV-positive people who use illicit drugs (PWUD) in Vancouver, Canada. Cohort data was confidentially linked to comprehensive clinical profiles, including records of all antiretroviral therapy (ART) dispensations and longitudinal plasma HIV-1 RNA viral load (VL) monitoring. We used generalized estimating equations (GEEs) to estimate the longitudinal bivariable and multivariable relationships between at least daily cannabis use and two key clinical outcomes: overall engagement in ART care, and achieving a non-detectable VL among ART-exposed participants. Results Between December 2005 and June 2015, 874 HIV-positive PWUD (304 [35%] non-male) were included in this study. In total, 788 (90%) were engaged in HIV care at least once over the study period, of whom 670 (85%) achieved non-detectable VL at least once. In multivariable analyses, ≥ daily cannabis use did not predict lower odds of ART care (Adjusted Odds Ratio [AOR]: 1.02, 95% confidence interval [CI]: 0.77–1.36) or VL non-detectability among ART-exposed (AOR: 0.96, 95% CI: 0.75–1.21). Conclusion Our results showed no statistically significant impact of daily cannabis use on the likelihood of ART care or VL non-detectability among ART-exposed HIV-positive PWUD. These findings are reassuring in light of the impending legalization of cannabis in Canada and ongoing efforts to expand TasP initiatives. PMID:28336000

Visceral leishmaniasis-hepatitis B/C coinfections: a rising necessity to triage patients for treatment.

PubMed

A, Abubakr O; M, Mohamed M; A, Hatim A; Elamin, Mohamed Y; Younis, Brima M; E, Mona E; Musa, Ahmed M; Elhassan, Ahmed M; G, Eltahir A

2014-01-01

Visceral leishmaniasis (VL) is a life-threatening infection caused by Leishmania species. In Sudan, VL is caused by L donovani. Most drugs used to treat VL, especially pentavalent antimony compounds (sodium stibogluconate, SSG), are potentially hepatotoxic. A number of fatal catastrophes happened because patients with VL-hepatitis B/C coinfection were indiscriminately treated with SSG in settings where VL and viral hepatitis coexist. This study aimed to study biochemical and hematological parameters of patients with VL-hepatitis B/C coinfections with the aim to modify treatment protocols to reduce coinfection.added morbidity and mortality. This was a prospective analytical, hospital-based, and case-controlled study. The study was done at Kassab Hospital and Professor Elhassan Centre for tropical medicine during the period of February 2008 to April 2013. Following informed consent by the participants, 78 parasitologically confirmed VL patients with either hepatitis B or C or both and 528 sex- and age-unmatched VL patients without hepatitis B/C coinfection (control group) were enrolled sequentially. Diagnosis of hepatitis B or C was made using immunochromatographic test kits and confirmed by an enzyme-linked immunosorbent assay. VL patients with hepatitis B/C coinfections had significantly increased levels of AST, ALT, and total bilirubin compared to the control group (P=.0001 for all), with significantly decreased levels of albumin and platelets counts (P=.0029 for both). VL-hepatitis B/C coinfections are an emerging entity that needs anti-leishmanial treatment modification. Alternative treatments like paromomycin and amphotericin B (AmBisome) could be reserved for these patients.

The Household Costs of Visceral Leishmaniasis Care in South-eastern Nepal

PubMed Central

Baltussen, Rob; Rijal, Suman; Boelaert, Marleen

2013-01-01

Background and objectives Visceral leishmaniasis (VL) is an important public health problem in south-eastern Nepal affecting very poor rural communities. Since 2005, Nepal is involved in a regional initiative to eliminate VL. This study assessed the economic impact of VL on households and examined whether the intensified VL control efforts induced by the government resulted in a decrease in household costs. Methods Between August and September 2010, a household survey was conducted among 168 patients that had been treated for VL within 12 months prior to the survey in five districts in south-eastern Nepal. We collected data on health-seeking behaviour, direct and indirect costs and coping strategies. Results The median total cost of one episode of VL was US$ 165 or 11% of annual household income. The median delay between the onset of symptoms and presentation to a qualified provider was 25 days. Once the patient presented to a qualified provider, the delay to correct diagnosis was minimal (median 3 days). Direct and indirect costs (income losses) represented 47% and 53% of total costs respectively. Households used multiple strategies to cope with the cost of illness, mainly mobilizing cash/savings (71%) or taking a loan (56%). Conclusions The provision of free VL diagnosis and drugs by the Nepalese control programme has been an important policy measure to reduce the cost of VL to households. But despite the free VL drugs, the economic burden is still important for households. More effort should be put into reducing indirect costs, in particular the length of treatment, and preventing the transmission of VL through vector control. PMID:23469298

The household costs of visceral leishmaniasis care in south-eastern Nepal.

PubMed

Uranw, Surendra; Meheus, Filip; Baltussen, Rob; Rijal, Suman; Boelaert, Marleen

2013-01-01

Visceral leishmaniasis (VL) is an important public health problem in south-eastern Nepal affecting very poor rural communities. Since 2005, Nepal is involved in a regional initiative to eliminate VL. This study assessed the economic impact of VL on households and examined whether the intensified VL control efforts induced by the government resulted in a decrease in household costs. Between August and September 2010, a household survey was conducted among 168 patients that had been treated for VL within 12 months prior to the survey in five districts in south-eastern Nepal. We collected data on health-seeking behaviour, direct and indirect costs and coping strategies. The median total cost of one episode of VL was US$ 165 or 11% of annual household income. The median delay between the onset of symptoms and presentation to a qualified provider was 25 days. Once the patient presented to a qualified provider, the delay to correct diagnosis was minimal (median 3 days). Direct and indirect costs (income losses) represented 47% and 53% of total costs respectively. Households used multiple strategies to cope with the cost of illness, mainly mobilizing cash/savings (71%) or taking a loan (56%). The provision of free VL diagnosis and drugs by the Nepalese control programme has been an important policy measure to reduce the cost of VL to households. But despite the free VL drugs, the economic burden is still important for households. More effort should be put into reducing indirect costs, in particular the length of treatment, and preventing the transmission of VL through vector control.

Environmental suitability for Lutzomyia longipalpis in a subtropical city with a recently established visceral leishmaniasis transmission cycle, Argentina.

PubMed

Berrozpe, Pablo; Lamattina, Daniela; Santini, María Soledad; Araujo, Analía Vanesa; Utgés, María Eugenia; Salomón, Oscar Daniel

2017-10-01

Visceral leishmaniasis (VL) is an endemic disease in northeastern Argentina including the Corrientes province, where the presence of the vector and canine cases of VL were recently confirmed in December 2008. The objective of this study was to assess the modelling of micro- and macro-habitat variables to evaluate the urban environmental suitability for the spatial distribution of Lutzomyia longipalpis presence and abundance in an urban scenario. Sampling of 45 sites distributed throughout Corrientes city (Argentina) was carried out using REDILA-BL minilight traps in December 2013. The sampled specimens were identified according to methods described by Galati (2003). The analysis of variables derived from the processing of satellite images (macro-habitat variables) and from the entomological sampling and surveys (micro-habitat variables) was performed using the statistical software R. Three generalised linear models were constructed composed of micro- and macro-habitat variables to explain the spatial distribution of the abundance of Lu. longipalpis and one composed of micro-habitat variables to explain the occurrence of the vector. A total of 609 phlebotominae belonging to five species were collected, of which 56% were Lu. longipalpis. In addition, the presence of Nyssomyia neivai and Migonemya migonei, which are vectors of tegumentary leishmaniasis, were also documented and represented 34.81% and 6.74% of the collections, respectively. The explanatory variable normalised difference vegetation index (NDVI) described the abundance distribution, whereas the presence of farmyard animals was important for explaining both the abundance and the occurrence of the vector. The results contribute to the identification of variables that can be used to establish priority areas for entomological surveillance and provide an efficient transfer tool for the control and prevention of vector-borne diseases.

Environmental suitability for Lutzomyia longipalpis in a subtropical city with a recently established visceral leishmaniasis transmission cycle, Argentina

PubMed Central

Berrozpe, Pablo; Lamattina, Daniela; Santini, María Soledad; Araujo, Analía Vanesa; Utgés, María Eugenia; Salomón, Oscar Daniel

2017-01-01

BACKGROUND Visceral leishmaniasis (VL) is an endemic disease in northeastern Argentina including the Corrientes province, where the presence of the vector and canine cases of VL were recently confirmed in December 2008. OBJECTIVES The objective of this study was to assess the modelling of micro- and macro-habitat variables to evaluate the urban environmental suitability for the spatial distribution of Lutzomyia longipalpis presence and abundance in an urban scenario. METHODS Sampling of 45 sites distributed throughout Corrientes city (Argentina) was carried out using REDILA-BL minilight traps in December 2013. The sampled specimens were identified according to methods described by Galati (2003). The analysis of variables derived from the processing of satellite images (macro-habitat variables) and from the entomological sampling and surveys (micro-habitat variables) was performed using the statistical software R. Three generalised linear models were constructed composed of micro- and macro-habitat variables to explain the spatial distribution of the abundance of Lu. longipalpis and one composed of micro-habitat variables to explain the occurrence of the vector. FINDINGS A total of 609 phlebotominae belonging to five species were collected, of which 56% were Lu. longipalpis. In addition, the presence of Nyssomyia neivai and Migonemya migonei, which are vectors of tegumentary leishmaniasis, were also documented and represented 34.81% and 6.74% of the collections, respectively. The explanatory variable normalised difference vegetation index (NDVI) described the abundance distribution, whereas the presence of farmyard animals was important for explaining both the abundance and the occurrence of the vector. MAIN CONCLUSIONS The results contribute to the identification of variables that can be used to establish priority areas for entomological surveillance and provide an efficient transfer tool for the control and prevention of vector-borne diseases. PMID:28953995

Long-Term Resolution of Viral Breakthrough after Changing HIV Viral Load Assay.

PubMed

Obeid, Karam M; Sural, Preethi; Szpunar, Susan; Johnson, Leonard B

2011-01-01

Viral load (VL) measurement assays differ in their sensitivity with polymerase chain reaction assays (PCR) being more sensitive than branched DNA (bDNA) assays. We evaluated virologic outcomes of patients and physicians' response to increased VL after a switch from bDNA to PCR assay. Retrospective, case-control study on 65 HIV+ patients receiving highly active antiretroviral therapy (HAART). Cases included patients with undetectable VL by bDNA that became detectable after the switch; controls were patients that remained undetectable. Records were reviewed up to 1 year after the switch. A total of 58.5% patients had detectable VL after the switch. Repeat VL testing and resistance testing were ordered in 15.4% and 23.1% of these patients, respectively. By 1 year, VL was undetectable in 82.8% of cases and 92% of controls (P = .30), without change in HAART. Transient viremia after changing VL assay reflects the different sensitivity of these assays with no impact on patients' outcomes compared to controls.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites.

PubMed

Tajebe, Fitsumbrhan; Getahun, Mulusew; Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew; Kropf, Pascale

2017-07-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity.

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites

PubMed Central

Adem, Emebet; Hailu, Asrat; Lemma, Mulualem; Fikre, Helina; Raynes, John; Tamiru, Aschalew; Mulugeta, Zemenay; Diro, Ermias; Toulza, Frederic; Shkedy, Ziv; Ayele, Tadesse; Modolell, Manuel; Munder, Markus; Müller, Ingrid; Takele, Yegnasew

2017-01-01

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity. PMID:28732017

Ten Year Trends in Community HIV Viral Load in Barbados: Implications for Treatment as Prevention

PubMed Central

Landis, R. Clive; Branch-Beckles, Songee Lynn; Crichlow, Shawna; Hambleton, Ian R.; Best, Anton

2013-01-01

Background Treatment as prevention is a paradigm in HIV medicine which describes the public health benefit of antiretroviral therapy (ART). It is based on research showing substantial reductions in the risk of HIV transmission in persons with optimally suppressed HIV-1 Viral Loads (VL). The present study describes ten year VL trends at the national HIV treatment unit and estimates VL suppression at a population level in Barbados, a Caribbean island with a population of 277,000, an estimated adult HIV prevalence of 1.2%, and served by a single treatment unit. Methods The national HIV treatment centre of the Barbados Ministry of Health has a client VL database extending back to inception of the clinic in 2002 (n = 1,462 clients, n = 17,067 VL measurements). Optimal VL suppression was defined at a threshold value of ≤200 viral copies/mL. Results Analysis of VL trends showed a statistically significant improvement in VL suppression between 2002 to 2011, from 33.6% of clients achieving the 200 copies/mL threshold in 2002 to 70.3% in 2011 (P<0.001). Taking into account the proportion of clients alive and in care and on ART, the known diagnosed HIV population in Barbados, and estimates of unknown HIV infections, this translates into an estimated 26.2% VL suppression at a population level at the end of 2010. Conclusions We have demonstrated a significant trend towards optimal VL suppression in clients utilizing the services of the national HIV treatment program in Barbados over a 10-year period. Estimates of VL suppression at a population level are similar to reports in developed countries that applied similar methodologies and this could suggest a public health benefit of ART in minimizing the risk of sexual transmission of HIV. Continued efforts are warranted to extend HIV testing to hidden populations in Barbados and linking infected persons to care earlier in their disease. PMID:23520523

Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay.

PubMed

Gous, Natasha; Scott, Lesley; Berrie, Leigh; Stevens, Wendy

2016-01-01

Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert's random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32-0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services.

Viral load testing and the use of test results for clinical decision making for HIV treatment in Cameroon: An insight into the clinic-laboratory interface.

PubMed

Awungafac, George; Amin, Elvis T; Fualefac, Akemfua; Takah, Noah F; Agyingi, Lucy A; Nwobegahay, Julius; Ondoa, Pascale; Njukeng, Patrick A

2018-01-01

The viral load (VL) in patients receiving antiretroviral therapy (ART) is the best predictor of treatment outcome. The anticipated benefits of VL monitoring depend on the actual uptake of VL test results for clinical decisions. The objective of this study was to assess the uptake and utilization of VL test results for clinical decisions on HIV treatment in Cameroon, from 2013 to 2017. This was a retrospective cohort analysis of data from files of patients receiving ART at Buea, Limbe, Bamenda and Bafoussam regional hospital HIV treatment centers. A simple random pick of six file blocks was performed in each shelf that corresponded to a year of initiation, and the contents of all selected files were reviewed and the information needed for the study entered a structured questionnaire. The data collected was recorded in Epi Info (version 7.1.5.2), and analyzed using SATA (version 12.1; StataCorp LP). Eight hundred and thirty files were reviewed. The mean duration on ART was 39.4±12 months. Viral load testing uptake was 24.33% and only one VL test had been done by all patients. Approximately 65% of the patients did the first VL after more than 24 months on ART. The median turnaround (TAT) time for VL testing was 6 days (Interquartile range (IQR) 3-7days). Among 201 patients who did a VL test, 94.55% had VL suppression (≤1000copies/mm3). Approximately 54% of the patients with virologic failure were switched to a second-line regimen. The uptake of viral load testing is low in North West, South West and West Regions of Cameroon. The current TAT for VL testing is plausible. The rate of switch to second line regimen is low. It is time to strengthen the scale up of VL testing and improve the rate of switch to second-line regimen in Cameroon.

Comparison among ultrasonic, electrical apparatus, and toxic chemicals for vestibular lesion in mice.

PubMed

Yamaoka, Yusuke; Abe, Chikara; Morita, Hironobu

2018-02-01

The vestibular lesion (VL) is required to examine the physiological function of the vestibular system in animals. Toxic chemicals or electrical apparatus have been used for the VL, however, they are not ideal as they have low specificity, and can result in unintended damage, and systemic toxic effect. Localized vibration-induced VL, using an ultrasonicator, is expected to overcome the problems associated with chemical and electrical lesions. Thus, we examined the effect of the ultrasonication on the VL from the aspects of both the physiological function and histology in the present study. and Comparison with Existing Method(s) Complete VL, which was evaluated by deterioration of swimming skills, righting reflex, and body stability, was induced using an ultrasonicator or electrical apparatus. Histological evaluation shows that hair cell layers in the saccule and utricle were completely destroyed in both methods Furthermore, significant drop in body mass was observed in VL. However, abscess at the cranial base was observed in VL induced by the electrical apparatus in ICR mice. Complete chemically-induced VL was observed in C57BL/6J but not ICR mice, and systemic leakage of the toxic chemicals (arsenic) was not detectable even 1day after surgery. Compared to the electrical apparatus, the ultrasonicator is useful for inducing VL in ICR and C57BL/6J mice, as it results in less non-specific damage. Toxic chemicals can be used for inducing VL in C57BL/6J mice; however, this method does not ensure complete disruption of the hair cells in the saccule and utricle. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

Sandflies (Diptera: Psychodidae) in an urban area of Northeastern Brazil.

PubMed

Agra, Maria Claudia Ribeiro; Costa, Pietra Lemos; Duque, Anderson Enio Silva; Soares, Efraim Naftali Lopes; Alves, Leucio Câmara; Ramos, Rafael Antonio Nascimento; Carvalho, Gílcia Aparecida de

2016-01-01

The sandfly fauna is well studied globally. In Brazil, sandfly fauna is very diverse in the Northeast region, especially in states such as Maranhão, Ceará, and Bahia. However, in the State of Pernambuco, the distribution of these insects is still not well known. Therefore, the objective of this study was to identify the different species that constitute the sandfly fauna in an urban area in the Northeast region of Brazil, where an outbreak of visceral leishmaniasis (VL) was recently reported. The sandflies were collected from an urban area endemic for VL, at five collection points. The collection of samples was carried out from November 2014 to December 2015, using CDC light traps installed in intradomiciliary and peridomiciliary fashion. The collected sandflies (n = 297) belonged to eight species: Lutzomyia lenti, Lutzomyia longipalpis, Lutzomyia sallesi, Lutzomyia migonei, Lutzomyia walkeri, Lutzomyia capixaba, Lutzomyia carmelinoi, and Lutzomyia whitmani. Most of the specimens collected were peridomiciliary (247/297, 83%). L. lenti (154/297, 52%) was the most frequently sampled species, followed by L. longipalpis (88/297, 29.6%), and L. sallesi (42/297, 14.1%), which together accounted for over 90% of the collected sandfly specimens. The continued presence of L. longipalpis in urban areas, including that in intradomiciliary areas, with a predominance of females, is crucial because of the high possibility of them causing VL outbreaks, since this species is the main vector of Leishmania infantum in Brazil.

The Economic Burden of Visceral Leishmaniasis in Sudan: An Assessment of Provider and Household Costs

PubMed Central

Meheus, Filip; Abuzaid, Abuzaid A.; Baltussen, Rob; Younis, Brima M.; Balasegaram, Manica; Khalil, Eltahir A. G.; Boelaert, Marleen; Musa, Ahmed M.

2013-01-01

Visceral leishmaniasis (VL) is a neglected parasitic disease that is fatal if left untreated and is endemic in eastern Sudan. We estimated the direct and indirect costs of treatment of VL from the perspective of the provider and the household at three public hospitals in Gedaref State. The median total cost for one VL episode was estimated to be US$450. Despite the free provision of VL drugs at public hospitals, households bore 53% of the total cost of VL with one episode of VL representing 40% of the annual household income. More than 75% of households incurred catastrophic out-of-pocket expenditures. The length of treatment of 30 days led to important costs for both health providers and households. Alternative treatment regimens that reduce the duration of treatment are urgently needed. PMID:24189368

NASA Global Atmospheric Sampling Program (GASP) data report for tape VL0015, VL0016, VL0017, VL0018, VL0019, and VL0020

NASA Technical Reports Server (NTRS)

Papthakos, L. C.; Briehl, D.

1981-01-01

This is the twelfth of a series of reports which describes the data currently available from GASP, including flight routes and dates, instrumentation, data processing procedures, and data tape specifications. In-situ measurements of atmospheric ozone, cabin ozone, carbon monoxide, water vapor, particles, clouds, condensation nuclei, filter samples and related meteorological and flight information obtained during 1732 flights of aircraft N533PA, N4711U, N655PA, and VH-EBE from January 5, 1978 through October 9, 1978 are reported. These data are now available from the National Climatic Center, Asheville, NC, 22801. In addition to the GASP data, tropopause pressures obtained from time ans space interpolation of National Meteorological Center archived data for the dates of the flights are included.

Changes in the epidemiology of visceral leishmaniasis in Brazil from 2001 to 2014.

PubMed

Reis, Lisiane Lappe Dos; Balieiro, Antônio Alcirley da Silva; Fonseca, Fernanda Rodrigues; Gonçalves, Maria Jacirema Ferreira

2017-01-01

Visceral leishmaniasis (VL) is a neglected disease, with territorial expansion and regional differences in Brazil that require explanation. This study aimed to describe changes in the epidemiology of VL in Brazil from 2001 to 2014. The incidence rates, sociodemographic and clinical data, and case evolution were subgrouped from 2001 to 2006 and from 2007 to 2014 and presented descriptively. Spatial distribution of disease incidence rates and changes in the spatial and temporal pattern were examined. In total, 47,859 VL cases were reported in Brazil between 2001 and 2014, with predominance in the Northeast macroregion (55%), though the incidence rate in this region declined between the two study periods. The State of Tocantins had the highest crude rate (26.2/100,000 inhabitants), which was responsible for VL increasing in the North macroregion. VL predominated in the urban zone (70%), in children under 4 years (34%); however, an increase in the incidence of VL in adults older than 40 years was identified, with 12.3% and 31% in the first and second period, respectively. The mapping of crude rates and autochthonous canine cases showed territorial expansion. The temporal distribution of VL was consistent in Brazil in general, with no pattern observed, but regional differences were found. The incidence of VL is increasing in Brazil. In addition to the State of Tocantins, which had the highest rate, new outbreaks of VL have occurred in the South macroregion of Brazil with small decreases identified in the incidence rate in the Northeast.

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

PubMed Central

Kisler, Lee-Bareket; Gurion, Ilan; Granovsky, Yelena; Sinai, Alon; Sprecher, Elliot; Shamay-Tsoory, Simone

2018-01-01

The modulatory role of the primary motor cortex (M1), reflected by an inhibitory effect of M1-stimulation on clinical pain, motivated us to deepen our understanding of M1’s role in pain modulation. We used Transcranial Magnetic Stimulation (TMS)-induced virtual lesion (VL) to interrupt with M1 activity during noxious heat pain. We hypothesized that TMS-VL will effect experimental pain ratings. Three VL protocols were applied consisting of single-pulse TMS to transiently interfere with right M1 activity: (1) VLM1- TMS applied to 11 subjects, 20 msec before the individual’s first pain-related M1 peak activation, as determined by source analysis (sLORETA), (2) VL-50 (N = 16; TMS applied 50 ms prior to noxious stimulus onset), and (3) VL+150 (N = 16; TMS applied 150 ms after noxious stimulus onset). Each protocol included 3 conditions ('pain-alone', ' TMS-VL', and ‘SHAM-VL’), each consisted of 30 noxious heat stimuli. Pain ratings were compared, in each protocol, for TMS-VL vs. SHAM-VL and vs. pain-alone conditions. Repeated measures analysis of variance, corrected for multiple comparisons revealed no significant differences in the pain ratings between the different conditions within each protocol. Therefore, our results from this exploratory study suggest that a single pulse TMS-induced VL that is targeted to M1 failed to interrupt experimental pain processing in the specific three stimulation timing examined here. PMID:29630681

Epidemiological aspects and spatial distribution of human and canine visceral leishmaniasis in an endemic area in northeastern Brazil.

PubMed

Campos, Roseane; Santos, Márcio; Tunon, Gabriel; Cunha, Luana; Magalhães, Lucas; Moraes, Juliana; Ramalho, Danielle; Lima, Sanmy; Pacheco, José Antônio; Lipscomb, Michael; Ribeiro de Jesus, Amélia; Pacheco de Almeida, Roque

2017-05-11

Visceral leishmaniasis (VL) is a systemic disease endemic in tropical countries and transmitted through sand flies. In particular, Canis familiaris (or domesticated dogs) are believed to be a major urban reservoir for the parasite causing the disease Leishmania. The average number of human VL cases was 58 per year in the state of Sergipe. The city of Aracaju, capital of Sergipe in Northeastern Brazil, had 159 cases of VL in humans. Correlatively, the percentage of serologically positive dogs for leishmaniasis increased from 4.73% in 2008 to 12.69% in 2014. Thus, these studies aimed to delineate the spatial distribution and epidemiological aspects of human and canine VL as mutually supportive for increased incidence. The number of human cases of VL and the frequency of canine positive serology for VL both increased between 2008 and 2014. Spatial distribution analyses mapped areas of the city with the highest concentration of human and canine VL cases. The neighbourhoods that showed the highest disease frequency were located on the outskirts of the city and in urbanised areas or subjected to development. Exponential increase in VL-positive dogs further suggests that the disease is expanding in urban areas, where it can serve as a reservoir for transmission of dogs to humans via the sand fly vector.

Functional and Muscle-Size Effects of Flywheel Resistance Training with Eccentric-Overload in Professional Handball Players

PubMed Central

García-López, David; de Paz, José A

2017-01-01

Abstract The aim of the study was to analyse the effects of 6 week (15 sessions) flywheel resistance training with eccentric-overload (FRTEO) on different functional and anatomical variables in professional handball players. Twenty-nine athletes were recruited and randomly divided into two groups. The experimental group (EXP, n = 15) carried out 15 sessions of FRTEO in the leg-press exercise, with 4 sets of 7 repetitions at a maximum-concentric effort. The control group (CON, n = 14) performed the same number of training sessions including 4 sets of 7 maximum repetitions (7RM) using a weight-stack leg-press machine. The results which were measured included maximal dynamic strength (1RM), muscle power at different submaximal loads (PO), vertical jump height (CMJ and SJ), 20 m sprint time (20 m), T-test time (T-test), and Vastus-Lateralis muscle (VL) thickness. The results of the EXP group showed a substantially better improvement (p < 0.05-0.001) in PO, CMJ, 20 m, T-test and VL, compared to the CON group. Moreover, athletes from the EXP group showed significant improvements concerning all the variables measured: 1RM (ES = 0.72), PO (ES = 0.42 - 0.83), CMJ (ES = 0.61), SJ (ES = 0.54), 20 m (ES = 1.45), T-test (ES = 1.44), and VL (ES = 0.63 - 1.64). Since handball requires repeated short, explosive effort such as accelerations and decelerations during sprints with changes of direction, these results suggest that FRTEO affects functional and anatomical changes in a way which improves performance in well-trained professional handball players. PMID:29339993

Plasmacytoid dendritic cell and functional HIV Gag p55-specific T cells before treatment interruption can inform set-point plasma HIV viral load after treatment interruption in chronically suppressed HIV-1(+) patients.

PubMed

Papasavvas, Emmanouil; Foulkes, Andrea; Yin, Xiangfan; Joseph, Jocelin; Ross, Brian; Azzoni, Livio; Kostman, Jay R; Mounzer, Karam; Shull, Jane; Montaner, Luis J

2015-07-01

The identification of immune correlates of HIV control is important for the design of immunotherapies that could support cure or antiretroviral therapy (ART) intensification-related strategies. ART interruptions may facilitate this task through exposure of an ART partially reconstituted immune system to endogenous virus. We investigated the relationship between set-point plasma HIV viral load (VL) during an ART interruption and innate/adaptive parameters before or after interruption. Dendritic cell (DC), natural killer (NK) cell and HIV Gag p55-specific T-cell functional responses were measured in paired cryopreserved peripheral blood mononuclear cells obtained at the beginning (on ART) and at set-point of an open-ended interruption from 31 ART-suppressed chronically HIV-1(+) patients. Spearman correlation and linear regression modeling were used. Frequencies of plasmacytoid DC (pDC), and HIV Gag p55-specific CD3(+)  CD4(-)  perforin(+)  IFN-γ(+) cells at the beginning of interruption associated negatively with set-point plasma VL. Inclusion of both variables with interaction into a model resulted in the best fit (adjusted R(2)  = 0·6874). Frequencies of pDC or HIV Gag p55-specific CD3(+)  CD4(-)  CSFE(lo)  CD107a(+) cells at set-point associated negatively with set-point plasma VL. The dual contribution of pDC and anti-HIV T-cell responses to viral control, supported by our models, suggests that these variables may serve as immune correlates of viral control and could be integrated in cure or ART-intensification strategies. © 2015 John Wiley & Sons Ltd.

Two different secondary metabolism gene clusters occupied the same ancestral locus in fungal dermatophytes of the arthrodermataceae.

PubMed

Zhang, Han; Rokas, Antonis; Slot, Jason C

2012-01-01

Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes) colonize keratinized tissue, such as skin, frequently causing superficial mycoses in humans and other mammals, reptiles, and birds. Competition with native microflora likely underlies the propensity of these dermatophytes to produce a diversity of antibiotics and compounds for scavenging iron, which is extremely scarce, as well as the presence of an unusually large number of putative secondary metabolism gene clusters, most of which contain non-ribosomal peptide synthetases (NRPS), in their genomes. To better understand the historical origins and diversification of NRPS-containing gene clusters we examined the evolution of a variable locus (VL) that exists in one of three alternative conformations among the genomes of seven dermatophyte species. The first conformation of the VL (termed VLA) contains only 539 base pairs of sequence and lacks protein-coding genes, whereas the other two conformations (termed VLB and VLC) span 36 Kb and 27 Kb and contain 12 and 10 genes, respectively. Interestingly, both VLB and VLC appear to contain distinct secondary metabolism gene clusters; VLB contains a NRPS gene as well as four porphyrin metabolism genes never found to be physically linked in the genomes of 128 other fungal species, whereas VLC also contains a NRPS gene as well as several others typically found associated with secondary metabolism gene clusters. Phylogenetic evidence suggests that the VL locus was present in the ancestor of all seven species achieving its present distribution through subsequent differential losses or retentions of specific conformations. We propose that the existence of variable loci, similar to the one we studied, in fungal genomes could potentially explain the dramatic differences in secondary metabolic diversity between closely related species of filamentous fungi, and contribute to host adaptation and the generation of metabolic diversity.

Sexual Risk Behavior Among Virologically Detectable Human Immunodeficiency Virus-Infected Young Men Who Have Sex With Men.

PubMed

Wilson, Patrick A; Kahana, Shoshana Y; Fernandez, Maria Isabel; Harper, Gary W; Mayer, Kenneth; Wilson, Craig M; Hightow-Weidman, Lisa B

2016-02-01

Human immunodeficiency virus (HIV) diagnoses continue to increase among young men who have sex with men (YMSM). Many YMSM living with HIV engage in sexual risk behaviors, and those who have a detectable viral load can transmit HIV to sex partners. Understanding factors that are related to sexual risk taking among virologically detectable (VL+) YMSM can inform prevention and treatment efforts. To describe differences between virologically suppressed (VL-) and VL+ YMSM living with HIV and to identify correlates of condomless anal intercourse (CAI) and serodiscordant CAI among VL+ YMSM. In this cross-sectional survey conducted from December 1, 2009, through June 30, 2012, we studied 991 HIV-infected YMSM 15 to 26 years of age at 20 adolescent HIV clinics in the United States. Data analysis was conducted December 1, 2013, through July 31, 2015. Demographic, behavioral, and psychosocial assessments obtained using audio computer-assisted self-interviews. Viral load information was obtained via blood draw or medical record abstraction. Of the 991 participants, 688 (69.4%) were VL+ and 458 (46.2%) reported CAI, with 310 (31.3%) reporting serodiscordant CAI in the past 3 months. The VL+ YMSM were more likely than the VL- YMSM to report CAI (detectable, 266 [54.7%]; suppressed, 91 [44.4%]; P = .01) and serodiscordant CAI (detectable, 187 [34.9%]; suppressed, 57 [25.0%]; P < .01). Multivariable analyses indicated that among VL+ YMSM, those reporting problematic substance use were more likely to report CAI (adjusted odds ratio [AOR], 1.46; 95% CI, 1.02-2.10) and serodiscordant CAI (AOR, 1.45; 95% CI, 1.06-1.99). Black VL+ YMSM were less likely to report CAI (AOR, 0.63; 95% CI, 0.44-0.90) or serodiscordant CAI (AOR, 0.66; 95% CI, 0.46-0.94) compared with other VL+ YMSM. In addition, VL+ YMSM who disclosed their HIV status to sex partners were more likely to report CAI compared with nondisclosing YMSM (AOR, 1.35; 95% CI, 1.01-1.81). Transgender participants were less likely to report CAI than cisgender participants (AOR, 0.35; 95% CI, 0.14-0.85). Last, VL+ YMSM who reported currently being employed were less likely to report serodiscordant CAI than those who were unemployed (AOR, 0.74; 95% CI, 0.55-0.99). Targeted multilevel interventions are needed to reduce HIV transmission risk behaviors among YMSM living with HIV, particularly among those who are VL+.

Human Anti-V3 HIV-1 Monoclonal Antibodies Encoded by the VH5-51/VL Lambda Genes Define a Conserved Antigenic Structure

PubMed Central

Gorny, Miroslaw K.; Sampson, Jared; Li, Huiguang; Jiang, Xunqing; Totrov, Maxim; Wang, Xiao-Hong; Williams, Constance; O'Neal, Timothy; Volsky, Barbara; Li, Liuzhe; Cardozo, Timothy; Nyambi, Phillipe; Zolla-Pazner, Susan; Kong, Xiang-Peng

2011-01-01

Preferential usage of immunoglobulin (Ig) genes that encode antibodies (Abs) against various pathogens is rarely observed and the nature of their dominance is unclear in the context of stochastic recombination of Ig genes. The hypothesis that restricted usage of Ig genes predetermines the antibody specificity was tested in this study of 18 human anti-V3 monoclonal Abs (mAbs) generated from unrelated individuals infected with various subtypes of HIV-1, all of which preferentially used pairing of the VH5-51 and VL lambda genes. Crystallographic analysis of five VH5-51/VL lambda-encoded Fabs complexed with various V3 peptides revealed a common three dimensional (3D) shape of the antigen-binding sites primarily determined by the four complementarity determining regions (CDR) for the heavy (H) and light (L) chains: specifically, the H1, H2, L1 and L2 domains. The CDR H3 domain did not contribute to the shape of the binding pocket, as it had different lengths, sequences and conformations for each mAb. The same shape of the binding site was further confirmed by the identical backbone conformation exhibited by V3 peptides in complex with Fabs which fully adapted to the binding pocket and the same key contact residues, mainly germline-encoded in the heavy and light chains of five Fabs. Finally, the VH5-51 anti-V3 mAbs recognized an epitope with an identical 3D structure which is mimicked by a single mimotope recognized by the majority of VH5-51-derived mAbs but not by other V3 mAbs. These data suggest that the identification of preferentially used Ig genes by neutralizing mAbs may define conserved epitopes in the diverse virus envelopes. This will be useful information for designing vaccine immunogen inducing cross-neutralizing Abs. PMID:22164215

Intramuscular adipose tissue determined by T1-weighted MRI at 3T primarily reflects extramyocellular lipids.

PubMed

Akima, Hiroshi; Hioki, Maya; Yoshiko, Akito; Koike, Teruhiko; Sakakibara, Hisataka; Takahashi, Hideyuki; Oshida, Yoshiharu

2016-05-01

The purpose of this study was to assess relationships between intramuscular adipose tissue (IntraMAT) content determined by MRI and intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) determined by (1)H magnetic resonance spectroscopy ((1)H MRS) or echo intensity determined by B-mode ultrasonography of human skeletal muscles. Thirty young and elderly men and women were included. T1-weighted MRI was taken from the right mid-thigh to measure IntraMAT content of the vastus lateralis (VL) and biceps femoris (BF) using a histogram shape-based thresholding technique. IMCL and EMCL were measured from the VL and BF at the right mid-thigh using (1)H MRS. Ultrasonographic images were taken from the VL and BF of the right mid-thigh to measure echo intensity based on gray-scale level for quantitative analysis. There was a significant correlation between IntraMAT content by MRI and EMCL of the VL and BF (VL, r=0.506, P<0.01; BF, r=0.591, P<0.001) and between echo intensity and EMCL of the VL and BF (VL, r=0.485, P<0.05; BF, r=0.648, P<0.01). IntraMAT content was also significantly correlated with echo intensity of the VL and BF (VL, r=0.404, P<0.05; BF, r=0.493, P<0.01). Our study suggests that IntraMAT content determined by T1-weighted MRI at 3T primarily reflects extramyocellular lipids, not intramyocellular lipids, in human skeletal muscles. Copyright © 2016 Elsevier Inc. All rights reserved.

Prevalence of malnutrition and associated risk factors among adult visceral leishmaniasis patients in Northwest Ethiopia: a cross sectional study.

PubMed

Mengesha, Bewketu; Endris, Mengistu; Takele, Yegnasew; Mekonnen, Kalehiwot; Tadesse, Takele; Feleke, Amsalu; Diro, Ermias

2014-02-04

Visceral leishmaniasis (VL) causes considerable morbidity and mortality in Ethiopia. Data on the prevalence and associated risk factors on malnutrition among VL patients in Ethiopia are scarce. This study aimed to assess the prevalence of malnutrition and its associated risk factor among VL patients in Northwest Ethiopia. An institution-based cross-sectional study was conducted from June to September 2012 at four leishmaniasis treatment sites in Northwest Ethiopia. Four hundred and three adult VL patients were enrolled in the study. Malnutrition was defined as a body mass index (BMI) ≤ 18.5 kg/m2. The data collected from the VL patients included sex, age, residence, occupation, weight, height, laboratory results (HIV, hemoglobin, intestinal parasites). Multivariate logistic regression model was used to determine the strength of association between malnutrition and associated risk factors. Among 403 adult VL patients 385 (95.5%) were malnourished. Twenty eight percent (n = 113), 30.3% (n = 122), and 37.2% (n = 150) were mildly, moderately and severely malnourished, respectively. The prevalence of intestinal parasitic infection was 47.6% (n = 192) and it was associated with malnutrition (P = 0.01). The prevalence of VL-HIV co-infection was 10.4% (n = 42). Hook worm, Giardia intestinalis and Ascaris lumbircoides were the leading prevalent intestinal parasites. Factors such as age, sex, residence, occupation, HIV status and anemia were not associated with severe malnutrition. The prevalence of malnutrition in VL patients was very high and it was associated with intestinal parasitic infections. Therefore, screening of severely malnourished VL patients for intestinal parasitic infections during admission is recommended.

Impact of ASHA training on active case detection of visceral leishmaniasis in Bihar, India.

PubMed

Das, Vidya Nand Ravi; Pandey, Ravindra Nath; Pandey, Krishna; Singh, Varsha; Kumar, Vijay; Matlashewski, Greg; Das, Pradeep

2014-05-01

One of the major challenges for management of visceral leishmaniasis (VL) is early diagnosis of cases to improve treatment outcome and reduce transmission. We have therefore investigated active case detection of VL with the help of accredited social health activists (ASHA). ASHAs are women who live in the community and receive performance-based incentives for overseeing maternal and other health-related issues in their village. Through conducting interviews with 400 randomly selected ASHAs from four primary health care centers (PHCs), it was observed that their level of knowledge about visceral leishmaniasis (VL) regarding transmission, diagnosis, and treatment was limited. The baseline data indicated that less than 10% of VL cases seeking treatment at the PHCs were referred by ASHAs. To increase the knowledge and the referral rate of VL cases by ASHAs, training sessions were carried out during the monthly ASHA meetings at their respective PHCs. Following a single training session, the referral rate increased from less than 10% to over 27% and the overall knowledge about VL substantially improved. It was not possible, however, to demonstrate that ASHA training reduced the time that individuals had fever before treatment at the PHC. Training ASHAs to identify VL cases in villages for early diagnosis and treatment at the local PHC is feasible and should be undertaken routinely to improve knowledge about VL.

Options to Expand HIV Viral Load Testing in South Africa: Evaluation of the GeneXpert® HIV-1 Viral Load Assay

PubMed Central

Gous, Natasha; Scott, Lesley; Berrie, Leigh; Stevens, Wendy

2016-01-01

Background Expansion of HIV viral load (VL) testing services are required to meet increased targets for monitoring patients on antiretroviral treatment. South Africa currently tests >4million VLs per annum in 16 highly centralised, automated high-throughput laboratories. The Xpert HIV-1 VL assay (Cepheid) was evaluated against in-country predicates, the Roche Cobas Taqmanv2 and Abbott HIV-1RT, to investigate options for expanding VL testing using GeneXpert’s random access, polyvalent capabilities and already established footprint in South Africa with the Xpert MTB/RIF assay (207 sites). Additionally, the performance of Xpert HIV-1VL on alternative, off-label specimen types, Dried Blood Spots (DBS) and whole blood, was investigated. Method Precision, accuracy (agreement) and clinical misclassification (1000cp/ml) of Xpert HIV-1VL plasma was compared to Taqmanv2 (n = 155) and Abbott HIV-1 RT (n = 145). Misclassification of Xpert HIV-1VL was further tested on DBS (n = 145) and whole blood (n = 147). Results Xpert HIV-1VL demonstrated 100% concordance with predicate platforms on a standardised frozen, plasma panel (n = 42) and low overall percentage similarity CV of 1.5% and 0.9% compared to Taqmanv2 and Abbott HIV-1 RT, respectively. On paired plasma clinical specimens, Xpert HIV-1VL had low bias (SD 0.32–0.37logcp/ml) and 3% misclassification at the 1000cp/ml threshold compared to Taqmanv2 (fresh) and Abbott HIV-1 RT (frozen), respectively. Xpert HIV-1VL on whole blood and DBS increased misclassification (upward) by up to 14% with increased invalid rate. All specimen testing was easy to perform and compatible with concurrent Xpert MTB/RIF Tuberculosis testing on the same instrument. Conclusion The Xpert HIV-1VL on plasma can be used interchangeably with existing predicate platforms in South Africa. Whole blood and DBS testing requires further investigation, but polyvalency of the GeneXpert offers a solution to extending VL testing services. PMID:27992495

HIV-1 DNA levels in peripheral blood mononuclear cells and cannabis use are associated with intermittent HIV shedding in semen of men who have sex with men on successful antiretroviral regimens.

PubMed

Ghosn, Jade; Leruez-Ville, Marianne; Blanche, Jérôme; Delobelle, Aurore; Beaudoux, Céline; Mascard, Laurence; Lecuyer, Hervé; Canestri, Ana; Landman, Roland; Zucman, David; Ponscarme, Diane; Rami, Agathe; Viard, Jean-Paul; Spire, Bruno; Rouzioux, Christine; Costagliola, Dominique; Suzan-Monti, Marie

2014-06-01

Few data exist on the efficacy of combined antiretroviral therapy (cART) in semen of human immunodeficiency virus type 1 (HIV-1) infected men who have sex with men (MSM) with sustained control of HIV replication in blood. HIV-1 infected MSM on successful cART for >6 months were enrolled. HIV-RNA was quantified in seminal plasma (spVL) and in blood plasma (bpVL) from 2 paired samples collected 4 weeks apart. Relationship between spVL and bpVL (measured by an ultrasensitive assay, LOQ 10 copies/mL), total peripheral blood mononuclear cells (PBMC)-associated HIV-DNA, sexually transmitted infections (STIs), and self-reported socio-behavioral characteristics was assessed using GEE logistic regression. In total, 157 patients were included. Median time with bpVL <50 copies/mL was 3.3 years. spVL was detectable in 23/304 samples (prevalence 7.6%). Median spVL was 145 cp/mL (100-1475). spVL was detectable on the first, on the second, and on both samples in 5, 14, and 2 men, respectively. In sum, 33 individuals (21%) had STIs (asymptomatic in 24/33). Residual bpVL was undetectable by ultrasensitive assay in 225/300 samples (75%). After multivariable adjustments, PBMC-associated HIV-DNA (OR 2.6[1.2; 6.0], for HIV-DNA > 2.5 log10 cp/10(6) PBMC, P = .02), and cannabis use during sexual intercourse (OR 2.8[1.2; 6.7], P = .02) were the only factors associated significantly with spVL. We show that HIV-RNA can be detected intermittently in semen of HIV-1 infected MSM despite successful cART. The size of blood HIV-1 reservoir predicted spVL detection. Our results indicated also that the possible effect of cannabis should be taken into account when developing prevention interventions targeted toward HIV-infected MSM on successful cART. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Noninvasive Diagnosis of Visceral Leishmaniasis: Development and Evaluation of Two Urine-Based Immunoassays for Detection of Leishmania donovani Infection in India

PubMed Central

Ejazi, Sarfaraz Ahmad; Bhattacharya, Pradyot; Bakhteyar, Md. Asjad Karim; Mumtaz, Aquil Ahmad; Pandey, Krishna; Das, Vidya Nand Ravi; Das, Pradeep; Rahaman, Mehebubar; Goswami, Rama Prosad; Ali, Nahid

2016-01-01

Background Visceral Leishmaniasis (VL), a severe parasitic disease, could be fatal if diagnosis and treatment is delayed. Post kala-azar dermal leishmaniasis (PKDL), a skin related outcome, is a potential reservoir for the spread of VL. Diagnostic tests available for VL such as tissue aspiration are invasive and painful although they are capable of evaluating the treatment response. Serological tests although less invasive than tissue aspiration are incompetent to assess cure. Parasitological examination of slit-skin smear along with the clinical symptoms is routinely used for diagnosis of PKDL. Therefore, a noninvasive test with acceptable sensitivity and competency, additionally, to decide cure would be an asset in disease management and control. Methodology/principal findings We describe here, the development of antibody-capture ELISA and field adaptable dipstick test as noninvasive diagnostic tools for VL and PKDL and as a test of cure in VL treatment. Sensitivity and specificity of urine-ELISA were 97.94% (95/97) and 100% (75/75) respectively, for VL. Importantly, dipstick test demonstrated 100% sensitivity (97/97) and specificity (75/75) in VL diagnosis. Degree of agreement of the two methods with tissue aspiration was 98.83% (κ = 0.97) and 100% (κ = 1), for ELISA and dipstick test, respectively. Both the tests had 100% positivity for PKDL (14/14) cases. ELISA and dipstick test illustrated treatment efficacy in about 90% (16/18) VL cases when eventually turned negative after six months of treatment. Conclusions/significance ELISA and dipstick test found immensely effective for diagnosis of VL and PKDL through urine samples thus, may substitute the existing invasive diagnostics. Utility of these tests as indirect methods of monitoring parasite clearance can define infected versus cured. Urine-based dipstick test is simple, sensitive and above all noninvasive method that may help not only in active VL case detection but also to ascertain treatment response. It can therefore, be deployed widely for interventions in disease management of VL particularly in poor resource outskirts. PMID:27741241

Plasma viraemia in HIV-positive pregnant women entering antenatal care in South Africa

PubMed Central

Myer, Landon; Phillips, Tamsin K; Hsiao, Nei-Yuan; Zerbe, Allison; Petro, Gregory; Bekker, Linda-Gail; McIntyre, James A; Abrams, Elaine J

2015-01-01

Introduction Plasma HIV viral load (VL) is the principle determinant of mother-to-child HIV transmission (MTCT), yet there are few data on VL in populations of pregnant women in sub-Saharan Africa. We examined the distribution and determinants of VL in HIV-positive women seeking antenatal care (ANC) in Cape Town, South Africa. Methods Consecutive HIV-positive pregnant women making their first antenatal clinic visit were recruited into a cross-sectional study of viraemia in pregnancy, including a brief questionnaire and specimens for VL testing and CD4 cell enumeration. Results & discussion Overall 5551 pregnant women sought ANC during the study period, of whom 1839 (33%) were HIV positive and 1521 (85%) were included. Approximately two-thirds of HIV-positive women in the sample (n=947) were not on antiretrovirals at the time of the first ANC visit, and the remainder (38%, n=574) had initiated antiretroviral therapy (ART) prior to conception. For women not on ART, the median VL was 3.98 log10 copies/mL; in this group, the sensitivity of CD4 cell counts ≤350 cells/µL in detecting VL>10,000 copies/mL was 64% and this increased to 78% with a CD4 threshold of ≤500 cells/µL. Among women on ART, 78% had VL<50 copies/mL and 13% had VL >1000 copies/mL at the time of their ANC visit. Conclusions VL >10,000 copies/mL was commonly observed in women not on ART with CD4 cell counts >350 cells/µL, suggesting that CD4 cell counts may not be adequately sensitive in identifying women at greatest risk of MTCT. A large proportion of women entering ANC initiated ART before conception, and in this group more than 10% had VL>1000 copies/mL despite ART use. VL monitoring during pregnancy may help to identify pregnancies that require additional clinical attention to minimize MTCT risk and improve maternal and child health outcomes. PMID:26154734

A review of visceral leishmaniasis during the conflict in South Sudan and the consequences for East African countries.

PubMed

Al-Salem, Waleed; Herricks, Jennifer R; Hotez, Peter J

2016-08-22

Visceral leishmaniasis (VL), caused predominantly by Leishmania donovani and transmitted by both Phlebotomus orientalis and Phlebotomus martini, is highly endemic in East Africa where approximately 30 thousands VL cases are reported annually. The largest numbers of cases are found in Sudan - where Phlebotomus orientalis proliferate in Acacia forests especially on Sudan's eastern border with Ethiopia, followed by South Sudan, Ethiopia, Somalia, Kenya and Uganda. Long-standing civil war and unrest is a dominant determinant of VL in East African countries. Here we attempt to identify the correlation between VL epidemics and civil unrest. In this review, literature published between 1955 and 2016 have been gathered from MSF, UNICEF, OCHA, UNHCR, PubMed and Google Scholar to analyse the correlation between conflict and human suffering from VL, which is especially apparent in South Sudan. Waves of forced migration as a consequence of civil wars between 1983 and 2005 have resulted in massive and lethal epidemics in southern Sudan. Following a comprehensive peace agreement, but especially with increased allocation of resources for disease treatment and prevention in 2011, cases of VL declined reaching the lowest levels after South Sudan declared independence. However, in the latest epidemic that began in 2014 after the onset of a civil war in South Sudan, more than 1.5 million displaced refugees have migrated internally to states highly endemic for VL, while 800,000 have fled to neighboring countries. We find a strong relationship between civil unrest and VL epidemics which tend to occur among immunologically naïve migrants entering VL-endemic areas and when Leishmania-infected individuals migrate to new areas and establish additional foci of disease. Further complicating factors in East Africa's VL epidemics include severe lack of access to diagnosis and treatment, HIV/AIDS co-infection, food insecurity and malnutrition. Moreover, cases of post-kala-azar dermal leishmaniasis (PKDL) can serve as important reservoirs of anthroponotic Leishmania parasites.

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification

PubMed Central

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-01-01

Abstract The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS. Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined. A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was <0.5 log cps/mL with all 3 assays but >25% of the specimens differed by >0.5 log cps/mL. All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1). The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens. PMID:27902602

Sensitivity and specificity of dried blood spots for HIV-1 viral load quantification: A laboratory assessment of 3 commercial assays.

PubMed

Pannus, Pieter; Claus, Maarten; Gonzalez, Maria Mercedes Perez; Ford, Nathan; Fransen, Katrien

2016-11-01

The use of dried blood spots (DBS) instead of plasma as a specimen type for HIV-1 viral load (VL) testing facilitates the decentralization of specimen collection and can increase access to VL testing in resource-limited settings. The performance of DBS for VL testing is lower, however, when compared to the gold standard sample type plasma. In this diagnostic accuracy study, we evaluated 3 VL assays with DBS.Participants were recruited between August 2012 and April 2015. Both plasma and DBS specimens were prepared and tested for HIV-1 VL with the Roche CAP/CTM HIV-1 test v2.0, the Abbott RealTime HIV-1, and the bioMérieux NucliSENS EasyQ HIV-1 v2.0. Sensitivity and specificity to detect treatment failure at a threshold of 1000 cps/mL with DBS were determined.A total of 272 HIV-positive patients and 51 HIV-negative people were recruited in the study. The mean difference or bias between plasma and DBS VL was <0.5 log cps/mL with all 3 assays but >25% of the specimens differed by >0.5 log cps/mL.All 3 assays had comparable sensitivities around 80% and specificities around 90%. Upward misclassification rates were around 10%, but downward misclassification rates ranged from 20.3% to 23.6%. Differences in between assays were not statistically significant (P > 0.1).The 3 VL assays evaluated had suboptimal performance with DBS but still performed better than immunological or clinical monitoring. Even after the introduction of the much-anticipated point-of-care VL devices, it is expected that DBS will remain important as a complementary option for supporting access to VL monitoring, particularly in rural, resource-limited settings. Manufacturers should accelerate efforts to develop more reliable, sensitive and specific methods to test VL on DBS specimens.

Bacterial Sepsis in Patients with Visceral Leishmaniasis in Northwest Ethiopia

PubMed Central

Takele, Yegnasew; Woldeyohannes, Desalegn; Tiruneh, Moges; Mohammed, Rezika; Lynen, Lutgarde; van Griensven, Johan

2014-01-01

Background and Objectives. Visceral leishmaniasis (VL) is one of the neglected diseases affecting the poorest segment of world populations. Sepsis is one of the predictors for death of patients with VL. This study aimed to assess the prevalence and factors associated with bacterial sepsis, causative agents, and their antimicrobial susceptibility patterns among patients with VL. Methods. A cross-sectional study was conducted among parasitologically confirmed VL patients suspected of sepsis admitted to the University of Gondar Hospital, Northwest Ethiopia, from February 2012 to May 2012. Blood cultures and other clinical samples were collected and cultured following the standard procedures. Results. Among 83 sepsis suspected VL patients 16 (19.3%) had culture confirmed bacterial sepsis. The most frequently isolated organism was Staphylococcus aureus (68.8%; 11/16), including two methicillin-resistant isolates (MRSA). Patients with focal bacterial infection were more likely to have bacterial sepsis (P < 0.001). Conclusions. The prevalence of culture confirmed bacterial sepsis was high, predominantly due to S. aureus. Concurrent focal bacterial infection was associated with bacterial sepsis, suggesting that focal infections could serve as sources for bacterial sepsis among VL patients. Careful clinical evaluation for focal infections and prompt initiation of empiric antibiotic treatment appears warranted in VL patients. PMID:24895569

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

PubMed Central

Romero, Gustavo A. S.; Boelaert, Marleen

2010-01-01

Background While three countries in South Asia decided to eliminate anthroponotic visceral leishmaniasis (VL) by 2015, its control in other regions seems fraught with difficulties. Is there a scope for more effective VL control in the Americas where transmission is zoonotic? We reviewed the evidence on VL control strategies in Latin America—diagnosis, treatment, veterinary interventions, vector control—with respect to entomological and clinical outcomes. Methodology/Principal Findings We searched the electronic databases of MEDLINE, LILACS, and the Cochrane Central Register of Controlled Trials, from 1960 to November 2008 and references of selected articles. Intervention trials as well as observational studies that evaluated control strategies of VL in the Americas were included. While the use of rapid diagnostic tests for VL diagnosis seems well established, there is a striking lack of evidence from clinical trials for drug therapy and few well designed intervention studies for control of vectors or canine reservoirs. Conclusion Elimination of zoonotic VL in the Americas does not seem a realistic goal at this point given the lack of political commitment, gaps in scientific knowledge, and the weakness of case management and surveillance systems. Research priorities and current strategies should be reviewed with the aim of achieving better VL control. PMID:20098726

Low castes have poor access to visceral leishmaniasis treatment in Bihar, India.

PubMed

Pascual Martínez, F; Picado, A; Roddy, P; Palma, P

2012-05-01

Bihar, the poorest state in India, concentrates most of the visceral leishmaniasis (VL) cases in the country. A large proportion of the poor rural communities where VL is endemic are marginalized by their socio-economic status, intrinsically related to the caste system. In this study, we evaluated whether people from low socio-economic strata had difficulties accessing VL treatment in Bihar. As a secondary outcome, we evaluated whether people delaying their VL treatment had poorer clinical indicators at admission. Data on 2187 patients with VL treated by Médecins Sans Frontières (MSF) in Vaishali district from July 2007 to December 2008 were analysed. Patients who reported having onset of symptoms ≥8 weeks before admission were defined as 'late presenters'. Logistic regression models were used to evaluate whether low castes had higher risk to be 'late presenters' compared to the rest of castes and whether 'late presenters' had poorer indicators at admission (i.e. haemoglobin level, spleen size). After adjusting for age, gender and distance to VL treatment facility, Mushars (the lowest caste in Bihar) had twice the odds to be 'late presenters' compared to the rest of castes (OR 2.05, 95% CI: 1.24-2.38). Subjects that had VL symptoms for ≥8 weeks had a larger spleen and lower haemoglobin level than those that were treated earlier. Low castes have poor access to VL treatment in Bihar, and late presenters have poorer clinical indicators at admission. These findings have implications at individual and community levels and should stimulate targeted VL control programmes to ensure that marginalized communities in Bihar are properly treated. © 2012 Blackwell Publishing Ltd.

Vocal local versus pharmacological treatments for pain management in tubal ligation procedures in rural Kenya: a non-inferiority trial.

PubMed

Keogh, Sarah C; Fry, Kenzo; Mbugua, Edwin; Ayallo, Mark; Quinn, Heidi; Otieno, George; Ngo, Thoai D

2014-02-04

Vocal local (VL) is a non-pharmacological pain management technique for gynecological procedures. In Africa, it is usually used in combination with pharmacological analgesics. However, analgesics are associated with side-effects, and can be costly and subject to frequent stock-outs, particularly in remote rural settings. We compared the effectiveness of VL + local anesthesia + analgesics (the standard approach), versus VL + local anesthesia without analgesics, on pain and satisfaction levels for women undergoing tubal ligations in rural Kenya. We conducted a site-randomised non-inferiority trial of 884 women receiving TLs from 40 Marie Stopes mobile outreach sites in Kisii and Machakos Districts. Twenty sites provided VL + local anesthesia + analgesics (control), while 20 offered VL + local anesthesia without additional analgesics (intervention). Pain was measured using a validated 11-point Numeric Rating Scale; satisfaction was measured using 11-point scales. A total of 461 women underwent tubal ligations with VL + local anesthesia, while 423 received tubal ligations with VL + local anesthesia + analgesics. The majority were aged ≥30 years (78%), and had >3 children (99%). In a multivariate analysis, pain during the procedure was not significantly different between the two groups. The pain score after the procedure was significantly lower in the intervention group versus the control group (by 0.40 points; p = 0.041). Satisfaction scores were equally high in both groups; 96% would recommend the procedure to a friend. VL + local anesthesia is as effective as VL + local anesthesia + analgesics for pain management during tubal ligation in rural Kenya. Avoiding analgesics is associated with numerous benefits including cost savings and fewer issues related to the maintenance, procurement and monitoring of restricted opioid drugs, particularly in remote low-resource settings where these systems are weak. Pan-African Clinical Trials Registry PACTR201304000495942.

Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis

PubMed Central

Smit, Pieter W.; Sollis, Kimberly A.; Fiscus, Susan; Ford, Nathan; Vitoria, Marco; Essajee, Shaffiq; Barnett, David; Cheng, Ben; Crowe, Suzanne M.; Denny, Thomas; Landay, Alan; Stevens, Wendy; Habiyambere, Vincent; Perriens, Joseph H.; Peeling, Rosanna W.

2014-01-01

Background Dried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID. Methods and Findings Thirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies. Conclusions Although limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation. Trial Registration PROSPERO Registration #: CRD42013003621. PMID:24603442

Epidemiological profile of patients co-infected with visceral leishmaniasis and HIV/AIDS in Northeast, Brazil.

PubMed

Viana, Graça Maria de Castro; Silva, Marcos Antonio Custódio Neto da; Garcia, João Victor de Sousa; Guimarães, Helaine Dias; Arcos, Gelson Farias; Santos, Augusto Viana Arouche; Paixão, Pedro Viana da; Nascimento, Maria do Desterro Soares Brandão; Galvão, Carolina de Souza

2017-01-01

Visceral leishmaniasis (VL) and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) co-infection has been a research topic of interest worldwide. In Brazil, it has been observed that there is a relative underreporting and failure in the understanding and management of this important association. The aim of this study was to analyze epidemiological and clinical aspects of patients with VL with and without HIV/AIDS. We conducted an observational and analytical study of patients with VL followed in a Reference Service in the State of Maranhão, Brazil from 2007-2013. In total 126 patients were enrolled, of which 61 (48.4%) were co-infected with HIV/AIDS. There were more males among those with HIV/AIDS (85.2%, P>0.05) or with VL only (81.5%, P>0.05). These findings significantly differed based on age group (P<0.003); the majority of patients were aged 31-40 years (41.0%) and 21-30 years (32.3%) among those with and without HIV/AIDS co-infection, respectively. The incidence of diarrhea and splenomegaly significantly differed between the two groups (P=0.0014 and P=0.019, respectively). The myelogram parasitic examination was used most frequently among those with HIV/AIDS (91.8%), followed by those with VL only (69.2%). VL recurrences and mortality were significantly higher in the HIV/AIDS co-infected patients (P<0.0001 and P=0.012, respectively). Patients with VL with or without HIV/AIDS co-infection were mostly adult men. Diarrhea was more frequent in HIV/AIDS co-infected patients, whereas splenomegaly was more common in patients with VL only. In the group of HIV/AIDS co-infected patients, there was a higher rate of VL recurrence and mortality.

Positive Influence of Behavior Change Communication on Knowledge, Attitudes, and Practices for Visceral Leishmaniasis/Kala-azar in India.

PubMed

Srinivasan, Raghavan; Ahmad, Tanwir; Raghavan, Vidya; Kaushik, Manisha; Pathak, Ramakant

2018-03-21

Visceral leishmaniasis (VL) is endemic to 54 districts in 4 states of India. Poor awareness of the disease and inappropriate health-seeking behavior are major challenges to eliminating the disease. Between February 2016 and March 2017, we implemented a behavior change communication (BCC) intervention in 33 districts of Bihar, 4 districts of Jharkhand, and 3 districts of West Bengal using a mix of channels, including group and interpersonal communication, to improve knowledge, attitudes, and practices of communities, frontline health workers, and opinion leaders. We conducted an impact assessment in October 2016, after the second indoor residual spraying (IRS) round, in Bihar and Jharkhand to evaluate the effect of the BCC intervention. Villages in 10 districts of Bihar and 4 districts in Jharkhand were selected for inclusion in the assessment. Selected villages were categorized as either intervention or control based on where project activities were conducted. Households were randomly selected proportional to caste composition, and interviewers surveyed the head of the household on whether the house was sprayed during the last IRS round and on knowledge, attitudes, and practices related to VL. We interviewed 700 households in intervention villages and 350 households in control villages and conducted correlation analysis to explore the association between IRS refusal and socioeconomic variables, and tested for association between IRS refusal and exposure to BCC activities. Odds ratios (ORs) were calculated. We reached an estimated 3.3 million contacts in Bihar and Jharkhand through the intervention's BCC activities. IRS refusal rates were significantly lower in intervention households than control households (mean=7.95% vs. 24.45%, respectively; OR, 0.27; 95% confidence interval [CI], 0.11 to 0.62; P <.001). Households in intervention villages were more aware than those in control villages that VL is spread by sand flies (68.4% vs. 7.4%, respectively; P <.001) and of IRS as an effective control measure (82.3% vs. 41.7%, respectively; P <.001). A greater percentage of households in intervention villages than control villages indicated they would encourage a patient to go to primary health centers for diagnosis and treatment of VL (77.0% vs. 39.4%, respectively) and to encourage others to accept IRS (78.6% vs. 44.6%, respectively; P <.001). Households that were exposed to community-based BCC activities largely using group and interpersonal communication had better knowledge, attitudes, and practices related to VL, including acceptance of IRS as a preventive measure, than households not exposed. BCC activities are thus an important component of VL elimination strategies. © Srinivasan et al.

Dynamics of Viremia in Primary HIV-1 infection in Africans: Insights from Analyses of Host and Viral Correlates

PubMed Central

Prentice, Heather A.; Price, Matthew A.; Porter, Travis R.; Cormier, Emmanuel; Mugavero, Michael J.; Kamali, Anatoli; Karita, Etienne; Lakhi, Shabir; Sanders, Eduard J.; Anzala, Omu; Amornkul, Pauli N.; Allen, Susan; Hunter, Eric; Kaslow, Richard A.; Gilmour, Jill; Tang, Jianming

2014-01-01

In HIV-1 infection, plasma viral load (VL) has dual implications for pathogenesis and public health. Based on well-known patterns of HIV-1 evolution and immune escape, we hypothesized that VL is an evolving quantitative trait that depends heavily on duration of infection (DOI), demographic features, human leukocyte antigen (HLA) genotypes and viral characteristics. Prospective data from 421 African seroconverters with at least four eligible visits did show relatively steady VL beyond 3 months of untreated infection, but host and viral factors independently associated with cross-sectional and longitudinal VL often varied by analytical approaches and sliding time windows. Specifically, the effects of age, HLA-B*53 and infecting HIV-1 subtypes (A1, C and others) on VL were either sporadic or highly sensitive to time windows. These observations were strengthened by the addition of 111 seroconverters with 2–3 eligible VL results, suggesting that DOI should be a critical parameter in epidemiological and clinical studies. PMID:24418560

Is the polymorphism at position -1082 of IL-10 gene associated with visceral leishmaniasis?

PubMed

Hajilooi, Mehrdad; Ahmadi, Alireza; Lotfi, Pegah; Matini, Mohammad; Jafari, Davood; Bazmani, Ahad; Momeni, Mohammad

2014-08-01

Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL.

Is the Polymorphism at Position -1082 of IL-10 Gene Associated with Visceral Leishmaniasis?

PubMed Central

HAJILOOI, Mehrdad; AHMADI, Alireza; LOTFI, Pegah; MATINI, Mohammad; JAFARI, Davood; BAZMANI, Ahad; MOMENI, Mohammad

2014-01-01

Abstract Background Immune responses play critical roles in the leishmaniasis eradication. IL-10 is a key regulator of immune responses, and the polymorphisms within its promoter region are associated with alteration in its expression. Therefore, this study was designed to examine the correlation between polymorphism at the -1082 position of the IL-10 gene and visceral leishmaniasis (VL). Methods The IL-10 -1082 polymorphism and anti-Leishmania antibody titration were examined in 110 patients with clinical presentation of VL and seropositive for the Leishmania (group 1), 74 seropositive patients but without clinical presentation (group 2) and 113 healthy controls (group 3) using the PCR-RFLP and immunofluorescence techniques, respectively. Results The polymorphism at IL-10 -1082 (A/G) position was significantly associated with VL and A/G genotype was significantly higher in VL patients when compared to the groups 2 and 3 (P< 0.001). However, the results demonstrated that the A and G alleles were not associated with VL (P= 0.263). Conclusions Previous investigations have shown that the polymorphism at the -1082 position of the IL-10 gene can influence its expression and also it has been proved that IL-10 level was increased during VL. Our results suggest that the A/G genotype may be considered as a risk factor for VL. PMID:25927040

Childhood visceral leishmaniasis.

PubMed

Bhattacharya, S K; Sur, Dipika; Karbwang, Juntra

2006-03-01

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. Nearly half of the VL cases occur in children (childhood or paediatric VL). The clinical manifestations of childhood VL are more or less same as in the adults. Prolonged fever with anorexia and loss of appetite are the major presenting features. Marked enlargement of the spleen and liver (spleen larger than liver) with moderate to severe anaemia and changes in hair take place. Bacterial infection is a common coinfection and intestinal parasitic infestations are very common in children with VL. Liver function tests, blood, urine and stool may show abnormalities. Confirmation of diagnosis is made by demonstration of parasite by microscopic examination and culture of materials obtained by bone marrow aspiration or splenic puncture. Sodium antimony gluconate (stibogluconate) has been the drug of choice for over past 50 yr. Pentamidine isothionate, though effective is relatively toxic. Amphotericin B is the most effective drug for the treatment of VL. Miltefosine is the first-ever oral drug, is highly effective. Post kala-azar dermal leishmaniasis (PKDL) in children poses a therapeutic challenge. In the absence of an ideal vaccine for VL, control measures would essentially include prevention of transmission through vector control and community awareness.

DNA vaccine against visceral leishmaniasis: a promising approach for prevention and control.

PubMed

Kumar, A; Samant, M

2016-05-01

The visceral leishmaniasis (VL) caused by Leishmania donovani parasite severely affects large populations in tropical and subtropical regions of the world. The arsenal of drugs available is limited, and resistance is common in clinical field isolates. Therefore, vaccines could be an important alternative for prevention against VL. Recently, some investigators advocated the protective efficacy of DNA vaccines, which induces the T cell-based immunity against VL. The vaccine antigens are selected as conserved in various Leishmania species and provide a viable strategy for DNA vaccine development. Our understanding for DNA vaccine development against VL is not enough and much technological advancement is required. Improved formulations and methods of delivery are required, which increase the uptake of DNA vaccine by cells; optimization of vaccine vectors/encoded antigens to augment and direct the host immune response in VL. Despite the many genes identified as vaccine candidates, the disappointing potency of the DNA vaccines in VL underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the design, strategy, safety issues, varied candidates, progress and challenges that play a role in their ability against VL. © 2016 John Wiley & Sons Ltd.

Identification of an Internal Ribosome Entry Segment in the 5′ Region of the Mouse VL30 Retrotransposon and Its Use in the Development of Retroviral Vectors

PubMed Central

López-Lastra, Marcelo; Ulrici, Sandrine; Gabus, Caroline; Darlix, Jean-Luc

1999-01-01

Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture. In this study, we addressed whether the 5′ region of VL30m could replace the 5′ leader of MoMLV functionally in a recombinant vector construct. Our data confirm that the putative packaging sequence of VL30 is located within the 5′ region (nucleotides 362 to 1149 with respect to the cap structure) and that it can replace the packaging sequence of MoMLV. We also show that VL30m contains an internal ribosome entry segment (IRES) in the 5′ region, as do MoMLV, Friend murine leukemia virus, Harvey murine sarcoma virus, and avian reticuloendotheliosis virus type A. Our data show that both the packaging and IRES functions of the 5′ region of VL30m RNA can be efficiently used to develop retrotransposon-based vectors. PMID:10482590

Identification of an internal ribosome entry segment in the 5' region of the mouse VL30 retrotransposon and its use in the development of retroviral vectors.

PubMed

López-Lastra, M; Ulrici, S; Gabus, C; Darlix, J L

1999-10-01

Mouse virus-like 30S RNAs (VL30m) constitute a family of retrotransposons, present at 100 to 200 copies, dispersed in the mouse genome. They display little sequence homology to Moloney murine leukemia virus (MoMLV), do not encode virus-like proteins, and have not been implicated in retroviral carcinogenesis. However, VL30 RNAs are efficiently packaged into MLV particles that are propagated in cell culture. In this study, we addressed whether the 5' region of VL30m could replace the 5' leader of MoMLV functionally in a recombinant vector construct. Our data confirm that the putative packaging sequence of VL30 is located within the 5' region (nucleotides 362 to 1149 with respect to the cap structure) and that it can replace the packaging sequence of MoMLV. We also show that VL30m contains an internal ribosome entry segment (IRES) in the 5' region, as do MoMLV, Friend murine leukemia virus, Harvey murine sarcoma virus, and avian reticuloendotheliosis virus type A. Our data show that both the packaging and IRES functions of the 5' region of VL30m RNA can be efficiently used to develop retrotransposon-based vectors.

Liposomal amphotericin B as a treatment for human leishmaniasis

PubMed Central

Balasegaram, Manica; Ritmeijer, Koert; Lima, Maria Angeles; Burza, Sakib; Ortiz Genovese, Gemma; Milani, Barbara; Gaspani, Sara; Potet, Julien; Chappuis, François

2012-01-01

Introduction: Leishmaniasis is a parasitic disease transmitted by phlebotomine sandflies. Between 700,000 and 1.2 million cases of cutaneous leishmaniasis and between 200,000 and 400,000 cases of visceral leishmaniasis (VL), which is fatal if left untreated, occur annually worldwide. Liposomal amphotericin B (LAMB), alone or in combination with other drugs, has been extensively studied as VL treatment, but data on routine field use are limited, and several challenges to patients' access to this life-saving drug remain. Areas covered: This article provides a review of clinical studies on LAMB for VL and other forms of leishmaniasis. The current development of generic versions of LAMB and related challenges are also discussed. Expert opinion: LAMB proved to be highly efficacious and safe in over 8000 VL patients treated by MÉdecins Sans Frontières in South Asia, and its use was feasible even at primary healthcare level. Despite requiring higher doses, LAMB is the drug of choice to treat vulnerable groups (e.g., pregnant or HIV positive) and relapsing VL patients in East Africa. LAMB should be included in national VL guidelines and registered in all VL endemic countries. Its cost should be further reduced and regulatory pathways to prove bioequivalence for generic LAMB products should be implemented. PMID:23167833

Optimizing insecticide allocation strategies based on houses and livestock shelters for visceral leishmaniasis control in Bihar, India.

PubMed

Gorahava, Kaushik K; Rosenberger, Jay M; Mubayi, Anuj

2015-07-01

Visceral leishmaniasis (VL) is the most deadly form of the leishmaniasis family of diseases, which affects numerous developing countries. The Indian state of Bihar has the highest prevalence and mortality rate of VL in the world. Insecticide spraying is believed to be an effective vector control program for controlling the spread of VL in Bihar; however, it is expensive and less effective if not implemented systematically. This study develops and analyzes a novel optimization model for VL control in Bihar that identifies an optimal (best possible) allocation of chosen insecticide (dichlorodiphenyltrichloroethane [DDT] or deltamethrin) based on the sizes of human and cattle populations in the region. The model maximizes the insecticide-induced sandfly death rate in human and cattle dwellings while staying within the current state budget for VL vector control efforts. The model results suggest that deltamethrin might not be a good replacement for DDT because the insecticide-induced sandfly deaths are 3.72 times more in case of DDT even after 90 days post spray. Different insecticide allocation strategies between the two types of sites (houses and cattle sheds) are suggested based on the state VL-control budget and have a direct implication on VL elimination efforts in a resource-limited region. © The American Society of Tropical Medicine and Hygiene.

The economic burden of visceral leishmaniasis for households in Nepal.

PubMed

Rijal, S; Koirala, S; Van der Stuyft, P; Boelaert, M

2006-09-01

Visceral leishmaniasis (VL) affects persons from the lowest socioeconomic strata of the community, but its economic impact is not precisely known. An exploratory survey to document the economic costs of VL to households was conducted in an endemic focus in eastern Nepal. Data were collected from the 20 households in this cluster. Cases of VL over the last 3 years were elicited and information on direct and indirect costs incurred due to the disease as well as income of the households over the last year was estimated. It was reported that 15.0% (16/107) of the residents had suffered from VL and that almost all of the patients had preferred, in the first instance, to visit the private services or local faith healers instead of visiting the local public health facility. Average total costs incurred per episode of VL were above the median annual per capita income, and six of the seven affected households either had to sell part of their livestock or to take a loan to cover the costs. Direct costs consisted of 53% of the total cost, with 75% of this cost incurred before the patients actually received any treatment for VL. This study demonstrates how VL can lead to catastrophic expenditure for affected households.

The initial effectiveness of liposomal amphotericin B (AmBisome) and miltefosine combination for treatment of visceral leishmaniasis in HIV co-infected patients in Ethiopia: A retrospective cohort study.

PubMed

Abongomera, Charles; Diro, Ermias; de Lima Pereira, Alan; Buyze, Jozefien; Stille, Kolja; Ahmed, Fareed; van Griensven, Johan; Ritmeijer, Koert

2018-05-01

North-west Ethiopia faces the highest burden world-wide of visceral leishmaniasis (VL) and HIV co-infection. VL-HIV co-infected patients have higher (initial) parasitological failure and relapse rates than HIV-negative VL patients. Whereas secondary prophylaxis reduces the relapse rate, parasitological failure rates remain high with the available antileishmanial drugs, especially when administered as monotherapy. We aimed to determine the initial effectiveness (parasitologically-confirmed cure) of a combination of liposomal amphotericin B (AmBisome) and miltefosine for treatment of VL in HIV co-infected patients. We conducted a retrospective cohort study at a Médecins Sans Frontières-supported health center in north-west Ethiopia. We included VL-HIV co-infected adults, treated for VL between January 2011 and August 2014, with AmBisome infusion (30 mg/kg total dose) and miltefosine orally for 28 days (100 mg/day). Proportions of initial treatment outcome categories were calculated. Predictors of initial parasitological failure and of death were determined using multivariable logistic regression. Of the 173 patients included, 170 (98.3%) were male and the median age was 32 years. The proportion of patients with primary VL (48.0%) and relapse VL (52.0%) were similar. The majority had advanced HIV disease (n = 111; 73.5%) and were on antiretroviral therapy prior to VL diagnosis (n = 106; 64.2%). Initial cure rate was 83.8% (95% confidence interval [CI], 77.6-88.6); death rate 12.7% (95% CI, 8.5-18.5) and parasitological failure rate 3.5% (95% CI, 1.6-7.4). Tuberculosis co-infection at VL diagnosis was predictive of parasitological failure (adjusted odds ratio (aOR), 8.14; p = 0.02). Predictors of death were age >40 years (aOR, 5.10; p = 0.009), hemoglobin ≤6.5 g/dL (aOR, 5.20; p = 0.002) and primary VL (aOR, 8.33; p = 0.001). Initial parasitological failure rates were very low with AmBisome and miltefosine combination therapy. This regimen seems a suitable treatment option. Knowledge of predictors of poor outcome may facilitate better management. These findings remain to be confirmed in clinical trials.

Regional differences in rates of HIV-1 viral load monitoring in Canada: Insights and implications for antiretroviral care in high income countries.

PubMed

Raboud, Janet M; Loutfy, Mona R; Su, DeSheng; Bayoumi, Ahmed M; Klein, Marina B; Cooper, Curtis; Machouf, Nima; Rourke, Sean; Walmsley, Sharon; Rachlis, Anita; Harrigan, P Richard; Smieja, Marek; Tsoukas, Christos; Montaner, Julio S G; Hogg, Robert S

2010-02-25

Viral load (VL) monitoring is an essential component of the care of HIV positive individuals. Rates of VL monitoring have been shown to vary by HIV risk factor and clinical characteristics. The objective of this study was to determine whether there are differences among regions in Canada in the rates of VL testing of HIV-positive individuals on combination antiretroviral therapy (cART), where the testing is available without financial barriers under the coverage of provincial health insurance programs. The Canadian Observational Cohort (CANOC) is a collaboration of nine Canadian cohorts of HIV-positive individuals who initiated cART after January 1, 2000. The study included participants with at least one year of follow-up. Generalized Estimating Equation (GEE) regression models were used to determine the effect of geographic region on (1) the occurrence of an interval of 9 months or more between two consecutive recorded VL tests and (2) the number of days between VL tests, after adjusting for demographic and clinical covariates. Overall and regional annual rates of VL testing were also reported. 3,648 individuals were included in the analysis with a median follow-up of 42.9 months and a median of 15 VL tests. In multivariable GEE logistic regression models, gaps in VL testing >9 months were more likely in Quebec (Odds Ratio (OR) = 1.72, p < 0.0001) and Ontario (OR = 1.78, p < 0.0001) than in British Columbia and among injection drug users (OR = 1.68, p < 0.0001) and were less likely among older individuals (OR = 0.77 per 10 years, p < 0.0001), among men having sex with men (OR = 0.62, p < 0.0001), within the first year of cART (OR = 0.15, p < 0.0001), among individuals on cART at the time of the blood draw (OR = 0.34, p < 0.0001) and among individuals with VL < 50 copies/ml at the previous visit (OR = 0.56, p < .0001). Significant variation in rates of VL testing and the probability of a significant gap in testing were related to geographic region, HIV risk factor, age, year of cART initiation, type of cART regimen, being in the first year of cART, AIDS-defining illness and whether or not the previous VL was below the limit of detection.

Visceral leishmaniasis diagnosis and reporting delays as an obstacle to timely response actions in Nepal and India.

PubMed

Boettcher, Jan P; Siwakoti, Yubaraj; Milojkovic, Ana; Siddiqui, Niyamat A; Gurung, Chitra K; Rijal, Suman; Das, Pradeep; Kroeger, Axel; Banjara, Megha R

2015-02-06

To eliminate visceral leishmaniasis (VL) in India and Nepal, challenges of VL diagnosis, treatment and reporting need to be identified. Recent data indicate that VL is underreported and patients face delays when seeking treatment. Moreover, VL surveillance data might not reach health authorities on time. This study quantifies delays for VL diagnosis and treatment, and analyses the duration of VL reporting from district to central health authorities in India and Nepal. A cross-sectional study conducted in 12 districts of Terai region, Nepal, and 9 districts of Bihar State, India, in 2012. Patients were interviewed in hospitals or at home using a structured questionnaire, health managers were interviewed at their work place using a semi-structured questionnaire and in-depth interviews were conducted with central level health managers. Reporting formats were evaluated. Data was analyzed using two-tailed Mann-Whitney U or Fisher's exact test. 92 VL patients having experienced 103 VL episodes and 49 district health managers were interviewed. Patients waited in Nepal 30 days (CI 18-42) before seeking health care, 3.75 times longer than in Bihar (8d; CI 4-12). Conversely, the lag time from seeking health care to receiving a VL diagnosis was 3.6x longer in Bihar (90d; CI 68-113) compared to Nepal (25d; CI 13-38). The time span between diagnosis and treatment was short in both countries. VL reporting time was in Nepal 19 days for sentinel sites and 76 days for "District Public Health Offices (DPHOs)". In Bihar it was 28 days for "District Malaria Offices". In Nepal, 73% of health managers entered data into computers compared to 16% in Bihar. In both countries reporting was mainly paper based and standardized formats were rarely used. To decrease the delay between onset of symptoms and getting a proper diagnosis and treatment the approaches in the two countries vary: In Nepal health education for seeking early treatment are needed while in Bihar the use of private and non-formal practitioners has to be discouraged. Reinforcement of VL sentinel reporting in Bihar, reorganization of DPHOs in Nepal, introduction of standardized reporting formats and electronic reporting should be conducted in both countries.

Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA

PubMed Central

Tjen-A-Looi, Stephanie C.; Li, Peng; Longhurst, John C.

2009-01-01

A long-loop pathway, involving the hypothalamic arcuate nucleus (ARC), ventrolateral periaqueductal gray (vlPAG), and the rostral ventrolateral medulla (rVLM), is essential in electroacupuncture (EA) attenuation of sympathoexcitatory cardiovascular reflex responses. The ARC provides excitatory input to the vlPAG, which, in turn, inhibits neuronal activity in the rVLM. Although previous studies have shown that endocannabinoid CB1 receptor activation modulates γ-aminobutyric acid (GABA)-ergic and glutamatergic neurotransmission in the dorsolateral PAG in stress-induced analgesia, an important role for endocannabinoids in the vlPAG has not yet been observed. We recently have shown (Fu LW, Longhurst JC. J Appl Physiol; doi:10.1152/japplphysiol.91648.2008) that EA reduces the local vlPAG concentration of GABA, but not glutamate, as measured with high-performance liquid chromatography from extracellular samples collected by microdialysis. We, therefore, hypothesized that, during EA, endocannabinoids, acting through CB1 receptors, presynaptically inhibit GABA release to disinhibit the vlPAG and ultimately modulate excitatory reflex blood pressure responses. Rats were anesthetized, ventilated, and instrumented to measure heart rate and blood pressure. Gastric distention-induced blood pressure responses of 18 ± 5 mmHg were reduced to 6 ± 1 mmHg by 30 min of low-current, low-frequency EA applied bilaterally at pericardial P 5–6 acupoints overlying the median nerves. Like EA, microinjection of the fatty acid amide hydrolase inhibitor URB597 (0.1 nmol, 50 nl) into the vlPAG to increase endocannabinoids locally reduced the gastric distention cardiovascular reflex response from 21 ± 5 to 3 ± 4 mmHg. This inhibition was reversed by pretreatment with the GABAA antagonist gabazine (27 mM, 50 nl), suggesting that endocannabinoids exert their action through a GABAergic receptor mechanism in the vlPAG. The EA-related inhibition from 18 ± 3 to 8 ± 2 mmHg was reversed to 14 ± 2 mmHg by microinjection of the CB1 receptor antagonist AM251 (2 nmol, 50 nl) into the vlPAG. Pretreatment with gabazine eliminated reversal following CB1-receptor blockade. Thus EA releases endocannabinoids and activates presynaptic CB1 receptors to inhibit GABA release in the vlPAG. Reduction of GABA release disinhibits vlPAG cells, which, in turn, modulate the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses. PMID:19325030

Nutritional supplements for patients being treated for active visceral leishmaniasis.

PubMed

Custodio, Estefanía; López-Alcalde, Jesús; Herrero, Mercè; Bouza, Carmen; Jimenez, Carolina; Storcksdieck Genannt Bonsmann, Stefan; Mouratidou, Theodora; López-Cuadrado, Teresa; Benito, Agustin; Alvar, Jorge

2018-03-26

Visceral leishmaniasis (VL) is a disease caused by a parasite, which can lead to death if untreated. Poor nutritional status hastens the progression of VL infection, and VL worsens malnutrition status. Malnutrition is one of the poor prognostic factors identified for leishmaniasis. However, the effects of nutritional supplementation in people treated for VL are not known. To assess the effects of oral nutritional supplements in people being treated with anti-leishmanial drug therapy for VL. We searched the Cochrane Infectious Diseases Group (CIDG) Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, and two trial registers up to 12 September 2017. We checked conference proceedings and WHO consultative meeting reports, the reference lists of key documents and existing reviews, and contacted experts and nutritional supplement companies. Randomized controlled trials (RCTs), quasi-randomized controlled trials (quasi-RCTs), and non-randomized controlled trials (NRCTs) of any oral nutritional supplement, compared to no nutritional intervention, placebo, or dietary advice alone, in people being treated for VL. Two review authors independently screened the literature search results for studies that met the inclusion criteria. We had planned for two review authors to independently extract data and assess the risk of bias of the included studies. We planned to follow the Cochrane standard methodological procedures for assessing risk of bias and analysing the data. We identified no eligible studies for this review, either completed or ongoing. We found no studies, either completed or ongoing, that assessed the effects of oral nutritional supplements in people with VL who were being treated with anti-leishmanial drug therapy. Thus, we could not draw any conclusions on the impact of these interventions on primary cure of VL, definitive cure of VL, treatment completion, self-reported recovery from illness or resolution of symptoms, weight gain, increased skinfold thickness, other measures of lean or total mass, or growth in children.This absence of evidence should not be interpreted as evidence of no effect for nutritional supplements in people under VL treatment. It means that we did not identify research that fulfilled our review inclusion criteria.The effects of oral nutritional supplements in people with VL who are being treated with anti-leishmanial drug therapy have yet to be determined by rigorous experimental studies, such as cluster-randomized trials, that focus on outcomes relevant for patients.

Trends in spatio-temporal dynamics of visceral leishmaniasis cases in a highly-endemic focus of Bihar, India: an investigation based on GIS tools.

PubMed

Mandal, Rakesh; Kesari, Shreekant; Kumar, Vijay; Das, Pradeep

2018-04-02

Visceral leishmaniasis (VL) in Bihar State (India) continues to be endemic, despite the existence of effective treatment and a vector control program to control disease morbidity. A clear understanding of spatio-temporal distribution of VL may improve surveillance and control implementation. This study explored the trends in spatio-temporal dynamics of VL endemicity at a meso-scale level in Vaishali District, based on geographical information systems (GIS) tools and spatial statistical analysis. A GIS database was used to integrate the VL case data from the study area between 2009 and 2014. All cases were spatially linked at a meso-scale level. Geospatial techniques, such as GIS-layer overlaying and mapping, were employed to visualize and detect the spatio-temporal patterns of a VL endemic outbreak across the district. The spatial statistic Moran's I Index (Moran's I) was used to simultaneously evaluate spatial-correlation between endemic villages and the spatial distribution patterns based on both the village location and the case incidence rate (CIR). Descriptive statistics such as mean, standard error, confidence intervals and percentages were used to summarize the VL case data. There were 624 endemic villages with 2719 (average 906 cases/year) VL cases during 2012-2014. The Moran's I revealed a cluster pattern (P < 0.05) of CIR distribution at the meso-scale level. On average, 68 villages were newly-endemic each year. Of which 93.1% of villages' endemicity were found to have occurred on the peripheries of the previous year endemic villages. The mean CIR of the endemic villages that were peripheral to the following year newly-endemic villages, compared to all endemic villages of the same year, was higher (P < 0.05). The results show that the VL endemicity of new villages tends to occur on the periphery of villages endemic in the previous year. High-CIR plays a major role in the spatial dispersion of the VL cases between non-endemic and endemic villages. This information can help achieve VL elimination throughout the Indian subcontinent by improving vector control design and implementation in highly-endemic district.

Epidemiology and clinical features of patients with visceral leishmaniasis treated by an MSF clinic in Bakool region, Somalia, 2004-2006.

PubMed

Raguenaud, Marie-Eve; Jansson, Anna; Vanlerberghe, Veerle; Van der Auwera, Geert; Deborggraeve, Stijn; Dujardin, Jean-Claude; Orfanos, Giannos; Reid, Tony; Boelaert, Marleen

2007-10-31

There are few reports describing the epidemiology of visceral leishmaniasis (VL) in Somalia. Over the years 2002 to 2005, a yearly average of 140 patients were reported from the Huddur centre in Bakool region, whereas in 2006, this number rose to 1002 patients. Given the limited amount of information on VL and the opportunity to compare features with the studies done in 2000 in this part of Somalia, we describe the epidemiologic and clinical features of patients who presented to the Huddur treatment centre of Bakool region, Somalia, using data routinely collected over a five-year observation period (2002-2006). Methods used included the analysis of routine data on VL cases treated in the Huddur treatment centre, a retrospective study of records of patients admitted between 2004 and 2006, community leaders interviews, and analysis of blood specimens taken for parasite species identification in Antwerp Institute of Tropical Medicine. A total of 1671 VL patients were admitted to the Huddur centre from January 2002 until December 2006. Nearly all patients presented spontaneously to the health centre. Since 2002, the average patient load was stable, with an average of 140 admissions per year. By the end of 2005, the number of admissions dramatically increased to reach a 7-fold increase in 2006. The genotype of L. donovani identified in 2006 was similar to the one reported in 2002. 82% of total patients treated for VL originated from two districts of Bakool region, Huddur and Tijelow districts. Clinical recovery rate was 93.2% and case fatality rate 3.9%. After four years of low but constant VL case findings, a major increase in VL was observed over a 16-month period in the Huddur VL centre. The profile of the patients was pediatric and mortality relatively low. Decentralized treatment centers, targeted active screening, and community sensitization will help decrease morbidity and mortality from VL in this endemic area. The true magnitude of VL in Somalia remains unknown. Further documentation to better understand transmission dynamics and thus define appropriate control measures will depend on the stability of the context and safe access to the Somali population.

Cytokine Responses to Novel Antigens in an Indian Population Living in an Area Endemic for Visceral Leishmaniasis

PubMed Central

Singh, Om Prakash; Stober, Carmel B.; Singh, Abhishek Kr.

2012-01-01

Background There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations. Methods Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC+ve, n = 20) or modified Quantiferon negative (EHC−ve, n = 9) endemic healthy controls (EHC). Results Active VL, cured VL and EHC+ve groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC+ve did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC+ve exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55–87.5% responders) and EHC+ve (40–65% responders) subjects. Conclusions Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates. PMID:23150744

Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis.

PubMed

Singh, Om Prakash; Stober, Carmel B; Singh, Abhishek Kr; Blackwell, Jenefer M; Sundar, Shyam

2012-01-01

There are no effective vaccines for visceral leishmaniasis (VL), a neglected parasitic disease second only to malaria in global mortality. We previously identified 14 protective candidates in a screen of 100 Leishmania antigens as DNA vaccines in mice. Here we employ whole blood assays to evaluate human cytokine responses to 11 of these antigens, in comparison to known defined and crude antigen preparations. Whole blood assays were employed to measure IFN-γ, TNF-α and IL-10 responses to peptide pools of the novel antigens R71, Q51, L37, N52, L302.06, J89, M18, J41, M22, M63, M57, as well as to recombinant proteins of tryparedoxin peroxidase (TRYP), Leishmania homolog of the receptor for activated C kinase (LACK) and to crude soluble Leishmania antigen (SLA), in Indian patients with active (n = 8) or cured (n = 16) VL, and in modified Quantiferon positive (EHC(+ve), n = 20) or modified Quantiferon negative (EHC(-ve), n = 9) endemic healthy controls (EHC). Active VL, cured VL and EHC(+ve) groups showed elevated SLA-specific IFN-γ, but only active VL patients produced IL-10 and EHC(+ve) did not make TNF-α. IFN-γ to IL-10 and TNF-α to IL-10 ratios in response to TRYP and LACK antigens were higher in cured VL and EHC(+ve) exposed individuals compared to active VL. Five of the eleven novel candidates (R71, L37, N52, J41, and M22) elicited IFN-γ and TNF-α, but not IL-10, responses in cured VL (55-87.5% responders) and EHC(+ve) (40-65% responders) subjects. Our results are consistent with an important balance between pro-inflammatory IFNγ and TNFγ cytokine responses and anti-inflammatory IL-10 in determining outcome of VL in India, as highlighted by response to both crude and defined protein antigens. Importantly, cured VL patients and endemic Quantiferon positive individuals recognise 5 novel vaccine candidate antigens, confirming our recent data for L. chagasi in Brazil, and their potential as cross-species vaccine candidates.

[Vascularloops in reconstructive microsurgery: A review of the literature].

PubMed

Shipkov, H; Traikova, N; Voinov, P; Boucher, F; Braye, F; Mojallal, A

2014-02-01

The success of free tissue transfer depends on the quality of vascular micro-anastomosis and recipient vessels. Adequate recipient vessels are sometimes not available near the recipient site for they can be either destroyed or of poor quality (radiotherapy, traumatism). In such cases, good quality recipient vessels are at a distance from the reconstructed site. If this distance is important flap pedicle lengthening implies - for the artery, for the vein or for both flap artery and vein. This lengthening can be carried out in two manners - by interpositional vein grafts (VG) or by a vascular loop (VL) in one or two stages. The aim of this study was to review the utilisation of VL and their type since their introduction in the clinical practice of reconstructive microsurgery. Two main types of VL are used - BV by VG and VL "in situ". Both of them can be carried out in one or two stages. Each of these techniques has its advantages and disadvantages. The overall data from the literature shows that VL are indicated in cases where both artery and vein are damaged or destroyed. There is not enough evidence concerning the VL in one or two stages but there are some tendencies in favour of the VL in one stage. The technique of VL seems to be more avantageous over the interpositional VG but with a smaller success rate compared to free-flaps with direct anastomosis to recipient vessels. Further studies are necessary to investigate these controversial questions. Copyright © 2013. Published by Elsevier SAS.

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4+ T-cell Count?

PubMed Central

Ghiglione, Yanina; Hormanstorfer, Macarena; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D.; Pando, María de los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Sued, Omar

2018-01-01

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4+ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4+ T-cell activation (p < 0.05). However, none of these cytokines had good predictive values to distinguish “progressors” from “non-progressors”. Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied. PMID:29342870

Biomarkers of Progression after HIV Acute/Early Infection: Nothing Compares to CD4⁺ T-cell Count?

PubMed

Turk, Gabriela; Ghiglione, Yanina; Hormanstorfer, Macarena; Laufer, Natalia; Coloccini, Romina; Salido, Jimena; Trifone, César; Ruiz, María Julia; Falivene, Juliana; Holgado, María Pía; Caruso, María Paula; Figueroa, María Inés; Salomón, Horacio; Giavedoni, Luis D; Pando, María de Los Ángeles; Gherardi, María Magdalena; Rabinovich, Roberto Daniel; Pury, Pedro A; Sued, Omar

2018-01-13

Progression of HIV infection is variable among individuals, and definition disease progression biomarkers is still needed. Here, we aimed to categorize the predictive potential of several variables using feature selection methods and decision trees. A total of seventy-five treatment-naïve subjects were enrolled during acute/early HIV infection. CD4⁺ T-cell counts (CD4TC) and viral load (VL) levels were determined at enrollment and for one year. Immune activation, HIV-specific immune response, Human Leukocyte Antigen (HLA) and C-C chemokine receptor type 5 (CCR5) genotypes, and plasma levels of 39 cytokines were determined. Data were analyzed by machine learning and non-parametric methods. Variable hierarchization was performed by Weka correlation-based feature selection and J48 decision tree. Plasma interleukin (IL)-10, interferon gamma-induced protein (IP)-10, soluble IL-2 receptor alpha (sIL-2Rα) and tumor necrosis factor alpha (TNF-α) levels correlated directly with baseline VL, whereas IL-2, TNF-α, fibroblast growth factor (FGF)-2 and macrophage inflammatory protein (MIP)-1β correlated directly with CD4⁺ T-cell activation ( p < 0.05). However, none of these cytokines had good predictive values to distinguish "progressors" from "non-progressors". Similarly, immune activation, HIV-specific immune responses and HLA/CCR5 genotypes had low discrimination power. Baseline CD4TC was the most potent discerning variable with a cut-off of 438 cells/μL (accuracy = 0.93, κ-Cohen = 0.85). Limited discerning power of the other factors might be related to frequency, variability and/or sampling time. Future studies based on decision trees to identify biomarkers of post-treatment control are warrantied.

Epidemiology of Visceral Leishmaniasis in a Reemerging Focus of Intense Transmission in Minas Gerais State, Brazil

PubMed Central

Peixoto, Jennifer Cunha; Tanure, Aline; Gomes, Marcela Esteves; Apolinário, Estefânia Conceição; Bodevan, Emerson Cotta; de Araújo, Holbiano Saraiva; Dias, Edelberto Santos; Pinheiro, Aimara da Costa

2013-01-01

This study was developed in the urban area of Governador Valadares, a reemerging focus of intense transmission of visceral leishmaniasis (VL) in Brazil, presenting 86 human cases of VL from 2008 to 2011. The disease prevailed in males (73.2%) with most patients between 0 and 9 years (44.1%) and a lethality rate of 16.2%. A canine survey was carried out on 16,529 domestic dogs in 35 districts in the area and it showed that 30.2% of them (4,992 dogs) were positive for VL by serum assays. Prevalence ratios for canine VL varied between 13.6% and 53.4%. The clinical exam of 343 seropositive dogs showed that 49.9% of them were considered symptomatic, with larger prevalence of canine VL being in short-furred animals (90%). The entomological survey was performed in eight districts, where 2,539 phlebotomines were captured, preferentially in the peridomicile (84.5%). Lutzomyia longipalpis was the predominant species (90%) suggesting its participation in the VL transmission in the area. The correlation between canine prevalence and L. longipalpis density was evaluated. PMID:24000322

Cost-effectiveness of point-of-care viral load monitoring of antiretroviral therapy in resource-limited settings: mathematical modelling study.

PubMed

Estill, Janne; Egger, Matthias; Blaser, Nello; Vizcaya, Luisa Salazar; Garone, Daniela; Wood, Robin; Campbell, Jennifer; Hallett, Timothy B; Keiser, Olivia

2013-06-01

Monitoring of HIV viral load in patients on combination antiretroviral therapy (ART) is not generally available in resource-limited settings. We examined the cost-effectiveness of qualitative point-of-care viral load tests (POC-VL) in sub-Saharan Africa. Mathematical model based on longitudinal data from the Gugulethu and Khayelitsha township ART programmes in Cape Town, South Africa. Cohorts of patients on ART monitored by POC-VL, CD4 cell count or clinically were simulated. Scenario A considered the more accurate detection of treatment failure with POC-VL only, and scenario B also considered the effect on HIV transmission. Scenario C further assumed that the risk of virologic failure is halved with POC-VL due to improved adherence. We estimated the change in costs per quality-adjusted life-year gained (incremental cost-effectiveness ratios, ICERs) of POC-VL compared with CD4 and clinical monitoring. POC-VL tests with detection limits less than 1000 copies/ml increased costs due to unnecessary switches to second-line ART, without improving survival. Assuming POC-VL unit costs between US$5 and US$20 and detection limits between 1000 and 10,000 copies/ml, the ICER of POC-VL was US$4010-US$9230 compared with clinical and US$5960-US$25540 compared with CD4 cell count monitoring. In Scenario B, the corresponding ICERs were US$2450-US$5830 and US$2230-US$10380. In Scenario C, the ICER ranged between US$960 and US$2500 compared with clinical monitoring and between cost-saving and US$2460 compared with CD4 monitoring. The cost-effectiveness of POC-VL for monitoring ART is improved by a higher detection limit, by taking the reduction in new HIV infections into account and assuming that failure of first-line ART is reduced due to targeted adherence counselling.

Molecular cloning and functional analysis of two FAD2 genes from American grape (Vitis labrusca L.).

PubMed

Lee, Kyeong-Ryeol; Kim, Sun Hee; Go, Young-Sam; Jung, Sung Min; Roh, Kyung Hee; Kim, Jong-Bum; Suh, Mi-Chung; Lee, Sukchan; Kim, Hyun Uk

2012-11-10

The synthesis of polyunsaturated fatty acids (PUFAs), the most abundant fatty acids in plants, begins with a reaction catalyzed by fatty acid desaturase 2 (FAD2; EC 1.3.1.35), also called microsomal oleate Δ12-desaturase. Since the FAD2 gene was first identified in Arabidopsis thaliana, FAD2 research has gained wide interest as the essential enzyme for synthesizing PUFA. Grapes are one of the most frequently cultivated fruits in the world, with most commercial growers cultivating Vitis vinifera and V. labrusca. Grapeseed oil contains a high proportion, 60-70% of linoleic acid (18:2). We cloned two putative FAD2 genes from V. labrusca cv. Campbell Early based on V. vinifera genome sequences. Deduced amino acid sequences of two putative genes showed that VlFAD2s show high similarity to Arabidopsis FAD2 and commonly contain six transmembrane domain, three histidine boxes and endoplasmic reticulum (ER) retrieval motif representing the characteristics of fatty acid desaturase. Phylogenetic analyses of various plant FAD2s showed that VlFAD2-1 and VlFAD2-2 are separately grouped with constitutive and seed-type FAD2s, respectively. Southern blot showed that one or two bands are found in each lane. Because Campbell Early is a hybrid cultivar, FAD2-1 and FAD2-2 genes may exist as one copy in V. labrusca. Expression analysis in different tissues indicated that VlFAD2-1 is a constitutive gene but VlFAD2-2 is a seed-type gene. Complementation experiments of fad2-1 mutant Arabidopsis with VlFAD2-1 or VlFAD2-2 demonstrated that VlFAD2-1 and VlFAD2-2 can restore low PUFA proportion of fad2 to normal PUFA proportion. Copyright © 2012 Elsevier B.V. All rights reserved.

R Wave in aVL Lead is a Robust Index of Left Ventricular Hypertrophy: A Cardiac MRI Study.

PubMed

Courand, Pierre-Yves; Grandjean, Adrien; Charles, Paul; Paget, Vinciane; Khettab, Fouad; Bricca, Giampiero; Boussel, Loïc; Lantelme, Pierre; Harbaoui, Brahim

2015-08-01

In patients free from overt cardiac disease, R wave in aVL lead (RaVL) is strongly correlated with left ventricular mass index (LVMI) assessed by transthoracic echocardiography. The aim of the present study was to extend this finding to other settings (cardiomyopathy or conduction disorders), by comparing ECG criteria of left ventricular hypertrophy (LVH) to cardiac MRI (CMR). In 501 patients, CMR and ECG were performed within a median-period of 5 days. CMR LVH cut-offs used were 83 g/m2 in men and 67 g/m2 in women. RaVL was independently correlated with LVMI in patients with or without myocardial infarction (MI) (N = 300 and N = 201, respectively). SV3 was independently correlated with LVMI and LV enlargement only in patients without MI. In the whole cohort, RaVL had area under receiver-operating characteristic curve of 0.729 (specificity 98.3%, sensitivity 19.6%, optimal cut-off 1.1 mV). The performance of RaVL was remarkable in women, in Caucasians, and in the presence of right bundle branch block. It decreased in case of MI. Overall, it is proposed that below 0.5 mV and above 1.0 mV, RaVL is sufficient to exclude or establish LVH. Between 0.5 and 1 mV, composite indices (Cornell voltage or product) should be used. Using this algorithm allowed classifying appropriately 85% of the patients. Our results showed that RaVL is a good index of LVH with a univocal threshold of 1.0 mV in various clinical conditions. SV3 may be combined to RaVL in some conditions, namely LV enlargement to increase its performance. © American Journal of Hypertension, Ltd 2015. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

HIV-1 infections with multiple founders are associated with higher viral loads than infections with single founders.

PubMed

Janes, Holly; Herbeck, Joshua T; Tovanabutra, Sodsai; Thomas, Rasmi; Frahm, Nicole; Duerr, Ann; Hural, John; Corey, Lawrence; Self, Steve G; Buchbinder, Susan P; McElrath, M Juliana; O'Connell, Robert J; Paris, Robert M; Rerks-Ngarm, Supachai; Nitayaphan, Sorachai; Pitisuttihum, Punnee; Kaewkungwal, Jaranit; Robb, Merlin L; Michael, Nelson L; Mullins, James I; Kim, Jerome H; Gilbert, Peter B; Rolland, Morgane

2015-10-01

Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically linked HIV-1 founder variants represent a minority of HIV-1 infections, we found--n two different cohorts--hat more diverse HIV-1 populations in early infection were associated with significantly higher VL 1 year after HIV-1 diagnosis.

Mode of Delivery among HIV-Infected Pregnant Women in Philadelphia, 2005-2013.

PubMed

Thompson, Dana R; Momplaisir, Florence M; Adams, Joëlla W; Yehia, Baligh R; Anderson, Emily A; Alleyne, Gregg; Brady, Kathleen A

2015-01-01

Current guidelines call for HIV-infected women to deliver via scheduled Caesarean when the maternal HIV viral load (VL) is >1,000 copies/ml. We describe the mode of delivery among HIV-infected women and evaluate adherence to relevant recommendations. We performed a population-based surveillance analysis of HIV-infected pregnant women in Philadelphia from 2005 to 2013, comparing mode of delivery (vaginal, scheduled Caesarean, or emergent Caesarean) by VL during pregnancy, closest to the time of delivery (≤1,000 copies/ml versus an unknown VL or VL >1,000 copies/ml) and associated factors in multivariable analysis. Our cohort included 824 deliveries from 648 HIV-infected women, of whom 69.4% had a VL ≤1,000 copies/ml and 30.6% lacked a VL or had a VL >1,000 copies/ml during pregnancy, closest to the time of delivery. Mode of delivery varied by VL: 56.6% of births were vaginal, 30.1% scheduled Caesarean, and 13.3% emergent Caesarean when the VL was ≤1,000 copies/ml; when the VL was unknown or >1,000 copies/ml, 32.9% of births were vaginal, 49.9% scheduled Caesarean and 17.5% emergent Caesarean. In multivariable analyses, Hispanic women (adjusted odds ratio (AOR) 0.17, 95% Confidence Interval (CI) 0.04-0.76) and non-Hispanic black women (AOR 0.27, 95% CI 0.10-0.77) were less to likely to deliver via scheduled Caesarean compared to non-Hispanic white women. Women who delivered prior to 38 weeks' gestation (AOR 0.37, 95% CI 0.18-0.76) were also less likely to deliver via scheduled Caesarean compared to women who delivered after 38 weeks' gestation. An interaction term for race and gestational age at delivery was significant in multivariable analysis. Non-Hispanic black (AOR 0.06, 95% CI 0.01-0.36) and Hispanic women (AOR 0.03, 95% CI 0.00-0.59) were more likely to deliver prematurely and less likely to deliver via scheduled C-section compared to non-Hispanic white women. Having a previous Caesarean (AOR 27.77, 95% CI 8.94-86.18) increased the odds of scheduled Caesarean delivery. Only half of deliveries for women with an unknown VL or VL >1,000 copies/ml occurred via scheduled Caesarean. Delivery prior to 38 weeks, particularly among minority women, resulted in a missed opportunity to receive a scheduled Caesarean. However, even when delivering at or after 38 weeks' gestation, a significant proportion of women did not get a scheduled Caesarean when indicated, suggesting a need for focused public health interventions to increase the proportion of women achieving viral suppression during pregnancy and delivering via scheduled Caesarean when indicated.

Kids, Take a Look at This! Visual Literacy Skills in the School Curriculum

ERIC Educational Resources Information Center

Vermeersch, Lode; Vandenbroucke, Anneloes

2015-01-01

Although the paradigm of visual literacy (VL) is rapidly emerging, the construct itself still lacks operational specificity. Based on a semiotic understanding of visual culture as an ongoing process of "making meaning", we present in this study a skill-based classification of VL, differentiating four sets of VL skills: perception;…

Toward a Cohesive Theory of Visual Literacy

ERIC Educational Resources Information Center

Avgerinou, Maria D.; Pettersson, Rune

2011-01-01

Despite the fact that to date Visual Literacy (VL) scholars have not arrived at a general consensus for a theoretical organization of the VL field, important conceptual investigations have emerged over the past four decades. In this paper we discuss and synthesize those studies. We then present a first attempt toward a cohesive theory of VL. The…

Sexual Risk Behavior Among Virologically Detectable Human Immunodeficiency Virus–Infected Young Men Who Have Sex With Men

PubMed Central

Wilson, Patrick A.; Kahana, Shoshana Y.; Fernandez, Maria Isabel; Harper, Gary W.; Mayer, Kenneth; Wilson, Craig M.; Hightow-Weidman, Lisa B.

2016-01-01

Importance Human immunodeficiency virus (HIV) diagnoses continue to increase among young men who have sex with men (YMSM). Many YMSM living with HIV engage in sexual risk behaviors, and those who have a detectable viral load can transmit HIV to sex partners. Understanding factors that are related to sexual risk taking among virologically detectable (VL+) YMSM can inform prevention and treatment efforts. Objectives To describe differences between virologically suppressed (VL−) and VL+ YMSM living with HIV and to identify correlates of condomless anal intercourse (CAI) and serodiscordant CAI among VL+ YMSM. Design, Setting, and Participants In this cross-sectional survey conducted from December 1, 2009, through June 30, 2012, we studied 991 HIV-infected YMSM 15 to 26 years of age at 20 adolescent HIV clinics in the United States. Data analysis was conducted December 1, 2013, through July 31, 2015. Main Outcomes and Measures Demographic, behavioral, and psychosocial assessments obtained using audio computer-assisted self-interviews. Viral load information was obtained via blood draw or medical record abstraction. Results Of the 991 participants, 688 (69.4%) were VL+ and 458 (46.2%) reported CAI, with 310 (31.3%) reporting serodiscordant CAI in the past 3 months. The VL+ YMSM were more likely than the VL− YMSM to report CAI (detectable, 266 [54.7%]; suppressed, 91 [44.4%]; P = .01) and serodiscordant CAI (detectable, 187 [34.9%]; suppressed, 57 [25.0%]; P < .01). Multivariable analyses indicated that among VL+ YMSM, those reporting problematic substance use were more likely to report CAI (adjusted odds ratio [AOR], 1.46; 95% CI, 1.02-2.10) and serodiscordant CAI (AOR, 1.45; 95% CI, 1.06-1.99). Black VL+ YMSM were less likely to report CAI (AOR, 0.63; 95% CI, 0.44-0.90) or serodiscordant CAI (AOR, 0.66; 95% CI, 0.46-0.94) compared with other VL+ YMSM. In addition, VL+ YMSM who disclosed their HIV status to sex partners were more likely to report CAI compared with nondisclosing YMSM (AOR, 1.35; 95% CI, 1.01-1.81). Transgender participants were less likely to report CAI than cisgender participants (AOR, 0.35; 95% CI, 0.14-0.85). Last, VL+ YMSM who reported currently being employed were less likely to report serodiscordant CAI than those who were unemployed (AOR,0.74; 95% CI, 0.55-0.99). Conclusions and Relevance Targeted multilevel interventions are needed to reduce HIV transmission risk behaviors among YMSM living with HIV, particularly among those who are VL+. PMID:26641367

Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systematic literature review.

PubMed

Santana, Iuri Usêda; Dias, Blenda; Nunes, Eduardo Araújo Santana; Rocha, Francisco Airton Castro da; Silva, Francisco Saraiva; Santiago, Mittermayer Barreto

2015-06-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection. To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles. The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test. In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin. Copyright © 2015 Elsevier Inc. All rights reserved.

Video laryngoscopy vs. direct laryngoscopy: Which should be chosen for endotracheal intubation during cardiopulmonary resuscitation? A prospective randomized controlled study of experienced intubators.

PubMed

Kim, Jong Won; Park, Sang O; Lee, Kyeong Ryong; Hong, Dae Young; Baek, Kwang Je; Lee, Young Hwan; Lee, Jeong Hun; Choi, Pil Cho

2016-08-01

This study compared endotracheal intubation (ETI) performance during cardiopulmonary resuscitation (CPR) between direct laryngoscopy (DL) and video laryngoscopy (VL) (GlideScope(®)) by experienced intubators (>50 successful ETIs). This was a prospective randomized controlled study conducted in an emergency department between 2011 and 2013. Intubators who used DL or VL were randomly allocated to ETI during CPR. Data were collected from recorded video clips and rhythm sheets. The success, speed, complications, and chest compressions interruption were compared between the two devices. Total 140 ETIs by experienced intubators using DL (n=69) and VL (n=71) were analysed. There were no significant differences between DL and VL in the ETI success rate (92.8% vs. 95.8%; p=0.490), first-attempt success rate (87.0% vs. 94.4%; p=0.204), and median time to complete ETI (51 [36-67] vs. 42 [34-62]s; p=0.143). In both groups, oesophageal intubation and dental injuries seldom occurred. However, longer chest compressions interruption occurred using DL (4.0 [1.0-11.0]s) compared with VL (0.0 [0.0-1.0]s) and frequent serious no-flow (interruption>10s) occurred with DL (18/69 [26.1%]) compared with VL (0/71) (p<0.001). For highly experienced intubators (>80 successful ETIs), frequent serious no-flow occurred in DL (14/55 [25.5%] vs. 0/57 in VL). The ETI success, speed and complications during CPR did not differ significantly between the two devices for experienced intubators. However, the VL was superior in terms of completion of ETI without chest compression interruptions. Clinical Research Information Service (CRIS) in South Korea KCT0000849. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epidemiological patterns of mortality due to visceral leishmaniasis and HIV/AIDS co-infection in Brazil, 2000-2011.

PubMed

Martins-Melo, Francisco Rogerlândio; Lima, Mauricélia da Silveira; Alencar, Carlos Henrique; Ramos, Alberto Novaes; Heukelbach, Jorg

2014-06-01

Visceral leishmaniasis (VL)-HIV/AIDS co-infection is an emerging health problem with high case fatality. This study presents the epidemiological and clinical aspects of deaths related to VL-HIV/AIDS co-infection in Brazil. This was a nationwide population-based study based on mortality data obtained from the Brazilian Mortality Information System. We included all deaths between 2000 and 2011 (about 12.5 million), and analyzed those in which VL and HIV/AIDS were mentioned in the same death certificate. VL and HIV/AIDS were mentioned in 272 deaths. HIV/AIDS was the underlying cause in 59.6% (162/272) of deaths by VL-HIV/AIDS co-infection, and VL the underlying cause in 39.3% (107/272). Predominating characteristics were: male gender (79.0%, 215/272), age 30-39 years (41.0%, 111/271), brown race/color (61.6%, 159/258) and residence in the Northeast region (47.4%, 129/272). Average annual age-adjusted mortality rate was 0.13 deaths/1 000 000 inhabitants. Deaths were distributed in 20 of 27 Brazilian states. There was an increasing trend of mortality (annual percent change: 16.4%). Infectious/parasitic (58.8%) and respiratory (51.1%) diseases/disorders, particularly sepsis, respiratory failure and pneumonia, were most commonly associated with deaths related to this co-infection. VL-HIV/AIDS co-infection is an increasing public health problem in Brazil. The systematic description of the epidemiological characteristics and magnitude of mortality related to VL-HIV/AIDS co-infection reflects the need to intensify control measures and disease surveillance. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Impact and Programmatic Implications of Routine Viral Load Monitoring in Swaziland

PubMed Central

Parker, Lucy Anne; Azih, Charles; Okello, Velephi; Maphalala, Gugu; Jouquet, Guillaume; Kerschberger, Bernhard; Mekeidje, Calorine; Cyr, Joanne; Mafikudze, Arnold; Han, Win; Lujan, Johnny; Teck, Roger; Antierens, Annick; van Griensven, Johan; Reid, Tony

2014-01-01

Objective: To assess the programmatic quality (coverage of testing, counseling, and retesting), cost, and outcomes (viral suppression, treatment decisions) of routine viral load (VL) monitoring in Swaziland. Design: Retrospective cohort study of patients undergoing routine VL monitoring in Swaziland (October 1, 2012 to March 31, 2013). Results: Of 5563 patients eligible for routine VL testing monitoring in the period of study, an estimated 4767 patients (86%) underwent testing that year. Of 288 patients with detectable VL, 210 (73%) underwent enhanced adherence counseling and 202 (70%) had a follow-up VL within 6 months. Testing coverage was slightly lower in children, but coverage of retesting was similar between and age groups and sexes. Of those with a follow-up test, 126 (62%) showed viral suppression. The remaining 78 patients had World Health Organization–defined virologic failure; 41 (53%) were referred by the doctor for more adherence counseling, and 13 (15%) were changed to second-line therapy, equating to an estimated rate of 1.2 switches per 100 patient-years. Twenty-four patients (32%) were transferred out, lost to follow-up, or not reviewed by doctor. The “fully loaded” cost of VL monitoring was $35 per patient-year. Conclusions: Achieving good quality VL monitoring is feasible and affordable in resource-limited settings, although close supervision is needed to ensure good coverage of testing and counseling. The low rate of switch to second-line therapy in patients with World Health Organization–defined virologic failure seems to reflect clinician suspicion of ongoing adherence problems. In our study, the main impact of routine VL monitoring was reinforcing adherence rather than increasing use of second-line therapy. PMID:24872139

Plasma HIV viral rebound following protocol-indicated cessation of ART commenced in primary and chronic HIV infection.

PubMed

Hamlyn, Elizabeth; Ewings, Fiona M; Porter, Kholoud; Cooper, David A; Tambussi, Giuseppe; Schechter, Mauro; Pedersen, Court; Okulicz, Jason F; McClure, Myra; Babiker, Abdel; Weber, Jonathan; Fidler, Sarah

2012-01-01

The magnitude of HIV viral rebound following ART cessation has consequences for clinical outcome and onward transmission. We compared plasma viral load (pVL) rebound after stopping ART initiated in primary (PHI) and chronic HIV infection (CHI). Two populations with protocol-indicated ART cessation from SPARTAC (PHI, n = 182) and SMART (CHI, n = 1450) trials. Time for pVL to reach pre-ART levels after stopping ART was assessed in PHI using survival analysis. Differences in pVL between PHI and CHI populations 4 weeks after stopping ART were examined using linear and logistic regression. Differences in pVL slopes up to 48 weeks were examined using linear mixed models and viral burden was estimated through a time-averaged area-under-pVL curve. CHI participants were categorised by nadir CD4 at ART stop. Of 171 PHI participants, 71 (41.5%) rebounded to pre-ART pVL levels, at a median of 50 (95% CI 48-51) weeks after stopping ART. Four weeks after stopping treatment, although the proportion with pVL ≥ 400 copies/ml was similar (78% PHI versus 79% CHI), levels were 0.45 (95% CI 0.26-0.64) log(10) copies/ml lower for PHI versus CHI, and remained lower up to 48 weeks. Lower CD4 nadir in CHI was associated with higher pVL after ART stop. Rebound for CHI participants with CD4 nadir >500 cells/mm(3) was comparable to that experienced by PHI participants. Stopping ART initiated in PHI and CHI was associated with viral rebound to levels conferring increased transmission risk, although the level of rebound was significantly lower and sustained in PHI compared to CHI.

Just-in-Time Video Laryngoscopy Versus Direct Laryngoscopy for Neonatal Intubation.

PubMed

Grgurich, Erin; Arnemann, Cynthia; Amon, Kim; Horton, Rose; Carlson, Jestin N

As neonatal endotracheal intubation (ETI) is a low-frequency, high-consequence event, it is essential that providers have access to resources to aid in ETI. We sought to determine the impact of video laryngoscopy (VL) with just-in-time training on intubation outcomes over direct laryngoscopy (DL) when performed by neonatal nurses. We conducted a prospective, randomized, crossover study with neonatal nurses employed at a level 2 neonatal intensive care unit (NICU). Nurses performed both DL and VL on a neonatal mannequin using a CMAC (Karl Storz Corp, Tuttlingen, Germany) either with the assistance of the screen (VL) or without (DL). Before performing the intubation, providers were given a just-in-time, brief education presentation and allowed to practice with the device. Each ETI attempt was reviewed to obtain the percentage of glottic opening (POGO) score, time to intubation (TTI, time from insertion of the blade into the mouth until the first breath was delivered), and time from blade insertion until the best POGO score. We enrolled 19 participants, with a median (interquartile range) of 20 (9-26) years of experience and having a median of 2 (1-3) intubations within the past year. None had used VL in the NICU previously. Median TTI did not differ between DL and VL: 19.9 (15.3-41.5) vs 20.3 (17.9-24.4) (P = 1). POGO scores and the number of attempts also did not differ between DL and VL. In our simulated setting, just-in-time VL training provided similar intubation outcomes compared with DL in ETI performed by neonatal nurses. Just-in-time VL education may be an alternative to traditional DL for neonatal intubations.

Early virologic response to abacavir/lamivudine and tenofovir/emtricitabine during ACTG A5202

PubMed Central

Grant, Philip M.; Tierney, Camlin; Budhathoki, Chakra; Daar, Eric S.; Sax, Paul E.; Collier, Ann C.; Fischl, Margaret A.; Zolopa, Andrew R.; Balamane, Maya; Katzenstein, David

2014-01-01

Background ACTG A5202 randomized treatment-naive individuals to tenofovir-emtricitabine (TDF/FTC) or abacavir-lamivudine (ABC/3TC) combined with efavirenz (EFV) or atazanavir/ritonavir (ATV/r). Individuals in the high screening viral load (VL) stratum (≥100,000 copies/mL) had increased rates of virologic failure with ABC/3TC. Objective Compare regimen-specific early virologic response. Methods Using Wilcoxon rank-sum tests, we compared regimen-specific VL changes from entry to week 4 in A5202 subjects (n=1813) and from entry to week 1, 2 and 4 in a 179-patient substudy. We evaluated associations between week 4 VL change and time to virologic failure with Cox proportional-hazards models. Results TDF/FTC- and ABC/3TC produced similar Week 4 viral load declines in the entire study population and in the high VL stratum. EFV produced greater VL declines from baseline at week 4 than ATV/r (median −2.1 vs. −1.9 log10 copies/mL; p<0.001). In the substudy of subjects with week 1, 2 and 4 VL data, there was no difference in viral load decline in those randomized to TDF/FTC versus ABC/3TC, but EFV resulted in greater VL decline from entry at each of these timepoints than ATV/r. Smaller Week 4 viral load decline was associated with increased risk of virologic failure. Conclusions Within all treatment arms, a less robust week 4 virologic response was associated with higher risk for subsequent virologic failure. However, between-regimen differences in week 4 VL declines did not parallel the previously reported differences in longer term virologic efficacy in A5202, suggesting that between-regimen differences in responses were not due to intrinsic differences in antiviral activity. PMID:24334181

Comparison between Roche and Xpert in HIV-1 RNA quantitation: A high concordance between the two techniques except for a CRF02_AG subtype variant with high viral load titters detected by Roche but undetected by Xpert.

PubMed

Avidor, Boaz; Matus, Natalia; Girshengorn, Shirley; Achsanov, Svetlana; Gielman, Simona; Zeldis, Irene; Schweitzer, Inbal; Adler, Amos; Turner, Dan

2017-08-01

HIV-1 viral load (VL) testing is important to predict viral progression and to monitor the response to antiretroviral therapy. New HIV-1 VL tests are continuously introduced to the market. Their performance is usually compared to Abbott and/or Roche HIV-1 VL assays, as reference. The Xpert HIV-1 VL test was recently introduced, but its performance compared to Roche has not been sufficiently studied. To compare the Xpert assay with Roche and to assess its use in the HIV clinical laboratory. A total of 383 plasma samples of HIV-1 infected patients previously tested by Roche, were retrospectively tested by Xpert to determine concordance between the two assays. Samples included a diversity of HIV-1 subtypes and a wide range of VLs. There was a high concordance between the two assays, except for a CRF02_AG subtype variant with high VL titters, that was detected by Roche but undetected by Xpert. The 5' long terminal repeat gene region of this virus, targeted by the Xpert assay, was amplified and sequenced. A 25 nucleotide insert was identified, but was unmatched to any known sequences of HIV-1. This particular insert, however could not explain the false-negativity by the Xpert assay. This study underlines the challenge to routine VL testing due to the high genetic diversity of HIV-1. Clinicians should, therefore be advised that a negative VL in cases where the clinical picture does not match the laboratory report, might in fact be, a false-negative result of the VL assay. Copyright © 2017 Elsevier B.V. All rights reserved.

New insights into leishmaniasis in the immunosuppressed

PubMed Central

Akuffo, Hannah; van Griensven, Johan; Burza, Sakib; Moreno, Javier; Herrero, Mercè

2018-01-01

Immunosuppression contributes significantly to the caseload of visceral leishmaniasis (VL). HIV coinfection, solid organ transplantation, malnutrition, and helminth infections are the most important immunosuppression-related factors. This review briefly describes the challenges of these associations. East Africa and the Indian subcontinent are the places where HIV imposes the highest burden in VL. In the highlands of Northern Ethiopia, migrant rural workers are at a greater risk of coinfection and malnutrition, while in India, HIV reduces the sustainability of a successful elimination programme. As shown from a longitudinal cohort in Madrid, VL is an additional threat to solid organ transplantation. The association with malnutrition is more complex since it can be both a cause and a consequence of VL. Different regimes for therapy and secondary prevention are discussed as well as the role of nutrients on the prophylaxis of VL in poverty-stricken endemic areas. PMID:29746470

Reduction in HIV community viral loads following the implementation of a "Treatment as Prevention" strategy over 2 years at a population-level among men who have sex with men in Hangzhou, China.

PubMed

He, Lin; Yang, Jiezhe; Ma, Qiaoqin; Zhang, Jiafeng; Xu, Yun; Xia, Yan; Chen, Wanjun; Wang, Hui; Zheng, Jinlei; Jiang, Jun; Luo, Yan; Xu, Ke; Zhang, Xingliang; Xia, Shichang; Pan, Xiaohong

2018-02-01

Previous studies have shown that the increased coverage of antiretroviral therapy (ART) could reduce the community viral load (CVL) and reduce the occurrence of new HIV infections. However, the impact on the reduction of HIV transmission among men who have sex with men (MSM) is much less certain. The frequency of HIV infections in MSM have been rapidly increasing in recent years in Hangzhou, China. The "Treatment as Prevention" strategy was implemented at a population-level for HIV-infected MSM from January 2014 to June 2016 in Hangzhou; it aimed to increase the ART coverage, reduce the CVL, and reduce HIV transmission. We investigated a subset of MSM diagnosed with HIV pre- and post-implementation of the strategy, using random sampling methods. Viral load (VL) testing was performed for all enrolled individuals; the lower limits of detection were 20 and 50 copies/mL. The data on infections were collected from the national epidemiology database of Hangzhou. Logistic regression analyses were conducted to identify factors associated with the differences in social demographic characteristics and available VL data. The ART coverage increased from 60.7% (839/1383) during the pre-implementation period to 92.3% (2183/2365) during the post-implementation period in Hangzhou. A total of 940 HIV-infected MSM were selected for inclusion in this study: 490 (52.1%) and 450 (47.9%) MSM in the pre- and post-implementation periods, respectively. In total, 89.5% (841/940) of patients had data available on VL rates. The mean CVL was 579 copies/mL pre-implementation and this decreased to 33 copies/mL post-implementation (Kruskal-Wallis < 0.001). The mean CVL decreased for all variables investigated post-implementation of the treatment strategy (P < 0.05). The undetectable VL (≤400 copies/mL) rate pre-implementation period was 50.0% which increased to 84.7% post-implementation (P < 0.001). The mean CVL at the county level significantly decreased in each county post-implementation (Kruskal-Wallis < 0.05). Our study confirmed a population-level association between increased ART coverage and decreased mean CVL; overall 84.7% of HIV infected MSM had an undetectable VL and were no longer infectious.

An unusual cysteine VL87 affects the antibody fragment conformations without interfering with the disulfide bond formation.

PubMed

Attallah, Carolina; Aguilar, María Fernanda; Garay, A Sergio; Herrera, Fernando E; Etcheverrigaray, Marina; Oggero, Marcos; Rodrigues, Daniel E

2017-10-01

The Cys residues are almost perfectly conserved in all antibodies. They contribute significantly to the antibody fragment stability. The relevance of two natural contiguous Cys residues of an anti-recombinant human-follicle stimulation hormone (rhFSH) in a format of single-chain variable fragment (scFv) was studied. This scFv contains 5 Cys residues: V H 22 and V H 92 in the variable heavy chain (V H ) and V L 23, V L 87 and V L 88 in the variable light chain (V L ). The influence of two unusual contiguous Cys at positions V L 87 and V L 88 was studied by considering the wild type fragment and mutant variants: V L -C88S, V L -C87S, V L -C87Y. The analysis was carried out using antigen-binding ability measurement by indirect specific ELISA and a detailed molecular modeling that comprises homology methods, long molecular dynamics simulations and docking. We found that V L -C87 affected the antibody fragment stability without interfering with the disulfide bond formation. The effect of mutating the V L -C87 by a usual residue at this position like Tyr caused distant structural changes at the V H region that confers a higher mobility to the V H -CDR2 and V H -CDR3 loops improving the scFv binding to the antigen. Copyright © 2017 Elsevier Ltd. All rights reserved.

EMG normalization to study muscle activation in cycling.

PubMed

Rouffet, David M; Hautier, Christophe A

2008-10-01

The value of electromyography (EMG) is sensitive to many physiological and non-physiological factors. The purpose of the present study was to determine if the torque-velocity test (T-V) can be used to normalize EMG signals into a framework of biological significance. Peak EMG amplitude of gluteus maximus (GMAX), vastus lateralis (VL), rectus femoris (RF), biceps femoris long head (BF), gastrocnemius medialis (GAS) and soleus (SOL) was calculated for nine subjects during isometric maximal voluntary contractions (IMVC) and torque-velocity bicycling tests (T-V). Then, the reference EMG signals obtained from IMVC and T-V bicycling tests were used to normalize the amplitude of the EMG signals collected for 15 different submaximal pedaling conditions. The results of this study showed that the repeatability of the measurements between IMVC (from 10% to 23%) and T-V (from 8% to 20%) was comparable. The amplitude of the peak EMG of VL was 99+/-43% higher (p<0.001) when measured during T-V. Moreover, the inter-individual variability of the EMG patterns calculated for submaximal cycling exercises differed significantly when using T-V bicycling normalization method (GMAX: 0.33+/-0.16 vs. 1.09+/-0.04, VL: 0.07+/-0.02 vs. 0.64+/-0.14, SOL: 0.07+/-0.03 vs. 1.00+/-0.07, RF: 1.21+/-0.20 vs. 0.92+/-0.13, BF: 1.47+/-0.47 vs. 0.84+/-0.11). It was concluded that T-V bicycling test offers the advantage to be less time and energy-consuming and to be as repeatable as IMVC tests to measure peak EMG amplitude. Furthermore, this normalization method avoids the impact of non-physiological factors on the amplitude of the EMG signals so that it allows quantifying better the activation level of lower limb muscles and the variability of the EMG patterns during submaximal bicycling exercises.

Two Different Secondary Metabolism Gene Clusters Occupied the Same Ancestral Locus in Fungal Dermatophytes of the Arthrodermataceae

PubMed Central

Zhang, Han; Rokas, Antonis; Slot, Jason C.

2012-01-01

Background Dermatophyte fungi of the family Arthrodermataceae (Eurotiomycetes) colonize keratinized tissue, such as skin, frequently causing superficial mycoses in humans and other mammals, reptiles, and birds. Competition with native microflora likely underlies the propensity of these dermatophytes to produce a diversity of antibiotics and compounds for scavenging iron, which is extremely scarce, as well as the presence of an unusually large number of putative secondary metabolism gene clusters, most of which contain non-ribosomal peptide synthetases (NRPS), in their genomes. To better understand the historical origins and diversification of NRPS-containing gene clusters we examined the evolution of a variable locus (VL) that exists in one of three alternative conformations among the genomes of seven dermatophyte species. Results The first conformation of the VL (termed VLA) contains only 539 base pairs of sequence and lacks protein-coding genes, whereas the other two conformations (termed VLB and VLC) span 36 Kb and 27 Kb and contain 12 and 10 genes, respectively. Interestingly, both VLB and VLC appear to contain distinct secondary metabolism gene clusters; VLB contains a NRPS gene as well as four porphyrin metabolism genes never found to be physically linked in the genomes of 128 other fungal species, whereas VLC also contains a NRPS gene as well as several others typically found associated with secondary metabolism gene clusters. Phylogenetic evidence suggests that the VL locus was present in the ancestor of all seven species achieving its present distribution through subsequent differential losses or retentions of specific conformations. Conclusions We propose that the existence of variable loci, similar to the one we studied, in fungal genomes could potentially explain the dramatic differences in secondary metabolic diversity between closely related species of filamentous fungi, and contribute to host adaptation and the generation of metabolic diversity. PMID:22860027

Characterization of the ABA Receptor VlPYL1 That Regulates Anthocyanin Accumulation in Grape Berry Skin

PubMed Central

Gao, Zhen; Li, Qin; Li, Jing; Chen, Yujin; Luo, Meng; Li, Hui; Wang, Jiyuan; Wu, Yusen; Duan, Shuyan; Wang, Lei; Song, Shiren; Xu, Wenping; Zhang, Caixi; Wang, Shiping; Ma, Chao

2018-01-01

ABA plays a crucial role in controlling several ripening-associated processes in grape berries. The soluble proteins named as PYR (pyrabactin resistant)/PYL (PYR-like)/RCAR (regulatory component of ABA receptor) family have been characterized as ABA receptors. Here, the function of a grape PYL1 encoding gene involved in the response to ABA was verified through heterologous expression. The expression level of VlPYL1 was highest in grape leaf and fruit tissues of the cultivar Kyoho, and the expression of VlPYL1 was increased during fruit development and showed a reduction in ripe berries. Over-expression of VlPYL1 enhances ABA sensitivity in Arabidopsis. Using the transient overexpression technique, the VlPYL1 gene was over-expressed in grape berries. Up-regulation of the VlPYL1 gene not only promoted anthocyanin accumulation but also induced a set of ABA-responsive gene transcripts, including ABF2 and BG3. Although tobacco rattle virus (TRV)-induced gene silencing (VIGS) was not successfully applied in the “Kyoho” grape, the application of the transient overexpression technique in grape fruit could be used as a novel tool for studying grape fruit development. PMID:29868057

[Distribution of Lutzomyia longipalpis in the Argentine Mesopotamia, 2010].

PubMed

Salomon, Oscar D; Fernandez, Maria S; Santini, María S; Saavedra, Silvina; Montiel, Natalia; Ramos, Marina A; Rosa, Juan R; Szelag, Enrique A; Martinez, Mariela F

2011-01-01

The first case of visceral leishmaniasis (VL) in Argentina was reported in 2006 in Posadas, Misiones. During the summer 2008-2009 Lutzomyia longipalpis, the VL vector, and canine VL cases were already spread along the province of Corrientes. In order to know the distribution of VL risk, systematic captures of the vector were performed between February and March 2010, in 18 areas of the provinces of Entre Ríos and Corrientes, and the city of Puerto Iguazú, Misiones, with a total of 313 traps/night. We confirmed the presence of Lu. longipalpis, for the first time in Chajarí (Entre Ríos), Alvear, La Cruz, Curuzú Cuatiá and Bella Vista (Corrientes), and Puerto Iguazú (Misiones). In Santo Tome and Monte Caseros (Corrientes), where the vector had been previously reported, traps with more samples were obtained with 830 and 126 Lu. Longipalpis trap/site/night respectively. These results show that the vector of urban VL continues spreading in the Argentine territory. Simultaneously, the spread of the parasite and the resulting human VL cases are associated with the dispersion of reservoirs, infected dogs, with or without clinical symptoms or signs, due to human transit.

Serological and molecular tools to diagnose visceral leishmaniasis: 2-years’ experience of a single center in Northern Italy

PubMed Central

Ortalli, Margherita; Attard, Luciano; Vanino, Elisa; Gaibani, Paolo; Vocale, Caterina; Rossini, Giada; Cagarelli, Roberto; Pierro, Anna; Billi, Patrizia; Mastroianni, Antonio; Di Cesare, Simona; Codeluppi, Mauro; Franceschini, Erica; Melchionda, Fraia; Gramiccia, Marina; Scalone, Aldo; Gentilomi, Giovanna A.; Landini, Maria P.

2017-01-01

The diagnosis of visceral leishmaniasis (VL) remains challenging, due to the limited sensitivity of microscopy, the poor performance of serological methods in immunocompromised patients and the lack of standardization of molecular tests. The aim of this study was to implement a combined diagnostic workflow by integrating serological and molecular tests with standardized clinical criteria. Between July 2013 and June 2015, the proposed workflow was applied to specimens obtained from 94 in-patients with clinical suspicion of VL in the Emilia-Romagna region, Northern Italy. Serological tests and molecular techniques were employed. Twenty-one adult patients (22%) had a confirmed diagnosis of VL by clinical criteria, serology and/or real-time polymerase chain reaction; 4 of these patients were HIV-positive. Molecular tests exhibited higher sensitivity than serological tests for the diagnosis of VL. In our experience, the rK39 immunochromatographic test was insufficiently sensitive for use as a screening test for the diagnosis of VL caused by L. infantum in Italy. However, as molecular tests are yet not standardized, further studies are required to identify an optimal screening test for Mediterranean VL. PMID:28832646

Epidemiology and Clinical Features of Patients with Visceral Leishmaniasis Treated by an MSF Clinic in Bakool Region, Somalia, 2004–2006

PubMed Central

Raguenaud, Marie-Eve; Jansson, Anna; Vanlerberghe, Veerle; Van der Auwera, Geert; Deborggraeve, Stijn; Dujardin, Jean-Claude; Orfanos, Giannos; Reid, Tony; Boelaert, Marleen

2007-01-01

Background There are few reports describing the epidemiology of visceral leishmaniasis (VL) in Somalia. Over the years 2002 to 2005, a yearly average of 140 patients were reported from the Huddur centre in Bakool region, whereas in 2006, this number rose to 1002 patients. Given the limited amount of information on VL and the opportunity to compare features with the studies done in 2000 in this part of Somalia, we describe the epidemiologic and clinical features of patients who presented to the Huddur treatment centre of Bakool region, Somalia, using data routinely collected over a five-year observation period (2002–2006). Methodology Methods used included the analysis of routine data on VL cases treated in the Huddur treatment centre, a retrospective study of records of patients admitted between 2004 and 2006, community leaders interviews, and analysis of blood specimens taken for parasite species identification in Antwerp Institute of Tropical Medicine. Principal Findings A total of 1671 VL patients were admitted to the Huddur centre from January 2002 until December 2006. Nearly all patients presented spontaneously to the health centre. Since 2002, the average patient load was stable, with an average of 140 admissions per year. By the end of 2005, the number of admissions dramatically increased to reach a 7-fold increase in 2006. The genotype of L. donovani identified in 2006 was similar to the one reported in 2002. 82% of total patients treated for VL originated from two districts of Bakool region, Huddur and Tijelow districts. Clinical recovery rate was 93.2% and case fatality rate 3.9%. Conclusions After four years of low but constant VL case findings, a major increase in VL was observed over a 16-month period in the Huddur VL centre. The profile of the patients was pediatric and mortality relatively low. Decentralized treatment centers, targeted active screening, and community sensitization will help decrease morbidity and mortality from VL in this endemic area. The true magnitude of VL in Somalia remains unknown. Further documentation to better understand transmission dynamics and thus define appropriate control measures will depend on the stability of the context and safe access to the Somali population. PMID:17989791

Routine viral load monitoring in HIV-infected infants and children in low- and middle-income countries: challenges and opportunities.

PubMed

Arpadi, Stephen M; Shiau, Stephanie; De Gusmao, Eduarda Pimentel; Violari, Avy

2017-11-01

The objective of this commentary is to review considerations for implementing routine viral load (VL) monitoring programmes for HIV-infected infants and children living in low- and middle-income countries (LMIC). Since 2013, the World Health Organization (WHO) guidelines recommend VL testing as the preferred monitoring approach for all individuals treated with ART in order to assess treatment response, detect treatment failure and determine the need to switch to a second-line regimen in a timely manner. More recently, WHO guidelines from 2016 identify HIV-infected infants and children as a priority group for routine VL monitoring. There are a number of reasons why HIV-infected infants and children should be prioritized for routine VL monitoring. Data from national VL monitoring programmes as well as systematic reviews and meta-analyses from LMIC indicate rates of viral suppression are lower for infants and children compared to adults. The number of antiretroviral drugs and palatable formulations suitable for young children are limited. In addition, emotional and developmental issues particular to children can make daily medication administration difficult and pose a challenge to adherence and achievement of sustained viral suppression. VL monitoring can be instrumental for identifying those in need of additional adherence support, reducing regimen switches and preserving treatment options. The needs of infants and children warrant consideration in all aspects of VL monitoring services. If capacity for paediatric venipuncture is not assured, platforms that accept dried blood spot specimens are necessary in order for infants and children to have equitable access. Healthcare systems also need to prepare to manage the substantial number of infants and children identified with elevated VL, including adherence interventions that are appropriate for children. Establishing robust systems to evaluate processes and outcomes of routine VL monitoring services and to support drug forecasting and supply management is essential to determine best practices for infants and children in LMIC. The particular concerns of HIV-infected infants and children warrant attention during all phases of planning and implementation of VL monitoring services. There are a number of key areas, including frequency of monitoring, blood specimen type and adherence challenges, where specific approaches tailored for infants and children may be required. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Real-time PCR in detection and quantitation of Leishmania donovani for the diagnosis of Visceral Leishmaniasis patients and the monitoring of their response to treatment

PubMed Central

Ghosh, Prakash; Khan, Md. Anik Ashfaq; Duthie, Malcolm S.; Vallur, Aarthy C.; Picone, Alessandro; Howard, Randall F.; Reed, Steven G.

2017-01-01

Sustained elimination of Visceral Leishmaniasis (VL) requires the reduction and control of parasite reservoirs to minimize the transmission of Leishmania donovani infection. A simple, reproducible and definitive diagnostic procedure is therefore indispensable for the early and accurate detection of parasites in VL, Relapsed VL (RVL) and Post Kala-azar Dermal Leishmaniasis (PKDL) patients, all of whom are potential reservoirs of Leishmania parasites. To overcome the limitations of current diagnostic approaches, a novel quantitative real-time polymerase chain reaction (qPCR) method based on Taqman chemistry was devised for the detection and quantification of L. donovani in blood and skin. The diagnostic efficacy was evaluated using archived peripheral blood buffy coat DNA from 40 VL, 40 PKDL, 10 RVL, 20 cured VL, and 40 cured PKDL along with 10 tuberculosis (TB) cases and 80 healthy endemic controls. Results were compared to those obtained using a Leishmania-specific nested PCR (Ln-PCR). The real time PCR assay was 100% (95% CI, 91.19–100%) sensitive in detecting parasite genomes in VL and RVL samples and 85.0% (95% CI, 70.16–94.29%) sensitive for PKDL samples. In contrast, the sensitivity of Ln-PCR was 77.5% (95% CI, 61.55–89.16%) for VL samples, 100% (95%CI, 69.15–100%) for RVL samples, and 52.5% (95% CI, 36.13–68.49%) for PKDL samples. There was significant discordance between the two methods with the overall sensitivity of the qPCR assay being considerably higher than Ln-PCR. None of the assay detected L. donovani DNA in buffy coats from cured VL cases, and reduced infectious burdens were demonstrated in cured PKDL cases who remained positive in 7.5% (3/40) and 2.5% (1/40) cases by real-time PCR and Ln-PCR, respectively. Both assays were 100% (95% CI, 95.98–100) specific with no positive signals in either endemic healthy control or TB samples. The real time PCR assay we developed offers a molecular tool for accurate detection of circulating L. donovani parasites in VL, PKDL and RVL patients, as well as being capable of assessing response to treatment. As such, this real time PCR assay represents an important contribution in efforts to eliminate VL. PMID:28957391

Bonding to Different PEEK Compositions: The Impact of Dental Light Curing Units

PubMed Central

Lümkemann, Nina; Eichberger, Marlis; Stawarczyk, Bogna

2017-01-01

This study investigated the impact of different light curing units (LCUs) for the polymerization of adhesive system visio.link (VL) on the tensile bond strength (TBS) of different PEEK compositions. For TBS measurements, 216 PEEK specimens with varying amounts of TiO2 (PEEK/0%, PEEK/20%, PEEK/>30%) were embedded, polished, air abraded (Al2O3, 50 µm, 0.4 MPa), conditioned using VL, and polymerized using either a halogen LCU (HAL-LCU) or a LED LCU (LED-LCU) for chairside or labside application, respectively. After thermocycling (5000×, 5/55 °C), TBS was measured, and fracture types were determined. Data was analyzed using a 2-way ANOVA followed by Tukey–HSD, Kruskal–Wallis H and Mann–Whitney U tests as well as a Chi2-test and a Ciba–Geigy table (p < 0.05). Globally, the light curing units, followed by PEEK composition, was shown to have the highest impact on TBS. The HAL-LCUs, compared to the LED-LCUs, resulted in a higher TBS for all PEEK compositions—without significant differences between chairside and labside units. Regarding the different PEEK compositions, PEEK/20%, compared to PEEK/0%, resulted in a higher TBS when both, HAL-LCUs or LED-LCUs were used for labside application. In comparison with PEEK/>30%, PEEK/20% resulted in a higher TBS after using HAL-LCU for labside application. No significant differences were found between PEEK/0% and PEEK/>30%. HAL-LCU with PEEK/20% for labside application showed a higher TBS than HAL-LCU with PEEK/20% for chairside application, whereas LED-LCU with PEEK/>30% for chairside application showed a higher TBS than LED-LCU with PEEK/>30% for labside application. PMID:28772427

High frequency of subclinical Leishmania infection among HIV-infected patients living in the endemic areas of visceral leishmaniasis in Fars province, southern Iran.

PubMed

Rezaei, Z; Sarkari, B; Dehghani, M; Layegh Gigloo, A; Afrashteh, M

2018-06-02

Visceral leishmaniasis (VL) is a major health concern in patients with HIV infection in endemic areas of VL. In these areas, a substantial number of infected individuals are asymptomatic and the risk of acute VL infection in HIV/VL co-infected cases is high. The current study aimed to determine the prevalence of asymptomatic VL infection among HIV-infected patients in Fars province, southern Iran. Subjects of the study were 251 HIV-confirmed patients who all were clinically asymptomatic for leishmaniasis. Blood samples were obtained from each participant. Anti-Leishmania antibodies were detected in the sera using ELISA. DNA was extracted from the buffy coat of each subject and PCR amplified, targeting an ITS-2 gene of Leishmania. PCR products were purified from the gel and were sequenced. Overall, 19 out of 251 (7.6%) HIV-infected patients were found to be infected with Leishmania, using serological or molecular methods. Anti-Leishmania antibodies were detected in 13 (5.2%) patients and leishmanial DNA in 8 (3.2%) of the patients. The sequence analysis of DNA-positive cases revealed the species of the parasite as L. infantum. The high prevalence of VL among the patients with HIV is a serious challenge which demands further attention to improve the prophylaxis and treatment measurements of VL/HIV co-infection and thereby promoting the life expectancy and quality of life of these patients.

Signals from the ventrolateral thalamus to the motor cortex during locomotion

PubMed Central

Marlinski, Vladimir; Nilaweera, Wijitha U.; Zelenin, Pavel V.; Sirota, Mikhail G.

2012-01-01

The activity of the motor cortex during locomotion is profoundly modulated in the rhythm of strides. The source of modulation is not known. In this study we examined the activity of one of the major sources of afferent input to the motor cortex, the ventrolateral thalamus (VL). Experiments were conducted in chronically implanted cats with an extracellular single-neuron recording technique. VL neurons projecting to the motor cortex were identified by antidromic responses. During locomotion, the activity of 92% of neurons was modulated in the rhythm of strides; 67% of cells discharged one activity burst per stride, a pattern typical for the motor cortex. The characteristics of these discharges in most VL neurons appeared to be well suited to contribute to the locomotion-related activity of the motor cortex. In addition to simple locomotion, we examined VL activity during walking on a horizontal ladder, a task that requires vision for correct foot placement. Upon transition from simple to ladder locomotion, the activity of most VL neurons exhibited the same changes that have been reported for the motor cortex, i.e., an increase in the strength of stride-related modulation and shortening of the discharge duration. Five modes of integration of simple and ladder locomotion-related information were recognized in the VL. We suggest that, in addition to contributing to the locomotion-related activity in the motor cortex during simple locomotion, the VL integrates and transmits signals needed for correct foot placement on a complex terrain to the motor cortex. PMID:21994259

A small and efficient dimerization/packaging signal of rat VL30 RNA and its use in murine leukemia virus-VL30-derived vectors for gene transfer.

PubMed

Torrent, C; Gabus, C; Darlix, J L

1994-02-01

Retroviral genomes consist of two identical RNA molecules associated at their 5' ends by the dimer linkage structure located in the packaging element (Psi or E) necessary for RNA dimerization in vitro and packaging in vivo. In murine leukemia virus (MLV)-derived vectors designed for gene transfer, the Psi + sequence of 600 nucleotides directs the packaging of recombinant RNAs into MLV virions produced by helper cells. By using in vitro RNA dimerization as a screening system, a sequence of rat VL30 RNA located next to the 5' end of the Harvey mouse sarcoma virus genome and as small as 67 nucleotides was found to form stable dimeric RNA. In addition, a purine-rich sequence located at the 5' end of this VL30 RNA seems to be critical for RNA dimerization. When this VL30 element was extended by 107 nucleotides at its 3' end and inserted into an MLV-derived vector lacking MLV Psi +, it directed the efficient encapsidation of recombinant RNAs into MLV virions. Because this VL30 packaging signal is smaller and more efficient in packaging recombinant RNAs than the MLV Psi + and does not contain gag or glyco-gag coding sequences, its use in MLV-derived vectors should render even more unlikely recombinations which could generate replication-competent viruses. Therefore, utilization of the rat VL30 packaging sequence should improve the biological safety of MLV vectors for human gene transfer.

Mode of Delivery among HIV-Infected Pregnant Women in Philadelphia, 2005-2013

PubMed Central

Adams, Joëlla W.; Anderson, Emily A.

2015-01-01

Objective Current guidelines call for HIV-infected women to deliver via scheduled Caesarean when the maternal HIV viral load (VL) is >1,000 copies/ml. We describe the mode of delivery among HIV-infected women and evaluate adherence to relevant recommendations. Study Design We performed a population-based surveillance analysis of HIV-infected pregnant women in Philadelphia from 2005 to 2013, comparing mode of delivery (vaginal, scheduled Caesarean, or emergent Caesarean) by VL during pregnancy, closest to the time of delivery (≤1,000 copies/ml versus an unknown VL or VL >1,000 copies/ml) and associated factors in multivariable analysis. Results Our cohort included 824 deliveries from 648 HIV-infected women, of whom 69.4% had a VL ≤1,000 copies/ml and 30.6% lacked a VL or had a VL >1,000 copies/ml during pregnancy, closest to the time of delivery. Mode of delivery varied by VL: 56.6% of births were vaginal, 30.1% scheduled Caesarean, and 13.3% emergent Caesarean when the VL was ≤1,000 copies/ml; when the VL was unknown or >1,000 copies/ml, 32.9% of births were vaginal, 49.9% scheduled Caesarean and 17.5% emergent Caesarean. In multivariable analyses, Hispanic women (adjusted odds ratio (AOR) 0.17, 95% Confidence Interval (CI) 0.04–0.76) and non-Hispanic black women (AOR 0.27, 95% CI 0.10–0.77) were less to likely to deliver via scheduled Caesarean compared to non-Hispanic white women. Women who delivered prior to 38 weeks’ gestation (AOR 0.37, 95% CI 0.18–0.76) were also less likely to deliver via scheduled Caesarean compared to women who delivered after 38 weeks’ gestation. An interaction term for race and gestational age at delivery was significant in multivariable analysis. Non-Hispanic black (AOR 0.06, 95% CI 0.01–0.36) and Hispanic women (AOR 0.03, 95% CI 0.00–0.59) were more likely to deliver prematurely and less likely to deliver via scheduled C-section compared to non-Hispanic white women. Having a previous Caesarean (AOR 27.77, 95% CI 8.94–86.18) increased the odds of scheduled Caesarean delivery. Conclusions Only half of deliveries for women with an unknown VL or VL >1,000 copies/ml occurred via scheduled Caesarean. Delivery prior to 38 weeks, particularly among minority women, resulted in a missed opportunity to receive a scheduled Caesarean. However, even when delivering at or after 38 weeks’ gestation, a significant proportion of women did not get a scheduled Caesarean when indicated, suggesting a need for focused public health interventions to increase the proportion of women achieving viral suppression during pregnancy and delivering via scheduled Caesarean when indicated. PMID:26657902

Hidden danger: Unexpected scenario in the vector-parasite dynamics of leishmaniases in the Brazil side of triple border (Argentina, Brazil and Paraguay)

PubMed Central

Gonçalves, André Luiz; Piechnik, Claudio Adriano; Baggio, Rafael Antunes; Boeger, Walter Antônio; Buchman, Themis Leão; Michaliszyn, Mario Sergio; Rodrigues dos Santos, Demilson; Celestino, Adão; Aquino, José; Leandro, André de Souza; da Paz, Otacílio Lopes de Souza; Limont, Marcelo; Bisetto, Alceu; Shaw, Jeffrey Jon; Yadon, Zaida Estela; Salomon, Oscar Daniel

2018-01-01

Every year about 3 million tourists from around the world visit Brazil, Argentina and Paraguay´s triple border region where the Iguaçu Falls are located. Unfortunately, in recent years an increasing number of autochthonous canine and human visceral leishmaniasis (VL) cases have been reported. The parasite is Leishmania (Leishmania) infantum and it is transmitted by sand flies (Phlebotominae). To assess the risk factors favorable for the establishment and spread of potential vectors the Centers for Disease Control and Prevention light trap (CDC-light trap) collections were made in the Foz do Iguaçu (FI) and Santa Terezinha de Itaipu (STI) townships and along two transects between them. Our study determined the Phlebotominae fauna, the factors that affect the presence and abundance of Lutzomyia longipalpis and Nyssomyia whitmani, the presence of L. infantum in different sand fly species and which Leishmania species are present in this region. Lutzomyia longipalpis was the prevalent species and its distribution was related to the abundance of dogs. Leishmania infantum was found in Lu. longipalpis, Ny. whitmani, Ny. neivai and a Lutzomyia sp. All the results are discussed within the Stockholm Paradigm and focus on their importance in the elaboration of public health policies in international border areas. This region has all the properties of stable VL endemic foci that can serve as a source of the disease for neighboring municipalities, states and countries. Most of the urban areas of tropical America are propitious for Lu. longipalpis establishment and have large dog populations. Pan American Health Organization´s initiative in supporting the public health policies in the border areas of this study is crucial and laudable. However, if stakeholders do not act quickly in controlling VL in this region, the scenario will inevitable become worse. Moreover, L. (Viannia) braziliensis found in this study supports the need to develop public health policies to avoid the spread of cutaneous leishmaniasis. The consequences of socioeconomic attributes, boundaries and frontiers on the spread of diseases cannot be neglected. For an efficient control, it is essential that urban planning is articulated with the neighboring cities. PMID:29624586

Next-Generation DNA Sequencing of VH/VL Repertoires: A Primer and Guide to Applications in Single-Domain Antibody Discovery.

PubMed

Henry, Kevin A

2018-01-01

Immunogenetic analyses of expressed antibody repertoires are becoming increasingly common experimental investigations and are critical to furthering our understanding of autoimmunity, infectious disease, and cancer. Next-generation DNA sequencing (NGS) technologies have now made it possible to interrogate antibody repertoires to unprecedented depths, typically by sequencing of cDNAs encoding immunoglobulin variable domains. In this chapter, we describe simple, fast, and reliable methods for producing and sequencing multiplex PCR amplicons derived from the variable regions (V H , V H H or V L ) of rearranged immunoglobulin heavy and light chain genes using the Illumina MiSeq platform. We include complete protocols and primer sets for amplicon sequencing of V H /V H H/V L repertoires directly from human, mouse, and llama lymphocytes as well as from phage-displayed V H /V H H/V L libraries; these can be easily be adapted to other types of amplicons with little modification. The resulting amplicons are diverse and representative, even using as few as 10 3 input B cells, and their generation is relatively inexpensive, requiring no special equipment and only a limited set of primers. In the absence of heavy-light chain pairing, single-domain antibodies are uniquely amenable to NGS analyses. We present a number of applications of NGS technology useful in discovery of single-domain antibodies from phage display libraries, including: (i) assessment of library functionality; (ii) confirmation of desired library randomization; (iii) estimation of library diversity; and (iv) monitoring the progress of panning experiments. While the case studies presented here are of phage-displayed single-domain antibody libraries, the principles extend to other types of in vitro display libraries.

Health-related quality of life of HIV infected adults with and without Visceral Leishmaniasis in Northwest Ethiopia.

PubMed

Alemayehu, Mekuriaw; Wubshet, Mamo; Mesfin, Nebiyu; Tamiru, Aschalew; Gebayehu, Abebaw

2017-08-30

Health-related quality of life (HRQoL) is an important outcome measure among HIV infected patients receiving antiretroviral therapy (ART). When HIV infected patients coinfected with Visceral Leishmaniasis (VL) the problem become severe because VL accelerates HIV replication and disease progression. The impact of VL on the quality of life of HIV infected patients has not been studied. In this study in Ethiopia, we compared the quality of life of HIV infected patients with and without VL. A cross-sectional study was conducted from October 2015 to September 2016 in selected health centers and hospitals, in Northwest Ethiopia. Data on quality of life was collected by trained nurses. The instrument used to collect the data was the short Amharic version of the World Health Organization Quality of Life for HIV clients (WHOQoL-HIV). Depression was assessed using the validated version of Kessler scale. Data was entered and analyzed using SPSS version 20. Descriptive statistics, bivariate and multivariate linear regression model was used to summarize the results. A total of 590 study participants were included in the study with response rate of 95%. Of the 590 patients included in our study 125 (21%) were HIV-VL coinfection. HIV-VL coinfected patients had a lower quality of life in all the domains as compared to HIV patients without VL. Depression was consistently and strongly associated with all the quality of life domains of both groups. Also, in HIV infected patients a longer duration in ART was associated with higher HRQoL domains except for the spiritual and level of independence domains. With regard to HIV-VL coinfected patients, a longer duration in ART was associated with psychological, spiritual and level of independence domains of HRQoL. Demographics, clinical, and treatment characteristics resulted few significant associations with HRQoL domains of both groups. HIV-VL coinfected patients had a poor quality of life in all the domains of the WHOQoL-HIV instrument. Depression, duration of ART and education were strongly associated with the quality of life. Depression should be targeted for intervention to improve the quality of life.

On the front line of HIV virological monitoring: barriers and facilitators from a provider perspective in resource-limited settings.

PubMed

Rutstein, S E; Golin, C E; Wheeler, S B; Kamwendo, D; Hosseinipour, M C; Weinberger, M; Miller, W C; Biddle, A K; Soko, A; Mkandawire, M; Mwenda, R; Sarr, A; Gupta, S; Mataya, R

2016-01-01

Scale-up of viral load (VL) monitoring for HIV-infected patients on antiretroviral therapy (ART) is a priority in many resource-limited settings, and ART providers are critical to effective program implementation. We explored provider-perceived barriers and facilitators of VL monitoring. We interviewed all providers (n = 17) engaged in a public health evaluation of dried blood spots for VL monitoring at five ART clinics in Malawi. All ART clinics were housed within district hospitals. We grouped themes at patient, provider, facility, system, and policy levels. Providers emphasized their desire for improved ART monitoring strategies, and frustration in response to restrictive policies for determining which patients were eligible to receive VL monitoring. Although many providers pled for expansion of monitoring to include all persons on ART, regardless of time on ART, the most salient provider-perceived barrier to VL monitoring implementation was the pressure of work associated with monitoring activities. The work burden was exacerbated by inefficient data management systems, highlighting a critical interaction between provider-, facility-, and system-level factors. Lack of integration between laboratory and clinical systems complicated the process for alerting providers when results were available, and these communication gaps were intensified by poor facility connectivity. Centralized second-line ART distribution was also noted as a barrier: providers reported that the time and expenses required for patients to collect second-line ART frequently obstructed referral. However, provider empowerment emerged as an unexpected facilitator of VL monitoring. For many providers, this was the first time they used an objective marker of ART response to guide clinical management. Providers' knowledge of a patient's virological status increased confidence in adherence counseling and clinical decision-making. Results from our study provide unique insight into provider perceptions of VL monitoring and indicate the importance of policies responsive to individual and environmental challenges of VL monitoring program implementation. Findings may inform scale-up by helping policy-makers identify strategies to improve feasibility and sustainability of VL monitoring.

Experimental Estimation of CLASP Spatial Resolution: Results of the Instrument's Optical Alignment

NASA Technical Reports Server (NTRS)

Giono, Gabrial; Katsukawa, Yukio; Ishikawa, Ryoko; Narukage, Noriyuki; Bando, Takamasa; Kano, Ryohei; Suematsu, Yoshinori; Kobayashi, Ken; Winebarger, Amy; Auchere, Frederic

2015-01-01

The Chromospheric Lyman-Alpha SpectroPolarimeter (CLASP) is a sounding-rocket experiment currently being built at the National Astronomical Observatory of Japan. This instrument aims to probe for the first time the magnetic field strength and orientation in the solar upper-chromosphere and lower-transition region. CLASP will measure the polarization of the Lyman-Alpha line (121.6nm) with an unprecedented accuracy, and derive the magnetic field information through the Hanle effect. Although polarization accuracy and spectral resolution are crucial for the Hanle effect detection, spatial resolution is also important to get reliable context image via the slit-jaw camera. As spatial resolution is directly related with the alignment of optics, it is also a good way of ensuring the alignment of the instrument to meet the scientific requirement. This poster will detail the experiments carried out to align CLASP's optics (telescope and spectrograph), as both part of the instrument were aligned separately. The telescope was aligned in double-pass mode, and a laser interferometer (He-Ne) was used to measure the telescope's wavefront error (WFE). The secondary mirror tilt and position were adjusted to remove comas and defocus aberrations from the WFE. Effect of gravity on the WFE measurement was estimated and the final WFE derived in zero-g condition for CLASP telescope will be presented. In addition, an estimation of the spot shape and size derived from the final WFE will also be shown. The spectrograph was aligned with a custom procedure: because Ly-??light is absorbed by air, the spectrograph's off-axis parabolic mirrors were aligned in Visible Light (VL) using a custom-made VL grating instead of the flight Ly-? grating. Results of the alignment in Visible Light will be shown and the spot shape recorded with CCDs at various position along the slit will be displayed. Results from both alignment experiment will be compared to the design requirement, and will be combined in order to estimate CLASP spatial resolution after its alignment in visible light.

Returning HIV-1 viral load results to participant-selected health facilities in national Population-based HIV Impact Assessment (PHIA) household surveys in three sub-Saharan African Countries, 2015 to 2016.

PubMed

Saito, Suzue; Duong, Yen T; Metz, Melissa; Lee, Kiwon; Patel, Hetal; Sleeman, Katrina; Manjengwa, Julius; Ogollah, Francis M; Kasongo, Webster; Mitchell, Rick; Mugurungi, Owen; Chimbwandira, Frank; Moyo, Crispin; Maliwa, Vusumuzi; Mtengo, Helecks; Nkumbula, Tepa; Ndongmo, Clement B; Vere, Nora Skutayi; Chipungu, Geoffrey; Parekh, Bharat S; Justman, Jessica; Voetsch, Andrew C

2017-11-01

Logistical complexities of returning laboratory test results to participants have precluded most population-based HIV surveys conducted in sub-Saharan Africa from doing so. For HIV positive participants, this presents a missed opportunity for engagement into clinical care and improvement in health outcomes. The Population-based HIV Impact Assessment (PHIA) surveys, which measure HIV incidence and the prevalence of viral load (VL) suppression in selected African countries, are returning VL results to health facilities specified by each HIV positive participant within eight weeks of collection. We describe the performance of the specimen and data management systems used to return VL results to PHIA participants in Zimbabwe, Malawi and Zambia. Consenting participants underwent home-based counseling and HIV rapid testing as per national testing guidelines; all confirmed HIV positive participants had VL measured at a central laboratory on either the Roche CAP/CTM or Abbott m2000 platform. On a bi-weekly basis, a dedicated data management team produced logs linking the VL test result with the participants' contact information and preferred health facility; project staff sent test results confidentially via project drivers, national courier systems, or electronically through an adapted short message service (SMS). Participants who provided cell phone numbers received SMS or phone call alerts regarding availability of VL results. From 29,634 households across the three countries, 78,090 total participants 0 to 64 years in Zimbabwe and Malawi and 0 to 59 years in Zambia underwent blood draw and HIV testing. Of the 8391 total HIV positive participants identified, 8313 (99%) had VL tests performed and 8245 (99%) of these were returned to the selected health facilities. Of the 5979 VL results returned in Zimbabwe and Zambia, 85% were returned within the eight-week goal with a median turnaround time of 48 days (IQR: 33 to 61). In Malawi, where exact return dates were unavailable all 2266 returnable results reached the health facilities by 11 weeks. The first three PHIA surveys returned the vast majority of VL results to each HIV positive participant's preferred health facility within the eight-week target. Even in the absence of national VL monitoring systems, a system to return VL results from a population-based survey is feasible, but it requires developing laboratory and data management systems and dedicated staff. These are likely important requirements to strengthen return of results systems in routine clinical care. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Surface erosion caused on Mars from Viking descent engine plume

USGS Publications Warehouse

Hutton, R.E.; Moore, H.J.; Scott, R.F.; Shorthill, R.W.; Spitzer, C.R.

1980-01-01

During the Martian landings the descent engine plumes on Viking Lander 1 (VL-1) and Viking Lander 2 (VL-2) eroded the Martian surface materials. This had been anticipated and investigated both analytically and experimentally during the design phase of the Viking spacecraft. This paper presents data on erosion obtained during the tests of the Viking descent engine and the evidence for erosion by the descent engines of VL-1 and VL-2 on Mars. From these and other results, it is concluded that there are four distinct surface materials on Mars: (1) drift material, (2) crusty to cloddy material, (3) blocky material, and (4) rock. ?? 1980 D. Reidel Publishing Co.

Antiretroviral treatment interruptions induced by the Kenyan postelection crisis are associated with virological failure.

PubMed

Mann, Marita; Diero, Lameck; Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W; Sidle, John; Buziba, Nathan; Kantor, Rami

2013-10-01

Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. We determined effects of unplanned TIs after the 2007-2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Unplanned conflict-related TIs are associated with increased likelihood of virological failure.

[Investigations into the topical problems of forensic-medical expertise of gunshot and blast injuries in the works of V.L. Popov and his disciples].

PubMed

Bozhchenko, A P; Tolmachev, I A

2013-01-01

The professional activity of professor V.L. Popov is considered with special reference to the major achievements of himself and his disciples in the field of forensic medical ballistics. The essence of provisions formulated by V.L. Popov on the mechanisms of formation and extent of gunshot injuries is discussed with regard to their importance for the determination of the large shooting distance. V.L. Popov is the founder of the scientific and pedagogical school that was justifiably regarded as the largest in this country and remains as such. The main achievements of this school have been obtained in studies of gunshot injuries.

[Construction of the lentiviral expression vector for anti-p185(erbB2) mouse/human chimeric antibody].

PubMed

Liu, Fang; Li, Li; Zhang, Wei; Wang, Qi

2013-04-01

This research was to construct the lentiviral expression vector for anti- p185(erbB2) mouse/human chimeric antibody and to determine the expression of the chimeric antibody gene in 293T cells transfected with this vector. The genes (vL and vH) coding light and heavy chain of variable regions of anti-p185(erbB2) mAb and the constant regions of human IgG1 (kappa and gamma1) were cloned with PCR method. The target genes were assembled by three-primers PCR method to obtain the chimeric light chain (L) and the chimeric heavy chain (H). Both chains inserted into the down stream and upper stream of IRES gene of the plasmid pVAX1/IRES respectively. We digested the plasmid pVAX1/ H-IRES-L with endoenzyme and subcloned H-IRES-L into the lentiviral vector pWPI. The enzyme digestion and sequence analysis showed that the lentiviral expression vector pWPI/H-IRES-L was constructed correctly. Then, it was transfected into 293T cells and after 48h, GFP protein expression in 293T cells were detected by fluorescent microscope and the chimeric antibody expression was detected by RT-PCR and direct ELISA. The results showed that after 293T cells were transfected with recombination plasmid, both light and heavy chains of the chimeric antibody genes could express together. The chimeric antibody expressed could bind to p185(erbB2) specifically. This research may lay a sound foundation for further study of anti-p185(erbB2) engineered antibody.

Soil and surface temperatures at the Viking landing sites

NASA Technical Reports Server (NTRS)

Kieffer, H. H.

1976-01-01

The annual temperature range for the Martian surface at the Viking lander sites is computed on the basis of thermal parameters derived from observations made with the infrared thermal mappers. The Viking lander 1 (VL1) site has small annual variations in temperature, whereas the Viking lander 2 (VL2) site has large annual changes. With the Viking lander images used to estimate the rock component of the thermal emission, the daily temperature behavior of the soil alone is computed over the range of depths accessible to the lander; when the VL1 and VL2 sites were sampled, the daily temperature ranges at the top of the soil were 183 to 263 K and 183 to 268 K, respectively. The diurnal variation decreases with depth with an exponential scale of about 5 centimeters. The maximum temperature of the soil sampled from beneath rocks at the VL2 site is calculated to be 230 K. These temperature calculations should provide a reference for study of the active chemistry reported for the Martian soil.

Influence of nerve growth factor on developing dorso-medial and ventro-lateral neurons of chick and mouse trigeminal ganglia.

PubMed

Davies, A; Lumsden, A

1983-01-01

Trigeminal ganglia have been removed from five, six, seven and eight day chick embryos and explants of the dorso-medial (DM) and ventro-lateral (VL) parts of the maxillomandibular lobe were grown in tissue culture. Quantitative methods were used to assess the influence of nerve growth factor (NGF) on fiber outgrowth from these explants. At all ages outgrowth from DM explants was significantly greater than from VL explants, the difference being most pronounced between the extreme DM and VL poles of the maxillomandibular lobe. These observations are interpreted as indicating the existence of two distinct populations of neurons in terms of their response to NGF rather than the consequence of the asynchronous differentiation and maturation of the VL and DM neurons. A similar study of 10, 11 and 12 day embryonic mouse trigeminal ganglia revealed no significant difference in neurite outgrowth between DM and VL regions grown in the presence or absence of NGF. Copyright © 1983. Published by Elsevier Ltd.

Seroconversion of sentinel chickens as a biomarker for monitoring exposure to visceral Leishmaniasis

PubMed Central

Soares, Bárbara Ribeiro; Souza, Ana Paula Almeida; Prates, Deboraci Brito; de Oliveira, Camila I.; Barral-Netto, Manoel; Miranda, José Carlos; Barral, Aldina

2013-01-01

Leishmania infantum chagasi causes visceral leishmaniasis (VL); it is transmitted by the sand fly Lutzomyia longipalpis that injects saliva and parasites into the host's skin during a blood meal. Chickens represent an important blood source for sand flies and their presence in the endemic area is often cited as a risk factor for VL transmission. However, the role of chickens in VL epidemiology has not been well defined. Here, we tested if chicken antibodies against Lu. longipalpis salivary gland sonicate (SGS) could be used as markers of exposure to sand fly bites. All naturally exposed chickens in a VL endemic area in Brazil developed anti-SGS IgY antibodies. Interestingly, Lu. longipalpis recombinant salivary proteins rLJM17 and rLJM11 were also able to detect anti-SGS IgY antibodies. Taken together, these results show that chickens can be used to monitor the presence of Lu. longipalpis in the peri-domiciliary area in VL endemic regions, when used as sentinel animals. PMID:23912591

Seroconversion of sentinel chickens as a biomarker for monitoring exposure to visceral leishmaniasis.

PubMed

Soares, Bárbara Ribeiro; Souza, Ana Paula Almeida; Prates, Deboraci Brito; de Oliveira, Camila I; Barral-Netto, Manoel; Miranda, José Carlos; Barral, Aldina

2013-01-01

Leishmania infantum chagasi causes visceral leishmaniasis (VL); it is transmitted by the sand fly Lutzomyia longipalpis that injects saliva and parasites into the host's skin during a blood meal. Chickens represent an important blood source for sand flies and their presence in the endemic area is often cited as a risk factor for VL transmission. However, the role of chickens in VL epidemiology has not been well defined. Here, we tested if chicken antibodies against Lu. longipalpis salivary gland sonicate (SGS) could be used as markers of exposure to sand fly bites. All naturally exposed chickens in a VL endemic area in Brazil developed anti-SGS IgY antibodies. Interestingly, Lu. longipalpis recombinant salivary proteins rLJM17 and rLJM11 were also able to detect anti-SGS IgY antibodies. Taken together, these results show that chickens can be used to monitor the presence of Lu. longipalpis in the peri-domiciliary area in VL endemic regions, when used as sentinel animals.

Soil and surface temperatures at the viking landing sites.

PubMed

Kieffer, H H

1976-12-11

The annual temperature range for the martian surface at the Viking lander sites is computed on the basis of thermal parameters derived from observations made with the infrared thermal mappers. The Viking lander 1 (VL1) site has small annual variations in temperature, whereas the Viking lander 2 (VL2) site has large annual changes. With the Viking lander images used to estimate the rock component of the thermal emission, the daily temperature behavior of the soil alone is computed over the range of depths accessible to the lander; when the VL1 and VL2 sites were sampled, the daily temperature ranges at the top of the soil were 183 to 263 K and 183 to 268 K, respectively. The diurnal variation decreases with depth with an exponential scale of about 5 centimeters. The maximum temperature of the soil sampled from beneath rocks at the VL2 site is calculated to be 230 K. These temperature calculations should provide a reference for study of the active chemistry reported for the martian soil.

Abundance of Lutzomyia longipalpis in urban households as risk factor of transmission of visceral leishmaniasis

PubMed Central

Vianna, Elisa Neves; Morais, Maria Helena Franco; de Almeida, Andréa Sobral; Sabroza, Paulo Chagastelles; Reis, Ilka Afonso; Dias, Edelberto Santos; Carneiro, Mariângela

2016-01-01

Urban occurrence of human and canine visceral leishmaniasis (VL) is linked to households with characteristics conducive to the presence of sand flies. This study proposes an ad hoc classification of households according to the environmental characteristics of receptivity to phlebotominae and an entomological study to validate the proposal. Here we describe the phlebotominae population found in intra- and peridomiciliary environments and analyse the spatiotemporal distribution of the VL vector Lutzomyia longipalpis of households receptive to VL. In the region, 153 households were classified into levels of receptivity to VL followed by entomological surveys in 40 of those properties. Kruskal-Wallis verified the relationship between the households’ classification and sand fly abundance and Kernel analysis evaluated L. longipalpis spatial distribution: of the 740 sand flies were captured, 91% were L. longipalpis; 82% were found peridomiciliary whilst the remaining 18% were found intradomiciliary. No statistically significant association was found between sandflies and households levels. L. longipalpis counts were concentrated in areas of high vulnerability and some specific households were responsible for the persistence of the infestation. L. longipalpis prevails over other sand fly species for urban VL transmission. The entomological study may help target the surveillance and vector control strategies to domiciles initiating and/or maintaining VL outbreaks. PMID:27223866

Epidemiology of visceral leishmaniasis in Algeria: an update.

PubMed

Adel, Amel; Boughoufalah, Amel; Saegerman, Claude; De Deken, Redgi; Bouchene, Zahida; Soukehal, Abdelkrim; Berkvens, Dirk; Boelaert, Marleen

2014-01-01

Visceral leishmaniasis (VL), a zoonotic disease caused by Leishmania infantum, is endemic in Algeria. This report describes a retrospective epidemiological study conducted on human VL to document the epidemiological profile at national level. All human VL cases notified by the National Institute of Public Health between 1998 and 2008 were investigated. In parallel all VL cases admitted to the university hospitals of Algiers were surveyed to estimate the underreporting ratio. Fifteen hundred and sixty-two human VL cases were reported in Algeria between 1998-2008 with an average annual reported incidence rate of 0.45 cases per 100,000 inhabitants, of which 81.42% were in the age range of 0-4 years. Cases were detected year-round, with a peak notification in May and June. One hundred and seventy patients were admitted to the university hospitals in Algiers in the same period, of which less than one in ten had been officially notified. Splenomegaly, fever, pallor and pancytopenia were the main clinical and laboratory features. Meglumine antimoniate was the first-line therapy for paediatric VL whereas the conventional amphotericin B was used for adult patients. Visceral leishmaniasis in Algeria shows the epidemiological profile of a paediatric disease with a decrease of the annual reported incidence rate. However, vigilance is required because of huge underreporting and an apparent propagation towards the south.

Cytokine Responses to Novel Antigens in a Peri-Urban Population in Brazil Exposed to Leishmania infantum chagasi

PubMed Central

Stober, Carmel B.; Jeronimo, Selma M. B.; Pontes, Nubia N.; Miller, E. Nancy; Blackwell, Jenefer M.

2012-01-01

Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen–driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36–71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates. PMID:22826477

Neural substrates underlying fear-evoked freezing: the periaqueductal grey–cerebellar link

PubMed Central

Koutsikou, Stella; Crook, Jonathan J; Earl, Emma V; Leith, J Lianne; Watson, Thomas C; Lumb, Bridget M; Apps, Richard

2014-01-01

The central neural pathways involved in fear-evoked behaviour are highly conserved across mammalian species, and there is a consensus that understanding them is a fundamental step towards developing effective treatments for emotional disorders in man. The ventrolateral periaqueductal grey (vlPAG) has a well-established role in fear-evoked freezing behaviour. The neural pathways underlying autonomic and sensory consequences of vlPAG activation in fearful situations are well understood, but much less is known about the pathways that link vlPAG activity to distinct fear-evoked motor patterns essential for survival. In adult rats, we have identified a pathway linking the vlPAG to cerebellar cortex, which terminates as climbing fibres in lateral vermal lobule VIII (pyramis). Lesion of pyramis input–output pathways disrupted innate and fear-conditioned freezing behaviour. The disruption in freezing behaviour was strongly correlated to the reduction in the vlPAG-induced facilitation of α-motoneurone excitability observed after lesions of the pyramis. The increased excitability of α-motoneurones during vlPAG activation may therefore drive the increase in muscle tone that underlies expression of freezing behaviour. By identifying the cerebellar pyramis as a critical component of the neural network subserving emotionally related freezing behaviour, the present study identifies novel neural pathways that link the PAG to fear-evoked motor responses. PMID:24639484

Cytokine responses to novel antigens in a peri-urban population in Brazil exposed to Leishmania infantum chagasi.

PubMed

Stober, Carmel B; Jeronimo, Selma M B; Pontes, Nubia N; Miller, E Nancy; Blackwell, Jenefer M

2012-10-01

Visceral leishmaniasis (VL) is fatal if untreated, and there are no vaccines for this disease. High levels of CD4-derived interferon-γ (IFN-γ) in the presence of low levels of interleukin-10 (IL-10) predicts vaccine success. Tumor necrosis factor-α (TNF-α) is also important in this process. We characterized human immune responses in three groups exposed to Leishmania infantum chagasi in Brazil: 1) drug-cured VL patients (recovered VL); 2) asymptomatic persons with positive Leishmania-specific delayed-type hypersensitivity skin reactions (DTH+); and 3) DTH-negative household contacts. Magnitude of DTH correlated with crude Leishmania antigen-driven IFN-γ, TNF-α, and IL-5, but not IL-10. DTH+ persons showed equivalent levels of IFN-γ, but higher levels of IL-10, to tryparedoxin peroxidase and Leishmania homolog of receptor for activated C kinase compared with recovered VL patients. The IFN-γ:IL-10 and TNF-α:IL-10 ratios were higher in recovered VL patients than in DTH+ persons. Seven of 11 novel candidates (R71, L37, N52, L302.06, M18, J41, and M22) elicited cytokine responses (36-71% of responders) in recovered VL patients and DTH+ persons. This result confirmed their putative status as cross-species vaccine/immunotherapeutic candidates.

[Identification of human monoclonal HIV-1-neutralizing antibodies from phage antibody library by cell-based screening].

PubMed

Zhang, Na; Man, Lai; Sun, Jian-ping; Meng, Jia-zi; He, Yu-xian

2013-09-01

To identify human monoclonal HIV-l-neutralizing antibodies from an HIV-1 CRF07BC specific phage display antibody library by cell-based screening. 293T cells were transfected by pCH064. 2-Env plas mid and then used to biopan the phage antibody library. The positive phage clones were screened by cell based ELISA and sequenced for the variable region of heavy (VH) and light (VL) chains. The expressed Fabs were purified by Ni(+2) -NTA column and analyzed by SDS-PAGE. The cell- and gp120 protein-based ELISA as well as flow cytometry were used to measure Fab's binding activity. The neutralizing activity of Fabs was assessed by HIV-1 pseudoviruses. After 4-round biopanning, the binding phages to transfected cells were enriched about 650-folds. A total of 28 positive clones were screened out by cell ELISA and sequence analysis identified 5 different Fabs possessing unique VH and VL (2801, 2837, 2863, 2870 and 2920). Interestingly, these Fabs reacted with the Env-transfected 293T cells but not soluble gp120 proteins, suggesting that they might target conformation-dependent epitopes presenting on viral Env complex. We found that three Fabs (2801, 2863, 2870) exhibited potent neutralizing activity against CRF07_BC isolate CH120. 6 with IC50 of 2.24, 0.89 and 3.09 microg/mL respectively, and that 2801 and 2863 cross-neutral ized the subtype B isolate SF162 at IC50 of 0.69 and 3.52 microg/mL respectively. In conclusion, the HIV-1 Env-transfected 293T cells can be used to efficiently enrich and screen the phage antibody library and isolate human monoclonal HIV-1-neutralizing Fabs that target the Env complex-dependent conformational epitopes. Therefore, our studies provide a powerful platform for exploring the mechanism of HIV-1 neu tralizing response and for designing AIDS vaccines.

The circadian rhythm induced by the heterogeneous network structure of the suprachiasmatic nucleus

NASA Astrophysics Data System (ADS)

Gu, Changgui; Yang, Huijie

2016-05-01

In mammals, the master clock is located in the suprachiasmatic nucleus (SCN), which is composed of about 20 000 nonidentical neuronal oscillators expressing different intrinsic periods. These neurons are coupled through neurotransmitters to form a network consisting of two subgroups, i.e., a ventrolateral (VL) subgroup and a dorsomedial (DM) subgroup. The VL contains about 25% SCN neurons that receive photic input from the retina, and the DM comprises the remaining 75% SCN neurons which are coupled to the VL. The synapses from the VL to the DM are evidently denser than that from the DM to the VL, in which the VL dominates the DM. Therefore, the SCN is a heterogeneous network where the neurons of the VL are linked with a large number of SCN neurons. In the present study, we mimicked the SCN network based on Goodwin model considering four types of networks including an all-to-all network, a Newman-Watts (NW) small world network, an Erdös-Rényi (ER) random network, and a Barabási-Albert (BA) scale free network. We found that the circadian rhythm was induced in the BA, ER, and NW networks, while the circadian rhythm was absent in the all-to-all network with weak cellular coupling, where the amplitude of the circadian rhythm is largest in the BA network which is most heterogeneous in the network structure. Our finding provides an alternative explanation for the induction or enhancement of circadian rhythm by the heterogeneity of the network structure.

Immunomodulatory properties of 1,2-dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15.

PubMed

Malfitano, Anna Maria; Laezza, Chiara; Bertini, Simone; Marasco, Daniela; Tuccinardi, Tiziano; Bifulco, Maurizio; Manera, Clementina

2017-04-01

1,2-Dihydro-4-hydroxy-2-oxo-1,8-naphthyridine-3-carboxamide derivative VL15 has been recently developed as a selective cannabinoid CB2 receptor compound. Given the high selectivity of this compound at the cannabinoid CB2 receptor and the well-known protective function of this receptor in neurological disorders with autoimmune component like multiple sclerosis, we assessed the immunomodulatory properties of VL15. We assessed on activated peripheral blood mononuclear cells), proliferation and viability, cell cycle progression and measured activation markers and the expression of phosphorylated proteins. We found that VL15 reduces PBMC proliferation slightly affecting cell vitality, blocks the cell cycle progression and down-regulates the levels of T cell activation markers as well as the expression of phosphorylated proteins, NF-kB, IKKαβ, IKBα, ERK and Akt. VL15 was also used in drug-permeability assays on Caco-2 cell line to evaluate its oral bioavailability and on MDCKII-hMDR1 cell lines to estimate its propensity to cross the blood-brain barrier by passive diffusion, in order to potentially maintain its efficiency on the infiltrating auto-reactive lymphocytes in the central nervous system. In these models, VL15 showed high intestinal absorption and good blood-brain barrier penetration. Our findings suggest that VL15, by controlling the immune response, might find potential application as orally administered drug in pathologies like multiple sclerosis. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

A small and efficient dimerization/packaging signal of rat VL30 RNA and its use in murine leukemia virus-VL30-derived vectors for gene transfer.

PubMed Central

Torrent, C; Gabus, C; Darlix, J L

1994-01-01

Retroviral genomes consist of two identical RNA molecules associated at their 5' ends by the dimer linkage structure located in the packaging element (Psi or E) necessary for RNA dimerization in vitro and packaging in vivo. In murine leukemia virus (MLV)-derived vectors designed for gene transfer, the Psi + sequence of 600 nucleotides directs the packaging of recombinant RNAs into MLV virions produced by helper cells. By using in vitro RNA dimerization as a screening system, a sequence of rat VL30 RNA located next to the 5' end of the Harvey mouse sarcoma virus genome and as small as 67 nucleotides was found to form stable dimeric RNA. In addition, a purine-rich sequence located at the 5' end of this VL30 RNA seems to be critical for RNA dimerization. When this VL30 element was extended by 107 nucleotides at its 3' end and inserted into an MLV-derived vector lacking MLV Psi +, it directed the efficient encapsidation of recombinant RNAs into MLV virions. Because this VL30 packaging signal is smaller and more efficient in packaging recombinant RNAs than the MLV Psi + and does not contain gag or glyco-gag coding sequences, its use in MLV-derived vectors should render even more unlikely recombinations which could generate replication-competent viruses. Therefore, utilization of the rat VL30 packaging sequence should improve the biological safety of MLV vectors for human gene transfer. Images PMID:8289369

Programmed death 1-mediated T cell exhaustion during visceral leishmaniasis impairs phagocyte function.

PubMed

Esch, Kevin J; Juelsgaard, Rachel; Martinez, Pedro A; Jones, Douglas E; Petersen, Christine A

2013-12-01

Control of Leishmania infantum infection is dependent upon Th1 CD4(+) T cells to promote macrophage intracellular clearance of parasites. Deficient CD4(+) T cell effector responses during clinical visceral leishmaniasis (VL) are associated with elevated production of IL-10. In the primary domestic reservoir of VL, dogs, we define occurrence of both CD4(+) and CD8(+) T cell exhaustion as a significant stepwise loss of Ag-specific proliferation and IFN-γ production, corresponding to increasing VL symptoms. Exhaustion was associated with a 4-fold increase in the population of T cells with surface expression of programmed death 1 (PD-1) between control and symptomatic populations. Importantly, exhausted populations of CD8(+) T cells and to a lesser extent CD4(+) T cells were present prior to onset of clinical VL. VL-exhausted T cells did not undergo significant apoptosis ex vivo after Ag stimulation. Ab block of PD-1 ligand, B7.H1, promoted return of CD4(+) and CD8(+) T cell function and dramatically increased reactive oxygen species production in cocultured monocyte-derived phagocytes. As a result, these phagocytes had decreased parasite load. To our knowledge, we demonstrate for the first time that pan-T cell, PD-1-mediated, exhaustion during VL influenced macrophage-reactive oxygen intermediate production. Blockade of the PD-1 pathway improved the ability of phagocytes isolated from dogs presenting with clinical VL to clear intracellular parasites. T cell exhaustion during symptomatic canine leishmaniasis has implications for the response to vaccination and therapeutic strategies for control of Leishmania infantum in this important reservoir species.

An outbreak investigation of visceral leishmaniasis among residents of Dharan town, eastern Nepal, evidence for urban transmission of Leishmania donovani

PubMed Central

2013-01-01

Background Visceral leishmaniasis (VL) is a predominantly rural disease, common in the low lands of eastern Nepal. Since 1997 VL cases have also been reported among residents of the city of Dharan. Our main research objective was to find out whether there had been local transmission of VL inside the city. Methods We conducted an outbreak investigation including a case–control study; cases were all urban residents treated for VL between 2000 and 2008 at BP Koirala Institute of Health Sciences, a university hospital in the city. For each case, we selected four random controls, with no history of previous VL; frequency-matched for age. Cases and controls were subjected to a structured interview on the main exposures of interest and potential confounders; a binominal multilevel model was used to analyze the data. We also collected entomological data from all neighborhoods of the city. Results We enrolled 115 VL patients and 448 controls. Cases were strongly clustered, 70% residing in 3 out of 19 neighborhoods. We found a strong association with socio-economic status, the poorest being most at risk. Housing was a risk factor independent from socio-economic status, most at risk were those living in thatched houses without windows. ‘Sleeping upstairs’ and ‘sleeping on a bed’ were strongly protective, OR of 0.08 and 0.25 respectively; proximity to a case was a strong risk factor (OR 3.79). Sand flies were captured in all neighborhoods; in collections from several neighborhoods presence of L. donovani could be demonstrated by PCR. Conclusion The evidence found in this study is consistent with transmission of anthroponotic VL within the city. The vector P. argentipes and the parasite L. donovani have both been identified inside the town. These findings are highly relevant for policy makers; in VL endemic areas appropriate surveillance and disease control measures must be adopted not only in rural areas but in urban areas as well. PMID:23327548

Validating a self-report measure of HIV viral suppression: an analysis of linked questionnaire and clinical data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study.

PubMed

Carter, Allison; de Pokomandy, Alexandra; Loutfy, Mona; Ding, Erin; Sereda, Paul; Webster, Kath; Nicholson, Valerie; Beaver, Kerrigan; Hogg, Robert S; Kaida, Angela

2017-03-24

We assessed the validity of a self-report measure of undetectable viral load (VL) among women with HIV in British Columbia (BC), Canada. Questionnaire data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study was linked with population-based clinical data from the BC Centre for Excellence in HIV/AIDS. Self-reported undetectable VL was assessed by the question: "What was your most recent VL, undetectable (i.e. <50 copies/mL) or detectable (i.e. ≥50 copies/mL)?" Laboratory measurements of VL <50 copies/mL (closest to/before study visit) were the criterion for validity analyses. We measured positive and negative predictive values (PPV, NPV) and likelihood ratios (LR+, LR-). Of 356 participants, 99% were linked to clinical data. Those unlinked (n = 1), missing self-report VL (n = 18), or missing self-report and laboratory VL (n = 1) were excluded. Among the remaining 336: median age was 44 (IQR 37-51); 96% identified as cis-gender; 84% identified as heterosexual; and 45% identified as Indigenous, 40% White, 8% African, Caribbean, or Black, and 8% other/multiple ethnicities. Overall, 85% self-reported having an undetectable VL while 82% had clinical data indicating viral suppression. The PPV was 93.7 (95% CI 90.2-96.2) indicating that 94% of women who self-reported being undetectable truly were. The NPV was 80.4 (95% CI 66.9-90.2). LR+ was 3.2 (2.1-4.6) and LR- was 0.05 (0.03-0.10). Our self-report measure assessing undetectable VL strongly predicted true viral suppression among Canadian women with HIV. This measure can be used in research settings without laboratory data in regions with high rates of VL testing and suppression.

Recovery of antigen-specific T cell responses from dogs infected with Leishmania (L.) infantum by use of vaccine associated TLR-agonist adjuvant.

PubMed

Schaut, Robert G; Grinnage-Pulley, Tara L; Esch, Kevin J; Toepp, Angela J; Duthie, Malcolm S; Howard, Randall F; Reed, Steven G; Petersen, Christine A

2016-10-17

Visceral leishmaniasis (VL), caused by infection with the obligate intracellular protozoan parasite Leishmania infantum, is a fatal disease of dogs and humans. Protection against VL requires a T helper 1 (Th1) skewed CD4 + T response, but despite this knowledge, there are currently no approved-to-market vaccines for humans and only three veterinary-use vaccines globally. As VL progresses from asymptomatic to symptomatic, L. infantum-specific interferon gamma (IFNγ) driven-Th1 responses become dampened and a state of immune exhaustion established. T cell exhaustion and other immunoregulatory processes, starting during asymptomatic disease, are likely to hinder vaccine-induced responses if vaccine is administered to infected, but asymptomatic and seronegative, individuals. In this study we evaluated how immune exhaustion, shown previously by our group to worsen in concert with VL progression, effected the capacity of vaccine candidate antigen/toll-like receptor (TLR) agonist combinations to promote protective CD4 + T cell responses during progressive VL. In conjunction with Th1 responses, we also evaluated concomitant stimulation of immune-balanced IL-10 regulatory cytokine production by these vaccine products in progressive VL canine T cells. Vaccine antigen L111f in combination with TLR agonists significantly recovered CD4 + T cell IFNγ intracellular production in T cells from asymptomatic VL dogs. Vaccine antigen NS with TLR agonists significantly recovered CD4 + T cell production in both endemic control and VL dogs. Combinations of TLR agonists and vaccine antigens overcame L. infantum induced cellular exhaustion, allowing robust Th1 CD4 + T cell responses from symptomatic dogs that previously had dampened responses to antigen alone. Antigen-agonist adjuvants can be utilized to promote more robust vaccine responses from infected hosts in endemic areas where vaccination of asymptomatic, L. infantum-infected animals is likely. Copyright © 2016. Published by Elsevier Ltd.

U3 long terminal repeat-mediated induction of intracellular immunity by a murine retrovirus: a novel model of latency for retroviruses.

PubMed Central

Gorska-Flipot, I; Huang, M; Cantin, M; Rassart, E; Massé, G; Jolicoeur, P

1992-01-01

BL/VL3 radiation leukemia virus (RadLV) is a thymotropic, highly leukemogenic murine leukemia virus (MuLV) which is unable to replicate in vitro in mouse fibroblasts. We have previously reported that the U3 long terminal repeat region of its genome is responsible for this block (E. Rassart, Y. Paquette, and P. Jolicoeur, J. Virol. 62:3840-3848, 1988). By using hybrids of permissive and resistant cells infected with BL/VL3 RadLV or fibrotropic MuLV, we found that the resistant phenotype was dominant. Investigation to determine at which step of the virus cycle the block operates revealed that integration, transcription, and translation of the BL/VL3 viral genome occurred at normal levels in nonpermissive cells. The BL/VL3 RadLV Pr65gag proteins made in nonpermissive cells were also myristylated and located at the membrane, and the levels of their cleaved products were similar to those of fibrotropic MuLV. However, processing of BL/VL3 RadLV Pr85env was impaired in nonpermissive cells. Virions were not released into the culture medium of nonpermissive cells, as measured by reverse transcriptase activity and by content in p30 or gp70 protein and as documented by lower levels of budding particles seen by electron microscopy. These results indicate that BL/VL3 RadLV replication is blocked at a late stage of the virus cycle, i.e., at virion assembly. Interestingly, these BL/VL3 RadLV-infected nonpermissive fibroblasts were resistant to superinfection by fibrotropic Moloney MuLV, and this resistance also occurred at a late step of the Moloney virus cycle. Since this block is dominant, it appears that the U3 long terminal repeat region of the BL/VL3 viral genome has the ability to induce a cellular suppressor factor(s), thus bringing intracellular immunity against itself and against other ecotropic MuLVs. Images PMID:1433513

Performance characteristics of finger-stick dried blood spots (DBS) on the determination of human immunodeficiency virus (HIV) treatment failure in a pediatric population in Mozambique

PubMed Central

Chang, Joy; de Sousa, Amina; Sabatier, Jennifer; Assane, Mariamo; Zhang, Guoqing; Bila, Dulce; Vaz, Paula; Alfredo, Charity; Cossa, Loide; Bhatt, Nilesh; Koumans, Emilia H.; Yang, Chunfu; Rivadeneira, Emilia; Jani, Ilesh; Houston, James C.

2017-01-01

Quantitative plasma viral load (VL) at 1000 copies /mL was recommended as the threshold to confirm antiretroviral therapy (ART) failure by the World Health Organization (WHO). Because of ongoing challenges of using plasma for VL testing in resource-limited settings (RLS), especially for children, this study collected 717 DBS and paired plasma samples from children receiving ART ≥1 year in Mozambique and compared the performance of DBS using Abbott’s VL test with a paired plasma sample using Roche’s VL test. At a cut-off of 1000 copies/mL, sensitivity of DBS using Abbott DBS VL test was 79.9%, better than 71.0% and 63.9% at 3000 and 5000 copies/mL, respectively. Specificities were 97.6%, 98.8%, 99.3% at 1000, 3000, and 5000 copies/mL, respectively. The Kappa value at 1000 copies/mL, 0.80 (95% CI: 0.73, 0.87), was higher than 0.73 (95% CI: 0.66, 0.80) and 0.66 (95% CI: 0.59, 0.73) at 3000, 5000 copies/mL, respectively, also indicating better agreement. The mean difference between the DBS and plasma VL tests with 95% limits of agreement by Bland-Altman was 0.311 (-0.908, 1.530). Among 73 children with plasma VL between 1000 to 5000 copies/mL, the DBS results were undetectable in 53 at the 1000 copies/mL threshold. While one DBS sample in the Abbott DBS VL test may be an alternative method to confirm ART failure at 1000 copies/mL threshold when a plasma sample is not an option for treatment monitoring, because of sensitivity concerns between 1,000 and 5,000 copies/ml, two DBS samples may be preferred accompanied by careful patient monitoring and repeat testing. PMID:28704560

Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

PubMed Central

Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

2014-01-01

Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

Changes in muscle architecture and performance during a competitive season in female softball players.

PubMed

Nimphius, Sophia; McGuigan, Michael R; Newton, Robert U

2012-10-01

The purpose of this research was (a) to examine the performance changes that occur in elite female softball players during 20 weeks of softball training (that included 14 weeks of periodized resistance training [RT]) and (b) to examine the relationship between percent change (%change) in muscle architecture variables and %change in strength, speed, and change of direction performance. Ten female softball players (age = 18.1 ± 1.6 years, height = 166.5 ± 8.9 cm, weight = 72.4 ± 10.8 kg) from a state Australian Institute of Sport softball team were tested for maximal lower-body strength using a 3 repetition maximum for a predicted 1 repetition maximum (1RM) and peak force, peak velocity (PV), and peak power (PP) were measured during jump squats (JS) unloaded and loaded. In addition, the first base (1B) and the second base (2B) sprint performance, change of direction (505) on dominant (D) and nondominant (ND) sides, aerobic capacity, and muscle architecture characteristics of vastus lateralis (VL) including muscle thickness (MT), fascicle length (FL), and pennation angle (θp) were examined. The testing sessions occurred pre, mid, and post training (total 20 week pre- and in-season training period). Changes over time were analyzed by repeated-measures analysis of variance. The relationship between %change in muscle architecture variables and strength, speed, and change of direction variables from pre to post were assessed by Pearson product-moment correlation coefficient. Significant improvements in PV and PP occurred at all JS loads pre- to mid-testing and pre- to post-testing. Significant increases occurred pre-post in absolute 1RM, relative 1RM, 505 ND, and 2B sprint. The strongest relationships were found between %change in VL MT and 1B sprint (r = -0.80, p = 0.06), %change in VL FL and 2B sprint (r = -0.835, p = 0.02), and %change in relative 1RM and 505 D (r = -0.70, p = 0.04). In conclusion, gains in strength, power, and performance can occur during the season in elite softball players who are also engaged in a periodized RT program. Furthermore, changes in performance measures are associated with changes in muscle architecture.

Risk factors of visceral leishmaniasis: a case control study in north-western Ethiopia.

PubMed

Yared, Solomon; Deribe, Kebede; Gebreselassie, Araya; Lemma, Wessenseged; Akililu, Essayas; Kirstein, Oscar D; Balkew, Meshesha; Warburg, Alon; Gebre-Michael, Teshome; Hailu, Asrat

2014-10-14

Visceral leishmaniasis (VL, also called ''kala-azar"), is a life threatening neglected tropical infectious disease which mainly affects the poorest of the poor. VL is prevalent in Ethiopia particularly in the northwest of the country. Understanding the risk factors of VL infection helps in its prevention and control. The aim of the present study was to identify the factors associated with VL. A case-control study was carried out during the period of January-July 2013 in northwest Ethiopia. Cases and controls were diagnosed using clinical presentation, the rk39 rapid diagnostic test and Direct Agglutination Test (DAT). A total of 283 (84.8% males versus 15.2% females) participants were interviewed. 90 cases and 193 controls were involved, matched by age, sex and geographical location with a ratio of 1:2 (case: controls). Univariate and backward multivariate conditional logistic regression were used to identify risk factors of VL. Elevated odds of VL was associated with goat ownership (OR = 6.4; 95%: confidence interval [Cl]: 1.5-28.4), living in houses with cracked wall (OR = 6.4; 95% Cl: 1.6-25.6), increased family size (OR = 1.3; 95% Cl: 1.0-1.8) and the number of days spent in the farm field (OR = 1.1; 95% Cl: 1.0-1.2). However, daily individual activities around the home and farm fields, mainly sleeping on a bed (OR = 0.2; 95%: Cl 0.03-0.9), sleeping outside the house under a bed net (OR = 0.1; 95% Cl: 0.02-0.36)] and smoking plant parts in the house during the night time (OR = 0.1; 95% Cl: 0.01-0.6) were associated with decreased odds of being VL case. Our findings showed that use of bed net and smoke could be helpful for the prevention of VL in the area particularly among individuals who spend most of their time in the farm. VL control effort could be focused on improving housing conditions, such as sealing cracks and crevices inside and outside houses. Further research is warranted to elucidate the role of goats in the transmission of L. donovani, assess the impact of bed nets and the role of the traditional practice of smoking plants.

Antiretroviral-treated HIV-1 patients can harbour resistant viruses in CSF despite an undetectable viral load in plasma.

PubMed

Soulie, Cathia; Grudé, Maxime; Descamps, Diane; Amiel, Corinne; Morand-Joubert, Laurence; Raymond, Stéphanie; Pallier, Coralie; Bellecave, Pantxika; Reigadas, Sandrine; Trabaud, Mary-Anne; Delaugerre, Constance; Montes, Brigitte; Barin, Francis; Ferré, Virginie; Jeulin, Hélène; Alloui, Chakib; Yerly, Sabine; Signori-Schmuck, Anne; Guigon, Aurélie; Fafi-Kremer, Samira; Haïm-Boukobza, Stéphanie; Mirand, Audrey; Maillard, Anne; Vallet, Sophie; Roussel, Catherine; Assoumou, Lambert; Calvez, Vincent; Flandre, Philippe; Marcelin, Anne-Geneviève

2017-08-01

HIV therapy reduces the CSF HIV RNA viral load (VL) and prevents disorders related to HIV encephalitis. However, these brain disorders may persist in some cases. A large population of antiretroviral-treated patients who had a VL > 1.7 log 10 copies/mL in CSF with detectable or undetectable VL in plasma associated with cognitive impairment was studied, in order to characterize discriminatory factors of these two patient populations. Blood and CSF samples were collected at the time of neurological disorders for 227 patients in 22 centres in France and 1 centre in Switzerland. Genotypic HIV resistance tests were performed on CSF. The genotypic susceptibility score was calculated according to the last Agence Nationale de Recherche sur le Sida et les hépatites virales Action Coordonnée 11 (ANRS AC11) genotype interpretation algorithm. Among the 227 studied patients with VL > 1.7 log 10 copies/mL in CSF, 195 had VL detectable in plasma [median (IQR) HIV RNA was 3.7 (2.7-4.7) log 10 copies/mL] and 32 had discordant VL in plasma (VL < 1.7 log 10 copies/mL). The CSF VL was lower (median 2.8 versus 4.0 log 10 copies/mL; P  <   0.001) and the CD4 cell count was higher (median 476 versus 214 cells/mm 3 ; P  <   0.001) in the group of patients with VL < 1.7 log 10 copies/mL in plasma compared with patients with plasma VL > 1.7 log 10 copies/mL. Resistance to antiretrovirals was observed in CSF for the two groups of patients. Fourteen percent of this population of patients with cognitive impairment and detectable VL in CSF had well controlled VL in plasma. Thus, it is important to explore CSF HIV (VL and genotype) even if the HIV VL is controlled in plasma because HIV resistance may be observed. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Cost-effectiveness of diagnostic-therapeutic strategies for paediatric visceral leishmaniasis in Morocco

PubMed Central

Alonso, Sergi; Tachfouti, Nabil; Najdi, Adil; Sicuri, Elisa; Picado, Albert

2017-01-01

Introduction Visceral leishmaniasis (VL) is a neglected parasitic disease with a high fatality rate if left untreated. Endemic in Morocco, as well as in other countries in the Mediterranean basin, VL mainly affects children living in rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow (BM) aspirates is used to diagnose VL and meglumine antimoniate (SB) is the first line of treatment. Less invasive, more efficacious and safer alternatives exist. In this study we estimate the cost-effectiveness of alternative diagnostic-therapeutic algorithms for paediatric VL in Morocco. Methods A decision tree was used to estimate the cost-effectiveness of using BM or rapid diagnostic tests (RDTs) as diagnostic tools and/or SB or two liposomal amphotericin B (L-AmB) regimens: 6-day and 2-day courses to treat VL. Incremental cost-effectiveness ratios, expressed as cost per death averted, were estimated by comparing costs and effectiveness of the alternative algorithms. A threshold analysis evaluated at which price L-AmB became cost-effective compared with current practices. Results Implementing RDT and/or L-AmB treatments would be cost-effective in Morocco according to the WHO thresholds. Introducing the 6-day course L-AmB, current second-line treatment, would be highly cost-effective if L-AmB price was below US$100/phial. The 2-day L-AmB treatment, current standard treatment of paediatric VL in France, is highly cost-effective, with L-AmB at its market price (US$165/phial). Conclusions The results of this study should encourage the implementation of RDT and/or short-course L-AmB treatments for paediatric VL management in Morocco and other North African countries. PMID:29018581

Cost-effectiveness of diagnostic-therapeutic strategies for paediatric visceral leishmaniasis in Morocco.

PubMed

Alonso, Sergi; Tachfouti, Nabil; Najdi, Adil; Sicuri, Elisa; Picado, Albert

2017-01-01

Visceral leishmaniasis (VL) is a neglected parasitic disease with a high fatality rate if left untreated. Endemic in Morocco, as well as in other countries in the Mediterranean basin, VL mainly affects children living in rural areas. In Morocco, the direct observation of Leishmania parasites in bone marrow (BM) aspirates is used to diagnose VL and meglumine antimoniate (SB) is the first line of treatment. Less invasive, more efficacious and safer alternatives exist. In this study we estimate the cost-effectiveness of alternative diagnostic-therapeutic algorithms for paediatric VL in Morocco. A decision tree was used to estimate the cost-effectiveness of using BM or rapid diagnostic tests (RDTs) as diagnostic tools and/or SB or two liposomal amphotericin B (L-AmB) regimens: 6-day and 2-day courses to treat VL. Incremental cost-effectiveness ratios, expressed as cost per death averted, were estimated by comparing costs and effectiveness of the alternative algorithms. A threshold analysis evaluated at which price L-AmB became cost-effective compared with current practices. Implementing RDT and/or L-AmB treatments would be cost-effective in Morocco according to the WHO thresholds. Introducing the 6-day course L-AmB, current second-line treatment, would be highly cost-effective if L-AmB price was below US$100/phial. The 2-day L-AmB treatment, current standard treatment of paediatric VL in France, is highly cost-effective, with L-AmB at its market price (US$165/phial). The results of this study should encourage the implementation of RDT and/or short-course L-AmB treatments for paediatric VL management in Morocco and other North African countries.

Blood flow occlusion-related O2 extraction "reserve" is present in different muscles of the quadriceps but greater in deeper regions after ramp-incremental test.

PubMed

Iannetta, Danilo; Okushima, Dai; Inglis, Erin Calaine; Kondo, Narihiko; Murias, Juan M; Koga, Shunsaku

2018-05-03

It was recently demonstrated that an O 2 extraction reserve, as assessed by the near-infrared spectroscopy (NIRS)-derived deoxygenation signal ([HHb]), exists in the superficial region of vastus lateralis (VL) muscle during an occlusion performed at the end of a ramp-incremental test. However, it is unknown whether this reserve is present and/or different in magnitude in other portions and depths of the quadriceps muscles. We tested the hypothesis that O 2 extraction would exist in other regions of this muscle but greater in deep compared to more superficial portions. Superficial and deep VL (VL-s and VL-d, respectively) as well as superficial rectus femoris (RF-s) were monitored by a combination of low- and high- power time resolved (TRS) NIRS. During the occlusion immediately post ramp-incremental test there was a significant overshoot in the [HHb] signal (P<0.05). However, the magnitude of this increase was greater in VL-d (93.2{plus minus}42.9%) compared to VL-s (55.0{plus minus}19.6%) and RF-s (47.8{plus minus}14.0%) (P<0.05). The present study demonstrated that an O2 extraction reserve exists in different pools of active muscle fibers of the quadriceps at the end of a ramp exercise to exhaustion. The greater magnitude in the reserve observed in the deeper portion of VL, however, suggests that this portion of muscle may present a greater surplus of oxygenated blood, likely due to a greater population of slow-twitch fibers. These findings add to the notion that the plateau in the [HHb] signal towards the end of a ramp-incremental exercise does not indicate the upper limit of O 2 extraction.

Comparison of physical, chemical, and sensorial characteristics between U.S.-imported and Northwestern Mexico retail beef.

PubMed

González-Rios, H; Peña-Ramos, A; Valenzuela, M; Zamorano-García, L; Cumplido-Barbeitia, G; González-Méndez, N F; Huerta-Leidenz, N

2010-01-01

To compare beef from Northwestern Mexico (NMEX) and that imported from the United States in physical-chemical (PC) and sensory traits, samples of ribeye (m. Longissimus dorsi thoracis, LDT) and knuckle (m. Vastus lateralis, VL) of Mexican (64 LDT; 51 VL) and U.S. (28 LDT; 25 VL) origin were purchased randomly from select retail stores located in 3 cities of NMEX. PC evaluation measured contents of moisture, fat and cholesterol, Warner-Bratzler shear force (WBSF), pH, CIE L*, a*, and b*, cooking loss, and normalized fatty acid profile (FAP). Trained panelists evaluated raw and cooked samples for 2 and 6 different organoleptic traits, respectively. Mexican and U.S.-imported LDT steaks did not differ (P>0.05) in PC traits. VL samples differed in L*, b*, hue*, WBSF, and fat content by country of origin (COO). The WBSF for cooked VL samples from the United States was lower (P < 0.05) and fat content was greater (P<0.05) than those for NMEX steaks. The FAP varied between muscles; Mexican LDT had a higher content of C18:0, while VL from the United States had a higher proportion of polyunsaturated fatty acids (PUFA) and a higher PUFA/Saturated ratio (P<0.05). Although sensory traits tended to be rated higher for Mexican LDT and VL steaks, no statistical differences with U.S.-imported samples were detected (P > 0.05). Results indicated that domestic and U.S. retail steaks sold in the NMEX are similar in eating quality and PC, whereas differences observed in FAP deserve further attention from a nutritional standpoint. © 2010 Institute of Food Technologists®

Angiotensin AT1 receptors modulate the anxiogenic effects of angiotensin (5-8) injected into the rat ventrolateral periaqueductal gray.

PubMed

Genaro, Karina; Fabris, Débora; Fachim, Helene A; Prado, Wiliam A

2017-10-01

Losartan and PD 123,319 are non-peptide angiotensin (Ang) receptor antagonists for the AT1 and AT2 subtypes of Ang II receptors, respectively. The tetrapeptide Ang (5-8) is the smallest Ang-peptide that elicits anxiogenic effects on unconditioned and conditioned experimental models upon injection into the ventrolateral column of the periaqueductal gray (vlPAG), and Ang (5-8) can be synthesized (from Ang II or Ang III) and inactivated in this mesencephalic structure. The vlPAG is also known to play a central role in mechanisms of fear and anxiety. We therefore utilized male Wistar rats to examine the effects of losartan and PD 123,319 injections, selective antagonists of the AT1 and AT2 receptors, respectively, into the vlPAG in the elevated plus-maze, a classic rat model of anxiety, and against the anxiogenic effect of Ang (5-8) (0.4 nmol/0.25μL) upon injection into the same region. The anxiolytic profile was dependent on the dose of intra-vlPAG losartan, whereas no effects on experimental anxiety were observed in the plus-maze following PD 123,319 injection. The anxiogenic effect of Ang (5-8) injection into the vlPAG remained unchanged in the PD 123,319-pretreated rats, but the effect did not occur in losartan-pretreated rats. The results led us to suggest that the anxiogenic effect of Ang (5-8) injection into the vlPAG may depend on the local activation of AT1, but not AT2 receptors. Activation of AT1 receptors in structures nearby vlPAG may be tonically involved in fear and experimental anxiety. Copyright © 2017. Published by Elsevier Inc.

Towards elimination of visceral leishmaniasis in the Indian subcontinent-Translating research to practice to public health.

PubMed

Hirve, Siddhivinayak; Kroeger, Axel; Matlashewski, Greg; Mondal, Dinesh; Banjara, Megha Raj; Das, Pradeep; Be-Nazir, Ahmed; Arana, Byron; Olliaro, Piero

2017-10-01

The decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders, has coordinated and financed research for the development of new innovative tools and strategies to support the regional VL elimination initiative. This paper describes the process of the TDR's engagement and contribution to this initiative. Multiple databases were searched to identify 152 scientific papers and reports with WHO funding or authorship affiliation around the following 3 framework strategies: detection of new cases, morbidity reduction, and prevention of infection. TDR has played a critical role in the evaluation and subsequent use of the 39-aminoacid-recombinant kinesin antigen (rK39) rapid diagnostic test (RDT) as a confirmatory test for VL in the national program. TDR has supported the clinical research and development of miltefosine and single-dose liposomal amphotericin B as a first-line treatment against VL. TDR has engaged with in-country researchers, national programme managers, and partners to generate evidence-based interventions for early detection and treatment of VL patients. TDR evaluated the quality, community acceptance, and cost effectiveness of indoor residual spraying, insecticide-treated bed nets, insecticide-impregnated durable wall linings, insecticidal paint, and environmental management as tools for integrated vector management in reducing sandfly density. TDR's engagement with country policy makers, scientists, and clinicians in the development of effective diagnosis, treatment, case detection, and vector control represents an important example of TDR's stewardship toward the elimination of VL in the Indian subcontinent.

Factors affecting volume calculation with single photon emission tomography (SPECT) method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, T.H.; Lee, K.H.; Chen, D.C.P.

1985-05-01

Several factors may influence the calculation of absolute volumes (VL) from SPECT images. The effect of these factors must be established to optimize the technique. The authors investigated the following on the VL calculations: % of background (BG) subtraction, reconstruction filters, sample activity, angular sampling and edge detection methods. Transaxial images of a liver-trunk phantom filled with Tc-99m from 1 to 3 ..mu..Ci/cc were obtained in 64x64 matrix with a Siemens Rota Camera and MDS computer. Different reconstruction filters including Hanning 20,32, 64 and Butterworth 20, 32 were used. Angular samplings were performed in 3 and 6 degree increments. ROI'smore » were drawn manually and with an automatic edge detection program around the image after BG subtraction. VL's were calculated by multiplying the number of pixels within the ROI by the slice thickness and the x- and y- calibrations of each pixel. One or 2 pixel per slice thickness was applied in the calculation. An inverse correlation was found between the calculated VL and the % of BG subtraction (r=0.99 for 1,2,3 ..mu..Ci/cc activity). Based on the authors' linear regression analysis, the correct liver VL was measured with about 53% BG subtraction. The reconstruction filters, slice thickness and angular sampling had only minor effects on the calculated phantom volumes. Detection of the ROI automatically by the computer was not as accurate as the manual method. The authors conclude that the % of BG subtraction appears to be the most important factor affecting the VL calculation. With good quality control and appropriate reconstruction factors, correct VL calculations can be achieved with SPECT.« less

Changing Antiretroviral Eligibility Criteria: Impact on the Number and Proportion of Adults Requiring Treatment in Swaziland.

PubMed

Bock, Naomi N; Emerson, Ruth C; Reed, Jason B; Nkambule, Rejoice; Donnell, Deborah J; Bicego, George T; Okello, Velephi; Philip, Neena M; Ehrenkranz, Peter D; Duong, Yen T; Moore, Janet S; Justman, Jessica E

2016-03-01

Early initiation of antiretroviral treatment (ART) at CD4 cell count ≥ 500 cells per microliter reduces morbidity and mortality in HIV-infected adults. We determined the proportion of HIV-infected people with high viral load (VL) for whom transmission prevention would be an additional benefit of early treatment. A randomly selected subset of a nationally representative sample of HIV-infected adults in Swaziland in 2012. Eight to 12 months after a national survey to determine adult HIV prevalence, 1067 of 5802 individuals identified as HIV-infected were asked to participate in a follow-up cross-sectional assessment. CD4 cell enumeration, VL measurements, and ART status were obtained to estimate the proportion of currently untreated adults and of the entire HIV-infected population with high VL (≥ 1000 copies/mL) whose treatment under a test-and-treat or VL threshold eligibility strategy would reduce HIV transmission. Of the 927 (87% of 1067) participants enrolled, 466 (50%) reported no ART use. Among them, 424 (91%) had VL ≥ 1000 copies per milliliter; of these, 148 (35%) were eligible for ART at the then existing CD4 count threshold of <350 cells per microliter; an additional 107 (25%) were eligible with expanded CD4 criterion of <500 cells per microliter; and 169 (40%) remained ART ineligible. Thus, 36% of the 466 currently untreated and 18% of the total 927 had high VL yet remained ART ineligible under a CD4 criterion of <500 cells per microliter. A test-and-treat or VL threshold for treatment eligibility is necessary to maximize the HIV transmission prevention benefits of ART.

Pharmacokinetic/Pharmacodynamic Predictors of Clinical Potency for Hepatitis C Virus Nonnucleoside Polymerase and Protease Inhibitors

PubMed Central

Morcos, Peter N.; Le Pogam, Sophie; Ou, Ying; Frank, Karl; Lave, Thierry; Smith, Patrick

2012-01-01

This analysis was conducted to determine whether the hepatitis C virus (HCV) viral kinetics (VK) model can predict viral load (VL) decreases for nonnucleoside polymerase inhibitors (NNPolIs) and protease inhibitors (PIs) after 3-day monotherapy studies of patients infected with genotype 1 chronic HCV. This analysis includes data for 8 NNPolIs and 14 PIs, including VL decreases from 3-day monotherapy, total plasma trough concentrations on day 3 (Cmin), replicon data (50% effective concentration [EC50] and protein-shifted EC50 [EC50,PS]), and for PIs, liver-to-plasma ratios (LPRs) measured in vivo in preclinical species. VK model simulations suggested that achieving additional log10 VL decreases greater than one required 10-fold increases in the Cmin. NNPolI and PI data further supported this result. The VK model was successfully used to predict VL decreases in 3-day monotherapy for NNPolIs based on the EC50,PS and the day 3 Cmin. For PIs, however, predicting VL decreases using the same model and the EC50,PS and day 3 Cmin was not successful; a model including LPR values and the EC50 instead of the EC50,PS provided a better prediction of VL decrease. These results are useful for designing phase 1 monotherapy studies for NNPolIs and PIs by clarifying factors driving VL decreases, such as the day 3 Cmin and the EC50,PS for NNPolIs or the EC50 and LPR for PIs. This work provides a framework for understanding the pharmacokinetic/pharmacodynamic relationship for other HCV drug classes. The availability of mechanistic data on processes driving the target concentration, such as liver uptake transporters, should help to improve the predictive power of the approach. PMID:22470110

Linkage and retention in care and the time to HIV viral suppression and viral rebound - New York City.

PubMed

Robertson, McKaylee; Laraque, Fabienne; Mavronicolas, Heather; Braunstein, Sarah; Torian, Lucia

2015-01-01

The success of antiretroviral therapy (ART) as treatment for the individual patient and as prevention requires the achievment and maintenance of human immunodeficiency virus (HIV) viral suppression. Linkage to and retention in care are required for access to ART. We describe the impact of care on viral suppression using routinely reported surveillance data. We included New York City residents ≥13 years of age, diagnosed with HIV/AIDS from 1 July 2005 to 30 June 2009 with a viral load (VL) or CD4 reported within six months of diagnosis and ≥1 VL reported from 1 July 2005 to 30 June 2011. To examine viral rebound, we restricted the analysis to those who achieved viral suppression and had a subsequent VL measure reported by 30 June 2011. Cox proportional hazards models were used to evaluate factors associated with time to viral suppression (VL ≤ 400 copies/mL) and rebound (VL > 1000 copies/mL). Initiation of care within three months of diagnosis (CD4/VL report within three months of diagnosis), female sex, and an initial CD4 < 350 (cells/mm(3)) at diagnosis significantly increased the likelihood of viral suppression. Irregular care (no CD4/VL reported every six months), younger age, non-white race/ethnicity, having an initial CD4 ≥ 350 at diagnosis, and AIDS diagnosis by 2010 increased the likelihood of rebound. These findings lend support to interventions for improving linkage to and maintenance in regular care as a way to achieve and maintain suppression. Surveillance data represent an ideal means for monitoring engagement in care and viral suppression at the population level.

Utility of Mobile Communication Devices as a Tool to Improve Adherence to Antiretroviral Treatment in HIV-infected Children and Young Adults in Argentina.

PubMed

Stankievich, Erica; Malanca, Adriana; Foradori, Irene; Ivalo, Silvina; Losso, Marcelo

2018-04-01

Optimal adherence is critical to achieve the benefits of antiretroviral treatment (ART). The aim of the study is to evaluate the use of mobile devices as a strategy to improve adherence to ART, measured by viral load (VL) in HIV+ patients less than 25 years of age. A prospective study was conducted in a cohort of HIV+ patients less than 25 years of age. HIV+ patients, on ART, VL >1000 copies/mL, using mobile devices and suboptimal adherence were included. The intervention was based on a mobile generic contact twice a month using text message and Facebook during 32 weeks. Extended communications were generated by the patient. VL was performed before and after the intervention. Twenty-five patients were included. Three were excluded and 22 patients were enrolled. Mean age was 17.2 ± 6.1 years (range: 6-25); 15 (68%) were female; mean baseline VL was 25,100 copies/mL (range: 1020-500,000 copies/mL), mean log was 4.3 (range: 3-5.7 log). Each participant received a total of 16 contacts; 84% (296) were answered by the patient and 54% (189) of the contacts generated extended communications. After the strategy implementation, 20/22 VL results were available: 13/20 (65%) were undetectable, 14/20 (70%) had VL < 1000 copies/mL and 6/20 (30%) VLs had no changes. The use of mobile devices and social networks is a valid tool to improve ART adherence in HIV+ pediatric and young adults, evaluated through VL. The strategy is feasible. The reminder messages trigger additional communications between patients and health provider and better engagement with HIV care. Longer follow-up time is needed.

Activation of reciprocal pathways between arcuate nucleus and ventrolateral periaqueductal gray during electroacupuncture: involvement of VGLUT3

PubMed Central

Guo, Zhi-Ling; Longhurst, John C.

2010-01-01

Electroacupuncture (EA) at the Jianshi-Neiguan acupoints (P5-P6, overlying the median nerve) attenuates sympathoexcitatory responses through activation of the arcuate nucleus (ARC) and ventrolateral periaqueductal gray (vlPAG). Activation of the ARC or vlPAG respectively leads to neuronal excitation of the both nuclei during EA. However, direct projections between these two nuclei that could participate in central neural processing during EA have not been identified. The vesicular glutamate transporter 3 (VGLUT3) marks glutamatergic neurons. Thus, the present study evaluated direct neuronal projections between the ARC and vlPAG during EA, focusing on neurons containing VGLUT3. Seven to ten days after unilateral microinjection of a rodamine-conjugated microsphere retrograde tracer (100 nl) into the vlPAG or ARC, rats were subjected to EA or served as a sham-operated control. Low frequency (2 Hz) EA was performed bilaterally for 30 min at the P5-P6 acupoints. Perikarya containing the microsphere tracer were found in the ARC and vlPAG of both groups. Compared to controls (needle placement without electrical stimulation), c-Fos immunoreactivity and neurons double-labeled with c-Fos, an immediate early gene and the tracer were increased significantly in the ARC and vlPAG of EA-treated rats (both P<0.01). Moreover, some neurons were triple-labeled with c-Fos, the retrograde tracer and VGLUT3 in the two nuclei following EA stimulation (P<0.01, both nuclei). These results suggest that direct reciprocal projections between the ARC and vlPAG are available to participate in prolonged modulation by EA of sympathetic activity and that VGLUT3-containing neurons are an important neuronal phenotype involved in this process. PMID:20836994

Towards elimination of visceral leishmaniasis in the Indian subcontinent—Translating research to practice to public health

PubMed Central

Kroeger, Axel; Matlashewski, Greg; Mondal, Dinesh; Banjara, Megha Raj; Das, Pradeep; Be-Nazir, Ahmed; Arana, Byron; Olliaro, Piero

2017-01-01

Background The decade following the Regional Strategic Framework for Visceral Leishmaniasis (VL) elimination in 2005 has shown compelling progress in the reduction of VL burden in the Indian subcontinent. The Special Programme for Research and Training in Tropical Diseases (TDR), hosted by the World Health Organization (WHO) and other stakeholders, has coordinated and financed research for the development of new innovative tools and strategies to support the regional VL elimination initiative. This paper describes the process of the TDR’s engagement and contribution to this initiative. Methodology/principal findings Multiple databases were searched to identify 152 scientific papers and reports with WHO funding or authorship affiliation around the following 3 framework strategies: detection of new cases, morbidity reduction, and prevention of infection. TDR has played a critical role in the evaluation and subsequent use of the 39-aminoacid–recombinant kinesin antigen (rK39) rapid diagnostic test (RDT) as a confirmatory test for VL in the national program. TDR has supported the clinical research and development of miltefosine and single-dose liposomal amphotericin B as a first-line treatment against VL. TDR has engaged with in-country researchers, national programme managers, and partners to generate evidence-based interventions for early detection and treatment of VL patients. TDR evaluated the quality, community acceptance, and cost effectiveness of indoor residual spraying, insecticide-treated bed nets, insecticide-impregnated durable wall linings, insecticidal paint, and environmental management as tools for integrated vector management in reducing sandfly density. Conclusions/significance TDR’s engagement with country policy makers, scientists, and clinicians in the development of effective diagnosis, treatment, case detection, and vector control represents an important example of TDR’s stewardship toward the elimination of VL in the Indian subcontinent. PMID:29023446

Motor units in vastus lateralis and in different vastus medialis regions show different firing properties during low-level, isometric knee extension contraction.

PubMed

de Souza, Leonardo Mendes Leal; Cabral, Hélio Veiga; de Oliveira, Liliam Fernandes; Vieira, Taian Martins

2018-04-01

Architectural differences along vastus medialis (VM) and between VM and vastus lateralis (VL) are considered functionally important for the patellar tracking, knee joint stability and knee joint extension. Whether these functional differences are associated with a differential activity of motor units between VM and VL is however unknown. In the present study, we, therefore, investigate neuroanatomical differences in the activity of motor units detected proximo-distally from VM and from the VL muscle. Nine healthy volunteers performed low-level isometric knee extension contractions (20% of their maximum voluntary contraction) following a trapezoidal trajectory. Surface electromyograms (EMGs) were recorded from VM proximal and distal regions and from VL using three linear adhesive arrays of eight electrodes. The firing rate and recruitment threshold of motor units decomposed from EMGs were then compared among muscle regions. Results show that VL motor units reached lower mean firing rates in comparison with VM motor units, regardless of their position within VM (P < .040). No significant differences in firing rate were found between proximal and distal, VM motor units (P = .997). Furthermore, no significant differences in the recruitment threshold were observed for all motor units analysed (P = .108). Our findings possibly suggest the greater potential of VL to generate force, due to its fibres arrangement, may account for the lower discharge rate observed for VL then either proximally or distally detected motor units in VM. Additionally, the present study opens new perspectives on the importance of considering muscle architecture in investigations of the neural aspects of motor behaviour. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatial population dynamics and temporal analysis of the distribution of Lutzomyia longipalpis (Lutz & Neiva, 1912) (Diptera: Psychodidae: Phlebotominae) in the city of Clorinda, Formosa, Argentina.

PubMed

Gómez-Bravo, Andrea; German, Alba; Abril, Marcelo; Scavuzzo, Marcelo; Salomón, Oscar D

2017-07-25

Lutzomyia longipalpis, the vector for the causal agent of visceral leishmaniasis (VL), has extended its distribution in the southern cone in the Americas. The first urban record of Lu. longipalpis in Argentina was from the City of Clorinda in 2004. The aim of this study was to analyse the monthly distribution and abundance of Lu. longipalpis and to evaluate its association with environmental and climatic variables in Clorinda City, Province of Formosa. Phlebotominae sampling was performed using CDC light mini-traps that were placed in different sites of the city between January 2012 and December 2013. Environmental variables including the normalised difference vegetation index, normalized difference water index, land surface temperature and precipitation were evaluated using a spatiotemporal model. A total of 4996 phlebotomine sandflies were captured during the study period, and eight species were reported: Lu. longipalpis, Migonemyia migonei, Nyssomyia whitmani, Ny. neivai, Brumptomyia guimaraesi, Evandromyia cortelezzii/sallesi, Psathyromyia bigeniculata and Expapillata firmatoi. This is the first urban record of Ex. firmatoi in Argentina. Lutzomyia longipalpis was the most abundant species between 2012 and 2013, and it appeared in all the sampled sites. Moreover, the model applied showed that ground humidity and temperature were significantly associated with the abundance of Lu. longipalpis. This longitudinal approach at city scale allows for modelling that explains more than 60% of the temporal variability of the abundance of Lu. longipalpis based exclusively on satellite obtained data. The results support the hypothesis of steady 'hot spots' of abundance with time, while other sites could change its abundance due to eventual microenvironment changes. The Lu. longipalpis abundance driving factors are breeding site-related variables, highlighting the importance both for modelling and surveillance to use lag data.

Cytosolic tryparedoxin of Leishmania donovani modulates host immune response in visceral leishmaniasis.

PubMed

Suman, Shashi Shekhar; Amit, Ajay; Singh, Krishn Pratap; Gupta, Parool; Equbal, Asif; Kumari, Arti; Topno, Roshan Kamal; Ravidas, Vidyananda; Pandey, Krishna; Bimal, Sanjiva; Das, Pradeep; Ali, Vahab

2018-08-01

Leishmaniasis is a neglected tropical disease caused by the unicellular protozoan parasite of genus Leishmania. Tryparedoxin (TXN) is a low molecular mass dithiol protein belonging to oxidoreductases super-family; which function in concert with tryparedoxin peroxidase (TXNPx) as a system in protozoan parasites including Leishmania. Leishmanial hydroperoxides detoxification cascade uses trypanothione as electron donor to reduce hydroperoxide inside the macrophages during infection. However, the mechanism by which tryparedoxin can contribute in progression of visceral leishmaniasis (VL) and its impact on host's cellular immune response during infection in Indian VL patient is unknown. In this study, we purified a ∼17 kDa recombinant cytosolic tryparedoxin (cTXN) protein of Leishmania donovani (rLdcTXN) and investigated its immunological responses in peripheral blood monocytes (PBMC) isolated from VL patients. The protein significantly enhanced the promastigotes count after 96 h of culture showing a direct correlation with parasite growth. Furthermore, stimulation of PBMC isolated from VL patients with rLdcTXN resulted in up-regulation of IL-4 and IL-10 production whereas IL-12 and IFN-γ was significantly down-regulated suggesting a pivotal role of cTXN in provoking the immune suppression during VL. Our study demonstrates the importance of cTXN protein which can potentially modulate the outcome of disease through suppressing host protective Th1 response in VL patients. Copyright © 2018 Elsevier Ltd. All rights reserved.

Molecular and Serological Evidence of Leishmania Infection in Stray Dogs from Visceral Leishmaniasis-Endemic Areas of Bangladesh.

PubMed

Akter, Shirin; Alam, Mohammad Zahangir; Nakao, Ryo; Yasin, Golam; Kato, Hirotomo; Katakura, Ken

2016-10-05

Visceral leishmaniasis (VL), or kala-azar, is mainly caused by two closely related Leishmania species, Leishmania infantum and Leishmania donovani Leishmania infantum is responsible for zoonotic VL, with dogs as the main reservoir host in the Mediterranean, the Middle East, Asia, and South America. In the Indian subcontinent, VL is caused by L. donovani and is considered anthroponotic, although the only known vector, the sand fly, is zoophilic in nature. The role of domestic and stray dogs in VL transmission is still unclear in this area. We screened 50 stray dogs from VL-endemic areas of Bangladesh for serological and molecular evidence of Leishmania infection. We detected anti-Leishmania antibodies in six (12%) dog serum samples using rK39 immunochromatographic tests. We observed Leishmania kinetoplast DNA in 10 (20%) buffy coat DNA samples by real-time polymerase chain reaction (PCR), five of which were positive based on internal transcribed spacer 1-PCR. A sequencing analysis of the amplified products confirmed that the parasitic DNA was derived from L. donovani Our findings support the hypothesis that stray dogs are an animal reservoir for L. donovani in this endemic region. Further studies are required to determine the precise role of dogs in the epidemiology of VL in Bangladesh. © The American Society of Tropical Medicine and Hygiene.

Clinical and Laboratory Analysis of Patients with Leishmaniasis: A Retrospective Study from a Tertiary Care Center in New Delhi

PubMed Central

GUPTA, Nitin; KANT, Kamla; MIRDHA, Bijay Ranjan

2017-01-01

Background: Leishmaniasis manifests as visceral (VL), cutaneous (CL) or a dermal sequel of VL, known as Post kala-azar dermal leishmaniasis (PKDL). The aim of the study was to analyze the clinical and laboratory features of cases diagnosed with leishmaniasis. Methods: This hospital-based retrospective study included all cases of VL, PKDL, and CL diagnosed between Jan 2011 to Jan 2016 at All India Institute of Medical Sciences, New Delhi. Clinical and laboratory profile of the diagnosed cases were analyzed in detail. All diagnosed cases were mapped according to the state and the district from which the cases originated. Results: A total of 91 VL cases and 4 PKDL cases were reviewed. Only one case of CL (1 female) and mucocutaneous leishmaniasis (1 female) were observed during the study period. Majority of the cases of VL (75/91) originated from Bihar. The most common presenting symptoms in all our patients were fever (97.8%), weight loss (40.6%) and abdominal discomfort (17.6%) while the most common presenting signs were hepatosplenomegaly (45.8%), isolated splenomegaly (23.1%) and skin pigmentation (11%). The most common laboratory abnormality was anaemia followed by thrombocytopenia and leucopenia. Conclusion: VL is globally recognized as a neglected tropical disease. Even after continued effort to bring down its transmission in India, it continues to affect the endemic states with reports from new pockets. PMID:29317889

Epidemiology of Visceral Leishmaniasis in Algeria: An Update

PubMed Central

Adel, Amel; Boughoufalah, Amel; Saegerman, Claude; De Deken, Redgi; Bouchene, Zahida; Soukehal, Abdelkrim; Berkvens, Dirk; Boelaert, Marleen

2014-01-01

Visceral leishmaniasis (VL), a zoonotic disease caused by Leishmania infantum, is endemic in Algeria. This report describes a retrospective epidemiological study conducted on human VL to document the epidemiological profile at national level. All human VL cases notified by the National Institute of Public Health between 1998 and 2008 were investigated. In parallel all VL cases admitted to the university hospitals of Algiers were surveyed to estimate the underreporting ratio. Fifteen hundred and sixty-two human VL cases were reported in Algeria between 1998–2008 with an average annual reported incidence rate of 0.45 cases per 100,000 inhabitants, of which 81.42% were in the age range of 0–4 years. Cases were detected year-round, with a peak notification in May and June. One hundred and seventy patients were admitted to the university hospitals in Algiers in the same period, of which less than one in ten had been officially notified. Splenomegaly, fever, pallor and pancytopenia were the main clinical and laboratory features. Meglumine antimoniate was the first-line therapy for paediatric VL whereas the conventional amphotericin B was used for adult patients. Visceral leishmaniasis in Algeria shows the epidemiological profile of a paediatric disease with a decrease of the annual reported incidence rate. However, vigilance is required because of huge underreporting and an apparent propagation towards the south. PMID:24949958

Modulation of GSH with exogenous agents leads to changes in glyoxalase 1 enzyme activity in VL-17A cells exposed to chronic alcohol plus high glucose.

PubMed

Kumar, S Mathan; Swaminathan, Kavitha; Clemens, Dahn L; Dey, Aparajita

2014-02-01

Gluthathione (GSH) is a major cellular antioxidant. The present study utilizing VL-17A cells exposed to chronic alcohol plus high glucose investigated the changes in oxidative stress, toxicity, and glyoxalase 1 activity as a detoxification pathway due to changes in GSH level through GSH supplementation with N-acetyl cysteine (NAC) or ursodeoxycholic acid (UDCA) and its depletion through buthionine sulfoximine (BSO) or diethyl maleate (DEM). Glyoxalase 1 plays an important role in detoxification of methylglyoxal which is formed as a precursor of advanced glycated end products formed due to high glucose mediated oxidative stress. Significant changes in glyoxalase 1 activity utilizing methylglyoxal or glyoxal as substrates occurred with NAC or UDCA or BSO or DEM supplementation in chronic alcohol plus high glucose treated VL-17A cells. NAC or UDCA administration in chronic alcohol plus high glucose treated VL-17A cells increased viability and decreased ROS levels, lipid peroxidation and 3-nitrotyrosine adduct formation. Similarly, GSH depletion with BSO or DEM had an opposite effect on the parameters in chronic alcohol plus high glucose treated VL-17A cells. In conclusion, modulation of GSH with NAC or UDCA or BSO or DEM leads to significant changes in oxidative stress, glyoxalase 1 enzyme activity and toxicity in chronic alcohol plus high glucose treated VL-17A cells.

Measurement of varus-valgus and internal-external rotational knee laxities in vivo--Part II: relationship with anterior-posterior and general joint laxity in males and females.

PubMed

Shultz, Sandra J; Shimokochi, Yohei; Nguyen, Anh-Dung; Schmitz, Randy J; Beynnon, Bruce D; Perrin, David H

2007-08-01

We examined sex differences in general joint laxity (GJL), and anterior-posterior displacement (ANT-POST), varus-valgus rotation (VR-VL), and internal-external rotation (INT-EXT) knee laxities, and determined whether greater ANT and GJL predicted greater VR-VL and INT-EXT. Twenty subjects were measured for GJL, and scored on a scale of 0-9. ANT and POST were measured using a standard knee arthrometer at 133 N. VR-VL and INT-EXT were measured using a custom joint laxity testing device, defined as the angular displacements (deg) of the tibia relative to the femur produced by 0-10 Nm of varus-valgus torques, and 0-5 Nm of internal-external torques, respectively. INT-EXT were measured during both non-weight-bearing (NWB) and weight-bearing (WB = 40% body weight) conditions while VR-VL were measured NWB. All laxity measures were greater for females compared to males except for POST. ANT and GJL positively predicted 62.5% of the variance in VR-VL and 41.8% of the variance in WB INT-EXT. ANT was the sole predictor of INT-EXT in NWB, explaining 42.3% of the variance. These findings suggest that subjects who score higher on clinical measures of GJL and ANT are also likely to have greater VR-VL and INT-EXT knee laxities.

Application of Recombinant Proteins for Serodiagnosis of Visceral Leishmaniasis in Humans and Dogs.

PubMed

Farahmand, Mahin; Nahrevanian, Hossein

2016-07-01

Visceral leishmaniasis (VL) is a zoonotic disease caused by leishmania species. Dogs are considered to be the main reservoir of VL. A number of methods and antigen-based assays are used for the diagnosis of leishmaniasis. However, currently available methods are mainly based on direct examination of tissues for the presence of parasites, which is highly invasive. A variety of serological tests are commonly applied for VL diagnosis, including indirect fluorescence antibody test, enzyme-linked immunosorbent assay (ELISA), dot-ELISA, direct agglutination test, Western-blotting, and immunochromatographic test. However, when soluble antigens are used, serological tests are less specific due to cross-reactivity with other parasitic diseases. Several studies have attempted to replace soluble antigens with recombinant proteins to improve the sensitivity and the specificity of the immunodiagnostic tests. Major technological advances in recombinant antigens as reagents for the serological diagnosis of VL have led to high sensitivity and specificity of these serological tests. A great number of recombinant proteins have been shown to be effective for the diagnosis of leishmania infection in dogs, the major reservoir of L. infantum. Although few recombinant proteins with high efficacy provide reasonable results for the diagnosis of human and canine VL, more optimization is still needed for the appropriate antigens to provide high-throughput performance. This review aims to explore the application of different recombinant proteins for the serodiagnosis of VL in humans and dogs.

Epidemiological aspects of human and canine visceral leishmaniasis in Montes Claros, State of Minas Gerais, Brazil, between 2007 and 2009.

PubMed

Prado, Patrícia Fernandes do; Rocha, Marília Fonseca; Sousa, Joel Fontes de; Caldeira, Dênio Iuri; Paz, Gustavo Fontes; Dias, Edelberto Santos

2011-10-01

Visceral leishmaniasis (VL) is an expanding zoonosis in Brazil and is becoming urbanized in several Brazilian regions. This study aims to describe the epidemiological features of human and canine VL in the municipality of Montes Claros, State of Minas Gerais, by focusing on their spatial distribution. Data concerning human cases and reactive dogs for VL from 2007 to 2009 were obtained from the Information System for Disease Notification (SINAN) and from reports of the local Centro de Controle de Zoonoses (CCZ), respectively. The addresses of human and canine cases have been georeferenced and localized in thematic maps, allowing their spatial visualization as well as the identification of areas at risk of VL transmission. Ninety-five cases of human VL were reported in the period. The 0-9-year-old age group (48.4%) was the most affected, within which the majority consisted of male patients (64%). Of the samples collected for the canine serological survey, 2,919 (6.3%) were reactive to VL. The spatial localization of these cases shows that the disease was scattered in the urban area of the municipality. Areas showing a higher dissemination risk were concentrated in the central, northwestern, and southern regions of the city. Identifying the areas most at risk in urban Montes Claros may help guide actions toward local epidemiological vigilance and control.

Martian soil stratigraphy and rock coatings observed in color-enhanced Viking Lander images

NASA Technical Reports Server (NTRS)

Strickland, E. L., III

1979-01-01

Subtle color variations of martian surface materials were enhanced in eight Viking Lander (VL) color images. Well-defined soil units recognized at each site (six at VL-1 and four at VL-2), are identified on the basis of color, texture, morphology, and contact relations. The soil units at the Viking 2 site form a well-defined stratigraphic sequence, whereas the sequence at the Viking 1 site is only partially defined. The same relative soil colors occur at the two sites, suggesting that similar soil units are widespread on Mars. Several types of rock surface materials can be recognized at the two sites; dark, relatively 'blue' rock surfaces are probably minimally weathered igneous rock, whereas bright rock surfaces, with a green/(blue + red) ratio higher than that of any other surface material, are interpreted as a weathering product formed in situ on the rock. These rock surface types are common at both sites. Soil adhering to rocks is common at VL-2, but rare at VL-1. The mechanism that produces the weathering coating on rocks probably operates planet-wide.

Wind reconstruction algorithm for Viking Lander 1

NASA Astrophysics Data System (ADS)

Kynkäänniemi, Tuomas; Kemppinen, Osku; Harri, Ari-Matti; Schmidt, Walter

2017-06-01

The wind measurement sensors of Viking Lander 1 (VL1) were only fully operational for the first 45 sols of the mission. We have developed an algorithm for reconstructing the wind measurement data after the wind measurement sensor failures. The algorithm for wind reconstruction enables the processing of wind data during the complete VL1 mission. The heater element of the quadrant sensor, which provided auxiliary measurement for wind direction, failed during the 45th sol of the VL1 mission. Additionally, one of the wind sensors of VL1 broke down during sol 378. Regardless of the failures, it was still possible to reconstruct the wind measurement data, because the failed components of the sensors did not prevent the determination of the wind direction and speed, as some of the components of the wind measurement setup remained intact for the complete mission. This article concentrates on presenting the wind reconstruction algorithm and methods for validating the operation of the algorithm. The algorithm enables the reconstruction of wind measurements for the complete VL1 mission. The amount of available sols is extended from 350 to 2245 sols.

Properties of an equine herpesvirus 1 mutant devoid of the internal inverted repeat sequence of the genomic short region

PubMed Central

Ahn, ByungChul; Zhang, Yunfei; Osterrieder, Nikolaus; O'Callaghan, Dennis J.

2010-01-01

The 150 kbp genome of equine herpesvirus -1 (EHV-1) is composed of a unique long (UL) region and a unique short (Us) segment, which is flanked by identical internal and terminal repeat (IR and TR) sequences of 12.7kbp. We constructed an EHV-1 lacking the entire IR (vL11ΔIR) and showed that the IR is dispensable for EHV-1 replication but that the vL11ΔIR exhibits a smaller plaque size and delayed growth kinetics. Western blot analyses of cells infected with vL11ΔIR showed that the synthesis of viral proteins encoded by the immediate-early, early, and late genes was reduced at immediate-early and early times, but by late stages of replication reached wild type levels. Intranasal infection of CBA mice revealed that the vL11ΔIR was significantly attenuated as mice infected with the vL11ΔIR showed a reduced lung viral titer and greater ability to survive infection compared to mice infected with parental or revertant virus. PMID:21176938

A strategy to identify linker-based modules for the allosteric regulation of antibody-antigen binding affinities of different scFvs

PubMed Central

Thie, Holger

2017-01-01

ABSTRACT Antibody single-chain variable fragments (scFvs) are used in a variety of applications, such as for research, diagnosis and therapy. Essential for these applications is the extraordinary specificity, selectivity and affinity of antibody paratopes, which can also be used for efficient protein purification. However, this use is hampered by the high affinity for the protein to be purified because harsh elution conditions, which may impair folding, integrity or viability of the eluted biomaterials, are typically required. In this study, we developed a strategy to obtain structural elements that provide allosteric modulation of the affinities of different antibody scFvs for their antigen. To identify suitable allosteric modules, a complete set of cyclic permutations of calmodulin variants was generated and tested for modulation of the affinity when substituting the linker between VH and VL. Modulation of affinity induced by addition of different calmodulin-binding peptides at physiologic conditions was demonstrated for 5 of 6 tested scFvs of different specificities and antigens ranging from cell surface proteins to haptens. In addition, a variety of different modulator peptides were tested. Different structural solutions were found in respect of the optimal calmodulin permutation, the optimal peptide and the allosteric effect for scFvs binding to different antigen structures. Significantly, effective linker modules were identified for scFvs with both VH-VL and VL-VH architecture. The results suggest that this approach may offer a rapid, paratope-independent strategy to provide allosteric regulation of affinity for many other antibody scFvs. PMID:28055297

Visceral leishmaniasis with Roth spots

PubMed Central

Meena, Jagdish; Juneja, Monica; Mishra, Devendra; Vats, Pallavi; Pawaria, Arti

2014-01-01

Visceral leishmaniasis (VL) is caused by the protozoan parasite Leishmania donovani and transmitted by the bite of infected sandfly Phlebotomus argentipes. The protozoa is obliged intracellularly and causes a wide spectrum of clinical syndromes: VL (‘kala azar’), cutaneous leishmaniasis and mucocutaneous leishmaniasis (espundia). Kala azar is the most aggressive form and if untreated causes high mortality. Here, we describe a case of VL that presented to us with high-grade fever and found to have Roth spots that were resolved after 15 days of therapy. PMID:25988048

Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection

PubMed Central

Hickling, Stephen; Hurst, Jacob; Meyerowitz, Jodi; Willberg, Christian B.; Robinson, Nicola; Brown, Helen; Kinloch, Sabine; Babiker, Abdel; Nwokolo, Nneka; Fox, Julie; Fidler, Sarah; Phillips, Rodney; Frater, John

2016-01-01

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n = 122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression. Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed. Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants. Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches. PMID:27415828

Improving the affinity of an antibody for its antigen via long-range electrostatic interactions.

PubMed

Fukunaga, Atsushi; Tsumoto, Kouhei

2013-12-01

To address how long-range electrostatic force can affect antibody-antigen binding, we focused on the interactions between human cardiac troponin I and its specific single-chain antibodies (scFvs). We first isolated two scFvs against two linear epitopes with distinct isoelectric points. For the scFv against the acidic epitope (A1scFv), we mutated five residues of framework region 3 of the light chain to Lys or Arg, designated as the K- or R-mutant, respectively. For the scFv against the basic epitope (A2scFv), we mutated four or three residues in framework region 3 of the light or heavy chain to Asp, to generate the VL- and VH-mutant, respectively. Surface plasmon resonance analyses showed that the kon values of all of the mutants were greater than that of wild type, even though framework region 3 does not make direct contact with the epitope. The affinity of the K-mutant was pM range, and that of the R-mutant improved further by more than two orders of magnitude due to a decrease in the dissociation rate constant. For the A2scFv mutants, the affinity of the VL-mutant for its target improved through an increase in the kon value without a decrease in the koff value. The stability slightly decreased in all mutants. These results suggest that introducing electrostatic interaction can improve the affinity of an antibody for its target, even if the mutation reduces stability of the antibody.

Coupling mechanism in the gate and oscillator model of the SCN

NASA Astrophysics Data System (ADS)

Li, Ying; Liu, Zengrong

2016-09-01

In mammals, the suprachiasmatic nucleus (SCN) of the hypothalamus is considered as the master circadian pacemaker. The SCN is divided into two subgroups of gate and oscillator cells: the ventrolateral (VL) neurons, which receive the periodic light-dark (LD) signal, and the dorsomedial (DM) neurons, which are coupled to the VL cells. The fundamental question is how the individual cellular oscillators, expressing a wide range of periods, interact and assemble to create an integrated pacemaker that can govern behavioral and physiological rhythmicity and be reset by environmental light. The key is that the heterogeneous network formed by the cellular clocks within the SCN must synchronize to maintain timekeeping activity. Based on the structural and functional heterogeneity of the SCN, the authors bring forward a mathematical model including gate cells and oscillator cells with a wide range of periods. The gate neurons offer daily injection to oscillator neurons and the activation of gate is determined by the output of the oscillator neurons. In this model, the authors consider two kinds of coupling: interior coupling among the oscillator cells and exterior coupling from the gate cells to the oscillator cells. The authors mainly analyze the combined effects of these two kinds of coupling on the entrainment of the oscillator cells in the DM part. It is found that the interior coupling is conducive to entrainment, but a stronger coupling is not beneficial to entrainment. The gate mechanism in exterior coupling is more propitious to entrainment than continuous coupling. This study helps to understand collective circadian rhythm in the mammals.

Cytomegalovirus (CMV) DNA quantification in bronchoalveolar lavage fluid of immunocompromised patients with CMV pneumonia.

PubMed

Beam, Elena; Germer, Jeffrey J; Lahr, Brian; Yao, Joseph D C; Limper, Andrew Harold; Binnicker, Matthew J; Razonable, Raymund R

2018-01-01

Cytomegalovirus (CMV) pneumonia causes major morbidity and mortality. Its diagnosis requires demonstration of viral cytopathic changes in tissue, entailing risks of lung biopsy. This study aimed to determine CMV viral load (VL) thresholds in bronchoalveolar lavage fluid (BALF) for diagnosis of CMV pneumonia in immunocompromised patients. CMV VL in BALF was studied in 17 patients (83% transplant recipients) and 21 control subjects with and without CMV pneumonia, respectively, using an FDA-approved PCR assay (Cobas ® AmpliPrep/Cobas TaqMan ® CMV Test, Roche Molecular Systems, Inc.) calibrated to the WHO International Standard for CMV DNA (NIBSC: 09/162). Receiver operating characteristic curve analysis produced a BALF CMV VL threshold of 34 800, IU/mL with 91.7% sensitivity and 100.0% specificity for diagnosis of possible, probable, and proven CMV pneumonia in transplant patients, while a threshold of 656 000 IU/mL yielded 100% sensitivity and specificity among biopsy-proven cases. For all immunocompromised patients, a VL threshold of 274 IU/mL was selected. VL thresholds also were normalized to BALF cell count yielding a threshold of 0.32 IU/10 6 cells with 91.7% sensitivity and 90.5% specificity for possible, probable, and proven CMV pneumonia in transplant recipients. Monitoring CMV VL in BALF may be a less invasive method for diagnosing CMV pneumonia in immunocompromised patients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Heterobimetallic Complexes That Bond Vanadium to Iron, Cobalt, and Nickel.

PubMed

Clouston, Laura J; Bernales, Varinia; Cammarota, Ryan C; Carlson, Rebecca K; Bill, Eckhard; Gagliardi, Laura; Lu, Connie C

2015-12-21

Zero-valent iron, cobalt, and nickel were installed into the metalloligand V[N(o-(NCH2P((i)Pr)2)C6H4)3] (1, VL), generating the heterobimetallic trio FeVL (2), CoVL (3), and NiVL (4), respectively. In addition, the one-electron-oxidized analogues [FeVL]X ([2(ox)]X, where X(-) = BPh4 or PF6) and [CoVL]BPh4 ([3(ox)]BPh4) were prepared. The complexes were characterized by a host of physical methods, including cyclic voltammetry, X-ray crystallography, magnetic susceptibility, electronic absorption, NMR, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies. The CoV and FeV heterobimetallic compounds have short M-V bond lengths that are consistent with M-M multiple bonding. As revealed by theoretical calculations, the M-V bond is triple in 2, 2(ox), and 3(ox), double in 3, and dative (Ni → V) in 4. The (d-d)(10) species, 2 and 3(ox), are diamagnetic and exhibit large diamagnetic anisotropies of -4700 × 10(-36) m(3)/molecule. Complexes 2 and 3(ox) are also characterized by intense visible bands at 760 and 610 nm (ε > 1000 M(-1) cm(-1)), respectively, which correspond to an intermetal (M → V) charge-transfer transition. Magnetic susceptibility measurements and EPR characterization establish S = (1)/2 ground states for (d-d)(9) 2(ox) and (d-d)(11) 3, while (d-d)(12) 4 is S = 1 based on Evans' method.

Feasibility of a combined camp approach for vector control together with active case detection of visceral leishmaniasis, post kala-azar dermal leishmaniasis, tuberculosis, leprosy and malaria in Bangladesh, India and Nepal: an exploratory study.

PubMed

Banjara, Megha R; Kroeger, Axel; Huda, Mamun M; Kumar, Vijay; Gurung, Chitra K; Das, Murari L; Rijal, Suman; Das, Pradeep; Mondal, Dinesh

2015-06-01

We assessed the feasibility and results of active case detection (ACD) of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and other febrile diseases as well as of bednet impregnation for vector control. Fever camps were organized and analyzed in twelve VL endemic villages in Bangladesh, India, and Nepal. VL, PKDL, tuberculosis, malaria and leprosy were screened among the febrile patients attending the camps, and existing bednets were impregnated with a slow release insecticide. Among the camp attendees one new VL case and two PKDL cases were detected in Bangladesh and one VL case in Nepal. Among suspected tuberculosis cases two were positive in India but none in the other countries. In India, two leprosy cases were found. No malaria cases were detected. Bednet impregnation coverage during fever camps was more than 80% in the three countries. Bednet impregnation led to a reduction of sandfly densities after 2 weeks by 86% and 32%, and after 4 weeks by 95% and 12% in India and Nepal respectively. The additional costs for the control programmes seem to be reasonable. It is feasible to combine ACD camps for VL and PKDL along with other febrile diseases, and vector control with bednet impregnation. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.

'Virtual lesion' in pain research; a study on magnetic stimulation of the primary motor cortex.

PubMed

Granovsky, Y; Liem, K S; Weissman-Fogel, I; Yarnitsky, D; Chistyakov, A; Sinai, A

2016-02-01

'Virtual lesion' ('VL') is a transient disruption of cortical activity during task performance. It can be induced by single pulses or short trains of transcranial magnetic stimulation (TMS) directed to functionally relevant brain areas. We applied 'VL' methodology of a short train of TMS given on top of experimental tonic pain, expecting to see changes in pain scores. Thirty young healthy subjects (15 women) were assessed with active ('VL') or 'sham' TMS in different sessions, randomly. In each session, 30 sec-long contact heat (47.5 °C, right forearm) was applied stand-alone ('baseline') and with 5 sec-long 10 Hz-TMS over left primary motor cortex (M1) starting at 17 sec of the heat stimulation. Pain scores decreased after 'VL' or 'sham' (p < 0.001). Independently of the type of TMS, pain reduction was stronger in women (p = 0.012). A triple Sex x Stimulation type ('VL' or 'sham') x Condition ('baseline' heat pain vs. heat pain with TMS) interaction (p = 0.027) indicated stronger pain reduction by 'VL' in women (p = 0.008) and not in men (p = 0.78) as compared to 'baseline'. Pain catastrophizing and perceived stress ratings affected the model (p = 0.010 and p < 0.001, respectively), but without sex differences. This study indicates that interactions between cortical excitability of the motor cortex and nociceptive processing may be gender-related. © 2015 European Pain Federation - EFIC®

Implementation of a virtual laryngoscope system using efficient reconstruction algorithms.

PubMed

Luo, Shouhua; Yan, Yuling

2009-08-01

Conventional fiberoptic laryngoscope may cause discomfort to the patient and in some cases it can lead to side effects that include perforation, infection and hemorrhage. Virtual laryngoscopy (VL) can overcome this problem and further it may lower the risk of operation failures. Very few virtual endoscope (VE) based investigations of the larynx have been described in the literature. CT data sets from a healthy subject were used for the VL studies. An algorithm of preprocessing and region-growing for 3-D image segmentation is developed. An octree based approach is applied in our VL system which facilitates a rapid construction of iso-surfaces. Some locating techniques are used for fast rendering and navigation (fly-through). Our VL visualization system provides for real time and efficient 'fly-through' navigation. The virtual camera can be arranged so that it moves along the airway in either direction. Snap shots were taken during fly-throughs. The system can automatically adjust the direction of the virtual camera and prevent collisions of the camera and the wall of the airway. A virtual laryngoscope (VL) system using OpenGL (Open Graphics Library) platform for interactive rendering and 3D visualization of the laryngeal framework and upper airway is established. OpenGL is supported on major operating systems and works with every major windowing system. The VL system runs on regular PC workstations and was successfully tested and evaluated using CT data from a normal subject.

Heterobimetallic Complexes That Bond Vanadium to Iron, Cobalt, and Nickel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clouston, Laura J.; Bernales, Varinia; Cammarota, Ryan C.

2015-12-21

Zero-valent iron, cobalt, and nickel were installed into the metalloligand V[N(o-(NCH2P(iPr)2)C6H4)3] (1, VL), generating the heterobimetallic trio FeVL (2), CoVL (3), and NiVL (4), respectively. In addition, the one-electron-oxidized analogues [FeVL]X ([2ox]X, where X– = BPh4 or PF6) and [CoVL]BPh4 ([3ox]BPh4) were prepared. The complexes were characterized by a host of physical methods, including cyclic voltammetry, X-ray crystallography, magnetic susceptibility, electronic absorption, NMR, electron paramagnetic resonance (EPR), and Mössbauer spectroscopies. The CoV and FeV heterobimetallic compounds have short M–V bond lengths that are consistent with M–M multiple bonding. As revealed by theoretical calculations, the M–V bond is triple in 2,more » 2ox, and 3ox, double in 3, and dative (Ni → V) in 4. The (d–d)10 species, 2 and 3ox, are diamagnetic and exhibit large diamagnetic anisotropies of -4700 × 10–36 m3/molecule. Complexes 2 and 3ox are also characterized by intense visible bands at 760 and 610 nm (ε > 1000 M–1 cm–1), respectively, which correspond to an intermetal (M → V) charge-transfer transition. Magnetic susceptibility measurements and EPR characterization establish S = 1/2 ground states for (d–d)9 2ox and (d–d)11 3, while (d–d)12 4 is S = 1 based on Evans’ method.« less

Risk factors for visible lesions or positive laboratory tests in bovine tuberculosis reactor cattle in Northern Ireland.

PubMed

O'Hagan, M J H; Courcier, E A; Drewe, J A; Gordon, A W; McNair, J; Abernethy, D A

2015-07-01

An observational case-control study was conducted to investigate risk factors for confirmed bovine tuberculosis (bTB) infection in cattle reacting positively to the single intradermal comparative cervical test (SICCT) in Northern Ireland in the years 1998, 2002 and 2006. Macroscopic lesions were detected at slaughter (positive visible lesion (VL) status) in 43.0% of reactor cattle, whilst 45.3% of those sampled were confirmed as bTB positive due to the presence of lesions or positive histopathology/mycobacterial culture (positive bTB status). In 97.5% of the reactors, the VL status and bTB status were either both negative or both positive. Generalized linear mixed model analyses were conducted on data of 24,923 reactor cattle with the variables herd identifier, local veterinary office (DVO) and abattoir being used as random effects within all the models generated at univariable and multivariable level. The other variables within the dataset were used as fixed effects. Significant risk factors associated with VL status and bTB status at multivariable level (p<0.05) included age at death, breed, sex, test year, net increase in skin thickness at bovine tuberculin injection site, epidemiological status of skin test, total number of reactors at the disclosure test, mean herd size and prior response to the skin test. These risk factors are likely related to the time since infection, the strength of the challenge of infection and the susceptibility of the animal. These findings are important as the detection of visible lesions and the confirmation of bTB are an integral part of the overall bTB control programme in Northern Ireland and the veterinary meat inspection and hygiene programme. The visible lesion status and bTB status of an animal can affect the way in which bTB breakdowns are managed, since failure to detect visible lesions and recovery of Mycobacterium bovis can lead to a less stringent follow-up after other risk factors have been taken into account. Copyright © 2015 Elsevier B.V. All rights reserved.

Service impact of a change in HIV-1 viral load quantification assay.

PubMed

Tipple, Craig; Oomeer, Soonita; Dosekun, Olamide; Mackie, Nicola

2014-01-01

Due to discontinuation of the Siemens Versant HIV-1 RNA (bDNA) assay in the UK, our laboratory switched to the Roche Cobas Ampliprep/Taqman HIV-1 viral load (VL) assay (Roche) in April 2013. This assay has a lower cut-off of 20 RNA copies/mL (compared with <50 for the Siemens assay). Our laboratory demonstrated previously that a significant proportion (18%) of patients undetectable using bDNA HIV-1 RNA quantification exhibited low level viraemia (LLV) using the new assay. Local guidelines recommend that patients stable on therapy receive twice-yearly VLs. We evaluated the impact of the introduction of the new assay on our clinical service. A retrospective cohort analysis of treated patients with stable undetectable VL by bDNA (<50 copies/mL) followed by ≥ one low-level (<400 copies/mL) VL with the Roche assay. Demographic data were collected in addition to frequency of VL testing and genotypic resistance assays. Referrals to virtual clinic (VC) were recorded. Patients were identified using laboratory data and information collected from electronic patient records. RESULTS were analyzed with SPSS v18. One hundred and ninety patients were included. 79.5% male; 60.6% homosexual; mean age of 46 years. Duration on stable treatment was 46.35 (std. dev. 38.15) months. Current treatment regimens were 43.3% PI-based; 43.3% NNRTI-based and 13.7% other. Patients were stratified into VL 20-49 copies/mL (n=109); VL 50-199 copies/mL (n=71) and VL 200-399 copies/mL (n=10). In total, there were 471 VLs measured of which 274 were additional as a result of the assay switch. This resulted in six HIV-1 genotype requests and 16 VC discussions (Table 1). Longer duration on HAART was associated with reduced frequency of VL testing. The relative risk of ongoing detectability according to drug class are: PI 1.62 (95% CI 1.18-2.21); NNRTI 0.507 (95% CI 0.30-0.85) and other 1.09 (95% CI 0.48-2.43). Changes in assay can result in difficulties in interpretation of patient results. The assay switch in our service had significant impact on patient and staff time and cost with an increase in patient recalls; increased frequency of VL measurement, genotypes and discussions in VC. Choice of assay is paramount to running an efficient and cost-effective clinical service.

Prediction of high-risk areas for visceral leishmaniasis using socioeconomic indicators and remote sensing data

PubMed Central

2014-01-01

Spatial heterogeneity in the incidence of visceral leishmaniasis (VL) is an important aspect to be considered in planning control actions for the disease. The objective of this study was to predict areas at high risk for visceral leishmaniasis (VL) based on socioeconomic indicators and remote sensing data. We applied classification and regression trees to develop and validate prediction models. Performance of the models was assessed by means of sensitivity, specificity and area under the ROC curve. The model developed was able to discriminate 15 subsets of census tracts (CT) with different probabilities of containing CT with high risk of VL occurrence. The model presented, respectively, in the validation and learning samples, sensitivity of 79% and 52%, specificity of 75% and 66%, and area under the ROC curve of 83% and 66%. Considering the complex network of factors involved in the occurrence of VL in urban areas, the results of this study showed that the development of a predictive model for VL might be feasible and useful for guiding interventions against the disease, but it is still a challenge as demonstrated by the unsatisfactory predictive performance of the model developed. PMID:24885128

Impact of rectal gonorrhoea and chlamydia on HIV viral load in the rectum: potential significance for onward transmission.

PubMed

Davies, Olubanke; Costelloe, Sinead; Cross, Gemma; Dew, Tracy; O'Shea, Siobhan; White, John; Fox, Julie

2017-09-01

The aim of this study was to investigate the effect of asymptomatic rectal bacterial sexually transmitted infections (STIs) on rectal HIV viral load (VL). A prospective cohort study of HIV-positive men who have sex with men attending a tertiary centre in London, UK, for their routine HIV care was performed. Forty-two HIV-positive men who have sex with men were recruited between January and August 2014. In participants on antiretroviral therapy (ART), there was no significant difference in rectal VL in those with and without STI ( p = 0.4). All rectal HIV VLs were below the limit of detection (<100 copies/µg of total RNA) whether an STI was present or not. In those not on ART, rectal HIV VL was on average 0.6log 10 lower post STI treatment. The presence of asymptomatic rectal chlamydia and gonorrhoea was not associated with increased rectal HIV VL in those fully suppressed on ART. In the context of effective ART, the presence of rectal gonorrhoea or chlamydia does not appear to increase rectal HIV VL and the risk of increased viral infectivity.

VL: a further case of erroneous recollection.

PubMed

Craik, Fergus I M; Barense, Morgan D; Rathbone, Clare J; Grusec, Joan E; Stuss, Donald T; Gao, Fuqiang; Scott, Christopher J M; Black, Sandra E

2014-04-01

We report a single-case study of a female patient (VL) who exhibited frequent episodes of erroneous recollections triggered by everyday events. Based on neuropsychological testing, VL was classified as suffering from mild to moderate dementia (MMSE=18) and was given a diagnosis of probable Alzheimer׳s disease. Her memory functions were uniformly impaired but her verbal abilities were generally well preserved. A structural MRI scan showed extensive areas of gray matter atrophy particularly in frontal and medial-temporal (MTL) areas. Results of experimental recognition tests showed that VL had very high false alarm rates on tests using pictures, faces and auditory stimuli, but lower false alarm rates on verbal tests. We provide a speculative account of her erroneous recollections in terms of her MTL and frontal pathology. In outline, we suggest that owing to binding failures in MTL regions, VL׳s recognition processes were forced to rely on earlier than normal stages of analysis. Environmental features on a given recognition trial may have combined with fragments persisting from previous trials resulting in erroneous feelings of familiarity and of recollection that were not discounted or edited out, due to her impaired frontal processes. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Application of loop-mediated isothermal amplification assay for the sensitive and rapid diagnosis of visceral leishmaniasis and post-kala-azar dermal leishmaniasis.

PubMed

Verma, Sandeep; Avishek, Kumar; Sharma, Vanila; Negi, Narendra Singh; Ramesh, Venkatesh; Salotra, Poonam

2013-04-01

Loop-mediated isothermal amplification (LAMP) is at the forefront in the search for innovative diagnostics for rapid and specific amplification of target DNA under isothermal conditions. We have applied LAMP assay using SYBR Green for clear-cut naked eye detection of Leishmania (Leishmania) donovani in 200 clinical samples of visceral leishmaniasis (VL) and post-kala-azar dermal leishmaniasis (PKDL). The assay was positive in 53/55 VL blood samples (sensitivity, 96.4%; 95% confidence interval [CI], 87.7-99%), 15/15 VL bone marrow aspirate samples (sensitivity, 100%; 95% CI, 79.6-100%), 60/62 PKDL tissue biopsy samples (sensitivity, 96.8%; 95% CI, 88.9-99.1%), and 1/68 control samples (specificity, 98.5%; 95% CI, 92.1-99.7%). The assay was specific for L. (L.) donovani, the causative species for VL and negative for L. (L.) infantum, L. (L.) tropica, and L. (L.) major. This is the first comprehensive clinical study demonstrating the applicability of the LAMP assay for a rapid and reliable molecular diagnosis of VL and PKDL. Copyright © 2013 Elsevier Inc. All rights reserved.

Effect of vildagliptin, a dipeptidyl peptidase 4 inhibitor, on cardiac hypertrophy induced by chronic beta-adrenergic stimulation in rats

PubMed Central

2014-01-01

Background Heart failure with left ventricular (LV) hypertrophy is often associated with insulin resistance and inflammation. Recent studies have shown that dipeptidyl peptidase 4 (DPP4) inhibitors improve glucose metabolism and inflammatory status. We therefore evaluated whether vildagliptin, a DPP4 inhibitor, prevents LV hypertrophy and improves diastolic function in isoproterenol-treated rats. Methods Male Wistar rats received vehicle (n = 20), subcutaneous isoproterenol (2.4 mg/kg/day, n = 20) (ISO), subcutaneous isoproterenol (2.4 mg/kg/day + oral vildagliptin (30 mg/kg/day, n = 20) (ISO-VL), or vehicle + oral vildagliptin (30 mg/kg/day, n = 20) (vehicle-VL) for 7 days. Results Blood pressure was similar among the four groups, whereas LV hypertrophy was significantly decreased in the ISO-VL group compared with the ISO group (heart weight/body weight, vehicle: 3.2 ± 0.40, ISO: 4.43 ± 0.39, ISO-VL: 4.14 ± 0.29, vehicle-VL: 3.16 ± 0.16, p < 0.05). Cardiac catheterization revealed that vildagliptin lowered the elevated LV end-diastolic pressure observed in the ISO group, but other parameters regarding LV diastolic function such as the decreased minimum dp/dt were not ameliorated in the ISO-VL group. Histological analysis showed that vildagliptin attenuated the increased cardiomyocyte hypertrophy and perivascular fibrosis, but it did not affect angiogenesis in cardiac tissue. In the ISO-VL group, quantitative PCR showed attenuation of increased mRNA expression of tumor necrosis factor-α, interleukin-6, insulin-like growth factor-l, and restoration of decreased mRNA expression of glucose transporter type 4. Conclusions Vildagliptin may prevent LV hypertrophy caused by continuous exposure to isoproterenol in rats. PMID:24521405

A new simplified volume-loaded heterotopic rabbit heart transplant model with improved techniques and a standard operating procedure.

PubMed

Lu, Wei; Zheng, Jun; Pan, Xu-Dong; Li, Bing; Zhang, Jin-Wei; Wang, Long-Fei; Sun, Li-Zhong

2015-04-01

The classic non-working (NW) heterotopic heart transplant (HTX) model in rodents had been widely used for researches related to immunology, graft rejection, evaluation of immunosuppressive therapies and organ preservation. But unloaded models are considered not suitable for some researches. Accordingly, We have constructed a volume-loaded (VL) model by a new and simple technique. Thirty male New Zealand White rabbits were randomly divided into two groups, group NW with 14 rabbits and group VL with 16 rabbits, which served as donors and recipients. We created a large and nonrestrictive shunt to provide left heart a sufficient preload. The donor superior vena cave and ascending aorta (AO) were anastomosed to the recipient abdominal aorta (AAO) and inferior vena cava (IVC), respectively. No animals suffered from paralysis, pneumonia and lethal bleeding. Recipients' mortality and morbidity were 6.7% (1/15) and 13.3% (2/15), respectively. The cold ischemia time in group VL is slight longer than that in group NW. The maximal aortic velocity (MAV) of donor heart was approximately equivalent to half that of native heart in group VL. Moreover, the similar result was achieved in the parameter of late diastolic mitral inflow velocity between donor heart and native heart in group VL. The echocardiography (ECHO) showed a bidirectional flow in donor SVC of VL model, inflow during diastole and outflow during systole. PET-CT imaging showed the standard uptake value (SUV) of allograft was equal to that of native heart in both groups on the postoperative day 3. We have developed a new VL model in rabbits, which imitates a native heart hemodynamically while only requiring a minor additional procedure. Surgical technique is simple compared with currently used HTX models. We also developed a standard operating procedure that significantly improved graft and recipient survival rate. This study may be useful for investigations in transplantation in which a working model is required.

Task-Dependent Intermuscular Motor Unit Synchronization between Medial and Lateral Vastii Muscles during Dynamic and Isometric Squats.

PubMed

Mohr, Maurice; Nann, Marius; von Tscharner, Vinzenz; Eskofier, Bjoern; Nigg, Benno Maurus

2015-01-01

Motor unit activity is coordinated between many synergistic muscle pairs but the functional role of this coordination for the motor output is unclear. The purpose of this study was to investigate the short-term modality of coordinated motor unit activity-the synchronized discharge of individual motor units across muscles within time intervals of 5ms-for the Vastus Medialis (VM) and Lateralis (VL). Furthermore, we studied the task-dependency of intermuscular motor unit synchronization between VM and VL during static and dynamic squatting tasks to provide insight into its functional role. Sixteen healthy male and female participants completed four tasks: Bipedal squats, single-leg squats, an isometric squat, and single-leg balance. Monopolar surface electromyography (EMG) was used to record motor unit activity of VM and VL. For each task, intermuscular motor unit synchronization was determined using a coherence analysis between the raw EMG signals of VM and VL and compared to a reference coherence calculated from two desynchronized EMG signals. The time shift between VM and VL EMG signals was estimated according to the slope of the coherence phase angle spectrum. For all tasks, except for singe-leg balance, coherence between 15-80Hz significantly exceeded the reference. The corresponding time shift between VM and VL was estimated as 4ms. Coherence between 30-60Hz was highest for the bipedal squat, followed by the single-leg squat and the isometric squat. There is substantial short-term motor unit synchronization between VM and VL. Intermuscular motor unit synchronization is enhanced for contractions during dynamic activities, possibly to facilitate a more accurate control of the joint torque, and reduced during single-leg tasks that require balance control and thus, a more independent muscle function. It is proposed that the central nervous system scales the degree of intermuscular motor unit synchronization according to the requirements of the movement task at hand.

Task-Dependent Intermuscular Motor Unit Synchronization between Medial and Lateral Vastii Muscles during Dynamic and Isometric Squats

PubMed Central

Mohr, Maurice; Nann, Marius; von Tscharner, Vinzenz; Eskofier, Bjoern; Nigg, Benno Maurus

2015-01-01

Purpose Motor unit activity is coordinated between many synergistic muscle pairs but the functional role of this coordination for the motor output is unclear. The purpose of this study was to investigate the short-term modality of coordinated motor unit activity–the synchronized discharge of individual motor units across muscles within time intervals of 5ms–for the Vastus Medialis (VM) and Lateralis (VL). Furthermore, we studied the task-dependency of intermuscular motor unit synchronization between VM and VL during static and dynamic squatting tasks to provide insight into its functional role. Methods Sixteen healthy male and female participants completed four tasks: Bipedal squats, single-leg squats, an isometric squat, and single-leg balance. Monopolar surface electromyography (EMG) was used to record motor unit activity of VM and VL. For each task, intermuscular motor unit synchronization was determined using a coherence analysis between the raw EMG signals of VM and VL and compared to a reference coherence calculated from two desynchronized EMG signals. The time shift between VM and VL EMG signals was estimated according to the slope of the coherence phase angle spectrum. Results For all tasks, except for singe-leg balance, coherence between 15–80Hz significantly exceeded the reference. The corresponding time shift between VM and VL was estimated as 4ms. Coherence between 30–60Hz was highest for the bipedal squat, followed by the single-leg squat and the isometric squat. Conclusion There is substantial short-term motor unit synchronization between VM and VL. Intermuscular motor unit synchronization is enhanced for contractions during dynamic activities, possibly to facilitate a more accurate control of the joint torque, and reduced during single-leg tasks that require balance control and thus, a more independent muscle function. It is proposed that the central nervous system scales the degree of intermuscular motor unit synchronization according to the requirements of the movement task at hand. PMID:26529604

Identification of immune biomarkers related to disease progression and treatment efficacy in human visceral leishmaniasis.

PubMed

Portela, Áquila S B; Costa, Lourena E; Salles, Beatriz C S; Lima, Mariana P; Santos, Thaís T O; Ramos, Fernanda F; Lage, Daniela P; Martins, Vívian T; Caligiorne, Rachel B; Lessa, Daniela R; Silva, Fabiana R; Machado, Amanda S; Nascimento, Guilherme F; Gama, Isabela S; Chávez-Fumagalli, Miguel A; Teixeira, Antonio L; Rocha, Manoel O C; Rocha, Regina L; Coelho, Eduardo A F

2018-03-01

Visceral leishmaniasis (VL) is a potentially fatal disease, in which the treatment based on chemotherapy is considered toxic. The cure of disease is associated with the life-long Th1-type immunity against the infection. The Th1-related cytokines production by peripheral blood mononuclear cells (PBMCs) seems to be crucial for host control of parasite load and clinical cure. In the current study, we used five proteins (IgE-dependent histamine-releasing factor [HRF], LiHyD, LiHyV, LiHyT and LiHyp6) recently shown to be antigenic and/or immunogenic in the canine VL, aiming to evaluate the antigen-specific antibody levels and cytokine production in PBMCs culture supernatants collected from VL patients before and after anti-VL treatment. In the results, when PBMCs were exposed to rHRF, rLiHyD and rLiHyT, higher IFN-γ and lower IL-10 levels were observed in all patients that were treated and clinically cured. Analysis of specific antibody subclasses was in line with in vitro cellular response, since a higher IgG2 production was found in the treated and cured patients, when compared to the IgG1 subclass levels. In addition, evaluating the diagnostic efficacy of the recombinant molecules, the rHRF, rLiHyD and rLiHyT proteins showed the best results in the serology assays to identify all VL patients, as well as these antigens were not recognized by antibodies in sera from non-infected subjects or those with leishmaniasis-related diseases. Our results corroborate the view that clinical cure of VL is associated with a sustained Th1-related response, and indicate the potential use of rHRF, rLiHyD and rLiHyT as immune biomarkers of VL treatment. Copyright © 2017 Elsevier GmbH. All rights reserved.

Association of chemokine receptor gene (CCR2-CCR5) haplotypes with acquisition and control of HIV-1 infection in Zambians

PubMed Central

2011-01-01

Background Polymorphisms in chemokine (C-C motif) receptors 2 and 5 genes (CCR2 and CCR5) have been associated with HIV-1 infection and disease progression. We investigated the impact of CCR2-CCR5 haplotypes on HIV-1 viral load (VL) and heterosexual transmission in an African cohort. Between 1995 and 2006, cohabiting Zambian couples discordant for HIV-1 (index seropositive and HIV-1 exposed seronegative {HESN}) were monitored prospectively to determine the role of host genetic factors in HIV-1 control and heterosexual transmission. Genotyping for eight CCR2 and CCR5 variants resolved nine previously recognized haplotypes. By regression and survival analytic techniques, controlling for non-genetic factors, we estimated the effects of these haplotypic variants on a) index partner VL, b) seroconverter VL, c) HIV-1 transmission by index partners, d) HIV-1 acquisition by HESN partners. Results Among 567 couples, 240 virologically linked transmission events had occurred through 2006. HHF*2 homozygosity was associated with significantly lower VL in seroconverters (mean beta = -0.58, log10 P = 0.027) and the HHD/HHE diplotype was associated with significantly higher VL in the seroconverters (mean beta = 0.54, log10 P = 0.014) adjusted for age and gender in multivariable model. HHD/HHE was associated with more rapid acquisition of infection by the HESNs (HR = 2.0, 95% CI = 1.20-3.43, P = 0.008), after adjustments for index partner VL and the presence of genital ulcer or inflammation in either partner in Cox multivariable models. The HHD/HHE effect was stronger in exposed females (HR = 2.1, 95% CI = 1.14-3.95, P = 0.018). Conclusions Among Zambian discordant couples, HIV-1 coreceptor gene haplotypes and diplotypes appear to modulate HIV-1 VL in seroconverters and alter the rate of HIV-1 acquisition by HESNs. These associations replicate or resemble findings reported in other African and European populations. PMID:21429204

Virological efficacy of abacavir: systematic review and meta-analysis.

PubMed

Cruciani, Mario; Mengoli, Carlo; Malena, Marina; Serpelloni, Giovanni; Parisi, Saverio G; Moyle, Graeme; Bosco, Oliviero

2014-12-01

The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness and safety of abacavir/lamivudine and tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have reviewed the available evidence. Systematic review and meta-analysis of RCTs using standard Cochrane Collaboration methodologies. We calculated risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks. Where available, results were analysed according to VL screening levels (<100,000 or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and meta-regression. Meta-analytical pooling of RCTs with a direct comparison of abacavir/lamivudine and tenofovir/emtricitabine according to baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions of subjects with VL <50 copies/mL were similar in the overall comparison (RR 0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99-1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta-regression analysis at 48 weeks confirms the results of subgroup analysis. Similar virological results were found at 96 weeks (four trials, 2003 patients). Differences in the occurrence of adverse events requiring discontinuation of treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this difference, mostly related to suspected abacavir hypersensitivity reaction, was not statistically significant. Our cumulative, cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Catalytic immunoglobulin gene delivery in a mouse model of Alzheimer's disease: prophylactic and therapeutic applications.

PubMed

Kou, Jinghong; Yang, Junling; Lim, Jeong-Eun; Pattanayak, Abhinandan; Song, Min; Planque, Stephanie; Paul, Sudhir; Fukuchi, Ken-Ichiro

2015-02-01

Accumulation of amyloid beta-peptide (Aβ) in the brain is hypothesized to be a causal event leading to dementia in Alzheimer's disease (AD). Aβ vaccination removes Aβ deposits from the brain. Aβ immunotherapy, however, may cause T cell- and/or Fc-receptor-mediated brain inflammation and relocate parenchymal Aβ deposits to blood vessels leading to cerebral hemorrhages. Because catalytic antibodies do not form stable immune complexes and Aβ fragments produced by catalytic antibodies are less likely to form aggregates, Aβ-specific catalytic antibodies may have safer therapeutic profiles than reversibly-binding anti-Aβ antibodies. Additionally, catalytic antibodies may remove Aβ more efficiently than binding antibodies because a single catalytic antibody can hydrolyze thousands of Aβ molecules. We previously isolated Aβ-specific catalytic antibody, IgVL5D3, with strong Aβ-hydrolyzing activity. Here, we evaluated the prophylactic and therapeutic efficacy of brain-targeted IgVL5D3 gene delivery via recombinant adeno-associated virus serotype 9 (rAAV9) in an AD mouse model. One single injection of rAAV9-IgVL5D3 into the right ventricle of AD model mice yielded widespread, high expression of IgVL5D3 in the unilateral hemisphere. IgVL5D3 expression was readily detectable in the contralateral hemisphere but to a much lesser extent. IgVL5D3 expression was also confirmed in the cerebrospinal fluid. Prophylactic and therapeutic injection of rAAV9-IgVL5D3 reduced Aβ load in the ipsilateral hippocampus of AD model mice. No evidence of hemorrhages, increased vascular amyloid deposits, increased proinflammatory cytokines, or infiltrating T-cells in the brains was found in the experimental animals. AAV9-mediated anti-Aβ catalytic antibody brain delivery can be prophylactic and therapeutic options for AD.

Durable Viral Suppression and Transmission Risk Potential Among Persons With Diagnosed HIV Infection: United States, 2012-2013.

PubMed

Crepaz, Nicole; Tang, Tian; Marks, Gary; Mugavero, Michael J; Espinoza, Lorena; Hall, H Irene

2016-10-01

We examined durable viral suppression, cumulative viral load (VL) burden, and transmission risk potential among human immunodeficiency virus (HIV)-diagnosed persons in care. Using data from the National HIV Surveillance System from 17 jurisdictions with complete reporting of VL test results, we determined the percentage of persons in HIV care who achieved durable viral suppression (all VL results <200 copies/mL) and examined viremia copy-years and time spent above VL levels that increase the risk of HIV transmission during 2012-2013. Of 265 264 persons in HIV care in 2011, 238 641 had at least 2 VLs in 2012-2013. The median number of VLs per individual during the 2-year period was 5. Approximately 62% had durable viral suppression. The remaining 38% had high VL burden (geometric mean of viremia copy-years, 7261) and spent an average of 438 days, 316 days, and 215 days (60%, 43.2%, and 29.5% of the 2-year period) above 200, 1500, and 10 000 copies/mL. Women, blacks/African Americans, Hispanics/Latinos, persons with HIV infection attributed to transmission other than male-to-male sexual contact, younger age groups, and persons with gaps in care had higher viral burden and transmission risk potential. Two-thirds of persons in HIV care had durable viral suppression during a 2-year period. One-third had high VL burden and spent substantial time above VL levels with increased risk of onward transmission. More intervention efforts are needed to improve retention in care and medication adherence so that more persons in HIV care achieve durable viral suppression. Published by Oxford University Press for the Infectious Diseases Society of America 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Trends in CD4 counts in HIV-infected patients with HIV viral load monitoring while on combination antiretroviral treatment: results from The TREAT Asia HIV Observational Database

PubMed Central

2010-01-01

Background The aim of this study was to examine the relationship between trends in CD4 counts (slope) and HIV viral load (VL) after initiation of combination antiretroviral treatment (cART) in Asian patients in The TREAT Asia HIV Observational Database (TAHOD). Methods Treatment-naive HIV-infected patients who started cART with three or more and had three or more CD4 count and HIV VL tests were included. CD4 count slopes were expressed as changes of cells per microliter per year. Predictors of CD4 count slopes from 6 months after initiation were assessed by random-effects linear regression models. Results A total of 1676 patients (74% male) were included. The median time on cART was 4.2 years (IQR 2.5-5.8 years). In the final model, CD4 count slope was associated with age, concurrent HIV VL and CD4 count, disease stage, hepatitis B or C co-infection, and time since cART initiation. CD4 count continues to increase with HIV VL up to 20 000 copies/mL during 6-12 months after cART initiation. However, the HIV VL has to be controlled below 5 000, 4 000 and 500 copies/mL for the CD4 count slope to remain above 20 cells/microliter per year during 12-18, 18-24, and beyond 24 months after cART initiation. Conclusions After cART initiation, CD4 counts continued to increase even when the concurrent HIV VL was detectable. However, HIV VL needed to be controlled at a lower level to maintain a positive CD4 count slope when cART continues. The effect on long-term outcomes through the possible development of HIV drug resistance remains uncertain. PMID:21182796

Measurement of recent exposure to Phlebotomus argentipes, the vector of Indian visceral Leishmaniasis, by using human antibody responses to sand fly saliva.

PubMed

Clements, Meredith F; Gidwani, Kamlesh; Kumar, Rajiv; Hostomska, Jitka; Dinesh, Diwakar S; Kumar, Vijay; Das, Pradeep; Müller, Ingrid; Hamilton, Gordon; Volfova, Vera; Boelaert, Marleen; Das, Murari; Rijal, Suman; Picado, Albert; Volf, Petr; Sundar, Shyam; Davies, Clive R; Rogers, Matthew E

2010-05-01

Antibody (IgG) responses to the saliva of Phlebotomus argentipes were investigated using serum samples from regions of India endemic and non-endemic for visceral leishmaniasis (VL). By pre-adsorbing the sera against the saliva of the competing human-biting but non-VL vector P. papatasi, we significantly improved the specificity of a P. argentipes saliva enzyme-linked immunosorbent assay. Using this method, we observed a statistically significant correlation between antibodies to P. argenitpes saliva and the average indoor density of female sand flies. Additionally, the method was able to detect recent changes in vector exposure when sera from VL patients were assayed before, during, and after hospitalization and protected from sand fly bites under untreated bed nets. Collectively, these results highlight the utility of antibodies to P. argentipes saliva as an important tool to evaluate VL vector control programs.

Factors Associated with HIV Viral Load in a Respondent Driven Sample in Los Angeles

PubMed Central

King, WD; Larkins, S; Hucks-Ortiz, C; Wang, J; Gorbach, P; Veniegas, R; Shoptaw, S

2008-01-01

This study used a modified version of the Behavioral Model for Vulnerable Populations to examine the predisposing, enabling, and need factors associated with detectable viral load (VL). HIV status was measured using saliva and confirmed by blood. Of 835 persons enrolled, 193 were HIV positive and provided VL counts. A multistage logistic regression demonstrated that the predisposing factors of homelessness and recent substance abuse, particularly methamphetamine abuse, had a negative association with VL. The negative association of homelessness was lessened with the introduction of enabling and need utilization factors in the model. In contrast, the negative association with recent substance abuse on VL was sustained in the final model. Provision of HIV care and medications attenuated the negative association of homelessness within this sample. Guided policy to address substance abuse among those who are HIV positive is needed to improve biological outcomes. PMID:18064555

[Object-oriented remote sensing image classification in epidemiological studies of visceral leishmaniasis in urban areas].

PubMed

Almeida, Andréa Sobral de; Werneck, Guilherme Loureiro; Resendes, Ana Paula da Costa

2014-08-01

This study explored the use of object-oriented classification of remote sensing imagery in epidemiological studies of visceral leishmaniasis (VL) in urban areas. To obtain temperature and environmental information, an object-oriented classification approach was applied to Landsat 5 TM scenes from the city of Teresina, Piauí State, Brazil. For 1993-1996, VL incidence rates correlated positively with census tracts covered by dense vegetation, grass/pasture, and bare soil and negatively with areas covered by water and densely populated areas. In 2001-2006, positive correlations were found with dense vegetation, grass/pasture, bare soil, and densely populated areas and negative correlations with occupied urban areas with some vegetation. Land surface temperature correlated negatively with VL incidence in both periods. Object-oriented classification can be useful to characterize landscape features associated with VL in urban areas and to help identify risk areas in order to prioritize interventions.

Immunotherapy and Immunochemotherapy in Visceral Leishmaniasis: Promising Treatments for this Neglected Disease

PubMed Central

Roatt, Bruno Mendes; Aguiar-Soares, Rodrigo Dian de Oliveira; Coura-Vital, Wendel; Ker, Henrique Gama; Moreira, Nádia das Dores; Vitoriano-Souza, Juliana; Giunchetti, Rodolfo Cordeiro; Carneiro, Cláudia Martins; Reis, Alexandre Barbosa

2014-01-01

Leishmaniasis has several clinical forms: self-healing or chronic cutaneous leishmaniasis or post-kala-azar dermal leishmaniasis; mucosal leishmaniasis; visceral leishmaniasis (VL), which is fatal if left untreated. The epidemiology and clinical features of VL vary greatly due to the interaction of multiple factors including parasite strains, vectors, host genetics, and the environment. Human immunodeficiency virus infection augments the severity of VL increasing the risk of developing active disease by 100–2320 times. An effective vaccine for humans is not yet available. Resistance to chemotherapy is a growing problem in many regions, and the costs associated with drug identification and development, make commercial production for leishmaniasis, unattractive. The toxicity of currently drugs, their long treatment course, and limited efficacy are significant concerns. For cutaneous disease, many studies have shown promising results with immunotherapy/immunochemotherapy, aimed to modulate and activate the immune response to obtain a therapeutic cure. Nowadays, the focus of many groups centers on treating canine VL by using vaccines and immunomodulators with or without chemotherapy. In human disease, the use of cytokines like interferon-γ associated with pentavalent antimonials demonstrated promising results in patients that did not respond to conventional treatment. In mice, immunomodulation based on monoclonal antibodies to remove endogenous immunosuppressive cytokines (interleukin-10) or block their receptors, antigen-pulsed syngeneic dendritic cells, or biological products like Pam3Cys (TLR ligand) has already been shown as a prospective treatment of the disease. This review addresses VL treatment, particularly immunotherapy and/or immunochemotherapy as an alternative to conventional drug treatment in experimental models, canine VL, and human disease. PMID:24982655

Evaluation of a new set of recombinant antigens for the serological diagnosis of human and canine visceral leishmaniasis

PubMed Central

Nascimento, Marilia B.; Santos, Wagner J. T.; Medeiros, Zulma M.; Lima Neto, Adelino S.; Costa, Dorcas L.; Costa, Carlos H. N.; dos Santos, Washington L. C.; Pontes de Carvalho, Lain C.; Oliveira, Geraldo G. S.

2017-01-01

Current strategies for the control of zoonotic visceral leishmaniasis (VL) rely on its efficient diagnosis in both human and canine hosts. The most promising and cost effective approach is based on serologic assays with recombinant proteins. However, no single antigen has been found so far which can be effectively used to detect the disease in both dogs and humans. In previous works, we identified Leishmania infantum antigens with potential for the serodiagnosis of VL. Here, we aimed to expand the panel of the available antigens for VL diagnosis through another screening of a genomic expression library. Seven different protein-coding gene fragments were identified, five of which encoding proteins which have not been previously studied in Leishmania and rich in repetitive motifs. Poly-histidine tagged polypeptides were generated from six genes and evaluated for their potential for diagnosis of VL by ELISA (Enzyme Linked ImmunoSorbent Assay) with sera from infected humans and dogs. None of those was valid for the detection of human VL (26–52% sensitivity) although their performance was increased in the canine sera (48–91% sensitivity), with one polypeptide useful for the diagnosis of canine leishmaniasis. Next, we assayed a mixture of three antigens, found to be best for human or canine VL, among 13 identified through different screenings. This “Mix” resulted in similar levels of sensitivity for both human (84%) and canine (88%) sera. With improvements, this validates the use of multiple proteins, including antigens identified here, as components of a single system for the diagnosis of both forms of leishmaniasis. PMID:28957332

Verticillium longisporum Infection Affects the Leaf Apoplastic Proteome, Metabolome, and Cell Wall Properties in Arabidopsis thaliana

PubMed Central

Floerl, Saskia; Majcherczyk, Andrzej; Possienke, Mareike; Feussner, Kirstin; Tappe, Hella; Gatz, Christiane; Feussner, Ivo; Kües, Ursula; Polle, Andrea

2012-01-01

Verticillium longisporum (VL) is one of the most devastating diseases in important oil crops from the family of Brassicaceae. The fungus resides for much time of its life cycle in the extracellular fluid of the vascular system, where it cannot be controlled by conventional fungicides. To obtain insights into the biology of VL-plant interaction in the apoplast, the secretome consisting of the extracellular proteome and metabolome as well as cell wall properties were studied in the model Brassicaceae, Arabidopsis thaliana. VL infection resulted in increased production of cell wall material with an altered composition of carbohydrate polymers and increased lignification. The abundance of several hundred soluble metabolites changed in the apoplast of VL-infected plants including signalling and defence compounds such as glycosides of salicylic acid, lignans and dihydroxybenzoic acid as well as oxylipins. The extracellular proteome of healthy leaves was enriched in antifungal proteins. VL caused specific increases in six apoplast proteins (three peroxidases PRX52, PRX34, P37, serine carboxypeptidase SCPL20, α-galactosidase AGAL2 and a germin-like protein GLP3), which have functions in defence and cell wall modification. The abundance of a lectin-like, chitin-inducible protein (CILLP) was reduced. Since the transcript levels of most of the induced proteins were not elevated until late infection time points (>20 dpi), whereas those of CILLP and GLP3 were reduced at earlier time points, our results may suggest that VL enhances its virulence by rapid down-regulation and delay of induction of plant defence genes. PMID:22363647

Evaluation of a new set of recombinant antigens for the serological diagnosis of human and canine visceral leishmaniasis.

PubMed

Magalhães, Franklin B; Castro Neto, Artur L; Nascimento, Marilia B; Santos, Wagner J T; Medeiros, Zulma M; Lima Neto, Adelino S; Costa, Dorcas L; Costa, Carlos H N; Dos Santos, Washington L C; Pontes de Carvalho, Lain C; Oliveira, Geraldo G S; de Melo Neto, Osvaldo P

2017-01-01

Current strategies for the control of zoonotic visceral leishmaniasis (VL) rely on its efficient diagnosis in both human and canine hosts. The most promising and cost effective approach is based on serologic assays with recombinant proteins. However, no single antigen has been found so far which can be effectively used to detect the disease in both dogs and humans. In previous works, we identified Leishmania infantum antigens with potential for the serodiagnosis of VL. Here, we aimed to expand the panel of the available antigens for VL diagnosis through another screening of a genomic expression library. Seven different protein-coding gene fragments were identified, five of which encoding proteins which have not been previously studied in Leishmania and rich in repetitive motifs. Poly-histidine tagged polypeptides were generated from six genes and evaluated for their potential for diagnosis of VL by ELISA (Enzyme Linked ImmunoSorbent Assay) with sera from infected humans and dogs. None of those was valid for the detection of human VL (26-52% sensitivity) although their performance was increased in the canine sera (48-91% sensitivity), with one polypeptide useful for the diagnosis of canine leishmaniasis. Next, we assayed a mixture of three antigens, found to be best for human or canine VL, among 13 identified through different screenings. This "Mix" resulted in similar levels of sensitivity for both human (84%) and canine (88%) sera. With improvements, this validates the use of multiple proteins, including antigens identified here, as components of a single system for the diagnosis of both forms of leishmaniasis.

Biochemical and nutritional evaluation of patients with visceral leishmaniasis before and after treatment with leishmanicidal drugs.

PubMed

Gatto, Mariana; de Abreu, Mariana Miziara; Tasca, Karen Ingrid; Simão, José Cláudio; Fortaleza, Carlos Magno Castelo Branco; Pereira, Paulo Câmara Marques; Calvi, Sueli Aparecida

2013-01-01

Visceral leishmaniasis (VL) is caused by the intracellular protozoan Leishmania donovani complex. VL may be asymptomatic or progressive and is characterized by fever, anemia, weight loss and the enlargement of the spleen and liver. The nutritional status of the patients with VL is a major determinant of the progression, severity and mortality of the disease, as it affects the clinical progression of the disease. Changes in lipoproteins and plasma proteins may have major impacts in the host during infection. Thus, our goal was evaluate the serum total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides, glucose, albumin, globulin and total protein levels, as well as the body composition, of VL patients before and after treatment. Nutritional evaluation was performed using the bioelectrical impedance analysis (BIA) to assess body composition. Biochemical data on the serum total cholesterol, HDL, LDL, triglycerides, glucose, albumin, globulin and total protein were collected from the medical charts of the patients. BIA indicated that both pre-treatment and post-treatment patients exhibited decreased phase angles compared to the controls, which is indicative of disease. Prior to treatment, the patients exhibited lower levels of total body water compared to the controls. Regarding the biochemical evaluation, patients with active VL exhibited lower levels of total cholesterol, HDL, LDL and albumin and higher triglyceride levels compared to patients after treatment and the controls. Treatment increased the levels of albumin and lipoproteins and decreased the triglyceride levels. Our results suggest that patients with active VL present biochemical and nutritional changes that are reversed by treatment.

The cost of vision loss in Canada. 1. Methodology.

PubMed

Gordon, Keith D; Cruess, Alan F; Bellan, Lorne; Mitchell, Scott; Pezzullo, M Lynne

2011-08-01

This paper outlines the methodology used to estimate the cost of vision loss in Canada. The results of this study will be presented in a second paper. The cost of vision loss (VL) in Canada was estimated using a prevalence-based approach. This was done by estimating the number of people with VL in a base period (2007) and the costs associated with treating them. The cost estimates included direct health system expenditures on eye conditions that cause VL, as well as other indirect financial costs such as productivity losses. Estimates were also made of the value of the loss of healthy life, measured in Disability Adjusted Life Years or DALY's. To estimate the number of cases of VL in the population, epidemiological data on prevalence rates were applied to population data. The number of cases of VL was stratified by gender, age, ethnicity, severity and cause. The following sources were used for estimating prevalence: Population-based eye studies; Canadian Surveys; Canadian journal articles and research studies; and International Population Based Eye Studies. Direct health costs were obtained primarily from Health Canada and Canadian Institute for Health Information (CIHI) sources, while costs associated with productivity losses were based on employment information compiled by Statistics Canada and on economic theory of productivity loss. Costs related to vision rehabilitation (VR) were obtained from Canadian VR organizations. This study shows that it is possible to estimate the costs for VL for a country in the absence of ongoing local epidemiological studies. Copyright © 2011 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved.

Field Evaluation of Dried Blood Spots for Routine HIV-1 Viral Load and Drug Resistance Monitoring in Patients Receiving Antiretroviral Therapy in Africa and Asia

PubMed Central

Monleau, Marjorie; Eymard-Duvernay, Sabrina; Dagnra, Anoumou; Kania, Dramane; Ngo-Giang-Huong, Nicole; Touré-Kane, Coumba; Truong, Lien X. T.; Chaix, Marie-Laure; Delaporte, Eric; Ayouba, Ahidjo; Peeters, Martine

2014-01-01

Dried blood spots (DBS) can be used in developing countries to alleviate the logistic constraints of using blood plasma specimens for viral load (VL) and HIV drug resistance (HIVDR) testing, but they should be assessed under field conditions. Between 2009 and 2011, we collected paired plasma-DBS samples from treatment-experienced HIV-1-infected adults in Burkina Faso, Cameroon, Senegal, Togo, Thailand, and Vietnam. The DBS were stored at an ambient temperature for 2 to 4 weeks and subsequently at −20°C before testing. VL testing was performed on the plasma samples and DBS using locally available methods: the Abbott m2000rt HIV-1 test, generic G2 real-time PCR, or the NucliSENS EasyQ version 1.2 test. In the case of virological failure (VF), i.e., a plasma VL of ≥1,000 copies/ml, HIVDR genotyping was performed on paired plasma-DBS samples. Overall, we compared 382 plasma-DBS sample pairs for DBS VL testing accuracy. The sensitivities of the different assays in different laboratories for detecting VF using DBS varied from 75% to 100% for the m2000rt test in labs B, C, and D, 91% to 93% for generic G2 real-time PCR in labs A and F, and 85% for the NucliSENS test in lab E. The specificities varied from 82% to 97% for the m2000rt and NucliSENS tests and reached only 60% for the generic G2 test. The NucliSENS test showed good agreement between plasma and DBS VL but underestimated the DBS VL. The lowest agreement was observed for the generic G2 test. Genotyping was successful for 96/124 (77%) DBS tested, and 75/96 (78%) plasma-DBS pairs had identical HIVDR mutations. Significant discrepancies in resistance interpretations were observed in 9 cases, 6 of which were from the same laboratory. DBS can be successfully used as an alternative to blood plasma samples for routine VL and HIVDR monitoring in African and Asian settings. However, the selection of an adequate VL measurement method and the definition of the VF threshold should be considered, and laboratory performance should be monitored. PMID:24478491

Detectable Viral Load in Late Pregnancy among Women in the Rwanda Option B+ PMTCT Program: Enrollment Results from the Kabeho Study

PubMed Central

Gill, Michelle M.; Hoffman, Heather J.; Bobrow, Emily A.; Mugwaneza, Placidie; Ndatimana, Dieudonne; Ndayisaba, Gilles F.; Baribwira, Cyprien; Guay, Laura; Asiimwe, Anita

2016-01-01

There are limited viral load (VL) data available from programs implementing “Option B+,” lifelong antiretroviral treatment (ART) to all HIV-positive pregnant and postpartum women, in resource-limited settings. Extent of viral suppression from a prevention of mother-to-child transmission of HIV program in Rwanda was assessed among women enrolled in the Kigali Antiretroviral and Breastfeeding Assessment for the Elimination of HIV (Kabeho) Study. ARV drug resistance testing was conducted on women with VL>2000 copies/ml. In April 2013-January 2014, 608 pregnant or early postpartum HIV-positive women were enrolled in 14 facilities. Factors associated with detectable enrollment VL (>20 copies/ml) were examined using generalized estimating equations. The most common antiretroviral regimen (56.7%, 344/607) was tenofovir/lamivudine/efavirenz. Median ART duration was 13.5 months (IQR 3.0–48.8); 76.1% of women were on ART at first antenatal visit. Half of women (315/603) had undetectable RNA-PCR VL and 84.6% (510) had <1,000 copies/ml. Detectable VL increased among those on ART > 36 months compared to those on ART 4–36 months (72/191, 37.7% versus 56/187, 29.9%), though the difference was not significant. The odds of having detectable enrollment VL decreased significantly as duration on ART at enrollment increased (AOR = 0.99, 95% CI: 0.9857, 0.9998, p = 0.043). There was a higher likelihood of detectable VL for women with lower gravidity (AOR = 0.90, 95% CI: 0.84, 0.97, p = 0.0039), no education (AOR = 2.25, (95% CI: 1.37, 3.70, p = 0.0004), nondisclosure to partner (AOR = 1.97, 95% CI: 1.21, 3.21, p = 0.0063) and side effects (AOR = 2.63, 95% CI: 1.72, 4.03, p<0.0001). ARV drug resistance mutations were detected in all of the eleven women on ART > 36 months with genotyping available. Most women were receiving ART at first antenatal visit, with relatively high viral suppression rates. Shorter ART duration was associated with higher VL, with a concerning increasing trend for higher viremia and drug resistance among women on ART for >3 years. PMID:28006001

Climatic factors and population density of Lutzomyia longipalpis (Lutz & Neiva, 1912) in an urban endemic area of visceral leishmaniasis in midwest Brazil.

PubMed

de Oliveira, Everton Falcão; dos Santos Fernandes, Carlos Eurico; Araújo e Silva, Elaine; Brazil, Reginaldo Peçanha; de Oliveira, Alessandra Gutierrez

2013-12-01

The life cycle of vectors and the reservoirs that participate in the chain of infectious diseases have a strong relationship with the environmental dynamics of the ecosystems in which they live. Oscillations in population abundance and seasonality of insects can be explained by factors inherent in each region and time period. Therefore, knowledge of the relationship and influence of environmental factors on the population of Lutzomyia longipalpis is necessary because of the high incidence of visceral leishmaniasis (VL) in Brazil. This study evaluates the influence of abiotic variables on the population density and seasonal behavior of L. longipalpis in an urban endemic area of VL in Brazil. The sand fly captures were performed every two months between November, 2009 and November, 2010 in the peridomicile of 13 randomly selected residences. We captured 1,367 specimens of L. longipalpis, and the ratio of male/female flies was 2.86:1. The comparison of the total male specimens in the two seasons showed a statistical difference in the wet season, but there was no significant difference when considering the total females. With respect to climatic variables, a significant negative association was observed only with wind speed. During periods of high wind speeds, the population density of this vector decreased. The presence of L. longipalpis was found in all months of the study with bimodal behavior and population peaks during the wet season. © 2013 The Society for Vector Ecology.

[Current and future ecological niche of Leishmaniasis (Kinetoplastida: Trypanosomatidae) in the Neotropical region].

PubMed

Moo-Llanes, David A

2016-09-01

The leishmaniasis is a complex disease system, caused by the protozoan parasite Leishmania and transmitted to humans by the vector Lutzomyia spp. Since it is listed as a neglected disease according to the World Health Organization, the aim of this study was to determine the current and future niche of cutaneous and visceral leishmaniasis in the Neotropical region. We built the ecological niche model (ENM) of cutaneous (N= 2 910 occurrences) and visceral (N= 851 occurrences) leishmaniasis using MaxEnt algorithm. Nine bioclimatic variables (BIO1, BIO4, BIO5, BIO6, BIO7, BIO12, BIO13, BIO14, BIO15 (downloaded from the Worldclim) and disease occurrences data were used for the construction of ENM for three periods (current, 2050 and 2070) and four climate change scenarios (RCP 2.6, 4.5, 6.0 y 8.5). We analyzed the number of pixels occupied, identity niche, modified niche (stable, loss, and gain) and seasonality. Our analyses indicated the expansion for cutaneous leishmaniasis (CL), a comparison for visceral leishmaniasis (VL). We rejected the null hypothesis of niche identity between CL and VL with Hellinger’s index = 0.91 (0.92-0.98) and Schoener’s Index = 0.67 (0.85-1.00) but with an overlap niche of 56.3 %. The differences between the two leishmaniasis types were detected in relation to RCP scenarios and niche shifts (area gained / loss). Seasonality was more important for CL. We provided a current picture of CL and VL distributions and the predicted distributional changes associated to different climate change scenarios for the Neotropical region. We can anticipate that increasing range is likely although it will depend locally on the future trends in weather seasonality.

Surface-EMG analysis for the quantification of thigh muscle dynamic co-contractions during normal gait.

PubMed

Strazza, Annachiara; Mengarelli, Alessandro; Fioretti, Sandro; Burattini, Laura; Agostini, Valentina; Knaflitz, Marco; Di Nardo, Francesco

2017-01-01

The research purpose was to quantify the co-contraction patterns of quadriceps femoris (QF) vs. hamstring muscles during free walking, in terms of onset-offset muscular activation, excitation intensity, and occurrence frequency. Statistical gait analysis was performed on surface-EMG signals from vastus lateralis (VL), rectus femoris (RF), and medial hamstrings (MH), in 16315 strides walked by 30 healthy young adults. Results showed full superimpositions of MH with both VL and RF activity from terminal swing, 80 to 100% of gait cycle (GC), to the successive loading response (≈0-15% of GC), in around 90% of the considered strides. A further superimposition was detected during the push-off phase both between VL and MH activation intervals (38.6±12.8% to 44.1±9.6% of GC) in 21.9±13.6% of strides, and between RF and MH activation intervals (45.9±5.3% to 50.7±9.7 of GC) in 32.7±15.1% of strides. These findings led to identify three different co-contractions among QF and hamstring muscles during able-bodied walking: in early stance (in ≈90% of strides), in push-off (in 25-30% of strides) and in terminal swing (in ≈90% of strides). The co-contraction in terminal swing is the one with the highest levels of muscle excitation intensity. To our knowledge, this analysis represents the first attempt for quantification of QF/hamstring muscles co-contraction in young healthy subjects during normal gait, able to include the physiological variability of the phenomenon. Copyright © 2016 Elsevier B.V. All rights reserved.

A Methodological Approach to Quantifying Plyometric Intensity.

PubMed

Jarvis, Mark M; Graham-Smith, Phil; Comfort, Paul

2016-09-01

Jarvis, MM, Graham-Smith, P, and Comfort, P. A Methodological approach to quantifying plyometric intensity. J Strength Cond Res 30(9): 2522-2532, 2016-In contrast to other methods of training, the quantification of plyometric exercise intensity is poorly defined. The purpose of this study was to evaluate the suitability of a range of neuromuscular and mechanical variables to describe the intensity of plyometric exercises. Seven male recreationally active subjects performed a series of 7 plyometric exercises. Neuromuscular activity was measured using surface electromyography (SEMG) at vastus lateralis (VL) and biceps femoris (BF). Surface electromyography data were divided into concentric (CON) and eccentric (ECC) phases of movement. Mechanical output was measured by ground reaction forces and processed to provide peak impact ground reaction force (PF), peak eccentric power (PEP), and impulse (IMP). Statistical analysis was conducted to assess the reliability intraclass correlation coefficient and sensitivity smallest detectable difference of all variables. Mean values of SEMG demonstrate high reliability (r ≥ 0.82), excluding ECC VL during a 40-cm drop jump (r = 0.74). PF, PEP, and IMP demonstrated high reliability (r ≥ 0.85). Statistical power for force variables was excellent (power = 1.0), and good for SEMG (power ≥0.86) excluding CON BF (power = 0.57). There was no significant difference (p > 0.05) in CON SEMG between exercises. Eccentric phase SEMG only distinguished between exercises involving a landing and those that did not (percentage of maximal voluntary isometric contraction [%MVIC] = no landing -65 ± 5, landing -140 ± 8). Peak eccentric power, PF, and IMP all distinguished between exercises. In conclusion, CON neuromuscular activity does not appear to vary when intent is maximal, whereas ECC activity is dependent on the presence of a landing. Force characteristics provide a reliable and sensitive measure enabling precise description of intensity in plyometric exercises. The present findings provide coaches and scientists with an insightful and precise method of measuring intensity in plyometrics, which will allow for greater control of programming variables.

The poorest of the poor: a poverty appraisal of households affected by visceral leishmaniasis in Bihar, India.

PubMed

Boelaert, M; Meheus, F; Sanchez, A; Singh, S P; Vanlerberghe, V; Picado, A; Meessen, B; Sundar, S

2009-06-01

To provide data about wealth distribution in visceral leishmaniasis (VL)-affected communities compared to that of the general population of Bihar State, India. After extensive disease risk mapping, 16 clusters with high VL transmission were selected in Bihar. An exhaustive census of all households in the clusters was conducted and socio-economic household characteristics were documented by questionnaire. Data on the general Bihar population taken from the National Family Health Survey of India were used for comparison. An asset index was developed based on Principal Components Analysis and the distribution of this asset index for the VL communities was compared with that of the general population of Bihar. 83% of households in communities with high VL attack rates belonged to the two lowest quintiles of the Bihar wealth distribution. All socio-economic indicators showed significantly lower wealth for those households. Visceral leishmaniasis clearly affects the poorest of the poor in India. They are most vulnerable, as this vector-born disease is linked to poor housing and unhealthy habitats. The disease leads the affected households to more destitution because of its impact on household income and wealth. Support for the present VL elimination initiative is important in the fight against poverty.

Rapid Tests and the Diagnosis of Visceral Leishmaniasis and Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Coinfection.

PubMed

Barbosa Júnior, Walter Lins; Ramos de Araújo, Paulo Sérgio; Dias de Andrade, Luiz; Aguiar Dos Santos, Ana Maria; Lopes da Silva, Maria Almerice; Dantas-Torres, Filipe; Medeiros, Zulma

2015-11-01

After the emergence of the human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), the number of visceral leishmaniasis (VL)-HIV/AIDS coinfections has increased worldwide. Herein, we assessed the usefulness of an rK39-based immunochromatographic test (rK39 ICT) (DiaMed-IT LEISH(®); DiaMed AG, Cressier-sur-Morat, Switzerland) and a latex agglutination test (KAtex; Kalon Biological, Guildford, United Kingdom) for urinary antigen detection to diagnose VL in 15 HIV/AIDS patients from northeastern Brazil. VL diagnosis was based on clinical findings, cytology, serology, parasite DNA, and/or urinary antigen detection. VL was confirmed in seven out of 15 HIV/AIDS patients. Only three patients were positive in bone marrow cytology, three patients were conventional polymerase chain reaction (PCR) positive, while six were real-time PCR positive. All patients were direct agglutination test (DAT) (Royal Tropical Institute, Amsterdam, The Netherlands) positive; of these, four were positive by rK39 ICT and five by KAtex. Large-scale studies are needed to validate the use of the KAtex in the national public health laboratory network in Brazil, aiming at improving the diagnosis of VL in HIV/AIDS patients in this country. © The American Society of Tropical Medicine and Hygiene.

Short communication: human immunodeficiency virus rebound in blood and seminal plasma following discontinuation of antiretroviral therapy.

PubMed

Costiniuk, Cecilia T; Kovacs, Colin; Routy, Jean-Pierre; Singer, Joel; Gurunathan, Sanjay; Sekaly, Rafick-Pierre; Angel, Jonathan B

2013-02-01

Although there is discordance between human immunodeficiency virus (HIV) blood plasma and seminal plasma viral loads (VL), little is known about the dynamics of VL rebound in these compartments upon discontinuation of highly active antiretroviral therapy (HAART). Therefore, we sought to examine the relationship between blood and semen VL rebound after discontinuation of HAART. Participants in this substudy were men enrolled from two centers of a multicenter, placebo-controlled randomized trial of HIV therapeutic vaccination using ALVAC with or without Remune. With at least 2 years of sustained virologic suppression and following a 20-week vaccination course, subjects underwent structured HAART interruption. Fourteen men provided semen samples. Seven to 12 weeks after HAART interruption, all 14 men had detectable blood VLs whereas 8 of 14 had detectable seminal VLs. There was a significant correlation between blood and seminal VLs (Spearman r=0.58, p=0.03) at the time of semen collection. An earlier time to detectable blood VL after HAART interruption was associated with higher seminal VL (Spearman r=-0.64, p=0.02). These findings support the compartmentalization of HIV and underscore the importance of understanding the genital tract as an HIV reservoir in the quest to minimize HIV transmission.

Climate change adaptation frameworks: an evaluation of plans for coastal Suffolk, UK

NASA Astrophysics Data System (ADS)

Armstrong, J.; Wilby, R.; Nicholls, R. J.

2015-11-01

This paper asserts that three principal frameworks for climate change adaptation can be recognised in the literature: scenario-led (SL), vulnerability-led (VL) and decision-centric (DC) frameworks. A criterion is developed to differentiate these frameworks in recent adaptation projects. The criterion features six key hallmarks as follows: (1) use of climate model information; (2) analysis of metrics/units; (3) socio-economic knowledge; (4) stakeholder engagement; (5) adaptation of implementation mechanisms; (6) tier of adaptation implementation. The paper then tests the validity of this approach using adaptation projects on the Suffolk coast, UK. Fourteen adaptation plans were identified in an online survey. They were analysed in relation to the hallmarks outlined above and assigned to an adaptation framework. The results show that while some adaptation plans are primarily SL, VL or DC, the majority are hybrid, showing a mixture of DC/VL and DC/SL characteristics. Interestingly, the SL/VL combination is not observed, perhaps because the DC framework is intermediate and attempts to overcome weaknesses of both SL and VL approaches. The majority (57 %) of adaptation projects generated a risk assessment or advice notes. Further development of this type of framework analysis would allow better guidance on approaches for organisations when implementing climate change adaptation initiatives, and other similar proactive long-term planning.

Climate change adaptation frameworks: an evaluation of plans for coastal, Suffolk, UK

NASA Astrophysics Data System (ADS)

Armstrong, J.; Wilby, R.; Nicholls, R. J.

2015-06-01

This paper asserts that three principal frameworks for climate change adaptation can be recognised in the literature: Scenario-Led (SL), Vulnerability-Led (VL) and Decision-Centric (DC) frameworks. A criterion is developed to differentiate these frameworks in recent adaptation projects. The criterion features six key hallmarks as follows: (1) use of climate model information; (2) analysis metrics/units; (3) socio-economic knowledge; (4) stakeholder engagement; (5) adaptation implementation mechanisms; (6) tier of adaptation implementation. The paper then tests the validity of this approach using adaptation projects on the Suffolk coast, UK. Fourteen adaptation plans were identified in an online survey. They were analysed in relation to the hallmarks outlined above and assigned to an adaptation framework. The results show that while some adaptation plans are primarily SL, VL or DC, the majority are hybrid showing a mixture of DC/VL and DC/SL characteristics. Interestingly, the SL/VL combination is not observed, perhaps because the DC framework is intermediate and attempts to overcome weaknesses of both SL and VL approaches. The majority (57 %) of adaptation projects generated a risk assessment or advice notes. Further development of this type of framework analysis would allow better guidance on approaches for organisations when implementing climate change adaptation initiatives, and other similar proactive long-term planning.

Noradrenaline Triggers GABAA Inhibition of Bed Nucleus of the Stria Terminalis Neurons Projecting to the Ventral Tegmental Area

PubMed Central

Dumont, Éric C.; Williams, John T.

2014-01-01

The lateral part of the ventral bed nucleus of the stria terminalis (vlBNST) is a critical site for the antiaversive effects of noradrenergic drugs during opioid withdrawal. The objective of the present study is to identify the cellular action(s) of noradrenaline in the vlBNST after withdrawal from a 5 d treatment with morphine. The vlBNST is a heterogeneous cell group with multiple efferent projections. Therefore, neurons projecting to the midbrain were identified by retrograde transport of fluorescent microspheres injected in the ventral tegmental area (VTA). Whole-cell voltage clamp recordings of these neurons and of those sharing physiological properties were done in brain slices. Noradrenaline activated α1-adrenergic receptors to increase GABAA-IPSC frequency. Noradrenaline produced a similar increase in GABAA-IPSCs during acute opioid withdrawal, but this increase resulted from activation of β-adrenergic receptors, adenylyl cyclase, and protein kinase A, as well as α1-adrenergic receptors. Given that neurons in the vlBNST send an excitatory projection to the VTA, noradrenaline may reduce excitatory drive to mesolimbic dopamine cells. This mechanism might contribute to the withdrawal-induced inhibition of dopamine neurons and explain how noradrenergic drugs microinjected into the vlBNST reduce aversive aspects of opioid withdrawal. PMID:15385602

Are the Viking Lander sites representative of the surface of Mars?

NASA Technical Reports Server (NTRS)

Jakosky, B. M.; Christensen, P. R.

1986-01-01

Global remote sensing data of the Martian surface, collected by earth- and satellite-based instruments, are compared with data from the two Viking Landers to determine if the Lander data are representative of the Martian surface. The landing sites are boulder-strewn and feature abundant fine material and evidence of strong eolian forces. One site (VL-1) is in a plains-covered basin which is associated with volcanic activity; the VL-2 site is in the northern plains. Thermal IR, broadband albedo, color imaging and radar remote sensing has been carried out of the global Martian surface. The VL-1 data do not fit a general correlation observed between increases in 70-cm radar cross-sections and thermal inertia. A better fit is found with 12.5-cm cross sections, implying the presence of a thinner or discontinuous duricrust at the VL-1 site, compared to other higher-inertia regions. A thin dust layer is also present at the VL-2 site, based on the Lander reflectance data. The Lander sites are concluded to be among the three observed regions of anomalous reflectivity, which can be expected in low regions selected for the landings. Recommendations are furnished for landing sites of future surface probes in order to choose sites more typical of the global Martian surface.

Leishmaniasis acquired by travellers to endemic regions in Europe: a EuroTravNet multi-centre study.

PubMed

Ehehalt, Urs; Schunk, Mirjam; Jensenius, Mogens; van Genderen, Perry J J; Gkrania-Klotsas, Effrossyni; Chappuis, François; Schlagenhauf, Patricia; Castelli, Francesco; Lopez-Velez, Rogelio; Parola, Philippe; Burchard, Gerd D; Cramer, Jakob P

2014-01-01

Leishmaniasis is a disease caused by protozoan parasites of the genus Leishmania. Clinical manifestations of leishmaniasis include cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). About 90% of cases occur in the tropics or subtropics but the disease is also endemic in the Mediterranean area. No systematic analysis on leishmaniasis in travellers visiting endemic areas in Europe is available. Within the European travel medicine network EuroTravNet, we performed a retrospective analysis in travellers who acquired leishmaniasis within Europe diagnosed between 2000 and 2012. Forty cases of leishmaniasis (30 CL and 10 VL) were identified; the majority were acquired in Spain (n = 20, 50%), Malta and Italy (each n = 7, 18%). Median age was 48 years (range 1-79). Three of eight (37.5%) of the VL patients were on immunosuppressive therapy. The most frequent reason for travel was tourism (83%). Median duration of travel for patients with CL and VL was 2 weeks with ranges of 1-21 weeks in CL and 1-67 weeks in VL, respectively (P = 0.03). Health professionals should include leishmaniasis in the differential diagnosis in patients returning from southern Europe - including short-term travellers - with typical skin lesions or systemic alterations like fever, hepatosplenomegaly and pancytopenia. Copyright © 2013 Elsevier Ltd. All rights reserved.

Multidisease testing for HIV and TB using the GeneXpert platform: A feasibility study in rural Zimbabwe

PubMed Central

Fajardo, Emmanuel; Mbofana, Elton; Maparo, Tatenda; Garone, Daniela; Metcalf, Carol; Bygrave, Helen; Kao, Kekeletso; Zinyowera, Sekesai

2018-01-01

Background HIV Viral Load and Early Infant Diagnosis technologies in many high burden settings are restricted to centralized laboratory testing, leading to long result turnaround times and patient attrition. GeneXpert (Cepheid, CA, USA) is a polyvalent near point-of-care platform and is widely implemented for Xpert MTB/RIF diagnosis. This study sought to evaluate the operational feasibility of integrated HIV VL, EID and MTB/RIF testing in new GeneXpert platforms. Methods Whole blood samples were collected from consenting patients due for routine HIV VL testing and DBS samples from infants due for EID testing, at three rural health facilities in Zimbabwe. Sputum samples were collected from all individuals suspected of TB. GeneXpert testing was reserved for all EID, all TB suspects and priority HIV VL at each site. Blood samples were further sent to centralized laboratories for confirmatory testing. GeneXpert polyvalent testing results and patient outcomes, including infrastructural and logistical requirements are reported. The study was conducted over a 10-month period. Results The fully automated GeneXpert testing device, required minimal training and biosafety considerations. A total of 1,302 HIV VL, 277 EID and 1,581 MTB/RIF samples were tested on a four module GeneXpert platform in each study site. Xpert HIV-1 VL testing was prioritized for patients who presented with advanced HIV disease, pregnant women, adolescents and suspected ART failures patients. On average, the study sites had a GeneXpert utilization rate of 50.4% (Gutu Mission Hospital), 63.5% (Murambinda Mission Hospital) and 17.5% (Chimombe Rural Health Centre) per month. GeneXpert polyvalent testing error rates remained lower than 4% in all sites. Decentralized EID and VL testing on Xpert had shorter overall median TAT (1 day [IQR: 0–4] and 1 day [IQR: 0–1] respectively) compared to centralized testing (17 days [IQR: 13–21] and 26 days [IQR: 23–32] respectively). Among patients with VL >1000 copies/ml (73/640; 11.4%) at GMH health facility, median time to enhanced adherence counselling was 8 days and majority of those with documented outcomes had re-suppressed VL (20/32; 62.5%). Median time to ART initiation among Xpert EID positive infants at GMH was 1 day [IQR: 0–1]. Conclusion Implementation of near point-of-care GeneXpert platform for integrated multi-disease testing within district and sub-district healthcare settings is feasible and will increase access to VL, and EID testing to priority populations. Quality management systems including monitoring of performance indicators, together with regular on-site supervision are crucial, and near-POC test results must be promptly actioned-on by clinicians for patient management. PMID:29499042

Multidisease testing for HIV and TB using the GeneXpert platform: A feasibility study in rural Zimbabwe.

PubMed

Ndlovu, Zibusiso; Fajardo, Emmanuel; Mbofana, Elton; Maparo, Tatenda; Garone, Daniela; Metcalf, Carol; Bygrave, Helen; Kao, Kekeletso; Zinyowera, Sekesai

2018-01-01

HIV Viral Load and Early Infant Diagnosis technologies in many high burden settings are restricted to centralized laboratory testing, leading to long result turnaround times and patient attrition. GeneXpert (Cepheid, CA, USA) is a polyvalent near point-of-care platform and is widely implemented for Xpert MTB/RIF diagnosis. This study sought to evaluate the operational feasibility of integrated HIV VL, EID and MTB/RIF testing in new GeneXpert platforms. Whole blood samples were collected from consenting patients due for routine HIV VL testing and DBS samples from infants due for EID testing, at three rural health facilities in Zimbabwe. Sputum samples were collected from all individuals suspected of TB. GeneXpert testing was reserved for all EID, all TB suspects and priority HIV VL at each site. Blood samples were further sent to centralized laboratories for confirmatory testing. GeneXpert polyvalent testing results and patient outcomes, including infrastructural and logistical requirements are reported. The study was conducted over a 10-month period. The fully automated GeneXpert testing device, required minimal training and biosafety considerations. A total of 1,302 HIV VL, 277 EID and 1,581 MTB/RIF samples were tested on a four module GeneXpert platform in each study site. Xpert HIV-1 VL testing was prioritized for patients who presented with advanced HIV disease, pregnant women, adolescents and suspected ART failures patients. On average, the study sites had a GeneXpert utilization rate of 50.4% (Gutu Mission Hospital), 63.5% (Murambinda Mission Hospital) and 17.5% (Chimombe Rural Health Centre) per month. GeneXpert polyvalent testing error rates remained lower than 4% in all sites. Decentralized EID and VL testing on Xpert had shorter overall median TAT (1 day [IQR: 0-4] and 1 day [IQR: 0-1] respectively) compared to centralized testing (17 days [IQR: 13-21] and 26 days [IQR: 23-32] respectively). Among patients with VL >1000 copies/ml (73/640; 11.4%) at GMH health facility, median time to enhanced adherence counselling was 8 days and majority of those with documented outcomes had re-suppressed VL (20/32; 62.5%). Median time to ART initiation among Xpert EID positive infants at GMH was 1 day [IQR: 0-1]. Implementation of near point-of-care GeneXpert platform for integrated multi-disease testing within district and sub-district healthcare settings is feasible and will increase access to VL, and EID testing to priority populations. Quality management systems including monitoring of performance indicators, together with regular on-site supervision are crucial, and near-POC test results must be promptly actioned-on by clinicians for patient management.

Aptima HIV-1 Quant Dx--A fully automated assay for both diagnosis and quantification of HIV-1.

PubMed

Nair, Sangeetha Vijaysri; Kim, Hee Cheol; Fortunko, Jacqueline; Foote, Tracy; Peling, Tashi; Tran, Cuong; Nugent, Charles Thomas; Joo, Sunghae; Kang, Youna; Wilkins, Bana; Lednovich, Kristen; Worlock, Andrew

2016-04-01

Separate assays are available for diagnosis and viral load (VL) monitoring of HIV-1. Studies have shown that using a single test for both confirmatory diagnosis and VL increases linkage to care. To validate a single assay for both diagnosis and VL monitoring of HIV-1 on the fully automated Panther platform. Validate the assay by assessing specificity, sensitivity, subtype detection, seroconversion, reproducibility and linearity. Also assess diagnostic agreement with the Procleix(®) Ultrio Elite™ discriminatory assay (Procleix), and agreement of VL results (method comparison) with Ampliprep/COBAS TaqMan HIV-1 version 2.0 (CAP/CTM), using clinical samples. The assay was specific (100%) and sensitive with a 95% limit of detection of 12 copies/mL with the 3rd WHO standards. Aptima detected HIV in seroconversion panels 6 and 11 days before p24 antigen and antibody tests, respectively. Diagnostic agreement with Procleix, was 100%. Regression analysis showed good agreement of VL results between Aptima and CAP/CTM with a slope of 1.02, intercept of 0.07, and correlation coefficient (R(2)) of 0.97. Aptima was more sensitive than CAP/CTM. Equivalent quantification was seen on testing clinical samples and isolates belonging to HIV group M, N, O and P and commercially available subtype panels. Assay results were linear (R(2) 0.9994) with standard deviation of <0.17 log copies across assay range. The good specificity, sensitivity, precision, subtype performance and clinical agreement with other assays demonstrated by Aptima combined with the complete automation provided by the Panther platform makes Aptima a good candidate for both VL monitoring and diagnosis of HIV-1. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Shedding of Hepatitis C Virus Into the Rectum of HIV-infected Men Who Have Sex With Men.

PubMed

Foster, Andrew L; Gaisa, Michael M; Hijdra, Rosanne M; Turner, Samuel S; Morey, Tristan J; Jacobson, Karen B; Fierer, Daniel S

2017-02-01

For over a decade we have known of an epidemic of sexually transmitted hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM), but there still remains significant controversy over which bodily fluid(s) are responsible for HCV transmission in these men. We enrolled HIV-infected MSM with recent and chronic HCV infection and quantified HCV from rectal fluid obtained by blind swab. We compared the rectal HCV viral load (VL) with paired blood HCV VL. We found rectal HCV shedding in 20 (47%) of 43 men, only one (2%) of whom had visible bleeding. Detection of rectal HCV shedding was associated with blood VL > 5 log 10 IU/mL (p = .01), and 85% with blood VL > 5 log 10 IU/mL had rectal shedding. The HCV VL of the rectal fluid ranged from 2.6 to 5.5 log 10 IU/mL. Based on the median rectal fluid VL, the surface of an average human penis would be exposed to at least 2,300 IU of HCV for the duration of anal intercourse. This study provides the first direct evidence to our knowledge that a sufficient quantity of HCV is shed into the rectum in HIV-infected men with HCV infection to directly infect an inserted penis or be passed indirectly through fomite-like transmission to the rectum of sex partner. We must develop an appropriate public health campaign to educate MSM about these routes of HCV infection to reverse the HCV epidemic among HIV-infected MSM. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

The Semen Microbiome and Its Relationship with Local Immunology and Viral Load in HIV Infection

PubMed Central

Liu, Cindy M.; Osborne, Brendan J. W.; Hungate, Bruce A.; Shahabi, Kamnoosh; Huibner, Sanja; Lester, Richard; Dwan, Michael G.; Kovacs, Colin; Contente-Cuomo, Tania L.; Benko, Erika; Aziz, Maliha

2014-01-01

Semen is a major vector for HIV transmission, but the semen HIV RNA viral load (VL) only correlates moderately with the blood VL. Viral shedding can be enhanced by genital infections and associated inflammation, but it can also occur in the absence of classical pathogens. Thus, we hypothesized that a dysregulated semen microbiome correlates with local HIV shedding. We analyzed semen samples from 49 men who have sex with men (MSM), including 22 HIV-uninfected and 27 HIV-infected men, at baseline and after starting antiretroviral therapy (ART) using 16S rRNA gene-based pyrosequencing and quantitative PCR. We studied the relationship of semen bacteria with HIV infection, semen cytokine levels, and semen VL by linear regression, non-metric multidimensional scaling, and goodness-of-fit test. Streptococcus, Corynebacterium, and Staphylococcus were common semen bacteria, irrespective of HIV status. While Ureaplasma was the more abundant Mollicutes in HIV-uninfected men, Mycoplasma dominated after HIV infection. HIV infection was associated with decreased semen microbiome diversity and richness, which were restored after six months of ART. In HIV-infected men, semen bacterial load correlated with seven pro-inflammatory semen cytokines, including IL-6 (p = 0.024), TNF-α (p = 0.009), and IL-1b (p = 0.002). IL-1b in particular was associated with semen VL (r2 = 0.18, p = 0.02). Semen bacterial load was also directly linked to the semen HIV VL (r2 = 0.15, p = 0.02). HIV infection reshapes the relationship between semen bacteria and pro-inflammatory cytokines, and both are linked to semen VL, which supports a role of the semen microbiome in HIV sexual transmission. PMID:25058515

Nuclear imprisonment of host cellular mRNA by nsp1β protein of porcine reproductive and respiratory syndrome virus.

PubMed

Han, Mingyuan; Ke, Hanzhong; Zhang, Qingzhan; Yoo, Dongwan

2017-05-01

Positive-strand RNA genomes function as mRNA for viral protein synthesis which is fully reliant on host cell translation machinery. Competing with cellular protein translation apparatus needs to ensure the production of viral proteins, but this also stifles host innate defense. In the present study, we showed that porcine reproductive and respiratory syndrome virus (PRRSV), whose replication takes place in the cytoplasm, imprisoned host cell mRNA in the nucleus, which suggests a novel mechanism to enhance translation of PRRSV genome. PRRSV nonstructural protein (nsp) 1β was identified as the nuclear protein playing the role for host mRNA nuclear retention and subversion of host protein synthesis. A SAP (SAF-A/B, Acinus, and PIAS) motif was identified in nsp1β with the consensus sequence of 126 -LQxxLxxxGL- 135 . In situ hybridization unveiled that SAP mutants were unable to cause nuclear retention of host cell mRNAs and did not suppress host protein synthesis. In addition, these SAP mutants reverted PRRSV-nsp1β-mediated suppression of interferon (IFN) production, IFN signaling, and TNF-α production pathway. Using reverse genetics, a series of SAP mutant PRRS viruses, vK124A, vL126A, vG134A, and vL135A were generated. No mRNA nuclear retention was observed during vL126A and vL135A infections. Importantly, vL126A and vL135A did not suppress IFN production. For other arteriviruses, mRNA nuclear accumulation was also observed for LDV-nsp1β and SHFV-nsp1β. EAV-nsp1 was exceptional and did not block the host mRNA nuclear export. Copyright © 2017 Elsevier Inc. All rights reserved.

Virus-like attachment sites as structural landmarks of plants retrotransposons.

PubMed

Ochoa Cruz, Edgar Andres; Cruz, Guilherme Marcello Queiroga; Vieira, Andréia Prata; Van Sluys, Marie-Anne

2016-01-01

The genomic data available nowadays has enabled the study of repetitive sequences and their relationship to viruses. Among them, long terminal repeat retrotransposons (LTR-RTs) are the largest component of most plant genomes, the Gypsy and Copia superfamilies being the most common. Recently it has been found that Del lineage, an LTR-RT of Gypsy superfamily, has putative virus-like attachment (vl-att) sites. This signature, originally described for retroviruses, is recognized by retroviral integrase conferring specificity to the integration process. Here we retrieved 26,092 putative complete LTR-RTs from 10 lineages found in 10 fully sequenced angiosperm genomes and found putative vl-att sites that are a conserved structural landmark across these genomes. Furthermore, we reveal that each plant genome has a distinguishable LTR-RT lineage amplification pattern that could be related to the vl-att sites diversity. We used these patterns to generate a specific quick-response (QR) code for each genome that could be used as a barcode of identification of plants in the future. The universal distribution of vl-att sites represents a new structural feature common to plant LTR-RTs and retroviruses. This is an important finding that expands the information about the structural similarity between LTR-RT and retroviruses. We speculate that the sequence diversity of vl-att sites could be important for the life cycle of retrotransposons, as it was shown for retroviruses. All the structural vl-att site signatures are strong candidates for further functional studies. Moreover, this is the first identification of specific LTR-RT content and their amplification patterns in a large dataset of LTR-RT lineages and angiosperm genomes. These distribution patterns could be used in the future with biotechnological identification purposes.

Implementation and Operational Research: Programmatic Feasibility of Dried Blood Spots for the Virological Follow-up of Patients on Antiretroviral Treatment in Nord Kivu, Democratic Republic of the Congo

PubMed Central

Serrano, Laetitia; Muwonga, Jeremie; Kabuayi, Jean Pierre; Kambale, Alain; Mutaka, Fidèle; Fujiwara, Paula I.; Decosas, Josef; Peeters, Martine; Delaporte, Eric

2016-01-01

Background: As part of its policy to shift monitoring of antiretroviral therapy (ART) to primary health care (PHC) workers, the Ministry of Health of the Democratic Republic of Congo (DRC) tested the feasibility of using dried blood spots (DBS) for viral load (VL) quantification and genotypic drug resistance testing in off-site high-throughput laboratories. Methods: DBS samples from adults on ART were collected in 13 decentralized PHC facilities in the Nord-Kivu province and shipped during program quarterly supervision to a reference laboratory 2000 km away, where VL was quantified with a commercial assay (m2000rt, Abbott). A second DBS was sent to a World Health Organization (WHO)-accredited laboratory for repeat VL quantification on a subset of samples with a generic assay (Biocentric) and genotypic drug resistance testing when VL >1000 copies per milliliter. Findings: Constraints arose because of an interruption in national laboratory funding rather than to technical or logistic problems. All samples were assessed by both VL assays to allow ART adjustment. Median DBS turnaround time was 37 days (interquartile range: 9–59). Assays performed unequally with DBS, impacting clinical decisions, quality assurance, and overall cost-effectiveness. Based on m2000rt or generic assay, 31.3% of patients were on virological failure (VF) and 14.8% presented resistance mutations versus 50.3% and 15.4%, respectively. Conclusion: This study confirms that current technologies involving DBS make virological monitoring of ART possible at PHC level, including in challenging environments, provided organizational issues are addressed. Adequate core funding of HIV laboratories and adapted choice of VL assays require urgent attention to control resistance to ART as coverage expands. PMID:26413848

The alpha-TIF (VP16) homologue (ETIF) of equine herpesvirus 1 is essential for secondary envelopment and virus egress.

PubMed

von Einem, Jens; Schumacher, Daniel; O'Callaghan, Dennis J; Osterrieder, Nikolaus

2006-03-01

The equine herpesvirus 1 (EHV-1) alpha-trans-inducing factor homologue (ETIF; VP16-E) is a 60-kDa virion component encoded by gene 12 (ORF12) that transactivates the immediate-early gene promoter. Here we report on the function of EHV-1 ETIF in the context of viral infection. An ETIF-null mutant from EHV-1 strain RacL11 (vL11deltaETIF) was constructed and analyzed. After transfection of vL11deltaETIF DNA into RK13 cells, no infectious virus could be reconstituted, and only single infected cells or small foci containing up to eight infected cells were detected. In contrast, after transfection of vL11deltaETIF DNA into a complementing cell line, infectious virus could be recovered, indicating the requirement of ETIF for productive virus infection. The growth defect of vL11deltaETIF could largely be restored by propagation on the complementing cell line, and growth on the complementing cell line resulted in incorporation of ETIF in mature and secreted virions. Low- and high-multiplicity infections of RK13 cells with phenotypically complemented vL11deltaETIF virus resulted in titers of virus progeny similar to those used for infection, suggesting that input ETIF from infection was recycled. Ultrastructural studies of vL11deltaETIF-infected cells demonstrated a marked defect in secondary envelopment at cytoplasmic membranes, resulting in very few enveloped virions in transport vesicles or extracellular space. Taken together, our results demonstrate that ETIF has an essential function in the replication cycle of EHV-1, and its main role appears to be in secondary envelopment.

Highly active antiretroviral therapy including protease inhibitors does not confer a unique CD4 cell benefit. The AVANTI and INCAS Study Groups.

PubMed

2000-07-07

To determine if triple combination therapy, particularly including HIV protease inhibitors (PI), confers an unique immunological benefit that is independent of reductions of plasma viral load (pVL). The correlation between changes from baseline in CD4 cell count and pVL was examined at all time points up to 52 weeks in three randomized clinical trials (AVANTI-2, AVANTI-3 and INCAS) that compared dual nucleoside therapy with triple combination therapy. Individual pVL and CD4 cell counts changes from baseline were entered into multivariate linear regression models for patients receiving double therapy and for those receiving triple therapy including a PI and/or a non-nucleoside reverse transcriptase inhibitor (NNRTI), and the null hypothesis was tested. After 52 weeks of therapy, the relationship between changes from baseline CD4 cell count and pVL was independent of whether patients were assigned double or triple therapy (P = 0.23 and 0.69 for intercept and slope, respectively), or whether patients were assigned triple therapy including a PI or triple therapy including an NNRTI (P = 0.92 and 0.95, respectively). Less than 5% of patients ever had 'discordant' increases in both CD4 cell count and pVL compared with baseline, and this proportion was unrelated to the class of therapy used. 'Discordant' decreases from baseline in both parameters were observed in up to 35% of individuals. The correlation between pVL and CD4 cell count changes from baseline improved over time on therapy, regardless of the therapeutic regimen involved. The data provide no evidence for a CD4 cell count benefit of highly active antiretroviral therapy (HAART) unique to triple therapy or PI-containing regimens.

Longer duration of homelessness is associated with a lower likelihood of non-detectable plasma HIV-1 RNA viral load among people who use illicit drugs in a Canadian setting.

PubMed

Loh, Jane; Kennedy, Mary Clare; Wood, Evan; Kerr, Thomas; Marshall, Brandon; Parashar, Surita; Montaner, Julio; Milloy, M-J

2016-11-01

Homelessness is common among people who use drugs (PWUD) and, for those living with HIV/AIDS, an important contributor to sub-optimal HIV treatment outcomes. This study aims to investigate the relationship between the duration of homelessness and the likelihood of plasma HIV-1 RNA viral load (VL) non-detectability among a cohort of HIV-positive PWUD. We used data from the ACCESS study, a long-running prospective cohort study of HIV-positive PWUD linked to comprehensive HIV clinical records including systematic plasma HIV-1 RNA VL monitoring. We estimated the longitudinal relationship between the duration of homelessness and the likelihood of exhibiting a non-detectable VL (i.e., <500 copies/mL plasma) using generalized linear mixed-effects modelling. Between May 1996 and June 2014, 922 highly active antiretroviral therapy-exposed participants were recruited and contributed 8188 observations. Of these, 4800 (59%) were characterized by non-detectable VL. Participants reported they were homeless in 910 (11%) interviews (median: six months, interquartile range: 6-12 months). A longer duration of homelessness was associated with lower odds of VL non-detectability (adjusted odds ratio = 0.71 per six-month period of homelessness, 95% confidence interval: 0.60-0.83) after adjustment for age, ancestry, drug use patterns, engagement in addiction treatment, and other potential confounders. Longer durations of episodes of homelessness in this cohort of HIV-positive illicit drug users were associated with a lower likelihood of plasma VL non-detectability. Our findings suggest that interventions that seek to promptly house homeless individuals, such as Housing First approaches, might assist in maximizing the clinical and public health benefits of antiretroviral therapy among people living with HIV/AIDS.

HIV viral suppression in Oman: Encouraging progress toward achieving the United Nations 'third 90'.

PubMed

Elgalib, Ali; Shah, Samir; Al-Habsi, Zeyana; Al-Fouri, Maha; Al-Sawafi, Halima; Al-Noumani, Jalila; Al-Baloushi, Adil; Al-Alawi, Saad; Al-Badi, Salma; Mohammed, Zainab; Al-Ghafri, Jokha; Suleimani, Asma; Al-Mashani, Huda; Raju, Jyothish; Al-Riyami, Saada; Al-Shukri, Muna; Wahab, Abdul; Hussain, Bilal; Al-Naabi, Khalifa; Narayan, Anantha; Oliveros, Noreen; Prasad, George; Hussein, Ahmed; Kashyp, Rajeev; Al-Shardi, Khalid; Nada, Ahmed; Akhwand, Shakil; Kamble, Bina; Al-Aamri, Kawthar; Al-Mukhaini, Suad; Al-Kindi, Hanan; Khamis, Faryal; Al-Maani, Amal; Al-Abaidani, Idris; Al-Abri, Seif

2018-05-18

To assess the impact of capacity-building interventions introduced by the Oman National AIDS Programme on the quality of HIV care in the country. HIV viral load (VL) suppression and loss to follow-up (LTFU) rates were calculated for the period before (in December 2015; n=1098) and after (in June 2017; n=1185) the introduction of the interventions: training, support, and care pathway development. Three HIV VL cuts-offs at last measurement in the year of interest were used to define VL suppression. In the intention-to-treat (ITT) analysis, rates of VL <200 copies/ml and <1000 copies/ml increased from 51.9% in 2015 to 65.5% in 2017 (relative risk (RR) 1.26, 95% confidence interval (CI) 1.17-1.36) and from 58.1% in 2015 to 70.9% in 2017 (RR 1.22, 95% CI 1.14-1.30), respectively; p<0.0001 for both. Similarly, in the on-treatment analysis, rates of VL <200 copies/ml and <1000copies/ml increased from 64.2% in 2015 to 76.9% in 2017 (RR 1.20, 95% CI 1.12-1.28) and from 71.9% in 2015 to 83.2% in 2017 (RR 1.16, 95% CI 1.10-1.22), respectively. Fewer patients were LTFU in 2017 than in 2015 (14.7% (157/1061) vs. 19.2% (188/981); RR 0.77, 95% CI 0.64-0.94). Achieving the UNAIDS target of 90% of HIV patients on treatment having VL suppression by 2020 is feasible in Oman. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Drug Susceptibility and Resistance Mutations After First-Line Failure in Resource Limited Settings

PubMed Central

Wallis, Carole L.; Aga, Evgenia; Ribaudo, Heather; Saravanan, Shanmugam; Norton, Michael; Stevens, Wendy; Kumarasamy, Nagalingeswaran; Bartlett, John; Katzenstein, David

2014-01-01

Background. The development of drug resistance to nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) has been associated with baseline human immunodeficiency virus (HIV)-1 RNA level (VL), CD4 cell counts (CD4), subtype, and treatment failure duration. This study describes drug resistance and levels of susceptibility after first-line virologic failure in individuals from Thailand, South Africa, India, Malawi, Tanzania. Methods. CD4 and VL were captured at AIDs Clinical Trial Group (ACTG) A5230 study entry, a study of lopinavir/ritonavir (LPV/r) monotherapy after first-line virologic failure on an NNRTI regimen. HIV drug-resistance mutation associations with subtype, site, study entry VL, and CD4 were evaluated using Fisher exact and Kruskall–Wallis tests. Results. Of the 207 individuals who were screened for A5230, sequence data were available for 148 individuals. Subtypes observed: subtype C (n = 97, 66%) AE (n = 27, 18%), A1 (n = 12, 8%), and D (n = 10, 7%). Of the 148 individuals, 93% (n = 138) and 96% (n = 142) had at least 1 reverse transcriptase (RT) mutation associated with NRTI and NNRTI resistance, respectively. The number of NRTI mutations was significantly associated with a higher study screening VL and lower study screening CD4 (P < .001). Differences in drug-resistance patterns in both NRTI and NNRTI were observed by site. Conclusions. The degree of NNRTI and NRTI resistance after first-line virologic failure was associated with higher VL at study entry. Thirty-two percent of individuals remained fully susceptible to etravirine and rilpivirine, protease inhibitor resistance was rare. Some level of susceptibility to NRTI remained; however, VL monitoring and earlier virologic failure detection may result in lower NRTI resistance. PMID:24795328

Neospora caninum and Leishmania infantum Co-Infection in Domestic Dogs (Canis familiaris) in Meshkin-Shahr District, Northwestern Iran

PubMed Central

Sharifdini, M; Mohebali, M; Keshavarz, H; Hosseininejad, M; Hajjaran, H; Akhoundi, B; Foroushani, A Rahimi; Zarei, Z; Charehdar, S

2011-01-01

Background: Mediterranean visceral leishmaniasis (MVL) is an infectious disease that affects both human and animals. Domestic dogs (Canis familiaris) are principal reservoir hosts of MVL caused by Leishmania infantum. Dogs are definitive hosts for Neospora caninum and a risk factor for infecting intermediate hosts. The immunosuppression caused by visceral leishmaniasis (VL) can promote the occurrence of co-infections with other agents such as neosporosis. This study aimed to determine the frequency of co-infection of the both protozoan parasites in the endemic areas of VL from Meshkin-Shahr District, north-west of Iran. Methods: Altogether, 171 serum samples were collected from domestic dogs of Meshkin-Shahr District by multistage cluster sampling from October 2008 to August 2009. The collected serum samples were tested for the detection of simultaneous infection of L. infantum and N. caninum using direct agglutination test (DAT) and indirect ELISA, respectively. Results: Of the 171 domestic dogs, 27 (15.8%) and 52 (30.4%) were showed antibodies against L. infantum and N. caninum, respectively. Simultaneous infections of N. caninum and L. infantum was found in 16 (9.4%) of the dogs. In VL-positive and VL-negative dogs, N. caninum infection was found in 59.3% and 25.0%, respectively. A statistically significant difference was found between VL-positive and VL-negative dogs with N. caninum infection (P= 0.001). Conclusion: These findings indicate that Meshkin-Shahr District in northwestern Iran is an active focus of canine visceral leishmaniasis (CVL). Neospora caninum and L. infantum co-infection is prevalent in the area and infection by L. infantum seems to enhance susceptibility to N. caninum infection in domestic dogs. PMID:22808419

Esmolol acutely alters oxygen supply-demand balance in exercising muscles of healthy humans.

PubMed

Proctor, David N; Luck, J Carter; Maman, Stephan R; Leuenberger, Urs A; Muller, Matthew D

2018-04-01

Beta-adrenoreceptor antagonists (β blockers) reduce systemic O 2 delivery and blood pressure (BP) during exercise, but the subsequent effects on O 2 extraction within the active limb muscles are unknown. In this study, we examined the effects of the fast-acting, β 1 selective blocker esmolol on systemic hemodynamics and leg muscle O 2 saturation (near infrared spectroscopy, NIRS) during submaximal leg ergometry. Our main hypothesis was that esmolol would augment exercise-induced reductions in leg muscle O 2 saturation. Eight healthy adults (6 men, 2 women; 23-67 year) performed light and moderate intensity bouts of recumbent leg cycling before (PRE), during (β 1 -blocked), and 45 min following (POST) intravenous infusion of esmolol. Oxygen uptake, heart rate (HR), BP, and O 2 saturation (SmO 2 ) of the vastus lateralis (VL) and medial gastrocnemius (MG) muscles were measured continuously. Esmolol attenuated the increases in HR and systolic BP during light (-12 ± 9 bpm and -26 ± 12 mmHg vs. PRE) and moderate intensity (-20 ± 10 bpm and -40 ± 18 mmHg vs. PRE) cycling (all P < 0.01). Exercise-induced reductions in SmO 2 occurred to a greater extent during the β 1 -blockade trial in both the VL (P = 0.001 vs. PRE) and MG muscles (P = 0.022 vs. PRE). HR, SBP and SmO 2 were restored during POST (all P < 0.01 vs. β 1 -blocked). In conclusion, esmolol rapidly and reversibly increases O 2 extraction within exercising muscles of healthy humans. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Organization of projections from the anterior pole of the nucleus reticularis thalami (NRT) to subdivisions of the motor thalamus: light and electron microscopic studies in the rhesus monkey.

PubMed

Ilinsky, I A; Ambardekar, A V; Kultas-Ilinsky, K

1999-07-05

Projections to the motor-related thalamic nuclei from the anterior pole of the reticular thalamic nucleus (NRT) were studied after injections of biotinylated dextran amine and wheat germ agglutinin conjugated horseradish peroxidase at light and electron microscopic levels, respectively. Each injection resulted in anterograde labeling in the three subdivisions of the ventral anterior nucleus (pars parvicellularis, VApc; pars densicellularis, VAdc; and pars magnocellularis, VAmc) and in the ventral lateral nucleus (VL). NRT fibers had beaded shapes and coursed in a posterior direction giving rise to relatively diffuse terminal plexuses. The average size of the beads (0.7 microm2) and their density per 100 microm of fiber length (23.7-25.7) were similar between the nuclei studied. At the electron microscopic level, anterogradely labeled boutons displayed positive immunoreactivity for gamma-aminobutyric acid (GABA), contained pleomorphic synaptic vesicles, and formed relatively long (approximately 0.4 microm) symmetric synaptic contacts. Usually, a single terminal formed synapses on more than one postsynaptic structure. Synaptic contacts were on projection and local circuit neurons and targeted mainly their distal dendrites. In the VAmc, synapses on local circuit neurons composed 48% of the total sample, in the VAdc/VApc and in the VL the proportion was higher, 65% and 62%, respectively. The results suggest that the input from the anterior pole of the monkey reticular nucleus to the motor-related thalamic nuclei is organized differently from what is known on the organization of connections of NRT with sensory thalamic nuclei in other species in that the terminal fields of individual fibers are diffuse rather than focal and that at least 50% of synapses are established on GABAergic local circuit neurons.

Neural dissociations between meaningful and mere inconsistency in impression updating

PubMed Central

Todorov, Alexander

2016-01-01

Recent neuroimaging work has identified a network of regions that work in concert to update impressions of other people, particularly in response to inconsistent behavior. However, the specific functional contributions of these regions to the updating process remain unclear. Using fMRI, we tested whether increases in activity triggered by inconsistent behavior reflect changes in the stored representations of other people in response to behavioral inconsistency, or merely a response to the inconsistency itself. Participants encountered a series of individuals whose behavior either changed in an attributionally meaningful fashion or was merely inconsistent with the immediately preceding behavior. We observed that left ventrolateral prefrontal cortex (vlPFC) and left inferior frontal gyrus (IFG) were preferentially recruited in response to unexpected, immoral behavior, whereas a separate set of regions (including dorsal anterior cingulate cortex, posterior cingulate cortex and temporoparietal junction/inferior parietal lobule) was preferentially recruited in response to more mundane inconsistencies in behavior. These results shed light on the distributed systems supporting impression updating. Specifically, while many regions supporting updating may primarily respond to moment-to-moment changes in behavior, a subset of regions (e.g. vlPFC and IFG) may contribute to updating person representations in response to trait-relevant changes in behavior. PMID:27217118

Poverty, hunger, education, and residential status impact survival in HIV.

PubMed

McMahon, James; Wanke, Christine; Terrin, Norma; Skinner, Sally; Knox, Tamsin

2011-10-01

Despite combination antiretroviral therapy (ART), HIV infected people have higher mortality than non-infected. Lower socioeconomic status (SES) predicts higher mortality in many chronic illnesses but data in people with HIV is limited. We evaluated 878 HIV infected individuals followed from 1995 to 2005. Cox proportional hazards for all-cause mortality were estimated for SES measures and other factors. Mixed effects analyses examined how SES impacts factors predicting death. The 200 who died were older, had lower CD4 counts, and higher viral loads (VL). Age, transmission category, education, albumin, CD4 counts, VL, hunger, and poverty predicted death in univariate analyses; age, CD4 counts, albumin, VL, and poverty in the multivariable model. Mixed models showed associations between (1) CD4 counts with education and hunger; (2) albumin with education, homelessness, and poverty; and (3) VL with education and hunger. SES contributes to mortality in HIV infected persons directly and indirectly, and should be a target of health policy in this population.

Dairy fat blend improves brain DHA and neuroplasticity and regulates corticosterone in mice.

PubMed

Dinel, A L; Rey, C; Bonhomme, C; Le Ruyet, P; Joffre, C; Layé, S

2016-06-01

Mimicking the breast milk lipid composition appears to be necessary for infant formula to cover the brain's needs in n-3 PUFA. In this study, we evaluated the impact of partial replacement of vegetable oil (VL) in infant formula by dairy fat (DL) on docosahexaenoic acid (DHA) brain level, neuroplasticity and corticosterone in mice. Mice were fed with balanced VL or balanced DL diets enriched or not in DHA and arachidonic acid (ARA) from the first day of gestation. Brain DHA level, microglia number, neurogenesis, corticosterone and glucocorticoid receptor expression were measured in the offsprings. DL diet increased DHA and neuroplasticity in the brain of mice at postnatal day (PND) 14 and at adulthood compared to VL. At PND14, ARA and DHA supplementation increased DHA in VL but not in DL mice brain. Importantly, DHA and ARA supplementation further improved neurogenesis and decreased corticosterone level in DL mice at adulthood. In conclusion, dairy lipids improve brain DHA level and neuroplasticity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Venous Lake of the Lips Treated Using Photocoagulation with High-Intensity Diode Laser

PubMed Central

Galletta, Vivian C.; de Paula Eduardo, Carlos; Migliari, Dante A.

2010-01-01

Abstract Objective: To evaluate the effectiveness of photocoagulation with high-intensity diode laser in the treatment of venous lake (VL) lesions. Background Data: VL is a common vascular lesion characterized by elevated, usually dome-shaped papules, ranging in color from dark blue to dark purple, seen more frequently in elderly patients. They often occur as single lesions on the ears, face, lips, or neck. Once formed, lesions persist throughout life. Although these lesions are usually asymptomatic, they can bleed if injured. Methods: Seventeen patients (7 men and 10 women) with VL on the lip were treated using a noncontact diode laser (wavelength 808 nm, power output 2–3 W in continuous wave). Results: After only one irradiation exposure, all lesions were successfully treated. Healing was completed in approximately 2 to 3 weeks, and none of the patients experienced complications. Postoperative discomfort and scarring were not present or were minimal. Conclusion: Photocoagulation with high-intensity diode laser is an effective, bloodless procedure for the treatment of VL. PMID:19811083

Dynamic representation of partially occluded objects in primate prefrontal and visual cortex

PubMed Central

Choi, Hannah; Shea-Brown, Eric

2017-01-01

Successful recognition of partially occluded objects is presumed to involve dynamic interactions between brain areas responsible for vision and cognition, but neurophysiological evidence for the involvement of feedback signals is lacking. Here, we demonstrate that neurons in the ventrolateral prefrontal cortex (vlPFC) of monkeys performing a shape discrimination task respond more strongly to occluded than unoccluded stimuli. In contrast, neurons in visual area V4 respond more strongly to unoccluded stimuli. Analyses of V4 response dynamics reveal that many neurons exhibit two transient response peaks, the second of which emerges after vlPFC response onset and displays stronger selectivity for occluded shapes. We replicate these findings using a model of V4/vlPFC interactions in which occlusion-sensitive vlPFC neurons feed back to shape-selective V4 neurons, thereby enhancing V4 responses and selectivity to occluded shapes. These results reveal how signals from frontal and visual cortex could interact to facilitate object recognition under occlusion. PMID:28925354

Wood typification by Venturi easy ambient sonic spray ionization mass spectrometry: the case of the endangered Mahogany tree.

PubMed

Cabral, Elaine C; Simas, Rosineide C; Santos, Vanessa G; Queiroga, Carmen L; da Cunha, Valnei S; de Sá, Gilberto F; Daroda, Romeu J; Eberlin, Marcos N

2012-01-01

Venturi easy ambient sonic spray ionization mass spectrometry in both its liquid (V(L) -EASI-MS) and solid sample modes (V(S) -EASI-MS) is shown to provide nearly immediate and secure typification of woods, as demonstrated for Mahogany, an endangered and most valuable type of tropical wood. This reddish wood displays unique phytochemical markers (phragmalin-type limonoids) which are rapidly detected from the wood surface by V(S) -EASI-MS or from a simple methanol extract of a tiny wood chip by V(L) -EASI-MS. Unique profiles were obtained for Mahogany (Swietenia macrophylla) whereas genuine samples of six other similar types of woods, which are commonly falsified by artificial coloring and commercialized as Mahogany, display also typical but dissimilar pythochemical profiles as compared to that of the authentic wood. Variable and atypical chemical profiles were observed for artificially colored woods. Secure chemical characterization via V(S) -EASI-MS or V(s) -EASI-MS fingerprints of Mahogany and other types of woods with similar appearance should help to control the illegal logging and trade of this and other endangered woods and their falsification, and to create certified standards. Copyright © 2012 John Wiley & Sons, Ltd.

Second-Line Antiretroviral Therapy in a Workplace and Community-Based Treatment Programme in South Africa: Determinants of Virological Outcome

PubMed Central

Johnston, Victoria; Fielding, Katherine; Charalambous, Salome; Mampho, Mildred; Churchyard, Gavin; Phillips, Andrew; Grant, Alison D.

2012-01-01

Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART. Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ≥400 copies/ml. Predictors of VL<400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios. Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL<400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL<400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL<400. Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed. PMID:22666338

Projecting the epidemiological effect, cost-effectiveness and transmission of HIV drug resistance in Vietnam associated with viral load monitoring strategies.

PubMed

Pham, Quang Duy; Wilson, David P; Nguyen, Thuong Vu; Do, Nhan Thi; Truong, Lien Xuan; Nguyen, Long Thanh; Zhang, Lei

2016-05-01

The objective of this study was to investigate the potential epidemiological impact of viral load (VL) monitoring and its cost-effectiveness in Vietnam, where transmitted HIV drug resistance (TDR) prevalence has increased from <5% to 5%-15% in the past decade. Using a population-based mathematical model driven by data from Vietnam, we simulated scenarios of various combinations of VL testing coverage, VL thresholds for second-line ART initiation and availability of HIV drug-resistance tests. We assessed the cost per disability-adjusted life year (DALY) averted for each scenario. Projecting expected ART scale-up levels, to approximately double the number of people on ART by 2030, will lead to an estimated 18 510 cases (95% CI: 9120-34 600 cases) of TDR and 55 180 cases (95% CI: 40 540-65 900 cases) of acquired drug resistance (ADR) in the absence of VL monitoring. This projection corresponds to a TDR prevalence of 16% (95% CI: 11%-24%) and ADR of 18% (95% CI: 15%-20%). Annual or biennial VL monitoring with 30% coverage is expected to relieve 12%-31% of TDR (2260-5860 cases), 25%-59% of ADR (9620-22 650 cases), 2%-6% of HIV-related deaths (360-880 cases) and 19 270-51 400 DALYs during 2015-30. The 30% coverage of VL monitoring is estimated to cost US$4848-5154 per DALY averted. The projected additional cost for implementing this strategy is US$105-268 million over 2015-30. Our study suggests that a programmatically achievable 30% coverage of VL monitoring can have considerable benefits for individuals and leads to population health benefits by reducing the overall national burden of HIV drug resistance. It is marginally cost-effective according to common willingness-to-pay thresholds. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Real versus virtual phenotype to guide treatment in heavily pretreated patients: 48-week follow-up of the Genotipo-Fenotipo di Resistenza (GenPheRex) trial.

PubMed

Mazzotta, Francesco; Lo Caputo, Sergio; Torti, Carlo; Tinelli, Carmine; Pierotti, Piera; Castelli, Francesco; Lazzarin, Adriano; Angarano, Gioacchino; Maserati, Renato; Gianotti, Nicola; Ladisa, Nicoletta; Quiros-Roldan, Eugenia; Rinehart, Alex R; Carosi, Giampiero

2003-03-01

We compared viroimmunologic response after real phenotype (r-PHT) versus virtual phenotype (v-PHT) in patients failing highly active antiretroviral therapy (HAART). A total of 201 patients with >2 years of exposure, more than six experienced drugs, >1000 HIV RNA copies/mL, and on stable HAART for >6 months were randomized to the r-PHT or v-PHT arm. The primary end point was the proportion of HIV plasma viral load (pVL) <400 copies/mL. Secondary end points were absolute pVL change, proportion of pVL reduction >0.5 log(10) copies/mL, and absolute CD4 cell change. In the intention-to-treat-last observation carried forward analysis, study outcomes were not significantly different between arms over 48 weeks of follow-up: 20% and 24% pVL <400 copies/mL; 58% and 61% pVL reduction >0.5 log(10) copies/mL; -0.92 and -0.94(10) log copies/mL mean pVL decrease; and +41.6 and +94.4 cells/mm(3) mean absolute CD4 increase in the r-PHT and v-PHT arms, respectively. On-treatment analyses gave similar results. In the multivariate analysis of pVL <400 copies/mL, the following covariates were independent predictors at week 48: adherence (OR p= 0.25; p=.002), baseline CD4 (OR = 4.39; p=.007), intravenous drug use as risk factor for HIV acquisition (OR = 0.33; p=.024), and sensitivity score of the new regimens by biologic cut-offs (OR = 1.84; p=.029). Prescribed drugs for which patients were naive resulted in marginal prediction (OR = 1.93; p=.054). In conclusion, virologic and immunologic outcomes did not differ when r-PHT or v-PHT was used in this cohort of heavily pretreated patients. Several factors should be considered to take better advantage of resistance testing, including treatment history, clinical status, and patients' ability to adhere to treatment.

Development of a rapid loop-mediated isothermal amplification assay for diagnosis and assessment of cure of Leishmania infection.

PubMed

Verma, Sandeep; Singh, Ruchi; Sharma, Vanila; Bumb, Ram Avtar; Negi, Narendra Singh; Ramesh, V; Salotra, Poonam

2017-03-23

Leishmaniasis is a spectrum of diseases with great relevance to public health. Conventional diagnostic methods are time consuming, needing trained personnel. A robust, rapid and cost effective diagnostic test is warranted for on-time diagnosis and field application. We have developed a loop mediated isothermal amplification (LAMP) assay with primers (n = 6) based on Leishmania donovani kDNA for detection of Leishmania infection, using a closed tube to prevent cross-contamination. The assay was used to detect Leishmania infection in biological samples obtained from patients of visceral leishmaniasis (VL), post kala-azar dermal leishmaniasis (PKDL) and cutaneous leishmaniasis (CL). The assay was positive for L. donovani, L. tropica and L. major parasites, with the highest sensitivity towards L. donovani (1 fg DNA). The high sensitivity of the assay for detection of L. donovani was reflected in its ability to detect parasite DNA within 30 min of amplification time with a threshold detection limit of ≥25 copies per reaction. The assay detected parasite in 64 of 66 VL blood samples (sensitivity, 96.9%; 95% CI: 89.6-99.2%), 15 of 15 VL bone marrow aspirate samples (sensitivity, 100%; 95% CI:79.6-100%), 65 of 67 PKDL tissue biopsy samples (sensitivity, 97%; 95% CI:89.7-99.2%). The assay was evaluated in a few cases of CL wherein it was found positive in 8 of 10 tissue biopsies (sensitivity, 80%; 95% CI: 49-94.3%). The assay was negative in all control blood (n = 76) and tissue biopsy (n = 24) samples (specificity, 100%; 95% CI: 96.3-100%). Further, the assay was evaluated for its utility in assessment of cure in treated VL and PKDL patients. The assay detected parasite DNA in 2 of 20VL blood samples and 2 of 21 PKDL tissue samples. Out of 4 cases that were positive for parasite DNA at post treatment stage, 2 patients (1VL and 1 PKDL) returned with relapse. The study demonstrated a Leishmania genus specific closed tube LAMP assay for reliable and rapid molecular diagnosis of VL and PKDL with potential for application in assessment of cure.

Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil.

PubMed

Sevá, Anaiá da Paixão; Mao, Liang; Galvis-Ovallos, Fredy; Tucker Lima, Joanna Marie; Valle, Denis

2017-02-01

Visceral leishmaniasis (VL) is an important neglected disease caused by a protozoan parasite, and represents a serious public health problem in many parts of the world. It is zoonotic in Europe and Latin America, where infected dogs constitute the main domestic reservoir for the parasite and play a key role in VL transmission to humans. In Brazil this disease is caused by the protozoan Leishmania infantum chagasi, and is transmitted by the sand fly Lutzomyia longipalpis. Despite programs aimed at eliminating infection sources, the disease continues to spread throughout the Country. VL in São Paulo State, Brazil, first appeared in the northwestern region, spreading in a southeasterly direction over time. We integrate data on the VL vector, infected dogs and infected human dispersion from 1999 to 2013 through an innovative spatial temporal Bayesian model in conjunction with geographic information system. This model is used to infer the drivers of the invasion process and predict the future progression of VL through the State. We found that vector dispersion was influenced by vector presence in nearby municipalities at the previous time step, proximity to the Bolívia-Brazil gas pipeline, and high temperatures (i.e., annual average between 20 and 23°C). Key factors affecting infected dog dispersion included proximity to the Marechal Rondon Highway, high temperatures, and presence of the competent vector within the same municipality. Finally, vector presence, presence of infected dogs, and rainfall (approx. 270 to 540mm/year) drove the dispersion of human VL cases. Surprisingly, economic factors exhibited no noticeable influence on disease dispersion. Based on these drivers and stochastic simulations, we identified which municipalities are most likely to be invaded by vectors and infected hosts in the future. Prioritizing prevention and control strategies within the identified municipalities may help halt the spread of VL while reducing monitoring costs. Our results contribute important knowledge to public and animal health policy planning, and suggest that prevention and control strategies should focus on vector control and on blocking contact between vectors and hosts in the priority areas identified to be at risk.

Risk analysis and prediction of visceral leishmaniasis dispersion in São Paulo State, Brazil

PubMed Central

Mao, Liang; Galvis-Ovallos, Fredy; Tucker Lima, Joanna Marie; Valle, Denis

2017-01-01

Visceral leishmaniasis (VL) is an important neglected disease caused by a protozoan parasite, and represents a serious public health problem in many parts of the world. It is zoonotic in Europe and Latin America, where infected dogs constitute the main domestic reservoir for the parasite and play a key role in VL transmission to humans. In Brazil this disease is caused by the protozoan Leishmania infantum chagasi, and is transmitted by the sand fly Lutzomyia longipalpis. Despite programs aimed at eliminating infection sources, the disease continues to spread throughout the Country. VL in São Paulo State, Brazil, first appeared in the northwestern region, spreading in a southeasterly direction over time. We integrate data on the VL vector, infected dogs and infected human dispersion from 1999 to 2013 through an innovative spatial temporal Bayesian model in conjunction with geographic information system. This model is used to infer the drivers of the invasion process and predict the future progression of VL through the State. We found that vector dispersion was influenced by vector presence in nearby municipalities at the previous time step, proximity to the Bolívia-Brazil gas pipeline, and high temperatures (i.e., annual average between 20 and 23°C). Key factors affecting infected dog dispersion included proximity to the Marechal Rondon Highway, high temperatures, and presence of the competent vector within the same municipality. Finally, vector presence, presence of infected dogs, and rainfall (approx. 270 to 540mm/year) drove the dispersion of human VL cases. Surprisingly, economic factors exhibited no noticeable influence on disease dispersion. Based on these drivers and stochastic simulations, we identified which municipalities are most likely to be invaded by vectors and infected hosts in the future. Prioritizing prevention and control strategies within the identified municipalities may help halt the spread of VL while reducing monitoring costs. Our results contribute important knowledge to public and animal health policy planning, and suggest that prevention and control strategies should focus on vector control and on blocking contact between vectors and hosts in the priority areas identified to be at risk. PMID:28166251

Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study

PubMed Central

Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

2017-01-01

Introduction Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. Methods and analysis The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethics and dissemination Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY00001466). Results will be presented at international conferences and published in academic peer-reviewed journals. Trial registration NCT03066128; Pre-results. PMID:28963304

Sensitive and less invasive confirmatory diagnosis of visceral leishmaniasis in Sudan using loop-mediated isothermal amplification (LAMP)

PubMed Central

Mukhtar, Maowia; Ali, Sababil S.; Boshara, Salah A.; Albertini, Audrey; Monnerat, Séverine; Bessell, Paul; Mori, Yasuyoshi; Kubota, Yutaka; Ndung’u, Joseph M.

2018-01-01

Background Confirmatory diagnosis of visceral leishmaniasis (VL), as well as diagnosis of relapses and test of cure, usually requires examination by microscopy of samples collected by invasive means, such as splenic, bone marrow or lymph node aspirates. This causes discomfort to patients, with risks of bleeding and iatrogenic infections, and requires technical expertise. Molecular tests have great potential for diagnosis of VL using peripheral blood, but require well-equipped facilities and trained personnel. More user-friendly, and field-amenable options are therefore needed. One method that could meet these requirements is loop-mediated isothermal amplification (LAMP) using the Loopamp Leishmania Detection Kit, which comes as dried down reagents that can be stored at room temperature, and allows simple visualization of results. Methodology/Principal findings The Loopamp Leishmania Detection Kit (Eiken Chemical Co., Japan), was evaluated in the diagnosis of VL in Sudan. A total of 198 VL suspects were tested by microscopy of lymph node aspirates (the reference test), direct agglutination test-DAT (in house production) and rK28 antigen-based rapid diagnostic test (OnSite Leishmania rK39-Plus, CTK Biotech, USA). LAMP was performed on peripheral blood (whole blood and buffy coat) previously processed by: i) a direct boil and spin method, and ii) the QIAamp DNA Mini Kit (QIAgen). Ninety seven of the VL suspects were confirmed as cases by microscopy of lymph node aspirates. The sensitivity and specificity for each of the tests were: rK28 RDT 98.81% and 100%; DAT 88.10% and 78.22%; LAMP-boil and spin 97.65% and 99.01%; LAMP-QIAgen 100% and 99.01%. Conclusions/Significance Due to its simplicity and high sensitivity, rK28 RDT can be used first in the diagnostic algorithm for primary VL diagnosis, the excellent performance of LAMP using peripheral blood indicates that it can be also included in the algorithm for diagnosis of VL as a simple test when parasitological confirmatory diagnosis is required in settings that are lower than the reference laboratory, avoiding the need for invasive lymph node aspiration. PMID:29444079

Comprehensive Utilization of Biomass Process Residues Rich in Cellulose

NASA Astrophysics Data System (ADS)

Zhong, Mei; Li, Qiang; Yu, Jian; Dong, Li; Wang, Yin; Xu, Guangwen

2010-11-01

This article investigated the method preparing porous material (PM) with VL and SL. Applications of the prepared material was tested in removal aqueous phenol and COD in tarry water and as the catalyst support for selective catalytic reduction (SCR) of NO in flue gas. The results showed that the optimal activation condition in CO2 for the carbonized VL at 800° C was at 875° C for 1 h, which provided large BET surface area and micropore volume. This material exhibited the highest adsorption to aqueous phenol among all the tested materials including a commercial activated carbon made from coconut shell, showing the potential application of the VL-base porous material in wastewater treatment. The study demonstrated also that the vanadium-base selective catalytic reduction (SCR) catalyst supported on the VL-base porous material (V2O5/VL-PM) provided fairly good activity as well SO2 resistance at temperatures round 200° C for SCR of NO. The activation of the carbonized SL material in H2O was better than that in CO2 for developing the pore structure of the porous material. Steam can improve the formation of mesopore than CO2. This was confirmed by the conclusion that higher COD removal rate was occurred on the PM-1 from SL when H2O was used as an activator.

Skeletal muscle plasticity with marathon training in novice runners.

PubMed

Luden, N; Hayes, E; Minchev, K; Louis, E; Raue, U; Conley, T; Trappe, S

2012-10-01

The purpose of this study was to investigate leg muscle adaptation in runners preparing for their first marathon. Soleus and vastus lateralis (VL) biopsies were obtained from six recreational runners (23 ± 1 years, 61 ± 3 kg) before (T1), after 13 weeks of run training (T2), and after 3 weeks of taper and marathon (T3). Single muscle fiber size, contractile function (strength, speed, and power) and oxidative enzyme activity [citrate synthase (CS)] were measured at all three time points, and fiber type distribution was determined before and after the 16-week intervention. Training increased VO(2max) ∼9% (P<0.05). All soleus parameters were unchanged. VL MHC I fiber diameter increased (+8%; P<0.05) from T1 to T2. VL MHC I V(o) (-12%), MHC I power (-22%) and MHC IIa power (-29%) were reduced from T1 to T2 (P<0.05). No changes in VL single fiber contractile properties were observed from T2 to T3. No change was observed in soleus CS activity, whereas VL CS activity increased 66% (P<0.05). Our observations indicate that modest marathon training elicits very specific skeletal muscle adaptations that likely support the ability to perform 42.2 km of continuous running - further strengthening the existing body of evidence for skeletal muscle specificity. © 2011 John Wiley & Sons A/S.

Muscle Activation of Vastus Medialis Oblique and Vastus Lateralis in Sling-Based Exercises in Patients with Patellofemoral Pain Syndrome: A Cross-Over Study

PubMed Central

Chang, Wen-Dien; Huang, Wei-Syuan; Lai, Ping-Tung

2015-01-01

Objectives. To examine what changes are caused in the activity of the vastus medialis oblique (VMO) and vastus lateralis (VL) at the time of sling-based exercises in patients with patellofemoral pain syndrome (PFPS) and compare the muscular activations in patients with PFPS among the sling-based exercises. Methods. This was a cross-over study. Sling-based open and closed kinetic knee extension and hip adduction exercises were designed for PFPS, and electromyography was applied to record maximal voluntary contraction during the exercises. The VMO and VL activations and VMO : VL ratios for the three exercises were analyzed and compared. Results. Thirty male (age = 21.19 ± 0.68 y) and 30 female (age = 21.12 ± 0.74 y) patients with PFPS were recruited. VMO activations during the sling-based open and closed kinetic knee extension exercises were significantly higher (P = 0.04 and P = 0.001) than those during hip adduction exercises and VMO : VL ratio for the sling-based closed kinetic knee extension and hip adduction exercises approximated to 1. Conclusions. The sling-based closed kinetic knee extension exercise produced the highest VMO activation. It also had an appropriate VMO : VL ratio similar to sling-based hip adduction exercise and had beneficial effects on PFPS. PMID:26504480

Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis

PubMed Central

BLASER, Nello; WETTSTEIN, Celina; ESTILL, Janne; VIZCAYA, Luisa SALAZAR; WANDELER, Gilles; EGGER, Matthias; KEISER, Olivia

2014-01-01

Objectives HIV ‘treatment as prevention’ (TasP) describes early treatment of HIV-infected patients intended to reduce viral load (VL) and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and of the relation of HIV transmission risk to VL. Design Systematic review and meta-analysis. Methods We searched PubMed and Embase databases for studies that established a relationship between VL and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analyzed assumptions about the relationship between VL and transmission risk, and between duration of primary infection and transmission risk. Results We found 36 eligible articles, based on six different study populations. Studies consistently found that larger VLs lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40. Conclusions Assumptions and estimates of the relationship between VL and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account. PMID:24691205

Leishmania infantum Induces the Release of sTREM-1 in Visceral Leishmaniasis

PubMed Central

Bomfim, Lays G. S.; Magalhães, Lucas S.; Santos-Filho, Marcello A. A.; Peres, Nalu T. A.; Corrêa, Cristiane B.; Tanajura, Diego M.; Silva, Angela M.; Lipscomb, Michael W.; Borges, Valéria M.; Jesus, Amélia R.; Almeida, Roque P.; de Moura, Tatiana R.

2017-01-01

Visceral leishmaniasis (VL) is a systemic transmissible disease that remains to be a major global health problem. The inflammatory response during VL is characterized by the release of several cytokines and other pro-inflammatory mediators. Triggering Receptor Expressed on Myeloid Cells (TREM) are a group of evolutionarily conserved membrane-bound surface receptors expressed on neutrophils and monocytes. Engagement of TREM-1 directs intracellular signaling events that drive cytokine production, degranulation, and phagocytosis. In certain inflammatory-associated diseases, TREM-1 can also be found as a soluble form (sTREM-1), which can negatively regulate TREM-1 receptor signaling. In these studies, we now find that high levels of circulating sTREM-1 correlate directly with VL disease severity. In particular, high levels of sTREM-1 were observed in non-survivor VL patients. Furthermore, these levels of sTREM-1 positively correlated with liver size and negatively correlated with leukocyte counts and hemoglobin concentration. Moreover, we found that neutrophils exposure in vitro to Leishmania infantum modulates TREM-1, DAP12, and IL-8 gene expression, while also increasing release of sTREM-1. Finally, results revealed that higher sTREM-1 levels are associated with increasing parasite ratio. Taken together, these studies suggest that L. infantum may modulate TREM-1 in neutrophils and high levels of this molecule is associated with severe VL. PMID:29201022

Visibility of Prominences Using the He i D3 Line Filter on the PROBA-3/ASPIICS Coronagraph

NASA Astrophysics Data System (ADS)

Jejčič, S.; Heinzel, P.; Labrosse, N.; Zhukov, A. N.; Bemporad, A.; Fineschi, S.; Gunár, S.

2018-02-01

We determine the optimal width and shape of the narrow-band filter centered on the He i D3 line for prominence and coronal mass ejection (CME) observations with the ASPIICS ( Association of Spacecraft for Polarimetric and Imaging Investigation of the Corona of the Sun) coronagraph onboard the PROBA-3 ( Project for On-board Autonomy) satellite, to be launched in 2020. We analyze He i D3 line intensities for three representative non-local thermal equilibrium prominence models at temperatures 8, 30, and 100 kK computed with a radiative transfer code and the prominence visible-light (VL) emission due to Thomson scattering on the prominence electrons. We compute various useful relations at prominence line-of-sight velocities of 0, 100, and 300 km s-1 for 20 Å wide flat filter and three Gaussian filters with a full-width at half-maximum (FWHM) equal to 5, 10, and 20 Å to show the relative brightness contribution of the He i D3 line and the prominence VL to the visibility in a given narrow-band filter. We also discuss possible signal contamination by Na i D1 and D2 lines, which otherwise may be useful to detect comets. Our results mainly show that i) an optimal narrow-band filter should be flat or somewhere between flat and Gaussian with an FWHM of 20 Å in order to detect fast-moving prominence structures, ii) the maximum emission in the He i D3 line is at 30 kK and the minimal at 100 kK, and iii) the ratio of emission in the He i D3 line to the VL emission can provide a useful diagnostic for the temperature of prominence structures. This ratio is up to 10 for hot prominence structures, up to 100 for cool structures, and up to 1000 for warm structures.

CD4-dependent characteristics of coreceptor use and HIV type 1 V3 sequence in a large population of therapy-naive individuals.

PubMed

Low, Andrew J; Marchant, David; Brumme, Chanson J; Brumme, Zabrina L; Dong, Winnie; Sing, Tobias; Hogg, Robert S; Montaner, Julio S G; Gill, Vikram; Cheung, Peter K; Harrigan, P Richard

2008-02-01

We investigated the associations between coreceptor use, V3 loop sequence, and CD4 count in a cross-sectional analysis of a large cohort of chronically HIV-infected, treatment-naive patients. HIV coreceptor usage was determined in the last pretherapy plasma sample for 977 individuals initiating HAART in British Columbia, Canada using the Monogram Trofile Tropism assay. Relative light unit (RLU) readouts from the Trofile assay, as well as HIV V3 loop sequence data, were examined as a function of baseline CD4 cell count for 953 (97%) samples with both phenotype and genotype data available. Median CCR5 RLUs were high for both R5 and X4-capable samples, while CXCR4 RLUs were orders of magnitude lower for X4 samples (p < 0.001). CCR5 RLUs in R5 samples (N = 799) increased with decreasing CD4 count (p < 0.001), but did not vary with plasma viral load (pVL) (p = 0.74). In X4 samples (N = 178), CCR5 RLUs decreased with decreasing CD4 count (p = 0.046) and decreasing pVL (p = 0.097), while CXCR4 RLUs increased with decreasing pVL (p = 0.0008) but did not vary with CD4 (p = 0.96). RLUs varied with the presence of substitutions at V3 loop positions 11, 25, and 6-8. The prevalence and impact of substitutions at codons 25 and 6-8 were CD4 dependent as was the presence of amino acid mixtures in the V3; substitutions at position 11 were CD4 independent. Assay RLU measures predictably vary with both immunological and virological parameters. The ability to predict X4 virus using genotypic determinants at positions 25 and 6-8 of the V3 loop is CD4 dependent, while position 11 appears to be CD4 independent.

Mobile Text Messaging to Improve Medication Adherence and Viral Load in a Vulnerable Canadian Population Living With Human Immunodeficiency Virus: A Repeated Measures Study

PubMed Central

King, Elizabeth; Kinvig, Karen; Steif, Jonathan; Qiu, Annie Q; Maan, Evelyn J; Albert, Arianne YK; Pick, Neora; Alimenti, Ariane; Kestler, Mary H; Money, Deborah M; Lester, Richard T

2017-01-01

Background Combination antiretroviral therapy (cART) as treatment for human immunodeficiency virus (HIV) infection is effective and available, but poor medication adherence limits benefits, particularly in vulnerable populations. In a Kenyan randomized controlled trial, a weekly text-messaging intervention (WelTel) improved cART adherence and HIV viral load (VL). Despite growing evidence for short message service (SMS) text-message interventions in HIV care, there is a paucity of data utilizing these interventions in marginalized or female cohorts. Objective This study was undertaken to assess whether the standardized WelTel SMS text-message intervention applied to a vulnerable, predominantly female, population improved cART adherence and VL. Methods We conducted a repeated measures study of the WelTel intervention in high-risk HIV-positive persons by measuring change in VL, CD4 count, and self-reported adherence 12 months before and 12 months after the WelTel intervention was introduced. Inclusion criteria included VL ≥200 copies/mL, indication for treatment, and meeting vulnerability criteria. Participants were given a mobile phone with unlimited texting (where required), and weekly check-in text messages were sent for one year from the WelTel computer platform. Clinical data were collected for control and intervention years. Participants were followed by a multidisciplinary team in a clinical setting. Outcomes were assessed using Wilcoxon signed ranks tests for change in CD4 and VL from control year to study end and mixed-effects logistic regressions for change in cART adherence and appointment attendance. A secondary analysis was conducted to assess the effect of response rate on the outcome by modeling final log10 VL by number of responses while controlling for mean log10 VL in the control year. Results Eighty-five participants enrolled in the study, but 5 withdrew (final N=80). Participants were predominantly female (90%, 72/80) with a variety of vulnerabilities. Mean VL decreased from 1098 copies/mL in the control year to 439 copies/mL at study end (P=.004). Adherence to cART significantly improved (OR 1.14, IQR 1.10-1.18; P<.001), whereas appointment attendance decreased slightly with the intervention (OR 0.81, IQR 0.67-0.99; P=.03). A response was received for 46.57% (1753/3764) of messages sent and 9.62% (362/3764) of text messages sent were replied to with a problem. An outcome analysis examining relationship between reply rate and VL did not meet statistical significance (P=.07), but may be worthy of investigating further in a larger study. Conclusions WelTel may be an effective tool for improving cART adherence and reducing VLs among high-risk, vulnerable HIV-positive persons. Trial Registration Clinicaltrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/6qK57zCwv) PMID:28572079

JPRS Report, Science & Technology, USSR: Life Sciences

DTIC Science & Technology

1987-07-16

A.K. Naumova, V.l. Korenev , et al.; GENETIKA, No 1, Jan 86) 53 MICROBIOLOGY Immobilization of Microorganisms on Latex for Production of...pp 166-168 [Article by A.K. Naumova, V.l. Korenev , B.V. Leonov, V.V. Tsibinogin and L.L. Kiselev, Institute of Molecular Biology, USSR Academy of

Visual Literacy (VL) in Teacher Preparation: Measurement to Direction

ERIC Educational Resources Information Center

Farrell, Teresa A.

2015-01-01

An abridgment of the dissertation "Measuring Visual Literacy Ability in Graduate Level Pre-Service Teachers" by Teresa A. Farrell, this quantitative descriptive study was designed to establish a baseline of VL ability within this population using a national pool of graduate level students enrolled in teacher preparation programs.…

MSL/SAM Measurements of Non Condensable Volatiles, Comparison with Viking Lander, and Implications for Seasonal Cycle

NASA Astrophysics Data System (ADS)

Atreya, Sushil; Squyres, Steve; Mahaffy, Paul; Leshin, Laurie; Franz, Heather; Trainer, Melissa; Wong, Michael; McKay, Christopher; Navarro-Gonzalez, Rafael; ScienceTeam, MarsScienceLab

2013-04-01

The first measurements of the composition of the Martian atmosphere above Gale Crater by the Sample Analysis at Mars (SAM) instrument on Curiosity Rover revealed that although the volume mixing ratios (vmr) of the gases are generally similar to those measured by the Viking Lander 2 (VL2) thirty five years ago [2], they are notably different for N2 and 40Ar [1]. SAM finds a vmr of 1.9% each for N2 and Ar, so that N2 is 30% lower while Ar is 21% greater than the corresponding VL2 values, resulting in a 40% lower N2/Ar ratio compared to the VL2 result. The Ar/N ratio is used to assess the degree of mixing between the Martian atmosphere and the internal gas component of Mars meteorites due to the shock of impact ejection [e.g. 3]. The above differences in N2 and 40Ar seem to result either from different instrument characteristics or time variable atmospheric phenomena or both. The VL2 data were taken during northern summer (48°N, Ls=135°), whereas the SAM measurements correspond to the beginning of spring season (4.5°S, Ls=182-190°). Previous observations by Mars Odyssey Gamma Ray Spectrometer over three years have shown that the Ar mixing ratio increased by a factor of 6 over the south polar region in the winter [4]. However, the data are controversial for the equatorial region, ranging from no seasonal change [4] to as much as a 35% change [5]. No significant change was seen between the equator (SAM) and the midlatitude northern summer (VL2), however [4]. Thus the difference between the SAM and VL2 Ar does not appear to be related to different seasons. On the other hand, the vmr's of non-condensable volatiles (NCV), N2, Ar and CO, at any latitude are expected to vary seasonally due to the annual, global CO2 cycle. Diurnal changes are not expected, considering the long lifetimes of NCV's that exceed the martian year [6]. In addition to Ar, seasonal changes have been recorded in CO from ground-based [7] and MRO/CRISM observations [8], but show a much smaller increase of a factor of 2-3 over south polar region in the winter. No data exist on the seasonal behavior of N2. For the first time, SAM will monitor the seasonal behavior of N2 over the two-year prime mission of Curiosity, together with other NCV's, Ar and CO, which will reveal whether they track one another, as expected, and whether the present SAM ratio of N2/Ar =1 holds up over the seasons at roughly one-half the value obtained by Viking. These data will in turn provide crucial constraints to climate evolution and general circulation models of Mars. (www.umich.edu/~atreya). References: [1] Mahaffy P.R. et al., EGU 2013. [2] Owen T. et al., JGR 82, 4635-4639, 1977. [3] Aoudjehane, H.C. et al., Science 338, 785-788, 2012. [4] Sprague A.L. et al., JGR 117, E04005, 2012. [5] Economou T.E. and Pierrehumbert R.T., Abstract 2179.pdf, LPI Conference, 2010. [6] Wong A.S., Atreya S.K., Encrenaz T., JGR.108 (E4), 5026, doi:10.1029/2002JE002003. [7] Encrenaz T. et al., A&A 459, 265-270, 2006. [8] Smith M.D. et al., JGR.114, E00D03, doi:10.1029/2008JE003288, 2009.

[Association between inflammatory markers and microbial translocation in patients with human immunodeficiency virus infection taking antiretroviral treatment].

PubMed

Reus Bañuls, Sergio; Portilla Sogorb, Joaquín; Sanchez-Paya, José; Boix Martínez, Vicente; Giner Oncina, Livia; Frances, Rubén; Such, José; Merino Lucas, Esperanza; Gimeno Gascón, Adelina

2014-01-21

Inflammatory biomarkers are increased in patients with human immunodeficiency virus (HIV) infection. Antiretroviral treatment (ART) improves some parameters but do not normalize them. The aim of this study is to determine those factors (including microbial translocation) associated with higher inflammation in HIV treated patients. Transversal observational study. HIV patients receiving ART with an HIV viral load (VL)<400 copies/mL. Selection of patients: consecutively between November 2011 and January 2012. Main variable: plasma levels of interleukin 6 (IL-6) and tumour necrosis factor α (TNF-α). Main explanatory variable: microbial translocation markers (16S ribosomal DNA and sCD14). Patients with IL-6 or TNF-α levels above percentile 75 (group 1) were compared with the rest of patients (group 2). Odds ratio (OR) were determined. Eighty-one patients were included (73% male, median age 45 years, 48% stage C). Twenty-six percent had chronic hepatitis C. Median CD4 cell was 493/mm(3) and 30% had detectable HIV VL. 16S ribosomal DNA was detected in 21% of patients. Factors associated with the higher levels of inflammatory markers were 16S ribosomal DNA (OR 77, P<.0001), sCD14 levels (P<.0001) and history of cardiovascular disease (OR 15, P<.01). In multivariate analysis, associations remained for 16S ribosomal DNA (OR 62, P<.0001) and previous cardiovascular disease (OR 25, P<.01). In patients with HIV infection receiving treatment, the higher levels of inflammatory markers are associated with microbial translocation and past cardiovascular events. Copyright © 2013 Elsevier España, S.L. All rights reserved.

On the impact of the resolution on the surface and subsurface Eastern Tropical Atlantic warm bias

NASA Astrophysics Data System (ADS)

Martín-Rey, Marta; Lazar, Alban

2016-04-01

The tropical variability has a great importance for the climate of adjacent areas. Its sea surface temperature anomalies (SSTA) affect in particular the Brazilian Nordeste and the Sahelian region, as well as the tropical Pacific or the Euro-Atlantic sector. Nevertheless, the state-of the art climate models exhibits very large systematic errors in reproducing the seasonal cycle and inter-annual variability in the equatorial and coastal Africa upwelling zones (up to several °C for SST). Theses biases exist already, in smaller proportions though, in forced ocean models (several 1/10th of °C), and affect not only the mixed layer but also the whole thermocline. Here, we present an analysis of the impact of horizontal and vertical resolution changes on these biases. Three different DRAKKAR NEMO OGCM simulations have been analysed, associated to the same forcing set (DFS4.4) with different grid resolutions: "REF" for reference (1/4°, 46 vertical levels), "HH" with a finer horizontal grid (1/12°, 46 v.l.) and "HV" with a finer vertical grid (1/4°, 75 v.l.). At the surface, a more realistic seasonal SST cycle is produced in HH in the three upwellings, where the warm bias decreases (by 10% - 20%) during boreal spring and summer. A notable result is that increasing vertical resolution in HV causes a shift (in advance) of the upwelling SST seasonal cycles. In order to better understand these results, we estimate the three upwelling subsurface temperature errors, using various in-situ datasets, and provide thus a three-dimensional view of the biases.

Soil crusts on Mars

NASA Technical Reports Server (NTRS)

Moore, H. J.

1991-01-01

Three distinct soillike materials sampled by the Viking landers (VL) on Mars are (in order of increasing strength): (1) drift; (2) crusty to cloddy; and (3) blocky. Relative strengths of these materials are manifested by footpad penetrations during landing (VL 1), depths of deep holes, motor currents during sampling, sampler backhoe penetrations, comminutor motor currents, impact pits, trench tailings, and successful acquisitions of the coarse fraction (only blocky material). Cementation by S Cl compounds probably contributes to the relative strengths. This is shown where the weight pct. of SO3 + Cl of each material is plotted against their relative strengths. A similar result is obtained using SO3 alone, but not with Cl which is deficient in VL 2 samples.

A Principled Way of Assessing Visualization Literacy.

PubMed

Boy, Jeremy; Rensink, Ronald A; Bertini, Enrico; Fekete, Jean-Daniel

2014-12-01

We describe a method for assessing the visualization literacy (VL) of a user. Assessing how well people understand visualizations has great value for research (e. g., to avoid confounds), for design (e. g., to best determine the capabilities of an audience), for teaching (e. g., to assess the level of new students), and for recruiting (e. g., to assess the level of interviewees). This paper proposes a method for assessing VL based on Item Response Theory. It describes the design and evaluation of two VL tests for line graphs, and presents the extension of the method to bar charts and scatterplots. Finally, it discusses the reimplementation of these tests for fast, effective, and scalable web-based use.

Soluble CD26/CD30 levels in visceral leishmaniasis: markers of disease activity

PubMed Central

Ajdary, S; Riazi-Rad, F; Jafari-Shakib, R; Mohebbali, M

2006-01-01

Leishmania infantum is the causative agent of zoonotic visceral leishmaniasis (VL). If untreated the disease could be fatal; however, in some cases the infection can run a subclinical course. In subclinical infections a Th1-response predominates, while Th2-responses and/or probably Treg cells are related to unfavourable outcome of the disease in active VL. In the present study we determined the levels of soluble (s) CD26 and CD30 co-stimulatory molecules in sera from patients with active VL, asymptomatic individuals and healthy volunteers. Results showed a significant difference in both sCD26 and sCD30 between infected cases and normal individuals (P ≤ 0·001). However, there was no significant difference in sCD26 levels between asymptomatic cases and patients, although the difference was not significant. sCD30 levels were significantly higher in VL patients than asymptomatic cases (P ≤ 0·001). These findings suggest a possible association between sCD26 and sCD30 levels and the clinical manifestation of L. infantum infection. PMID:16792672

Evaluation of Two rK39 Dipstick Tests, Direct Agglutination Test, and Indirect Fluorescent Antibody Test for Diagnosis of Visceral Leishmaniasis in a New Epidemic Site in Highland Ethiopia

PubMed Central

Cañavate, Carmen; Herrero, Merce; Nieto, Javier; Cruz, Israel; Chicharro, Carmen; Aparicio, Pilar; Mulugeta, Abate; Argaw, Daniel; Blackstock, Anna J.; Alvar, Jorge; Bern, Caryn

2011-01-01

We assessed the performance characteristics of two rK39 immunochromatographic tests, a direct agglutination test (DAT), and an indirect immunofluorescent antibody test (IFAT) in the site of a new epidemic of visceral leishmaniasis (VL) in northwestern Ethiopia. The study population was composed of 179 patients with suspected VL and 67 controls. The sensitivities of Kalazar Detect®, DiaMed-IT Leish®, DAT, and IFAT in 35 polymerase chain reaction–confirmed VL cases were 94.3%, 91.4%, 91.4%, and 100%, respectively, and the specificities were 98.5%, 94%, 98.5%, and 98.5%, respectively. In a Bayesian latent class analysis of all 246 specimens, the estimated sensitivities were 90.5%, 89%, 88.8%, and 96% for Kalazar Detect®, DiaMed-IT Leish®, DAT, and IFAT, respectively; DAT showed the highest estimated specificity (97.4%). Both rK39 immunochromatographic tests perform as well as DAT, and are suitable for VL diagnosis in first-level health centers in this area of Ethiopia. PMID:21212210

Cross-Sectional Study to Assess Risk Factors for Leishmaniasis in an Endemic Region in Sri Lanka

PubMed Central

Ranasinghe, Shalindra; Wickremasinghe, Rajitha; Munasinghe, Asoka; Hulangamuwa, Sanjeeva; Sivanantharajah, Sundaramoorthy; Seneviratne, Kamal; Bandara, Samantha; Athauda, Indira; Navaratne, Chaturi; Silva, Ositha; Wackwella, Hasini; Matlashewski, Greg; Wickremasinghe, Renu

2013-01-01

Sri Lanka reports significantly more cutaneous leishmaniasis (CL) cases than visceral leishmaniasis (VL) cases, both of which are caused by Leishmania donovani MON-37. A cross-sectional study conducted in an area with a high prevalence of CL prevalent included 954 participants of an estimated population of 61,674 to estimate the number of CL cases, ascertain whether there is a pool of asymptomatic VL cases, and identify risk factors for transmission. A total of 31 cases of CL were identified, of whom 21 were previously diagnosed and 10 were new cases. Using rK39 rapid diagnostic test to detect antibodies against Leishmania spp., we found that only one person was seropositive but did not have clinical symptoms of CL or VL, which indicated low transmission of VL in this area. χ2 test, independent sample t-test, and multivariate analysis of sociodemographic and spatial distribution of environmental risk factors showed that living near paddy fields is associated with increased risk for transmission of CL (P ≤ 0.01). PMID:23918217

Results of an experimental aerodynamic investigation to obtain static stability and control characteristics of the SSV configurations: The 2A(VL70-000089B) model 1 and 3(VL70-000139B) model 2 orbiter at Mach numbers of 2.5, 3.9 and 4.6 in the NASA LaRC 4 X 4-foot UPWT (OA44)

NASA Technical Reports Server (NTRS)

Esparza, V.; Milam, M. D.

1974-01-01

Investigation of space shuttle orbiter configurations 2A(VL70-000089B) and 3(VL70-000139B) was performed at the Langley Research Center Unitary Plan Wind Tunnel (UPWT) from June 1, 1973, to June 15, 1973, for 60 test hours. The primary test objectives were to obtain stability and control characteristics for Configurations 2A and 3 and an alternate forebody used with Configuration 3. In addition, hinge moments were measured on the elevons and rudder for Configuration 2A only. The configurations were tested at Mach numbers 2.5, 3.9 and 4.6. Pitch runs were made at angles of attack from -4 to 44 deg and sideslip angles from -4 to +6. Static pressures were measured at the fuselage base for use in force data correction.

Effect of 5 weeks horizontal bed rest on human muscle thickness and architecture of weight bearing and non-weight bearing muscles.

PubMed

de Boer, Maarten D; Seynnes, Olivier R; di Prampero, Pietro E; Pisot, Rado; Mekjavić, Igor B; Biolo, Gianni; Narici, Marco V

2008-09-01

The aim of the present study was to investigate the changes in thickness, fascicle length (L (f)) and pennation angle (theta) of the antigravity gastrocnemius medialis (GM) and vastus lateralis (VL) muscles, and the non-antigravity tibialis anterior (TA) and biceps brachii (BB) muscles measured by ultrasonography in ten healthy males (aged 22.3 +/- 2.2 years) in response to 5 weeks of horizontal bed rest (BR). After BR, muscle thickness decreased by 12.2 +/- 8.8% (P < 0.05) and 8.0 +/- 9.1% (P < 0.005) in the GM and VL, respectively. No changes were observed in the TA and BB muscles. L (f) and theta decreased by 4.8 +/- 5.0% (P < 0.05) and 14.3 +/- 6.8% (P < 0.005) in the GM and by 5.9 +/- 5.3% (P < 0.05) and 13.5 +/- 16.2% (P < 0.005) in the VL, again without any changes in the TA and BB muscles. The finding that amongst the antigravity muscles of the lower limbs, the GM deteriorated to a greater extent than the VL is possibly related to the differences in relative load that this muscle normally experiences during daily loading. The dissimilar response in antigravity and non-antigravity muscles to unloading likely reflects differences in loading under normal conditions. The significant structural alterations of the GM and VL muscles highlight the rapid remodelling of muscle architecture occurring with disuse.

Evaluation of viral load thresholds for predicting new WHO Stage 3 and 4 events in HIV-infected children receiving highly active antiretroviral therapy

PubMed Central

Siberry, George K; Harris, D. Robert; Oliveira, Ricardo Hugo; Krauss, Margot R.; Hofer, Cristina B.; Tiraboschi, Adriana Aparecida; Marques, Heloisa; Succi, Regina C.; Abreu, Thalita; Negra, Marinella Della; Mofenson, Lynne M.; Hazra, Rohan

2012-01-01

Background This study evaluated a wide range of viral load (VL) thresholds to identify a cut-point that best predicts new clinical events in children on stable highly-active antiretroviral therapy (HAART). Methods Cox proportional hazards modeling was used to assess the adjusted risk of World Health Organization stage 3 or 4 clinical events (WHO events) as a function of time-varying CD4, VL, and hemoglobin values in a cohort study of Latin American children on HAART ≥ 6 months. Models were fit using different VL cut-points between 400 and 50,000 copies/mL, with model fit evaluated on the basis of the minimum Akaike Information Criterion (AIC) value, a standard model fit statistic. Results Models were based on 67 subjects with WHO events out of 550 subjects on study. The VL cutpoints of > 2600 copies/mL and > 32,000 copies/mL corresponded to the lowest AIC values and were associated with the highest hazard ratios [2.0 (p = 0.015) and 2.1 (p = 0.0058), respectively] for WHO events. Conclusions In HIV-infected Latin American children on stable HAART, two distinct VL thresholds (> 2,600 copies/mL and > 32,000 copies/mL) were identified for predicting children at significantly increased risk of HIV-related clinical illness, after accounting for CD4 level, hemoglobin level, and other significant factors. PMID:22343177

Ventrolateral orbital cortex oxytocin attenuates neuropathic pain through periaqueductal gray opioid receptor.

PubMed

Taati, Mina; Tamaddonfard, Esmaeal

2018-06-01

Oxytocin plays an important role in supraspinal modulation of pain. In the present study, we investigated the effects of ventrolateral orbital cortex (VLOC) microinjection of oxytocin on neuropathic pain after blockade of opioid receptors in this area and ventrolateral periaqueductal gray (vlPAG). Neuropathic pain was induced by complete transcection of preoneal and tibial branches of sciatic nerve. The VLOC and vlPAG were unilaterally (contralateral to the sciatic nerve-injured side) and bilaterally implanted with guide cannulas, respectively. Mechanical paw withdrawal threshold (PWT) was measured using von Frey filaments. Area under curve (AUC) was also calculated. Microinjection of oxytocin (5, 10 and 20 ng/site) into the VLOC increased PWT. Antiallodynia induced by oxytocin (20 ng/site) was inhibited by prior intra-VLOC administration of atosiban (an oxytocin receptor antagonist, 100 ng/site) and naloxone (an opioid receptor antagonist, 500 ng/site). Prior microinjection of naloxone (500 ng/site) into the vlPAG also inhibited antiallodynia induced by intra-VLOC microinjection of oxytocin (20 ng/site). All the VLOC and vlPAG microinjected drugs did not alter locomotor activity. It is concluded that oxytocin and its receptor may be involved in modulation of neuropathic pain at the VLOC level. Opioid receptors of VLOC and vlPAG might be involved in the antiallodynic effect of the VLOC-microinjected oxytocin. Copyright © 2017 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Leukodepletion as a Point-of-Care Method for Monitoring HIV-1 Viral Load in Whole Blood

PubMed Central

Titchmarsh, Logan; Zeh, Clement; Verpoort, Thierry; Allain, Jean-Pierre

2014-01-01

In order to limit the interference of HIV-1 cellular nucleic acids in estimating viral load (VL), the feasibility of leukodepletion of a small whole-blood (WB) volume to eliminate only leukocyte cell content was investigated, using a selection of filters. The efficacy of leukocyte filtration was evaluated by counting, CD45 quantitative PCR, and HIV-1 DNA quantification. Plasma HIV-1 was tested by real-time reverse transcription (RT)-PCR. A specific, miniaturized filter was developed and tested for leukocyte and plasma virus retention, WB sample dilution, and filtration parameters in HIV-1-spiked WB samples. This device proved effective to retain >99.9% of white blood cells in 100 μl of WB without affecting plasma VL. The Samba sample preparation chemistry was adapted to use a leukodepleted WB sample for VL monitoring using the point-of-care Samba-1 semiautomated system. The clinical performance of the assay was evaluated by testing 207 consecutive venous EDTA WB samples from HIV-1-infected patients attending a CD4 testing clinic. Most patients were on antiretroviral treatment (ART), but their VL status was unknown. Compared to the Roche Cobas AmpliPrep/Cobas TaqMan HIV-1 test, the new Samba assay had a concordance of 96.5%. The use of the Samba system with a VL test for WB might contribute to HIV-1 ART management and reduce loss-to-follow-up rates in resource-limited settings. PMID:25428162

Intervarietal variations in various oxidative stress markers and antioxidant potential of finger millet (Eleusine coracana) subjected to drought stress.

PubMed

Bartwal, Arti; Pande, Anjali; Sharma, Priyadarshini; Arora, Sandeep

2016-07-01

Drought is a major form of abiotic stress leading to lower crop productivity. Experiment was carried out for selecting the most tolerant genotype among six different genotypes of finger millet under drought stress. Seeds of six finger millet genotypes were sown in pots and grown for 35 days. After this period, drought was induced by withholding watering for stressed plants while control plants were watered regularly for comparison. Among all six different varieties of finger millet screened (PR202, PES400, PRM6107, VL283, VL328 and VL149) under varying intensities of drought stress,PRM6107 and PR202 showed highest stress tolerance by limiting excessive accumulation of reactive oxygen species (ROS) through activation of ROS scavenging antioxidative enzymes. A 200% increase in ascorbate content was recorded in PRM6107 and PR202, while in other varieties limited increase in ascorbate content was observed. Maximum decrease in chlorophyll content was observed in VL328 (83%) while least drop was observed in VL149 (65%). Relative water content indicated that PR202 was able to retain maximum water content under stress, as it recorded least drop in relative water content (55%), contributing to its better survival under stress. In conclusion finger millet genotypes PRM6107 and PR202 possessed maximum drought tolerance potential and thus may be used for allele mining of drought tolerant genes, which can further be employed for the development of more drought stress tolerant staple crops using biotechnological approach.

Minimal Invasive Approach for Lips Venous Lake Treatment by 980 nm Diode Laser with Emphasis on the Aesthetic Results. А Clinical Series.

PubMed

Voynov, Parvan P; Tomov, Georgi T; Mateva, Nonka G

2016-01-01

A venous lake (VL) is a vascular lesion with common occurrence in many patients, manifested as a dark blue-to-violet compressible papule, caused by dilation of venules. The main reasons for the treatment of VL are aesthetic. The haemorrhaging episodes or impairment of oral normal functions are also under considerations. Treatment of lip VL includes surgical excision, selective photocoagulation, cryotherapy, sclerotherapy and electrodessication. The high-intensity diode laser is an option. The 980 nm diode laser is selectively absorbed by haemoglobin and selectively destroys blood vessels, minimising injury to the surrounding healthy skin. The purpose of this study was to evaluate the effectiveness of diode laser in the treatment of VL lesions with the accent on the postoperative defects and aesthetic results. 35 patients aged 37 to 71 were included in this study. A 980 nm diode laser was used in noncontact mode, under local anaesthesia in continuous wave (2-3W, for 20-60s). All patients received only one procedure. Healing process was completed within 2 to 4 weeks after treatment with no scarring. None of the typical adverse effects were observed in the process of healing. Selective photocoagulation is an effective method for treatment of VL. Lower morbidity, minimal patient discomfort and satisfactory functional and aesthetic results are favourable for patients. To optimise the results and to reduce the adverse effects, basic knowledge on lasers and laser-tissue interactions is requisite.

Predicting HIV RNA virologic outcome at 52-weeks follow-up in antiretroviral clinical trials. The INCAS and AVANTI Study Groups.

PubMed

Raboud, J M; Rae, S; Montaner, J S

2000-08-15

To determine the ability of intermediate plasma viral load (pVL) measurements to predict virologic outcome at 52 weeks of follow-up in clinical trials of antiretroviral therapy. Individual patient data from three clinical trials (INCAS, AVANTI-2 and AVANTI-3) were combined into a single database. Virologic success was defined to be plasma viral load (pVL) <500 copies/ml at week 52. The sensitivity and specificity of intermediate pVL measurements below the limit of detection, 100, 500, 1000, and 5000 copies/ml to predict virologic success were calculated. The sensitivity, specificity, and positive and negative predictive values of a pVL measurement <1000 copies/ml at week 16 to predict virologic outcome at week 52 were 74%, 74%, 48%, and 90%, respectively, for patients on double therapy. For patients on triple therapy, the sensitivity, specificity, and positive and negative predictive values of a pVL measurement <50 copies/ml at week 16 to predict virologic outcome were 68%, 68%, 80%, and 47%, respectively. For patients receiving double therapy, a poor virologic result at an intermediate week of follow-up is a strong indicator of virologic failure at 52 weeks whereas intermediate virologic success is no guarantee of success at 1 year. For patients on triple therapy, disappointing intermediate results do not preclude virologic success at 1 year and intermediate successes are more likely to be sustained.

A Digital Repository and Execution Platform for Interactive Scholarly Publications in Neuroscience.

PubMed

Hodge, Victoria; Jessop, Mark; Fletcher, Martyn; Weeks, Michael; Turner, Aaron; Jackson, Tom; Ingram, Colin; Smith, Leslie; Austin, Jim

2016-01-01

The CARMEN Virtual Laboratory (VL) is a cloud-based platform which allows neuroscientists to store, share, develop, execute, reproduce and publicise their work. This paper describes new functionality in the CARMEN VL: an interactive publications repository. This new facility allows users to link data and software to publications. This enables other users to examine data and software associated with the publication and execute the associated software within the VL using the same data as the authors used in the publication. The cloud-based architecture and SaaS (Software as a Service) framework allows vast data sets to be uploaded and analysed using software services. Thus, this new interactive publications facility allows others to build on research results through reuse. This aligns with recent developments by funding agencies, institutions, and publishers with a move to open access research. Open access provides reproducibility and verification of research resources and results. Publications and their associated data and software will be assured of long-term preservation and curation in the repository. Further, analysing research data and the evaluations described in publications frequently requires a number of execution stages many of which are iterative. The VL provides a scientific workflow environment to combine software services into a processing tree. These workflows can also be associated with publications and executed by users. The VL also provides a secure environment where users can decide the access rights for each resource to ensure copyright and privacy restrictions are met.

The Endocrine Society guidelines: when the confidence cart goes before the evidence horse.

PubMed

Brito, Juan P; Domecq, Juan P; Murad, Mohammed H; Guyatt, Gordon H; Montori, Victor M

2013-08-01

In 2005, the Endocrine Society (TES) adopted the GRADE system of developing clinical practice guidelines. Grading of Recommendations, Assessment, Development, and Evaluation working group guidance suggests that strong recommendations based on low or very low (L/VL) confidence may often be inappropriate, and has offered a taxonomy of paradigmatic situations in which strong recommendations based on L/VL confidence estimates may be appropriate. We sought to characterize strong recommendations of TES based on L/VL confidence evidence. We identified all strong recommendations based on L/VL confidence evidence published in TES guidelines between 2005 and 2011. We identified those consistent with one of the paradigmatic situations in the taxonomy. Two hundred six of 357 (58%) of the recommendations of TES were strong; of these, 121 (59%) were based on L/VL confidence evidence. Of these 121, 35 (29%) were consistent with one of the paradigmatic situations. The most common situation (13, 11%) was of a strong recommendation against the intervention because of low confidence evidence for benefit and high confidence evidence for harm. The remaining 86 (71%) comprised 43 (36%) "best practice" statements for which sensible alternatives do not exist; 5 (4%) in which recommendations were for "additional research"; 5 (4%) in which greater confidence in the estimates was warranted; and 33 (27%) for which we could not find a compelling explanation for the incongruence. Guideline panels should beware of formulating strong recommendations when confidence in estimates is low. Our taxonomy when such recommendations are appropriate may be helpful.

Evaluation of chemical spraying and environmental management efficacy in areas with minor previous application of integrated control actions for visceral leishmaniasis in Brazil.

PubMed

Lara-Silva, Fabiana de Oliveira; Michalsky, Érika Monteiro; Fortes-Dias, Consuelo Latorre; Fiuza, Vanessa de Oliveira Pires; Dias, Edelberto Santos

2017-12-01

Leishmaniases are vector-borne diseases that are transmitted to humans through the bite of Leishmania-infected phlebotomine sand flies (Diptera:Psychodidae). The main proved vector of visceral leishmaniais (VL) in the New World - Lutzomyia longipalpis - is well-adapted to urban areas and has extensive distribution within the five geographical regions of Brazil. Integrated public health actions directed for the vector, domestic reservoir and humans for the control of VL are preferentially applied in municipalities with higher epidemiological risk of transmission. In this study, we evaluated the individual impact of two main vector control actions - chemical spraying and environmental management - in two districts with no reported cases of human VL. Although belonging to an endemic municipality for VL in Brazil, the integrated control actions have not been applied in these districts due to the absence of human cases. The number of L. longipalpis captured in a two-year period was used as indicator of the population density of the vector. After chemical spraying a tendency of reduction in L. longipalpis was observed but with no statistical significance compared to the control. Environmental management was effective in that reduction and it may help in the control of VL by reducing the population density of the vector in a preventive and more permanent action, perhaps associated with chemical spraying. Copyright © 2017 Elsevier B.V. All rights reserved.

HIV status and viral loads among men testing positive for rectal gonorrhoea and chlamydia, Maricopa County, Arizona, USA, 2011-2013.

PubMed

Taylor, M M; Newman, D R; Gonzalez, J; Skinner, J; Khurana, R; Mickey, T

2015-04-01

Men diagnosed with rectal gonorrhoea (GC) and chlamydia (CT) have engaged in unprotected receptive anal intercourse. We reviewed the HIV positivity and HIV viral loads (VLs) of men who had rectal GC and CT testing to evaluate potential HIV acquisition and transmission risk. Rectal GC and CT testing data for men attending the Maricopa County STD clinic during the period from 1 October 2011 to 30 September 2013 were cross-matched with HIV surveillance data to identify men with HIV coinfection. We examined HIV status, HIV diagnosis date, and the values of VL collected nearest to the date of reported rectal infection. During the 2-year time period, 1591 men were tested for rectal GC and CT. Of the men tested, 506 (31.8%) were positive for GC (13.2%), CT (12.2%) or both (6.4%); 119 (23.5%) of those with rectal GC or CT were coinfected with HIV. Among the 275 men with HIV at the time of rectal testing, 54 (19.6%) had no reported VL; 63 (22.9%) had an undetectable VL (< 20 HIV-1 RNA copies/mL) and 158 (57.4%) had a detectable VL collected within 1 year of rectal diagnosis. Mean VL was higher among HIV and rectal GC/CT coinfected cases compared with men with HIV alone (174 316 vs. 57 717 copies/mL, respectively; P = 0.04). Approximately one-third of men undergoing rectal testing were positive for GC or CT and one-quarter of men with rectal GC or CT also had HIV infection. Of the HIV-infected men tested for rectal GC or CT, more than half had a detectable VL collected near the time of rectal testing, demonstrating a risk for transmitting HIV. © 2014 British HIV Association.

Specimen origin, type and testing laboratory are linked to longer turnaround times for HIV viral load testing in Malawi

PubMed Central

Chipungu, Geoffrey; Kim, Andrea A.; Sarr, Abdoulaye; Ali, Hammad; Mwenda, Reuben; Nkengasong, John N.; Singer, Daniel

2017-01-01

Background Efforts to reach UNAIDS’ treatment and viral suppression targets have increased demand for viral load (VL) testing and strained existing laboratory networks, affecting turnaround time. Longer VL turnaround times delay both initiation of formal adherence counseling and switches to second-line therapy for persons failing treatment and contribute to poorer health outcomes. Methods We utilized descriptive statistics and logistic regression to analyze VL testing data collected in Malawi between January 2013 and March 2016. The primary outcomes assessed were greater-than-median pretest phase turnaround time (days elapsed from specimen collection to receipt at the laboratory) and greater-than-median test phase turnaround time (days from receipt to testing). Results The median number of days between specimen collection and testing increased 3-fold between 2013 (8 days, interquartile range (IQR) = 6–16) and 2015 (24, IQR = 13–39) (p<0.001). Multivariable analysis indicated that the odds of longer pretest phase turnaround time were significantly higher for specimen collection districts without laboratories capable of conducting viral load tests (adjusted odds ratio (aOR) = 5.16; 95% confidence interval (CI) = 5.04–5.27) as well as for Malawi’s Northern and Southern regions. Longer test phase turnaround time was significantly associated with use of dried blood spots instead of plasma (aOR = 2.30; 95% CI = 2.23–2.37) and for certain testing months and testing laboratories. Conclusion Increased turnaround time for VL testing appeared to be driven in part by categorical factors specific to the phase of turnaround time assessed. Given the implications of longer turnaround time and the global effort to scale up VL testing, addressing these factors via increasing efficiencies, improving quality management systems and generally strengthening the VL spectrum should be considered essential components of controlling the HIV epidemic. PMID:28235013

First comparative transcriptomic analysis of wild adult male and female Lutzomyia longipalpis, vector of visceral leishmaniasis.

PubMed

McCarthy, Christina B; Santini, María Soledad; Pimenta, Paulo F P; Diambra, Luis A

2013-01-01

Leishmaniasis is a vector-borne disease with a complex epidemiology and ecology. Visceral leishmaniasis (VL) is its most severe clinical form as it results in death if not treated. In Latin America VL is caused by the protist parasite Leishmania infantum (syn. chagasi) and transmitted by Lutzomyia longipalpis. This phlebotomine sand fly is only found in the New World, from Mexico to Argentina. However, due to deforestation, migration and urbanisation, among others, VL in Latin America is undergoing an evident geographic expansion as well as dramatic changes in its transmission patterns. In this context, the first VL outbreak was recently reported in Argentina, which has already caused 7 deaths and 83 reported cases. Insect vector transcriptomic analyses enable the identification of molecules involved in the insect's biology and vector-parasite interaction. Previous studies on laboratory reared Lu. longipalpis have provided a descriptive repertoire of gene expression in the whole insect, midgut, salivary gland and male reproductive organs. Nevertheless, the study of wild specimens would contribute a unique insight into the development of novel bioinsecticides. Given the recent VL outbreak in Argentina and the compelling need to develop appropriate control strategies, this study focused on wild male and female Lu. longipalpis from an Argentine endemic (Posadas, Misiones) and a Brazilian non-endemic (Lapinha Cave, Minas Gerais) VL location. In this study, total RNA was extracted from the sand flies, submitted to sequence independent amplification and high-throughput pyrosequencing. This is the first time an unbiased and comprehensive transcriptomic approach has been used to analyse an infectious disease vector in its natural environment. Transcripts identified in the sand flies showed characteristic profiles which correlated with the environment of origin and with taxa previously identified in these same specimens. Among these, various genes represented putative targets for vector control via RNA interference (RNAi).

First Comparative Transcriptomic Analysis of Wild Adult Male and Female Lutzomyia longipalpis, Vector of Visceral Leishmaniasis

PubMed Central

McCarthy, Christina B.; Santini, María Soledad; Pimenta, Paulo F. P.; Diambra, Luis A.

2013-01-01

Leishmaniasis is a vector-borne disease with a complex epidemiology and ecology. Visceral leishmaniasis (VL) is its most severe clinical form as it results in death if not treated. In Latin America VL is caused by the protist parasite Leishmania infantum (syn. chagasi) and transmitted by Lutzomyia longipalpis. This phlebotomine sand fly is only found in the New World, from Mexico to Argentina. However, due to deforestation, migration and urbanisation, among others, VL in Latin America is undergoing an evident geographic expansion as well as dramatic changes in its transmission patterns. In this context, the first VL outbreak was recently reported in Argentina, which has already caused 7 deaths and 83 reported cases. Insect vector transcriptomic analyses enable the identification of molecules involved in the insect's biology and vector-parasite interaction. Previous studies on laboratory reared Lu. longipalpis have provided a descriptive repertoire of gene expression in the whole insect, midgut, salivary gland and male reproductive organs. Nevertheless, the study of wild specimens would contribute a unique insight into the development of novel bioinsecticides. Given the recent VL outbreak in Argentina and the compelling need to develop appropriate control strategies, this study focused on wild male and female Lu. longipalpis from an Argentine endemic (Posadas, Misiones) and a Brazilian non-endemic (Lapinha Cave, Minas Gerais) VL location. In this study, total RNA was extracted from the sand flies, submitted to sequence independent amplification and high-throughput pyrosequencing. This is the first time an unbiased and comprehensive transcriptomic approach has been used to analyse an infectious disease vector in its natural environment. Transcripts identified in the sand flies showed characteristic profiles which correlated with the environment of origin and with taxa previously identified in these same specimens. Among these, various genes represented putative targets for vector control via RNA interference (RNAi). PMID:23554910

Monitoring virologic responses to antiretroviral therapy in HIV-infected adults in Kenya: evaluation of a low-cost viral load assay.

PubMed

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S; Valentine, Fred

2009-08-28

A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log(10) copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of > or =400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure.

Monitoring Virologic Responses to Antiretroviral Therapy in HIV-Infected Adults in Kenya: Evaluation of a Low-Cost Viral Load Assay

PubMed Central

Sivapalasingam, Sumathi; Wangechi, Beatrice; Marshed, Fatuma; Laverty, Maura; Essajee, Shaffiq; Holzman, Robert S.; Valentine, Fred

2009-01-01

Background A key advantage of monitoring HIV viral load (VL) in persons receiving antiretroviral therapy (ART) is the ability to detect virologic failure before clinical deterioration or resistance occurs. Detection of virologic failure will help clarify the need for enhanced adherence counseling or a change to second- line therapy. Low-cost, locally performable alternates to expensive VL assays are needed where resources are limited. Methodology/Principal Findings We monitored the response to 48-week ART in 100 treatment-naïve Kenyan adults using a low-cost VL measurement, the Cavidi reverse transcriptase (RT) assay and gold-standard assays, Roche RNA PCR and Bayer Versant HIV-1 RNA (bDNA) assays. In Altman-Bland plots, the mean difference in viral loads between the three assays was small (<0.5 log10 copies/mL). However, the limits of agreement between the methods exceeded the biologically relevant change of 0.5 log copies/ml. Therefore, the RT assay cannot be used interchangeably with the other assays to monitor individual patients. The RT assay was 100% sensitive in detecting viral loads of ≥400 copies/ml compared to gold-standard assays. After 24 weeks of treatment, viral load measured by the RT assay was undetectable in 95% of 65 patients with undetectable RNA PCR VL (<400 copies/ml), 90% of 67 patients with undetectable bDNA VL, and 96% of 57 patients with undetectable VL in both RNA PCR and bDNA assays. The negative predictive value of the RT assay was 100% compared to either assay; the positive predictive value was 86% compared to RNA PCR and 70% compared to bDNA. Conclusion The RT assay compared well with gold standard assays. Our study highlights the importance of not interchanging viral load assays when monitoring an individual patient. Furthermore, the RT assay may be limited by low positive predictive values when used in populations with low prevalence of virologic failure. PMID:19714253

Clinical comparison of branched DNA and reverse transcriptase-PCR and nucleic acid sequence-based amplification assay for the quantitation of circulating recombinant form_BC HIV-1 RNA in plasma.

PubMed

Pan, Pinliang; Tao, Xiaoxia; Zhang, Qi; Xing, Wenge; Sun, Xianguang; Pei, Lijian; Jiang, Yan

2007-12-01

To investigate the correlation between three viral load assays for circulating recombinant form (CRF)_BC. Recent studies in HIV-1 molecular epidemiology, reveals that CRF_BC is the dominant subtype of HIV-1 virus in mainland China, representing over 45% of the HIV-1 infected population. The performances of nucleic acid sequence-based amplification (NASBA), branched DNA (bDNA) and reverse transcriptase polymerase chain reaction (RT-PCR) were compared for the HIV-1 viral load detection and quantitation of CRF_BC in China. Sixteen HIV-1 positive and three HIV-1 negative samples were collected. Sequencing of the positive samples in the gp41 region was conducted. The HIV-1 viral load values were determined using bDNA, RT-PCR and NASBA assays. Deming regression analysis with SPSS 12.0 (SPS Inc., Chicago, Illinois, USA) was performed for data analysis. Sequencing and phylogenetic analysis of env gene (gp41) region of the 16 HIV-1 positive clinical specimens from Guizhou Province in southwest China revealed the dominance of the subtype CRF_BC in that region. A good correlation of their viral load values was observed among three assays. Pearson's correlation between RT-PCR and bDNA is 0.969, Lg(VL)RT-PCR = 0.969 * Lg(VL)bDNA + 0.55; Pearson's correlation between RT-PCR and NASBA is 0.968, Lg(VL)RT-PCR = 0.968 * Lg(VL)NASBA + 0.937; Pearson's correlation between NASBA and bDNA is 0.980, Lg(VL)NASBA = 0.980 * Lg(VL)bDNA - 0.318. When testing with 3 different assays, RT-PCR, bDNA and NASBA, the group of 16 HIV-1 positive samples showed the viral load value was highest for RT-PCR, followed by bDNA then NASBA, which is consistent with the former results in subtype B. The three viral load assays are highly correlative for CRF_BC in China.

Monitoring the quality of HIV-1 viral load testing through a proficiency testing program using dried tube specimens in resource-limited settings.

PubMed

Nguyen, Shon; Ramos, Artur; Chang, Joy; Li, Bin; Shanmugam, Vedapuri; Boeras, Debrah; Nkengasong, John N; Yang, Chunfu; Ellenberger, Dennis

2015-04-01

HIV-1 viral load (VL) levels are used for monitoring disease progression and antiretroviral therapy outcomes in HIV-infected patients. To assess the performance of laboratories conducting HIV-1 VL testing in resource-limited settings, the U.S. Centers for Disease Control and Prevention implemented a voluntary, free-of-charge, external quality assurance program using dried tube specimens (DTSs). Between 2010 and 2012, DTS proficiency testing (PT) panels consisting of 5 specimens were distributed at ambient temperature to participants. The results from the participants (n≥6) using the same assay were grouped, analyzed, and graded as acceptable within a group mean±3 standard deviations. Mean proficiency scores were calculated by dividing the combined PT scores by the number of testing cycles using a linear regression model. Between 2010 and 2012, the number of participants enrolled increased from 32 in 16 countries to 114 in 44 countries. A total of 78.2% of the participants reported results using 10 different VL assays. The rates of reporting of acceptable results by the participants were 96.6% for the Abbott assay, 96.3% for the Roche Cobas assay, 94.5% for the Roche Amplicor assay, 93.0% for the Biocentric assay, and 89.3% for the NucliSens assay. The overall mean proficiency scores improved over time (P=0.024). DTSs are a good alternative specimen type to plasma specimens for VL PT programs, as they do not require cold chain transportation and can be used on PCR-based assays. Our data suggest that the CDC HIV-1 VL PT program using DTSs positively impacts the testing performance of the participants, which might translate into better and more accurate VL testing services for patients. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Knee and Hip Joint Kinematics Predict Quadriceps and Hamstrings Neuromuscular Activation Patterns in Drop Jump Landings.

PubMed

Malfait, Bart; Dingenen, Bart; Smeets, Annemie; Staes, Filip; Pataky, Todd; Robinson, Mark A; Vanrenterghem, Jos; Verschueren, Sabine

2016-01-01

The purpose was to assess if variation in sagittal plane landing kinematics is associated with variation in neuromuscular activation patterns of the quadriceps-hamstrings muscle groups during drop vertical jumps (DVJ). Fifty female athletes performed three DVJ. The relationship between peak knee and hip flexion angles and the amplitude of four EMG vectors was investigated with trajectory-level canonical correlation analyses over the entire time period of the landing phase. EMG vectors consisted of the {vastus medialis(VM),vastus lateralis(VL)}, {vastus medialis(VM),hamstring medialis(HM)}, {hamstring medialis(HM),hamstring lateralis(HL)} and the {vastus lateralis(VL),hamstring lateralis(HL)}. To estimate the contribution of each individual muscle, linear regressions were also conducted using one-dimensional statistical parametric mapping. The peak knee flexion angle was significantly positively associated with the amplitudes of the {VM,HM} and {HM,HL} during the preparatory and initial contact phase and with the {VL,HL} vector during the peak loading phase (p<0.05). Small peak knee flexion angles were significantly associated with higher HM amplitudes during the preparatory and initial contact phase (p<0.001). The amplitudes of the {VM,VL} and {VL,HL} were significantly positively associated with the peak hip flexion angle during the peak loading phase (p<0.05). Small peak hip flexion angles were significantly associated with higher VL amplitudes during the peak loading phase (p = 0.001). Higher external knee abduction and flexion moments were found in participants landing with less flexed knee and hip joints (p<0.001). This study demonstrated clear associations between neuromuscular activation patterns and landing kinematics in the sagittal plane during specific parts of the landing. These findings have indicated that an erect landing pattern, characterized by less hip and knee flexion, was significantly associated with an increased medial and posterior neuromuscular activation (dominant hamstrings medialis activity) during the preparatory and initial contact phase and an increased lateral neuromuscular activation (dominant vastus lateralis activity) during the peak loading phase.

Interferon-γ–Inducible Protein 10 (IP-10) as a Screening Tool to Optimize Human Immunodeficiency Virus RNA Monitoring in Resource-Limited Settings

PubMed Central

Pastor, Lucía; Casellas, Aina; Carrillo, Jorge; Maculuve, Sonia; Jairoce, Chenjerai; Paredes, Roger; Blanco, Julià; Naniche, Denise

2017-01-01

Abstract Background Achieving effective antiretroviral treatment (ART) monitoring is a key determinant to ensure viral suppression and reach the UNAIDS 90-90-90 targets. The gold standard for detecting virological failure is plasma human immunodeficiency virus (HIV) RNA (viral load [VL]) testing; however, its availability is very limited in low-income countries due to cost and operational constraints. Methods HIV-1–infected adults on first-line ART attending routine visits at the Manhiça District Hospital, Mozambique, were previously evaluated for virologic failure. Plasma levels of interferon-γ–inducible protein 10 (IP-10) were quantified by enzyme-linked immunosorbent assay. Logistic regression was used to build an IP-10–based model able to identify individuals with VL >150 copies/mL. From the 316 individuals analyzed, 253 (80%) were used for model training and 63 (20%) for validation. Receiver operating characteristic curves were employed to evaluate model prediction. Results From the individuals included in the training set, 34% had detectable VL. Mean age was 41 years, 70% were females, and median time on ART was 3.4 years. IP-10 levels were significantly higher in subjects with detectable VL (108.2 pg/mL) as compared to those with undetectable VL (38.0 pg/mL) (P < .0001, U test). IP-10 univariate model demonstrated high classification performance (area under the curve = 0.85 [95% confidence interval {CI}, .80–.90]). Using a cutoff value of IP-10 ≥44.2 pg/mL, the model identified detectable VL with 91.9% sensitivity (95% CI, 83.9%–96.7%) and 59.9% specificity (95% CI, 52.0%–67.4%), values confirmed in the validation set. Conclusions IP-10 is an accurate biomarker to screen individuals on ART for detectable viremia. Further studies should evaluate the benefits of IP-10 as a triage approach to monitor ART in resource-limited settings. PMID:29020145

Analysis of the Wbt Vertex from the Measurement of Triple Differential Angular Decay Rates of Single Top Quarks Produced in the T-Channel at □S =8 TeV with ATLAS Detector

NASA Astrophysics Data System (ADS)

Su, Jun

The electroweak production and subsequent decay of single top quarks is determined by the properties of the Wtb vertex, which can be described by the complex parameters of an effective Lagrangian. An analysis of angular distributions of the decay products of single top quarks produced in the t-channel constrains these parameters simultaneously. The thesis presents an analysis using 20.2 fb-1 of proton-proton collision data at a centre-of-mass energy of 8 TeV collected with the ATLAS detector at the LHC. The fraction ƒ1 of decays containing transversely polarised W bosons is measured to be ƒ1 = 0:296 +0:048 -0:051 (stat. + syst.). The phase delta_ between amplitudes for transversely and longitudinally polarised W bosons recoiling against left-handed b quarks, is measured to be delta_ = 0:002pi+0:016pi -0:017pi (stat. + syst.), giving no indication of CP violation. The fraction of longitudinal to transverse W bosons accompanied by right-handed b-quarks are also constrained at 95% C.L. to ƒ+1 < 0:118 and ƒ+ 0 < 0:085. Based on these measurements limits are placed at 95% C.L. on the ratio of the complex coupling parameters gR and VL such that Re [gR =VL] epsilon [-0:122; 0:168] and Im [gR=VL] epsilon [-0:066; 0:059]. Constraints are also placed on the magnitudes of the ratios | VL/VL|, and |g L/VL|. Finally the polarisation of single top quarks in the t-channel is constrained to be P > 0:718 (95% C.L.). None of the above measurements make assumptions on the value of any of the other parameters or couplings and all of them are in agreement with the Standard Model.

Comparison of the Pentax AirwayScope and McGrath MAC videolaryngoscope for endotracheal intubation in patients with a normal airway

PubMed Central

Lee, Jiyoung; Kwak, Hyun Jeong; Lee, Ji Yeon; Chang, Min Young; Lee, Sook Young; Kim, Jong Yeop

2017-01-01

Abstract Various videolaryngoscopes (VLs) have been developed to provide a better laryngeal view and facilitate difficult intubations. The goal of this study was to compare 2 VLs, the Pentax AWS and the McGrath VL, with respect to intubation time and ease of intubation. One hundred forty patients aged 19 to 65 years (American Society of Anesthesiologists classification I or II), who required tracheal intubation for elective surgery, were randomly assigned to 1 of the 2 groups: the Pentax AWS (n = 70) or the McGrath VL (n = 70). The primary outcome was time to intubation (TTI) measured by a blind observer. The intubation difficulty scale (IDS), percentage of glottic opening (POGO) scale, glottic grade, use of optimal external laryngeal manipulation (OELM), and ease of intubation were also recorded. The Pentax AWS provided a better laryngeal view than the McGrath VL with respect to the Cormack-Lehane (CL) glottic grade (1/2a/2b) (63/7/0 vs 43/24/3, P < .001) and the POGO scale (median [interquartile range, IQR]) (100 [100–100] vs 100 [80–100], P < .001). The IDS was significantly lower in the Pentax AWS group compared with the McGrath VL group (median [IQR]) (0 [0–0] vs 0 [0–1], P < .001). However, the TTI was similar in both the Pentax AWS and McGrath VL groups (median [IQR]) (30 [27–34] vs 32 [27–35] seconds, P = .440). OELM and ease of intubation were also similar between the 2 groups. The Pentax AWS offered a superior laryngeal view compared with the McGrath VL. There was no significant difference in either the intubation time or ease of intubation using these 2 devices in patients with normal airways. PMID:29145308

Effectiveness Study of Paromomycin IM Injection (PMIM) for the Treatment of Visceral Leishmaniasis (VL) in Bangladesh.

PubMed

Jamil, Kazi M; Haque, Rashidul; Rahman, Ridwanur; Faiz, M Abul; Bhuiyan, Abu Toha Md Rezwanul Haque; Kumar, Amresh; Hassan, Syed Misbah; Kelly, Heather; Dhalaria, Pritu; Kochhar, Sonali; Desjeux, Philippe; Bhuiyan, Mohammad A A; Khan, Mohammed M; Ghosh, Raj Shankar

2015-01-01

This study was conducted in Bangladeshi patients in an outpatient setting to support registration of Paromomycin Intramuscular Injection (PMIM) as a low-cost treatment option in Bangladesh. This Phase IIIb, open-label, multi-center, single-arm trial assessed the efficacy and safety of PMIM administered at 11 mg/kg (paromomycin base) intramuscularly once daily for 21 consecutive days to children and adults with VL in a rural outpatient setting in Bangladesh. Patients ≥5 and ≤55 years were eligible if they had signs and symptoms of VL (intermittent fever, weight loss/decreased appetite, and enlarged spleen), positive rK39 test, and were living in VL-endemic areas. Compliance was the percentage of enrolled patients who received 21 daily injections over no more than 22 days. Efficacy was evaluated by initial clinical response, defined as resolution of fever and reduction of splenomegaly at end of treatment, and final clinical response, defined as the absence of new clinical signs and symptoms of VL 6 months after end of treatment. Safety was assessed by evaluation of adverse events. A total of 120 subjects (49% pediatric) were enrolled. Treatment compliance was 98.3%. Initial clinical response in the Intent-to-Treat population was 98.3%, and final clinical response 6 months after end of treatment was 94.2%. Of the 119 subjects who received ≥1 dose of PMIM, 28.6% reported at least one adverse event. Injection site pain was the most commonly reported adverse event. Reversible renal impairment and/or hearing loss were reported in 2 subjects. PMIM was an effective and safe treatment for VL in Bangladesh. The short treatment duration and lower cost of PMIM compared with other treatment options may make this drug a preferred treatment to be investigated as part of a combination therapy regimen. This study supports the registration of PMIM for use in government health facilities in Bangladesh. ClinicalTrials.gov identifier: NCT01328457.

Effects on interaction kinetics of mutations at the VH-VL interface of Fabs depend on the structural context.

PubMed

Khalifa, M B; Weidenhaupt, M; Choulier, L; Chatellier, J; Rauffer-Bruyère, N; Altschuh, D; Vernet, T

2000-01-01

The influence of framework residues belonging to VH and VL modules of antibody molecules on antigen binding remains poorly understood. To investigate the functional role of such residues, we have performed semi-conservative amino acid replacements at the VH-VL interface. This work was carried out with (i) variants of the same antibody and (ii) with antibodies of different specificities (Fab fragments 145P and 1F1h), in order to check if functional effects are additive and/or similar for the two antibodies. Interaction kinetics of Fab mutants with peptide and protein antigens were measured using a BIACORE instrument. The substitutions introduced at the VH-VL interface had no significant effects on k(a) but showed small, significant effects on k(d). Mutations in the VH module affected k(d) not only for the two different antibodies but also for variants of the same antibody. These effects varied both in direction and in magnitude. In the VL module, the double mutation F(L37)L-Q(L38)L, alone or in combination with other mutations, consistently decreased k(d) about two-fold in Fab 145P. Other mutations in the VL module had no effect on k(d) in 145P, but always decreased k(d) in 1F1h. Moreover, in both systems, small-magnitude non-additive effects on k(d) were observed, but affinity variations seemed to be limited by a threshold. When comparing functional effects in antibodies of different specificity, no general rules could be established. In addition, no clear relationship could be pointed out between the nature of the amino acid change and the observed functional effect. Our results show that binding kinetics are affected by alteration of framework residues remote from the binding site, although these effects are unpredictable for most of the studied changes. Copyright 2000 John Wiley & Sons, Ltd.

Optimizing prevention of HIV mother to child transmission: Duration of antiretroviral therapy and viral suppression at delivery among pregnant Malawian women

PubMed Central

Miller, William C.; Tang, Jennifer H.; Hoffman, Irving F.; Mthiko, Bryan C.; Phulusa, Jacob; John, Mathias; Jumbe, Allan; Hosseinipour, Mina C.

2018-01-01

Background Effective antiretroviral therapy during pregnancy minimizes the risk of vertical HIV transmission. Some women present late in their pregnancy for first antenatal visit; whether these women achieve viral suppression by delivery and how suppression varies with time on ART is unclear. Methods We conducted a prospective cohort study of HIV-infected pregnant women initiating antiretroviral therapy for the first time at Bwaila Hospital in Lilongwe, Malawi from June 2015 to November 2016. Multivariable Poisson models with robust variance estimators were used to estimate risk ratios (RR) and 95% confidence intervals (CI) of the association between duration of ART and both viral load (VL) ≥1000 copies/ml and VL ≥40 copies/ml at delivery. Results Of the 252 women who had viral load testing at delivery, 40 (16%) and 78 (31%) had VL ≥1000 copies/ml and VL ≥40 copies/ml, respectively. The proportion of women with poor adherence to ART was higher among women who were on ART for ≤12 weeks (9/50 = 18.0%) than among those who were on ART for 13–35 weeks (18/194 = 9.3%). Compared to women who were on ART for ≤12 weeks, women who were on ART for 13–20 weeks (RR = 0.52; 95% CI: 0.36–0.74) or 21–35 weeks (RR = 0.26; 95% CI: 0.14–0.48) had a lower risk of VL ≥40 copies/ml at delivery. Similar comparisons for VL ≥1000 copies/ml at delivery showed decrease in risk although not significant for those on ART 13–20 weeks. Conclusion Longer duration of ART during pregnancy was associated with suppressed viral load at delivery. Early ANC attendance in pregnancy to facilitate prompt ART initiation for HIV-positive women is essential in the effort to eliminate HIV vertical transmission. PMID:29614083

No perinatal HIV-1 transmission from women with effective antiretroviral therapy starting before conception.

PubMed

Mandelbrot, Laurent; Tubiana, Roland; Le Chenadec, Jerome; Dollfus, Catherine; Faye, Albert; Pannier, Emmanuelle; Matheron, Sophie; Khuong, Marie-Aude; Garrait, Valerie; Reliquet, Veronique; Devidas, Alain; Berrebi, Alain; Allisy, Christine; Elleau, Christophe; Arvieux, Cedric; Rouzioux, Christine; Warszawski, Josiane; Blanche, Stéphane

2015-12-01

The efficacy of preventing perinatal transmission (PT) of human immunodeficiency virus type 1 (HIV-1) depends on both viral load (VL) and treatment duration. The objective of this study was to determine whether initiating highly active antiretroviral therapy (ART) before conception has the potential to eliminate PT. A total of 8075 HIV-infected mother/infant pairs included from 2000 to 2011 in the national prospective multicenter French Perinatal Cohort (ANRS-EPF) received ART, delivered live-born children with determined HIV infection status, and did not breastfeed. PT was analyzed according to maternal VL at delivery and timing of ART initiation. The overall rate of PT was 0.7% (56 of 8075). No transmission occurred among 2651 infants born to women who were receiving ART before conception, continued ART throughout the pregnancy, and delivered with a plasma VL <50 copies/mL (upper 95% confidence interval [CI], 0.1%). VL and timing of ART initiation were independently associated with PT in logistic regression. Regardless of VL, the PT rate increased from 0.2% (6 of 3505) for women starting ART before conception to 0.4% (3 of 709), 0.9% (24 of 2810), and 2.2% (23 of 1051) for those starting during the first, second, or third trimester (P < .001). Regardless of when ART was initiated, the PT rate was higher for women with VLs of 50-400 copies/mL near delivery than for those with <50 copies/mL (adjusted odds ratio, 4.0; 95% CI, 1.9-8.2). Perinatal HIV-1 transmission is virtually zero in mothers who start ART before conception and maintain suppression of plasma VL. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Post-kala-azar dermal leishmaniasis in the Indian subcontinent: A threat to the South-East Asia Region Kala-azar Elimination Programme.

PubMed Central

Zijlstra, Eduard E.; Alves, Fabiana; Rijal, Suman; Arana, Byron; Alvar, Jorge

2017-01-01

Background The South-East Asia Region Kala-azar Elimination Programme (KAEP) is expected to enter the consolidation phase in 2017, which focuses on case detection, vector control, and identifying potential sources of infection. Post-kala-azar dermal leishmaniasis (PKDL) is thought to play a role in the recurrence of visceral leishmaniasis (VL)/kala-azar outbreaks, and control of PKDL is among the priorities of the KAEP. Methodology and principal finding We reviewed the literature with regard to PKDL in Asia and interpreted the findings in relation to current intervention methods in the KAEP in order to make recommendations. There is a considerable knowledge gap regarding the pathophysiology of VL and PKDL, especially the underlying immune responses. Risk factors (of which previous VL treatments may be most important) are poorly understood and need to be better defined. The role of PKDL patients in transmission is largely unknown, and there is insufficient information about the importance of duration, distribution and severity of the rash, time of onset, and self-healing. Current intervention methods focus on active case detection and treatment of all PKDL cases with miltefosine while there is increasing drug resistance. The prevention of PKDL by improved VL treatment currently receives insufficient attention. Conclusion and significance PKDL is a heterogeneous and dynamic condition, and patients differ with regard to time of onset after VL, chronicity, and distribution and appearance of the rash, as well as immune responses (including tendency to self-heal), all of which may vary over time. It is essential to fully describe the pathophysiology in order to make informed decisions on the most cost-effective approach. Emphasis should be on early detection of those who contribute to transmission and those who are in need of treatment, for whom short-course, effective, and safe drug regimens should be available. The prevention of PKDL should be emphasised by innovative and improved treatment for VL, which may include immunomodulation. PMID:29145397

Population Levels and Geographic Distribution of HIV RNA in Rural Ugandan and Kenyan Communities and Sero-Discordant Couples: a Cross-Sectional Analysis

PubMed Central

Jain, Vivek; Petersen, Maya L.; Liegler, Teri; Byonanebye, Dathan M.; Kwarisiima, Dalsone; Chamie, Gabriel; Sang, Norton; Black, Doug; Clark, Tamara D.; Ladai, Andras; Plenty, Albert; Kabami, Jane; Ssemmondo, Emmanuel; Bukusi, Elizabeth A.; Cohen, Craig R.; Charlebois, Edwin D.; Kamya, Moses R.; Havlir, Diane V.

2017-01-01

Background As Sub-Saharan Africa transitions to a new era of universal ART, up-to-date assessments of HIV RNA (viral load, VL) suppression at a population level are needed to understand demographic and geographic sources of ongoing viremia and to inform interventions to optimize ART delivery. We sought to measure population viral load (VL) metrics to assess current viral suppression levels and characterize demographic groups and geographic locations with high-level detectable viremia in East Africa. Methods In the SEARCH HIV test-and-treat study (NCT01864683), we conducted baseline HIV testing (89% uptake) and HIV RNA assessments in 32 rural communities in 2013–2014 in Uganda and Kenya (N=303,461). We measured VL in 8,828 HIV+ adults, and defined viral suppression as VL<500 copies/mL. To assess geographic sources of transmission risk, we determined the proportion of all adults (both HIV-positive and HIV-negative) with detectable VL (termed ‘local prevalence of viremia’). Transmission risk ‘hotspots’ were defined as geopolitical subunits within communities with >5.0% local prevalence of viremia. We also assessed sero-discordant couples, measuring the proportion in which the HIV+ partner had detectable viremia. Findings Viral suppression was 82% (3,427/4,202) among adults on ART, and 51% (4,490/8,828) among all HIV+ adults. Regional viral suppression among HIV+ adults was 48% (West Uganda), 45% (East Uganda) and 53% (Western Kenya). Transmission risk ‘hotspots’ included 1/21 W.Uganda, 0/18 E.Uganda, and 16/26 Kenya geopolitical subunits. In Uganda, sero-discordancy was 3.1% (492 discordant/16,023 total couples). In 58% of discordant couples, the HIV+ partner was viremic (14% had VL>100,000). In Kenya, sero-discordancy was 10.0% (859/8,616 total couples). In 53%, the HIV+ partner was viremic (15% with VL>100,000). Interpretation Prior to the 2013–2014 start of the SEARCH trial, 51% of East African HIV+ adults had viral suppression, reflecting ART scale-up efforts to date. However, geographic ‘hotspots’ of potential HIV transmission risk as well as detectable viremia among sero-discordant couples warrant intensified interventions. Funding US National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. President’s Emergency Plan for AIDS Relief (PEPFAR). PMID:27989576

Epidemiological characteristics of visceral leishmaniasis in Morocco (1990-2014): an update.

PubMed

Mniouil, Meryem; Fellah, Hajiba; Amarir, Fatima; Et-Touys, Abdeslamd; Bekhti, Khadija; Adlaoui, El Bachir; Bakri, Youssef; Nhammi, Haddou; Sadak, Abderrahim; Sebti, Faiza

2017-06-01

Leishmaniases are parasitic diseases frequent in the Mediterranean Basin. Visceral leishmaniasis (VL) is a notifiable parasitic disease that increased in incidence in Morocco over the past few years and has recently emerged in several new foci, causing a public health problem in Morocco. The aim of this study is to describe the spatio-temporal distribution of VL in Morocco between 1990 and 2014 period in order to highlight important features and trends of VL and its epidemiology and to assess whether the activity of the unit reflects the situation of the disease at the national level and whether it could constitute an indicator of public health relevance. Two thousand four hundred and twenty one cases were reported in Morocco between 1990 and 2014 with an average annual reported incidence rate of 0.4 cases per 100.000 inhabitants. Before 1996 the average annual incidence of VL was 50 cases on average. After this date the number of cases increased and then remained stable with around 100-150 cases per year. Children whose age varies between 1 and 4 years old are the most affected with 1327 (74%) of total cases; nevertheless the adult starts to be affected by the disease. In 2000, 65% of positive cases of VL are concentrated at both northern regions: Taza-Al Hoceima- Taounate with 45% of cases, Tanger- Tetouan mainly represented by Chefchaoun with 20% of cases. The Fez-Boulemane region located in the center recorded 12% of cases. Throughout the years the map VL distribution has been progressively changed and spatial spread of the disease to the center is noted in 2007. 2014 has been marked by an even greater extension of the disease to the center and south of Morocco. Nationally in 2014, 34 of 75 provinces and prefectures are affected compared to 2000, when 22 out of 82 provinces and prefectures were affected. Leishmania infantum was identified the causative agent based on species- specific PCR-Lei70 assay. VL remains a sporadically endemic parasitic disease in Morocco with a progressive extension of its range of distribution. Such a situation would relate to the geographical succession of Phlebotomine sand fly vectors, the difficulty of actions against the canine population reservoirs of L. infantum and unfavorable socio-economic factors. Copyright © 2016. Published by Elsevier B.V.

Dispersal of Lutzomyia longipalpis and expansion of canine and human visceral leishmaniasis in São Paulo State, Brazil.

PubMed

Oliveira, Agda Maria; Vieira, Carolina Portugal; Dibo, Margareth Regina; Guirado, Marluci Monteiro; Rodas, Lilian Aparecida Colebrusco; Chiaravalloti-Neto, Francisco

2016-12-01

Visceral leishmaniasis (VL), a neglected disease, is a serious public health problem that affects millions of people worldwide. The objectives of the study were to evaluate the sensitivity of Lutzomyia longipalpis and canine VL (CVL) autochthony early detection and describe the spatial and temporal dispersal of vector and expansion of VL in a Brazilian state. We obtained data on the leishmaniasis vector and VL cases in São Paulo State (SP), Brazil, from the Division of Endemic Disease Control and from the Epidemiological Surveillance Center of the São Paulo State Department of Health. Data were analyzed for 645 municipalities and 63 microregions and presented as thematic and flow maps. Following the verified presence of L. longipalpis in Araçatuba in 1997, the first autochthonous cases of canine VL (CVL) (1998) and of human VL (HVL) (1999) in São Paulo were reported, both in Araçatuba. From 1997 to 2014, the urban presence of the leishmaniasis vector was verified in 167 (25.9%) municipalities with cases of CVL reported in 108 (16.7%) and cases of HVL in 84 (13%). The sensitivities for vector presence early detection in relation to the identification of CVL and HVL autochthony were, respectively, equal to 76.4 and 92.5%. The sensitivity for CVL autochthony early detection in relation to the HVL autochthony identification was 75.8%. Vector dispersal and expansion of CVL and HVL were from the northwest to the southeast of the state, primarily flanking the Marechal Rondon highway at a constant rate of progression of 10, seven, and six new municipalities affected per year, respectively. We concluded that the sensitivity for vector presence and CVL autochthony presented reasonable accuracy and most of the time the vector presence and, specially, the CVL and HVL autochthony were identified in the main cities of the microregions of SP. Vector dispersal and expansion of VL started in 1997 near the state border of SP with the state of Mato Grosso do Sul. It has advanced from the northwest to the southeast flanking the Marechal Rondon highway at an arithmetic progression rate outward from the main cities of the microregions. Autochthonous cases of CVL and HVL emerged in SP, in general, after the verified presence of L. longipalpis. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Antiretroviral resistance at virological failure in the NEAT 001/ANRS 143 trial: raltegravir plus darunavir/ritonavir or tenofovir/emtricitabine plus darunavir/ritonavir as first-line ART.

PubMed

Lambert-Niclot, S; George, E C; Pozniak, A; White, E; Schwimmer, C; Jessen, H; Johnson, M; Dunn, D; Perno, C F; Clotet, B; Plettenberg, A; Blaxhult, A; Palmisano, L; Wittkop, L; Calvez, V; Marcelin, A G; Raffi, F

2016-04-01

To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of <100,000 copies/mL, 25.0% for a VL of ≥100,000 copies/mL and <500,000 copies/mL and 53.8% for a VL of ≥500,000 copies/mL (PTREND = 0.007). Of note, 4/15 participants with IN RAM had a VL < 200 copies/mL at time of testing. In the NEAT001/ANRS143 trial, there was no RAM at virological failure in the standard tenofovir/emtricitabine plus darunavir/ritonavir regimen, contrasting with a rate of 29.5% (mostly IN mutations) in the raltegravir plus darunavir/ritonavir NRTI-sparing regimen. The cumulative risk of IN RAM after 96 weeks of follow-up in participants initiating ART with raltegravir plus darunavir/ritonavir was 3.9%. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Protocol for a randomised controlled implementation trial of point-of-care viral load testing and task shifting: the Simplifying HIV TREAtment and Monitoring (STREAM) study.

PubMed

Dorward, Jienchi; Garrett, Nigel; Quame-Amaglo, Justice; Samsunder, Natasha; Ngobese, Hope; Ngomane, Noluthando; Moodley, Pravikrishnen; Mlisana, Koleka; Schaafsma, Torin; Donnell, Deborah; Barnabas, Ruanne; Naidoo, Kogieleum; Abdool Karim, Salim; Celum, Connie; Drain, Paul K

2017-09-27

Achieving the Joint United Nations Programme on HIV and AIDS 90-90-90 targets requires models of HIV care that expand antiretroviral therapy (ART) coverage without overburdening health systems. Point-of-care (POC) viral load (VL) testing has the potential to efficiently monitor ART treatment, while enrolled nurses may be able to provide safe and cost-effective chronic care for stable patients with HIV. This study aims to demonstrate whether POC VL testing combined with task shifting to enrolled nurses is non-inferior and cost-effective compared with laboratory-based VL monitoring and standard HIV care. The STREAM (Simplifying HIV TREAtment and Monitoring) study is an open-label, non-inferiority, randomised controlled implementation trial. HIV-positive adults, clinically stable at 6 months after ART initiation, will be recruited in a large urban clinic in South Africa. Approximately 396 participants will be randomised 1:1 to receive POC HIV VL monitoring and potential task shifting to enrolled nurses, versus laboratory VL monitoring and standard South African HIV care. Initial clinic follow-up will be 2-monthly in both arms, with VL testing at enrolment, 6 months and 12 months. At 6 months (1 year after ART initiation), stable participants in both arms will qualify for a differentiated care model involving decentralised ART pickup at community-based pharmacies. The primary outcome is retention in care and virological suppression at 12 months from enrolment. Secondary outcomes include time to appropriate entry into the decentralised ART delivery programme, costs per virologically suppressed patient and cost-effectiveness of the intervention compared with standard care. Findings will inform the scale up of VL testing and differentiated care in HIV-endemic resource-limited settings. Ethical approval has been granted by the University of KwaZulu-Natal Biomedical Research Ethics Committee (BFC296/16) and University of Washington Institutional Review Board (STUDY00001466). Results will be presented at international conferences and published in academic peer-reviewed journals. NCT03066128; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Visceral leishmaniasis in selected communities of Hamar and Banna-Tsamai districts in Lower Omo Valley, South West Ethiopia: Sero-epidemological and Leishmanin Skin Test Surveys.

PubMed

Bekele, Fitsum; Belay, Tariku; Zeynudin, Ahmed; Hailu, Asrat

2018-01-01

Visceral leishmaniasis [VL] is a debilitating parasitic disease which invariably kills untreated patients. The disease is caused by Leishmania (L.) donovani or L. infantum, and transmitted by the bite of female phlebotomine sandflies. VL often remains subclinical but can become symptomatic with an acute/subacute or chronic course. Globally, the Eastern Africa region is one of the main VL endemic areas. The disease is prevalent in numerous foci within Eritrea, Ethiopia, Kenya, Somalia, Sudan South Sudan, and Uganda. In Ethiopia, the Lower Omo plain is one of the many VL endemic regions. The objective of this study was to determine the prevalence of asymptomatic visceral leishmaniasisin Hamar and Banna-Tsamai districts of the South Omo plains where VL is becoming an emerging health problem of neglected communities. A community based cross-sectional survey was conducted in 2013 between 25th of July and 14th of August. A total of 1682 individuals living in 404 households were included in the study. Socio-demographic and clinical data were collected from each of the participants and venous blood was also collected for the detection of antibodies to visceral leishmaniasis using Direct Agglutination Test. Leishmanin Skin Test was performed to detect the exposure to the parasite. The surveys included 14 villages located in areas where VL had been reported. In a study population of 1682 individuals, the overall positive leishmanian skin test and sero-prevalence rates respectively were 8.6% and 1.8%. A statistically significant variation in the rate of positive LST response was observed in different study sites and age groups. Positive LST response showed an increasing trend with age. The sero-prevalence rate also showed a statistically significant variation among different study sites. Higher rates of sero-prevalence were observed in children and adolescents. The LST and sero-prevalence rates in Hamar District exceeded significantly that of Banna-Tsamai District (10.7% versus 5.8% for LST; and 2.6% versus 0.7% for sero-prevalence). The prevalence of asymptomatic VL infection in Hamar and Banna-Tsamai districts during the study period in 2013 was low compared to rates previously reported in other endemic areas of Ethiopia. This could be due to the fact that the disease is emerging in Hamar and Banna-Tsamai districts. Based on records of a nearby Hospital, increasing numbers of active VL cases have been reported in these districts through the years 2006-2012, especially in Hamar District. Both districts are important destinations of tourism, and thus the importance of surveillance should be emphasized. Detailed epidemiological and entomological studies are recommended.

Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity

PubMed Central

Groves, Maria AT; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

2014-01-01

In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics. PMID:24256948

Emtricitabine Seminal Plasma and Blood Plasma Population Pharmacokinetics in HIV-Infected Men in the EVARIST ANRS-EP 49 Study

PubMed Central

Tréluyer, Jean-Marc; Illamola, Silvia M.; Bouazza, Naïm; Foissac, Frantz; De Sousa Mendes, Maïlys; Lui, Gabrielle; Chenevier-Gobeaux, Camille; Suzan-Monti, Marie; Rouzioux, Christine; Assoumou, Lambert; Viard, Jean-Paul; Hirt, Déborah; Urien, Saïk; Ghosn, Jade

2015-01-01

We aimed to describe blood plasma (BP) and seminal plasma (SP) pharmacokinetics of emtricitabine (FTC) in HIV-1-infected men, assess its penetration in the male genital tract, and evaluate its impact on seminal plasma HIV load (spVL) detection. Men from the EVARIST ANRS EP49 study receiving combined antiretroviral therapy with FTC and with suppressed BP viral load were included in the study. A total of 236 and 209 FTC BP and SP concentrations, respectively, were available. A population pharmacokinetic model was developed with Monolix 4.1.4. The impact of FTC seminal exposure on spVL detection was explored by receiver operating characteristic (ROC) curves and mixed-effects logistic regressions. FTC BP pharmacokinetics was described by a two-compartment model. The addition of an effect compartment with different input and output constants best described FTC SP pharmacokinetics. No covariates were found to explain the variability in SP. FTC exposures (area under the concentration-time curve from 0 to 24 h [AUC0–24]) were higher in SP than in BP (median AUC0–24, 38.04 and 12.95 mg · liter−1 · h, respectively). The median (range) SP-to-BP AUC0–24 ratio was 2.91 (0.84 to 10.08). Less than 1% of FTC AUC0–24 ratios were lower than 1. The impact of FTC SP AUC0–24 or FTC SP-to-BP AUC0–24 ratio on spVL detection was not significant (P = 0.943 or 0.893, respectively). This is the first population model describing FTC pharmacokinetics simultaneously in both BP and SP. FTC distributes well in the male genital tract with higher FTC concentrations in SP than in BP. FTC seminal plasma exposures were considered efficient in the majority of men. PMID:26282407

Fiber orientation measurements by diffusion tensor imaging improve hydrogen-1 magnetic resonance spectroscopy of intramyocellular lipids in human leg muscles.

PubMed

Valaparla, Sunil K; Gao, Feng; Daniele, Giuseppe; Abdul-Ghani, Muhammad; Clarke, Geoffrey D

2015-04-01

Twelve healthy subjects underwent hydrogen-1 magnetic resonance spectroscopy ([Formula: see text]) acquisition ([Formula: see text]), diffusion tensor imaging (DTI) with a [Formula: see text]-value of [Formula: see text], and fat-water magnetic resonance imaging (MRI) using the Dixon method. Subject-specific muscle fiber orientation, derived from DTI, was used to estimate the lipid proton spectral chemical shift. Pennation angles were measured as 23.78 deg in vastus lateralis (VL), 17.06 deg in soleus (SO), and 8.49 deg in tibialis anterior (TA) resulting in a chemical shift between extramyocellular lipids (EMCL) and intramyocellular lipids (IMCL) of 0.15, 0.17, and 0.19 ppm, respectively. IMCL concentrations were [Formula: see text], [Formula: see text], and [Formula: see text] in SO, VL, and TA, respectively. Significant differences were observed in IMCL and EMCL pairwise comparisons in SO, VL, and TA ([Formula: see text]). Strong correlations were observed between total fat fractions from [Formula: see text] and Dixon MRI for VL ([Formula: see text]), SO ([Formula: see text]), and TA ([Formula: see text]). Bland-Altman analysis between fat fractions (FFMRS and FFMRI) showed good agreement with small limits of agreement (LoA): [Formula: see text] (LoA: [Formula: see text] to 0.69%) in VL, [Formula: see text] (LoA: [Formula: see text] to 1.33%) in SO, and [Formula: see text] (LoA: [Formula: see text] to 0.47%) in TA. The results of this study demonstrate the variation in muscle fiber orientation and lipid concentrations in these three skeletal muscle types.

Elimination of Kala-Azar from the Southeast Asia Region.

PubMed

Bhattacharya, Sujit K; Dash, Aditya Prasad

2017-04-01

AbstractVisceral leishmaniasis (VL), popularly known as kala-azar, is essentially a disease of poverty. Kala-azar is caused by a parasite, Leishmania donovani . Recent review indicates that worldwide 98 countries are endemic for kala-azar. Approximately 0.2-0.4 million new VL cases occur each year worldwide. More than 90% of global VL cases occur in Bangladesh, Brazil, Ethiopia, India, South Sudan, and Sudan. This trend is slowly changing due to the progress in kala-azar elimination in southeast Asia, where Bangladesh has reported an average of some 600 new cases in 2014-2015. With the advancement in our knowledge about the disease and development of tools to diagnose and treat VL, it was considered that elimination of kala-azar was possible from India, Nepal, and Bangladesh. The three countries signed a memorandum of understanding in 2005 for collaboration. Miltefosine is the first ever oral drug developed to treat VL, which was later replaced by lipid amphotericin B. The main components of the strategy are early diagnosis using rK39 strip test and complete treatment utilizing miltefosine for 28 days. Dichlorodiphenyltrichloroethane or pyrethroids were deployed for vector control. There was much to be desired for better performance of the vector control activity. Pharmacovigilance and monitoring of drug resistance were the weakest part of the program. In the post-elimination phase, surveillance reinforced by active case finding will of a crucial factor for sustainability of the elimination. A strong political will is required to ensure elimination of kala-azar from the Indian subcontinent and its sustainability in the post-elimination phase.

Differential development of antinociceptive tolerance to morphine and fentanyl is not linked to efficacy in the ventrolateral periaqueductal gray of the rat

PubMed Central

Bobeck, Erin N.; Haseman, Rachel A.; Hong, Dana; Ingram, Susan L.; Morgan, Michael M.

2012-01-01

Systemic administration of morphine typically produces greater tolerance than higher efficacy mu-opioid receptor (MOPr) agonists, such as fentanyl. The objective of the present study was to test this relationship by measuring antinociceptive efficacy and tolerance to morphine and fentanyl microinjected into the ventrolateral periaqueductal gray (vlPAG). MOPr agonist efficacy was evaluated by microinjecting the irreversible opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) into the vlPAG prior to a dose-response analysis of morphine and fentanyl antinociception. In contrast to systemic administration of morphine and fentanyl, microinjection of these drugs into the vlPAG had similar efficacy as measured by similar reductions in maximal antinociception following β-FNA administration. Analysis of tolerance revealed a rightward shift in the dose-response curve to a single pretreatment with morphine, but not fentanyl. Moreover, the magnitude of tolerance to morphine was comparable following one, four, or eight pretreatments. Tolerance to fentanyl also was evident following four or eight microinjections. These data are surprising in that antinociceptive efficacy appears to vary depending on the site of administration. Moreover, the similar efficacy following microinjection of morphine and fentanyl into the vlPAG was associated with comparable tolerance, with the one exception of no tolerance to acute administration of fentanyl. Perspective These data reveal that antinociceptive tolerance following vlPAG administration of opioids develops rapidly, is evident with both morphine and fentanyl, and the magnitude is relatively consistent regardless of the number of pretreatments. PMID:22766006

Phenyl-γ-valerolactones, flavan-3-ol colonic metabolites, protect brown adipocytes from oxidative stress without affecting their differentiation or function.

PubMed

Mele, Laura; Carobbio, Stefania; Brindani, Nicoletta; Curti, Claudio; Rodriguez-Cuenca, Sergio; Bidault, Guillaume; Mena, Pedro; Zanotti, Ilaria; Vacca, Michele; Vidal-Puig, Antonio; Del Rio, Daniele

2017-09-01

Consumption of products rich in flavan-3-ols, such as tea and cocoa, has been associated with decreased obesity, partially dependent on their capacity to enhance energy expenditure. Despite these phenolics having been reported to increase the thermogenic program in brown and white adipose tissue, flavan-3-ols are vastly metabolised in vivo to phenyl-γ-valerolactones. Therefore, we hypothesize that phenyl-γ-valerolactones may directly stimulate the differentiation and the activation of brown adipocytes. Immortalized brown pre-adipocytes were differentiated in presence of (R)-5-(3',4'-dihydroxyphenyl)-γ-valerolactone (VL1), (R)-5-(3´-hydroxyphenyl)-γ-valerolactone-4'-O-sulphate (VL2), (R)-5-phenyl-γ-valerolactone-3´,4´-di-O-sulphate (VL3), at concentrations of 2 or 10μM, whereas fully differentiated brown adipocyte were treated acutely (6-24h). None of the treatments regulated the expression levels of the uncouple protein 1, nor of the main transcription factors involved in brown adipogenesis. Similarly, mitochondrial content was unchanged after treatments. Moreover these compounds did not display peroxisome proliferator-activated receptor γ-agonist activity, as evaluated by luciferase assay, and did not enhance norepinephrine-stimulated lipolysis in mature adipocytes. However, both VL1 and VL2 prevented oxidative stress caused by H 2 O 2 . Phenyl-γ-valerolactones and their sulphated forms do not influence brown adipocyte development or function at physiological or supraphysiological doses in vitro, but they are active protecting brown adipocytes from increased reactive oxygen species production. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of a Flexible Intubating Scope in Combination with a Channeled Video Laryngoscope for Managing a Difficult Airway in the Emergency Department.

PubMed

Sowers, Nicholas; Kovacs, George

2016-02-01

Difficulty with intubation is not uncommon in the emergency setting. Video laryngoscopes (VLs) are commonly used to manage the difficult airway in the emergency department (ED). Intubation using a flexible bronchoscope, while considered the gold standard for managing the anticipated difficult airway in the operating room, is not commonly used in the ED. We present a case describing VL-assisted flexible scope intubation performed in the ED as a novel feasible approach to managing the difficult airway. A 65-year-old male, post cardiac arrest, with multiple unsuccessful attempts at prehospital intubation had rapid sequence intubation (RSI) performed and, despite obtaining a view with a King Vision™ VL, the skilled operator was unable to advance the endotracheal tube (ETT). An Ambu™ aScope3 flexible intubating scope (FIS) was placed through the ETT loaded in the channel of the King Vision and advanced through the cords to a position proximal to the carina. The ETT was then advanced easily over the FIS and down the trachea. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although video laryngoscopy is commonly used in the ED, intubation can prove difficult, despite having an adequate view of the glottis. Use of an FIS, however, through a channeled VL makes navigation of the ETT easier and facilitates tube advancement, which can be difficult with VL. Channeled VL-assisted use of an FIS is a viable option for managing the difficult airway. Copyright © 2016 Elsevier Inc. All rights reserved.

Operating length and velocity of human M. vastus lateralis fascicles during vertical jumping

PubMed Central

Nikolaidou, Maria Elissavet; Marzilger, Robert; Bohm, Sebastian; Mersmann, Falk

2017-01-01

Humans achieve greater jump height during a counter-movement jump (CMJ) than in a squat jump (SJ). However, the crucial difference is the mean mechanical power output during the propulsion phase, which could be determined by intrinsic neuro-muscular mechanisms for power production. We measured M. vastus lateralis (VL) fascicle length changes and activation patterns and assessed the force–length, force–velocity and power–velocity potentials during the jumps. Compared with the SJ, the VL fascicles operated on a more favourable portion of the force–length curve (7% greater force potential, i.e. fraction of VL maximum force according to the force–length relationship) and more disadvantageous portion of the force–velocity curve (11% lower force potential, i.e. fraction of VL maximum force according to the force–velocity relationship) in the CMJ, indicating a reciprocal effect of force–length and force–velocity potentials for force generation. The higher muscle activation (15%) could therefore explain the moderately greater jump height (5%) in the CMJ. The mean fascicle-shortening velocity in the CMJ was closer to the plateau of the power–velocity curve, which resulted in a greater (15%) power–velocity potential (i.e. fraction of VL maximum power according to the power–velocity relationship). Our findings provide evidence for a cumulative effect of three different mechanisms—i.e. greater force–length potential, greater power–velocity potential and greater muscle activity—for an advantaged power production in the CMJ contributing to the marked difference in mean mechanical power (56%) compared with SJ. PMID:28573027

Valley-locked thermospin effect in silicene and germanene with asymmetric magnetic field induced by ferromagnetic proximity effect

NASA Astrophysics Data System (ADS)

Zhai, Xuechao; Wang, Yun-Tong; Wen, Rui; Wang, Shu-Xuan; Tian, Yue; Zhou, Xingfei; Chen, Wei; Yang, Zhihong

2018-02-01

Silicene and germanene, as graphenelike materials with observable spin-orbit couplings and two distinctive valleys, have potential applications in future low-dissipation spintronics and valleytronics. We here propose a magnetic system of silicene or germanene intercalated between two ferromagetic (FM) dielectric layers, and find that the system with a proximity-induced asymmetric magnetic field supports an attractive phenomenon named the valley-locked spin-dependent Seebeck effect (VL-SSE) driven by a thermal gradient. The VL-SSE indicates that the carries from only one valley could be thermally excited, with opposite spin polarization counterpropagating along the thermal gradient direction, while nearly no carrier from the other insulating valley is excited due to the relatively wide band gap. It is also illustrated that the VL-SSE here does not survive in the usual FM or anti-FM systems, and can be destroyed by the overlarge temperature broadening. Moreover, we prove that the signal for VL-SSE can be weakened gradually with the enhancement of the local interlayer electric field, and be strengthened lineally by increasing the source-drain temperature difference in a caloritronic field effect transistor. Further calculations indicate that the VL-SSE is robust against many perturbations, including the global and local Fermi levels as well as the magnetic strength. These findings about the valley-locked thermospin effect provide a nontrivial and convenient dimension to control the quantum numbers of spin and valley and are expected to be applied in future spin-valley logic circuits and energy-saving devices.

Psychosocial and Neurohormonal Predictors of HIV Disease Progression (CD4 Cells and Viral Load): A 4 Year Prospective Study.

PubMed

Ironson, G; O'Cleirigh, C; Kumar, M; Kaplan, L; Balbin, E; Kelsch, C B; Fletcher, M A; Schneiderman, N

2015-08-01

Most studies of psychosocial predictors of disease progression in HIV have not considered norepinephrine (NE), a neurohormone related to emotion and stress, even though NE has been related to accelerated viral replication in vitro and impaired response to antiretroviral therapy (ART). We therefore examined NE, cortisol, depression, hopelessness, coping, and life event stress as predictors of HIV progression in a diverse sample. Participants (n = 177) completed psychological assessment, blood draws [CD4, viral load (VL)], and a 15 h urine sample (NE, cortisol) every 6 months over 4 years. Hierarchical linear modeling (HLM) was used to model slope in CD4 and VL controlling for ART at every time point, gender, age, race, SES, and initial disease status. NE (as well as depression, hopelessness, and avoidant coping) significantly predicted a greater rate of decrease in CD4 and increase in VL. Cortisol was not significantly related to CD4, but predicted VL increase. To our knowledge, this is the first study relating NE, in vivo, to accelerated disease progression over an extended time. It also extends our previous 2 year study by relating depressed mood and coping to accelerated disease progression over 4 years.

vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

PubMed

Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca E; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

2017-07-01

Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Visceral Leishmaniasis: Advancements in Vaccine Development via Classical and Molecular Approaches

PubMed Central

Joshi, Sumit; Rawat, Keerti; Yadav, Narendra Kumar; Kumar, Vikash; Siddiqi, Mohammad Imran; Dube, Anuradha

2014-01-01

Visceral leishmaniasis (VL) or kala-azar, a vector-borne protozoan disease, shows endemicity in larger areas of the tropical, subtropical and the Mediterranean countries. WHO report suggested that an annual incidence of VL is nearly 200,000 to 400,000 cases, resulting in 20,000 to 30,000 deaths per year. Treatment with available anti-leishmanial drugs are not cost effective, with varied efficacies and higher relapse rate, which poses a major challenge to current kala-azar control program in Indian subcontinent. Therefore, a vaccine against VL is imperative and knowing the fact that recovered individuals developed lifelong immunity against re-infection, it is feasible. Vaccine development program, though time taking, has recently gained momentum with the emergence of omic era, i.e., from genomics to immunomics. Classical as well as molecular methodologies have been overtaken with alternative strategies wherein proteomics based knowledge combined with computational techniques (immunoinformatics) speed up the identification and detailed characterization of new antigens for potential vaccine candidates. This may eventually help in the designing of polyvalent synthetic and recombinant chimeric vaccines as an effective intervention measures to control the disease in endemic areas. This review focuses on such newer approaches being utilized for vaccine development against VL. PMID:25202307

Miltefosine in the treatment of leishmaniasis: Clinical evidence for informed clinical risk management.

PubMed

Sundar, Shyam; Olliaro, Piero L

2007-10-01

Visceral leishmaniasis (VL) is a life-threatening disease. Traditional treatment with pentavalent antimony injections has become ineffective in the area with the world's highest prevalence of disease (North Bihar, India) and is becoming less effective elsewhere as well. A replacement is needed, best if it can be given to more patients outside the hospital. Miltefosine is the first oral drug registered for VL. Given daily under medical supervision for 4 weeks, it cures 94% of patients (both children and adults) and is reasonably safe. Miltefosine has great potential for improving access to treatment and overall control of VL and will be critical in the VL elimination campaign in the Indian subcontinent, but must be safeguarded or will be lost if misused. Its main limitations are adherence (and hence potential for selection of drug resistant parasites) and teratogenicity (pregnancy must be avoided during treatment and the following two months). This calls for responsible deployment, setting in place mechanisms to protect female patients in child-bearing age, monitoring effects and optimizing adherence in real-life conditions through directly observed therapy. One option to protect the useful life-span of miltefosine consists in shortening treatment duration by combining it with another drug.

Scalable production of mechanically tunable block polymers from sugar

PubMed Central

Xiong, Mingyong; Schneiderman, Deborah K.; Bates, Frank S.; Hillmyer, Marc A.; Zhang, Kechun

2014-01-01

Development of sustainable and biodegradable materials is essential for future growth of the chemical industry. For a renewable product to be commercially competitive, it must be economically viable on an industrial scale and possess properties akin or superior to existing petroleum-derived analogs. Few biobased polymers have met this formidable challenge. To address this challenge, we describe an efficient biobased route to the branched lactone, β-methyl-δ-valerolactone (βMδVL), which can be transformed into a rubbery (i.e., low glass transition temperature) polymer. We further demonstrate that block copolymerization of βMδVL and lactide leads to a new class of high-performance polyesters with tunable mechanical properties. Key features of this work include the creation of a total biosynthetic route to produce βMδVL, an efficient semisynthetic approach that employs high-yielding chemical reactions to transform mevalonate to βMδVL, and the use of controlled polymerization techniques to produce well-defined PLA–PβMδVL–PLA triblock polymers, where PLA stands for poly(lactide). This comprehensive strategy offers an economically viable approach to sustainable plastics and elastomers for a broad range of applications. PMID:24912182

Spasmodic dysphonia follow-up with videolaryngoscopy and voice spectrography during treatment with botulinum toxin.

PubMed

Esposito, Marcello; Dubbioso, R; Apisa, P; Allocca, R; Santoro, L; Cesari, U

2015-09-01

Spasmodic dysphonia (SD) is a focal dystonia of laryngeal muscles seriously impairing quality of voice. Adductor SD (ADSD) is the most common presentation of this disorder that can be identified by specialized phoniatricians and neurologists firstly on a clinical evaluation and then confirmed by videolaryngoscopy (VL). Botulinum toxin (BTX) injection with electromyographic guidance in muscles around vocal cords is the most effective treatment. Voice Handicap Index (VHI) questionnaire is the main tool to assess dysphonia and response to treatment. Objective of this study is to perform VL and voice spectrography (VS) to confirm the efficacy of BTX injections over time. 13 patients with ADSD were studied with VHI, VL and VS before and after 4 consecutive treatment with onobotulinumtoxin-A. For each treatment vocal improvement was proved by a significant reduction of VHI score and increase of maximum time phonation and harmonic-to-noise ratio while VL showed the absence of spasm in most of patients. No change of the response to BTX was found between injections. This study supports the efficacy of the treatment of SD with BTX with objective measurements and suggests that the efficacy of recurring treatments is stable over time.

Electromagnetic pulse (EMP) coupling codes for use with the vulnerability/lethality (VIL) taxonomy. Final report, June-October 1984

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mar, M.H.

1995-07-01

Based on the vulnerability Lethality (V/L) taxonomy developed by the Ballistic Vulnerability Lethality Division (BVLD) of the Survivability Lethality Analysis Directorate (SLAD), a nuclear electromagnetic pulse (EMP) coupling V/L analysis taxonomy has been developed. A nuclear EMP threat to a military system can be divided into two levels: (1) coupling to a system level through a cable, antenna, or aperture; and (2) the component level. This report will focus on the initial condition, which includes threat definition and target description, as well as the mapping process from the initial condition to damaged components state. EMP coupling analysis at a systemmore » level is used to accomplish this. This report introduces the nature of EMP threat, interaction between the threat and target, and how the output of EMP coupling analysis at a system level becomes the input to the component level analysis. Many different tools (EMP coupling codes) will be discussed for the mapping process, which correponds to the physics of phenomenology. This EMP coupling V/L taxonomy and the models identified in this report will provide the tools necessary to conduct basic V/L analysis of EMP coupling.« less

Investigational Drugs for Visceral Leishmaniasis

PubMed Central

Sundar, Shyam; Chakravarty, Jaya

2014-01-01

Introduction The armamentarium of antileishmanials is small. It is further being threatened by development of resistance and decreasing sensitivity to the available drugs. Development of newer drugs are sorely needed. Areas covered Literature search on investigational drugs for visceral leishmaniasis (VL) was done on PubMed. Those candidates with at least in vitro and in vivo activity against leishmania species causing VL were reviewed. Among the investigational drugs the nitroimidazole compound fexinidazole is the one of the few drugs which has reached phase II trials. Although the (S)-PA-824 is in phase II trials for the treatment of tuberculosis its R enantiomer has shown good antileishmanial activity. Development of sitamaquin, which has completed phase II studies has been stopped for VL due to its low efficacy. Many novel delivery system and oral formulations of Amphotericin B which are cheap and less toxic are in investigational stages, and will go a long way in improving the treatment of VL. Expert opinion Very few new drugs have reached the clinical stage in the treatment of this neglected tropical disease. Thus, there is an urgent need for support from public private partnerships to ensure that drug candidates are promptly taken forward into development. PMID:25409760

Bipolar leads for use with permanently implantable cardiac pacing systems: a review of limitations of traditional and coaxial configurations and the development and testing of new conductor, insulation, and electrode designs.

PubMed

Tyers, G F; Mills, P; Clark, J; Cheesman, M; Yeung-Lai-Wah, J A; Brownlee, R R

1997-01-01

The unacceptable rate of mechanical failures, threshold problems, and recalls experienced with many coaxial bipolar cardiac pacing lead designs are reviewed in detail. To address these problems, redundant insulation coradial atrial and ventricular tined leads (AL and VL, respectively) with iridium oxide electrodes were developed and subjected to extensive accelerated testing. There were no mechanical failures. The new lead body design proved to be much more durable than widely used trifilar MP35N configurations. The data reviewed and early and current test results are strongly supportive of tightly coupled insulation being a major factor in improving lead durability as long as the insulating material is not stressed. In addition to improving flex life, insulation adherence to the conductor may reduce the potential for ionic degradation. Pacing and sensing thresholds in animal studies of the new leads were within the reported range for leads with steroid eluting electrodes. A multicenter Canadian clinical trial was initiated with the first implant in early January 1994. By November 1995, 110 VL and 82 AL had been placed in 124 patients and followed for a mean of 11 +/- 6 months; maximum 21, total 1355. There were 60 males and 64 females with a mean age of 64 +/- 16 years, range 15-88. Primary indications for pacing were AV block in 61 patients, sick sinus syndrome in 53, vasovagal syncope in 4, and congestive heart failure in 7. Many patients had associated or primary tachyarrhythmias, including 111 with supraventricular and 12 with ventricular. Forty-two percent of patients (52/124) had prior cardiac procedures, including 18 open heart surgeries and 20 AV nodal ablations. At implant, 8 lead characteristics were rated good or excellent in 90% (746/829) of evaluations. X-ray visibility was of concern in 10% of patients (12/124). Three perioperative complications occurred, including displacement of one AL (1.2%) and one VL (0.9%). There were no subsequent mechanical (connector, conductor, or insulation) or functional (exit block, micro or macro displacement, or over- or undersensing) problems. Implant pacing thresholds (PT) at 0.45 ms were AL, 0.6 +/- 0.2 (74) and VL 0.4 +/- 0.2 V; impedance (Z) at 3.5 V output AL 373 +/- 77 (82) and VL 497 +/- 117 omega. Sensing thresholds (ST) were AL 3.1 +/- 1.6 (74) and VL 10.3 +/- 4.9 mV. Ventricular lead data were obtained for all patients (N = 110). Atrial lead data are incomplete, because some patients were in atrial fibrillation during implantation. After 12 months, AL PT at 1.5 V output was 0.18 +/- 0.10 ms (21) and at 2.5 V was 0.10 +/- 0.053 (22). Associated AL ST was 3.3 +/- 0.9 mV (21) AL Z 500 +/- 65 omega (25). After 18 months VL PT at 1.5 V was 0.15 +/- 0.10 ms (9) and at 2.5 V output was 0.09 +/- 0.04 ms (9). Associated VL ST was > 7.5 +/- 2.4 mV (9) and VL Z 497 +/- 105 omega (9). Follow-up time discrepancy is due to the VL being available 6 months earlier than the AL. There were no 30-day deaths and only one late death at 10 months in a patient with chronic atrial fibrillation. Death was unrelated to pacer or lead function. At 1 year, 68% AL (15/22) and 62% (24/39) captured at 0.5 V and < or = 1 ms pulse width output. Innovative adherent insulation coradial bipolar lead conductors of the design studied combined with coated iridium oxide electrodes provide for a negligible incidence of mechanical or functional failure with clinical follow-up now approaching 3 years. Excellent acute and chronic sensing and pacing thresholds have been documented. Late thresholds have continued to improve gradually. Long-term clinical pacing at < or = 1.5 V output with a large safety margin is feasible in essentially all patients. This coradial design produces very flexible < 5 French bipolar redundantly insulated lead bodies allowing both AL and VL to simultaneously pass through a single 10 French introducer sheath. (ABSTRACT TRUNCATED)

Development of Leishmania vaccines in the era of visceral leishmaniasis elimination.

PubMed

Engwerda, Christian R; Matlashewski, Greg

2015-07-01

A visceral leishmaniasis (VL) elimination target set for the Indian subcontinent in 2005 is being met in many endemic areas without a vaccine. This begs a question: is a VL vaccine needed if elimination targets can be met with current control programs? Here, we argue that a vaccine will be critical if the success of recent VL control efforts are to be sustained. However, not only do we require a safe and effective vaccine, but we also need to know how this should be used for maximum impact. In particular, identifying appropriate target populations to vaccinate will be crucial. © The Author 2015. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Mobile Text Messaging to Improve Medication Adherence and Viral Load in a Vulnerable Canadian Population Living With Human Immunodeficiency Virus: A Repeated Measures Study.

PubMed

King, Elizabeth; Kinvig, Karen; Steif, Jonathan; Qiu, Annie Q; Maan, Evelyn J; Albert, Arianne Yk; Pick, Neora; Alimenti, Ariane; Kestler, Mary H; Money, Deborah M; Lester, Richard T; Murray, Melanie Caroline Margaret

2017-06-01

Combination antiretroviral therapy (cART) as treatment for human immunodeficiency virus (HIV) infection is effective and available, but poor medication adherence limits benefits, particularly in vulnerable populations. In a Kenyan randomized controlled trial, a weekly text-messaging intervention (WelTel) improved cART adherence and HIV viral load (VL). Despite growing evidence for short message service (SMS) text-message interventions in HIV care, there is a paucity of data utilizing these interventions in marginalized or female cohorts. This study was undertaken to assess whether the standardized WelTel SMS text-message intervention applied to a vulnerable, predominantly female, population improved cART adherence and VL. We conducted a repeated measures study of the WelTel intervention in high-risk HIV-positive persons by measuring change in VL, CD4 count, and self-reported adherence 12 months before and 12 months after the WelTel intervention was introduced. Inclusion criteria included VL ≥200 copies/mL, indication for treatment, and meeting vulnerability criteria. Participants were given a mobile phone with unlimited texting (where required), and weekly check-in text messages were sent for one year from the WelTel computer platform. Clinical data were collected for control and intervention years. Participants were followed by a multidisciplinary team in a clinical setting. Outcomes were assessed using Wilcoxon signed ranks tests for change in CD4 and VL from control year to study end and mixed-effects logistic regressions for change in cART adherence and appointment attendance. A secondary analysis was conducted to assess the effect of response rate on the outcome by modeling final log 10 VL by number of responses while controlling for mean log 10 VL in the control year. Eighty-five participants enrolled in the study, but 5 withdrew (final N=80). Participants were predominantly female (90%, 72/80) with a variety of vulnerabilities. Mean VL decreased from 1098 copies/mL in the control year to 439 copies/mL at study end (P=.004). Adherence to cART significantly improved (OR 1.14, IQR 1.10-1.18; P<.001), whereas appointment attendance decreased slightly with the intervention (OR 0.81, IQR 0.67-0.99; P=.03). A response was received for 46.57% (1753/3764) of messages sent and 9.62% (362/3764) of text messages sent were replied to with a problem. An outcome analysis examining relationship between reply rate and VL did not meet statistical significance (P=.07), but may be worthy of investigating further in a larger study. WelTel may be an effective tool for improving cART adherence and reducing VLs among high-risk, vulnerable HIV-positive persons. Clinicaltrials.gov NCT02603536; https://clinicaltrials.gov/ct2/show/NCT02603536 (Archived by WebCite at http://www.webcitation.org/6qK57zCwv). ©Elizabeth King, Karen Kinvig, Jonathan Steif, Annie Q Qiu, Evelyn J Maan, Arianne YK Albert, Neora Pick, Ariane Alimenti, Mary H Kestler, Deborah M Money, Richard T Lester, Melanie Caroline Margaret Murray. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.06.2017.

Pan-Arctic patterns of planktonic heterotrophic microbial abundance and processes: Controlling factors and potential impacts of warming

NASA Astrophysics Data System (ADS)

Maranger, Roxane; Vaqué, Dolors; Nguyen, Dan; Hébert, Marie-Pier; Lara, Elena

2015-12-01

The Arctic Ocean is rapidly changing where increasing water temperatures and rapid loss of summer sea-ice will likely influence the structure and functioning of the entire ecosystem. The aim of this study was to synthesize the current state of knowledge on microbial abundances and processes from a regional Pan-Arctic perspective, characterize regulating factors and attempt to predict how patterns may change under a warming scenario. Here we identify some generalized patterns of different microbial variables between the Pacific-fed and the Atlantic-fed sectors of the Arctic Ocean. Bacterial production (BP), abundance and grazing rates by protists (GT) were all higher in the Atlantic-fed region. Bacterial loss by viral lyses (VL) was proportionally more important in the Pacific-fed sector, suggesting a reduced C transfer efficiency within the microbial loop of that region. Using a cross-comparative approach and all available data to build Arrhenius plots, we found a differential response to warming temperatures among various microbial processes. BP and GT responded similarly and more strongly to increases in temperature than VL did, suggesting a shift in the overall influence of viral mortality under a warming scenario. However, together with temperature, resource-related factors also exerted an influence in regulating these rates. We identified large information gaps for more classically studied microbial variable from several Arctic seas. Furthermore, there is limited information on less conventional pathways such as grazing by mixotrophic species, which may be playing a significant role in Arctic microbial trophodynamics. Although generalized patterns could be elucidated, more information is needed to predict and understand how a changing Arctic will alter microbial C pathways and major biogeochemical cycles on regional and seasonal scales.

Effects of fatigue on kinetic and kinematic variables during a 60-second repeated jumps test.

PubMed

McNeal, Jeni R; Sands, William A; Stone, Michael H

2010-06-01

The aim of this study was to investigate the effects of a maximal repeated-jumps task on force production, muscle activation and kinematics, and to determine if changes in performance were dependent on gender. Eleven male and nine female athletes performed continuous countermovement jumps for 60 s on a force platform while muscle activation was assessed using surface electromyography. Performances were videotaped and digitized (60 Hz). Data were averaged across three jumps in 10-s intervals from the initial jump to the final 10 s of the test. No interaction between time and gender was evident for any variable; therefore, all results represent data collapsed across gender. Preactivation magnitude decreased across time periods for anterior tibialis (AT, P < .001), gastrocnemius (GAS, P < .001) and biceps femoris (BF, P = .03), but not for vastus lateralis (VL, P = .16). Muscle activation during ground contact did not change across time for BF; however, VL, G, and AT showed significant reductions (all P < .001). Peak force was reduced at 40 s compared with the initial jumps, and continued to be reduced at 50 and 60 s (all P < .05). The time from peak force to takeoff was greater at 50 and 60 s compared with the initial jumps (P < .05). Both knee flexion and ankle dorsiflexion were reduced across time (both P < .001), whereas no change in relative hip angle was evident (P = .10). Absolute angle of the trunk increased with time (P < .001), whereas the absolute angle of the shank decreased (P < .001). In response to the fatiguing task, subjects reduced muscle activation and force production and altered jumping technique; however, these changes were not dependent on gender.

Scaling up HIV viral load - lessons from the large-scale implementation of HIV early infant diagnosis and CD4 testing.

PubMed

Peter, Trevor; Zeh, Clement; Katz, Zachary; Elbireer, Ali; Alemayehu, Bereket; Vojnov, Lara; Costa, Alex; Doi, Naoko; Jani, Ilesh

2017-11-01

The scale-up of effective HIV viral load (VL) testing is an urgent public health priority. Implementation of testing is supported by the availability of accurate, nucleic acid based laboratory and point-of-care (POC) VL technologies and strong WHO guidance recommending routine testing to identify treatment failure. However, test implementation faces challenges related to the developing health systems in many low-resource countries. The purpose of this commentary is to review the challenges and solutions from the large-scale implementation of other diagnostic tests, namely nucleic-acid based early infant HIV diagnosis (EID) and CD4 testing, and identify key lessons to inform the scale-up of VL. Experience with EID and CD4 testing provides many key lessons to inform VL implementation and may enable more effective and rapid scale-up. The primary lessons from earlier implementation efforts are to strengthen linkage to clinical care after testing, and to improve the efficiency of testing. Opportunities to improve linkage include data systems to support the follow-up of patients through the cascade of care and test delivery, rapid sample referral networks, and POC tests. Opportunities to increase testing efficiency include improvements to procurement and supply chain practices, well connected tiered laboratory networks with rational deployment of test capacity across different levels of health services, routine resource mapping and mobilization to ensure adequate resources for testing programs, and improved operational and quality management of testing services. If applied to VL testing programs, these approaches could help improve the impact of VL on ART failure management and patient outcomes, reduce overall costs and help ensure the sustainable access to reduced pricing for test commodities, as well as improve supportive health systems such as efficient, and more rigorous quality assurance. These lessons draw from traditional laboratory practices as well as fields such as logistics, operations management and business. The lessons and innovations from large-scale EID and CD4 programs described here can be adapted to inform more effective scale-up approaches for VL. They demonstrate that an integrated approach to health system strengthening focusing on key levers for test access such as data systems, supply efficiencies and network management. They also highlight the challenges with implementation and the need for more innovative approaches and effective partnerships to achieve equitable and cost-effective test access. © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

Dolutegravir-lamivudine as initial therapy in HIV-1 infected, ARV-naive patients, 48-week results of the PADDLE (Pilot Antiretroviral Design with Dolutegravir LamivudinE) study.

PubMed

Cahn, Pedro; Rolón, María José; Figueroa, María Inés; Gun, Ana; Patterson, Patricia; Sued, Omar

2017-05-09

A proof-of-concept study was designed to evaluate the antiviral efficacy, safety and tolerability of a two-drug regimen with dolutegravir 50 mg once daily (QD) plus lamivudine 300 mg once daily as initial highly active antiretroviral therapy (HAART) among antiretroviral (ARV)-naive patients. PADDLE is a pilot study including 20 treatment-naive adults. To be selected, participants had no IAS-USA-defined resistance, HIV-1 RNA ≤100,000 copies/mL at screening and negative HBsAg. Plasma viral load (pVL) was measured at baseline; days 2, 4, 7, 10, 14, 21 and 28; weeks 6, 8 and 12; and thereafter every 12 weeks up to 96 weeks. Primary endpoint was the proportion of patients with HIV-1 RNA <50 copies/mL in an intention to treat (ITT)-exposed analysis at 48 weeks (the FDA snapshot algorithm). Median HIV-1 RNA at entry was 24,128 copies/mL (interquartile range (IQR): 11,686-36,794). Albeit as per protocol, all patients had pVL ≤100,000 copies/mL at screening as required by inclusion criteria, four patients had ≥100,000 copies/mL at baseline. Median baseline CD4+ T-cell count was 507 per cubic millimetre (IQR: 296-517). A rapid decline in pVL was observed (median VL decay from baseline to week 12 was 2.74 logs). All patients were suppressed at week 8 onwards up to week 24. At week 48, 90% (18/20) reached the primary endpoint of a pVL <50 copies/mL. Median change in CD4 cell count between baseline and week 48 was 267 cells/mm 3 (IQR: 180-462). No major tolerability/toxicity issues were observed. Nineteen patients completed 48 weeks of the study, and one patient (with undetectable VL at last visit) committed suicide. One patient presented a low-level protocol-defined confirmed virological failure at week 36, being the only observed failure. This patient had pVL <50 copies/mL at the end-of-study visit without having changed the two-drug regimen. Observed failure rate was 5%. This is the first report of integrase strand transfer inhibitor/lamivudine dual regimen in ARV-naive patients. This novel dual regimen of dolutegravir and lamivudine warrants further clinical research and consideration as a potential therapeutic option for ARV-therapy-naive patients. NCT02211482.

Greater risk for viremia, immunosuppression, serious clinical events, and mortality with increasing age: the US perinatal HIV epidemic in its adolescence

PubMed Central

Neilan, Anne M.; Karalius, Brad; Patel, Kunjal; Van Dyke, Russell B.; Abzug, Mark J.; Agwu, Allison L.; Williams, Paige L.; Purswani, Murli; Kacanek, Deborah; Oleske, James M.; Burchett, Sandra K.; Wiznia, Andrew; Chernoff, Miriam; Seage, George R.; Ciaranello, Andrea L.

2017-01-01

Importance As perinatally HIV-infected youth (PHIVY) in the US grow older and more treatment-experienced, clinicians need updated information about the impact of age, CD4 count, viral load (VL), and antiretroviral drug (ARV) use on risks of opportunistic infections (OIs), key clinical events, and mortality in order to understand patient risks and improve care. Objective To determine the incidence or first occurrence during follow-up of key clinical events (including CDC-B and CDC-C events) and mortality among PHIVY stratified by age, CD4, and VL/ARV status. Design In the PHACS Adolescent Master Protocol (AMP) and IMPAACT P1074 multicenter cohort studies (2007–2015), we estimated event rates during person-time spent in key strata of age (7–12, 13–17, and 18–30 years), CD4 count (<200, 200–499, and ≥500 cells/μL), and VL/ARV status (< or ≥ 400 copies/mL; ARVs or no ARVs). Setting 41 ambulatory sites in the US, including Puerto Rico. Participants 1,562 participants in AMP and P1074 were eligible, 1446 PHIVY were included. Exposure(s) for observational studies Age, CD4 count, VL, ARV use. Main outcomes Clinical event rates stratified by person-time in age, CD4 count, and VL/ARV categories. Results During a mean follow-up of 4.9 years, higher incidences of CDC-B events, CDC-C events and mortality were observed as participants aged. Older PHIVY (13–17 and 18–30 year-olds) spent more time with VL ≥400 copies/mL and with CD4 <200/μL compared to 7–12 year-olds (30% and 44% vs. 22% of person-time with VL ≥400 copies/mL; 5% and 18% vs. 2% of person-time with CD4 <200/μL; p<0.01 for each comparison). We observed higher rates of CDC-B events, CDC-C events, bacterial infections, and mortality at lower CD4 counts, as expected. The mortality rate in older PHIVY was 6–12 times that of the general US population. Higher rates of sexually transmitted infections were also observed at lower CD4 counts, after adjusting for age. Conclusions and relevance Older PHIVY were at increased risk of viremia, immunosuppression, CDC-B events, CDC-C events, and mortality. Interventions to improve ART adherence and optimize models of care for PHIVY as they age are urgently needed to improve long-term outcomes among PHIVY. PMID:28346597

Leishmania Antigenuria to Predict Initial Treatment Failure and Relapse in Visceral Leishmaniasis/HIV Coinfected Patients: An Exploratory Study Nested Within a Clinical Trial in Ethiopia.

PubMed

van Griensven, Johan; Mengesha, Bewketu; Mekonnen, Tigist; Fikre, Helina; Takele, Yegnasew; Adem, Emebet; Mohammed, Rezika; Ritmeijer, Koert; Vogt, Florian; Adriaensen, Wim; Diro, Ermias

2018-01-01

Background: Biomarkers predicting the risk of VL treatment failure and relapse in VL/HIV coinfected patients are needed. Nested within a two-site clinical trial in Ethiopia (2011-2015), we conducted an exploratory study to assess whether (1) levels of Leishmania antigenuria measured at VL diagnosis were associated with initial treatment failure and (2) levels of Leishmania antigenuria at the end of treatment (parasitologically-confirmed cure) were associated with subsequent relapse. Methods: Leishmania antigenuria at VL diagnosis and cure was determined using KAtex urine antigen test and graded as negative (0), weak/moderate (grade 1+/2+) or strongly-positive (3+). Logistic regression and Kaplan-Meier methods were used to assess the association between antigenuria and (1) initial treatment failure, and (2) relapse over the 12 months after cure, respectively. Results: The analysis to predict initial treatment failure included sixty-three coinfected adults [median age: 30 years interquartile range (IQR) 27-35], median CD4 count: 56 cells/μL (IQR 38-113). KAtex results at VL diagnosis were negative in 11 (17%), weak/moderate in 17 (27%) and strongly-positive in 35 (36%). Twenty (32%) patients had parasitologically-confirmed treatment failure, with a risk of failure of 9% (1/11) with KAtex-negative results, 0% (0/17) for KAtex 1+/2+ and 54% (19/35) for KAtex 3+ results. Compared to KAtex-negative patients, KAtex 3+ patients were at increased risk of treatment failure [odds ratio 11.9 (95% CI 1.4-103.0); P : 0.025]. Forty-four patients were included in the analysis to predict relapse [median age: 31 years (IQR 28-35), median CD4 count: 116 cells/μL (IQR 95-181)]. When achieving VL cure, KAtex results were negative in 19 (43%), weak/moderate (1+/2+) in 10 (23%), and strongly positive (3+) in 15 patients (34%). Over the subsequent 12 months, eight out of 44 patients (18%) relapsed. The predicted 1-year relapse risk was 6% for KAtex-negative results, 14% for KAtex 1+/2+ and 42% for KAtex 3+ results [hazard ratio of 2.2 (95% CI 0.1-34.9) for KAtex 1+/2+ and 9.8 (95% CI 1.8-82.1) for KAtex 3+, compared to KAtex negative patients; P : 0.03]. Conclusion: A simple field-deployable Leishmania urine antigen test can be used for risk stratification of initial treatment failure and VL relapse in HIV-patients. A dipstick-format would facilitate field implementation.

Visceral Leishmaniasis

DTIC Science & Technology

2011-06-01

er than 1:256. These positive IFA tests are readily distin- guishable from the low-titer positive tests occasionally seen in malaria, typhoid fever ...leishmaniasis (VL), a chronic disease caused by parasites of the Leishmania donovani complex, is character- ized by irregular fever , enlargement of the...meaning “black sickness”, although hyperpigmenta- tion is not a common feature of the disease. Descriptive names for VL, such as Burdwan fever , Dumdum

NASA Global Atmospheric Sampling Program (GASP) data report for tapes VL0011 and VL0013

NASA Technical Reports Server (NTRS)

Holdeman, J. D.; Dudzinski, T. J.; Tiefermann, M. W.

1979-01-01

In-situ measurements of atmospheric ozone, carbon monoxide, clouds, and related meteorological and flight information obtained during 1122 flights of aircraft VH-EBE and N655PA from January 10 through October 2, 1977 are reported. In addition, tropopause pressures obtained from time and space interpolation of achieved data for the dates of the flights are included.

Polymerase Chain Reaction in the Diagnosis of Visceral Leishmaniasis Recurrence in the Setting of Negative Splenic Smears

PubMed Central

Hasnain, Golam; Basher, Ariful; Nath, Proggananda; Ghosh, Prakash; Hossain, Faria; Hossain, Shakhawat; Mondal, Dinesh

2016-01-01

This report presents two cases of visceral leishmaniasis (VL) recurrence where the microscopy of the splenic smear failed in diagnosis. However, a strong clinical suspicion compelled further evaluation by polymerase chain reaction (PCR), which validated the etiology. This short report highlights the usefulness of PCR in diagnosing cases of suspected smear-negative VL recurrence. PMID:26556834

Lack of a significant impact of Gag-Protease-mediated HIV-1 replication capacity on clinical parameters in treatment-naive Japanese individuals.

PubMed

Sakai, Keiko; Chikata, Takayuki; Brumme, Zabrina L; Brumme, Chanson J; Gatanaga, Hiroyuki; Gatanag, Hiroyuki; Oka, Shinichi; Takiguchi, Masafumi

2015-11-19

HLA class I-associated escape mutations in HIV-1 Gag can reduce viral replication, suggesting that associated fitness costs could impact HIV-1 disease progression. Previous studies in North American and African cohorts have reported reduced Gag-Protease mediated viral replication capacity (Gag-Pro RC) in individuals expressing protective HLA class I alleles including HLA-B*57:01, B*27:05, and B*81:01. These studies also reported significant positive associations between Gag-Pro RCs and plasma viral load (pVL). However, these HLA alleles are virtually absent in Japan, and the importance of Gag as an immune target is not clearly defined in this population. We generated chimeric NL4-3 viruses carrying patient-derived Gag-Protease from 306 treatment-naive Japanese individuals chronically infected with HIV-1 subtype B. We analyzed associations between Gag-Pro RC and clinical markers of HIV-1 infection and host HLA expression. We observed no significant correlation between Gag-Pro RC and pVL in Japan in the overall cohort. However, upon exclusion of individuals expressing Japanese protective alleles HLA-B*52:01 and B*67:01, Gag-Pro RC correlated positively with pVL and negatively with CD4 T-cell count. Our results thus contrast with studies from other global cohorts reporting significantly lower Gag-Pro RC among persons expressing protective HLA alleles, and positive relationships between Gag-Pro RC and pVL in the overall study populations. We also identified five amino acids in Gag-Protease significantly associated with Gag-Pro RC, whose effects on RC were confirmed by site-directed mutagenesis. However, of the four mutations that decreased Gag-Pro RC, none were associated with reductions in pVL in Japan though two were associated with lower pVL in North America. These data indicate that Gag fitness does not affect clinical outcomes in subjects with protective HLA class I alleles as well as the whole Japanese population. Moreover, the impact of Gag fitness costs on HIV-1 clinical parameters in chronic infection is likely low in Japan compared to other global populations.

Mortality and Case Fatality Due to Visceral Leishmaniasis in Brazil: A Nationwide Analysis of Epidemiology, Trends and Spatial Patterns

PubMed Central

Martins-Melo, Francisco Rogerlândio; Lima, Mauricélia da Silveira; Ramos, Alberto Novaes; Alencar, Carlos Henrique; Heukelbach, Jorg

2014-01-01

Background Visceral leishmaniasis (VL) is a significant public health problem in Brazil and several regions of the world. This study investigated the magnitude, temporal trends and spatial distribution of mortality related to VL in Brazil. Methods We performed a study based on secondary data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil from 2000 to 2011, in which VL was recorded as cause of death. We present epidemiological characteristics, trend analysis of mortality and case fatality rates by joinpoint regression models, and spatial analysis using municipalities as geographical units of analysis. Results In the study period, 12,491,280 deaths were recorded in Brazil. VL was mentioned in 3,322 (0.03%) deaths. Average annual age-adjusted mortality rate was 0.15 deaths per 100,000 inhabitants and case fatality rate 8.1%. Highest mortality rates were observed in males (0.19 deaths/100,000 inhabitants), <1 year-olds (1.03 deaths/100,000 inhabitants) and residents in Northeast region (0.30 deaths/100,000 inhabitants). Highest case fatality rates were observed in males (8.8%), ≥70 year-olds (43.8%) and residents in South region (17.7%). Mortality and case fatality rates showed a significant increase in Brazil over the period, with different patterns between regions: increasing mortality rates in the North (Annual Percent Change – APC: 9.4%; 95% confidence interval – CI: 5.3 to 13.6), and Southeast (APC: 8.1%; 95% CI: 2.6 to 13.9); and increasing case fatality rates in the Northeast (APC: 4.0%; 95% CI: 0.8 to 7.4). Spatial analysis identified a major cluster of high mortality encompassing a wide geographic range in North and Northeast Brazil. Conclusions Despite ongoing control strategies, mortality related to VL in Brazil is increasing. Mortality and case fatality vary considerably between regions, and surveillance and control measures should be prioritized in high-risk clusters. Early diagnosis and treatment are fundamental strategies for reducing case fatality of VL in Brazil. PMID:24699517

Knee and Hip Joint Kinematics Predict Quadriceps and Hamstrings Neuromuscular Activation Patterns in Drop Jump Landings

PubMed Central

Malfait, Bart; Dingenen, Bart; Smeets, Annemie; Staes, Filip; Pataky, Todd; Robinson, Mark A.; Vanrenterghem, Jos; Verschueren, Sabine

2016-01-01

Purpose The purpose was to assess if variation in sagittal plane landing kinematics is associated with variation in neuromuscular activation patterns of the quadriceps-hamstrings muscle groups during drop vertical jumps (DVJ). Methods Fifty female athletes performed three DVJ. The relationship between peak knee and hip flexion angles and the amplitude of four EMG vectors was investigated with trajectory-level canonical correlation analyses over the entire time period of the landing phase. EMG vectors consisted of the {vastus medialis(VM),vastus lateralis(VL)}, {vastus medialis(VM),hamstring medialis(HM)}, {hamstring medialis(HM),hamstring lateralis(HL)} and the {vastus lateralis(VL),hamstring lateralis(HL)}. To estimate the contribution of each individual muscle, linear regressions were also conducted using one-dimensional statistical parametric mapping. Results The peak knee flexion angle was significantly positively associated with the amplitudes of the {VM,HM} and {HM,HL} during the preparatory and initial contact phase and with the {VL,HL} vector during the peak loading phase (p<0.05). Small peak knee flexion angles were significantly associated with higher HM amplitudes during the preparatory and initial contact phase (p<0.001). The amplitudes of the {VM,VL} and {VL,HL} were significantly positively associated with the peak hip flexion angle during the peak loading phase (p<0.05). Small peak hip flexion angles were significantly associated with higher VL amplitudes during the peak loading phase (p = 0.001). Higher external knee abduction and flexion moments were found in participants landing with less flexed knee and hip joints (p<0.001). Conclusion This study demonstrated clear associations between neuromuscular activation patterns and landing kinematics in the sagittal plane during specific parts of the landing. These findings have indicated that an erect landing pattern, characterized by less hip and knee flexion, was significantly associated with an increased medial and posterior neuromuscular activation (dominant hamstrings medialis activity) during the preparatory and initial contact phase and an increased lateral neuromuscular activation (dominant vastus lateralis activity) during the peak loading phase. PMID:27101130

Measuring Retention in HIV Care: The Elusive Gold Standard

PubMed Central

Mugavero, Michael J.; Westfall, Andrew O.; Zinski, Anne; Davila, Jessica; Drainoni, Mari-Lynn; Gardner, Lytt I.; Keruly, Jeanne C.; Malitz, Faye; Marks, Gary; Metsch, Lisa; Wilson, Tracey E.; Giordano, Thomas P.

2012-01-01

Background Measuring retention in HIV primary care is complex as care includes multiple visits scheduled at varying intervals over time. We evaluated six commonly used retention measures in predicting viral load (VL) suppression and the correlation among measures. Methods Clinic-wide patient-level data from six academic HIV clinics were used for 12-months preceding implementation of the CDC/HRSA Retention in Care intervention. Six retention measures were calculated for each patient based upon scheduled primary HIV provider visits: count and dichotomous missed visits, visit adherence, 6-month gap, 4-month visit constancy, and the HRSA HAB retention measure. Spearman correlation coefficients and separate unadjusted logistic regression models compared retention measures to one another and with 12-month VL suppression, respectively. The discriminatory capacity of each measure was assessed with the c-statistic. Results Among 10,053 patients, 8,235 (82%) had 12-month VL measures, with 6,304 (77%) achieving suppression (VL<400 c/mL). All six retention measures were significantly associated (P<0.0001) with VL suppression (OR;95%CI, c-statistic): missed visit count (0.73;0.71–0.75,0.67), missed visit dichotomous (3.2;2.8–3.6,0.62), visit adherence (3.9;3.5–4.3,0.69), gap (3.0;2.6–3.3,0.61), visit constancy (2.8;2.5–3.0,0.63), HRSA HAB (3.8;3.3–4.4,0.59). Measures incorporating “no show” visits were highly correlated (Spearman coefficient=0.83–0.85), as were measures based solely upon kept visits (Spearman coefficient=0.72–0.77). Correlation coefficients were lower across these two groups of measures (Range=0.16–0.57). Conclusions Six retention measures displayed a wide range of correlation with one another, yet each measure had significant association and modest discrimination for VL suppression. These data suggest there is no clear gold standard, and that selection of a retention measure may be tailored to context. PMID:23011397

Substance abuse treatment in an urban HIV clinic: who enrolls and what are the benefits?

PubMed

Pisu, Maria; Cloud, Gretchen; Austin, Shamly; Raper, James L; Stewart, Katharine E; Schumacher, Joseph E

2010-03-01

Substance abuse treatment (SAT) is important for HIV medical care. Characteristics of those who choose SAT and effects of SAT on HIV clinical outcomes are not understood. We compared patients who enrolled and did not enroll in a SAT program offered within an HIV clinic, and evaluated the effect of SAT on CD4 T-cell counts and HIV plasma viral load (VL). Subjects were assessed and invited to enroll in SAT. Enrollees chose to receive psychological and psychiatric treatment, or motivational enhancement and relapse prevention, or residential SAT. We used logistic regressions to determine factors associated with enrollment (age, race, sex, HIV transmission risk factors, CD4 T-cell counts, and VL at assessment). A two-period (assessment and six months after SAT) data analysis was used to analyze the effect of SAT on CD4 T-cell count and log VL controlling for changes in HIV therapy. We find that, compared to Decliners (N=76), Enrollees (N=78) were more likely to be females (29.5% vs. 6.6%, OR=5.32, 95% CI 1.61-17.6), and to report injection drug use (IDU) as the HIV transmission risk factor (23.1% vs. 9.2%, OR=3.92, CI 1.38-11.1). Age (37.2 vs. 38.4), CD4 T-cell count (377.3 vs. 409.2), and log VL (3.21 vs. 2.99) at assessment were similar across the two groups (p>0.05). After six months, Enrollees and Decliners' CD4 T-cell counts increased and log VL decreased. SAT did not affect the change in CD4 T-cell count (p=0.51) or log VL (p=0.73). Similar results were found for patients with CD4 T-cell count < or =350 at assessment. In this small sample of HIV-infected patients with a limited follow-up period, women were more likely to enroll in SAT than men, and SAT reached those who needed it, e.g., IDUs. We did not find an effect of SAT on HIV clinical outcomes.

Transcriptional Profiling in Experimental Visceral Leishmaniasis Reveals a Broad Splenic Inflammatory Environment that Conditions Macrophages toward a Disease-Promoting Phenotype

PubMed Central

Spratt, Heidi; Travi, Bruno L.; Luxon, Bruce A.

2017-01-01

Visceral Leishmaniasis (VL), caused by the intracellular protozoan Leishmania donovani, is characterized by relentlessly increasing visceral parasite replication, cachexia, massive splenomegaly, pancytopenia and ultimately death. Progressive disease is considered to be due to impaired effector T cell function and/or failure of macrophages to be activated to kill the intracellular parasite. In previous studies, we used the Syrian hamster (Mesocricetus auratus) as a model because it mimics the progressive nature of active human VL. We demonstrated previously that mixed expression of macrophage-activating (IFN-γ) and regulatory (IL-4, IL-10, IL-21) cytokines, parasite-induced expression of macrophage arginase 1 (Arg1), and decreased production of nitric oxide are key immunopathologic factors. Here we examined global changes in gene expression to define the splenic environment and phenotype of splenic macrophages during progressive VL. We used RNA sequencing coupled with de novo transcriptome assembly, because the Syrian hamster does not have a fully sequenced and annotated reference genome. Differentially expressed transcripts identified a highly inflammatory spleen environment with abundant expression of type I and type II interferon response genes. However, high IFN-γ expression was ineffective in directing exclusive M1 macrophage polarization, suppressing M2-associated gene expression, and restraining parasite replication and disease. While many IFN-inducible transcripts were upregulated in the infected spleen, fewer were induced in splenic macrophages in VL. Paradoxically, IFN-γ enhanced parasite growth and induced the counter-regulatory molecules Arg1, Ido1 and Irg1 in splenic macrophages. This was mediated, at least in part, through IFN-γ-induced activation of STAT3 and expression of IL-10, which suggests that splenic macrophages in VL are conditioned to respond to macrophage activation signals with a counter-regulatory response that is ineffective and even disease-promoting. Accordingly, inhibition of STAT3 activation led to a reduced parasite load in infected macrophages. Thus, the STAT3 pathway offers a rational target for adjunctive host-directed therapy to interrupt the pathogenesis of VL. PMID:28141856

Characterization of HIV-1 antiretroviral drug resistance after second-line treatment failure in Mali, a limited-resources setting

PubMed Central

Maiga, Almoustapha Issiaka; Fofana, Djeneba Bocar; Cisse, Mamadou; Diallo, Fodié; Maiga, Moussa Youssoufa; Traore, Hamar Alassane; Maiga, Issouf Alassane; Sylla, Aliou; Fofana, Dionke; Taiwo, Babafemi; Murphy, Robert; Katlama, Christine; Tounkara, Anatole; Calvez, Vincent; Marcelin, Anne-Geneviève

2012-01-01

Objectives We describe the outcomes of second-line drug resistance profiles and predict the efficacy of drugs for third-line therapy in patients monitored without the benefit of plasma HIV-1 RNA viral load (VL) or resistance testing. Methods We recruited 106 HIV-1-infected patients after second-line treatment failure in Mali. VL was determined by the Abbott RealTime system and the resistance by the ViroSeq HIV-1 genotyping system. The resistance testing was interpreted using the latest version of the Stanford algorithm. Results Among the 106 patients, 93 had isolates successfully sequenced. The median age, VL and CD4 cells were respectively 35 years, 72 000 copies/mL and 146 cells/mm3. Patients were exposed to a median of 4 years of treatment and to six antiretrovirals. We found 20% of wild-type viruses. Resistance to etravirine was noted in 38%, to lopinavir in 25% and to darunavir in 12%. The duration of prior nucleos(t)ide reverse transcriptase inhibitor exposure was associated with resistance to abacavir (P < 0.0001) and tenofovir (P = 0.0001), and duration of prior protease inhibitor treatment with resistance to lopinavir (P < 0.0001) and darunavir (P = 0.06). Conclusion Long duration of therapy prior to failure was associated with high levels of resistance and is directly related to limited access to VL monitoring and delayed switches to second-line treatment, precluding efficacy of drugs for third-line therapy. This study underlines the need for governments and public health organizations to recommend the use of VL monitoring and also the availability of darunavir and raltegravir for third-line therapies in the context of limited-resource settings. PMID:22888273

Fiber orientation measurements by diffusion tensor imaging improve hydrogen-1 magnetic resonance spectroscopy of intramyocellular lipids in human leg muscles

PubMed Central

Valaparla, Sunil K.; Gao, Feng; Daniele, Giuseppe; Abdul-Ghani, Muhammad; Clarke, Geoffrey D.

2015-01-01

Abstract. Twelve healthy subjects underwent hydrogen-1 magnetic resonance spectroscopy (H1-MRS) acquisition (15×15×15  mm3), diffusion tensor imaging (DTI) with a b-value of 600  s mm−2, and fat-water magnetic resonance imaging (MRI) using the Dixon method. Subject-specific muscle fiber orientation, derived from DTI, was used to estimate the lipid proton spectral chemical shift. Pennation angles were measured as 23.78 deg in vastus lateralis (VL), 17.06 deg in soleus (SO), and 8.49 deg in tibialis anterior (TA) resulting in a chemical shift between extramyocellular lipids (EMCL) and intramyocellular lipids (IMCL) of 0.15, 0.17, and 0.19 ppm, respectively. IMCL concentrations were 8.66±1.24  mmol kg−1, 6.12±0.77  mmol kg−1, and 2.33±0.19  mmol kg−1 in SO, VL, and TA, respectively. Significant differences were observed in IMCL and EMCL pairwise comparisons in SO, VL, and TA (p<0.05). Strong correlations were observed between total fat fractions from H1-MRS and Dixon MRI for VL (r=0.794), SO (r=0.655), and TA (r=0.897). Bland-Altman analysis between fat fractions (FFMRS and FFMRI) showed good agreement with small limits of agreement (LoA): bias=−0.21% (LoA: −1.12% to 0.69%) in VL, bias=0.025% (LoA: −1.28% to 1.33%) in SO, and bias=−0.13% (LoA: −0.74% to 0.47%) in TA. The results of this study demonstrate the variation in muscle fiber orientation and lipid concentrations in these three skeletal muscle types. PMID:26158115

Molecular identification and polymorphism determination of cutaneous and visceral leishmaniasis agents isolated from human and animal hosts in Iran.

PubMed

Hajjaran, Homa; Mohebali, Mehdi; Mamishi, Setareh; Vasigheh, Farzaneh; Oshaghi, Mohammad Ali; Naddaf, Saied Reza; Teimouri, Aref; Edrissian, Gholam Hossein; Zarei, Zabiholah

2013-01-01

Amplification of internal transcript spacer 1 of ribosomal RNA (ITS1-RNA) gene followed by RFLP analysis and sequencing was used to identify the causing agents of cutaneous and visceral leishmaniasis (CL and VL) in humans and animal reservoir hosts from various geographical areas in Iran. We also used random amplified polymorphic DNA (RAPD-PCR) to obtain polymorphisms among isolates of Leishmania spp. Totally, 362 suspected human and animal cases including 173 CL, 49 VL, 60 rodents, and 80 domestic dogs were examined for Leishmania infection. From 112 culture-positive samples prepared from CL cases, 75 (67%) were infected with L. major and 37 (33%) with L. tropica. Of the 60 rodents examined, 25 (41.6%) harbored the Leishmania infection; 21 were infected with L. major and 4 with L. turanica. From 49 suspected VL, 29 were positive by direct agglutination test (DAT), whereas microscopy detected parasite in bone marrow of 25 and culture in 28 of the patients. Two VL patients were infected with L. tropica and 26 with L. infantum. Of the 80 domestic dogs, 56 showed anti-Leishmania antibodies with DAT. Of these, 55 were positive by both microscopy and culture. Molecular identity, obtained only for 47 samples, revealed L. infantum in 43 and L. tropica in 4 dogs. The polymorphisms among L. tropica and L. major isolates were 3.6% and 7.3%; the rate among human and canine VL isolates was 2.8% and 9.8%, respectively. Our results showed that at least four different Leishmania species with various polymorphisms circulate among humans and animal hosts in Iran.

Molecular Identification and Polymorphism Determination of Cutaneous and Visceral Leishmaniasis Agents Isolated from Human and Animal Hosts in Iran

PubMed Central

Mohebali, Mehdi; Mamishi, Setareh; Vasigheh, Farzaneh; Oshaghi, Mohammad Ali; Naddaf, Saied Reza; Teimouri, Aref; Edrissian, Gholam Hossein; Zarei, Zabiholah

2013-01-01

Amplification of internal transcript spacer 1 of ribosomal RNA (ITS1-RNA) gene followed by RFLP analysis and sequencing was used to identify the causing agents of cutaneous and visceral leishmaniasis (CL and VL) in humans and animal reservoir hosts from various geographical areas in Iran. We also used random amplified polymorphic DNA (RAPD-PCR) to obtain polymorphisms among isolates of Leishmania spp. Totally, 362 suspected human and animal cases including 173 CL, 49 VL, 60 rodents, and 80 domestic dogs were examined for Leishmania infection. From 112 culture-positive samples prepared from CL cases, 75 (67%) were infected with L. major and 37 (33%) with L. tropica. Of the 60 rodents examined, 25 (41.6%) harbored the Leishmania infection; 21 were infected with L. major and 4 with L. turanica. From 49 suspected VL, 29 were positive by direct agglutination test (DAT), whereas microscopy detected parasite in bone marrow of 25 and culture in 28 of the patients. Two VL patients were infected with L. tropica and 26 with L. infantum. Of the 80 domestic dogs, 56 showed anti-Leishmania antibodies with DAT. Of these, 55 were positive by both microscopy and culture. Molecular identity, obtained only for 47 samples, revealed L. infantum in 43 and L. tropica in 4 dogs. The polymorphisms among L. tropica and L. major isolates were 3.6% and 7.3%; the rate among human and canine VL isolates was 2.8% and 9.8%, respectively. Our results showed that at least four different Leishmania species with various polymorphisms circulate among humans and animal hosts in Iran. PMID:24286085

TRANSCUTANEOUS ELECTRICAL NERVE STIMULATION AT BOTH HIGH AND LOW FREQUENCIES ACTIVATES VENTROLATERAL PERIAQUEDUCTAL GREY TO DECREASE MECHANICAL HYPERALGESIA IN ARTHRITIC RATS

PubMed Central

Desantana, J. M.; Da Silva, L. F. S.; De Resende, M. A.; Sluka, K. A.

2014-01-01

Transcutaneous electric nerve stimulation (TENS) is widely used for the treatment of pain. TENS produces an opioid-mediated antinociception that utilizes the rostroventromedial medulla (RVM). Similarly, antinociception evoked from the periaqueductal grey (PAG) is opioid-mediated and includes a relay in the RVM. Therefore, we investigated whether the ventrolateral or dorsolateral PAG mediates antinociception produced by TENS in rats. Paw and knee joint mechanical withdrawal thresholds were assessed before and after knee joint inflammation (3% kaolin/carrageenan), and after TENS stimulation (active or sham). Cobalt chloride (CoCl2; 5 mM) or vehicle was microinjected into the ventrolateral periaqueductal grey (vlPAG) or dorsolateral periaqueductal grey (dlPAG) prior to treatment with TENS. Either high (100 Hz) or low (4 Hz) frequency TENS was then applied to the inflamed knee for 20 min. Active TENS significantly increased withdrawal thresholds of the paw and knee joint in the group microinjected with vehicle when compared to thresholds prior to TENS (P<0.001) or to sham TENS (P<0.001). The increases in withdrawal thresholds normally observed after TENS were prevented by microinjection of CoCl2 into the vlPAG, but not the dlPAG prior to TENS and were significantly lower than controls treated with TENS (P<0.001). In a separate group of animals, microinjection of CoCl2 into the vlPAG temporarily reversed the decreased mechanical withdrawal threshold suggesting a role for the vlPAG in the facilitation of joint pain. No significant difference was observed for dlPAG. We hypothesize that the effects of TENS are mediated through the vlPAG that sends projections through the RVM to the spinal cord to produce an opioid-mediated analgesia. PMID:19576962

Changes in proteomic profiles in different prostate lobes of male rats throughout growth and development and aging stages of the life span

PubMed Central

Das, Arunangshu; Bortner, James D.; Aliaga, Cesar A.; Baker, Aaron; Stanley, Anne; Stanley, Bruce A.; Kaag, Mathew; Richie, John P.; El-Bayoumy, Karam

2012-01-01

Background Aging-related changes in important cellular pathways in the prostate may promote a permissive environment for an increased risk for prostatic disease development such as prostate cancer. Our objectives were to examine for such changes, by systematically determining the effects of growth and development and aging on proteomic profiles in different lobes of the rat prostate. Methods Prostate lobes (dorsolateral lobe, DL and ventral lobe, VL) were obtained from male Fisher rats of various ages representing young (4 months), mature (12 months), old (18 months), and very old (24 months). Differentially expressed proteins between age groups in each lobe were identified using a proteomic approach, isobaric Tags for Relative and Absolute Quantitation (iTRAQ). Select changes in the DL and VL were verified by immunoblot analysis. Results iTRAQ identified 317 proteins with high confidence. iTRAQ discovered 12 and 6 proteins significantly modulated in response to growth and development in the DL and VL, respectively, and 42 and 29 proteins significantly modulated in response to aging in the DL and VL, respectively. Proteins modulated during growth and development in the DL and VL are involved in a variety of biological processes including cell communication and development, whereas proteins modulated during aging were predominantly related to antioxidant activity and immunity. Immunoblot analysis verified age-related changes for α-1 antitrypsin, annexin A1, hypoxia up-regulated protein 1, and 78 kDa glucose-regulated protein. Conclusions Aging results in changes in numerous prostatic proteins and pathways which are mainly linked to inflammation and may lead to prostatic disease development. PMID:22911278

Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

PubMed

Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

2016-10-01

Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Previous antiretroviral therapy for prevention of mother-to-child transmission of HIV does not hamper the initial response to PI-based multitherapy during subsequent pregnancy.

PubMed

Briand, Nelly; Mandelbrot, Laurent; Blanche, Stéphane; Tubiana, Roland; Faye, Albert; Dollfus, Catherine; Le Chenadec, Jérôme; Benhammou, Valérie; Rouzioux, Christine; Warszawski, Josiane

2011-06-01

Few data are available on the possible long-term negative effects of a short exposure to antiretroviral therapy (ART) for prevention of mother-to-child transmission (PMTCT). To determine whether ART for PMTCT, discontinued after delivery, affects the virological response to highly active antiretroviral therapy (HAART) administered during subsequent pregnancies. All current pregnancies of HIV-1-infected women enrolled in the French Perinatal Cohort (ANRS CO-01 EPF) between 2005 and 2009 and not receiving ART at the time of conception were eligible. We studied the association between history of exposure to ART during a previous pregnancy and detectable viral load (VL) under multitherapy at current delivery (VL ≥ 50 copies/mL). Among 1116 eligible women, 869 were ART naive and 247 had received PMTCT during a previous pregnancy. Previous ART was protease inhibitor (PI)-based HAART in 48%, non-PI-based HAART in 4%, nucleoside reverse transcriptase inhibitor bitherapy in 19% and zidovudine monotherapy in 29% of the women. At current pregnancy, women with or without prior exposure to ART had similar CD4 cell counts and VL before ART initiation. PI-based HAART was initiated in 90% of the women. VL was undetectable (<50 copies/mL) at delivery in 65% of previously ART-naive women, 72% of women previously exposed to HAART, 62% previously exposed to bitherapy, and 67% previously exposed to monotherapy for prophylaxis (P = 0.42). Detectable VL was not associated with previous exposure in multivariate analysis (adjusted OR for previous versus no previous exposure to ART: 0.92; 0.95% confidence interval: 0.59 to 1.44). Efficacy of PI-based combinations is not decreased in women previously exposed to various regimens of antiretroviral PMTCT.

Exposure to Violence and Virologic and Immunological Outcomes Among Youth with Perinatal HIV

PubMed Central

Kacanek, Deborah; Malee, Kathleen; Mellins, Claude A.; Tassiopoulos, Katherine; Smith, Renee; Grant, Mitzie; Lee, Sonia; Siddiqui, Danish Q.; Puga, Ana

2016-01-01

Purpose Exposure to violence in childhood has been linked to adverse health outcomes. Little is known about the prevalence and relationship of youth and caregiver violence exposure to clinical outcomes among youth with perinatal HIV infection (PHIV). We evaluated associations of youth and caregiver violence exposure with unsuppressed viral load (VL) (HIV RNA>400 copies/ml) and CD4%<25% among 8-15 year-old participants with PHIV in the Pediatric HIV/AIDS Cohort Study (PHACS) Adolescent Master Protocol (AMP). Methods Annual clinical examination, record abstraction and interview data were collected, including youth report of recent exposure to violence and caregivers' self-report of being assaulted/abused in adulthood. Multivariable logistic regression methods were used to calculate adjusted odds ratios (OR) for unsuppressed VL and CD4%<25%, controlling for socio-demographic characteristics. Results Among 268 youth with PHIV (53% girls, mean age 12.8 years, 21% white, 42% with household income<$20,000/year), 34% reported past year violence exposure; 30% had a caregiver who reported being assaulted in adulthood. One quarter of youth (24%) had unsuppressed VL, and 22% had CD4%<25%. Youth who were exposed to violence in the past year vs. those who were not had elevated odds of unsuppressed VL. Youth with indirect exposure to violence in the past year vs. those without had elevated odds of unsuppressed VL and CD4%<25% in adjusted models. Conclusion Youth with PHIV report a high prevalence of recent violence exposure, which was associated with poor virologic and immunologic outcomes. Reducing violence and providing support to youth with violence exposure and PHIV may improve health outcomes. PMID:27089837

Exposure to Violence and Virologic and Immunological Outcomes Among Youth With Perinatal HIV in the Pediatric HIV/AIDS Cohort Study.

PubMed

Kacanek, Deborah; Malee, Kathleen; Mellins, Claude A; Tassiopoulos, Katherine; Smith, Renee; Grant, Mitzie; Lee, Sonia; Siddiqui, Danish Q; Puga, Ana

2016-07-01

Exposure to violence in childhood has been linked to adverse health outcomes. Little is known about the prevalence and relationship of youth and caregiver violence exposure to clinical outcomes among youth with perinatal human immunodeficiency virus (HIV) infection (PHIV). We evaluated associations of youth and caregiver violence exposure with unsuppressed viral load (VL) (HIV RNA > 400 copies/mL) and CD4% <25% among 8- to 15-year-old participants with PHIV in the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol. Annual clinical examination, record abstraction, and interview data were collected, including youth report of recent exposure to violence and caregivers' self-report of being assaulted/abused in adulthood. Multivariable logistic regression methods were used to calculate adjusted odds ratios for unsuppressed VL and CD4% <25%, controlling for sociodemographic characteristics. Among 268 youth with PHIV (53% girls, mean age 12.8 years, 21% white, 42% with household income <$20,000/year), 34% reported past year violence exposure; 30% had a caregiver who reported being assaulted in adulthood. One quarter of youth (24%) had unsuppressed VL and 22% had CD4% <25%. Youth who were exposed to violence in the past year versus those who were not had elevated odds of unsuppressed VL. Youth with indirect exposure to violence in the past year versus those without had elevated odds of unsuppressed VL and CD4% <25% in adjusted models. Youth with PHIV report a high prevalence of recent violence exposure, which was associated with poor virologic and immunologic outcomes. Reducing violence and providing support to youth with violence exposure and PHIV may improve health outcomes. Copyright © 2016 Society for Adolescent Health and Medicine. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dewitt, Ann E.; Dong, Jian Y.; Wiley, H S.

Autocrine signaling is important in normal tissue physiology as well as pathological conditions. It is difficult to analyze these systems, however, because they are both self-contained and recursive. To understand how parameters, such as ligand production and receptor expression influence autocrine activity, we investigated a human epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) loop engineered into mouse B82 fibroblasts. We varied the level of ligand production using the tet-off expression system and used metalloprotease inhibitors to modulate ligand release. Receptor expression was varied using antagonistic, blocking antibodies. We compared autocrine ligand release to receptor activation using a microphysiometer-based assay andmore » analyzed our data with a quantitative model of ligand release and receptor dynamics. We found that the activity of our autocrine system could be described in terms of a simple ratio between the rate of ligand production (VL) and the rate of receptor production (VR). At a VL/VR ratio of < 0.3, essentially no ligand was found in the extracellular medium, but a significant number cell receptors (30-40%) were occupied. As the VL/VR ratio increased from 0.3 towards unity, receptor occupancy increased, and significant amounts of ligand now appeared in the medium. Above a VL/VR ratio of 1.0, receptor occupancy approached saturation and most of the released ligand was lost into the medium. Analysis of human mammary epithelial cells showed that a VL/VR ratio of < 5 x 10 -4 was sufficient to evoke >20% of a maximal proliferative response. This suggests that natural autocrine systems are active even when no ligand appears in the extracellular medium; i.e., they operate 'invisibly' to general detection.« less

Visceral Leishmaniasis in China: an Endemic Disease under Control

PubMed Central

Wu, Ming-Shui; Chen, Yun-Fu; Wang, Jun-Yun; Zhou, Xiao-Nong; Liao, Li-Fu; Chen, Jian-Ping; Chow, Larry M. C.

2015-01-01

SUMMARY Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species: Phlebotomus chinensis, P. longiductus, P. wui, and P. alexandri. In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs. PMID:26354822

Personality and HIV Disease Progression: Role of NEO-PI-R Openness, Extraversion, and Profiles of Engagement

PubMed Central

O'Cleirigh, Conall; Schneiderman, Neil; Weiss, Alexander; Costa, Paul T.

2008-01-01

Objective To examine the role of the big five personality domains (Neuroticism, Extraversion, Openness, Agreeableness, Conscientiousness) and their respective facets and profiles on change in CD4 and log HIV-RNA copies/ml (VL) over 4 years. The examination of psychosocial predictors of disease progression in human immunodeficiency virus (HIV) has focused primarily on depression, coping, and stress, with little attention paid to stable individual differences. Methods A diverse sample of HIV-seropositive patients (n = 104) completed personality assessment (NEO-PI-R), underwent comprehensive psychological assessment and blood samples every 6 months for 4 years. Linear rates of change for CD4 cells and VL were modeled using Hierarchical Linear Modeling controlling for antiretrovirals (time dependent covariate), initial disease status, age, gender, ethnicity, and education. Results Domains that were significantly associated with slower disease progression over 4 years included Openness (CD4, VL), Extraversion (CD4, VL), and Conscientiousness (VL). Facets of the above domains that were significantly related to slower disease progression were assertiveness, positive emotions, and gregariousness (Extraversion); ideas, esthetics (Openness); achievement striving and order (Conscientiousness). In addition, profile analyses suggested personality styles which seem to underscore the importance of remaining engaged (e.g., Creative Interactors (E+O+), Upbeat Optimists (N−E+), Welcomers (E+A+), Go Getters (C+E+), and Directed (N−C+)) had slower disease progression, whereas the “homebody” profile (Low Extraversion-Low Openness) was significantly associated with faster disease progression. Conclusions These results provide good initial evidence of the relationship between personality and disease progression in HIV and suggest protective aspects of profiles of engagement. These finding may help identify those individuals at risk for poorer disease course and specify targets for psychosocial interventions. PMID:18256349

Serological Markers of Sand Fly Exposure to Evaluate Insecticidal Nets against Visceral Leishmaniasis in India and Nepal: A Cluster-Randomized Trial

PubMed Central

Gidwani, Kamlesh; Picado, Albert; Rijal, Suman; Singh, Shri Prakash; Roy, Lalita; Volfova, Vera; Andersen, Elisabeth Wreford; Uranw, Surendra; Ostyn, Bart; Sudarshan, Medhavi; Chakravarty, Jaya; Volf, Petr; Sundar, Shyam; Boelaert, Marleen; Rogers, Matthew Edward

2011-01-01

Background Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. Methods As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention. Results A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83–0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80–1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi. Conclusions This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions. PMID:21931871

Serological markers of sand fly exposure to evaluate insecticidal nets against visceral leishmaniasis in India and Nepal: a cluster-randomized trial.

PubMed

Gidwani, Kamlesh; Picado, Albert; Rijal, Suman; Singh, Shri Prakash; Roy, Lalita; Volfova, Vera; Andersen, Elisabeth Wreford; Uranw, Surendra; Ostyn, Bart; Sudarshan, Medhavi; Chakravarty, Jaya; Volf, Petr; Sundar, Shyam; Boelaert, Marleen; Rogers, Matthew Edward

2011-09-01

Visceral leishmaniasis is the world' second largest vector-borne parasitic killer and a neglected tropical disease, prevalent in poor communities. Long-lasting insecticidal nets (LNs) are a low cost proven vector intervention method for malaria control; however, their effectiveness against visceral leishmaniasis (VL) is unknown. This study quantified the effect of LNs on exposure to the sand fly vector of VL in India and Nepal during a two year community intervention trial. As part of a paired-cluster randomized controlled clinical trial in VL-endemic regions of India and Nepal we tested the effect of LNs on sand fly biting by measuring the antibody response of subjects to the saliva of Leishmania donovani vector Phlebotomus argentipes and the sympatric (non-vector) Phlebotomus papatasi. Fifteen to 20 individuals above 15 years of age from 26 VL endemic clusters were asked to provide a blood sample at baseline, 12 and 24 months post-intervention. A total of 305 individuals were included in the study, 68 participants provided two blood samples and 237 gave three samples. A random effect linear regression model showed that cluster-wide distribution of LNs reduced exposure to P. argentipes by 12% at 12 months (effect 0.88; 95% CI 0.83-0.94) and 9% at 24 months (effect 0.91; 95% CI 0.80-1.02) in the intervention group compared to control adjusting for baseline values and pair. Similar results were obtained for P. papatasi. This trial provides evidence that LNs have a limited effect on sand fly exposure in VL endemic communities in India and Nepal and supports the use of sand fly saliva antibodies as a marker to evaluate vector control interventions.

Visceral Leishmaniasis in China: an Endemic Disease under Control.

PubMed

Lun, Zhao-Rong; Wu, Ming-Shui; Chen, Yun-Fu; Wang, Jun-Yun; Zhou, Xiao-Nong; Liao, Li-Fu; Chen, Jian-Ping; Chow, Larry M C; Chang, Kwang Poo

2015-10-01

Visceral leishmaniasis (VL) caused by Leishmania spp. is an important vector-borne and largely zoonotic disease. In China, three epidemiological types of VL have been described: anthroponotic VL (AVL), mountain-type zoonotic VL (MT-ZVL), and desert-type ZVL (DT-ZVL). These are transmitted by four different sand fly species: Phlebotomus chinensis, P. longiductus, P. wui, and P. alexandri. In 1951, a detailed survey of VL showed that it was rampant in the vast rural areas west, northwest, and north of the Yangtze River. Control programs were designed and implemented stringently by the government at all administrative levels, resulting in elimination of the disease from most areas of endemicity, except the western and northwestern regions. The control programs consisted of (i) diagnosis and chemotherapy of patients, (ii) identification, isolation, and disposal of infected dogs, and (iii) residual insecticide indoor spraying for vector control. The success of the control programs is attributable to massive and effective mobilization of the general public and health workers to the cause. Nationally, the annual incidence is now very low, i.e., only 0.03/100,000 according to the available 2011 official record. The overwhelming majority of cases are reported from sites of endemicity in the western and northwestern regions. Here, we describe in some depth and breadth the current status of epidemiology, diagnosis, treatment, and prevention of the disease, with particular reference to the control programs. Pertinent information has been assembled from scattered literature of the past decades in different languages that are not readily accessible to the scientific community. The information provided constitutes an integral part of our knowledge on leishmaniasis in the global context and will be of special value to those interested in control programs. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Differential Changes with Age in Multiscale Entropy of Electromyography Signals from Leg Muscles during Treadmill Walking

PubMed Central

Kang, Hyun Gu; Dingwell, Jonathan B.

2016-01-01

Age-related gait changes may be due to the loss of complexity in the neuromuscular system. This theory is disputed due to inconsistent results from single-scale analyses. Also, behavioral adaptations may confound these changes. We examined whether EMG dynamics during gait is less complex in older adults over a range of timescales using the multiscale entropy method, and whether slower walking attenuates this effect. Surface EMG was measured from the left vastus lateralis (VL), biceps femoris (BF), gastrocnemius (GA), and tibialis anterior (TA) in 17 young and 18 older adults as they walked on a treadmill for 5 minutes at 0.8x-1.2x of preferred speed. Sample entropy (SE) and the complexity index (CI) of the EMG signals were calculated after successive coarse-graining to extract dynamics at timescales of 27 to 270 Hz, with m = 2 and r = 0.15 SD. SE and CI were lower across the timescales in older adults in VL and BF, but higher in GA (all p<0.001); these results held for VL and GA even after accounting for longer EMG burst durations in older adults. CI was higher during slower walking speed in VL and BF (p<0.001). Results were mostly similar for m = 3 and r = 0.01–0.35. Smaller r was more sensitive to age-related differences. The decrease in complexity with aging in the timescales studied was limited to proximal muscles, particularly VL. The increase in GA may be driven by other factors. Walking slower may reflect a behavioral adaptation that allows the nervous system to function with greater complexity. PMID:27570974

Comparison of electromyography fatigue threshold in lower limb muscles in trained cyclists and untrained non-cyclists.

PubMed

Smirmaul, B P C; Dantas, J L; Fontes, E B; Altimari, L R; Okano, A H; Moraes, A C

2010-01-01

The purpose of this study was to identify and compare the Electromyographic Fatigue Threshold (EMG(FT)) determined in the Vastus Lateralis (VL), Rectus Femoris (RF), Biceps Femoris (BF), Semitendinosus (ST) and Tibialis Anterior (TA) during stationary cycling in trained cyclists and non-cyclists. Using a cycle ergometer, 13 cyclists (28.4 +/- 6.9 years; 70.3 +/- 13 kg; 176.1 +/- 8.5 cm) and 11 non-cyclists (25.8 +/- 4 years; 73 +/- 9.1 kg; 175 +/- 6.4 cm), performed a maximum incremental test (ITmax) (90 rpm) to determine the (EMG(FT)). Maximal power output (W(PEAK)) reached by cyclists was higher than for non-cyclists (372.6 W and 248.9 W respectively) (P < 0.01). For the five muscles analyzed in cyclists, EMG(FT) occurred at 85.7% of cases in the VL, 92.9% in RE 78.6% in BE 78.6% in ST and 50% in TA, while in the non-cyclists group, this occurrence was 100% to muscle VL, 100% to RF, 92.6% to BF, 78.6% to ST, and 78.6% to TA. Analyzing the percentage corresponding to the power at EMG(FT) in relation to W(PEAK) reached, no differences between groups were observed for RF, BF and ST, however VL and TA, as well as the mean from all muscles were lower for cyclists than non-cyclists (P < 0.05). The present results showed that EMG(FT) is more easily identified in RF and VL muscles for both groups, and it may be an interesting method to evaluate the adaptive responses from aerobic and anaerobic metabolisms during cycling training programs.

Clinical characteristics and spatial distribution of Visceral leishmaniasis in children in São Paulo state: an emerging focus of Visceral leishmaniasis in Brazil

PubMed Central

Naufal Spir, Patricia Rodrigues; Prestes-Carneiro, Luiz Euribel; Fonseca, Elivelton Silva; Dayse, Aline; Giuffrida, Rogério

2017-01-01

Background: Visceral leishmaniasis (VL) is an emerging zoonosis, and Brazil harbors about 90% of those infected in Latin America. Since 1998, the disease has been spreading quickly in São Paulo state, and the western region is considered an emerging focus of VL in Brazil. Our aim was to evaluate the clinical characteristics and spatial distribution of VL in children referred to a public tertiary hospital located in the western region of São Paulo state, Brazil. Methods: Medical records of children up to 18 years of age who were diagnosed with VL between January 2006 and December 2010 were reviewed. Geospatial analysis was performed using the ArcGIS 10.2 platform. Results: Sixty-three patients were enrolled in the study; the median age was 3.3 ± 3.3 years. The median time interval between the onset of clinical symptoms and diagnosis was 16.1 ± 11.1 days, and the median time in the pediatric ward was 18.0 ± 9.4 days. Liposomal amphotericin B was the first-line treatment in 90.5% of the patients and 9.6% relapsed. One patient died (1.6%), and 19% were submitted to the pediatric intensive care unit. Conclusion: The short interval between the onset of symptoms, diagnosis, and treatment and the reduced number of days of hospitalization certainly influenced the small number of deaths, relapses, and severity among the children infected with VL. However, the disease is spreading fast in the western region of São Paulo state. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices. PMID:28221822

Clinical characteristics and spatial distribution of Visceral leishmaniasis in children in São Paulo state: an emerging focus of Visceral leishmaniasis in Brazil.

PubMed

Naufal Spir, Patricia Rodrigues; Prestes-Carneiro, Luiz Euribel; Fonseca, Elivelton Silva; Dayse, Aline; Giuffrida, Rogério; D'Andrea, Lourdes Aparecida Zampieri

2017-03-01

Visceral leishmaniasis (VL) is an emerging zoonosis, and Brazil harbors about 90% of those infected in Latin America. Since 1998, the disease has been spreading quickly in São Paulo state, and the western region is considered an emerging focus of VL in Brazil. Our aim was to evaluate the clinical characteristics and spatial distribution of VL in children referred to a public tertiary hospital located in the western region of São Paulo state, Brazil. Medical records of children up to 18 years of age who were diagnosed with VL between January 2006 and December 2010 were reviewed. Geospatial analysis was performed using the ArcGIS 10.2 platform. Sixty-three patients were enrolled in the study; the median age was 3.3 ± 3.3 years. The median time interval between the onset of clinical symptoms and diagnosis was 16.1 ± 11.1 days, and the median time in the pediatric ward was 18.0 ± 9.4 days. Liposomal amphotericin B was the first-line treatment in 90.5% of the patients and 9.6% relapsed. One patient died (1.6%), and 19% were submitted to the pediatric intensive care unit. The short interval between the onset of symptoms, diagnosis, and treatment and the reduced number of days of hospitalization certainly influenced the small number of deaths, relapses, and severity among the children infected with VL. However, the disease is spreading fast in the western region of São Paulo state. Thus, integrated actions and effective monitoring of the disease are needed to complement curative practices.

Sprinting performance on the Woodway Curve 3.0 is related to muscle architecture.

PubMed

Mangine, Gerald T; Fukuda, David H; Townsend, Jeremy R; Wells, Adam J; Gonzalez, Adam M; Jajtner, Adam R; Bohner, Jonathan D; LaMonica, Michael; Hoffman, Jay R; Fragala, Maren S; Stout, Jeffrey R

2015-01-01

To determine if unilateral measures of muscle architecture in the rectus femoris (RF) and vastus lateralis (VL) were related to (and predictive of) sprinting speed and unilateral (and bilateral) force (FRC) and power (POW) during a 30 s maximal sprint on the Woodway Curve 3.0 non-motorized treadmill. Twenty-eight healthy, physically active men (n = 14) and women (n = 14) (age = 22.9 ± 2.4 years; body mass = 77.1 ± 16.2 kg; height = 171.6 ± 11.2 cm; body-fa t = 19.4 ± 8.1%) completed one familiarization and one 30-s maximal sprint on the TM to obtain maximal sprinting speed, POW and FRC. Muscle thickness (MT), cross-sectional area (CSA) and echo intensity (ECHO) of the RF and VL in the dominant (DOM; determined by unilateral sprinting power) and non-dominant (ND) legs were measured via ultrasound. Pearson correlations indicated several significant (p < 0.05) relationships between sprinting performance [POW (peak, DOM and ND), FRC (peak, DOM, ND) and sprinting time] and muscle architecture. Stepwise regression indicated that POW(DOM) was predictive of ipsilateral RF (MT and CSA) and VL (CSA and ECHO), while POW(ND) was predictive of ipsilateral RF (MT and CSA) and VL (CSA); sprinting power/force asymmetry was not predictive of architecture asymmetry. Sprinting time was best predicted by peak power and peak force, though muscle quality (ECHO) and the bilateral percent difference in VL (CSA) were strong architectural predictors. Muscle architecture is related to (and predictive of) TM sprinting performance, while unilateral POW is predictive of ipsilateral architecture. However, the extent to which architecture and other factors (i.e. neuromuscular control and sprinting technique) affect TM performance remains unknown.

PERIAQUEDUCTAL GRAY NEUROPLASTICITY FOLLOWING CHRONIC MORPHINE VARIES WITH AGE: ROLE OF OXIDATIVE STRESS

PubMed Central

Bajic, Dusica; Berde, Charles B.; Commons, Kathryn G.

2012-01-01

The development of tolerance to the antinociceptive effects of morphine has been associated with networks within ventrolateral periaqueductal gray (vlPAG) and separately, nitric oxide signaling. Furthermore, it is known that the mechanisms that underlie tolerance differ with age. In this study, we used a rat model of antinociceptive tolerance to morphine at two ages, postnatal day (PD) 7 and adult, to determine if changes in the vlPAG related to nitric oxide signaling produced by chronic morphine exposure were age-dependent. Three pharmacological groups were analyzed: control, acute morphine, and chronic morphine group. Either morphine (10 mg/kg) or equal volume of normal saline was given subcutaneously twice daily for 6 ½ days. Animals were analyzed for morphine dose-response using Hot Plate test, and for the expression of several genes associated with nitric oxide metabolism was evaluated using rtPCR. In addition, the effect of morphine exposure on immunohistochemistry for Fos, and nNOS as well as nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) reaction at the vlPAG were measured. In both age groups acute morphine activated Fos in the vlPAG, and this effect was attenuated by chronic morphine, specifically in the vlPAG at the level of the laterodorsal tegmental nucleus (LDTg). In adults, but not PD7 rats, chronic morphine administration was associated with activation of nitric oxide function. In contrast, changes in the gene expression of PD7 rats suggested superoxide and peroxide metabolisms may be engaged. These data indicate that there is supraspinal neuroplasticity following morphine administration as early as PD7. Furthermore, oxidative stress pathways associated with chronic morphine exposure appear age-specific. PMID:22999971

A multi-state model examining patterns of transitioning among states of engagement in care in HIV-positive individuals initiating combination antiretroviral therapy

PubMed Central

Gillis, Jennifer; Loutfy, Mona; Bayoumi, Ahmed M; Antoniou, Tony; Burchell, Ann N; Walmsley, Sharon; Cooper, Curtis; Klein, Marina B.; Machouf, Nima; Montaner, Julio SG; Rourke, Sean B.; Tsoukas, Christos; Hogg, Robert; Raboud, Janet

2016-01-01

Background Common measures of engagement in care fail to acknowledge that infrequent follow-up may occur either intentionally among patients with sustained virologic suppression or unintentionally among patients with poor clinical outcomes. Methods Five states of HIV care were defined within the Canadian Observational Cohort (CANOC) Collaboration following combination antiretroviral therapy (cART) initiation: (1) guidelines HIV care (suppressed viral load (VL) and CD4 >200 cells/mm3, no gaps in cART >3 months, no gaps in CD4 or VL measurement >6 months), (2) successful care with decreased frequency of follow-up (as above except no gaps in CD4 or VL measurement >12 months), (3) suboptimal care (unsuppressed VL, CD4<200 cells/mm3 on 2 consecutive visits, ≥1 gap in cART >3 months, or ≥1 gap in CD4 or VL measurement >12 months), (4) loss to follow-up (no contact for 18 months), and (5) death. Multi-state models were used to determine factors associated with transitioning among states. Results 7810 participants were included. Younger age, female gender, Indigenous ethnicity and people who have injected drugs (PWID) were associated with increased likelihoods of transitioning from guidelines to suboptimal care and decreased likelihoods of transitioning from suboptimal to guidelines care. One-fifth of individuals in successful, decreased follow-up after cART initiation (mean sojourn time 0.72 years) were in suboptimal care in subsequent years. Conclusions Using routinely collected data, we have developed a flexible framework that characterizes patient transitions among states of HIV clinical care. We have demonstrated that multi-state models provide a useful approach to supplement ‘cascade of care’ work. PMID:27851713

Changes in proteomic profiles in different prostate lobes of male rats throughout growth and development and aging stages of the life span.

PubMed

Das, Arunangshu; Bortner, James D; Aliaga, Cesar A; Baker, Aaron; Stanley, Anne; Stanley, Bruce A; Kaag, Matthew; Richie, John P; El-Bayoumy, Karam

2013-03-01

Aging-related changes in important cellular pathways in the prostate may promote a permissive environment for an increased risk for prostatic disease development such as prostate cancer. Our objectives were to examine for such changes, by systematically determining the effects of growth and development and aging on proteomic profiles in different lobes of the rat prostate. Prostate lobes (dorsolateral lobe, DL and ventral lobe, VL) were obtained from male Fisher rats of various ages representing young (4 months), mature (12 months), old (18 months), and very old (24 months). Differentially expressed proteins between age groups in each lobe were identified using a proteomic approach, isobaric Tags for Relative and Absolute Quantitation (iTRAQ). Select changes in the DL and VL were verified by immunoblot analysis. iTRAQ identified 317 proteins with high confidence. iTRAQ discovered 12 and 6 proteins significantly modulated in response to growth and development in the DL and VL, respectively, and 42 and 29 proteins significantly modulated in response to aging in the DL and VL, respectively. Proteins modulated during growth and development in the DL and VL are involved in a variety of biological processes including cell communication and development, whereas proteins modulated during aging were predominantly related to antioxidant activity and immunity. Immunoblot analysis verified age-related changes for α-1 antitrypsin, annexin A1, hypoxia up-regulated protein 1, and 78 kDa glucose-regulated protein. Aging results in changes in numerous prostatic proteins and pathways which are mainly linked to inflammation and may lead to prostatic disease development. Copyright © 2012 Wiley Periodicals, Inc.

Induction of IL-10 and TGFβ from CD4+CD25+FoxP3+ T Cells Correlates with Parasite Load in Indian Kala-azar Patients Infected with Leishmania donovani

PubMed Central

Bhattacharya, Pradyot; Ghosh, Smriti; Ejazi, Sarfaraz Ahmad; Rahaman, Mehebubar; Pandey, Krishna; Ravi Das, Vidya Nand; Das, Pradeep; Goswami, Rama Prosad; Saha, Bibhuti; Ali, Nahid

2016-01-01

Background Visceral leishmaniasis (VL) is distinguished by a complex interplay of immune response and parasite multiplication inside host cells. However, the direct association between different immunological correlates and parasite numbers remains largely unknown. Methodology/Principal Findings We examined the plasma levels of different disease promoting/protective as well as Th17 cytokines and found IL-10, TGFβ and IL-17 to be significantly correlated with parasite load in VL patients (r = 0.52, 0.53 and 0.51 for IL-10, TGFβ and IL-17, respectively). We then extended our investigation to a more antigen-specific response and found leishmanial antigen stimulated levels of both IL-10 and TGFβ to be significantly associated with parasite load (r = 0.71 and 0.72 for IL-10 and TGFβ respectively). In addition to cytokines we also looked for different cellular subtypes that could contribute to cytokine secretion and parasite persistence. Our observations manifested an association between different Treg cell markers and disease progression as absolute numbers of CD4+CD25+ (r = 0.55), CD4+CD25hi (r = 0.61) as well as percentages of CD4+CD25+FoxP3+ T cells (r = 0.68) all correlated with parasite load. Encouraged by these results, we investigated a link between these immunological components and interestingly found both CD4+CD25+ and CD4+CD25+FoxP3+ Treg cells to secrete significantly (p<0.05) higher amounts of not only IL-10 but also TGFβ in comparison to corresponding CD25- T cells. Conclusions/Significance Our findings shed some light on source(s) of TGFβ and suggest an association between these disease promoting cytokines and Treg cells with parasite load during active disease. Moreover, the direct evidence of CD4+CD25+FoxP3+ Treg cells as a source of IL-10 and TGFβ during active VL could open new avenues for immunotherapy towards cure of this potentially fatal disease. PMID:26829554

Circadian force and EMG activity in hindlimb muscles of rhesus monkeys

NASA Technical Reports Server (NTRS)

Hodgson, J. A.; Wichayanuparp, S.; Recktenwald, M. R.; Roy, R. R.; McCall, G.; Day, M. K.; Washburn, D.; Fanton, J. W.; Kozlovskaya, I.; Edgerton, V. R.;

Fecundity and life table of different morphotypes of Phlebotomus argentipes (Diptera: Psychodidae).

PubMed

Dinesh, D S; Kumar, A J; Kumar, V; Ranjan, A; Das, P

2011-10-01

Phlebotomus argentipes Annandale and Brunetti (Diptera: Psychodidae), the established vector for Visceral Leishmaniasis (VL) have shown some morphological variations in India and its subcontinents. The variable egg laying capacity was found in different morphotypes of P. argentipes with maximum in type III followed by type I and II. The fecundity was enhanced by providing 25% glucose soaked filter paper surface in all types. However, significant increase was found in type-I (P < 0.05). The differences in fecundity indicate the biological variations among P. argentipes population. The findings will be helpful in searching out the sibling species among P. argentipes population.

Estimation in Latent Trait Models.

DTIC Science & Technology

1981-05-01

by k (V+l)t 21 jg=6 k (V+l) t22 j 2 _ B1 2 • 13 where 2 + (V) (\\+1) jl E( j ) (3.12) and j2 +) ( +i)) j2~l = E(B !iY,t ,v ) (3.13) 2 (V+l)2 (V M Step...Charles Myers Library Livingstone House 1 ERIC Facility-Acquisitions Livingstone Road 4833 Rugby Avenue Stratford Bethesda, MD 20014 London E15 2LJ

Imaging host-Leishmania interactions: significance in visceral leishmaniasis.

PubMed

Forestier, C-L

2013-01-01

Leishmaniasis is a neglected disease that is associated with a spectrum of clinical manifestations ranging from self-healing cutaneous lesions to fatal visceral infections, which primarily depends on the parasite species. In visceral leishmaniasis (VL), as opposed to cutaneous leishmaniasis (CL), parasites that infect host cells at the sand fly bite site have the striking ability to disseminate to visceral organs where they proliferate and persist for long periods of time. Imaging the dynamics of the host-Leishmania interaction in VL provides a powerful approach to understanding the mechanisms underlying host cell invasion, Leishmania dissemination and persistence within visceral organs and, to dissecting the immune responses to infection. Therefore, by allowing the visualization of the critical steps involved in the pathogenesis of VL, state-of-the-art microscopy technologies have the great potential to aid in the identification of better intervention strategies for this devastating disease. In this review, we emphasize the current knowledge and the potential significance of imaging technologies in understanding the infection process of visceralizing Leishmania species. Then, we discuss how application of innovative microscopy technologies to the study of VL will provide rich opportunities for investigating host-parasite interactions at a previously unexplored level and elucidating visceral disease-promoting mechanisms. © 2013 John Wiley & Sons Ltd.

Genetic characterization of commercial Saccharomyces cerevisiae isolates recovered from vineyard environments.

PubMed

Schuller, Dorit; Pereira, Leonor; Alves, Hugo; Cambon, Brigitte; Dequin, Sylvie; Casal, Margarida

2007-08-01

One hundred isolates of the commercial Saccharomyces cerevisiae strain Zymaflore VL1 were recovered from spontaneous fermentations carried out with grapes collected from vineyards located close to wineries in the Vinho Verde wine region of Portugal. Isolates were differentiated based on their mitochondrial DNA restriction patterns and the evaluation of genetic polymorphisms was carried out by microsatellite analysis, interdelta sequence typing and pulsed-field gel electrophoresis (PFGE). Genetic patterns were compared to those obtained for 30 isolates of the original commercialized Zymaflore VL1 strain. Among the 100 recovered isolates we found a high percentage of chromosomal size variations, most evident for the smaller chromosomes III and VI. Complete loss of heterozygosity was observed for two isolates that had also lost chromosomal heteromorphism; their growth and fermentative capacity in a synthetic must medium was also affected. A considerably higher number of variant patterns for interdelta sequence amplifications was obtained for grape-derived strains compared to the original VL1 isolates. Our data show that the long-term presence of strain VL1 in natural grapevine environments induced genetic changes that can be detected using different fingerprinting methods. The observed genetic changes may reflect adaptive mechanisms to changed environmental conditions that yeast cells encounter during their existence in nature. (c) 2007 John Wiley & Sons, Ltd.

An autoradiographic analysis of the cortical connections of the pallidal and cerebellar zones within the feline motor thalamus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wensel, J.P.

1989-01-01

The feline motor thalamus relays both basal ganglia and cerebellar inputs to the motor cortex. This complex is classically subdivided into three nuclei: the ventroanterior nucleus (VA), the ventrolateral nucleus (VL), and the ventromedial nucleus (VM). Poor correlation between recognized patterns of cortical and subcortical connectivity and traditional boundaries used to distinguish these nuclei complicate the elucidation of the role they play in the elaboration of motor behavior. The recent demonstration of complementarity for the pallidothalamic and dentatothalamic projections to the motor thalamus of the cat provided the foundation for a revision of these nuclear borders to reflect differences inmore » subcortical connectivity. Using a revised topography, this study analyzed the afferent and efferent connections of the feline VA and VL through the application of both anterograde and retrograde tracing techniques. The extent of the cerebellothalamic projection, as revealed by the bidirectional transport of WGA-HRP, was used to demarcate the boundary between VA and VL. Injections of tritiated amino acids into VA and VL allowed for the autoradiographic tracing of their cortical projections. Autoradiography was also used to demonstrate the distributions of corticothalamic projections from selected pericruciate and posterior parietal subfields to the motor thalamus.« less

A Self-Reported Adherence Measure to Screen for Elevated HIV Viral Load in Pregnant and Postpartum Women on Antiretroviral Therapy

PubMed Central

Brittain, Kirsty; Mellins, Claude A.; Zerbe, Allison; Remien, Robert H.; Abrams, Elaine J.; Myer, Landon; Wilson, Ira B.

2016-01-01

Maternal adherence to antiretroviral therapy (ART) is a concern and monitoring adherence presents a significant challenge in low-resource settings. We investigated the association between self-reported adherence, measured using a simple three-item scale, and elevated viral load (VL) among HIV-infected pregnant and postpartum women on ART in Cape Town, South Africa. This is the first reported use of this scale in a non-English speaking setting and it achieved good psychometric characteristics (Cronbach α = 0.79). Among 452 women included in the analysis, only 12 % reported perfect adherence on the self-report scale, while 92 % had a VL <1000 copies/mL. Having a raised VL was consistently associated with lower median adherence scores and the area under the curve for the scale was 0.599, 0.656 and 0.642 using a VL cut-off of ≥50, ≥1000 and ≥10000 copies/mL, respectively. This simple self-report adherence scale shows potential as a first-stage adherence screener in this setting. Maternal adherence monitoring in low resource settings requires attention in the era of universal ART, and the value of this simple adherence scale in routine ART care settings warrants further investigation. PMID:27278548

Health & Demographic Surveillance System Profile: The Muzaffarpur-TMRC Health and Demographic Surveillance System

PubMed Central

Malaviya, Paritosh; Picado, Albert; Hasker, Epco; Ostyn, Bart; Kansal, Sangeeta; Singh, Rudra Pratap; Shankar, Ravi; Boelaert, Marleen; Sundar, Shyam

2014-01-01

The Muzaffarpur-TMRC Health and Demographic Surveillance System (HDSS), established in 2007, was developed as an enlargement of the scope of a research collaboration on the project Visceral Leishmaniasis in Bihar, which had been ongoing since 2005. The HDSS is located in a visceral leishmaniasis (VL)-endemic area in the Muzaffarpur district of Bihar state in India. It is the only HDSS conducting research on VL, which is a vector-borne infectious disease transmitted by female phlebotomine sandflies and is fatal if left untreated. Currently the HDSS serves a population of over 105 000 in 66 villages. The HDSS collects data on vital events including pregnancies, births, deaths, migration and marriages, as well as other socio-economic indicators, at regular intervals. Incident VL cases are identified. The HDSS team is experienced in conducting both qualitative and quantitative studies, sample collection and rapid diagnostic tests in the field. In each village, volunteers connect the HDSS team with the community members. The Muzaffarpur-TMRC HDSS provides opportunities for studies on VL and other neglected tropical diseases (NTDs) and their interaction with demographic events such as migration. Queries related to research collaborations and data sharing can be sent to Dr Shyam Sundar at [drshyamsundar@hotmail.com]. PMID:25186307

[Comparison of different methods in dealing with HIV viral load data with diversified missing value mechanism on HIV positive MSM].

PubMed

Jiang, Z; Dou, Z; Song, W L; Xu, J; Wu, Z Y

2017-11-10

Objective: To compare results of different methods: in organizing HIV viral load (VL) data with missing values mechanism. Methods We used software SPSS 17.0 to simulate complete and missing data with different missing value mechanism from HIV viral loading data collected from MSM in 16 cities in China in 2013. Maximum Likelihood Methods Using the Expectation and Maximization Algorithm (EM), regressive method, mean imputation, delete method, and Markov Chain Monte Carlo (MCMC) were used to supplement missing data respectively. The results: of different methods were compared according to distribution characteristics, accuracy and precision. Results HIV VL data could not be transferred into a normal distribution. All the methods showed good results in iterating data which is Missing Completely at Random Mechanism (MCAR). For the other types of missing data, regressive and MCMC methods were used to keep the main characteristic of the original data. The means of iterating database with different methods were all close to the original one. The EM, regressive method, mean imputation, and delete method under-estimate VL while MCMC overestimates it. Conclusion: MCMC can be used as the main imputation method for HIV virus loading missing data. The iterated data can be used as a reference for mean HIV VL estimation among the investigated population.

Mechanisms of resistance and susceptibility to experimental visceral leishmaniosis: BALB/c mouse versus Syrian hamster model.

PubMed

Nieto, Ana; Domínguez-Bernal, Gustavo; Orden, José A; De La Fuente, Ricardo; Madrid-Elena, Nadia; Carrión, Javier

2011-02-23

Several animal models have been established to study visceral leishmaniosis (VL), a worldwide vector-borne disease affecting humans and domestic animals that constitutes a serious public health problem. BALB/c mice and Syrian hamsters are the most widely used experimental models. In this paper, we summarize the advantages and disadvantages of these two experimental models and discuss the results obtained using these models in different studies of VL. Studies using the BALB/c mouse model have underscored differences between the liver and spleen in the course of VL, indicating that pathological evaluation of the visceral organs is essential for understanding the immune mechanisms induced by Leishmania infantum infection. The main goal of this review is to collate the relevant literature on Leishmania pathogenesis into a sequence of events, providing a schematic view of the main components of adaptive and innate immunity in the liver and spleen after experimental infection with L. infantum or L. donovani. This review also presents several viewpoints and reflections about some controversial aspects of Leishmania research, including the choice of experimental model, route of administration, inoculum size and the relevance of pathology (intimately linked to parasite persistence): a thorough understanding of which is essential for future VL research and the successful development of efficient control strategies for Leishmania spp.

HisAK70: progress towards a vaccine against different forms of leishmaniosis.

PubMed

Domínguez-Bernal, Gustavo; Horcajo, Pilar; Orden, José A; Ruiz-Santa-Quiteria, José A; De La Fuente, Ricardo; Ordóñez-Gutiérrez, Lara; Martínez-Rodrigo, Abel; Mas, Alicia; Carrión, Javier

2015-12-09

Leishmania major and Leishmania infantum are among the main species that are responsible for cutaneous leishmaniosis (CL) and visceral leishmaniosis (VL), respectively. The leishmanioses represent the second-largest parasitic killer in the world after malaria. Recently, we succeeded in generating a plasmid DNA (pCMV-HISA70m2A) and demonstrated that immunized mice were protected against L. major challenge. The efficacy of the DNA-vaccine was further enhanced by the inclusion of KMP-11 antigen into the antibiotic-free plasmid pVAX1-asd. Here, we describe the use of a HisAK70 DNA-vaccine encoding seven Leishmania genes (H2A, H2B, H3, H4, A2, KMP11 and HSP70) for vaccination of mice to assess the induction of a resistant phenotype against VL and CL. HisAK70 was successful in vaccinated mice, resulting in a high amount of efficient sterile hepatic granulomas associated with a hepatic parasite burden fully resolved in the VL model; and resulting in 100% inhibition of parasite visceralization in the CL model. The results suggest that immunization with the HisAK70 DNA-vaccine may provide a rapid, suitable, and efficient vaccination strategy to confer cross-protective immunity against VL and CL.