Endocochlear potential generation is associated with intercellular communication in the stria vascularis: structural analysis in the viable dominant spotting mouse mutant.

PubMed

Carlisle, L; Steel, K; Forge, A

1990-11-01

Deafness in the viable dominant spotting mouse mutant is due to a primary defect of the stria vascularis which results in absence of the positive endocochlear potential in scala media. Endocochlear potentials were measured and the structure of stria vascularis of mutants with potentials close to zero was compared with that in normal littermate controls by use of morphometric methods. The stria vascularis was significantly thinner in mutants. Marginal cells were not significantly different from controls in terms of volume density or intramembrane particle density but the network density of tight junctions was significantly reduced in the mutants. A virtual absence of gap junctions between basal cells and marginal or intermediate cells was observed, but intramembrane particle density and junctional complexes between adjacent basal cells were not different from controls. The volume density of basal cells was significantly greater in mutants. Intermediate cells accounted for a significantly smaller volume density of the stria vascularis in mutants and had a lower density of intramembrane particles than controls. Melanocytes were not identified in the stria vascularis of mutants. These results suggest that communication between marginal, intermediate and basal cells might be important to the normal function of the stria vascularis.

Expression of alpha and beta subunit isoforms of Na,K-ATPase in the mouse inner ear and changes with mutations at the Wv or Sld loci.

PubMed

Schulte, B A; Steel, K P

1994-07-01

Mice homozygous for mutations at the viable dominant spotting (Wv) and Steel-dickie (Sld) loci exhibit a similar phenotype which includes deafness. The auditory dysfunction derives from failure of the stria vascularis to develop normally and to generate a high positive endocochlear potential (EP). Because strial function is driven by Na,K-ATPase its expression was investigated in inner ears of Wv/Wv and Sld/Sld mice and their wild-type littermates by immunostaining with antisera against four of the enzyme's subunit isoforms. Wild-type mice from two different genetic backgrounds showed an identical distribution of subunit isoforms among inner ear transport cells. Several epithelial cell types coexpressed the alpha 1 and beta 1 subunits. Vestibular dark cells showed no reactivity for beta 1 but expressed abundant beta 2, whereas, strial marginal cells stained strongly for both beta isoforms. The only qualitative difference between mutant and wild-type mice was the absence of beta 1 subunit in marginal cells of the mutant's stria. However, it is unlikely that this difference accounts for failure of mutants to generate a high EP because the beta 1 subunit is not present in the stria vascularis of either rats or gerbils with normal EP values. Strong immunostaining for Na,K-ATPase in lateral wall fibrocytes of normal mice along with diminished immunoreactivity in the mutants supports the concept that these strategically located transport fibrocytes actively resorb K+ leaked across Reissner's membrane into scala vestibuli or effluxed from hair cells and nerves into scala tympani. It is further speculated that the resorbed K+ normally is siphoned down its concentration gradient into the intrastrial space through gap junctions between fibrocytes and strial basal and intermediate cells where it is recycled back to endolymph via marginal cells. Thus, failure of mutants to generate a positive EP could be explained by the absence of intermediate cells which may form the final link in the conduit for moving K+ from perilymph to the intrastrial compartment.

Effects of perilymphatic pressure, sodium nitroprusside, and bupivacaine on cochlear fluid pH of guinea pigs.

PubMed

Suzuki, Masaaki; Kotani, Ryosuke

2015-01-01

Hydrostatic positive pressure and vasoconstrictor acidified the cochlear fluids, whereas the vasodilator made the fluids alkaline. CBF might play a role in regulating cochlea fluid pH. Cochlea fluid pH is highly dependent on the HCO3(-)/CO2 buffer system. Cochlear blood flow (CBF) supplies O2 and removes CO2. It is speculated that cochlear blood flow changes might affect the balance of the HCO3(-)/CO2 buffer system in the cochlea. It is known that the elevation of inner ear pressure decreases the CBF, and local application of vasodilating or vasoconstricting agents directly to the cochlea changes the CBF. The purpose of this study was to elucidate the effect of positive hydrostatic inner ear pressure and application of a vasodilator and vasoconstrictor of cochlear vessels on the pH of the endolymph and perilymph. The authors performed animal physiological experiments on 30 guinea pigs. Hydrostatic positive pressure was infused through a glass capillary tube inserted into the scala tympani of the basal turn. The vasodilator, nitric oxide donor (sodium nitroprusside; SNP), and the vasoconstrictor, bupivacaine, were placed topically onto the round window of the guinea pig cochlea. Endolymph pH (pHe) and endocochlear potential (EP) were monitored by double-barreled ion-selective microelectrodes in the second turn of the guinea pig cochlea. During the topical application study, scala vestibuli perilymph pH (pHv) was also measured simultaneously in the second turn. The application of hydrostatic positive pressure caused a decrease in pHe and EP. Positive perilymphatic pressure caused the endolymph to become acidic pressure-dependently. Application of 3.0% SNP evoked an increase in both the pHe and pHv, following by a gradual recovery to baseline levels. On the other hand, 0.5% bupivacaine caused a decrease in both the pHe and pHv. The EP during topical application showed slight, non-significant changes.

Functional expression of P2X4 receptor in capillary endothelial cells of the cochlear spiral ligament and its role in regulating the capillary diameter.

PubMed

Wu, T; Dai, M; Shi, X R; Jiang, Z G; Nuttall, A L

2011-07-01

The cochlear lateral wall generates the endocochlear potential (EP), which creates a driving force for the hair cell transduction current and is essential for normal hearing. Blood flow at the cochlear lateral wall is critically important for maintaining the EP. The vulnerability of the EP to hypoxia suggests that the blood flow in the cochlear lateral wall is dynamically and precisely regulated to meet the changing metabolic needs of the cochlear lateral wall. It has been reported that ATP, an important extracellular signaling molecule, plays an essential role in regulating cochlear blood flow. However, the cellular mechanism underlying ATP-induced regional blood flow changes has not been investigated. In the current study, we demonstrate that 1) the P2X4 receptor is expressed in endothelial cells (ECs) of spiral ligament (SL) capillaries. 2) ATP elicits a characteristic current through P2X4 on ECs in a dose-dependent manner (EC(50) = 0.16 mM). The ATP current has a reversal potential at ∼0 mV; is inhibited by 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro[3,2-e]-1,4-diazepin-2-one (5-BDBD), LaCl(3), pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid) tetrasodium salt hydrate (PPADS), and extracellular acidosis; and is less sensitive to α,β-methyleneadenosine 5'-triphosphate (α,β-MeATP) and 2'- and 3'-O-(4-benzoyl-benzoyl) adenosine 5'-triphosphate (BzATP). 3) ATP elicits a transient increase of intracellular Ca(2+) in ECs. 4) In accordance with the above in vitro findings, perilymphatic ATP (1 mM) caused dilation in SL capillaries in vivo by 11.5%. N(ω)-nitro-l-arginine methyl ester hydrochloride (l-NAME), a nonselective inhibitor of nitric oxide synthase, or 5-BDBD, the specific P2X4 inhibitor, significantly blocked the dilation. These findings support our hypothesis that extracellular ATP regulates cochlear lateral blood flow through P2X4 activation in ECs.

Endocochlear potential depends on Cl− channels: mechanism underlying deafness in Bartter syndrome IV

PubMed Central

Rickheit, Gesa; Maier, Hannes; Strenzke, Nicola; Andreescu, Corina E; De Zeeuw, Chris I; Muenscher, Adrian; Zdebik, Anselm A; Jentsch, Thomas J

2008-01-01

Human Bartter syndrome IV is an autosomal recessive disorder characterized by congenital deafness and severe renal salt and fluid loss. It is caused by mutations in BSND, which encodes barttin, a β-subunit of ClC-Ka and ClC-Kb chloride channels. Inner-ear-specific disruption of Bsnd in mice now reveals that the positive potential, but not the high potassium concentration, of the scala media depends on the presence of these channels in the epithelium of the stria vascularis. The reduced driving force for K+-entry through mechanosensitive channels into sensory hair cells entails a profound congenital hearing loss and subtle vestibular symptoms. Although retaining all cell types and intact tight junctions, the thickness of the stria is reduced early on. Cochlear outer hair cells degenerate over several months. A collapse of endolymphatic space was seen when mice had additionally renal salt and fluid loss due to partial barttin deletion in the kidney. Bsnd−/− mice thus demonstrate a novel function of Cl− channels in generating the endocochlear potential and reveal the mechanism leading to deafness in human Bartter syndrome IV. PMID:18833191

HPN-07, a free radical spin trapping agent, protects against functional, cellular and electrophysiological changes in the cochlea induced by acute acoustic trauma

PubMed Central

Hu, Ning; Du, Xiaoping; Li, Wei; West, Matthew B.; Choi, Chul-Hee; Floyd, Robert; Kopke, Richard D.

2017-01-01

Oxidative stress is considered a major cause of the structural and functional changes associated with auditory pathologies induced by exposure to acute acoustic trauma AAT). In the present study, we examined the otoprotective effects of 2,4-disulfophenyl-N-tert-butylnitrone (HPN-07), a nitrone-based free radical trap, on the physiological and cellular changes in the auditory system of chinchilla following a six-hour exposure to 4 kHz octave band noise at 105 dB SPL. HPN-07 has been shown to suppress oxidative stress in biological models of a variety of disorders. Our results show that administration of HPN-07 beginning four hours after acoustic trauma accelerated and enhanced auditory/cochlear functional recovery, as measured by auditory brainstem responses (ABR), distortion product otoacoustic emissions (DPOAE), compound action potentials (CAP), and cochlear microphonics (CM). The normally tight correlation between the endocochlear potential (EP) and evoked potentials of CAP and CM were persistently disrupted after noise trauma in untreated animals but returned to homeostatic conditions in HPN-07 treated animals. Histological analyses revealed several therapeutic advantages associated with HPN-07 treatment following AAT, including reductions in inner and outer hair cell loss; reductions in AAT-induced loss of calretinin-positive afferent nerve fibers in the spiral lamina; and reductions in fibrocyte loss within the spiral ligament. These findings support the conclusion that early intervention with HPN-07 following an AAT efficiently blocks the propagative ototoxic effects of oxidative stress, thereby preserving the homeostatic and functional integrity of the cochlea. PMID:28832600

A comparison of dehydration effects of V2-antagonist (OPC-31260) on the inner ear between systemic and round window applications.

PubMed

Takeda, Taizo; Takeda, Setsuko; Kakigi, Akinobu; Okada, Teruhiko; Nishioka, Rie; Taguchi, Daizo

2006-08-01

V2-antagonist (OPC-31260 (OPC)) application to the scala tympani reduced endolymphatic hydrops. In the present study, we investigated whether systemic administration or local infusion via the round window (RW application) of OPC would be more suitable for clinical use. In Experiment 1, the increase ratios of the cross-sectional area of the scala media of experimentally induced endolymphatic hydrops were quantitatively assessed among four groups of non-OPC application, RW application of xanthan gum, systemic application of OPC and RW application of OPC. In Experiment 2, the effects of systemic and RW applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM) were investigated. In Experiment 3, endocochlear DC potential (EP) was measured in guinea pigs with the RW application of OPC. Electron microscopic observations of the stria vascularis and the hair cells were also made. Both systemic and RW applications of OPC significantly reduced endolymphatic hydrops. However, systemic application resulted in the distension of the Reissner's membrane in the non-operated ear, which seemed to be caused by elevated p-VP levels resulting from the systemic application of OPC. In contrast, RW application of OPC produced no apparent toxic effects in the inner ear, as indicated electrophysiological or morphological changes. Thus, drug delivery via the round window is more useful for the clinical application of OPC for medical decompression.

A Point Mutation in the Gene for Asparagine-Linked Glycosylation 10B (Alg10b) Causes Nonsyndromic Hearing Impairment in Mice (Mus musculus)

PubMed Central

Probst, Frank J.; Corrigan, Rebecca R.; del Gaudio, Daniela; Salinger, Andrew P.; Lorenzo, Isabel; Gao, Simon S.; Chiu, Ilene; Xia, Anping

2013-01-01

The study of mouse hearing impairment mutants has led to the identification of a number of human hearing impairment genes and has greatly furthered our understanding of the physiology of hearing. The novel mouse mutant neurological/sensory 5 (nse5) demonstrates a significantly reduced or absent startle response to sound and is therefore a potential murine model of human hearing impairment. Genetic analysis of 500 intercross progeny localized the mutant locus to a 524 kilobase (kb) interval on mouse chromosome 15. A missense mutation in a highly-conserved amino acid was found in the asparagine-linked glycosylation 10B gene (Alg10b), which is within the critical interval for the nse5 mutation. A 20.4 kb transgene containing a wildtype copy of the Alg10b gene rescued the mutant phenotype in nse5/nse5 homozygous animals, confirming that the mutation in Alg10b is responsible for the nse5/nse5 mutant phenotype. Homozygous nse5/nse5 mutants had abnormal auditory brainstem responses (ABRs), distortion product otoacoustic emissions (DPOAEs), and cochlear microphonics (CMs). Endocochlear potentials (EPs), on the other hand, were normal. ABRs and DPOAEs also confirmed the rescue of the mutant nse5/nse5 phenotype by the wildtype Alg10b transgene. These results suggested a defect in the outer hair cells of mutant animals, which was confirmed by histologic analysis. This is the first report of mutation in a gene involved in the asparagine (N)-linked glycosylation pathway causing nonsyndromic hearing impairment, and it suggests that the hearing apparatus, and the outer hair cells in particular, are exquisitely sensitive to perturbations of the N-linked glycosylation pathway. PMID:24303013

ILDR1 null mice, a model of human deafness DFNB42, show structural aberrations of tricellular tight junctions and degeneration of auditory hair cells

PubMed Central

Morozko, Eva L.; Nishio, Ayako; Ingham, Neil J.; Chandra, Rashmi; Fitzgerald, Tracy; Martelletti, Elisa; Borck, Guntram; Wilson, Elizabeth; Riordan, Gavin P.; Wangemann, Philine; Forge, Andrew; Steel, Karen P.; Liddle, Rodger A.; Friedman, Thomas B.; Belyantseva, Inna A.

2015-01-01

In the mammalian inner ear, bicellular and tricellular tight junctions (tTJs) seal the paracellular space between epithelial cells. Tricellulin and immunoglobulin-like (Ig-like) domain containing receptor 1 (ILDR1, also referred to as angulin-2) localize to tTJs of the sensory and non-sensory epithelia in the organ of Corti and vestibular end organs. Recessive mutations of TRIC (DFNB49) encoding tricellulin and ILDR1 (DFNB42) cause human nonsyndromic deafness. However, the pathophysiology of DFNB42 deafness remains unknown. ILDR1 was recently reported to be a lipoprotein receptor mediating the secretion of the fat-stimulated cholecystokinin (CCK) hormone in the small intestine, while ILDR1 in EpH4 mouse mammary epithelial cells in vitro was shown to recruit tricellulin to tTJs. Here we show that two different mouse Ildr1 mutant alleles have early-onset severe deafness associated with a rapid degeneration of cochlear hair cells (HCs) but have a normal endocochlear potential. ILDR1 is not required for recruitment of tricellulin to tTJs in the cochlea in vivo; however, tricellulin becomes mislocalized in the inner ear sensory epithelia of ILDR1 null mice after the first postnatal week. As revealed by freeze-fracture electron microscopy, ILDR1 contributes to the ultrastructure of inner ear tTJs. Taken together, our data provide insight into the pathophysiology of human DFNB42 deafness and demonstrate that ILDR1 is crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs. PMID:25217574

Physiopathology of the cochlear microcirculation.

PubMed

Shi, Xiaorui

2011-12-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. Published by Elsevier B.V.

Physiopathology of the Cochlear Microcirculation

PubMed Central

Shi, Xiaorui

2011-01-01

Normal blood supply to the cochlea is critically important for establishing the endocochlear potential and sustaining production of endolymph. Abnormal cochlear microcirculation has long been considered an etiologic factor in noise-induced hearing loss, age-related hearing loss (presbycusis), sudden hearing loss or vestibular function, and Meniere's disease. Knowledge of the mechanisms underlying the pathophysiology of cochlear microcirculation is of fundamental clinical importance. A better understanding of cochlear blood flow (CoBF) will enable more effective management of hearing disorders resulting from aberrant blood flow. This review focuses on recent discoveries and findings related to the physiopathology of the cochlear microvasculature. PMID:21875658

Mice deficient in H+-ATPase a4 subunit have severe hearing impairment associated with enlarged endolymphatic compartments within the inner ear

PubMed Central

Lorente-Cánovas, Beatriz; Ingham, Neil; Norgett, Elizabeth E.; Golder, Zoe J.; Karet Frankl, Fiona E.; Steel, Karen P.

2013-01-01

SUMMARY Mutations in the ATP6V0A4 gene lead to autosomal recessive distal renal tubular acidosis in patients, who often show sensorineural hearing impairment. A first Atp6v0a4 knockout mouse model that recapitulates the loss of H+-ATPase function seen in humans has been generated and recently reported (Norgett et al., 2012). Here, we present the first detailed analysis of the structure and function of the auditory system in Atp6v0a4−/− knockout mice. Measurements of the auditory brainstem response (ABR) showed significantly elevated thresholds in homozygous mutant mice, which indicate severe hearing impairment. Heterozygote thresholds were normal. Analysis of paint-filled inner ears and sections from E16.5 embryos revealed a marked expansion of cochlear and endolymphatic ducts in Atp6v0a4−/− mice. A regulatory link between Atp6v0a4, Foxi1 and Pds has been reported and we found that the endolymphatic sac of Atp6v0a4−/− mice expresses both Foxi1 and Pds, which suggests a downstream position of Atp6v0a4. These mutants also showed a lack of endocochlear potential, suggesting a functional defect of the stria vascularis on the lateral wall of the cochlear duct. However, the main K+ channels involved in the generation of endocochlear potential, Kcnj10 and Kcnq1, are strongly expressed in Atp6v0a4−/− mice. Our results lead to a better understanding of the role of this proton pump in hearing function. PMID:23065636

Monitoring multiple sclerosis by multimodal evoked potentials: Numerically versus ordinally scaled scoring systems.

PubMed

Schlaeger, Regina; Hardmeier, Martin; D'Souza, Marcus; Grize, Leticia; Schindler, Christian; Kappos, Ludwig; Fuhr, Peter

2016-03-01

To compare the ability of different evoked potential scores (EPS) to monitor and predict the disease course in multiple sclerosis (MS). Seventy-two patients with MS or clinically isolated syndrome were investigated by visual, motor, and somatosensory EP and expanded disability status scale (EDSS) at baseline (T0) and months 6, 12, 24, 36 (T4). EP results were rated according to ordinal (o), semi-quantitative (sq), and quantitative (q) EPS. Spearman rank correlation and multivariable linear regression were used to investigate the associations between EPS and clinical disability. All EPS correlated with EDSS cross-sectionally (0.72⩽rho⩽0.87, all p<0.001) and longitudinally (0.39⩽rho⩽0.47, all p⩽0.004). EPS(T0) and EDSS(T0) together explained 85-86% of EDSS(T4) variance. A posteriori power calculation showed that the sample sizes needed to detect significant changes over 6 months in q-EPS, sq-EPS and o-EPS with 90% certainty would be 50, 129 and 222, respectively. q-EPS change(T1-T0) correlated with EDSS change(T4-T0) (rho=0.56, p<0.001), while sq-EPS and o-EPS changes(T1-T0) did not. All three EPS allow disease course monitoring in MS. However, the quantitative EPS detects clinically relevant short-term changes with a smaller sample size than semi-quantitative or ordinal EPS. These results underscore the potential of EPS to characterize MS disease evolution. Copyright © 2016. Published by Elsevier Ireland Ltd.

Clinical Applications for EPs in the ICU.

PubMed

Koenig, Matthew A; Kaplan, Peter W

2015-12-01

In critically ill patients, evoked potential (EP) testing is an important tool for measuring neurologic function, signal transmission, and secondary processing of sensory information in real time. Evoked potential measures conduction along the peripheral and central sensory pathways with longer-latency potentials representing more complex thalamocortical and intracortical processing. In critically ill patients with limited neurologic exams, EP provides a window into brain function and the potential for recovery of consciousness. The most common EP modalities in clinical use in the intensive care unit include somatosensory evoked potentials, brainstem auditory EPs, and cortical event-related potentials. The primary indications for EP in critically ill patients are prognostication in anoxic-ischemic or traumatic coma, monitoring for neurologic improvement or decline, and confirmation of brain death. Somatosensory evoked potentials had become an important prognostic tool for coma recovery, especially in comatose survivors of cardiac arrest. In this population, the bilateral absence of cortical somatosensory evoked potentials has nearly 100% specificity for death or persistent vegetative state. Historically, EP has been regarded as a negative prognostic test, that is, the absence of cortical potentials is associated with poor outcomes while the presence cortical potentials are prognostically indeterminate. In recent studies, the presence of middle-latency and long-latency potentials as well as the amplitude of cortical potentials is more specific for good outcomes. Event-related potentials, particularly mismatch negativity of complex auditory patterns, is emerging as an important positive prognostic test in patients under comatose. Multimodality predictive algorithms that combine somatosensory evoked potentials, event-related potentials, and clinical and radiographic factors are gaining favor for coma prognostication.

HIV Pre-Exposure Prophylaxis Stigma as a Multidimensional Barrier to Uptake Among Women Who Attend Planned Parenthood.

PubMed

Calabrese, Sarah K; Dovidio, John F; Tekeste, Mehrit; Taggart, Tamara; Galvao, Rachel W; Safon, Cara B; Willie, Tiara C; Caldwell, Abigail; Kaplan, Clair; Kershaw, Trace S

2018-05-22

PrEP uptake has lagged among US women. PrEP stigma is a recognized barrier to uptake among MSM but remains largely unexplored among women. This study examined the pervasiveness of PrEP stigma among US women and its implications for uptake. Setting/Methods: In a 2017 online survey of Planned Parenthood patients drawn from the three cities with the highest numbers of new HIV infections in Connecticut, 597 heterosexually-active, HIV-negative, PrEP-inexperienced women reported background characteristics, two dimensions of anticipated PrEP stigma (PrEP-user stereotypes and PrEP disapproval by others), and three indicators of potential PrEP uptake (interest in learning more about PrEP, intention to use PrEP, and comfort discussing PrEP with a provider). Participants commonly perceived PrEP-user stereotypes, with many believing that others would regard them as promiscuous (37%), HIV-positive (32%), bad (14%), or gay (11%) if they used PrEP. Thirty percent would feel ashamed to disclose PrEP use. Many participants expected disapproval by family (36%), sex partners (34%), and friends (25%). In adjusted analyses, perception of PrEP-user stereotypes was uniquely associated with lower comfort discussing PrEP with a provider. Expected PrEP disapproval by others was uniquely associated with less PrEP interest, less intention to use PrEP, and less comfort discussing PrEP with a provider. Exploratory moderation analyses suggested intention to use PrEP was greatest when participants anticipated low levels of both PrEP-user stereotypes and PrEP disapproval by others. Findings highlight the need for positive messaging targeting potential PrEP users and their social networks to increase PrEP acceptance and uptake.

[Evoked potentials extraction based on cross-talk resistant adaptive noise cancellation].

PubMed

Zeng, Qingning; Li, Ling; Liu, Qinghua; Yao, Dezhong

2004-06-01

As Evoked Potentials are much lower in amplitude with respect to the on-going EEC, many trigger-related signals are needed for common averaging technique to enable the extraction of single-trail evoked potentials (EP). How to acquire EP through fewer evocations is an important research project. This paper proposes a cross-talk resistant adaptive noise cancellation method to extract EP. Together with the use of filtering technique and the common averaging technique, the present method needs much less evocations to acquire EP signals. According to the simulating experiment, it needs only several evocations or even only one evocation to get EP signals in good quality.

Ion flow in cochlear hair cells and the regulation of hearing sensitivity.

PubMed

Patuzzi, Robert

2011-10-01

This paper discusses how ion transport proteins in the hair cells of the mammalian cochlea work to produce a sensitive but stable hearing organ. The transport proteins in the inner and outer hair cells are summarized (including their current voltage characteristics), and the roles of these proteins in determining intracellular Ca(2+), membrane potential, and ultimately cochlear sensitivity are discussed. The paper also discusses the role of the Ca(2+) sequestration sacs in outer hair cells in the autoregulation of hair cell membrane potential and cochlear gain, and how the underdamped control of Ca(2+) within these sacs may produce the observed slow oscillations in cochlear sensitivity and otoacoustic emissions after cochlear perturbations, including perilymphatic perfusions and prolonged low-frequency tones. The relative insensitivity of cochlear gain to short-term changes in the endocochlear potential is also discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

Stigma and Conspiracy Beliefs Related to Pre-exposure Prophylaxis (PrEP) and Interest in Using PrEP Among Black and White Men and Transgender Women Who Have Sex with Men

PubMed Central

Kalichman, Seth C.; Price, Devon; Finneran, Stephanie; Allen, Aerielle; Maksut, Jessica

2018-01-01

The HIV/AIDS epidemic in the US continues to persist, in particular, among race, sexual orientation, and gender minority populations. Pre-exposure prophylaxis (PrEP), or using antiretroviral medications for HIV prevention, is an effective option, but uptake of PrEP has been slow. Sociocultural barriers to using PrEP have been largely underemphasized, yet have the potential to stall uptake and, therefore, warrant further understanding. In order to assess the relationships between potential barriers to PrEP (i.e., PrEP stigma and conspiracy beliefs), and interest in PrEP, Black men and transgender women who have sex with men (BMTW, N = 85) and White MTW (WMTW, N = 179) were surveyed at a gay pride event in 2015 in a large southeastern US city. Bivariate and multivariate logistic regression analyses were completed to examine factors associated with PrEP interest. Among the full sample, moderate levels of PrEP awareness (63%) and low levels of use (9%) were observed. Believing that PrEP is for people who are promiscuous (stigma belief) was strongly associated with lack of interest in using PrEP, and individuals who endorsed this belief were more likely to report sexual risk taking behavior. Conspiracy beliefs related to PrEP were reported among a large minority of the sample (42%) and were more frequently reported among BMTW than WMTW. Given the strong emphasis on the use of biomedical strategies for HIV prevention, addressing sociocultural barriers to PrEP access is urgently needed and failure to do so will weaken the potential benefits of biomedical prevention. PMID:28108878

Attitudes and Acceptance of Oral and Parenteral HIV Preexposure Prophylaxis among Potential User Groups: A Multinational Study

PubMed Central

Gomez, Gabriela B.; Garnett, Geoffrey P.; Dybul, Mark R.; Piot, Peter K.

2012-01-01

Background The use of antiviral medications by HIV negative people to prevent acquisition of HIV or pre-exposure prophylaxis (PrEP) has shown promising results in recent trials. To understand the potential impact of PrEP for HIV prevention, in addition to efficacy data, we need to understand both the acceptability of PrEP among members of potential user groups and the factors likely to determine uptake. Methods and findings Surveys of willingness to use PrEP products were conducted with 1,790 members of potential user groups (FSWs, MSM, IDUs, SDCs and young women) in seven countries: Peru, Ukraine, India, Kenya, Botswana, Uganda and South Africa. Analyses of variance were used to assess levels of acceptance across different user groups and countries. Conjoint analysis was used to examine the attitudes and preferences towards hypothetical and known attributes of PrEP programs and medications. Overall, members of potential user groups were willing to consider taking PrEP (61% reported that they would definitely use PrEP). Current results demonstrate that key user groups in different countries perceived PrEP as giving them new possibilities in their lives and would consider using it as soon as it becomes available. These results were maintained when subjects were reminded of potential side effects, the need to combine condom use with PrEP, and for regular HIV testing. Across populations, route of administration was considered the most important attribute of the presented alternatives. Conclusions Despite multiple conceivable barriers, there was a general willingness to adopt PrEP in key populations, which suggests that if efficacious and affordable, it could be a useful tool in HIV prevention. There would be a willingness to experience inconvenience and expense at the levels included in the survey. The results suggest that delivery in a long lasting injection would be a good target in drug development. PMID:22247757

A comparative study of electrical potential sensors and Ag/AgCl electrodes for characterising spontaneous and event related electroencephalagram signals.

PubMed

Fatoorechi, M; Parkinson, J; Prance, R J; Prance, H; Seth, A K; Schwartzman, D J

2015-08-15

Electroencephalography (EEG) is still a widely used imaging tool that combines high temporal resolution with a relatively low cost. Ag/AgCl metal electrodes have been the gold standard for non-invasively monitoring electrical brain activity. Although reliable, these electrodes have multiple drawbacks: they suffer from noise, such as offset potential drift, and usability issues, for example, difficult skin preparation and cross-coupling of adjacent electrodes. In order to tackle these issues a prototype Electric Potential Sensor (EPS) device based on an auto-zero operational amplifier was developed and evaluated. The EPS is a novel active ultrahigh impedance capacitively coupled sensor. The absence of 1/f noise makes the EPS ideal for use with signal frequencies of ∼10Hz or less. A comprehensive study was undertaken to compare neural signals recorded by the EPS with a standard commercial EEG system. Quantitatively, highly similar signals were observed between the EPS and EEG sensors for both free running and evoked brain activity with cross correlations of higher than 0.9 between the EPS and a standard benchmark EEG system. These studies comprised measurements of both free running EEG and Event Related Potentials (ERPs) from a commercial EEG system and EPS. The EPS provides a promising alternative with many added benefits compared to standard EEG sensors, including reduced setup time and elimination of sensor cross-coupling. In the future the scalability of the EPS will allow the implementation of a whole head ultra-dense EPS array. Copyright © 2015 Elsevier B.V. All rights reserved.

Acceptability of Pre-Exposure Prophylaxis (PrEP) as an HIV prevention strategy: Barriers and facilitators to PrEP uptake among at-risk Peruvian populations

PubMed Central

Galea, Jerome T.; Kinsler, Janni J.; Salazar, Ximena; Lee, Sung-Jae; Giron, Maziel; Sayles, Jennifer N.; Cáceres, Carlos; Cunningham, William E.

2010-01-01

This study examined Pre-Exposure Prophylaxis (PrEP) acceptability among female sex workers, male-to-female transgendered persons, and men who have sex with men in Lima, Peru. Focus groups explored social issues associated with PrEP acceptability and conjoint analysis assessed preferences among eight hypothetical PrEP scenarios with varying attribute profiles and their relative impact on acceptability. Conjoint analysis revealed that PrEP acceptability ranged from 19.8 to 82.5 out of a possible score of 100 across the eight hypothetical PrEP scenarios. Out-of-pocket cost had the greatest impact on PrEP acceptability (25.2, p <0.001), followed by efficacy (21.4, p <0.001) and potential side effects (14.7, p <0.001). Focus group data supported these findings, and also revealed that potential sexual risk disinhibition, stigma and discrimination associated with PrEP use, and mistrust of health care professionals were also concerns. These issues will require careful attention when planning for PrEP roll-out if proven efficacious in ongoing clinical trials. PMID:21571973

Headbobber: A Combined Morphogenetic and Cochleosaccular Mouse Model to Study 10qter Deletions in Human Deafness

PubMed Central

Buniello, Annalisa; Hardisty-Hughes, Rachel E.; Pass, Johanna C.; Bober, Eva; Smith, Richard J.; Steel, Karen P.

2013-01-01

The recessive mouse mutant headbobber (hb) displays the characteristic behavioural traits associated with vestibular defects including headbobbing, circling and deafness. This mutation was caused by the insertion of a transgene into distal chromosome 7 affecting expression of native genes. We show that the inner ear of hb/hb mutants lacks semicircular canals and cristae, and the saccule and utricle are fused together in a single utriculosaccular sac. Moreover, we detect severe abnormalities of the cochlear sensory hair cells, the stria vascularis looks severely disorganised, Reissner's membrane is collapsed and no endocochlear potential is detected. Myo7a and Kcnj10 expression analysis show a lack of the melanocyte-like intermediate cells in hb/hb stria vascularis, which can explain the absence of endocochlear potential. We use Trp2 as a marker of melanoblasts migrating from the neural crest at E12.5 and show that they do not interdigitate into the developing strial epithelium, associated with abnormal persistence of the basal lamina in the hb/hb cochlea. We perform array CGH, deep sequencing as well as an extensive expression analysis of candidate genes in the headbobber region of hb/hb and littermate controls, and conclude that the headbobber phenotype is caused by: 1) effect of a 648 kb deletion on distal Chr7, resulting in the loss of three protein coding genes (Gpr26, Cpmx2 and Chst15) with expression in the inner ear but unknown function; and 2) indirect, long range effect of the deletion on the expression of neighboring genes on Chr7, associated with downregulation of Hmx3, Hmx2 and Nkx1.2 homeobox transcription factors. Interestingly, deletions of the orthologous region in humans, affecting the same genes, have been reported in nineteen patients with common features including sensorineural hearing loss and vestibular problems. Therefore, we propose that headbobber is a useful model to gain insight into the mechanisms underlying deafness in human 10qter deletion syndrome. PMID:23457544

Neurophysiological Effects of Meditation Based on Evoked and Event Related Potential Recordings

PubMed Central

Singh, Nilkamal; Telles, Shirley

2015-01-01

Evoked potentials (EPs) are a relatively noninvasive method to assess the integrity of sensory pathways. As the neural generators for most of the components are relatively well worked out, EPs have been used to understand the changes occurring during meditation. Event-related potentials (ERPs) yield useful information about the response to tasks, usually assessing attention. A brief review of the literature yielded eleven studies on EPs and seventeen on ERPs from 1978 to 2014. The EP studies covered short, mid, and long latency EPs, using both auditory and visual modalities. ERP studies reported the effects of meditation on tasks such as the auditory oddball paradigm, the attentional blink task, mismatched negativity, and affective picture viewing among others. Both EP and ERPs were recorded in several meditations detailed in the review. Maximum changes occurred in mid latency (auditory) EPs suggesting that maximum changes occur in the corresponding neural generators in the thalamus, thalamic radiations, and primary auditory cortical areas. ERP studies showed meditation can increase attention and enhance efficiency of brain resource allocation with greater emotional control. PMID:26137479

Neurophysiological Effects of Meditation Based on Evoked and Event Related Potential Recordings.

PubMed

Singh, Nilkamal; Telles, Shirley

2015-01-01

Evoked potentials (EPs) are a relatively noninvasive method to assess the integrity of sensory pathways. As the neural generators for most of the components are relatively well worked out, EPs have been used to understand the changes occurring during meditation. Event-related potentials (ERPs) yield useful information about the response to tasks, usually assessing attention. A brief review of the literature yielded eleven studies on EPs and seventeen on ERPs from 1978 to 2014. The EP studies covered short, mid, and long latency EPs, using both auditory and visual modalities. ERP studies reported the effects of meditation on tasks such as the auditory oddball paradigm, the attentional blink task, mismatched negativity, and affective picture viewing among others. Both EP and ERPs were recorded in several meditations detailed in the review. Maximum changes occurred in mid latency (auditory) EPs suggesting that maximum changes occur in the corresponding neural generators in the thalamus, thalamic radiations, and primary auditory cortical areas. ERP studies showed meditation can increase attention and enhance efficiency of brain resource allocation with greater emotional control.

A new role for evoked potentials in MS? Repurposing evoked potentials as biomarkers for clinical trials in MS.

PubMed

Hardmeier, Martin; Leocani, Letizia; Fuhr, Peter

2017-09-01

Evoked potentials (EP) characterize signal conduction in selected tracts of the central nervous system in a quantifiable way. Since alteration of signal conduction is the main mechanism of symptoms and signs in multiple sclerosis (MS), multimodal EP may serve as a representative measure of the functional impairment in MS. Moreover, EP have been shown to be predictive for disease course, and thus might help to select patient groups at high risk of progression for clinical trials. EP can detect deterioration, as well as improvement of impulse propagation, independently from the mechanism causing the change. Therefore, they are candidates for biomarkers with application in clinical phase-II trials. Applicability of EP in multicenter trials has been limited by different standards of registration and assessment.

Evoked potentials are useful for diagnosis of neuromyelitis optica spectrum disorder.

PubMed

Ohnari, Keiko; Okada, Kazumasa; Takahashi, Toshiyuki; Mafune, Kosuke; Adachi, Hiroaki

2016-05-15

Neuromyelitis optica spectrum disorder (NMOSD) has been differentiated from relapsing-remitting multiple sclerosis (RRMS) by clinical, laboratory, and pathological findings, including the presence of the anti-aquaporin 4 antibody. Measurement of evoked potentials (EPs) is often used for the diagnosis of RRMS, although the possibility of applying EPs to the diagnosis of NMOSD has not been investigated in detail. Eighteen patients with NMOSD and 28 patients with RRMS were included in this study. The patients' neurological symptoms and signs were examined and their EPs were recorded. Characteristic findings were absence of visual evoked potentials and absence of motor evoked potentials in the lower extremities in patients with NMOSD, and a delay in these potentials in patients with RRMS. Most patients with NMOSD did not present abnormal subclinical EPs, whereas many patients with RRMS did. None of the patients with NMOSD showed abnormalities in auditory brainstem responses. NMOSD can be differentiated from RRMS by EP data obtained in the early stages of these diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Hypocholesterolemic and bioactive potential of exopolysaccharide from a probiotic Enterococcus faecium K1 isolated from kalarei.

PubMed

Bhat, Bilqeesa; Bajaj, Bijender Kumar

2018-04-01

Bioprospecting of novel probiotic strains especially from unexplored eco-niches has been a continuous practice. Enterococcus faecium K1, an isolate from indigenously fermented milk product kalarei possesses numerous desirable functional attributes. In current study, E. faecium K1 has been used for EPS production, and it yielded 355 ± 0.019 mg/L EPS. EPS demonstrates remarkable hypocholesterolemic, antioxidant, antibiofilm, and emulsification characteristics. EPS is constituted of mannose, glucose and galactose. SEM analysis reveals flake like compact structure of EPS while TEM and X-ray diffractogram confirms the amorphous structure of EPS. FTIR substantiates the functional groups/bonds typical of polysaccharides. Thermal analysis indicates adequate stability of EPS at 237 °C with average weight loss of 22%. E. faecium K1 EPS possesses unique functional bioactivities and physicochemical characteristics, and may potentially be explored for applications in food/pharmaceutical industries. Copyright © 2018 Elsevier Ltd. All rights reserved.

Awareness and willingness to use HIV pre-exposure prophylaxis among men who have sex with men in low- and middle-income countries: a systematic review and meta-analysis

PubMed Central

Yi, Siyan; Tuot, Sovannary; Mwai, Grace W; Ngin, Chanrith; Chhim, Kolab; Pal, Khoundyla; Igbinedion, Ewemade; Holland, Paula; Choub, Sok Chamreun; Mburu, Gitau

2017-01-01

Abstract Introduction: To facilitate provision of pre-exposure prophylaxis (PrEP) in low- and middle-income countries (LMIC), a better understanding of potential demand and user preferences is required. This review assessed awareness and willingness to use oral PrEP among men who have sex with men (MSM) in LMIC. Methods: Electronic literature search of Cochrane library, Embase, PubMed, PsychINFO, CINHAL, Web of Science, and Google Scholar was conducted between July and September 2016. Reference lists of relevant studies were searched, and three authors contacted for additional data. Non-peer reviewed publications were excluded. Studies were screened for inclusion, and relevant data abstracted, assessed for bias, and synthesized. Results: In total, 2186 records were identified, of which 23 studies involving 14,040 MSM from LMIC were included. The proportion of MSM who were aware of PrEP was low at 29.7% (95% CI: 16.9–44.3). However, the proportion willing to use PrEP was higher, at 64.4% (95% CI: 53.3–74.8). Proportions of MSM aware of PrEP was <50% in 11 studies and 50–70% in 3 studies, while willingness to use PrEP was <50% in 6 studies, 50–70% in 9 studies, and over 80% in 5 studies. Several factors affected willingness to use PrEP. At the individual domain, poor knowledge of PrEP, doubts about its effectiveness, fear of side effects, low perception of HIV risk, and the need to adhere or take medicines frequently reduced willingness to use PrEP, while PrEP education and motivation to maintain good health were facilitators of potential use. Demographic factors (education, age, and migration) influenced both awareness and willingness to use PrEP, but their effects were not consistent across studies. At the social domain, anticipated stigma from peers, partners, and family members related to sexual orientation, PrEP, or HIV status were barriers to potential use of PrEP, while partner, peer, and family support were facilitators of potential use. At the structural domain, concerns regarding attitudes of healthcare providers, quality assurance, data protection, and cost were determinants of potential use. Conclusions: This review found that despite low levels of awareness of PrEP, MSM in LMIC are willing to use it if they are supported appropriately to deal with a range of individual, social, and structural barriers. PMID:28691439

Demographic Differences in PrEP-Related Stereotypes: Implications for Implementation.

PubMed

Golub, Sarit A; Gamarel, Kristi E; Surace, Anthony

2017-05-01

Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80 % of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants' identification of these stereotype categories differed significantly by demographic factors (i.e., race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners.

Prevalence of actual uptake and willingness to use pre-exposure prophylaxis to prevent HIV acquisition among men who have sex with men in Hong Kong, China

PubMed Central

Lau, Joseph T. F.; Fang, Yuan; Ip, Mary; Gross, Danielle L.

2018-01-01

Objectives This study was to investigate the prevalence of actual uptake of pre-exposure prophylaxis (PrEP), willingness to use daily oral PrEP under two cost scenarios, and potential issues related to PrEP use among men who have sex with men (MSM) with HIV negative/unknown sero-status in Hong Kong, China. Factors associated with the two measures of willingness were also investigated. Methods 403 eligible MSM completed the anonymous venue-based face-to-face interview/telephone interview. Results Only 1% had ever used PrEP. After being briefed about some facts of PrEP, the prevalence of willingness to use daily oral PrEP was 7.7% if they could purchase PrEP at private hospitals/clinics at HK$8,000 (US$1,032)/month (market rate) and 45.2% if free PrEP was provided by public hospitals/clinics in Hong Kong (free PrEP). After adjusted for significant background variables, significant factors of these two measures of willingness included: (1) number of correct responses to knowledge on PrEP, (2) perceived risk of HIV infection in the next six months, and (3) constructs of the Theory of Planned Behavior: positive and negative attitudes toward PrEP, perceived their significant others would support them take PrEP (perceived subjective norm), perceived number of local MSM who were willing to take PrEP (perceived descriptive norm), and confidence in using PrEP under the two scenarios (perceived behavioral control). Among all participants, 9.7% and 25.1% would start and discontinue using PrEP without consulting doctors; 26.0% would not take PrEP daily if it was provided for free, and 42.4% would not take up HIV testing every 3 months after using PrEP. Conclusion Different strategies should be considered for promoting PrEP at market rate and if free PrEP is made available. Future promotion should increase their knowledge about PrEP, modify their perceptions related to HIV and PrEP, and address some potential issues related to PrEP use. PMID:29432470

The Vaginal Microbiome and its Potential to Impact Efficacy of HIV Pre-exposure Prophylaxis for Women.

PubMed

Velloza, Jennifer; Heffron, Renee

2017-10-01

This review describes existing evidence addressing the potential modulation of pre-exposure prophylaxis (PrEP) products, specifically 1% tenofovir (TFV) gel and oral tenofovir-based PrEP, by vaginal dysbiosis and discusses future considerations for delivering novel, long-acting PrEP products to women at high risk for vaginal dysbiosis and HIV. We describe results from analyses investigating the modification of PrEP efficacy by vaginal dysbiosis and studies of biological mechanisms that could render PrEP ineffective in the presence of specific microbiota. A secondary analysis from the CAPRISA-004 cohort demonstrated that there is no effect of the 1% TFV gel in the presence of non-Lactobacillus dominant microbiota. Another recent analysis comparing oral tenofovir-based PrEP efficacy among women with and without bacterial vaginosis in the Partners PrEP Study found that oral PrEP efficacy is not modified by bacterial vaginosis. Gardnerella vaginalis, commonly present in women with vaginal dysbiosis, can rapidly metabolize TFV particularly when it is locally applied and thereby prevent TFV integration into cells. Given that vaginal dysbiosis appears to modulate efficacy for 1% TFV gel but not for oral tenofovir-based PrEP, vaginal dysbiosis is potentially less consequential to HIV protection from TFV in the context of systemic drug delivery and high product adherence. Vaginal dysbiosis may undermine the efficacy of 1% TFV gel to protect women from HIV but not the efficacy of oral PrEP. Ongoing development of novel ring, injectable, and film-based PrEP products should investigate whether vaginal dysbiosis can reduce efficacy of these products, even in the presence of high adherence.

Acceptability of pre-exposure prophylaxis as an HIV prevention strategy: barriers and facilitators to pre-exposure prophylaxis uptake among at-risk Peruvian populations.

PubMed

Galea, J T; Kinsler, J J; Salazar, X; Lee, S-J; Giron, M; Sayles, J N; Cáceres, C; Cunningham, W E

2011-05-01

This study examined pre-exposure prophylaxis (PrEP) acceptability among female sex workers, male-to-female transgendered persons and men who have sex with men in Lima, Peru. Focus groups explored social issues associated with PrEP acceptability and conjoint analysis assessed preferences among eight hypothetical PrEP scenarios with varying attribute profiles and their relative impact on acceptability. Conjoint analysis revealed that PrEP acceptability ranged from 19.8 to 82.5 out of a possible score of 100 across the eight hypothetical PrEP scenarios. Out-of-pocket cost had the greatest impact on PrEP acceptability (25.2, P < 0.001), followed by efficacy (21.4, P < 0.001) and potential side-effects (14.7, P < 0.001). Focus group data supported these findings, and also revealed that potential sexual risk disinhibition, stigma and discrimination associated with PrEP use, and mistrust of health-care professionals were also concerns. These issues will require careful attention when planning for PrEP roll-out.

Knowledge of Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Men Who Have Sex with Men in Denver, Colorado

PubMed Central

Al-Tayyib, Alia A.; Thrun, Mark W.; Haukoos, Jason S.; Walls, N. Eugene

2014-01-01

As part of the National HIV Behavioral Surveillance System among men who have sex with men (MSM) in Denver, Colorado, we assessed knowledge of pre-exposure prophylaxis (PrEP); willingness to use PrEP; and potential changes in risk behaviors among HIV-negative participants reporting sexual activity with a male partner in the preceding 12 months. We examined knowledge of PrEP before (2008) and after (2011) results of the iPrEx trial were available. Of the 425 participants in the 2008 sample, 91 (21 %) were aware of PrEP compared to 131 (28 %) of the 461 participants in the 2011 sample (adjusted prevalence ratio: 1.43, 95 % confidence interval: 1.18, 1.72). Despite the increase in 2011, few MSM in Denver were aware of PrEP. Educating high-risk MSM about the potential utility of PrEP as an adjunct to other effective prevention methods is needed when considering the addition of PrEP to the HIV prevention arsenal. PMID:23824227

Structural characterization and anticancer activity of extracellular polysaccharides from ascidian symbiotic bacterium Bacillus thuringiensis.

PubMed

Ramamoorthy, Sathishkumar; Gnanakan, Ananthan; S Lakshmana, Senthil; Meivelu, Moovendhan; Jeganathan, Arun

2018-06-15

In the present study, extracellular polysaccharides (EPS) producing bacterium Bacillus thuringiensis RSK CAS4 was isolated from ascidian Didemnum granulatum and its production was optimized by response surface methodology. Fructose and galactose were found as the major monosaccharides in the EPS from the strain RSK CAS4. Functional groups and structural characteristics of the EPS were characterized with FT-IR and 1 HNMR. The purified EPS showed potent antioxidant properties in investigation against DPPH, hydroxyl, superoxide free radicals. In vitro anticancer activity of purified EPS was evaluated on HEp-2 cells, A549 and Vero cell lines. Growth of cancer cells was inhibited by the EPS in a dose-dependent manner and maximum anticancer activity was found to be 76% against liver cancer at 1000 μg/ml. The antioxidant and anticancer potentials of theEPS from marine bacterium Bacillusthuringiensis RSK CAS4 suggests it as a potential natural source and its scopeas an alternative to synthetics for pharmaceutical application. Copyright © 2018 Elsevier Ltd. All rights reserved.

Awareness and Acceptability of Pre-exposure HIV Prophylaxis Among Men Who have Sex with Men in Baltimore.

PubMed

Fallon, Susan A; Park, Ju Nyeong; Ogbue, Christine Powell; Flynn, Colin; German, Danielle

2017-05-01

This paper assessed characteristics associated with awareness of and willingness to take pre-exposure prophylaxis (PrEP) among Baltimore men who have sex with men (MSM). We used data from BESURE-MSM3, a venue-based cross-sectional HIV surveillance study conducted among MSM in 2011. Multivariate regression was used to identify characteristics associated with PrEP knowledge and acceptability among 399 participants. Eleven percent had heard of PrEP, 48% would be willing to use PrEP, and none had previously used it. In multivariable analysis, black race and perceived discrimination against those with HIV were significantly associated with decreased awareness, and those who perceived higher HIV discrimination reported higher acceptability of PrEP. Our findings indicate a need for further education about the potential utility of PrEP in addition to other prevention methods among MSM. HIV prevention efforts should address the link between discrimination and potential PrEP use, especially among men of color.

Projecting future grassland performance in the Greater Platte River Basin to assess sustainability for potential biofuel feedstock areas

NASA Astrophysics Data System (ADS)

Gu, Y.; Wylie, B. K.; Phuyal, K.

2012-12-01

In previous studies, we used vegetation condition information from archival records of satellite data (i.e., 10-year time series of Normalized Difference Vegetation Index (NDVI) data), site geophysical and biophysical features (e.g., elevation, slope and aspect, and soils), and weather and climate drivers to build ecosystem performance (EP) models to dynamically monitor EP (DMEP) in the Greater Platte River Basin (GPRB). Ecosystem performance is a surrogate approach for measuring ecosystem productivity. We estimated ecosystem site potentials (i.e., long-term ecosystem productivities), weather-based expected EP (EEP), and rangeland conditions based on these EP models. Validation of the EP results using ground observations (e.g., percentage of bare soil, LANDFIRE maps, stocking rate, and crop yield data) demonstrated the reliability of these EP models. We used this DMEP method to identify grasslands that are potentially suitable for cellulosic biofuel feedstock (e.g., switchgrass) development in the GPRB. The objectives of this study are to (1) project the future grassland EP; (2) assess the changes and trends of the future EP; and (3) examine the future sustainability of the identified biofuel feedstock areas in the GPRB. We used the EP models and future climate projections to estimate future (e.g., 2050 and 2099) climate-based projections of grassland performance in the GPRB. The future climate data were derived from the National Center for Atmospheric Research (NCAR) Community Climate System Model 3.0 (CCSM3) "SRES A1B" (a "middle" emissions path) obtained from the "Bias Corrected and Downscaled WCRP CMIP3 Climate Projections" archive (http://gdo-dcp.ucllnl.org/downscaled_cmip3_projections). Results show that, under climate scenario A1B, the potential biofuel feedstock areas in the more mesic Eastern part of the GPRB will remain productive in the future (the spatially averaged EPs for these areas are 3335 kg ha-1 year-1, 3355 kg ha-1 year-1, and 3341 kg ha-1 year-1 for the site potential, the 2050 EEP, and the 2099 EEP, respectively). Therefore, the identified potential biofuel feedstock areas will continue to be sustainable for future biofuel development. On the other hand, the identified non-biofuel grasslands in the drier Western part of the GPRB would be expected to stay unproductive, with a slight decline in the EP trend in the future (spatially averaged EPs are 1983 kg ha-1 year-1, 1977 kg ha-1 year-1, and 1964 kg ha-1 year-1 for the site potential, the 2050 EEP, and the 2099 EEP, respectively). Thus, these areas will continue to be unsuitable for biofuel feedstock development in the future. The resulting future grassland EEP maps can be used as a reference by land managers to assess the future sustainability and feasibility of the potential biofuel feedstock areas.

Demographic differences in PrEP–related stereotypes: Implications for implementation

PubMed Central

Golub, Sarit. A.; Gamarel, Kristi E.; Surace, Anthony

2015-01-01

Qualitative interviews about pre-exposure prophylaxis (PrEP) stereotypes were conducted with a subsample of 160 MSM who participated in a PrEP messaging study. Negative stereotypes about PrEP users were identified by 80% of participants. Two types of stereotypes were most common: PrEP users are HIV-infected (and lying about it), and PrEP users are promiscuous and resistant to condom use. Participants’ identification of these stereotype categories differed significantly by demographic factors (i.e. race/ethnicity, education). Expanding access to PrEP requires recognizing potential differences in the experience or anticipation of PrEP-related stereotypes that might impact willingness to discuss PrEP with providers, friends, or partners. PMID:26143247

The prostaglandin EP1 receptor potentiates kainate receptor activation via a protein kinase C pathway and exacerbates status epilepticus

PubMed Central

Rojas, Asheebo; Gueorguieva, Paoula; Lelutiu, Nadia; Quan, Yi; Shaw, Renee; Dingledine, Raymond

2014-01-01

Prostaglandin E2 (PGE2) regulates membrane excitability, synaptic transmission, plasticity, and neuronal survival. The consequences of PGE2 release following seizures has been the subject of much study. Here we demonstrate that the prostaglandin E2 receptor 1 (EP1, or Ptger1) modulates native kainate receptors, a family of ionotropic glutamate receptors widely expressed throughout the central nervous system. Global ablation of the EP1 gene in mice (EP1-KO) had no effect on seizure threshold after kainate injection but reduced the likelihood to enter status epilepticus. EP1-KO mice that did experience typical status epilepticus had reduced hippocampal neurodegeneration and a blunted inflammatory response. Further studies with native prostanoid and kainate receptors in cultured cortical neurons, as well as with recombinant prostanoid and kainate receptors expressed in Xenopus oocytes, demonstrated that EP1 receptor activation potentiates heteromeric but not homomeric kainate receptors via a second messenger cascade involving phospholipase C, calcium and protein kinase C. Three critical GluK5 C-terminal serines underlie the potentiation of the GluK2/GluK5 receptor by EP1 activation. Taken together, these results indicate that EP1 receptor activation during seizures, through a protein kinase C pathway, increases the probability of kainic acid induced status epilepticus, and independently promotes hippocampal neurodegeneration and a broad inflammatory response. PMID:24952362

[Application of evoked potentials monitoring in total thoracoabdominal aorta aneurysm repair].

PubMed

Duan, Y Y; Zheng, J; Pan, X D; Zhu, J M; Liu, Y M; Ge, Y P; Cheng, L J; Sun, L Z

2016-04-05

To evaluate the application value of evoked potentials (EP) monitoring in patients undergoing aorta-iliac bypass for total thoracoabdominal aorta aneurysm repair (tTAAAR). A prospective study, with a total of 31 patients undergoing tTAAAR and intraoperative EP monitoring from June 2014 to April 2015 was carried out. The results of intraoperative evoked potentials, clinical outcomes and follow-up data of patients were collected for further evaluation. The EP wave disappeared [motor evoked potentials for (55.6±18.1) min, somatosensory evoked potentials for (50.3±18.7) min] after proximal descending aorta being clamped, and gradually recovered after the segment arteries of spine cord were reconstructed. The EP wave was restored to normal level at the end of operation in all the cases. The somatosensory evoked potentials remained unchanged in 2 cases (false negative). One case died after operation. No spinal cord injury occurred. The median follow-up after operation was 10 months (5-14 months). There was no delayed neurological deficit. EP provided an on-line monitoring of the condition of spinal cord function, which become an intraoperative protocol to avoid the irreversible injury of spinal cord.

Blood safety implications of donors using HIV pre-exposure prophylaxis.

PubMed

Seed, C R; Yang, H; Lee, J F

2017-07-01

HIV pre-exposure prophylaxis (PrEP) is the use of one or more antiretroviral medications (in combination) to prevent HIV infection. The most commonly used PrEP medication (Truvada ® , Gilead Sciences, Inc.) acts by inhibiting HIV-1 reverse transcriptase. If someone who is using PrEP unknowingly becomes HIV infected (termed 'PrEP breakthrough infection'), there may be suppressed viral replication resulting in a virus level undetectable by the most sensitive HIV NAT. Failure to seroconvert and seroreversion (loss of previously detectable HIV antibodies) have also both been observed with 2nd, 3rd and 4th generation screening immunoassays, as well as Western blot assays. If such a person was tested in the course of donating blood, the results may therefore be difficult to interpret. The index of suspicion for possible PrEP 'interference' should be highest in the context of concomitant low-level positive or 'greyzone' reactivity on HIV NAT and serological tests, which is an unusual pattern in acutely HIV-infected blood donors. Another possibility is detectable HIV RNA with negative HIV serology (i.e. a potential 'NAT yield' case) but without subsequent HIV seroconversion (or disappearance of HIV RNA). Excluding antiretroviral therapy or PrEP use by the donor in such circumstances would be important. The current rarity of PrEP breakthrough infection indicates that any potential safety risk is likely very small. However, considering the increasing use of PrEP we feel it is prudent for those interpreting HIV donor screening test results to consider the potential for PrEP interference. © 2017 International Society of Blood Transfusion.

Are Thai MSM Willing to Take PrEP for HIV Prevention? An Analysis of Attitudes, Preferences and Acceptance

PubMed Central

Ananworanich, Jintanat; Gomez, Gabriela B.; Hallett, Timothy B.; Dybul, Mark R.; Piot, Peter

2013-01-01

Objective We aimed to understand the attitudes, preferences and acceptance of oral and parenteral PrEP among men who have sex with men (MSM) in Thailand. Background Pre-exposure prophylaxis (PrEP), the use of antiretrovirals to prevent HIV acquisition, has shown promising results in recent trials. To assess the potential impact of this new HIV prevention method, in addition to efficacy data, we need to understand which psychosocial factors are likely to determine its uptake among members of potential user groups. Methods and Findings Surveys of willingness to use PrEP products were administered to MSM. Spearman’s rank tests were used to uncover associations between questionnaire items. Mann-Whitney tests were performed to ascertain differences between groups. Conjoint analysis was used to examine the attitudes and preferences of MSM towards PrEP attributes. Most participants were willing to consider taking PrEP (39.2% “yes, definitely” and 49.2% “yes, probably”) and perceived PrEP as giving them new possibilities in their lives (38.5% “a lot of hope” and 55.8% “some hope”), even after being instructed of potential side effects and costs. HIV testing was considered the most important attribute and a daily pill and longer lasting injection in the arm were the preferred routes of administration. Conclusions Despite its multiple challenges, MSM in Thailand would be willing to take PrEP, even if they had to experience inconvenience and expense. If PrEP were to be implemented in Thailand, our findings show that its uptake could be considerable. PMID:23342121

Brainstem auditory and somatosensory evoked potentials in relation to clinical and neuroimaging findings in Chiari type 1 malformation.

PubMed

Moncho, Dulce; Poca, Maria-Antonia; Minoves, Teresa; Ferré, Alejandro; Rahnama, Kimia; Sahuquillo, Juan

2015-04-01

The aim of this study was to describe the abnormalities found in the recordings of evoked potentials (EPs), in particular those of brainstem auditory evoked potentials and somatosensory evoked potentials, in a homogeneous series of patients with Chiari type 1 malformation (CM-1) and study their relationship with clinical symptoms and malformation severity. CM-1 is characterized by cerebellar tonsils that descend below the foramen magnum and may be associated with EP alterations. However, only a small number of authors have described these tests in CM-1, and the patient groups studied to date have been small and heterogeneous. The clinical findings, neuroimages, and EP findings were retrospectively studied in a cohort of 50 patients with CM-1. Seventy percent of patients had EP abnormalities (brainstem auditory evoked potential: 52%, posterior tibial nerve somatosensory evoked potential: 42%, and median nerve somatosensory evoked potential: 34%). The most frequent alteration was an increased central conduction time. Morphometric measurements differed between the normal and pathological groups, although no statistical significance was found when comparing these groups. A high percentage of patients with CM-1 show EP alterations regardless of their clinical or radiological findings, thus highlighting the necessity of performing these tests, especially in patients with few or no symptoms.

Experimental observation of the topological structure of exceptional points in an ultrathin hybridized metamaterial

NASA Astrophysics Data System (ADS)

Kang, Ming; Zhu, Weiren; Rukhlenko, Ivan D.

2017-12-01

The exceptional point (EP), which is one of the most important branch-type singularities exclusive to non-Hermitian systems, has been observed recently in various synthetic materials, giving rise to counterintuitive phenomena due to the nontrivial topology of the EP. Here, we present a direct experimental observation of the topological structure of the EPs via the angle-resolved transmission measurement of a hybridized metamaterial. Both eigenvalues and eigenvectors show branch-point singularities in the investigated biparametric space of frequency and incident angle. Importantly, the angle-resolved transmission coefficients provide all the information about the eigenvalues as well as the corresponding eigenvectors in the biparametric space, revealing the nontrivial topological structure of the EP, such as mode switching and the topological phase for a parameter loop encircling the EP. It is shown that the appearance of the EP in the scattering matrix is related directly to the perfect unidirectional transmission and the chirality of the EP corresponds to the maximum or minimum value of the asymmetric factor. Our investigation uncovers the capabilities of metamaterials for exploring the physics of EPs and their potential for having extreme optical properties, which provide potential applications in the spectral band ranging from microwaves to visible frequencies.

Unlocking the potential of established products: toward new incentives rewarding innovation in Europe.

PubMed

Nayroles, Gabrielle; Frybourg, Sandrine; Gabriel, Sylvie; Kornfeld, Åsa; Antoñanzas-Villar, Fernando; Espín, Jaime; Jommi, Claudio; Martini, Nello; de Pouvourville, Gérard; Tolley, Keith; Wasem, Jürgen; Toumi, Mondher

2017-01-01

Background : Many established products (EPs - marketed for eight years or more) are widely used off-label despite little evidence on benefit-risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods : Targeted literature search and expert panel meetings. Results : Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients' access to treatment options. Conclusion : There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems.

Unlocking the potential of established products: toward new incentives rewarding innovation in Europe

PubMed Central

Nayroles, Gabrielle; Frybourg, Sandrine; Gabriel, Sylvie; Kornfeld, Åsa; Antoñanzas-Villar, Fernando; Espín, Jaime; Jommi, Claudio; Martini, Nello; de Pouvourville, Gérard; Tolley, Keith; Wasem, Jürgen; Toumi, Mondher

2017-01-01

ABSTRACT Background: Many established products (EPs – marketed for eight years or more) are widely used off-label despite little evidence on benefit–risk ratio. This exposes patients to risks related to safety and lack of efficacy, and healthcare providers to liability. Introducing new indications for EPs may represent a high societal value; however, manufacturers rarely invest in R&D for EPs. The objective of this research was to describe incentives and disincentives for developing new indications for EPs in Europe and to investigate consequences of current policies. Methods: Targeted literature search and expert panel meetings. Results: Within the current European-level and national-level regulatory framework there are limited incentives for development of new indications with EPs. Extension of indication normally does not allow the price to be increased or maintained, the market protection period to be extended, or exclusion from a reference price system. New indication frequently triggers re-evaluation, resulting in price erosion, regardless of the level of added value with the new indication. In consequence, manufacturers are more prone to undertake R&D efforts at early to mid-stage of product life cycle rather than with EPs, or to invest in new chemical entities, even in therapeutic areas with broad off-label use. This represents a potentially missed opportunity as developing new indications for EPs offers an alternative to off-label use or lengthy and expensive R&D for new therapies, opens new opportunities for potentially cost-effective treatment alternatives, as well as greater equity in patients’ access to treatment options. Conclusion: There are potential benefits from the development of new indications for EPs that are currently not being realized due to a lack of regulatory and pricing incentives in Europe. Incentives for orphan or paediatric drugs have proven to be effective in promoting R&D. Similarly, incentives to promote R&D in EPs should be developed, for the benefit of patients and healthcare systems. PMID:28740616

Deposition kinetics of extracellular polymeric substances (EPS) on silica in monovalent and divalent salts.

PubMed

Zhu, Pingting; Long, Guoyu; Ni, Jinren; Tong, Meiping

2009-08-01

The deposition kinetics of extracellular polymeric substances (EPS) on silica surfaces were examined in both monovalent and divalent solutions under a variety of environmentally relevant ionic strength and pH conditions by employing a quartz crystal microbalance with dissipation (DCM-D). Soluble EPS (SEPS) and bound EPS (BEPS) were extracted from four bacterial strains with different characteristics. Maximum favorable deposition rates (k(fa)) were observed for all EPS at low ionic strengths in both NaCl and CaCl2 solutions. With the increase of ionic strength, k(fa) decreased due to the simultaneous occurrence of EPS aggregation in solutions. Deposition efficiency (alpha; the ratio of deposition rates obtained under unfavorable versus corresponding favorable conditions) for all EPS increased with increasing ionic strength in both NaCl and CaCl2 solutions, which agreed with the trends of zeta potentials and was consistent with the classic Derjaguin-Landau-Verwey-Overbeek (DLVO) theory. Comparison of alpha for SEPS and BEPS extracted from the same strain showed that the trends of alpha did not totally agree with trends of zeta potentials, indicating the deposition kinetics of EPS on silica surfaces were not only controlled by DLVO interactions, but also non-DLVO forces. Close comparison of alpha for EPS extracted from different sources showed alpha increased with increasing proteins to polysaccharides ratio. Subsequent experiments for EPS extracted from the same strain but with different proteins to polysaccharides ratios and from activated sludge also showed that alpha were largest for EPS with greatest proteins to polysaccharides ratio. Additional experiments for pure protein and solutions with different pure proteins to pure saccharides ratios further corroborated that larger proteins to polysaccharides ratio resulted in greater EPS deposition.

Acceptability of HIV Pre-Exposure Prophylaxis (PrEP) and Implementation Challenges Among Men Who Have Sex with Men in India: A Qualitative Investigation.

PubMed

Chakrapani, Venkatesan; Newman, Peter A; Shunmugam, Murali; Mengle, Shruta; Varghese, Jarvis; Nelson, Ruban; Bharat, Shalini

2015-10-01

This qualitative study explored the acceptability of HIV pre-exposure prophylaxis (PrEP) among MSM in India, and identified facilitators and barriers to future PrEP uptake. In 2014, we conducted 10 focus groups (n=61) among a purposive sample of diverse MSM recruited through community-based organizations in Chennai and Mumbai, and 10 key informant interviews with community leaders and health care providers. Participants' mean age was 26.1 years (SD 4.8); 62% completed secondary education, and 42% engaged in sex work. No focus group participants had heard of PrEP, but once explained, most reported they would likely use it. PrEP was alternately perceived as a 'back-up plan', a condom substitute, or a burden with concurrent condom use. Facilitators were potential for covert use, sex without condoms, and anxiety-less sex. Potential barriers emerged around stigma associated with PrEP use, fear of disclosures to one's family, wife, or male steady partner, and being labeled as HIV-positive or promiscuous by peers. Preferences emerged for intermittent rather than daily PrEP use, injectable PrEP, and free or subsidized access through community organizations or government hospitals. Key informants expressed additional concerns about risk compensation, non-adherence, and impact on ART availability for treatment. Demonstration projects are needed in India to support PrEP implementation tailored for at-risk MSM. Educational interventions for MSM should address concerns about PrEP effectiveness, side effects, and mitigate risk compensation. Community engagement may facilitate broad acceptability and challenge stigma around PrEP use. Importantly, provision of free or subsidized PrEP is necessary to making implementation feasible among low socioeconomic status MSM in India.

The Potential of Pre-Exposure Prophylaxis for Women in Violent Relationships.

PubMed

Braksmajer, Amy; Senn, Theresa E; McMahon, James

2016-06-01

HIV and intimate partner violence (IPV) are significant intersecting threats to women's health. Women in violent relationships have few feasible HIV risk reduction options as traditional prevention methods are largely dependent on a partner's cooperation. The purpose of this review is to explore potential benefits and drawbacks of pre-exposure prophylaxis (PrEP) use among women in the United States experiencing IPV. Advantages of PrEP use in this population include the potential for covert or autonomous use, coital independence, dual protection against sexual and injection risk, and facilitated connections to social services. A number of barriers, however, may interfere with the effective use of PrEP, including partner resistance, cost, frequent medical visits, gendered norms regarding sexuality, and stigma. To realize its potential for women in violent relationships, it will be necessary to incorporate PrEP into behavioral and structural interventions that encourage uptake, facilitate adherence, ensure women's safety, and challenge existing gender norms.

'PrEP is not ready for our community, and our community is not ready for PrEP': pre-exposure prophylaxis for HIV for people who inject drugs and limits to the HIV prevention response.

PubMed

Guise, Andy; Albers, Eliot Ross; Strathdee, Steffanie A

2017-04-01

Pre-exposure prophylaxis for HIV, or 'PrEP', is the use of antiretroviral medicines by people who are HIV-negative to protect themselves against acquiring HIV. PrEP has shown efficacy for preventing HIV acquisition. Despite the potential, many concerns have been voiced by people who inject drugs (PWID) and their organizations. There is a need to engage with these views and ensure their integration in to policy and strategy. This paper presents PWID views on PrEP to foster the uptake of these opinions into scientific and policy debate around PrEP METHODS: Critical analysis of a report of a community consultation led by the International Network of People who Use Drugs (INPUD). The INPUD report highlights enthusiasm from PWID for PrEP, but also three main concerns: the feasibility and ethics of PrEP, its potential use as a substitute for other harm reduction strategies and how a focus on PrEP heralds a re-medicalization of HIV. Each concern relates to evidenced gaps in essential services or opposition to harm reduction and PWID human rights. People who use drugs have fundamental concerns about the potential impacts of pre-exposure prophylaxis for HIV which reflect a 'fault line' in HIV prevention: a predominance of biomedical approaches over community perspectives. Greater community engagement in HIV prevention strategy is needed, or we risk continuing to ignore the need for action on the underlying structural drivers and social context of the HIV epidemic. © 2016 Society for the Study of Addiction.

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection.

PubMed

Di Biagio, Antonio; Riccardi, Niccolò; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians' knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP's financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice.

Pre-exposure prophylaxis of HIV

PubMed Central

Naswa, Smriti; Marfatia, Y. S.

2011-01-01

Pre-exposure prophylaxis (PrEP) is an experimental approach to HIV prevention and consists of antiretroviral drugs to be taken before potential HIV exposure in order to reduce the risk of HIV infection and continued during periods of risk. An effective PrEP could provide an additional safety net to sexually active persons at risk, when combined with other prevention strategies. Women represent nearly 60% of adults infected with HIV and PrEP can be a female-controlled prevention method for women who are unable to negotiate condom use. Two antiretroviral nucleoside analog HIV-1 reverse transcriptase inhibitor drugs are currently under trial as PrEP drugs, namely tenofovirdisoproxilfumarate (TDF) alone and TDF in combination with emricitabine (FTC), to be taken as daily single dose oral drugs. There are 11 ongoing trials of ARV-based prevention in different at risk populations across the world. The iPrex trial showed that daily use of oral TDF/FTC by MSM resulted in 44% reduction in the incidence of HIV. This led to publication of interim guidance by CDC to use of PrEP by health providers for MSM. Few other trials are Bangkok Tenofovir Study, Partners PrEP Study, FEM-PrEP study, and VOICE (MTN-003) study. Future trials are being formulated for intermittent PrEP (iPrEP) where drugs are taken before and after sex, “stand-in dose” iPrEP, vaginal or rectal PrEP, etc. There are various issues/concerns with PrEP such as ADRs and resistance to TDF/FTC, adherence to drugs, acceptability, sexual disinhibition, use of PrEP as first line of defense for HIV without other prevention strategies, and cost. The PrEP has a potential to address unmet need in public health if delivered as a part of comprehensive toolkit of prevention services, including risk-reduction, correct and consistent use of condoms, and diagnosis and treatment of sexually transmitted infections. PMID:21799568

How Stigma Surrounding the Use of HIV Preexposure Prophylaxis Undermines Prevention and Pleasure: A Call to Destigmatize "Truvada Whores".

PubMed

Calabrese, Sarah K; Underhill, Kristen

2015-10-01

Antiretroviral preexposure prophylaxis (PrEP; emtricitabine and tenofovir disoproxil fumarate [Truvada]) prevents HIV without penalizing sexual pleasure, and may even enhance pleasure (e.g., by reducing HIV-related anxiety). However, concern about sexual risk behavior increasing with PrEP use (risk compensation) and corresponding stereotypes of promiscuity may undermine PrEP's preventive potential. In this commentary, we review literature on sexual behavior change accompanying PrEP use, discuss risk compensation concerns and the "Truvada whore" stereotype as PrEP barriers, question the appropriateness of restricting PrEP access because of risk compensation, and consider sexual pleasure as a benefit of PrEP, an acceptable motive for seeking PrEP, and a core element of health. It is essential for science to trump stereotypes and sex-negative messaging in guiding decision-making affecting PrEP access and uptake.

Progressive Hearing Loss in Mice Carrying a Mutation in Usp53

PubMed Central

Kazmierczak, Marcin; Harris, Suzan L.; Kazmierczak, Piotr; Shah, Prahar; Starovoytov, Valentin; Ohlemiller, Kevin K.

2015-01-01

Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions. SIGNIFICANCE STATEMENT Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation. Here, we have identified a mutation in the Usp53 gene that causes progressive hearing loss in the mambo mouse line. We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis. PMID:26609154

Field evoked potentials in the globus pallidus of non-human primates.

PubMed

Prescott, Ian A; Marino, Robert A; Levy, Ron

2017-07-01

Stimulation-induced field evoked potentials (fEPs) have been described in the basal ganglia output nuclei of patients with Parkinson's disease and dystonia. The aim of this study was to ascertain whether fEPs were inducible in the external (GPe) and internal (GPi) segments of the globus pallidus in normal non-human primates (NHPs). Microelectrode recording and stimulation was performed in the GPe and GPi of 2 healthy NHPs. Stimulus response curves of the fEP response to changing pulse width and amplitude examined strength-duration relationships and allowed for calculation of fEP chronaxie in the GPe and GPi. Traditional localization techniques were also used, including comparison of neuronal firing rates, optic tract activation, and internal capsule activation. Notable differences were seen in the fEPs found in GPe compared to the fEPs found in GPi. The GPe fEP had a smaller chronaxie time and larger positive deflection amplitude compared to GPi. In addition, an earlier negative deflection was identified in both nuclei and a late negative deflection was observed in the GPe in contrast to reported fEPs in patients with movement disorders. fEPs proved valuable as an ancillary method in localizing the GPe and GPi in NHPs and may be useful in the operating room during human GPi deep brain stimulation or pallidotomy procedures. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

Willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia: findings from a qualitative study

PubMed Central

Bourne, Adam; Cassolato, Matteo; Thuan Wei, Clayton Koh; Wang, Bangyuan; Pang, Joselyn; Lim, Sin How; Azwa, Iskandar; Yee, Ilias; Mburu, Gitau

2017-01-01

Abstract Background: Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake. Methods: As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis. Results: Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to “at-risk” men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours. Conclusions: This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV. PMID:28782336

Willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia: findings from a qualitative study.

PubMed

Bourne, Adam; Cassolato, Matteo; Thuan Wei, Clayton Koh; Wang, Bangyuan; Pang, Joselyn; Lim, Sin How; Azwa, Iskandar; Yee, Ilias; Mburu, Gitau

2017-08-02

Men who have sex with men (MSM) continue to be disproportionately affected by HIV in Malaysia. Recent success has been observed within demonstration projects examining the efficacy of HIV pre-exposure prophylaxis (PrEP), an antiretroviral -based medication taken by HIV-negative men to prevent sero-conversion. In order for such promising findings to be translated in real-world settings, it is important to understand the acceptability of PrEP, including perceived barriers to access or uptake. As part of a larger mixed-methods study exploring acceptability and willingness to use PrEP among MSM in Malaysia, 19 men took part in audio-recorded focus group discussions hosted by a community-based HIV organization and facilitated by a trained researcher. Discussions focussed on awareness and potential information management, general perceptions of PrEP and potential motivations or barriers to the use of PrEP, including those at the personal, social, health system or structural level. Data were transcribed verbatim and underwent a detailed thematic analysis. Rather than perceiving PrEP as a replacement for condoms in terms of having safer sex, many participants viewed it as an additional layer protection, serving as a crucial barrier to infection on occasions where condom use was intended, but did not occur. It was also perceived as more valuable to "at-risk" men, such as those in HIV sero-discordant relationships or those with a higher number of sexual partners. Elements of discussion tended to suggest that some men taking PrEP may be subject to stigma from others, on the assumption they may be promiscuous or engage in high-risk sexual behaviours. This qualitative study indicates that, broadly speaking, PrEP may be acceptable to MSM in Malaysia. However, in order for its potential to be realized, and uptake achieved, educative interventions are required to inform the target population as to the efficacy and potential, positive impact of PrEP. Given concerns for how those taking it may be stigmatized, it is crucial that the use of PrEP is presented as a responsible course of action, and one of a range of strategies that men can use to keep themselves safe from HIV.

In situ synthesis of exopolysaccharides by Leuconostoc spp. and Weissella spp. and their rheological impacts in fava bean flour.

PubMed

Xu, Yan; Wang, Yaqin; Coda, Rossana; Säde, Elina; Tuomainen, Päivi; Tenkanen, Maija; Katina, Kati

2017-05-02

Fava bean flour is regarded as a potential plant-based protein source, but the addition of it at high concentration is restricted by its poor texture-improving ability and by anti-nutritional factors (ANF). Exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) are regarded as good texture modifiers. In this study, fava bean flour was fermented with Leuconostoc spp. and Weissella spp. with or without sucrose addition, in order to evaluate their potential in EPS production. The contents of free sugars, organic acids, mannitol and EPS in all fermented fava bean doughs were measured. Rheological properties of sucrose-enriched doughs, including viscosity flow curves, hysteresis loop and dynamic oscillatory sweep curves, were measured after fermentation. As one of the ANF, the degradation of raffinose family oligosaccharides (RFO) was also studied by analyzing RFO profiles of different doughs. Quantification of EPS revealed the potential of Leuconostoc pseudomesenteroides DSM 20193 in EPS production, and the rheological analysis showed that the polymers produced by this strain has the highest thickening and gelling capability. Furthermore, the viscous fava bean doughs containing plant proteins and synthesized in situ EPS may have a potential application in the food industry and fulfill consumers' increasing demands for "clean labels" and plant-originated food materials. Copyright © 2017 Elsevier B.V. All rights reserved.

Equivalency Programmes (EPs) for Promoting Lifelong Learning

ERIC Educational Resources Information Center

Haddad, Caroline, Ed.

2006-01-01

Equivalency programmes (EPs) refers to alternative education programmes that are equivalent to the formal education system in terms of curriculum and certification, policy support mechanisms, mode of delivery, staff training, and other support activities such as monitoring, evaluation and assessment. The development of EPs is potentially an…

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer.

PubMed

von der Emde, Laura; Goltz, Diane; Latz, Stefan; Müller, Stefan C; Kristiansen, Glen; Ellinger, Jörg; Syring, Isabella

2014-01-01

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors.

Prostaglandin receptors EP1-4 as a potential marker for clinical outcome in urothelial bladder cancer

PubMed Central

von der Emde, Laura; Goltz, Diane; Latz, Stefan; Müller, Stefan C; Kristiansen, Glen; Ellinger, Jörg; Syring, Isabella

2014-01-01

Prostaglandins, especially prostaglandin E2 (PGE2), and COX-2 play an important role in carcinogenesis of many tumors including bladder cancer (BCA). The PGE2 receptors EP1-4 regulate tumor cell growth, invasion and migration in different tumor entities but EP expression in BCA remains to be determined. In the present study we examined the expression of EP1-4 in non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and normal urothelial tissue (NU) using immunohistochemistry. Nuclear and cytoplasmic EP1-4 expression was correlated with clinicopathological parameters and survival of BCA patients. EP1, EP2 and EP3 were significantly less expressed in the cytoplasm und nucleus of NMIBC and MIBC than in NU; EP4 cytoplasmic staining in MIBC was significantly higher compared to NU. The cytoplasmic staining was significantly more abundant in MIBC than in NMIBC in all investigated receptors except EP2. The level of EP staining in NMIBC was correlated with staging and grading, especially cytoplasmic EP1. Nuclear staining of EP1 was an independent predictor of BCA recurrence-free survival in NMIBC patients. EP receptors are dysregulated in BCA. The increase of EP1 may be used as prognostic parameter in NMIBC patients and its dysregulation could be targeted by specific EP1 inhibitors. PMID:25520883

Prostaglandin E2 regulates melanocyte dendrite formation through activation of PKCζ

PubMed Central

Scott, Glynis; Fricke, Alex; Fender, Anne; McClelland, Lindy; Jacobs, Stacey

2007-01-01

Prostaglandins are lipid signaling intermediates released by keratinocytes in response to ultraviolet irradiation (UVR) in the skin. The main prostaglandin released following UVR is PGE2, a ligand for 4 related G-protein coupled receptors (EP1, EP2, EP3 and EP4). Our previous work established that PGE2 stimulates melanocyte dendrite formation through activation of the EP1 and EP3 receptors. The purpose of the present report is to define the signaling intermediates involved in EP1 and EP3-dependent dendrite formation in human melanocytes. We recently showed that activation of the atypical PKCζ isoform stimulates melanocyte dendricity in response to treatment with lysophosphatidylcholine. We therefore examined the potential contribution of PKCζ activation on EP1 and EP3-dependent dendrite formation in melanocytes. Stimulation of the EP1 and EP3 receptors by selective agonists activated PKCζ, and inhibition of PKCζ activation abrogated EP1 and EP3-receptor mediated melanocyte dendricity. Because of the importance of Rho-GTP binding proteins in the regulation of melanocyte dendricity, we also examined the effect of EP1 and EP3 receptor activation on Rac and Rho activity. Neither Rac nor Rho was activated upon treatment with EP1,3-receptor agonists. We show that melanocytes express only the EP3A1 isoform, but not the EP3B receptor isoform, previously associated with Rho activation, consistent with a lack of Rho stimulation by EP3 agonists. Our data suggest that PKCζ activation plays a predominant role in regulation of PGE2-dependent melanocyte dendricity. PMID:17850789

Large Amplitude Cortical Evoked Potentials in Nonepileptic Patients. Reviving an Old Neurophysiologic Tool to Help Detect CNS Pathology.

PubMed

Martín-Palomeque, Guillermo; Castro-Ortiz, Antonio; Pamplona-Valenzuela, Pilar; Saiz-Sepúlveda, Miguel Á; Cabañes-Martínez, Lidia; López, Jaime R

2017-01-01

Although large amplitude evoked potentials (EPs) are typically associated with progressive myoclonic epilepsy patients, giant EPs imply central nervous system (CNS) hyperexcitability and can be seen in various nonepileptic disorders. We performed a retrospective chart review including history, physical examination, imaging and diagnostic studies of nonepileptic patients with large amplitude somatosensory evoked potentials (SSEPs) and visual evoked potentials (VEPs) during 2007 to 2013. Large amplitude EPs were defined as follows: VEPs (N75-P100) >18 μV; and SSEPs (N20-P25) >6.4 μV. Recording montage for VEPs was Oz-Cz and SSEPs C3'/C4'-Fz. Fifty-two patients (33 females, 19 males; age range, 9-90 years) were identified. No CNS pathology was detected in 7 patients. All remaining patients were diagnosed with new CNS disorders including: vascular (37%); myelopathies (13%); demyelinating (11%); space occupying lesions (8.7%); syringomyelia (8.7%); hydrocephalus (6.5%); Vitamin B-12 deficiency (4.3%); multiple system atrophy (4.3%); and toxins (2.2%). This study supports the notion that large amplitude EP implies CNS hyperexcitability and CNS disease. These results confirm the utility of EP studies in patients with suspected CNS pathology.

United States family planning providers' knowledge of and attitudes towards preexposure prophylaxis for HIV prevention: a national survey.

PubMed

Seidman, Dominika; Carlson, Kimberly; Weber, Shannon; Witt, Jacki; Kelly, Patricia J

2016-05-01

The Centers for Disease Control and Prevention defines HIV prevention as a core family planning service. The HIV community identified family planning visits as key encounters for women to access preexposure prophylaxis (PrEP) for HIV prevention. No studies explore US family planning providers' knowledge of and attitudes towards PrEP. We conducted a national survey of clinicians to understand barriers and facilitators to PrEP implementation in family planning. Family planning providers recruited via website postings, national meetings, and email completed an anonymous survey in 2015. Descriptive statistics were performed. Among 604 respondents, 495 were eligible for analysis and 342 were potential PrEP prescribers (physicians, nurse practitioners, midwives or physicians assistants). Among potential prescribers, 38% correctly defined PrEP [95% confidence interval (CI): 32.5-42.8], 37% correctly stated the efficacy of PrEP (95% CI: 32.0-42.4), and 36% chose the correct HIV test after a recent exposure (95% CI: 30.6-40.8). Characteristics of those who answered knowledge questions correctly included age less than 35 years, practicing in the Northeast or West, routinely offering HIV testing, providing rectal sexually transmitted infection screening or having seen any PrEP guidelines. Even among providers in the Northeast and West, the proportion of respondents answering questions correctly was less than 50%. Thirty-six percent of respondents had seen any PrEP guidelines. Providers identified lack of training as the main barrier to PrEP implementation; 87% wanted PrEP education. To offer comprehensive HIV prevention services, family planning providers urgently need training on PrEP and HIV testing. US family planning providers have limited knowledge about HIV PrEP and HIV testing, and report lack of provider training as the main barrier to PrEP provision. Provider education is needed to ensure that family planning clients access comprehensive HIV prevention methods. Copyright © 2016 Elsevier Inc. All rights reserved.

Culturally Competent Sexual Healthcare as a Prerequisite for Obtaining Preexposure Prophylaxis: Findings from a Qualitative Study.

PubMed

Maloney, Kevin M; Krakower, Douglas S; Ziobro, Dale; Rosenberger, Joshua G; Novak, David; Mayer, Kenneth H

2017-08-01

Men who have sex with men (MSM) experience stigma in healthcare settings, which impedes disclosure of sexual behavior, potentially limiting uptake of preexposure prophylaxis (PrEP). The purpose of this study was to describe the context of this limitation and explore geographical variability. To understand how discomfort in healthcare settings affects PrEP utilization, we conducted two online focus groups with geographically diverse samples of MSM. Respondents identified primary care providers as preferred sources for PrEP, but potential uptake was limited by barriers to establishing nonjudgmental relationships with these providers. Improved patient-provider communication about sexual behaviors might increase PrEP use among MSM.

Characterization of a bovine isolate Lactobacillus mucosae DPC 6426 which produces an exopolysaccharide composed predominantly of mannose residues

USDA-ARS?s Scientific Manuscript database

Aim: Identification of exopolysaccharide (EPS)-producing lactobacilli as EPS production is potentially a very important trait among probiotic lactobacilli from technological and health promoting perspectives. Methods and Results: Characterization of EPS-producing Lactobacillus mucosae DPC 6426 in de...

The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae)

PubMed Central

Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

2016-01-01

Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster. The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose–response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P < 0.01) at low concentration (300 mg/l). In conclusion, MP + EP had the potential additive toxicity on lifespan and preadult development period for D. melanogaster. PMID:28076277

An electrophysiological follow up of patients with n-hexane polyneuropathy.

PubMed Central

Chang, Y C

1991-01-01

Electroneurographic (ENeG) and evoked potential (EP) studies were regularly performed on 11 printing workers with n-hexane polyneuropathy after cessation of exposure. At the initial examination, the ENeG studies simulated a demyelinative process. Further slowing of nerve conduction velocity, or further decreasing of action potential amplitude, or both in the follow up ENeG study were found in about half the patients. The motor distal latency did not worsen. Nerve conduction returned to normal earlier in the sensory than in the motor nerves. After the patients had regained full motor capability, conduction velocities in motor nerves were still significantly slowed. These ENeG characteristics correlate with the pathological and pathophysiological changes in experimental hexa-carbon neuropathies. The initial findings from the EP studies indicated a conduction abnormality in the central nervous system (CNS). Delayed worsening occurred in the amplitude of visual EPs in three patients. On serial follow up, the interpeak latency and interpeak amplitude of visual EPs improved little. Residual abnormalities were also found in the interpeak latency of auditory EPs in the brainstem and in the absolute latency of scalp somatosensory EPs from the peroneal nerve. Astroglial proliferation in the CNS probably impedes recovery of the abnormalities in EP. PMID:1993154

Marine Bacterial Polysaccharide EPS11 Inhibits Cancer Cell Growth via Blocking Cell Adhesion and Stimulating Anoikis

PubMed Central

Cao, Ruobing; Jin, Weihua; Shan, Yeqi; Wang, Ju; Liu, Ge; Kuang, Shan

2018-01-01

Tumor cells that acquire metastatic potential have developed resistance to anoikis, a cell death process, after detachment from their primary site to the second organ. In this study, we investigated the molecular mechanisms of a novel marine bacterial polysaccharide EPS11 which exerts its cytotoxic effects through affecting cancer cell adhesion and anoikis. Firstly, we found that EPS11 could significantly affect cell proliferation and block cell adhesion in A549 cells. We further demonstrated that the expression of several cell adhesion associated proteins is downregulated and the filiform structures of cancer cells are destroyed after EPS11 treatment. Interestingly, the destruction of filiform structures in A549 cells by EPS11 is in a dose-dependent manner, and the inhibitory tendency is very consistent with that observed in the cell adhesion assay, which confirms that filiform structures play important roles in modulating cell adhesion. Moreover, we showed that EPS11 induces apoptosis of A549 cells through stimulating βIII-tubulin associated anoikis: (i) EPS11 inhibits the expression of βIII-tubulin in both transcription and translation levels; and (ii) EPS11 treatment dramatically decreases the phosphorylation of protein kinase B (PKB or AKT), a critical downstream effector of βIII-tubulin. Importantly, EPS11 evidently inhibits the growth of A549-derived tumor xenografts in vivo. Thus, our results suggest that EPS11 may be a potential candidate for human non-small cell lung carcinoma treatment via blocking filiform structure mediated adhesion and stimulating βIII-tubulin associated anoikis. PMID:29518055

Similar simulation study on the characteristics of the electric potential response to coal mining

NASA Astrophysics Data System (ADS)

Niu, Yue; Li, Zhonghui; Kong, Biao; Wang, Enyuan; Lou, Quan; Qiu, Liming; Kong, Xiangguo; Wang, Jiali; Dong, Mingfu; Li, Baolin

2018-02-01

An electric potential (EP) can be generated during the failure process of coal and rock. In this article, a similar physical model of coal rock was built and the characteristics of the EP responding to the process of coal mining were studied. The results showed that, at the early mining stage, the structure of coal rock strata were stable in the simulation model, the support stress of overlying coal rock strata was low and the maximum subsidence was little, while the EP change was less. With the advancement of the working face, the support stress of the overlying coal rock strata in the mined-out area changed dramatically, the maximum subsidence increased constantly, the deformation and destruction were aggravated, and cracks expanded continuously. Meanwhile, the EP response was significant with fluctuation. When significant macro damage appeared in coal rock strata, the EP signal fluctuation was violent. The overlying coal rock strata were influenced by gravity and mining activity. During the mining process, the crack growth and the friction, together with slip between coal and rock particles, resulted in the response of EP. The change in EP was closely related to the damage state and stress distribution of the coal rock strata. EP monitoring has the advantages of accurate reflection and strong anti-interference in the field. Therefore, with further study, an EP monitoring method could be applied for monitoring and early warning of coal and rock dynamic disaster, and risk evaluation in the future. The strength of the EP and its fluctuation degree could serve as the key discrimination indexes.

Sample EP Flow Analysis of Severely Damaged Networks

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

Werley, Kenneth Alan; McCown, Andrew William

These are slides for a presentation at the working group meeting of the WESC SREMP Software Product Integration Team on sample EP flow analysis of severely damaged networks. The following topics are covered: ERCOT EP Transmission Model; Zoomed in to Houston and Overlaying StreetAtlas; EMPACT Solve/Dispatch/Shedding Options; QACS BaseCase Power Flow Solution; 3 Substation Contingency; Gen. & Load/100 Optimal Dispatch; Dispatch Results; Shed Load for Low V; Network Damage Summary; Estimated Service Areas (Potential); Estimated Outage Areas (potential).

Vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration applied at the nasion.

PubMed

Todd, Neil P M; McLean, Aisha; Paillard, Aurore; Kluk, Karolina; Colebatch, James G

2014-12-01

We report the results of a study to record vestibular evoked potentials (VsEPs) of cortical origin produced by impulsive acceleration (IA). In a sample of 12 healthy participants, evoked potentials recorded by 70 channel electroencephalography were obtained by IA stimulation at the nasion and compared with evoked potentials from the same stimulus applied to the forefingers. The nasion stimulation gave rise to a series of positive and negative deflections in the latency range of 26-72 ms, which were dependent on the polarity of the applied IA. In contrast, evoked potentials from the fingers were characterised by a single N50/P50 deflection at about 50 ms and were polarity invariant. Source analysis confirmed that the finger evoked potentials were somatosensory in origin, i.e. were somatosensory evoked potentials, and suggested that the nasion evoked potentials plausibly included vestibular midline and frontal sources, as well as contributions from the eyes, and thus were likely VsEPs. These results show considerable promise as a new method for assessment of the central vestibular system by means of VsEPs produced by IA applied to the head.

Optimizing content for pre-exposure prophylaxis (PrEP) counseling for men who have sex with men: Perspectives of PrEP users and high-risk PrEP naïve men.

PubMed

Wade Taylor, S; Mayer, Kenneth H; Elsesser, Steven M; Mimiaga, Matthew J; O'Cleirigh, Conall; Safren, Steven A

2014-05-01

Existing trials of antiretroviral (ARV) medication as chemoprophylaxis against HIV reveal that the degree of protection is primarily dependent on product adherence. However, there is a lack of data on targets for behavioral interventions to improve adherence to ARV as prevention. Information from individuals who have used ARV as pre-exposure prophylaxis (PrEP) can inform behavioral intervention development. Thirty-nine HIV-uninfected MSM at high risk for HIV acquisition participated in one of four semi-structured focus groups. Two of the focus groups consisted of MSM who had been prescribed and used PrEP in the context of a clinical trial; the other two consisted of high-risk MSM who had not previously used PrEP. An in-depth, within-case/across-case content analysis resulted in six descriptive themes potentially salient for a PrEP adherence behavioral intervention: (1) motivations to use PrEP, (2) barriers to PrEP use, (3) facilitators to PrEP use, (4) sexual decision-making in the context of PrEP, (5) prospective PrEP education content, and, (6) perceived effective characteristics of PrEP delivery personnel. Addressing these themes in behavioral interventions in the context of prescribing PrEP may result in the optimal "packaging" public health programs that implement PrEP for high-risk MSM.

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration.

PubMed

Zhou, Jian; Rogers, Jason H; Lee, Scott H; Sun, DongMing; Yao, Hai; Mao, Jeremy J; Kong, Kimi Y

2017-01-15

Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration.

Oral Mucosa Harbors a High Frequency of Endothelial Cells: A Novel Postnatal Cell Source for Angiogenic Regeneration

PubMed Central

Zhou, Jian; Rogers, Jason H.; Lee, Scott H.; Sun, DongMing; Yao, Hai; Mao, Jeremy J.

2017-01-01

Endothelial progenitor cells/endothelial cells (EPCs/ECs) have great potential to treat pathological conditions such as cardiac infarction, muscle ischemia, and bone fractures, but isolation of EPC/ECs from existing cell sources is challenging due to their low EC frequency. We have isolated endothelial progenitor (EP)-like cells from rat oral mucosa and characterized their yield, immunophenotype, growth, and in vivo angiogenic potential. The frequency of EP-like cells derived from oral mucosa is thousands of folds higher than EPCs derived from donor-match bone marrow samples. EP-like cells from oral mucosa were positive for EC markers CD31, VE-Cadherin, and VEGFR2. Oral mucosa-derived EP-like cells displayed robust uptake of acetylated low-density lipoprotein and formed stable capillary networks in Matrigel. Subcutaneously implanted oral mucosa-derived EP-like cells anastomosed with host blood vessels, implicating their ability to elicit angiogenesis. Similar to endothelial colony-forming cells, EP-like cells from oral mucosa have a significantly higher proliferative rate than human umbilical vein endothelial cells. These findings identify a putative EPC source that is easily accessible in the oral cavity, potentially from discarded tissue specimens, and yet with robust yield and potency for angiogenesis in tissue and organ regeneration. PMID:27832737

Extracellular Saccharide-Mediated Reduction of Au3+ to Gold Nanoparticles: New Insights for Heavy Metals Biomineralization on Microbial Surfaces.

PubMed

Kang, Fuxing; Qu, Xiaolei; Alvarez, Pedro J J; Zhu, Dongqiang

2017-03-07

Biomineralization is a critical process controlling the biogeochemical cycling, fate, and potential environmental impacts of heavy metals. Despite the indispensability of extracellular polymeric substances (EPS) to microbial life and their ubiquity in soil and aquatic environments, the role played by EPS in the transformation and biomineralization of heavy metals is not well understood. Here, we used gold ion (Au 3+ ) as a model heavy metal ion to quantitatively assess the role of EPS in biomineralization and discern the responsible functional groups. Integrated spectroscopic analyses showed that Au 3+ was readily reduced to zerovalent gold nanoparticles (AuNPs, 2-15 nm in size) in aqueous suspension of Escherichia coli or dissolved EPS extracted from microbes. The majority of AuNPs (95.2%) was formed outside Escherichia coli cells, and the removal of EPS attached to cells pronouncedly suppressed Au 3+ reduction, reflecting the predominance of the extracellular matrix in Au 3+ reduction. XPS, UV-vis, and FTIR analyses corroborated that Au 3+ reduction was mediated by the hemiacetal groups (aldehyde equivalents) of reducing saccharides of EPS. Consistently, the kinetics of AuNP formation obeyed pseudo-second-order reaction kinetics with respect to the concentrations of Au 3+ and the hemiacetal groups in EPS, with minimal dependency on the source of microbial EPS. Our findings indicate a previously overlooked, universally significant contribution of EPS to the reduction, mineralization, and potential detoxification of metal species with high oxidation state.

Home-based pre-exposure prophylaxis (PrEP) services for gay and bisexual men: An opportunity to address barriers to PrEP uptake and persistence

PubMed Central

Rendina, H. Jonathon; Grov, Christian

2017-01-01

Gay, bisexual, and other men who have sex with men (GBM) are disproportionately affected by the HIV epidemic. Despite the promise of pre-exposure prophylaxis (PrEP) in reducing HIV transmission risk, barriers for uptake and persistence exist. We sought to identify whether GBM in a nationwide cohort who have not yet initiated PrEP (n = 906) would prefer to get PrEP-related care from a primary care provider (PCP) compared to a specialist clinic or provider. We then sought to identify their level of interest and factors associated with preference for using home-based PrEP services (i.e., HB-PrEP), defined to participants as conducting HIV/STI self-testing from home with PrEP prescription mailing after an initial in-person clinic visit. We examined the associations of demographics, sexual HIV transmission risk, concern about frequent medical checkups associated with PrEP, health care access, and PrEP intentions with preferences for healthcare provider type and HB-PrEP. Concern about frequent medical checkups were associated with preferring a PCP for PrEP-related care, but men who perceived a barrier to bringing up the topic of PrEP with a doctor preferred a specialist clinic or provider more than a PCP. HB-PrEP was more appealing for younger men and those engaged in sexual HIV transmission risk, suggesting HB-PrEP could help reach GBM most vulnerable to HIV and in need of PrEP. HB-PrEP expansion has potential to increase PrEP uptake and persistence among GBM, particularly for men with barriers to clinic-based care and higher intentions to initiate PrEP. Clinical guidelines regarding HB-PrEP are needed to expand its use. PMID:29281688

Vestibular short-latency evoked potential abolished by low-frequency noise exposure in rats.

PubMed

Stewart, Courtney E; Kanicki, Ariane C; Altschuler, Richard A; King, W M

2018-02-01

The vestibular system plays a critical role in detection of head movements and is essential for normal postural control. Because of their anatomical proximity to the cochlea, the otolith organs are selectively exposed to sound pressure and are at risk for noise overstimulation. Clinical reports suggest a link between noise exposure and balance problems, but the structural and physiological basis for this linkage is not well understood. The goal of this study was to determine the effects of low-frequency noise (LFN) on the otolith organs by correlating changes in vestibular short-latency evoked potentials (VsEPs) with changes in saccular afferent endings following noise exposure. LFN exposure transiently abolished the VsEP and reduced the number of stained calyces within the sacculus. Although some recovery of the VsEP waveform could be observed within 3 days after noise, at 3 wk recovery was only partial in most animals, consistent with a reduced number of afferents with calyceal endings. These data show that a single intense noise exposure is capable of causing a vestibular deficit that appears to mirror the synaptic deficit associated with hidden hearing loss after noise-induced cochlear injury. NEW & NOTEWORTHY This is the first study to explore the effects of low-frequency high-intensity noise on vestibular short-latency evoked potential (VsEP) responses, which shows a linkage between attenuated noise-induced VsEPs and pathological changes to otolith organ afferents. This finding suggests a potential limitation of the VsEP for evaluation of vestibular dysfunction, since the VsEP measurement may assess the activity of a specific class rather than all afferents.

The difference in endolymphatic hydrostatic pressure elevation induced by isoproterenol between the ampulla and the cochlea.

PubMed

Inamoto, Ryuhei; Miyashita, Takenori; Matsubara, Ai; Hoshikawa, Hiroshi; Mori, Nozomu

2017-06-01

The purpose of the study was to investigate the difference in the responses of endolymphatic hydrostatic pressure to isoproterenol, β-adrenergic receptor agonist, between pars superior and pars inferior. The hydrostatic pressure of endolymph and perilymph and endolymphatic potential in the ampulla and the cochlea during the intravenous administration of isoproterenol were recorded using a servo-null system in guinea pigs. The hydrostatic pressure of endolymph and perilymph in the ampulla and cochlea was similar in magnitude. Isoproterenol significantly increased hydrostatic pressure of ampullar and cochlear endolymph and perilymph with no change in the ampullar endolymphatic potential and endocochlear potential, respectively. The isoproterenol-induced maximum change of endolymphatic hydrostatic pressure in ampulla was significantly (p<0.01) smaller than that in the cochlea. In ears with an obstructed endolymphatic sac, the action of isoproterenol on endolymphatic hydrostatic pressure in the ampulla disappeared like that in the cochlea. Isoproterenol elevates endolymphatic hydrostatic pressure in different manner between the vestibule and the cochlea. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention.

PubMed

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV.

The promises and challenges of pre-exposure prophylaxis as part of the emerging paradigm of combination HIV prevention

PubMed Central

Cáceres, Carlos F; Koechlin, Florence; Goicochea, Pedro; Sow, Papa-Salif; O'Reilly, Kevin R; Mayer, Kenneth H; Godfrey-Faussett, Peter

2015-01-01

Introduction Towards the end of the twentieth century, significant success was achieved in reducing incidence in several global HIV epidemics through ongoing prevention strategies. However, further progress in risk reduction was uncertain. For one thing, it was clear that social vulnerability had to be addressed, through research on interventions addressing health systems and other structural barriers. As soon as antiretroviral treatment became available, researchers started to conceive that antiretrovirals might play a role in decreasing either susceptibility in uninfected people or infectiousness among people living with HIV. In this paper we focus on the origin, present status, and potential contribution of pre-exposure prophylaxis (PrEP) within the combination HIV prevention framework. Discussion After a phase of controversy, PrEP efficacy trials took off. By 2015, daily oral PrEP, using tenofovir alone or in combination with emtricitabine, has been proven efficacious, though efficacy seems heavily contingent upon adherence to pill uptake. Initial demonstration projects after release of efficacy results have shown that PrEP can be implemented in real settings and adherence can be high, leading to high effectiveness. Despite its substantial potential, beliefs persist about unfeasibility in real-life settings due to stigma, cost, adherence, and potential risk compensation barriers. Conclusions The strategic synergy of behavioural change communication, biomedical strategies (including PrEP), and structural programmes is providing the basis for the combination HIV prevention framework. If PrEP is to ever become a key component of that framework, several negative beliefs must be confronted based on emerging evidence; moreover, research gaps regarding PrEP implementation must be filled, and appropriate prioritization strategies must be set up. Those challenges are significant, proportional to the impact that PrEP implementation may have in the global response to HIV. PMID:26198341

A novel approach to pharmaco-EEG for investigating analgesics: assessment of spectral indices in single-sweep evoked brain potentials.

PubMed

Gram, Mikkel; Graversen, Carina; Nielsen, Anders K; Arendt-Nielsen, Thomas; Mørch, Carsten D; Andresen, Trine; Drewes, Asbjørn M

2013-12-01

To compare results from analysis of averaged and single-sweep evoked brain potentials (EPs) by visual inspection and spectral analysis in order to identify an objective measure for the analgesic effect of buprenorphine and fentanyl. Twenty-two healthy males were included in a randomized study to assess the changes in EPs after 110 sweeps of painful electrical stimulation to the median nerve following treatment with buprenorphine, fentanyl or placebo patches. Bone pressure, cutaneous heat and electrical pain ratings were assessed. EPs and pain assessments were obtained before drug administration, 24, 48, 72 and 144 h after beginning of treatment. Features from EPs were extracted by three different approaches: (i) visual inspection of amplitude and latency of the main peaks in the average EPs, (ii) spectral distribution of the average EPs and (iii) spectral distribution of the EPs from single-sweeps. Visual inspection revealed no difference between active treatments and placebo (all P > 0.05). Spectral distribution of the averaged potentials showed a decrease in the beta (12-32 Hz) band for fentanyl (P = 0.036), which however did not correlate with pain ratings. Spectral distribution in the single-sweep EPs revealed significant increases in the theta, alpha and beta bands for buprenorphine (all P < 0.05) as well as theta band increase for fentanyl (P = 0.05). For buprenorphine, beta band activity correlated with bone pressure and cutaneous heat pain (both P = 0.04, r = 0.90). In conclusion single-sweep spectral band analysis increases the information on the response of the brain to opioids and may be used to identify the response to analgesics. © 2013 The Authors. British Journal of Clinical Pharmacology © 2013 The British Pharmacological Society.

A Closer Look at Racism and Heterosexism in Medical Students' Clinical Decision-Making Related to HIV Pre-Exposure Prophylaxis (PrEP): Implications for PrEP Education.

PubMed

Calabrese, Sarah K; Earnshaw, Valerie A; Krakower, Douglas S; Underhill, Kristen; Vincent, Wilson; Magnus, Manya; Hansen, Nathan B; Kershaw, Trace S; Mayer, Kenneth H; Betancourt, Joseph R; Dovidio, John F

2018-04-01

Social biases among healthcare providers could limit PrEP access. In this survey study of 115 US medical students, we examined associations between biases (racism and heterosexism) and PrEP clinical decision-making and explored prior PrEP education as a potential buffer. After viewing a vignette about a PrEP-seeking MSM patient, participants reported anticipated patient behavior (condomless sex, extra-relational sex, and adherence), intention to prescribe PrEP to the patient, biases, and background characteristics. Minimal evidence for racism affecting clinical decision-making emerged. In unadjusted analyses, heterosexism indirectly affected prescribing intention via all anticipated behaviors, tested as parallel mediators. Participants expressing greater heterosexism more strongly anticipated increased risk behavior and adherence problems, which were associated with lower prescribing intention. The indirect effect via condomless sex remained significant adjusting for background characteristics. Prior PrEP education did not buffer any indirect effects. Heterosexism may compromise PrEP provision to MSM and should be addressed in PrEP-related medical education.

Implications of electric potentials applied on a denitrifying process.

PubMed

Cadena Ramírez, Arturo; Texier, Anne-Claire; González, Ignacio; Gómez, Jorge

2018-03-20

The effect of three electric potentials (EP) (+104, -187 and -279 mV) applied to the denitrifying process was explored. It was observed that the denitrifying sludge was able to support the oxidation of p-cresol with the application of the EP in the absence of nitrate, but it was unable to drive the denitrification without an organic electron donor. On denitrification, the applied EP uncoupled the oxidative from the reductive process, favoring the p-cresol oxidation over the production of N2. Additionally, biochemical level effects were observed. At +104 and -279 mV potentials, the nitrate and nitrite consumption was affected as well as the p-hydroxybenzoate transformation. However, at -187 mV, effects seemed to occur only on the transport of substrates. This paper presents evidence that denitrification has very characteristic and different physiological behaviors for each EP assayed.

A Multi-US City Assessment of Awareness and Uptake of Pre-exposure Prophylaxis (PrEP) for HIV Prevention Among Black Men and Transgender Women Who Have Sex with Men.

PubMed

Eaton, Lisa A; Matthews, Derrick D; Driffin, Daniel D; Bukowski, Leigh; Wilson, Patrick A; Stall, Ron D

2017-07-01

The HIV epidemic among Black men and transgender women who have sex with men (BMTW) demands an urgent public health response. HIV point prevalence among this population ranges from 25 to 43%-a rate far exceeding any other group. Pre-exposure prophylaxis (PrEP) for HIV prevention is a very promising prevention tool; however, its full potential to slow the epidemic has yet to be realized. For the current study, random time-location sampling at Black Gay Pride Events was used to collect data from N = 1274 BMTW, from five US cities, reporting HIV-negative/unknown status. In-field HIV testing was also provided to participants. Participants were assessed on awareness and use of PrEP, health care factors, HIV testing history, psychosocial variables, and sex behaviors. About one third of participants were aware of PrEP (39%), and a small percentage of participants were users of PrEP (4.6%). In multivariable analyses, being in a relationship, testing for HIV in the past 6 months, and others being aware of one's sexuality were positively associated with PrEP awareness. Higher levels of internalized homophobia and greater numbers of female sex partners were positively associated with PrEP use, while education and condom use were negatively associated. Based on study findings, messaging and uptake of PrEP needs greater expansion and requires novel approaches for scale-up. Improving linkage to HIV testing services is likely critical for engaging BMTW with PrEP. The potential for PrEP to slow the HIV epidemic is high; however, we must strengthen efforts to ensure universal availability and uptake.

What Primary Care Providers Need to Know about Pre-Exposure Prophylaxis (PrEP) for HIV Prevention: Narrative Review

PubMed Central

Krakower, Douglas; Mayer, Kenneth H.

2013-01-01

As HIV prevalence climbs globally, including more than 50,000 new infections per year in the United States, we need effective HIV prevention strategies. The use of antiretrovirals for pre-exposure prophylaxis (known as “PrEP”) among high-risk HIV-uninfected persons is emerging as one such strategy. Randomized controlled trials have demonstrated that once daily oral PrEP decreased HIV incidence among at-risk MSM and African heterosexuals, including HIV serodiscordant couples. An additional randomized control trial of a pericoital topical application of antiretroviral microbicide gel reduced HIV incidence among at-risk heterosexual South African women. Two other studies in African women did not demonstrate the efficacy of oral or topical PrEP, raising concerns about adherence patterns and efficacy in this population. The FDA Antiretroviral Advisory Panel reviewed these studies and additional data in May 2012 and recommended the approval of oral tenofovir-emtricitabine for PrEP in high-risk populations. Patients may seek PrEP from their primary care providers and those on PrEP require monitoring. Thus, primary care providers should become familiar with PrEP. This review outlines the current state of knowledge about PrEP as it pertains to primary care including identification of individuals likely to benefit from PrEP, counseling to maximize adherence and minimize potential increases in risky behavior, and monitoring for potential drug toxicities, HIV acquisition, and antiretroviral drug resistance. Issues related to cost and insurance coverage are also discussed. Recent data suggest that PrEP, in conjunction with other prevention strategies, holds promise in helping to curtail the HIV epidemic. PMID:22821365

Sexual risk behaviors and acceptability of HIV pre-exposure prophylaxis among HIV-negative gay and bisexual men in serodiscordant relationships: a mixed methods study.

PubMed

Brooks, Ronald A; Landovitz, Raphael J; Kaplan, Rachel L; Lieber, Eli; Lee, Sung-Jae; Barkley, Thomas W

2012-02-01

The objective of this mixed methods study was to examine current sexual risk behaviors, acceptability and potential adoption of pre-exposure prophylaxis (PrEP) for HIV prevention, and sexual behavior intentions with PrEP adoption among HIV-negative gay and bisexual men (GBM) in HIV serodiscordant relationships. A multiracial/ethnic sample of 25 HIV-negative GBM in serodiscordant relationships completed a qualitative interview and a brief interviewer-administered survey. A modified grounded theory approach was used to identify key themes relating to acceptability and future adoption of PrEP. Participants reported engaging in sexual risk behaviors that place them at risk for HIV infection. Participants also reported a high level of acceptability for PrEP and willingness to adopt PrEP for HIV prevention. Qualitative themes explaining future PrEP adoption included: (1) the opportunity to engage in sex using a noncondom HIV prevention method, (2) protection from HIV infection, and (3) less anxiety when engaging in sex with an HIV-positive partner. Associated with the future adoption of PrEP, a majority (64%) of participants indicated the likelihood for an increase in sexual risk behaviors and a majority (60%) of participants also indicated the likelihood for a decrease or abandonment of condom use, both of which are in contrast to the findings from the large iPrEx study. These findings suggest that the use of PrEP by HIV-negative GBM in serodiscordant relationships carries with it the potential for risk compensation. The findings suggest that PrEP only be offered as part of a comprehensive HIV prevention strategy that includes ongoing risk reduction counseling in the delivery of PrEP to help moderate risk compensation.

Bacterial exopolysaccharides as a modern biotechnological tool for modification of fungal laccase properties and metal ion binding.

PubMed

Osińska-Jaroszuk, Monika; Jaszek, Magdalena; Starosielec, Magdalena; Sulej, Justyna; Matuszewska, Anna; Janczarek, Monika; Bancerz, Renata; Wydrych, Jerzy; Wiater, Adrian; Jarosz-Wilkołazka, Anna

2018-03-26

Four bacterial EPSs extracted from Rhizobium leguminosarum bv. trifolii Rt24.2, Sinorhizobium meliloti Rm1021, Bradyrhizobium japonicum USDA110, and Bradyrhizobium elkanii USDA76 were determined towards their metal ion adsorption properties and possible modification of Cerrena unicolor laccase properties. The highest magnesium and iron ion-sorption capacity (~ 42 and ~ 14.5%, respectively) was observed for EPS isolated from B. japonicum USDA110. An evident influence of EPSs on the stability of laccase compared to the control values (without EPSs) was shown after 30-day incubation at 25 °C. The residual activity of laccases was obtained in the presence of Rh76EPS and Rh1021EPS, i.e., 49.5 and 41.5% of the initial catalytic activity, respectively. This result was confirmed by native PAGE electrophoresis. The EPS effect on laccase stability at different pH (from 3.8 to 7.0) was also estimated. The most significant changes at the optimum pH value (pH 5.8) was observed in samples of laccase stabilized by Rh76EPS and Rh1021EPS. Cyclic voltamperometry was used for analysis of electrochemical parameters of laccase stabilized by bacterial EPS and immobilized on single-walled carbon nanotubes (SWCNTs) with aryl residues. Laccases with Rh76EPS and Rh1021EPS had an evident shift of the value of the redox potential compared to the control without EPS addition. In conclusion, the results obtained in this work present a new potential use of bacterial EPSs as a metal-binding component and a modulator of laccase properties especially stability of enzyme activity, which can be a very effective tool in biotechnology and industrial applications.

Which Patients in the Emergency Department Should Receive Preexposure Prophylaxis? Implementation of a Predictive Analytics Approach.

PubMed

Ridgway, Jessica P; Almirol, Ellen A; Bender, Alvie; Richardson, Andrew; Schmitt, Jessica; Friedman, Eleanor; Lancki, Nicola; Leroux, Ivan; Pieroni, Nina; Dehlin, Jessica; Schneider, John A

2018-05-01

Emergency Departments (EDs) have the potential to play a crucial role in HIV prevention by identifying and linking high-risk HIV-negative clients to preexposure prophylaxis (PrEP) care, but it is difficult to perform HIV risk assessment for all ED patients. We aimed to develop and implement an electronic risk score to identify ED patients who are potential candidates for PrEP. Using electronic medical record (EMR) data, we used logistic regression to model the outcome of PrEP eligibility. We converted the model into an electronic risk score and incorporated it into the EMR. The risk score is automatically calculated at triage. For patients whose risk score is above a given threshold, an automated electronic alert is sent to an HIV prevention counselor who performs real time HIV prevention counseling, risk assessment, and PrEP linkage as appropriate. The electronic risk score includes the following EMR variables: age, gender, gender of sexual partner, chief complaint, and positive test for sexually transmitted infection in the prior 6 months. A risk score ≥21 has specificity of 80.6% and sensitivity of 50%. In the first 5.5 months of implementation, the alert fired for 180 patients, 34.4% (62/180) of whom were women. Of the 51 patients who completed risk assessment, 68.6% (35/51) were interested in PrEP, 17.6% (9/51) scheduled a PrEP appointment, and 7.8% (4/51) successfully initiated PrEP. The measured number of successful PrEP initiations is likely an underestimate, as it does include patients who initiated PrEP with outside providers or referred acquaintances for PrEP care.

Evaluating filterability of different types of sludge by statistical analysis: The role of key organic compounds in extracellular polymeric substances.

PubMed

Xiao, Keke; Chen, Yun; Jiang, Xie; Zhou, Yan

2017-03-01

An investigation was conducted for 20 different types of sludge in order to identify the key organic compounds in extracellular polymeric substances (EPS) that are important in assessing variations of sludge filterability. The different types of sludge varied in initial total solids (TS) content, organic composition and pre-treatment methods. For instance, some of the sludges were pre-treated by acid, ultrasonic, thermal, alkaline, or advanced oxidation technique. The Pearson's correlation results showed significant correlations between sludge filterability and zeta potential, pH, dissolved organic carbon, protein and polysaccharide in soluble EPS (SB EPS), loosely bound EPS (LB EPS) and tightly bound EPS (TB EPS). The principal component analysis (PCA) method was used to further explore correlations between variables and similarities among EPS fractions of different types of sludge. Two principal components were extracted: principal component 1 accounted for 59.24% of total EPS variations, while principal component 2 accounted for 25.46% of total EPS variations. Dissolved organic carbon, protein and polysaccharide in LB EPS showed higher eigenvector projection values than the corresponding compounds in SB EPS and TB EPS in principal component 1. Further characterization of fractionized key organic compounds in LB EPS was conducted with size-exclusion chromatography-organic carbon detection-organic nitrogen detection (LC-OCD-OND). A numerical multiple linear regression model was established to describe relationship between organic compounds in LB EPS and sludge filterability. Copyright © 2016 Elsevier Ltd. All rights reserved.

Production of exopolysaccharide from rhizobia with potential biotechnological and bioremediation applications.

PubMed

Castellane, Tereza Cristina Luque; Persona, Michelli Romanoli; Campanharo, João Carlos; de Macedo Lemos, Eliana Gertrudes

2015-03-01

The potential use of rhizobia under controlled fermentation conditions may result in the production of new extracellular polymeric substances (EPS) having novel and superior properties that will open up new areas of industrial applications and thus increase their demand. The production of EPS and the stability of emulsions formed with soybean oil, diesel oil and toluene using different concentrations of purified EPS derived from wild-type and mutant strains of Rhizobium tropici SEMIA 4077 was investigated. The EPS was defined as a heteropolysaccharide composed of six constituent monosaccharides that displayed higher intrinsic viscosity and pseudoplastic non-Newtonian fluid behavior in an aqueous solution. The ratio between the total EPS production and the cellular biomass was 76.70 for the 4077::Z04 mutant strain and only 8.10 for the wild-type strain. The EPS produced by the wild-type R. tropici SEMIA 4077 resulted in more stable emulsions with the tested toluene than xanthan gum, and the emulsification indexes with hydrocarbons and soybean oil were higher than 50%, indicating strong emulsion-stabilizing capacity. These results demonstrate that the EPS of R. tropici strains could be attractive for use in industrial and environmental applications, as it had higher intrinsic viscosity and good emulsification activity. Copyright © 2015 Elsevier B.V. All rights reserved.

Structural characterization of Bacillus licheniformis Dahb1 exopolysaccharide-antimicrobial potential and larvicidal activity on malaria and Zika virus mosquito vectors.

PubMed

Abinaya, Muthukumar; Vaseeharan, Baskaralingam; Divya, Mani; Vijayakumar, Sekar; Govindarajan, Marimuthu; Alharbi, Naiyf S; Khaled, Jamal M; Al-Anbr, Mohammed N; Benelli, Giovanni

2018-04-27

Microbial polysaccharides produced by marine species play a key role in food and cosmetic industry, as they are nontoxic and biodegradable polymers. This investigation reports the isolation of exopolysaccharide from Bacillus licheniformis Dahb1 and its biomedical applications. Bacillus licheniformis Dahb1 exopolysaccharide (Bl-EPS) was extracted using the ethanol precipitation method and structurally characterized. FTIR and 1 H-NMR pointed out the presence of various functional groups and primary aromatic compounds, respectively. Bl-EPS exhibited strong antioxidant potential confirmed via DPPH radical, reducing power and superoxide anion scavenging assays. Microscopic analysis revealed that the antibiofilm activity of Bl-EPS (75 μg/ml) was higher against Gram-negative (Pseudomonas aeruginosa and Proteus vulgaris) bacteria over Gram-positive species (Bacillus subtilis and Bacillus pumilus). Bl-EPS led to biofilm inhibition against Candida albicans when tested at 75 μg/ml. The hemolytic assay showed low cytotoxicity of Bl-EPS at 5 mg/ml. Besides, Bl-EPS achieved LC 50 values < 80 μg/ml against larvae of mosquito vectors Anopheles stephensi and Aedes aegypti. Overall, our findings pointed out the multipurpose bioactivity of Bl-EPS, which deserves further consideration for pharmaceutical, environmental and entomological applications.

A MISO-ARX-Based Method for Single-Trial Evoked Potential Extraction.

PubMed

Yu, Nannan; Wu, Lingling; Zou, Dexuan; Chen, Ying; Lu, Hanbing

2017-01-01

In this paper, we propose a novel method for solving the single-trial evoked potential (EP) estimation problem. In this method, the single-trial EP is considered as a complex containing many components, which may originate from different functional brain sites; these components can be distinguished according to their respective latencies and amplitudes and are extracted simultaneously by multiple-input single-output autoregressive modeling with exogenous input (MISO-ARX). The extraction process is performed in three stages: first, we use a reference EP as a template and decompose it into a set of components, which serve as subtemplates for the remaining steps. Then, a dictionary is constructed with these subtemplates, and EPs are preliminarily extracted by sparse coding in order to roughly estimate the latency of each component. Finally, the single-trial measurement is parametrically modeled by MISO-ARX while characterizing spontaneous electroencephalographic activity as an autoregression model driven by white noise and with each component of the EP modeled by autoregressive-moving-average filtering of the subtemplates. Once optimized, all components of the EP can be extracted. Compared with ARX, our method has greater tracking capabilities of specific components of the EP complex as each component is modeled individually in MISO-ARX. We provide exhaustive experimental results to show the effectiveness and feasibility of our method.

The Combined Effect of Methyl- and Ethyl-Paraben on Lifespan and Preadult Development Period of Drosophila melanogaster (Diptera: Drosophilidae).

PubMed

Chen, Qi; Pan, Chenguang; Li, Yajuan; Zhang, Min; Gu, Wei

2016-01-01

Parabens are widely used as preservative substances in foods, pharmaceuticals, industrial products, and cosmetics. But several studies have cautioned that parabens have estrogenic or endocrine-disrupting properties. Drosophila melanogaster is an ideal model in vivo to detect the toxic effects of chemistry. The study was designed to assess the potential additive toxic effects of methylparaben (MP) and ethylparaben (EP) mixture (MP + EP) on lifespan and preadult development period in D. melanogaster The data revealed that the MP + EP can reduce the longevity of flies compared with the control group, consistent with a significant reduction in malondialdehyde levels and an increase in superoxide dismutase activities. Furthermore, MP + EP may have a greater toxic effect on longevity of flies than separate using with the same concentration. Additionally, parabens had a nonmonotonic dose-response effect on D. melanogaster preadult development period, showing that MP + EP delayed preadult development period compared with control group while individual MP or EP significantly shortened (P < 0.01) at low concentration (300 mg/l). In conclusion, MP + EP had the potential additive toxicity on lifespan and preadult development period for D. melanogaster. © The Author 2016. Published by Oxford University Press on behalf of the Entomological Society of America.

Concurrent targeting of EP1/EP4 receptors and COX-2 induces synergistic apoptosis in KSHV and EBV associated non-Hodgkin lymphoma cell lines

PubMed Central

Paul, Arun George; Chandran, Bala; Sharma-Walia, Neelam

2014-01-01

The effective anti-tumorigenic potential of non-steroidal anti-inflammatory drugs (NSAIDs) and eicosonoid (EP; EP1–4) receptor antagonists prompted us to test their efficacy in Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) related lymphomas. Our study demonstrated that (1) EP1–4 receptor protein levels vary among the various non-Hodgkin’s lymphoma (NHL) cell lines tested (BCBL-1:KSHV+/EBV−;BC-3: KSHV+/EBV−; Akata/EBV+: KSHV−/EBV+; and JSC-1 cells: KSHV+/EBV+ cells); (2) 5.0 µM of EP1 antagonist (SC-51322) had a significant anti-proliferative effect on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; (3) 50.0 µM of EP2 antagonist (AH6809) was required to induce a significant anti-proliferative effect on BCBL-1, Akata/EBV+, and JSC-1 cells; (4) 5.0 µM of EP4 antagonist (GW 627368X) had a significant anti-proliferative effect on BC-3, Akata/EBV+, and JSC-1 cells; (5) COX-2 selective inhibitor celecoxib (5.0µM) had significant anti-proliferative effects on BCBL-1, BC-3, Akata/EBV+, and JSC-1 cells; and (6) a combination of 1.0µM each of celecoxib, SC-51322 and GW 627368X could potentiate the pro-apoptotic properties of celecoxib or vice-versa. Overall, our studies identified the synergistic anti-proliferative effect of NSAIDs and EP receptor blockers on KSHV and EBV related B cell malignancies. PMID:23523954

Acceptability of an "on-demand" pre-exposure HIV prophylaxis trial among men who have sex with men living in France.

PubMed

Lorente, Nicolas; Fugon, Lionel; Carrieri, Maria Patrizia; Andreo, Christian; Le Gall, Jean-Marie; Cook, Emmanuel; Aboulker, Jean-Pierre; Capitant, Catherine; Molina, Jean-Michel; Spire, Bruno

2012-01-01

Although predictors of willingness to take daily, self-administered pre-exposure HIV prophylaxis (PrEP) for men who have sex with men (MSM) have been studied in the context of several PrEP trials internationally, little is known about MSM interested in participating in a trial on the use of PrEP on an "on -demand" basis, i.e., taking a first dose of combined tenofovir/emtricitabine a few hours before possible HIV sexual exposure and a second dose a few hours afterwards. A double-blind placebo randomized PrEP trial will soon begin in France to evaluate the effectiveness of PrEP in terms of reducing HIV infection rates, among MSM self-administering "on-demand" PrEP. To assess potential participants' characteristics associated with willingness to participate in the trial and identify barriers and facilitators to implementation, MSM completed a self-administered questionnaire, distributed via gay venues and community websites. Among the 443 respondents who reported being HIV-negative, 40% reported being interested in participating. Factors independently associated with interest included: reporting lower educational level, more than 20 male sexual partners in the previous year, reporting unprotected anal sex with casual partners and preferring PrEP follow-up visits in a devoted area within a hospital. There is great interest in participating in a future "on-demand" PrEP trial among HIV-negative MSM and particularly in those at potentially high risk of HIV exposure. Providing confidentiality and tailored counseling during PrEP follow-up are important issues.

The adequate stimulus for mammalian linear vestibular evoked potentials (VsEPs)

PubMed Central

Jones, Timothy A.; Jones, Sherri M.; Vijayakumar, Sarath; Brugeaud, Aurore; Bothwell, Marcella; Chabbert, Christian

2013-01-01

Short latency linear vestibular sensory evoked potentials (VsEPs) provide a means to objectively and directly assess the function of gravity receptors in mammals and birds. The importance of this functional measure is illustrated by its use in studies of the genetic basis of vestibular function and disease. Head motion is the stimulus for the VsEP. In the bird, it has been established that neurons mediating the linear VsEP respond collectively to the rate of change in linear acceleration during head movement (i.e. jerk) rather than peak acceleration. The kinematic element of motion responsible for triggering mammalian VsEPs has not been characterized in detail. Here we tested the hypothesis that jerk is the kinematic component of head motion responsible for VsEP characteristics. VsEP amplitudes and latencies changed systematically when peak acceleration level was held constant and jerk level was varied from ~0.9 to 4.6 g/ms. In contrast, responses remained relatively constant when kinematic jerk was held constant and peak acceleration was varied from ~0.9 to 5.5g in mice and ~0.44 to 2.75g in rats. Thus the mammalian VsEP depends on jerk levels and not peak acceleration. We conclude that kinematic jerk is the adequate stimulus for the mammalian VsEP. This sheds light on the behavior of neurons generating the response. The results also provide the basis for standardizing the reporting of stimulus levels, which is key to ensuring that response characteristics reported in the literature by many laboratories can be effectively compared and interpreted. PMID:21664446

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

Saeed, Noha M.; El-Demerdash, Ebtehal; Abdel-Rahman, Hanaa M.

Methyl palmitate (MP) and ethyl palmitate (EP) are naturally occurring fatty acid esters reported as inflammatory cell inhibitors. In the current study, the potential anti-inflammatory activity of MP and EP was evaluated in different experimental rat models. Results showed that MP and EP caused reduction of carrageenan-induced rat paw edema in addition to diminishing prostaglandin E2 (PGE2) level in the inflammatory exudates. In lipopolysaccharide (LPS)-induced endotoxemia in rats, MP and EP reduced plasma levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). MP and EP decreased NF-κB expression in liver and lung tissues and ameliorated histopathological changes caused by LPS.more » Topical application of MP and EP reduced ear edema induced by croton oil in rats. In the same animal model, MP and EP reduced neutrophil infiltration, as indicated by decreased myeloperoxidase (MPO) activity. In conclusion, this study demonstrates the effectiveness of MP and EP in combating inflammation in several experimental models. -- Highlights: ► Efficacy of MP and EP in combating inflammation was displayed in several models. ► MP and EP reduced carrageenan-induced rat paw edema and prostaglandin E2 level. ► MP and EP decreased TNF-α and IL-6 levels in experimental endotoxemia. ► MP and EP reduced NF-κB expression and histological changes in rat liver and lung. ► MP and EP reduced croton oil-induced ear edema and neutrophil infiltration.« less

PrEP in Italy: The time may be ripe but who's paying the bill? A nationwide survey on physicians' attitudes towards using antiretrovirals to prevent HIV infection

PubMed Central

Di Biagio, Antonio; Signori, Alessio; Maserati, Renato; Nozza, Silvia; Gori, Andrea; Bonora, Stefano; Borderi, Marco; Ripamonti, Diego; Rossi, Maria Cristina; Orofino, Giancarlo; Quirino, Tiziana; Nunnari, Giuseppe; Celesia, Benedetto Maurizio; Martini, Salvatore; Sagnelli, Caterina; Mazzola, Giovanni; Colletti, Pietro; Bartolozzi, Dario; Bini, Teresa; Ladisa, Nicoletta; Castelnuovo, Filippo; Saracino, Annalisa; Lo Caputo, Sergio

2017-01-01

Several studies have demonstrated the efficacy of the oral pre-exposure prophylaxis (PrEP) with tenofovir (with or without emtricitabine) on preventing HIV-negative partners of HIV infected patients to become infected through sexual contacts. PrEP is already available in the United States and now is approved by European Medicine Agency. In this setting we would like to gauge physicians’ knowledge, acquaintance with and attitude to include PrEP in their clinical practice. A cross sectional survey was conducted among Italian physicians expert on antiretroviral therapy. Out of 146 physicians, 35% of participants declared to be familiar with PrEP but only 46% of them believed that, currently, there are not enough reasons to make it available in Italy. 51% of physicians have already been attracted to prescribe it and 63.4% have been openly asked about PrEP. The main concerns noticed were: the risk of acquire other sexual transmitted diseases (STDs) (70% of physicians feared that PrEP could favor STDs spread), the potential harmful of PrEP if not adequately implemented and, especially the risk of possible side effects if not properly used. Nevertheless, 55.9% of participants believed that Health Authorities face an ethical obligation to make PrEP available as part of the strategies to protect from HIV transmission and half of the respondents asked for further researches to better define the role for PrEP. Attitudes regarding PrEP impact on Italian National Health Organization were also very interesting: 57.5% of participants did not believe that investing in PrEP would be an appropriate use of healthcare resources, while 70.6% affirmed that PrEP’s financial coverage should not be funded by the Italian National System of Health (SSN). This survey showed a high awareness of PrEP potential among Italian physicians coupled with a great deal of skepticism about how and if implementing it in clinical practice. PMID:28727818

Decaying and growing eigenmodes in open quantum systems: Biorthogonality and the Petermann factor

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

Lee, Soo-Young

2009-10-15

We study the biorthogonality between decaying and growing eigenmodes in one-dimensional potential barrier problems. It is shown that Petermann factors K{sub n} of the eigenmodes, a measure of nonorthogonality, are involved in decaying mechanism of an initially confined particle. We also show that the decay tail of the growing modes at an exceptional point (EP), where K{sub n} become infinite, is not exponential, but {approx}t{sup 2}e{sup -{gamma}{sub EP}t}, {gamma}{sub EP} the decay rate of the decaying mode at EP. In addition, the geometrical phase near an EP is illustrated by the evolution of wave function.

The future of pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) infection.

PubMed

Özdener, Ayşe Elif; Park, Tae Eun; Kalabalik, Julie; Gupta, Rachna

2017-05-01

People at high risk for HIV acquisition should be offered pre-exposure prophylaxis (PrEP). Tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) is currently the only medication recommended for pre-exposure prophylaxis (PrEP) by the Centers for Disease Control and Prevention (CDC) in people at high risk for HIV acquisition. This article will review medications currently under investigation and the future landscape of PrEP therapy. Areas covered: This article will review clinical trials that have investigated nontraditional regimens of TDF/FTC, antiretroviral agents from different drug classes such as integrase strand transfer inhibitors (INSTI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) as potential PrEP therapies. Expert commentary: Currently, there are several investigational drugs in the pipeline for PrEP against HIV infection. Increased utilization of PrEP therapy depends on provider identification of people at high risk for HIV transmission. Advances in PrEP development will expand options and access for people and reduce the risk of HIV acquisition.

Mutation Breeding of Extracellular Polysaccharide-Producing Microalga Crypthecodinium cohnii by a Novel Mutagenesis with Atmospheric and Room Temperature Plasma

PubMed Central

Liu, Bin; Sun, Zheng; Ma, Xiaonian; Yang, Bo; Jiang, Yue; Wei, Dong; Chen, Feng

2015-01-01

Extracellular polysaccharides (EPS) produced by marine microalgae have the potential to be used as antioxidants, antiviral agents, immunomodulators, and anti-inflammatory agents. Although the marine microalga Crypthecodinium cohnii releases EPS during the process of docosahexaenoic acid (DHA) production, the yield of EPS remains relatively low. To improve the EPS production, a novel mutagenesis of C. cohnii was conducted by atmospheric and room temperature plasma (ARTP). Of the 12 mutants obtained, 10 mutants exhibited significantly enhanced EPS yield on biomass as compared with the wild type strain. Among them, mutant M7 was the best as it could produce an EPS volumetric yield of 1.02 g/L, EPS yield on biomass of 0.39 g/g and EPS yield on glucose of 94 mg/g, which were 33.85%, 85.35% and 57.17% higher than that of the wild type strain, respectively. Results of the present study indicated that mutagenesis of the marine microalga C. cohnii by ARTP was highly effective leading to the high-yield production of EPS. PMID:25872142

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices.

PubMed

Sevelius, Jae M; Deutsch, Madeline B; Grant, Robert

2016-01-01

Globally, transgender ("trans") women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population. Available information, including but not limited to existing scientific literature, about trans women and PrEP was reviewed and critiqued based on author expertise, including PrEP clinical trials and rollout. To date, PrEP demonstration projects and clinical trials have largely excluded trans women, or have not included them in a meaningful way. Data collection strategies that fail to identify trans women in clinical trials and research further limit the ability to draw conclusions about trans women's unique needs and devise strategies to meet them. Gender-affirming providers and clinic environments are essential components of any sexual health programme that aims to serve trans women, as they will largely avoid settings that may result in stigmatizing encounters and threats to their identities. While there is currently no evidence to suggest drug-drug interactions between PrEP and commonly used feminizing hormone regimens, community concerns about potential interactions may limit interest in and uptake of PrEP among trans women. In scaling up PrEP for trans women, it is essential to engage trans communities, utilize trans-inclusive research and marketing strategies and identify and/or train healthcare providers to provide gender-affirming healthcare to trans women, including transition-related care such as hormone provision. PrEP implementation guidelines must consider and address trans women's unique barriers and facilitators to uptake and adherence.

The future of PrEP among transgender women: the critical role of gender affirmation in research and clinical practices

PubMed Central

Sevelius, Jae M; Deutsch, Madeline B; Grant, Robert

2016-01-01

Introduction Globally, transgender (“trans”) women are one of the key populations most disproportionately impacted by HIV. Pre-exposure prophylaxis (PrEP) is the newest and most promising biomedical HIV prevention intervention to date. This paper reviews relevant literature to describe the current state of the science and describes the potential role of PrEP among trans women, including a discussion of unique considerations for maximizing the impact of PrEP for this vulnerable population. Methods Available information, including but not limited to existing scientific literature, about trans women and PrEP was reviewed and critiqued based on author expertise, including PrEP clinical trials and rollout. Results To date, PrEP demonstration projects and clinical trials have largely excluded trans women, or have not included them in a meaningful way. Data collection strategies that fail to identify trans women in clinical trials and research further limit the ability to draw conclusions about trans women's unique needs and devise strategies to meet them. Gender-affirming providers and clinic environments are essential components of any sexual health programme that aims to serve trans women, as they will largely avoid settings that may result in stigmatizing encounters and threats to their identities. While there is currently no evidence to suggest drug-drug interactions between PrEP and commonly used feminizing hormone regimens, community concerns about potential interactions may limit interest in and uptake of PrEP among trans women. Conclusions In scaling up PrEP for trans women, it is essential to engage trans communities, utilize trans-inclusive research and marketing strategies and identify and/or train healthcare providers to provide gender-affirming healthcare to trans women, including transition-related care such as hormone provision. PrEP implementation guidelines must consider and address trans women's unique barriers and facilitators to uptake and adherence. PMID:27760683

Plant growth promotion and root colonization by EPS producing Enterobacter sp. RZS5 under heavy metal contaminated soil.

PubMed

Sayyed, R Z; Patel, P R; Shaikh, S S

2015-02-01

The heavy metal resistant bacterium isolated from field soil and identified as Enterobacter sp. RZS5 tolerates a high concentration (100-2000 μM) of various heavy metal ions such as Mn2+, Ni2+, Zn2+, Cu2+, CO2+ and Fe2+ when grown in such environment and produces exopolysaccharides (EPS). Here, we have demonstrated EPS production by Enterobacter sp. RZS5 during 60 h of growth in yeast extract mannitol broth (YEMB). The yield increased by two fold after the addition of 60 μM of Ca2+; 50 μM of Fe2+ and 60 μM of Mg2+ ions in YEMB, and the optimization of physico-chemical parameters. EPS was extracted with 30% (v/v) of isopropanol as against the commonly used 50% (v/v) isopropanol method. EPS-rich broth promoted seed germination, shoot height, root length, number of leaves and chlorophyll content of wheat (Triticum aestivum) seed and peanut (Arachis hypogaea) seed. The higher colony-forming unit of Enterobacter sp. in soil inoculated with EPS rich broth of Enterobacter sp. indicated the root colonizing potential and rhizosphere competence of the isolate. The FTIR spectra of the EPS extract confirmed the presence of the functional group characteristics of EPS known to exhibit a high binding affinity towards certain metal ions. This overall growth and vigour in plants along with the effective root colonization, reflected the potential of the isolate as an efficient bio-inoculant in bioremediation.

Do evoked potentials contribute to the functional follow-up and clinical prognosis of multiple sclerosis?

PubMed

Giffroy, Xavier; Maes, Nathalie; Albert, Adelin; Maquet, Pierre; Crielaard, Jean-Michel; Dive, Dominique

2017-03-01

The clinical variability and complexity of multiple sclerosis (MS) challenges the individual clinical course prognostication. This study aimed to find out whether multimodal evoked potentials (EP) correlate with the motor components of multiple sclerosis functional composite (MSFCm) and predict clinically relevant motor functional deterioration. One hundred MS patients were assessed at baseline (T 0 ) and about 7.5 years later (T 1 ), with visual, somatosensory and motor EP and rated on the Expanded Disability Status Scale (EDSS) and the MSFCm, including the 9 Hole Peg Test and the Timed 25 Foot Walk (T25FW). The Spearman correlation coefficient (r S ) was used to evaluate the cross-sectional and longitudinal relationship between EP Z scores and clinical findings. The predictive value of baseline electrophysiological data for clinical worsening (EDSS, 9-HPT, T25FW, MSFCm) during follow-up was assessed by logistic regression analysis. Unlike longitudinal correlations, cross-sectional correlations between EP Z scores and clinical outcomes were all significant and ranged between 0.22 and 0.67 (p < 0.05). The global EP Z score was systematically predictive of EDSS and MSFCm worsening over time (all p < 0.05). EP latency was a better predictor than amplitude, although weaker than latency and amplitude aggregation in the global EP Z score. The study demonstrates that EP numerical scores can be used for motor function monitoring and outcome prediction in patients with MS.

Planning for pre-exposure prophylaxis to prevent HIV transmission: challenges and opportunities

PubMed Central

2010-01-01

There are currently several ongoing or planned trials evaluating the efficacy of pre-exposure prophylaxis (PrEP) as a preventative approach to reducing the transmission of HIV. PrEP may prove ineffective, demonstrate partial efficacy, or show high efficacy and have the potential to reduce HIV infection in a significant way. However, in addition to the trial results, it is important that issues related to delivery, implementation and further research are also discussed. As a part of the ongoing discussion, in June 2009, the Bill & Melinda Gates Foundation sponsored a Planning for PrEP conference with stakeholders to review expected trial results, outline responsible educational approaches, and develop potential delivery and implementation strategies. The conference reinforced the need for continued and sustained dialogue to identify where PrEP implementation may fit best within an integrated HIV prevention package. This paper identifies the key action points that emerged from the Planning for PrEP meeting. PMID:20624303

Ketamine-Based Anesthetic Protocols and Evoked Potential Monitoring: A Risk/Benefit Overview.

PubMed

Stoicea, Nicoleta; Versteeg, Gregory; Florescu, Diana; Joseph, Nicholas; Fiorda-Diaz, Juan; Navarrete, Víctor; Bergese, Sergio D

2016-01-01

Since its discovery, ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist related to phencyclidine, has been linked to multiple adverse reactions sometimes described as "out of body" and "near death experiences," including emergence phenomena, delusions, hallucinations, delirium, and confusion. Due to these effects, ketamine has been withdrawn from mainstream anesthetic use in adult patients. Evoked potentials (EPs) are utilized to monitor neural pathways during surgery, detect intraoperative stress or damage, detect and define the level of neural lesions, and define abnormalities. Unfortunately, many of the volatile anesthetics commonly used during spinal and neurologic procedures suppress EP amplitude and monitoring. Ketamine has been found in several preclinical and clinical studies to actually increase EP amplitude and thus has been used as an analgesic adjunct in procedures where EP monitoring is critical. Once the gap in our knowledge of ketamine's risks has been sufficiently addressed in animal models, informed clinical trials should be conducted in order to properly incorporate ketamine-based anesthetic regimens during EP-monitored neurosurgeries.

A Novel Workflow to Enrich and Isolate Patient-Matched EpCAMhigh and EpCAMlow/negative CTCs Enables the Comparative Characterization of the PIK3CA Status in Metastatic Breast Cancer

PubMed Central

Lampignano, Rita; Yang, Liwen; Neumann, Martin H. D.; Franken, André; Fehm, Tanja; Niederacher, Dieter; Neubauer, Hans

2017-01-01

Circulating tumor cells (CTCs), potential precursors of most epithelial solid tumors, are mainly enriched by epithelial cell adhesion molecule (EpCAM)-dependent technologies. Hence, these approaches may overlook mesenchymal CTCs, considered highly malignant. Our aim was to establish a workflow to enrich and isolate patient-matched EpCAMhigh and EpCAMlow/negative CTCs within the same blood samples, and to investigate the phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) mutational status within single CTCs. We sequentially processed metastatic breast cancer (MBC) blood samples via CellSearch® (EpCAM-based) and via Parsortix™ (size-based) systems. After enrichment, cells captured in Parsortix™ cassettes were stained in situ for nuclei, cytokeratins, EpCAM and CD45. Afterwards, sorted cells were isolated via CellCelector™ micromanipulator and their genomes were amplified. Lastly, PIK3CA mutational status was analyzed by combining an amplicon-based approach with Sanger sequencing. In 54% of patients′ blood samples both EpCAMhigh and EpCAMlow/negative cells were identified and successfully isolated. High genomic integrity was observed in 8% of amplified genomes of EpCAMlow/negative cells vs. 28% of EpCAMhigh cells suggesting an increased apoptosis in the first CTC-subpopulation. Furthermore, PIK3CA hotspot mutations were detected in both EpCAMhigh and EpCAMlow/negative CTCs. Our workflow is suitable for single CTC analysis, permitting—for the first time—assessment of the heterogeneity of PIK3CA mutational status within patient-matched EpCAMhigh and EpCAMlow/negative CTCs. PMID:28858218

Exopolymer alteration of physical properties of sea ice and implications for ice habitability and biogeochemistry in a warmer Arctic

PubMed Central

Krembs, Christopher; Eicken, Hajo; Deming, Jody W.

2011-01-01

The physical properties of Arctic sea ice determine its habitability. Whether ice-dwelling organisms can change those properties has rarely been addressed. Following discovery that sea ice contains an abundance of gelatinous extracellular polymeric substances (EPS), we examined the effects of algal EPS on the microstructure and salt retention of ice grown from saline solutions containing EPS from a culture of the sea-ice diatom, Melosira arctica. We also experimented with xanthan gum and with EPS from a culture of the cold-adapted bacterium Colwellia psychrerythraea strain 34H. Quantitative microscopic analyses of the artificial ice containing Melosira EPS revealed convoluted ice-pore morphologies of high fractal dimension, mimicking features found in EPS-rich coastal sea ice, whereas EPS-free (control) ice featured much simpler pore geometries. A heat-sensitive glycoprotein fraction of Melosira EPS accounted for complex pore morphologies. Although all tested forms of EPS increased bulk ice salinity (by 11–59%) above the controls, ice containing native Melosira EPS retained the most salt. EPS effects on ice and pore microstructure improve sea ice habitability, survivability, and potential for increased primary productivity, even as they may alter the persistence and biogeochemical imprint of sea ice on the surface ocean in a warming climate. PMID:21368216

Exopolymer alteration of physical properties of sea ice and implications for ice habitability and biogeochemistry in a warmer Arctic.

PubMed

Krembs, Christopher; Eicken, Hajo; Deming, Jody W

2011-03-01

The physical properties of Arctic sea ice determine its habitability. Whether ice-dwelling organisms can change those properties has rarely been addressed. Following discovery that sea ice contains an abundance of gelatinous extracellular polymeric substances (EPS), we examined the effects of algal EPS on the microstructure and salt retention of ice grown from saline solutions containing EPS from a culture of the sea-ice diatom, Melosira arctica. We also experimented with xanthan gum and with EPS from a culture of the cold-adapted bacterium Colwellia psychrerythraea strain 34H. Quantitative microscopic analyses of the artificial ice containing Melosira EPS revealed convoluted ice-pore morphologies of high fractal dimension, mimicking features found in EPS-rich coastal sea ice, whereas EPS-free (control) ice featured much simpler pore geometries. A heat-sensitive glycoprotein fraction of Melosira EPS accounted for complex pore morphologies. Although all tested forms of EPS increased bulk ice salinity (by 11-59%) above the controls, ice containing native Melosira EPS retained the most salt. EPS effects on ice and pore microstructure improve sea ice habitability, survivability, and potential for increased primary productivity, even as they may alter the persistence and biogeochemical imprint of sea ice on the surface ocean in a warming climate.

Value of Laryngeal Electromyography in Spasmodic Dysphonia Diagnosis and Therapy.

PubMed

Yang, Qingwen; Xu, Wen; Li, Yun; Cheng, Liyu

2015-07-01

To investigate the role of laryngeal electromyography (LEMG) in the diagnosis and treatment of spasmodic dysphonia (SD). The clinical manifestations, characteristics of motor unit potentials (MUPs), recruitment potentials, and laryngeal nerve evoked potentials (EPs) in LEMG, as well as the changes after botulinum toxin (BTX) treatment, were analyzed in 39 patients with adductor SD. The main clinical manifestations were a strained voice and phonation interruptions; in addition, the patients displayed hyper-adducted vocal folds during phonation. LEMG revealed significantly increased amplitudes of the thyroarytenoid muscle MUPs. The recruitment potentials were in a dense bunch, discharging full interference patterns with significantly increased amplitudes; the mean and maximum amplitude of recruitment potentials were 3090 μV and 5000 μV, respectively. The amplitude of EPs of thyroarytenoid muscle increased significantly; the mean and maximum amplitudes were 10.3 mV and 26.3 mV, respectively. After BTX was injected, the LEMG revealed denervation changes, and the EPs weakened or disappeared in the injected muscle. SD could be diagnosed, and the therapeutic efficacy of SD treatments could be evaluated based on clinical characteristics combined with LEMG characteristics. The increased amplitudes of the recruitment potentials and EPs of the thyroarytenoid muscle were the characteristic indexes. After BTX was injected, denervated potential characteristics appeared in the muscles. © The Author(s) 2015.

"Why should I take drugs for your infection?": outcomes of formative research on the use of HIV pre-exposure prophylaxis in Nigeria.

PubMed

Idoko, John; Folayan, Morenike Oluwatoyin; Dadem, Nancin Yusufu; Kolawole, Grace Oluwatosin; Anenih, James; Alhassan, Emmanuel

2015-04-10

Nigeria has the second highest number of new HIV infections annually. Therefore, it is important to explore new strategies for preventing new infections. The introduction of pre-exposure prophylaxis (PrEP) for use by persons at high risk of HIV infection has new potential in preventing new HIV infections. The aim of this study is to explore the public opinion, community interest, and perceptions about the use and access to PrEP in Nigeria. This formative study used a mixed method approach to collect data on public opinions and perceptions on appropriate target groups for PrEP access, community interest, perceptions about the use of PrEP as an HIV-prevention tool, how best to communicate with participants about PrEP, concerns about PrEP use by serodiscordant couples, and suggestions for the design and implementation of a PrEP demonstration project. Telephone and in-depth interviews were conducted, and focus group discussions and consultative meetings were held with critical stakeholders engaged in HIV-prevention, treatment, care, and support programmes in Nigeria. An online survey was also conducted. HIV serodiscordant couples were identified as the appropriate target group for PrEP use. Most respondents felt that PrEP use by key affected populations would help reduce the HIV incidence. Stigma was identified as a major concern and a potential barrier for the acceptance and use of PrEP by HIV serodiscordant couples. Electronic and print media were identified as important means for massive public education to prevent stigma and create awareness about PrEP. In a male dominated society such as Nigeria, HIV-negative male partners in serodiscordant relationships may resist enrolment in PrEP programmes. This may be complicated by the fact that the identified index partner in most serodiscordant relationships in Nigeria is an HIV-positive woman, who is often diagnosed during pregnancy. PrEP uptake and use by HIV serodiscordant couples in Nigeria may face notable but surmountable challenges. Much depends on the appropriateness of actions taken by multiple players. Motivation of HIV-negative male partners to use PrEP and establishment of effective public education programmes in addressing stigma are essential.

Effect of pretreatment with epoxy compounds on the mechanical properties of bovine pericardial bioprosthetic materials.

PubMed

Xi, T; Liu, F; Xi, B

1992-07-01

Early failures of bovine pericardial heart valves are due to leaflet perforation, tearing and calcification. Since glutaraldehyde fixation has been shown to produce marked changes in leaflet mechanics and has been linked to development of calcification, bovine pericardium fixed with the four hydrophilic epoxy formulations and their mechanical properties are studied in this paper. We measured the thicknesses, shrinkage temperatures, stress relaxations and stress-strain curves of bovine pericardiums after different treatments with (1) non-treatment (fresh), (2) glutaraldehyde (GA), (3) epoxy compounds followed by the posttreatment with GA (EP 1#, EP 2#), and (4) epoxy compounds (EP 3# and EP 4#). Results of this study showed that the hydrophilic epoxy compounds are good crosslinking agents. There are no significant differences of shrinkage temperature and ultimate tensile stress among all tissue samples pretreated with GA, EP 1# and EP 2#. However, the stress relaxations of tissue-samples pretreated with epoxy compounds followed by the posttreatment with GA (EP 1# and EP 2#) are significantly slower than that pretreated with GA, and the strains at fracture of EP 1# and EP 2# are also significantly larger than that of GA or epoxy compounds. These facts show that the bovine pericardium pretreated with the epoxy compound followed by the posttreatment with GA (EP 1# and EP 2#) possesses greater tenacity and potential durability in dynamic stress.

Using Educational Prescriptions to Teach Medical Students Evidence-based Medicine

PubMed Central

Umscheid, Craig A.; Maenner, Matthew J.; Mull, Nikhil; Veesenmeyer, Angela F.; Farrar, John T.; Goldfarb, Stanley; Morrison, Gail; Albanese, Mark A.; Frohna, John G.; Feldstein, David A.

2018-01-01

Purpose To evaluate feasibility and impact of evidence-based medicine (EBM) educational prescriptions (EPs) in medical student clerkships. Methods Students answered clinical questions during clerkships using EPs, which guide learners through the “four As” of EBM. Epidemiology fellows graded EPs using a rubric. Feasibility was assessed using descriptive statistics and student and fellow end-of-study questionnaires, which also measured impact. In addition, for each EP, students reported patient impact. Impact on EBM skills was assessed by change in EP scores over time and scores on an EBM objective structured clinical exam (OSCE) that were compared to controls from the prior year. Results 117 students completed 402 EPs evaluated by 24 fellows. Average score was 7.34/9.00 (SD 1.58). 69 students (59%) and 21 fellows (88%) completed questionnaires. Most students thought EPs improved “Acquiring” and “Appraising.” Almost half thought EPs improved “Asking” and “Applying.” Fellows did not value grading EPs. For 18%of EPs, students reported a “change” or “potential change” in treatment. 56% “confirmed” treatment. EP scores increased by 1.27 (95% CI: 0.81–1.72). There were no differences in OSCE scores between cohorts. Conclusions Integrating EPs into clerkships is feasible and has impact, yet OSCEs were unchanged, and research fellows had limitations as evaluators. PMID:27075864

Preparing for pre-exposure prophylaxis: perceptions and readiness of Canadian pharmacists for the implementation of HIV pre-exposure prophylaxis.

PubMed

Yoong, Deborah; Naccarato, Mark; Sharma, Malika; Wilton, James; Senn, Heather; Tan, Darrell Hs

2016-07-01

Pre-exposure prophylaxis (PrEP) has been shown to reduce the risk of HIV transmission but has the potential to cause harm if not used properly. Pharmacists are well-positioned to foster PrEP's efficacy but little is known whether they would endorse it as an HIV prevention tool. The objective of the study was to determine Canadian HIV pharmacists' support for PrEP and to identify current barriers to promoting PrEP. Canadian pharmacists with experience in HIV care were invited to complete an online survey about their experiences, opinions, and learning needs regarding PrEP from December 2012 to January 2013. Among the 59 surveys received, 48 met criteria for final analysis. Overall, 33 (69%) respondents would provide education positively supporting the use of PrEP and 26 (54%) believed Health Canada should approve PrEP for use in Canada. Familiarity with the concept of PrEP and practice characteristics examined did not appear to be significantly associated with support for PrEP in univariable analyses. The principal barriers to promoting PrEP included inadequate drug coverage and insufficient knowledge to educate others. Many Canadian HIV pharmacists would endorse PrEP for high-risk patients; however, wider dissemination of information and lower drug costs may be needed to make PrEP more widely promoted. © The Author(s) 2015.

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

PubMed

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Pre-Exposure Prophylaxis: A Narrative Review of Provider Behavior and Interventions to Increase PrEP Implementation in Primary Care.

PubMed

Silapaswan, Andrew; Krakower, Douglas; Mayer, Kenneth H

2017-02-01

Since FDA approval of HIV pre-exposure prophylaxis (PrEP) for HIV prevention, attention has been focused on PrEP implementation. The CDC estimates that 1.2 million U.S. adults might benefit from PrEP, but only a minority are using PrEP, so there is a significant unmet need to increase access for those at risk for HIV. Given the large numbers of individuals who have indications for PrEP, there are not enough practicing specialists to meet the growing need for providers trained in providing PrEP. Moreover, since PrEP is a preventive intervention for otherwise healthy individuals, primary care providers (PCPs) should be primary prescribers of PrEP. There are important clinical considerations that providers should take into account when planning to prescribe PrEP, which are highlighted in the clinical case discussed. A growing body of research also suggests that some providers may be cautious about prescribing PrEP because of concerns regarding its "real-world" effectiveness, anticipated unintended consequences associated with its use, and ambiguity as to who should prescribe it. This review summarizes findings from studies that have assessed prescriber behavior regarding provision of PrEP, and offers recommendations on how to optimize PrEP implementation in primary care settings. Development and dissemination of educational interventions for PCPs and potential PrEP users are needed, including improved methods to assist clinicians in identifying appropriate PrEP candidates, and programs to promote medication adherence and access to social and behavioral health services. PCPs are well-positioned to prescribe PrEP and coordinate health-related services to improve the sexual health of their patients, but tailored educational programs are needed.

Thermal and rheological properties of a family of botryosphaerans produced by Botryosphaeria rhodina MAMB-05.

PubMed

Fonseca, Paulo R M S; Dekker, Robert F H; Barbosa, Aneli M; Silveira, Joana L M; Vasconcelos, Ana F D; Monteiro, Nilson K; Aranda-Selverio, Gabriel; da Silva, Maria de Lourdes Corradi

2011-09-02

Differential scanning calorimetry (DSC), thermogravimetry (TG) and Fourier-transform infra-red spectroscopy (FT-IR) analyses were performed to investigate changes in the physico-chemical properties of botryosphaerans, a family of exopolysaccharides (EPS) produced by the fungus Botryosphaeria rhodina MAMB-05 grown on glucose (EPS(GLC)), sucrose (EPS(SUC)) and fructose (EPS(FRU)). A slight endothermic transition and small mass loss attributable to the removal of water of hydration were observed in the DSC and TG analyses, respectively, for the three EPS samples. The FT-IR spectra confirmed no structural changes occurred during thermal treatment. Viscometry was utilized to obtain information on the rheological behaviour of the EPS in aqueous solutions. The Power Law and Cross Equations determined the natural pseudoplastic characteristics of the EPS. Comparatively, results obtained for EPS produced when B. rhodina MAMB-05 was grown on each of the three carbohydrate sources demonstrated similar apparent viscosity values for EPS(GLC) and EPS(SUC), while EPS(FRU) displayed the lowest apparent viscosity of the three botryosphaerans, suggesting a higher degree of ramification and lower Mw. EPS(GLC) and EPS(SUC) possessed similar degrees of ramification. The slight differences found in their viscosities can be explained by the differences in the type of branching among the three botryosphaerans, thus varying the strength of intermolecular interactions and consequently, consistency and viscosity. The physico-chemical studies of botryosphaerans represent the originality of this work, and the knowledge of these properties is an important criterion for potential applications.

Epicardial potentials computed from the body surface potential map using inverse electrocardiography and an individualised torso model improve sensitivity for acute myocardial infarction diagnosis.

PubMed

Daly, Michael J; Finlay, Dewar D; Guldenring, Daniel; Bond, Raymond R; McCann, Aaron J; Scott, Peter J; Adgey, Jennifer A; Harbinson, Mark T

2017-12-01

Epicardial potentials (EPs) derived from the body surface potential map (BSPM) improve acute myocardial infarction (AMI) diagnosis. In this study, we compared EPs derived from the 80-lead BSPM using a standard thoracic volume conductor model (TVCM) with those derived using a patient-specific torso model (PSTM) based on body mass index (BMI). Consecutive patients presenting to both the emergency department and pre-hospital coronary care unit between August 2009 and August 2011 with acute ischaemic-type chest pain at rest were enrolled. At first medical contact, 12-lead electrocardiograms and BSPMs were recorded. The BMI for each patient was calculated. Cardiac troponin T (cTnT) was sampled 12 hours after symptom onset. Patients were excluded from analysis if they had any ECG confounders to interpretation of the ST-segment. A cardiologist assessed the 12-lead ECG for ST-segment elevation myocardial infarction by Minnesota criteria and the BSPM. BSPM ST-elevation (STE) was ⩾0.2 mV in anterior, ⩾0.1 mV in lateral, inferior, right ventricular or high right anterior and ⩾0.05 mV in posterior territories. To derive EPs, the BSPM data were interpolated to yield values at 352 nodes of a Dalhousie torso. Using an inverse solution based on the boundary element method, EPs at 98 cardiac nodes positioned within a standard TVCM were derived. The TVCM was then scaled to produce a PSTM using a model developed from computed tomography in 48 patients of varying BMIs, and EPs were recalculated. EPs >0.3 mV defined STE. A cardiologist blinded to both the 12-lead ECG and BSPM interpreted the EP map. AMI was defined as cTnT ⩾0.1 µg/L. Enrolled were 400 patients (age 62 ± 13 years; 57% male); 80 patients had exclusion criteria. Of the remaining 320 patients, the BMI was an average of 27.8 ± 5.6 kg/m 2 . Of these, 180 (56%) had AMI. Overall, 132 had Minnesota STE on ECG (sensitivity 65%, specificity 89%) and 160 had BSPM STE (sensitivity 81%, specificity 90%). EP STE occurred in 165 patients using TVCM (sensitivity 88%, specificity 95%; p < 0.001) and in 206 patients using PSTM (sensitivity 98%, specificity 79%; p < 0.001). Of those with AMI by cTnT and EPs ⩽0.3 mV using TVCM ( n = 22), 18 (82%) patients had EPs >0.3 mV when an individualised PSTM was used. Among patients presenting with ischaemic-type chest pain at rest, EPs derived from BSPM using a novel PSTM significantly improve sensitivity for AMI diagnosis.

Seasonal PrEP for partners of migrant miners in southern Mozambique: a highly focused PrEP intervention

PubMed Central

Cremin, Ide; Morales, Fernando; Jewell, Britta L; O'Reilly, Kevin R; Hallett, Timothy B

2015-01-01

Introduction To be used most effectively, pre-exposure prophylaxis (PrEP) should be prioritized to those at high risk of acquisition and would ideally be aligned with time periods of increased exposure. Identifying such time periods is not always straightforward, however. Gaza Province in southern Mozambique is characterized by high levels of HIV transmission and circular labour migration to mines in South Africa. A strong seasonal pattern in births is observable, reflecting an increase in conception in December. Given the potential for increased HIV transmission between miners returning in December and their partners in Gaza Province, PrEP use by the latter would be a useful means of HIV prevention, especially for couples who wish to conceive. Methods A mathematical model was used to represent population-level adult heterosexual HIV transmission in Gaza Province. Increased HIV acquisition among partners of miners in December, coinciding with the miners’ return from South Africa, is represented. In addition to a PrEP intervention, the scale-up of treatment and recent scale-up of male circumcision that have occurred in Gaza are represented. Results Providing time-limited PrEP to the partners of migrant miners, as opposed to providing PrEP all year, would improve the cost per infection averted by 7.5-fold. For the cost per infection averted to be below US$3000, at least 85% of PrEP users would need to be good adherers and PrEP would need to be cheaper than US$115 per person per year. Uncertainty regarding incidence of HIV transmission among partners of miners each year in December has a strong influence on estimates of cost per infection averted. Conclusions Providing time-limited PrEP to partners of migrant miners in Gaza Province during periods of increased exposure would be a novel strategy for providing PrEP. This strategy would allow for a better prioritized intervention, with the potential to improve the efficiency of a PrEP intervention considerably, as well as providing important reproductive health benefits. PMID:26198340

Influence of in-situ synthesized exopolysaccharides on the quality of gluten-free sorghum sourdough bread.

PubMed

Galle, Sandra; Schwab, Clarissa; Dal Bello, Fabio; Coffey, Aidan; Gänzle, Michael G; Arendt, Elke K

2012-04-16

The majority of gluten-free breads on the market are of poor sensory and textural quality. Exopolysaccharides (EPS) formed from sucrose during sourdough fermentation can improve the technological properties of gluten-free breads and potentially replace hydrocolloids. In this study, the influence of in situ formed EPS on dough rheology and quality of gluten-free sorghum bread was investigated. Dextran forming Weissella cibaria MG1 was compared to reuteran producing Lactobacillus reuteri VIP and fructan forming L. reuteri Y2. EPS containing bread batters were prepared by adding 10% and 20% of sourdough. As control served batters and bread containing sourdoughs fermented without sucrose and batters and bread without sourdough addition. The amount of EPS formed in situ ranged from 0.6 to 8.0 g/kg sourdough. EPS formed during sourdough fermentation were responsible for the significant decrease in dough strength and elasticity, with in situ formed dextran exhibiting the strongest impact. Increased release of glucose and fructose from sucrose during fermentation enhanced CO₂ production of yeast. Organic acids in control sourdough breads induced hardening of the bread crumb. EPS formed during sourdough fermentation masked the effect of the organic acids and led to a softer crumb in the fresh and stored sorghum bread. Among EPS, dextran showed the best shelf life improvements. In addition to EPS, all three strains produced oligosaccharides during sorghum sourdough fermentation contributing to the nutritional benefits of gluten-free sorghum bread. Results of this study demonstrated that EPS formed during sourdough fermentation can be successfully applied in gluten-free sorghum flours to improve their bread-making potentials. Copyright © 2012 Elsevier B.V. All rights reserved.

From modeling to morals: imagining the future of HIV PREP in Lesotho.

PubMed

Kenworthy, Nora J; Bulled, Nicola

2013-08-01

Amidst growing global endorsements of new biomedical HIV prevention strategies, ARV-based pre-exposure prophylaxis (ARV PrEP) has garnered considerable attention as a potentially promising prevention strategy. Though it may offer more effective protection for certain at-risk groups than conventional prevention strategies (such as sexual partner reduction, condom use, and prevention of mother-to-child transmission), PrEP is more costly. PrEP requires more ongoing contact between individuals and providers, and a level of surveillance from the health system that is not necessary with other preventive measures. In this sense, it represents a new bio-technology for HIV prevention that poses particular challenges for worldwide implementation, given developing countries' struggling health systems and incomplete HIV treatment programs. Since the emergence of PrEP has stimulated ethical discussions premised on incomplete knowledge of efficacy and implementation, this paper explores the ethical parameters of a likely scenario for PrEP usage in a single, resource-poor country. We first develop a plausible model for PrEP deployment and utilization based on current PrEP research, while carefully considering the reigning institutional values of feasibility and effectiveness in global health approaches. Drawing on ethnographic research of HIV treatment and prevention approaches in Lesotho, we address ethical questions arising from this scenario of PrEP delivery. Lesotho presents a compelling and emblematic case study of PrEP's potential successes and pitfalls in a developing country, given the country's high HIV prevalence, struggles to achieve universal access to HIV treatment regimes, continued existence of stigma around the epidemic, and difficulties in addressing persistent social inequalities that fuel infections. © 2013 John Wiley & Sons Ltd.

Optimization of exopolysaccharide production from Pseudomonas stutzeri AS22 and examination of its metal-binding abilities.

PubMed

Maalej, H; Hmidet, N; Boisset, C; Buon, L; Heyraud, A; Nasri, M

2015-02-01

To investigate the effect of culture conditions and medium components on exopolysaccharide (EPS) production by Pseudomonas stutzeri AS22 and to access the EPS performance as a metal-binding exopolysaccharide. The EPS production conditions of Ps. stutzeri AS22 in submerged culture were optimized using two approaches for EPS quantification, and its metal-binding capacity was evaluated using both single and mixed metal ions systems. Maximum EPS level was achieved after 24 h of incubation at 30°C with an initial pH of 8.0, 250 rev min(-1) stirring level and 10% inoculum size. 50 g l(-1) starch, 5 g l(-1) yeast extract, 0.5 g l(-1) NaCl, 1.4 g l(-1) K2 HPO4, 0.4 g l(-1) MgSO4, 0.4 g l(-1) CaCl2 and 1 g l(-1) mannose were found to be the most suitable carbon, nitrogen, mineral and additional carbohydrate sources, respectively. From metal-binding experiments, the crude EPS showed interesting metal adsorption capacity adopting the order Pb > Co > Fe > Cu > Cd. Lead was preferentially biosorbed with a maximal uptake of 460 mg g(-1) crude EPS. Under the optimal culture requirements, EPS level reached 10.2 g l(-1) after 24 h of fermentation, seven times more than the production under initial conditions. According to the metal-binding assay, the crude EPS has potential to be used as a novel biosorbent in the treatment of heavy metals-contaminated water. Our results are interesting in terms of yield as well as efficiency for the potential use of the Ps. stutzeri exopolysaccharide as a metal-absorbent polymer in the bioremediation field. © 2014 The Society for Applied Microbiology.

Epithelial plasticity in prostate cancer: principles and clinical perspectives.

PubMed

Das, Rajdeep; Gregory, Philip A; Hollier, Brett G; Tilley, Wayne D; Selth, Luke A

2014-11-01

Over the past decade, the capacity of cancer cells to oscillate between epithelial and mesenchymal phenotypes, termed epithelial plasticity (EP), has been demonstrated to play a critical role in metastasis. This phenomenon may be particularly important for prostate cancer (PC) progression, since recent studies have revealed interplay between EP and signaling by the androgen receptor (AR) oncoprotein. Moreover, EP appears to play a role in dictating the response to therapies for metastatic PC. This review will evaluate preclinical and clinical evidence for the relevance of EP in PC progression and consider the potential of targeting and measuring EP as a means to treat and manage lethal forms of the disease. Copyright © 2014 Elsevier Ltd. All rights reserved.

Extracellular Polymeric Substances from Shewanella sp. HRCR-1 Biofilms: Characterization by Infrared Spectroscopy and Proteomics

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

Cao, Bin; Shi, Liang; Brown, Roslyn N.

This study characterizes the composition of extracellular polymeric substances (EPS) from Shewanella sp. HRCR-1 biofilms to provide insight into potential interactions of EPS with redox-active metals and radionuclides. Both bound and loosely associated EPS were extracted from Shewanella sp. HRCR-1 biofilms prepared using a hollow-fiber membrane biofilm reactor (HfMBR). FTIR spectra revealed the presence of proteins, polysaccharides, nucleic acids, membrane lipids, and fatty acids in both bound and loosely associated EPS. Using a global proteomic approach, a total of 58 extracellular and outer membrane proteins were identified in the EPS. These included homologues of multiple S. oneidensis MR-1 proteins thatmore » potentially contribute to key physiological biofilm processes, such as biofilm-promoting protein BpfA, surface-associated serine protease, nucleotidases (CpdB and UshA), an extracellular lipase, and oligopeptidases (PtrB and a M13 family oligopeptidase lipoprotein). In addition, 20 redox proteins were found in extracted EPS. Among the detected redox proteins were the homologues of two S. oneidensis MR-1 c-type cytochromes, MtrC and OmcA, which have been implicated in extracellular electron transfer. Given their detection in the EPS of Shewanella sp. HRCR 1 biofilms, c-type cytochromes may contribute to the possible redox activity of the biofilm matrix and play important roles in extracellular electron transfer reactions.« less

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers

PubMed Central

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

Introduction HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Discussion Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Conclusions Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes. PMID:27760688

Enhancing HIV Pre-exposure, Prophylaxis Practices via an Educational Intervention.

PubMed

Newman, Rebecca; Katchi, Tasleem; Karass, Michael; Gennarelli, Melissa; Goutis, Jason; Kifayat, Alina; Solanki, Shantanu; Yandrapalli, Srikanth; Forman, Leanne; Nabors, Christopher

2018-04-20

Pre-exposure prophylaxis (PrEP) for HIV involves using antiretroviral drugs to prevent individuals at high risk from acquiring HIV infection. Most practicing primary care providers believe PrEP to be safe and effective, but less than half have prescribed or referred for PrEP. Attitudes and prescribing patterns among house officers have not been well described previously. Can an educational intervention enhance HIV PrEP practices among internal medicine house officers? This study relied on a pretest/posttest design. All categorical trainees at a medium-sized internal medicine program were offered a baseline survey to assess their knowledge on PrEP. This was followed by a PrEP-focused educational intervention and a postintervention survey. Likert scales captured perceptions regarding safety, effectiveness, barriers, factors that would promote PrEP use, potential side effects, impact on risk-taking behavior, and provider comfort level in assessing behavioral risks and in PrEP prescribing. Data were analyzed using descriptive statistics, Wilcoxon signed rank test, and the Kruskal-Wallis test. Significance was accepted for P < 0.05. Forty-eight (100%) trainees participated in the educational session, 45 (94%) in a preintervention survey, and 36 (75%) in a postintervention survey. Before PrEP training, 22% of respondents were unaware of PrEP, 78% believed PrEP was effective, 66% believed PrEP was safe, 62% had fair or poor awareness of side effects; 18% of residents had referred for or prescribed PrEP, and 31% believed they were likely to prescribe PrEP in the next 6 months. After the intervention, 94% of trainees believed PrEP was effective (P < 0.001), 92% believed PrEP was safe (P < 0.001), and two-thirds believed they were likely to prescribe PrEP in the next 6 months. Brief, focused training on HIV prevention promotes awareness, acceptance, and likelihood of prescribing PrEP by internal medicine trainees.

PrEP implementation in the Asia-Pacific region: opportunities, implementation and barriers.

PubMed

Zablotska, Iryna; Grulich, Andrew E; Phanuphak, Nittaya; Anand, Tarandeep; Janyam, Surang; Poonkasetwattana, Midnight; Baggaley, Rachel; van Griensven, Frits; Lo, Ying-Ru

2016-01-01

HIV epidemics in the Asia-Pacific region are concentrated among men who have sex with men (MSM) and other key populations. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention intervention and could be a potential game changer in the region. We discuss the progress towards PrEP implementation in the Asia-Pacific region, including opportunities and barriers. Awareness about PrEP in the Asia-Pacific is still low and so are its levels of use. A high proportion of MSM who are aware of PrEP are willing to use it. Key PrEP implementation barriers include poor knowledge about PrEP, limited access to PrEP, weak or non-existent HIV prevention programmes for MSM and other key populations, high cost of PrEP, stigma and discrimination against key populations and restrictive laws in some countries. Only several clinical trials, demonstration projects and a few larger-scale implementation studies have been implemented so far in Thailand and Australia. However, novel approaches to PrEP implementation have emerged: researcher-, facility- and community-led models of care, with PrEP services for fee and for free. The WHO consolidated guidelines on HIV testing, treatment and prevention call for an expanded access to PrEP worldwide and have provided guidance on PrEP implementation in the region. Some countries like Australia have released national PrEP guidelines. There are growing community leadership and consultation processes to initiate PrEP implementation in Asia and the Pacific. Countries of the Asia-Pacific region will benefit from adding PrEP to their HIV prevention packages, but for many this is a critical step that requires resourcing. Having an impact on the HIV epidemic requires investment. The next years should see the region transitioning from limited PrEP implementation projects to growing access to PrEP and expansion of HIV prevention programmes.

Plant host and sugar alcohol induced exopolysaccharide biosynthesis in the Burkholderia cepacia complex.

PubMed

Bartholdson, S Josefin; Brown, Alan R; Mewburn, Ben R; Clarke, David J; Fry, Stephen C; Campopiano, Dominic J; Govan, John R W

2008-08-01

The species that presently constitute the Burkholderia cepacia complex (Bcc) have multiple roles; they include soil and water saprophytes, bioremediators, and plant, animal and human pathogens. Since the first description of pathogenicity in the Bcc was based on sour skin rot of onion bulbs, this study returned to this plant host to investigate the onion-associated phenotype of the Bcc. Many Bcc isolates, which were previously considered to be non-mucoid, produced copious amounts of exopolysaccharide (EPS) when onion tissue was provided as the sole nutrient. EPS production was not species-specific, was observed in isolates from both clinical and environmental sources, and did not correlate with the ability to cause maceration of onion tissue. Chemical analysis suggested that the onion components responsible for EPS induction were primarily the carbohydrates sucrose, fructose and fructans. Additional sugars were investigated, and all alcohol sugars tested were able to induce EPS production, in particular mannitol and glucitol. To investigate the molecular basis for EPS biosynthesis, we focused on the highly conserved bce gene cluster thought to be involved in cepacian biosynthesis. We demonstrated induction of the bce gene cluster by mannitol, and found a clear correlation between the inability of representatives of the Burkholderia cenocepacia ET12 lineage to produce EPS and the presence of an 11 bp deletion within the bceB gene, which encodes a glycosyltransferase. Insertional inactivation of bceB in Burkholderia ambifaria AMMD results in loss of EPS production on sugar alcohol media. These novel and surprising insights into EPS biosynthesis highlight the metabolic potential of the Bcc and show that a potential virulence factor may not be detected by routine laboratory culture. Our results also highlight a potential hazard in the use of inhaled mannitol as an osmolyte to improve mucociliary clearance in individuals with cystic fibrosis.

Widespread detection of a brominated flame retardant, hexabromocyclododecane, in expanded polystyrene marine debris and microplastics from South Korea and the Asia-Pacific coastal region.

PubMed

Jang, Mi; Shim, Won Joon; Han, Gi Myung; Rani, Manviri; Song, Young Kyoung; Hong, Sang Hee

2017-12-01

The role of marine plastic debris and microplastics as a carrier of hazardous chemicals in the marine environment is an emerging issue. This study investigated expanded polystyrene (EPS, commonly known as styrofoam) debris, which is a common marine debris item worldwide, and its additive chemical, hexabromocyclododecane (HBCD). To obtain a better understanding of chemical dispersion via EPS pollution in the marine environment, intensive monitoring of HBCD levels in EPS debris and microplastics was conducted in South Korea, where EPS is the predominant marine debris originate mainly from fishing and aquaculture buoys. At the same time, EPS debris were collected from 12 other countries in the Asia-Pacific region, and HBCD concentrations were measured. HBCD was detected extensively in EPS buoy debris and EPS microplastics stranded along the Korean coasts, which might be related to the detection of a quantity of HBCD in non-flame-retardant EPS bead (raw material). The wide detection of the flame retardant in sea-floating buoys, and the recycling of high-HBCD-containing EPS waste inside large buoys highlight the need for proper guidelines for the production and use of EPS raw materials, and the recycling of EPS waste. HBCD was also abundantly detected in EPS debris collected from the Asia-Pacific coastal region, indicating that HBCD contamination via EPS debris is a common environmental issue worldwide. Suspected tsunami debris from Alaskan beaches indicated that EPS debris has the potential for long-range transport in the ocean, accompanying the movement of hazardous chemicals. The results of this study indicate that EPS debris can be a source of HBCD in marine environments and marine food web. Copyright © 2017 Elsevier Ltd. All rights reserved.

Where to deploy pre-exposure prophylaxis (PrEP) in sub-Saharan Africa?

PubMed

Verguet, Stéphane; Stalcup, Meg; Walsh, Julia A

2013-12-01

Two randomised controlled trials showed that pre-exposure prophylaxis (PrEP) reduces HIV transmission between heterosexual men and women. We model the potential impact on transmission and cost-effectiveness of providing PrEP in sub-Saharan Africa. We use a deterministic, compartmental model of HIV transmission to evaluate the potential of a 5-year PrEP intervention targeting the adult population of 42 sub-Saharan African countries. We examine the incremental impact of adding PrEP at pre-existing levels of male circumcision and antiretroviral therapy (ART). The base case assumes efficacy of 68%; adherence at 80%; country coverage at 10% of the HIV-uninfected adult population; and annual costs of PrEP and ART at US$200 and US$880 per person, respectively. After 5 years, 390,000 HIV infections (95% UR 190,000 to 630,000) would be prevented, 24% of these in South Africa. HIV infections averted per 100 000 people (adult) would range from 500 in Lesotho to 10 in Somalia. Incremental cost-effectiveness would be US$5800/disability-adjusted life year (DALY) (95% UR 3100 to 13500). Cost-effectiveness would range from US$500/DALY in Lesotho to US$44 600/DALY in Eritrea. In a general adult population, PrEP is a high-cost intervention which will have maximum impact and be cost-effective only in countries that have high levels of HIV burden and low levels of male circumcision in the population. Hence, PrEP will likely be most effective in Southern Africa as a targeted intervention added to existing strategies to control the HIV pandemic.

Effect of trichostatin A on Burkitt's lymphoma cells: Inhibition of EPS8 activity through Phospho-Erk1/2 pathway.

PubMed

Sun, Peipei; Zhou, Xin; He, Yingzhi; Liu, Huimin; Wang, Yuxin; Chen, Yiran; Li, Meifang; He, Yanjie; Li, Guowei; Li, Yuhua

2018-03-18

Histone deacetylase inhibitors (HDACi) manifest great potential for treatment of Burkitt's lymphoma (BL), an aggressive B-cell lymphoma. Epidermal growth factor receptor pathway substrate 8 (EPS8) is confirmed overexpressed and associated with poor prognosis in solid tumors and leukemia. However, EPS8 expression and the relationship between EPS8 and HDACi on BL remains obscure. Here, we hypothesized that trichostatin A (TSA), a pan-HDACi, could inhibit BL cells by downregulating EPS8. We demonstrated that TSA reduced cell viability, induced apoptosis and cell arrest at G0/G1. Mechanismly, TSA attenuated EPS8 and downstream Phospho-Erk1/2 pathway. Knockdown of EPS8 resulted in a significant reduction in cellular proliferation and suppressed Phospho-Erk1/2 pathway activity, particularly when combined with TSA. Conversely, overexpression of EPS8 rescued this phenomenon. Then we showed that the combination of TSA and Epirubicin had a more significant effect when compared with TSA or Epirubicin alone. Finally, knockdown of EPS8 and TSA had a synergistic suppression effect on BALB/c nude mice. In conclusion, this study reveals that TSA affects BL cells by suppressing Phospho-Erk1/2 pathway through downregulating EPS8. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of the exopolysaccharide layer on biofilms, adhesion and resistance to stress in Lactobacillus johnsonii FI9785.

PubMed

Dertli, Enes; Mayer, Melinda J; Narbad, Arjan

2015-02-04

The bacterial cell surface is a crucial factor in cell-cell and cell-host interactions. Lactobacillus johnsonii FI9785 produces an exopolysaccharide (EPS) layer whose quantity and composition is altered in mutants that harbour genetic changes in their eps gene clusters. We have assessed the effect of changes in EPS production on cell surface characteristics that may affect the ability of L. johnsonii to colonise the poultry host and exclude pathogens. Analysis of physicochemical cell surface characteristics reflected by Zeta potential and adhesion to hexadecane showed that an increase in EPS gave a less negative, more hydrophilic surface and reduced autoaggregation. Autoaggregation was significantly higher in mutants that have reduced EPS, indicating that EPS can mask surface structures responsible for cell-cell interactions. EPS also affected biofilm formation, but here the quantity of EPS produced was not the only determinant. A reduction in EPS production increased bacterial adhesion to chicken gut explants, but made the bacteria less able to survive some stresses. This study showed that manipulation of EPS production in L. johnsonii FI9785 can affect properties which may improve its performance as a competitive exclusion agent, but that positive changes in adhesion may be compromised by a reduction in the ability to survive stress.

CJ-023,423, a novel, potent and selective prostaglandin EP4 receptor antagonist with antihyperalgesic properties.

PubMed

Nakao, Kazunari; Murase, Akio; Ohshiro, Hiroyuki; Okumura, Takako; Taniguchi, Kana; Murata, Yoko; Masuda, Masatoshi; Kato, Tomoki; Okumura, Yoshiyuki; Takada, Junji

2007-08-01

The prostaglandin (PG) EP(4) receptor subtype is expressed by peripheral sensory neurons. Although a potential role of EP(4) receptor in pain has been suggested, a limited number of selective ligands have made it difficult to explore the physiological functions of EP(4) or its potential as a new analgesic target. Here, we describe the in vitro and in vivo pharmacology of a novel EP(4) receptor antagonist, N-[({2-[4-(2-ethyl-4,6-dimethyl-1H-imidazo [4,5-c] pyridin-1-yl) phenyl]ethyl}amino) carbonyl]-4-methylbenzenesulfonamide (CJ-023,423). In vitro, CJ-023,423 inhibits [(3)H]PGE(2) binding to both human and rat EP(4) receptors with K(i) of 13 +/- 4 and 20 +/- 1 nM, respectively. CJ-023,423 is highly selective for the human EP(4) receptor over other human prostanoid receptor subtypes. It also inhibits PGE(2)-evoked elevation in intracellular cAMP at the human and rat EP(4) receptors with pA(2) of 8.3 +/- 0.03 and 8.2 +/- 0.2 nM, respectively. In vivo, oral administration of CJ-023,423 significantly reduces thermal hyperalgesia induced by intraplantar injection of PGE(2) (ED(50) = 12.8 mg/kg). CJ-023,423 is also effective in models of acute and chronic inflammatory pain. CJ-023,423 significantly reduces mechanical hyperalgesia in the carrageenan model. Furthermore, CJ-023,423 significantly reverses complete Freund's adjuvant-induced chronic inflammatory pain response. Taken together, the present data indicate that CJ-023,423, a highly potent and selective antagonist of both human and rat EP(4) receptors, produces antihyperalgesic effects in animal models of inflammatory pain. Thus, specific blockade of the EP(4) receptor signaling may represent a novel therapeutic approach for the treatment of inflammatory pain.

Present and future medical applications of microbial exopolysaccharides

PubMed Central

Moscovici, Misu

2015-01-01

Microbial exopolysaccharides (EPS) have found outstanding medical applications since the mid-20th century, with the first clinical trials on dextran solutions as plasma expanders. Other EPS entered medicine firstly as conventional pharmaceutical excipients (e.g., xanthan – as suspension stabilizer, or pullulan – in capsules and oral care products). Polysaccharides, initially obtained from plant or animal sources, became easily available for a wide range of applications, especially when they were commercially produced by microbial fermentation. Alginates are used as anti-reflux, dental impressions, or as matrix for tablets. Hyaluronic acid and derivatives are used in surgery, arthritis treatment, or wound healing. Bacterial cellulose is applied in wound dressings or scaffolds for tissue engineering. The development of drug controlled-release systems and of micro- and nanoparticulated ones, has opened a new era of medical applications for biopolymers. EPS and their derivatives are well-suited potentially non-toxic, biodegradable drug carriers. Such systems concern rating and targeting of controlled release. Their large area of applications is explained by the available manifold series of derivatives, whose useful properties can be thereby controlled. From matrix inclusion to conjugates, different systems have been designed to solubilize, and to assure stable transport in the body, target accumulation and variable rate-release of a drug substance. From controlled drug delivery, EPS potential applications expanded to vaccine adjuvants and diagnostic imaging systems. Other potential applications are related to the bioactive (immunomodulator, antitumor, antiviral) characteristics of EPS. The numerous potential applications still wait to be developed into commercial pharmaceuticals and medical devices. Based on previous and recent results in important medical-pharmaceutical domains, one can undoubtedly state that EPS medical applications have a broad future ahead. PMID:26483763

PrEP awareness and perceived barriers among single young men who have sex with men.

PubMed

Bauermeister, Jose A; Meanley, Steven; Pingel, Emily; Soler, Jorge H; Harper, Gary W

2013-10-01

Pre-exposure prophylaxis (PrEP) has the potential to help reduce new HIV infections among young men who have sex with men (YMSM). Using a cross-sectional survey of YMSM (N=1,507; ages 18-24), we gauged YMSM's PrEP awareness and PrEP-related beliefs regarding side effects, accessibility, and affordability. Overall, 27% of the sample had heard about PrEP; 1% reported ever using PrEP prior to sex. In a multivariate logistic regression, we found that YMSM were more likely to have heard about PrEP if they were older, more educated, were residentially unstable in the prior 30 days, had insurance, or reported having at least one sexually transmitted infection in their lifetime. We found no differences by race/ethnicity, history of incarceration, or recent sexual risk behavior. In multivariate linear regression models, Black and Latino YMSM were more likely than Whites to state they would not use PrEP because of side effect concerns. YMSM were more likely to indicate that they would not be able to afford PrEP if they did not have insurance or if they had a prior sexually transmitted infection, PrEP rollout may be hindered due to lack of awareness, as well as perceived barriers regarding its use. We propose strategies to maximize equity in PrEP awareness and access if it is to be scaled up among YMSM.

Construction of a Cordyceps sinensis exopolysaccharide-conjugated selenium nanoparticles and enhancement of their antioxidant activities.

PubMed

Xiao, Yidong; Huang, Qilin; Zheng, Zhaomin; Guan, Han; Liu, Shiyu

2017-06-01

A Cordyceps sinensis exopolysaccharide (EPS)-conjugated selenium nanoparticles (SeNPs) were successfully constructed through the reduction of SeO 3 2- . The EPS-SeNPs were characterized in terms of formation, morphology, size, Se distribution and phase by UV-vis, FT-IR, transmission electron microscopy (TEM), dynamic light scattering (DLS), energy dispersive X-ray (EDX) and wide angle X-ray diffraction (WAXD) measurements. Results revealed that the SeNPs conjugated to EPS were amorphous and could be well dispersed at a size range of 80-125nm. The interactions between the OH groups of EPS and SeNPs substituted for intermolecular interaction in native EPS to form new CO⋯Se bonds, resulting in good dispersion of SeNPs in the EPS matrix. Besides, the EPS-SeNPs at different Se/P ratios exhibited significant scavenging ability on superoxide anion radical (O 2 - ) and ABTS radical cation (ABTS + ) when compared to pure EPS, indicating that the conjugated SeNPs reinforced antioxidant effect of EPS. This work not only provides a simple and efficient way to construct well-dispersed SeNPs in aqueous system, and demonstrates the vital role of the EPS as a biopolymer template for dispersion, stabilization and size control of SeNPs, but also finds the EPS-SeNPs can potentially serve as a good antioxidant towards O 2 - and ABTS + . Copyright © 2017 Elsevier B.V. All rights reserved.

Susceptibility of nitinol to localized corrosion.

PubMed

Pound, Bruce G

2006-04-01

The effect of different conditions on the susceptibility of nitinol to localized corrosion was examined using the cyclic potentiodynamic polarization technique. Tests were performed on mechanically polished (MP) and electropolished (EP) nitinol wire in 0.9 wt % NaCl and phosphate-buffered saline (PBS). A polarization curve was also obtained for an EP stent in the NaCl. Differences between the breakdown potential and the corrosion potential (E(corr)) and between the protection potential and E(corr) were used to evaluate the susceptibility to pitting corrosion and crevice corrosion, respectively. The type of solution and, particularly, the surface condition affected the resistance of nitinol to pitting corrosion. Both EP and MP nitinol were more susceptible to breakdown in the NaCl than in PBS, indicating that the NaCl provides a more severe test environment than does PBS. Electropolishing increased the breakdown resistance of nitinol in PBS and the NaCl, as found in previous studies with Hank's solution. Surface condition, however, did not have a significant effect on the repassivation behavior of nitinol, as is also the case with titanium. The EP wire and stent showed similar breakdown and repassivation behavior in the NaCl, suggesting that the nature of the EP surface was similar in both cases. (c) 2005 Wiley Periodicals, Inc.

The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States.

PubMed

Adamson, Blythe J S; Carlson, Josh J; Kublin, James G; Garrison, Louis P

2017-05-24

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value.

The Potential Cost-Effectiveness of Pre-Exposure Prophylaxis Combined with HIV Vaccines in the United States

PubMed Central

Adamson, Blythe J. S.; Carlson, Josh J.; Kublin, James G.; Garrison, Louis P.

2017-01-01

This economic evaluation aims to support policy-making on the combined use of pre-exposure prophylaxis (PrEP) with HIV vaccines in development by evaluating the potential cost-effectiveness of implementation that would support the design of clinical trials for the assessment of combined product safety and efficacy. The target study population is a cohort of men who have sex with men (MSM) in the United States. Policy strategies considered include standard HIV prevention, daily oral PrEP, HIV vaccine, and their combination. We constructed a Markov model based on clinical trial data and the published literature. We used a payer perspective, monthly cycle length, a lifetime horizon, and a 3% discount rate. We assumed a price of $500 per HIV vaccine series in the base case. HIV vaccines dominated standard care and PrEP. At current prices, PrEP was not cost-effective alone or in combination. A combination strategy had the greatest health benefit but was not cost-effective (ICER = $463,448/QALY) as compared to vaccination alone. Sensitivity analyses suggest a combination may be valuable for higher-risk men with good adherence. Vaccine durability and PrEP drug prices were key drivers of cost-effectiveness. The results suggest that boosting potential may be key to HIV vaccine value. PMID:28538691

Barriers and Facilitators to Oral PrEP Use Among Transgender Women in New York City.

PubMed

Rael, Christine Tagliaferri; Martinez, Michelle; Giguere, Rebecca; Bockting, Walter; MacCrate, Caitlin; Mellman, Will; Valente, Pablo; Greene, George J; Sherman, Susan; Footer, Katherine H A; D'Aquila, Richard T; Carballo-Diéguez, Alex

2018-03-27

Transgender women may face a disparate risk for HIV/AIDS compared to other groups. In 2012, Truvada was approved for daily use as HIV pre-exposure prophylaxis (PrEP). However, there is a dearth of research about barriers and facilitators to PrEP in transgender women. This paper will shed light on transgender women living in New York City's perceived and actual challenges to using PrEP and potential strategies to overcome them. After completing an initial screening process, four 90-min focus groups were completed with n = 18 transgender women. Participants were asked what they like and dislike about PrEP. Participants identified the following barriers: uncomfortable side effects, difficulty taking pills, stigma, exclusion of transgender women in advertising, and lack of research on transgender women and PrEP. Facilitators included: reducing pill size, increasing the types of available HIV prevention products, and conducting scientific studies to evaluate PrEP in transgender women.

Physicochemical properties and membrane biofouling of extra-cellular polysaccharide produced by a Micrococcus luteus strain.

PubMed

Feng, Lei; Li, Xiufen; Song, Ping; Du, Guocheng; Chen, Jian

2014-07-01

The physicochemical properties of the extra-cellular polysaccharide (EPS) produced by a Micrococcus luteus strain, a dominating strain isolated from membrane biofouling layer, were determined in this study. The EPS isolated from this strain was measured to have an average molecular weight of 63,540 Da and some typical polysaccharide absorption peaks in Fourier transform infrared spectrum. Monosaccharide components of the EPS contained rhamnose, fucose, arabinose, xylose, mannose, galactose and glucose in a molar ratio of 0.2074:0.0454:0.0262:0.0446:1.7942:1.2086:0.4578. Pseudo plastic properties were also observed for the EPS through the rheological measurement. The EPS was further characterized for its behavior to cause membrane flux decline. The results showed that both flux declines for polyvinylidenefluoride (PVDF) and polypropylene membranes became more severe as EPS feed concentration increased. A higher irreversible fouling for the PVDF membrane suggested that the EPS had the larger fouling potential to this microfiltration membrane.

The Influence of pH of Extracting Water on the Composition of Seaweed Extracts and Their Beneficial Properties on Lepidium sativum.

PubMed

Godlewska, Katarzyna; Michalak, Izabela; Tuhy, Łukasz; Chojnacka, Katarzyna

2017-01-01

Baltic seaweeds were used to obtain aqueous extracts (E) through changing initial pH of deionised water added to algal biomass (EpH3·H 2 O, EpH7·H 2 O, and EpH10·H 2 O) and through changing pH of the mixture of algae and deionised water (EpH3, EpH7, and EpH10). Algal extracts were characterized in terms of the concentration of polyphenols and micro- and macroelements. The highest concentration of polyphenols was determined in extract EpH3 and the lowest in extract EpH10·H 2 O. It was found that the obtained extracts had similar concentrations of elements (except EpH3). The phytotoxicity of algal extracts (0.5, 2.5, and 10%) was examined in the germination tests on Lepidium sativum . No phytotoxic effects were observed. It was found that they had beneficial effects on the cultivated plants (length and weight). The best biostimulant effect was observed in the groups treated with EpH3 (2.5%), EpH7 (2.5%), and EpH7 (10%). The dry weight of plants was similar in all the groups. Algal extract also improved the multielemental composition of plant. The greatest concentration of total chlorophyll in plants was obtained by using extract EpH10·H 2 O, 0.5%. These results proved that algal extracts have high potential to be applied in cultivation of plants.

The Influence of pH of Extracting Water on the Composition of Seaweed Extracts and Their Beneficial Properties on Lepidium sativum

PubMed Central

Tuhy, Łukasz; Chojnacka, Katarzyna

2017-01-01

Baltic seaweeds were used to obtain aqueous extracts (E) through changing initial pH of deionised water added to algal biomass (EpH3·H2O, EpH7·H2O, and EpH10·H2O) and through changing pH of the mixture of algae and deionised water (EpH3, EpH7, and EpH10). Algal extracts were characterized in terms of the concentration of polyphenols and micro- and macroelements. The highest concentration of polyphenols was determined in extract EpH3 and the lowest in extract EpH10·H2O. It was found that the obtained extracts had similar concentrations of elements (except EpH3). The phytotoxicity of algal extracts (0.5, 2.5, and 10%) was examined in the germination tests on Lepidium sativum. No phytotoxic effects were observed. It was found that they had beneficial effects on the cultivated plants (length and weight). The best biostimulant effect was observed in the groups treated with EpH3 (2.5%), EpH7 (2.5%), and EpH7 (10%). The dry weight of plants was similar in all the groups. Algal extract also improved the multielemental composition of plant. The greatest concentration of total chlorophyll in plants was obtained by using extract EpH10·H2O, 0.5%. These results proved that algal extracts have high potential to be applied in cultivation of plants. PMID:28480222

Primary care clinicians' experiences prescribing HIV pre-exposure prophylaxis at a specialized community health centre in Boston: lessons from early adopters.

PubMed

Krakower, Douglas S; Maloney, Kevin M; Grasso, Chris; Melbourne, Katherine; Mayer, Kenneth H

2016-01-01

An estimated 1.2 million Americans have indications for using antiretroviral pre-exposure prophylaxis (PrEP) to prevent HIV acquisition. For many of these at-risk individuals, the best opportunity to learn about and receive PrEP will be during routine visits to their generalist primary care clinicians. However, few generalist clinicians have prescribed PrEP, primarily because of practical concerns about providing PrEP in primary care settings. The experiences of specialized primary care clinicians who have prescribed PrEP can inform the feasibility of PrEP provision by generalists. During January to February 2015, 35 primary care clinicians at a community health centre in Boston that specializes in the care of sexual and gender minorities completed anonymous surveys about their experiences and practices with PrEP provision. Responses were analyzed with descriptive statistics. Thirty-two clinicians (response rate=91%) completed the surveys. Nearly all clinicians (97%) had prescribed PrEP (median 20 patients, interquartile range 11-33). Most clinicians reported testing and risk-reduction counselling practices concordant with U.S. Centers for Disease Control and Prevention guidelines for PrEP. Clinicians indicated that patients using PrEP experienced medication toxicities infrequently and generally reported high adherence. However, some clinicians' practices differed from guideline recommendations, and some clinicians observed patients with increased risk behaviours. Most clinicians (79%) rated PrEP provision as easy to accomplish, and 97% considered themselves likely to prescribe PrEP in the future. In a primary care clinic with specialized expertise in HIV prevention, clinicians perceived that PrEP provision to large numbers of patients was safe, feasible and potentially effective. Efforts to engage generalist primary care clinicians in PrEP provision could facilitate scale-up of this efficacious intervention.

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients

PubMed Central

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-01

Background Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. Results EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. Conclusions EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy. PMID:29416671

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

PubMed

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

Neural network classification of clinical neurophysiological data for acute care monitoring

NASA Technical Reports Server (NTRS)

Sgro, Joseph

1994-01-01

The purpose of neurophysiological monitoring of the 'acute care' patient is to allow the accurate recognition of changing or deteriorating neurological function as close to the moment of occurrence as possible, thus permitting immediate intervention. Results confirm that: (1) neural networks are able to accurately identify electroencephalogram (EEG) patterns and evoked potential (EP) wave components, and measuring EP waveform latencies and amplitudes; (2) neural networks are able to accurately detect EP and EEG recordings that have been contaminated by noise; (3) the best performance was obtained consistently with the back propagation network for EP and the HONN for EEG's; (4) neural network performed consistently better than other methods evaluated; and (5) neural network EEG and EP analyses are readily performed on multichannel data.

Ketamine-Based Anesthetic Protocols and Evoked Potential Monitoring: A Risk/Benefit Overview

PubMed Central

Stoicea, Nicoleta; Versteeg, Gregory; Florescu, Diana; Joseph, Nicholas; Fiorda-Diaz, Juan; Navarrete, Víctor; Bergese, Sergio D.

2016-01-01

Since its discovery, ketamine, a non-competitive N-methyl D-aspartate (NMDA) receptor antagonist related to phencyclidine, has been linked to multiple adverse reactions sometimes described as “out of body” and “near death experiences,” including emergence phenomena, delusions, hallucinations, delirium, and confusion. Due to these effects, ketamine has been withdrawn from mainstream anesthetic use in adult patients. Evoked potentials (EPs) are utilized to monitor neural pathways during surgery, detect intraoperative stress or damage, detect and define the level of neural lesions, and define abnormalities. Unfortunately, many of the volatile anesthetics commonly used during spinal and neurologic procedures suppress EP amplitude and monitoring. Ketamine has been found in several preclinical and clinical studies to actually increase EP amplitude and thus has been used as an analgesic adjunct in procedures where EP monitoring is critical. Once the gap in our knowledge of ketamine's risks has been sufficiently addressed in animal models, informed clinical trials should be conducted in order to properly incorporate ketamine-based anesthetic regimens during EP-monitored neurosurgeries. PMID:26909017

Exopolysaccharides from yeast: insight into optimal conditions for biosynthesis, chemical composition and functional properties - review.

PubMed

Gientka, Iwona; Błażejak, Stanisław; Stasiak-Różańska, Lidia; Chlebowska-Śmigiel, Anna

2015-01-01

xopolysaccharides (EPS) are not a well-established group of metabolites. An industrial scale    of this EPS production is limited mainly by low yield biosynthesis. Until now, enzymes and biosynthesis pathways, as well as the role of regulatory genes, have not been described. Some of yeast EPS show antitumor, immunostimulatory and antioxidant activity. Others, absorb heavy metals and can function as bioactive components of food. Also, the potential of yeast EPS as thickeners or stabilizers can be found. Optimal conditions for the biosynthesis of yeast exopolysaccharides require strong oxygenation and low temperature of the culture, due to the physiology of the producer strains. The medium should contain sucrose as a carbon source and ammonium sulfate as inorganic nitrogen source, wherein the C:N ratio in the substrate should be 15:1. The cultures are long and the largest accumulation of polymers is observed after 4 or 5 days of culturing. The structure of yeast EPS is complex which affects the strain and culture condition. The EPS from yeast are linear mannans, pullulan, glucooligosaccharides, galactooligosaccharides and other heteropolysaccharides containing α-1,2; α-1,3; α-1,6; β-1,3; β-1,4 bonds. Mannose and glucose have the largest participation of carbohydrates for. t exopolysaccharides (EPS) are not a well-established group of metabolites. An industrial scale    of this EPS production is limited mainly by low yield biosynthesis. Until now, enzymes and biosynthesis pathways, as well as the role of regulatory genes, have not been described. Some of yeast EPS show antitumor, immunostimulatory and antioxidant activity. Others, absorb heavy metals and can function as bioactive components of food. Also, the potential of yeast EPS as thickeners or stabilizers can be found. Optimal conditions for the biosynthesis of yeast exopolysaccharides require strong oxygenation and low temperature of the culture, due to the physiology of the producer strains. The medium should contain sucrose as a carbon source and ammonium sulfate as inorganic nitrogen source, wherein the C:N ratio in the substrate should be 15:1. The cultures are long and the largest accumulation of polymers is observed after 4 or 5 days of culturing. The structure of yeast EPS is complex which affects the strain and culture condition. The EPS from yeast are linear mannans, pullulan, glucooligosaccharides, galactooligosaccharides and other heteropolysaccharides containing α-1,2; α-1,3; α-1,6; β-1,3; β-1,4 bonds. Mannose and glucose have the largest participation of carbohydrates formin. t exopolysaccharides (EPS) are not a well-established group of metabolites. An industrial scale    of this EPS production is limited mainly by low yield biosynthesis. Until now, enzymes and biosynthesis pathways, as well as the role of regulatory genes, have not been described. Some of yeast EPS show antitumor, immunostimulatory and antioxidant activity. Others, absorb heavy metals and can function as bioactive components of food. Also, the potential of yeast EPS as thickeners or stabilizers can be found. Optimal conditions for the biosynthesis of yeast exopolysaccharides require strong oxygenation and low temperature of the culture, due to the physiology of the producer strains. The medium should contain sucrose as a carbon source and ammonium sulfate as inorganic nitrogen source, wherein the C:N ratio in the substrate should be 15:1. The cultures are long and the largest accumulation of polymers is observed after 4 or 5 days of culturing. The structure of yeast EPS is complex which affects the strain and culture condition. The EPS from yeast are linear mannans, pullulan, glucooligosaccharides, galactooligosaccharides and other heteropolysaccharides containing α-1,2; α-1,3; α-1,6; β-1,3; β-1,4 bonds. Mannose and glucose have the largest participation of carbohydrates forming EPS.

Biological activities of the polysaccharides produced in submerged culture of two edible Pleurotus ostreatus mushrooms.

PubMed

Vamanu, Emanuel

2012-01-01

Exopolysaccharides (EPS) and internal (intracellular) polysaccharides (IPS) obtained from the Pleurotus ostreatus M2191 and PBS281009 cultivated using the batch system revealed an average of between 0.1-2 (EPS) and 0.07-1.5 g/L/day (IPS). The carbohydrate analysis revealed that the polysaccharides comprised 87-89% EPS and 68-74% IPS. The investigation of antioxidant activity in vitro revealed a good antioxidant potential, particularly for the IPS and EPS isolated from PBS281009, as proved by the EC(50) value for DPPH, ABTS scavenging activity, reducing power, and iron chelating activity.

Environmental interactions of the Space Station Freedom electric power system

NASA Technical Reports Server (NTRS)

Nahra, Henry K.; Lu, Cheng-Yi

1991-01-01

The Space Station Freedom operates in a low earth orbit (LEO) environment. Such operation results in different potential interactions with the Space Station systems including the Electric Power System (EPS). These potential interactions result in environmental effects which include neutral species effects such as atomic oxygen erosion, effects of micrometeoroid and orbital debris impacts, plasma effects, ionizing radiation, and induced contamination degradation effects. The EPS design and its interactions with the LEO environment are briefly described and the results of analyses and testing programs planned and performed thus far to resolve environmental concerns related to the EPS and its function in LEO environment.

"How I Wish This Thing Was Initiated 100 Years Ago!" Willingness to Take Daily Oral Pre-Exposure Prophylaxis among Men Who Have Sex with Men in Kenya.

PubMed

Karuga, Robinson Njoroge; Njenga, Serah Nduta; Mulwa, Rueben; Kilonzo, Nduku; Bahati, Prince; O'reilley, Kevin; Gelmon, Lawrence; Mbaabu, Stephen; Wachihi, Charles; Githuka, George; Kiragu, Michael

2016-01-01

The MSM population in Kenya contributes to 15% of HIV incidence. This calls for innovative HIV prevention interventions. Pre-exposure prophylaxis (PrEP) has been efficacious in preventing HIV among MSM in trials. There is limited data on the willingness to take daily oral PrEP in sub-Sahara Africa. PrEP has not been approved for routine use in most countries globally. This study aimed to document the willingness to take PrEP and barriers to uptake and adherence to PrEP in Kenya. The findings will inform the design of a PrEP delivery program as part of the routine HIV combination prevention. Eighty MSM were recruited in 2 Counties in December 2013. Quantitative data on sexual behaviour and willingness to take PrEP were collected using semi-structured interviews and analysed using SPSS. Qualitative data on knowledge of PrEP, motivators and barriers to uptake and adherence to PrEP were collected using in-depth interviews and FGDs and analysed using Nvivo. Analysis of data in willingness to take PrEP was conducted on the HIV negative participants (n = 55). 83% of MSM were willing to take daily oral HIV PrEP. Willingness to take PrEP was higher among the bi-sexual and younger men. Motivators for taking PrEP were the need to stay HIV negative and to protect their partners. History of poor medication adherence, fear of side effects and HIV stigma were identified as potential barriers to adherence. Participants were willing to buy PrEP at a subsidized price. There is willingness to take PrEP among MSM in Kenya and there is need to invest in targeted education and messaging on PrEP to enhance adherence, proper use and reduce stigma in the general population and among policy makers.

Adaptive interference cancel filter for evoked potential using high-order cumulants.

PubMed

Lin, Bor-Shyh; Lin, Bor-Shing; Chong, Fok-Ching; Lai, Feipei

2004-01-01

This paper is to present evoked potential (EP) processing using adaptive interference cancel (AIC) filter with second and high order cumulants. In conventional ensemble averaging method, people have to conduct repetitively experiments to record the required data. Recently, the use of AIC structure with second statistics in processing EP has proved more efficiency than traditional averaging method, but it is sensitive to both of the reference signal statistics and the choice of step size. Thus, we proposed higher order statistics-based AIC method to improve these disadvantages. This study was experimented in somatosensory EP corrupted with EEG. Gradient type algorithm is used in AIC method. Comparisons with AIC filter on second, third, fourth order statistics are also presented in this paper. We observed that AIC filter with third order statistics has better convergent performance for EP processing and is not sensitive to the selection of step size and reference input.

Electroencephalography and analgesics.

PubMed

Malver, Lasse Paludan; Brokjaer, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr

2014-01-01

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms 'analgesics', 'electroencephalography' and 'evoked potentials' for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. © 2013 The British Pharmacological Society.

Early disturbances in multimodal evoked potentials as a prognostic factor for long-term disability in relapsing-remitting multiple sclerosis patients.

PubMed

London, Frédéric; El Sankari, Souraya; van Pesch, Vincent

2017-04-01

The aim of this study was to investigate whether early alterations in evoked potentials (EPs) have a prognostic value in relapsing-remitting multiple sclerosis (RRMS). We retrospectively selected 108 early MS patients with a neurological follow-up ranging from 5 to 15years, in whom multimodal EPs (visual, brainstem auditory, somatosensory and motor) were performed at diagnosis. A conventional ordinal score was used to quantify the observed abnormalities. The extent of change in the composite EP score was well correlated to the Expanded Disability Status Scale (EDSS) at ten years (Y 10 ) and up to 15years (Y 11-15 ) after disease onset. Analysis of the predictive value of the EP score showed an increased risk of disability progression at Y 10 and Y 11-15 of 60% (p<0.0001) and 73% (p<0.0001) respectively in patients with an EP score >4. Conversely, the risk of disability progression at Y 10 and Y 11-15 associated with a lower EP score (⩽4) was reduced to 16% and 20% respectively. Our data support the good predictive value for long-term disability progression of multimodal EPs performed early after disease onset in RRMS patients. This study, performed in a homogeneous RRMS cohort with long term follow-up, demonstrates the value of an early comprehensive neurophysiological assessment as a marker for future disability. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Gravity receptor function in mice with graded otoconial deficiencies.

PubMed

Jones, Sherri M; Erway, Lawrence C; Johnson, Kenneth R; Yu, Heping; Jones, Timothy A

2004-05-01

The purpose of the present study was to examine gravity receptor function in mutant mouse strains with variable deficits in otoconia: lethal milk (lm), pallid (pa), tilted (tlt), mocha (mh), and muted (mu). Control animals were either age-matched heterozygotes or C57BL/6J (abbr. B6) mice. Gravity receptor function was measured using linear vestibular evoked potentials (VsEPs). Cage and swimming behaviors were also documented. Temporal bones were cleared to assess the overall otoconial deficit and to correlate structure and function for lm mice. Results confirmed the absence of VsEPs for mice that lacked otoconia completely. VsEP thresholds and amplitudes varied in mouse strains with variable loss of otoconia. Some heterozygotes also showed elevated VsEP thresholds in comparison to B6 mice. In lm mice, which have absent otoconia in the utricle and a variable loss of otoconia in the saccule, VsEPs were present and average P1/N1 amplitudes were highly correlated with the average loss of saccular otoconia (R = 0.77,p < 0.001). Cage and swimming behavior were not adversely affected in those animals with recordable VsEPs. Most, but not all, mice with absent VsEPs were unable to swim. Some animals were able to swim despite having no measurable gravity receptor response. The latter finding underscores the remarkable adaptive potential exhibited by neurobehavioral systems following profound sensory loss. It also shows that behavior alone may be an unreliable indicator of the extent of gravity receptor deficits.

Ion flow in stria vascularis and the production and regulation of cochlear endolymph and the endolymphatic potential.

PubMed

Patuzzi, Robert

2011-07-01

This paper reviews some of what is known about ion transport through the cells of the mammalian stria vascularis, and discusses how the endolymph and endocochlear potential in scala media are produced by the stria's main cell types. It discusses the role of each cells' ion transport proteins from an engineering perspective, and the advantages and disadvantages in using the different transport proteins in the different cells to perform their different roles. To aid this discussion, the use of spreadsheet analysis in the modelling of ion transport in single cells and homogenous epithelia is outlined, including the current-voltage (IV) characteristics of the three main categories of transport proteins (pores, ports and pumps), and the constraint equations that apply under various conditions (the voltage or ionic steady states in the open- and closed-circuit conditions). Also discussed are the circulation of K(+) within the cochlea, and the chloride, salt and water balance of scala media and stria vascularis, and what transport processes may be required to maintain such a balance. Copyright © 2011 Elsevier B.V. All rights reserved.

The influence of transducer operating point on distortion generation in the cochlea

NASA Astrophysics Data System (ADS)

Sirjani, Davud B.; Salt, Alec N.; Gill, Ruth M.; Hale, Shane A.

2004-03-01

Distortion generated by the cochlea can provide a valuable indicator of its functional state. In the present study, the dependence of distortion on the operating point of the cochlear transducer and its relevance to endolymph volume disturbances has been investigated. Calculations have suggested that as the operating point moves away from zero, second harmonic distortion would increase. Cochlear microphonic waveforms were analyzed to derive the cochlear transducer operating point and to quantify harmonic distortions. Changes in operating point and distortion were measured during endolymph manipulations that included 200-Hz tone exposures at 115-dB SPL, injections of artificial endolymph into scala media at 80, 200, or 400 nl/min, and treatment with furosemide given intravenously or locally into the cochlea. Results were compared with other functional changes that included action potential thresholds at 2.8 or 8 kHz, summating potential, endocochlear potential, and the 2 f1-f2 and f2-f1 acoustic emissions. The results demonstrated that volume disturbances caused changes in the operating point that resulted in predictable changes in distortion. Understanding the factors influencing operating point is important in the interpretation of distortion measurements and may lead to tests that can detect abnormal endolymph volume states.

Emergency physician perceptions of shared decision-making.

PubMed

Kanzaria, Hemal K; Brook, Robert H; Probst, Marc A; Harris, Dustin; Berry, Sandra H; Hoffman, Jerome R

2015-04-01

Despite the potential benefits of shared decision-making (SDM), its integration into emergency care is challenging. Emergency physician (EP) perceptions about the frequency with which they use SDM, its potential to reduce medically unnecessary diagnostic testing, and the barriers to employing SDM in the emergency department (ED) were investigated. As part of a larger project examining beliefs on overtesting, questions were posed to EPs about SDM. Qualitative analysis of two multispecialty focus groups was done exploring decision-making around resource use to generate survey items. The survey was then pilot-tested and revised to focus on advanced diagnostic imaging and SDM. The final survey was administered to EPs recruited at four emergency medicine (EM) conferences and 15 ED group meetings. This report addresses responses regarding SDM. A purposive sample of 478 EPs from 29 states were approached, of whom 435 (91%) completed the survey. EPs estimated that, on average, multiple reasonable management options exist in over 50% of their patients and reported employing SDM with 58% of such patients. Respondents perceived SDM as a promising solution to reduce overtesting. However, despite existing research to the contrary, respondents also commonly cited beliefs that 1) "many patients prefer that the physician decides," 2) "when offered a choice, many patients opt for more aggressive care than they need," and 3) "it is too complicated for patients to know how to choose." Most surveyed EPs believe SDM is a potential high-yield solution to overtesting, but many perceive patient-related barriers to its successful implementation. © 2015 by the Society for Academic Emergency Medicine.

Translating PrEP effectiveness into public health impact: key considerations for decision-makers on cost-effectiveness, price, regulatory issues, distributive justice and advocacy for access.

PubMed

Hankins, Catherine; Macklin, Ruth; Warren, Mitchell

2015-01-01

The extraordinary feat of proving the effectiveness of oral pre-exposure prophylaxis (PrEP) in clinical trials in different populations in a variety of settings may prove to have been easier than ensuring it is used well. Decision-makers must make difficult choices to realize the promise of antiretroviral prophylaxis for their countries. This paper outlines key economic, regulatory and distributive justice issues that must be addressed for effective and acceptable PrEP implementation. In considering the role that PrEP can play in combination prevention programmes, decision-makers must determine who can benefit most from PrEP, how PrEP can be provided safely and efficiently, and what kind of health system support will ensure successful implementation. To do this, they need contextualized information on disease burden by population, analyses of how PrEP services might best be delivered, and projections of the human resource and infrastructure requirements for each potential delivery model. There are cost considerations, varying cost-effectiveness results and regulatory challenges. The principles of ethics can inform thorny discussions about who should be prioritized for oral PrEP and how best to introduce it fairly. We describe the cost-effectiveness of PrEP in different populations at higher risk of HIV exposure, its price in low- and middle-income countries, and the current regulatory situation. We explore the principles of ethics that can inform resource allocation decision-making about PrEP anchored in distributive justice, at a time when universal access to antiretroviral treatment remains to be assured. We then highlight the role of advocacy in moving the PrEP agenda forward. The time is ripe now for decisions about whether, how and for whom PrEP should be introduced into a country's HIV response. It has the potential to contribute significantly to high impact HIV prevention if it is tailored to those who can most benefit from it and if current regulatory and pricing barriers can be overcome. Advocacy at all levels can help inform decision-making and push the access agenda to avert HIV infections among those at highest risk of HIV exposure. The benefits will accrue beyond the individual level to slow HIV transmission at the population level.

Barriers to uptake and use of pre-exposure prophylaxis (PrEP) among communities most affected by HIV in the UK: findings from a qualitative study in Scotland.

PubMed

Young, Ingrid; Flowers, Paul; McDaid, Lisa M

2014-11-20

To explore the acceptability of pre-exposure prophylaxis (PrEP) among gay, bisexual and men who have sex with men (MSM) and migrant African communities in Scotland, UK. Consecutive mixed qualitative methods consisting of focus groups (FGs) and in-depth interviews (IDIs) explored PrEP acceptability. Data were digitally recorded, transcribed and analysed thematically to identify anticipated and emerging themes. Participants were recruited through community sexual health and outreach support services, and from non-sexual health settings across Scotland. Inclusion criteria included identification as either MSM and/or from migrant African communities; 18 years and older; living in Scotland at the time of participation. 7 FGs were conducted (n=33): 5 with MSM (n=22) and 2 mixed-sex groups with African participants (n=11, women=8), aged 18-75 years. 34 IDIs were conducted with MSM (n=20) and African participants (n=14, women=10), aged 19-60 years. The sample included participants who were HIV-positive and HIV-negative or untested (HIV-positive FG participants, n=22; HIV-positive IDI participants, n=17). Understandings of PrEP effectiveness and concerns about maintaining regular adherence were identified as barriers to potential PrEP uptake and use. Low perception of HIV risk due to existing risk management strategies meant few participants saw themselves as PrEP candidates. Participants identified risk of other sexually transmitted infections and pregnancy as a concern which PrEP did not address for either themselves or their sexual partners. PrEP emerged as a contentious issue because of the potentially negative implications it had for HIV prevention. Many participants viewed PrEP as problematic because they perceived that others would stop using condoms if PrEP was to become available. PrEP implementation needs to identify appropriate communication methods in the context of diverse HIV literacy; address risk-reduction concerns and; demonstrate how PrEP can be part of a safe and comprehensive risk management strategy. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Ventilation changes associated with hatching and maturation of an endothermic phenotype in the Pekin duck, Anas platyrhynchos domestica.

PubMed

Sirsat, Tushar S; Dzialowski, Edward M

2016-04-15

Precocial birds begin embryonic life with an ectothermic metabolic phenotype and rapidly develop an endothermic phenotype after hatching. Switching to a high-energy, endothermic phenotype requires high-functioning respiratory and cardiovascular systems to deliver sufficient environmental oxygen to the tissues. We measured tidal volume (VT), breathing frequency (ƒ), minute ventilation (V̇e), and whole-animal oxygen consumption (V̇o2) in response to gradual cooling from 37.5°C (externally pipped paranates, EP) or 35°C (hatchlings) to 20°C along with response to hypercapnia during developmental transition from an ectothermic, EP paranate to endothermic hatchling. To examine potential eggshell constraints on EP ventilation, we repeated these experiments in artificially hatched early and late EP paranates. Hatchlings and artificially hatched late EP paranates were able to increase V̇o2significantly in response to cooling. EP paranates had high ƒ that decreased with cooling, coupled with an unchanging low VT and did not respond to hypercapnia. Hatchlings had significantly lower ƒ and higher VT and V̇e that increased with cooling and hypercapnia. In response to artificial hatching, all ventilation values quickly reached those of hatchlings and responded to hypercapnia. The timing of artificial hatching influenced the temperature response, with only artificially hatched late EP animals, exhibiting the hatchling ventilation response to cooling. We suggest one potential constraint on ventilatory responses of EP paranates is the rigid eggshell, limiting air sac expansion during inhalation and constraining VT Upon natural or artificial hatching, the VT limitation is removed and the animal is able to increase VT, V̇e, and thus V̇o2, and exhibit an endothermic phenotype. Copyright © 2016 the American Physiological Society.

Ventilation changes associated with hatching and maturation of an endothermic phenotype in the Pekin duck, Anas platyrhynchos domestica

PubMed Central

Sirsat, Tushar S.

2016-01-01

Precocial birds begin embryonic life with an ectothermic metabolic phenotype and rapidly develop an endothermic phenotype after hatching. Switching to a high-energy, endothermic phenotype requires high-functioning respiratory and cardiovascular systems to deliver sufficient environmental oxygen to the tissues. We measured tidal volume (VT), breathing frequency (ƒ), minute ventilation (V̇e), and whole-animal oxygen consumption (V̇o2) in response to gradual cooling from 37.5°C (externally pipped paranates, EP) or 35°C (hatchlings) to 20°C along with response to hypercapnia during developmental transition from an ectothermic, EP paranate to endothermic hatchling. To examine potential eggshell constraints on EP ventilation, we repeated these experiments in artificially hatched early and late EP paranates. Hatchlings and artificially hatched late EP paranates were able to increase V̇o2 significantly in response to cooling. EP paranates had high ƒ that decreased with cooling, coupled with an unchanging low VT and did not respond to hypercapnia. Hatchlings had significantly lower ƒ and higher VT and V̇e that increased with cooling and hypercapnia. In response to artificial hatching, all ventilation values quickly reached those of hatchlings and responded to hypercapnia. The timing of artificial hatching influenced the temperature response, with only artificially hatched late EP animals, exhibiting the hatchling ventilation response to cooling. We suggest one potential constraint on ventilatory responses of EP paranates is the rigid eggshell, limiting air sac expansion during inhalation and constraining VT. Upon natural or artificial hatching, the VT limitation is removed and the animal is able to increase VT, V̇e, and thus V̇o2, and exhibit an endothermic phenotype. PMID:26818053

Perceptions and attitudes about preexposure prophylaxis among seronegative partners and the potential of sexual disinhibition.

PubMed

Tripathi, Avnish; Whiteside, Y Omar; Duffus, Wayne A

2013-10-01

Preexposure prophylaxis (PrEP) is a promising strategy to prevent human immunodeficiency virus (HIV) infection, especially among high-risk individuals such as seronegative partners; however, many caveats such as the potential risk of sexual disinhibition and noncompliance need to be considered. We explored the sociodemographic and behavioral factors associated with the adoption of PrEP among HIV seronegative men who have sex with men and heterosexual partners. A prepiloted self-administered survey was conducted among seronegative partners in a Ryan White HIV/AIDS Clinic in South Carolina from 2010 to 2011. Bivariate and multivariable analyses were used to explore the data. The survey was completed by 89 seronegative partners. The median age was 42 years (interquartile range 32-50) and a majority was men (56%), black (70%), and heterosexual (74%). A majority (94%) was willing to use PrEP if available; however, 26% of subjects suggested that they would be more likely to have unprotected sex with an HIV-positive partner while using PrEP, and 27% suggested that it would be difficult to take a daily dose of PrEP and consistently use condoms. The multivariable results suggest that the belief that a condom is no longer needed while taking PrEP was more likely among those who did not use a condom during their last sexual intercourse (adjusted odds ratio 7.45; 95% confidence interval 1.57-35.45) and among those with a higher HIV knowledge score (adjusted odds ratio 0.43; 95% confidence interval 0.23-0.78). Overall, these results suggest high acceptability of PrEP among seronegative partners to lower the risk of HIV transmission; however, there is a substantial risk of sexual disinhibition and noncompliance while using PrEP that may be reduced by ongoing education.

Sexual partnerships and considerations for HIV antiretroviral pre-exposure prophylaxis utilization among high-risk substance using men who have sex with men.

PubMed

Mimiaga, Matthew J; Closson, Elizabeth F; Kothary, Vishesh; Mitty, Jennifer A

2014-01-01

Men who have sex with men (MSM) remain at great risk of HIV in the United States, representing 65 % of incident HIV infections. One factor contributing to the high rate of HIV infection among MSM is use of "recreational" drugs that are highly associated with unprotected anal sex. Pre-exposure chemoprophylaxis (PrEP) is a novel biomedical HIV prevention strategy that has the potential to reduce HIV transmission in MSM. Main and casual sex partners play a role in HIV prevention efforts for MSM. The study aimed to qualitatively explore the perceived influences of sexual relationships on promoting and inhibiting PrEP use among high-risk MSM who report regular drug use. Semi-structured qualitative interviews were conducted with 40 participants recruited in Boston, Massachusetts. Data were analyzed using descriptive qualitative analysis. Casual partners presented a distinct set of concerns from primary partnerships. MSM generally viewed main partners as a potential source of support for taking PrEP. Given their informal and often temporary nature, PrEP disclosure to casual partners was considered unnecessary. HIV-related stigma and substance use were also perceived as barriers to discussing PrEP use with casual partners. MSM articulated a high degree of personal agency regarding their ability to take PrEP. Findings suggest that behavioral interventions to improve PrEP utilization and adherence for high-risk MSM should be tailored to sex partner type and the parameters established between sex partners. Approaches to PrEP disclosure and partner engagement should be informed by the relative benefits and limitations characterized by these different types of relationships.

Loss of membranous Ep-CAM in budding colorectal carcinoma cells.

PubMed

Gosens, Marleen J E M; van Kempen, Léon C L; van de Velde, Cornelis J H; van Krieken, J Han J M; Nagtegaal, Iris D

2007-02-01

Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of beta-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this study, we hypothesize that the epithelial cell adhesion molecule (Ep-CAM) is involved in tumor budding. In order to address this question, we performed immunohistochemistry on Ep-CAM using three different antibodies (monoclonal antibodies Ber-ep4 and 311-1K1 and a polyclonal antibody) and a double staining on beta-catenin and Ep-CAM. In addition, Ep-CAM mRNA was monitored with mRNA in situ hybridization. Subsequently, we determined the effect of Ep-CAM staining patterns on tumor spread in rectal cancer. In contrast to the tumor mass, budding cells of colorectal carcinoma displayed lack of membranous but highly increased cytoplasmic Ep-CAM staining and nuclear translocation of beta-catenin. mRNA in situ hybridization suggested no differences in Ep-CAM expression between the invasive front and the tumor mass. Importantly, reduced Ep-CAM staining at the invasive margin of rectal tumor specimens (n=133) correlated significantly with tumor budding, tumor grade and an increased risk of local recurrence (P=0.001, P=0.04 and P=0.03, respectively). These data demonstrate abnormal processing of Ep-CAM at the invasive margin of colorectal carcinomas. Our observations indicate that loss of membranous Ep-CAM is associated with nuclear beta-catenin localization and suggest that this contributes to reduced cell-cell adhesions, increased migratory potential and tumor budding.

Sexual Behavior, Risk Compensation, and HIV Prevention Strategies Among Participants in the San Francisco PrEP Demonstration Project: A Qualitative Analysis of Counseling Notes.

PubMed

Carlo Hojilla, J; Koester, Kimberly A; Cohen, Stephanie E; Buchbinder, Susan; Ladzekpo, Deawodi; Matheson, Tim; Liu, Albert Y

2016-07-01

Pre-exposure prophylaxis (PrEP) is a viable HIV prevention strategy but risk compensation could undermine potential benefits. There are limited data that examine this phenomenon outside of clinical trials. We conducted a qualitative analysis of counseling notes from the San Francisco site of the US PrEP demonstration project to assess how men who have sex with men used PrEP as a prevention strategy and its impact on their sexual practices. Four major themes emerged from our analysis of 130 distinct notes associated with 26 participants. Prevention strategy decision-making was dynamic, often influenced by the context and perceived risk of a sexual encounter. Counselors noted that participants used PrEP in conjunction with other health promotion strategies like condoms, asking about HIV status of their sex partners, and seroadaptation. With few exceptions, existing risk reduction strategies were not abandoned upon initiation of PrEP. Risk-taking behavior was 'seasonal' and fluctuations were influenced by various personal, psychosocial, and health-related factors. PrEP also helped relieve anxiety regarding sex and HIV, particularly among serodiscordant partners. Understanding sexual decision-making and how PrEP is incorporated into existing prevention strategies can help inform future PrEP implementation efforts.

Sexual Behavior, Risk Compensation, and HIV Prevention Strategies Among Participants in the San Francisco PrEP Demonstration Project: A Qualitative Analysis of Counseling Notes

PubMed Central

Hojilla, J. Carlo; Koester, Kimberly A.; Cohen, Stephanie E.; Buchbinder, Susan; Ladzekpo, Deawodi; Matheson, Tim; Liu, Albert Y

2015-01-01

Pre-exposure prophylaxis (PrEP) is a viable HIV prevention strategy but risk compensation could undermine potential benefits. There are limited data that examine this phenomenon outside of clinical trials. We conducted a qualitative analysis of counseling notes from the San Francisco site of the US PrEP Demonstration Project to assess how men who have sex with men (MSM) used PrEP as a prevention strategy and its impact on their sexual practices. Four major themes emerged from our analysis of 130 distinct notes associated with 26 participants. Prevention strategy decision-making was dynamic, often influenced by the context and perceived risk of a sexual encounter. Counselors noted that participants used PrEP in conjunction with other health promotion strategies like condoms, asking about HIV status of their sex partners, and seroadaptation. With few exceptions, existing risk reduction strategies were not abandoned upon initiation of PrEP. Risk-taking behavior was ‘seasonal’ and fluctuations were influenced by various personal, psychosocial, and health-related factors. PrEP also helped relieve anxiety regarding sex and HIV, particularly among serodiscordant partners. Understanding sexual decision-making and how PrEP is incorporated into existing prevention strategies can help inform future PrEP implementation efforts. PMID:25835463

Projecting future grassland productivity to assess thesustainability of potential biofuel feedstock areas in theGreater Platte River Basin

USGS Publications Warehouse

Gu, Yingxin; Wylie, Bruce K.; Boyte, Stephen; Phuyal, Khem P.

2014-01-01

This study projects future (e.g., 2050 and 2099) grassland productivities in the Greater Platte River Basin (GPRB) using ecosystem performance (EP, a surrogate for measuring ecosystem productivity) models and future climate projections. The EP models developed from a previous study were based on the satellite vegetation index, site geophysical and biophysical features, and weather and climate drivers. The future climate data used in this study were derived from the National Center for Atmospheric Research Community Climate System Model 3.0 ‘SRES A1B’ (a ‘middle’ emissions path). The main objective of this study is to assess the future sustainability of the potential biofuel feedstock areas identified in a previous study. Results show that the potential biofuel feedstock areas (the more mesic eastern part of the GPRB) will remain productive (i.e., aboveground grassland biomass productivity >2750 kg ha−1 year−1) with a slight increasing trend in the future. The spatially averaged EPs for these areas are 3519, 3432, 3557, 3605, 3752, and 3583 kg ha−1 year−1 for current site potential (2000–2008 average), 2020, 2030, 2040, 2050, and 2099, respectively. Therefore, the identified potential biofuel feedstock areas will likely continue to be sustainable for future biofuel development. On the other hand, grasslands identified as having no biofuel potential in the drier western part of the GPRB would be expected to stay unproductive in the future (spatially averaged EPs are 1822, 1691, 1896, 2306, 1994, and 2169 kg ha−1 year−1 for site potential, 2020, 2030, 2040, 2050, and 2099). These areas should continue to be unsuitable for biofuel feedstock development in the future. These future grassland productivity estimation maps can help land managers to understand and adapt to the expected changes in future EP in the GPRB and to assess the future sustainability and feasibility of potential biofuel feedstock areas.

Extracellular polymeric substances govern the surface charge of biogenic elemental selenium nanoparticles.

PubMed

Jain, Rohan; Jordan, Norbert; Weiss, Stephan; Foerstendorf, Harald; Heim, Karsten; Kacker, Rohit; Hübner, René; Kramer, Herman; van Hullebusch, Eric D; Farges, François; Lens, Piet N L

2015-02-03

The origin of the organic layer covering colloidal biogenic elemental selenium nanoparticles (BioSeNPs) is not known, particularly in the case when they are synthesized by complex microbial communities. This study investigated the presence of extracellular polymeric substances (EPS) on BioSeNPs. The role of EPS in capping the extracellularly available BioSeNPs was also examined. Fourier transform infrared (FT-IR) spectroscopy and colorimetric measurements confirmed the presence of functional groups characteristic of proteins and carbohydrates on the BioSeNPs, suggesting the presence of EPS. Chemical synthesis of elemental selenium nanoparticles in the presence of EPS, extracted from selenite fed anaerobic granular sludge, yielded stable colloidal spherical selenium nanoparticles. Furthermore, extracted EPS, BioSeNPs, and chemically synthesized EPS-capped selenium nanoparticles had similar surface properties, as shown by ζ-potential versus pH profiles and isoelectric point measurements. This study shows that the EPS of anaerobic granular sludge form the organic layer present on the BioSeNPs synthesized by these granules. The EPS also govern the surface charge of these BioSeNPs, thereby contributing to their colloidal properties, hence affecting their fate in the environment and the efficiency of bioremediation technologies.

Gold nanoparticles and electroporation impose both separate and synergistic radiosensitizing effects in HT-29 tumor cells: an in vitro study.

PubMed

Rezaee, Zohre; Yadollahpour, Ali; Bayati, Vahid; Negad Dehbashi, Fereshteh

2017-01-01

Radiation therapy (RT) is the gold standard treatment for more than half of known tumors. Despite recent improvements in RT efficiency, the side effects of ionizing radiation (IR) in normal tissues are a dose-limiting factor that restricts higher doses in tumor treatment. One approach to enhance the efficiency of RT is the application of radiosensitizers to selectively increase the dose at the tumor site. Gold nanoparticles (GNPs) and electroporation (EP) have shown good potential as radiosensitizers for RT. This study aims to investigate the sensitizing effects of EP, GNPs, and combined GNPs-EP on the dose enhancement factor (DEF) for 6 MV photon energy. Radiosensitizing effects of EP, GNPs, and combinations of GNPs-EP were comparatively investigated in vitro for intestinal colon cancer (HT-29) and Chinese hamster ovary (CHO) cell lines by MTT assay and colony formation assay at 6 MV photon energy in six groups: IR (control group), GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR. Treatment of both cell lines with EP, GNPs, and combined GNPs-EP significantly enhanced the response of cells to irradiation. However, the HT-29 showed higher DEF values for all groups. In addition, the DEF value for HT-29 cells for GNPs+IR, GNPs (24 h)+IR, EP+IR, GNPs+EP+IR, and GNPs (24 h)+EP+IR was, respectively, 1.17, 1.47, 1.36, 2.61, and 2.89, indicating synergistic radiosensitizing effect for the GNPs (24 h)+EP+IR group. Furthermore, the synergistic effect was observed just for HT-29 tumor cell lines. Combined GNPs-EP protocols induced synergistic radiosensitizing effect in HT-29 cells, and the effect is also tumor specific. This combined therapy can be beneficially used for the treatment of intrinsically less radiosensitive tumors.

[The noncoherent components of evoked brain activity].

PubMed

Kovalev, V P; Novototskiĭ-Vlasov, V Iu

1998-01-01

Poststimulus spectral EEG changes and their correlation with evoked potential (EP) were analyzed. The non-stationary components of the brain evoked activity were revealed in 32 volunteers during simple motor reaction and choice reaction to visual stimuli. This nonstationary activity was manifested in poststimulus changes in the mean wave half-period duration (MWHPD) and mean wave half-period power of the delta- and beta-frequency oscillations computed in the EEG realizations after the EP subtraction. The latencies of high-frequency EP components fell into the intervals of the MWHPD decrease and increase in the power of beta-oscillations, and the latencies of low-frequency EP components coincided with the intervals of the MWHPD increase and decrease in the power of delta and beta-oscillations, which pointed to correlation of these changes with the EP.

Inhibition of sperm motility in male macaques with EP055, a potential non-hormonal male contraceptive.

PubMed

O'Rand, Michael G; Hamil, Katherine G; Adevai, Tiffany; Zelinski, Mary

2018-01-01

Men have two practical choices for contraception; the condom which has a high typical use failure rate or vasectomy. New male hormonal and non-hormonal contraceptives are under development that target either the production of sperm (spermatogenesis) or the delivery of sperm. One particular target is the sperm protein EPPIN, which is present on the surface of human spermatozoa. EP055 is a small organic compound that targets EPPIN on the surface of sperm and inhibits motility. EP055 was tested in cynomolgus (Macaca fascicularis) males to determine its plasma half-life after intravenous (i.v.) infusion of a single dose and for binding to its target tissues. Our initial study demonstrated a plasma half-life for EP055 of 10.6 minutes. In a second study examination of macaque testis, epididymis, and plasma after i.v. infusion of a single dose of compound EP055 (63.25 mg/kg) demonstrated that EP055 was detected in testis and epididymis two hours and six hours post-infusion. We initiated a trial in rhesus (Macaca mulatta) males to assess the availability of EP055 in semen and its effect on sperm motility as a measure of the drug's efficacy. Four macaques were infused with a low dose (75-80 mg/kg) followed by a recovery period and a subsequent high dose (125-130 mg/kg) of EP055. After high dose administration, sperm motility fell to approximately 20% of pretreatment levels within 6 hours post-infusion; no normal motility was observed at 30 hours post-infusion. Recovery of sperm motility was obvious by 78 hours post-infusion; with full recovery in all animals by 18 days post-infusion. EP055 has the potential to be a male contraceptive that would provide a reversible, short-lived pharmacological alternative.

Metal-Induced Production of a Novel Bioadsorbent Exopolysaccharide in a Native Rhodotorula mucilaginosa from the Mexican Northeastern Region.

PubMed

Garza-Gonzalez, Maria Teresa; Gonzalez Garza, Maria Teresa; Barboza Perez, Daniel; Vazquez Rodriguez, Augusto; Garcia-Gutierrez, Domingo Ixcoatl; Zarate, Xristo; Cantú Cardenas, Maria Elena; Urraca-Botello, Ludwing Ilytch; Lopez-Chuken, Ulrico Javier; Trevino-Torres, Alberto Ludovico; Cerino-Córdoba, Felipe de Jesus; Medina-Ruiz, Pavel; Villarreal-Chiu, Juan Francisco; Morones-Ramirez, Jose Ruben

2016-01-01

There is a current need to develop low-cost strategies to degrade and eliminate industrially used colorants discharged into the environment. Colorants discharged into natural water streams pose various threats, including: toxicity, degradation of aesthetics and inhibiting sunlight penetration into aquatic ecosystems. Dyes and colorants usually have complex aromatic molecular structures, which make them very stable and difficult to degrade and eliminate by conventional water treatment systems. The results in this work demonstrated that heavy metal-resistant Rhodotorula mucilaginosa strain UANL-001L isolated from the northeast region of Mexico produce an exopolysaccharide (EPS), during growth, which has colorant adsorption potential. The EPS produced was purified by precipitation and dialysis and was then physically and chemically characterized by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, and chemical elemental analysis. Here, the ability of the purified EPS produced to adsorb methylene blue (MB), which served as a model colorant, is studied. MB adsorption by the EPS is found to follow Langmuir Adsorption Isotherm kinetics at 25°C. Further, by calculating the Langmuir constant the adsorption capabilities of the EPS produced by the Rhodotorula mucilaginosa strain UANL-001L is compared to that of other adsorbents, both, microbially produced and from agroindustrial waste. The total adsorption capacity of the EPS, from the Rhodotorula mucilaginosa strain UANL-001L, was found to be two-fold greater than the best bioadsorbents reported in the literature. Finally, apart from determining which heavy metals stimulated EPS production in the strain, the optimal conditions of pH, heavy metal concentration, and rate of agitation of the growing culture for EPS production, was determined. The EPS reported here has the potential of aiding in the efficient removal of colorants both in water treatment plants and in situ in natural water streams.

Metal-Induced Production of a Novel Bioadsorbent Exopolysaccharide in a Native Rhodotorula mucilaginosa from the Mexican Northeastern Region

PubMed Central

Vazquez Rodriguez, Augusto; Garcia-Gutierrez, Domingo Ixcoatl; Zarate, Xristo; Cantú Cardenas, Maria Elena; Urraca-Botello, Ludwing Ilytch; Lopez-Chuken, Ulrico Javier; Trevino-Torres, Alberto Ludovico; Cerino-Córdoba, Felipe de Jesus; Medina-Ruiz, Pavel; Villarreal-Chiu, Juan Francisco; Morones-Ramirez, Jose Ruben

2016-01-01

There is a current need to develop low-cost strategies to degrade and eliminate industrially used colorants discharged into the environment. Colorants discharged into natural water streams pose various threats, including: toxicity, degradation of aesthetics and inhibiting sunlight penetration into aquatic ecosystems. Dyes and colorants usually have complex aromatic molecular structures, which make them very stable and difficult to degrade and eliminate by conventional water treatment systems. The results in this work demonstrated that heavy metal-resistant Rhodotorula mucilaginosa strain UANL-001L isolated from the northeast region of Mexico produce an exopolysaccharide (EPS), during growth, which has colorant adsorption potential. The EPS produced was purified by precipitation and dialysis and was then physically and chemically characterized by Scanning Electron Microscopy, Fourier Transform Infrared Spectroscopy, and chemical elemental analysis. Here, the ability of the purified EPS produced to adsorb methylene blue (MB), which served as a model colorant, is studied. MB adsorption by the EPS is found to follow Langmuir Adsorption Isotherm kinetics at 25°C. Further, by calculating the Langmuir constant the adsorption capabilities of the EPS produced by the Rhodotorula mucilaginosa strain UANL-001L is compared to that of other adsorbents, both, microbially produced and from agroindustrial waste. The total adsorption capacity of the EPS, from the Rhodotorula mucilaginosa strain UANL-001L, was found to be two-fold greater than the best bioadsorbents reported in the literature. Finally, apart from determining which heavy metals stimulated EPS production in the strain, the optimal conditions of pH, heavy metal concentration, and rate of agitation of the growing culture for EPS production, was determined. The EPS reported here has the potential of aiding in the efficient removal of colorants both in water treatment plants and in situ in natural water streams. PMID:26828867

PrEP implementation: moving from trials to policy and practice.

PubMed

Cáceres, Carlos F; O'Reilly, Kevin R; Mayer, Kenneth H; Baggaley, Rachel

2015-01-01

It is increasingly clear that the HIV response will not be sustainable if the number of infections is not significantly reduced. For two decades, research has been ongoing to identify new behavioural and biomedical strategies to prevent HIV infection. In the past few years, the efficacy of several new strategies has been demonstrated, including oral pre-exposure prophylaxis (PrEP; i.e. daily use of tenofovir/emtricitabine). Because several social, political and logistic barriers remain, however, optimal PrEP implementation will require a better dissemination of new evidence in a number of areas and additional implementation research from various disciplinary perspectives (i.e. social science, policy and ethics; health systems; and economics, including cost-effectiveness studies). Discussion of new evidence on those topics, as well as case studies of potential PrEP implementation in diverse environments, can improve the understanding of the role that PrEP may play in addressing the global HIV/AIDS epidemic.In light of these needs, the Network for Multidisciplinary Studies in ARV-based HIV Prevention (NEMUS) and the World Health Organization (WHO) were honoured to co-organize a special issue of JIAS aimed at contributing to a scholarly discussion of current conditions surrounding PrEP implementation, potential impact and efficiency, social science concerns and the study of PrEP implementation in specific country cases. The papers included in this monograph identify and cover many of the main aspects of the complex yet promising discussions around PrEP implementation today. This is a collection of timely contributions from global leaders in HIV research and policy that addresses geographic diversity, uses a trans-disciplinary approach and covers a variety of the complex issues raised by PrEP. As this publication will become accessible to all, we hope that it will remain a valuable resource for policy makers, programme managers, researchers and activists around the world at a moment of a paradigm shift of the global response to HIV.

PrEP implementation: moving from trials to policy and practice

PubMed Central

Cáceres, Carlos F; O'Reilly, Kevin R; Mayer, Kenneth H; Baggaley, Rachel

2015-01-01

Introduction It is increasingly clear that the HIV response will not be sustainable if the number of infections is not significantly reduced. Discussion For two decades, research has been ongoing to identify new behavioural and biomedical strategies to prevent HIV infection. In the past few years, the efficacy of several new strategies has been demonstrated, including oral pre-exposure prophylaxis (PrEP; i.e. daily use of tenofovir/emtricitabine). Because several social, political and logistic barriers remain, however, optimal PrEP implementation will require a better dissemination of new evidence in a number of areas and additional implementation research from various disciplinary perspectives (i.e. social science, policy and ethics; health systems; and economics, including cost-effectiveness studies). Discussion of new evidence on those topics, as well as case studies of potential PrEP implementation in diverse environments, can improve the understanding of the role that PrEP may play in addressing the global HIV/AIDS epidemic. In light of these needs, the Network for Multidisciplinary Studies in ARV-based HIV Prevention (NEMUS) and the World Health Organization (WHO) were honoured to co-organize a special issue of JIAS aimed at contributing to a scholarly discussion of current conditions surrounding PrEP implementation, potential impact and efficiency, social science concerns and the study of PrEP implementation in specific country cases. The papers included in this monograph identify and cover many of the main aspects of the complex yet promising discussions around PrEP implementation today. Conclusions This is a collection of timely contributions from global leaders in HIV research and policy that addresses geographic diversity, uses a trans-disciplinary approach and covers a variety of the complex issues raised by PrEP. As this publication will become accessible to all, we hope that it will remain a valuable resource for policy makers, programme managers, researchers and activists around the world at a moment of a paradigm shift of the global response to HIV. PMID:26198349

Intimacy motivations and pre-exposure prophylaxis (PrEP) adoption intentions among HIV-negative men who have sex with men (MSM) in romantic relationships

PubMed Central

Gamarel, Kristi E.; Golub, Sarit A.

2014-01-01

Background In the United States, men who have sex with men (MSM) in primary partnerships are at elevated risk for human immunodeficiency virus (HIV) infection. Pre-exposure prophylaxis (PrEP), a new biomedical prevention strategy, has potential to reduce HIV transmission. This study examined predictors of PrEP adoption intentions among HIV-negative MSM in primary partnerships. Methods The sample included HIV-negative MSM (n = 164) who participated in an ongoing cross-sectional study with an in-person interview examining PrEP adoption intentions. Results Higher HIV risk perception, intimacy motivations for condomless sex, recent condomless anal sex with outside partners, education, and age were each independently associated with PrEP adoption intentions. In a multivariate model, only age, education, and intimacy motivations for condomless sex were significantly associated with PrEP adoption intentions. Conclusions Intimacy motivations may play a central role in PrEP adoption for MSM couples. Incorporating relationship dynamics into biomedical strategies is a promising avenue for research and intervention. PMID:25124457

Beyond "getting drugs into bodies": social science perspectives on pre-exposure prophylaxis for HIV.

PubMed

Auerbach, Judith D; Hoppe, Trevor A

2015-01-01

Social scientists have much to contribute to the analysis of the real and potential contribution of pre-exposure prophylaxis (PrEP) to HIV prevention around the world. Beyond just a matter of clinical efficacy and getting pills into people's mouths, PrEP raises a number of important social-psychological questions that must be attended to in order to translate biomedical and clinical findings into uptake of PrEP among enough people at risk of HIV infection to produce population-level effectiveness. PrEP is a dynamic phenomenon with "dialectical" attributes that invite both optimism and cynicism as a desirable and effective HIV prevention strategy. PrEP disrupts traditional notions of "safe" and "unsafe" sex; it confers on its users a level of agency and control not generally achieved with condoms; and it affects sexual practices and sexual cultures in meaningful ways. As these dynamics play out in different contexts, and as new modes of PrEP administration emerge, it will be important for social scientists to be engaged in assessing their impact on PrEP implementation and effectiveness.

Exploring brainstem function in multiple sclerosis by combining brainstem reflexes, evoked potentials, clinical and MRI investigations.

PubMed

Magnano, Immacolata; Pes, Giovanni Mario; Pilurzi, Giovanna; Cabboi, Maria Paola; Ginatempo, Francesca; Giaconi, Elena; Tolu, Eusebio; Achene, Antonio; Salis, Antonio; Rothwell, John C; Conti, Maurizio; Deriu, Franca

2014-11-01

To investigate vestibulo-masseteric (VMR), acoustic-masseteric (AMR), vestibulo-collic (VCR) and trigemino-collic (TCR) reflexes in patients with multiple sclerosis (MS); to relate abnormalities of brainstem reflexes (BSRs) to multimodal evoked potentials (EPs), clinical and Magnetic Resonance Imaging (MRI) findings. Click-evoked VMR, AMR and VCR were recorded from active masseter and sternocleidomastoid muscles, respectively; TCR was recorded from active sternocleidomastoid muscles, following electrical stimulation of the infraorbital nerve. EPs and MRI were performed with standard techniques. Frequencies of abnormal BSRs were: VMR 62.1%, AMR 55.1%, VCR 25.9%, TCR 58.6%. Brainstem dysfunction was identified by these tests, combined into a four-reflex battery, in 86.9% of cases, by EPs in 82.7%, MRI in 71.7% and clinical examination in 37.7% of cases. The sensitivity of paired BSRs/EPs (93.3%) was significantly higher than combined MRI/clinical testing (70%) in patients with disease duration ⩽6.4years. BSR alterations significantly correlated with clinical, EP and MRI findings. The four-BSR battery effectively increases the performance of standard EPs in early detection of brainstem impairment, otherwise undetected by clinical examination and neuroimaging. Multiple BSR assessment usefully supplements conventional testing and monitoring of brainstem function in MS, especially in newly diagnosed patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Potential Healthcare Insurance and Provider Barriers to Pre-Exposure Prophylaxis Utilization Among Young Men Who Have Sex with Men.

PubMed

Marks, Sarah J; Merchant, Roland C; Clark, Melissa A; Liu, Tao; Rosenberger, Joshua G; Bauermeister, Jose; Mayer, Kenneth H

2017-11-01

Young adult men-who-have-sex-with-men (YMSM) continue to have among the highest incidence of HIV infection in the United States. Pre-exposure prophylaxis (PrEP) is an effective and safe method of preventing HIV infection; however, despite US Food and Drug Administration approval, utilization remains low, in part, due to structural barriers, particularly access to healthcare. In this study, we used social media to recruit black, Hispanic, and white HIV-uninfected 18- to 24-year-old YMSM. Participants completed an online survey about their sexual behavior, healthcare access, and previous use of PrEP. Of the 2297 YMSM surveyed, only 3.4% had used PrEP. PrEP use was associated with higher levels of education, living alone, older age, higher levels of sexual activity, and greater healthcare access, specifically having healthcare insurance and a clinic or primary care provider (PCP) from whom they received care. Among PrEP nonusers, 65% met at least one of the US Centers for Disease Control and Prevention recommended indications for PrEP use, and of these, 59% had healthcare insurance and received care in a clinic and/or had a PCP. Multi-variable multi-nomial logistic regression modeling identified disparities in access to healthcare by age, race/ethnicity, education, and region. Specifically, older YMSM, blacks and Hispanics, those with fewer years of formal education, and residents of the southern and the western United States were more likely to lack healthcare access. These results demonstrate both potential opportunities and barriers to the scale-up of PrEP among YMSM.

Did Mineral Surface Chemistry and Toxicity Contribute to Evolution of Microbial Extracellular Polymeric Substances?

PubMed Central

Campbell, Jay M.; Zhang, Nianli; Hickey, William J.

2012-01-01

Abstract Modern ecological niches are teeming with an astonishing diversity of microbial life in biofilms closely associated with mineral surfaces, which highlights the remarkable success of microorganisms in conquering the challenges and capitalizing on the benefits presented by the mineral–water interface. Biofilm formation capability likely evolved on early Earth because biofilms provide crucial cell survival functions. The potential toxicity of mineral surfaces toward cells and the complexities of the mineral–water–cell interface in determining the toxicity mechanisms, however, have not been fully appreciated. Here, we report a previously unrecognized role for extracellular polymeric substances (EPS), which form biofilms in shielding cells against the toxicity of mineral surfaces. Using colony plating and LIVE/DEAD staining methods in oxide suspensions versus oxide-free controls, we found greater viability of wild-type, EPS-producing strains of Pseudomonas aeruginosa PAO1 compared to their isogenic knockout mutant with defective biofilm-producing capacity. Oxide toxicity was specific to its surface charge and particle size. High resolution transmission electron microscopy (HRTEM) images and assays for highly reactive oxygen species (hROS) on mineral surfaces suggested that EPS shield via both physical and chemical mechanisms. Intriguingly, qualitative as well as quantitative measures of EPS production showed that toxic minerals induced EPS production in bacteria. By determining the specific toxicity mechanisms, we provide insight into the potential impact of mineral surfaces in promoting increased complexity of cell surfaces, including EPS and biofilm formation, on early Earth. Key Words: Mineral toxicity—Bacteria—EPS evolution—Biofilms—Cytotoxicity—Silica—Anatase—Alumina. Astrobiology 12, 785–798. PMID:22934560

Stimulus and recording variables and their effects on mammalian vestibular evoked potentials

NASA Technical Reports Server (NTRS)

Jones, Sherri M.; Subramanian, Geetha; Avniel, Wilma; Guo, Yuqing; Burkard, Robert F.; Jones, Timothy A.

2002-01-01

Linear vestibular evoked potentials (VsEPs) measure the collective neural activity of the gravity receptor organs in the inner ear that respond to linear acceleration transients. The present study examined the effects of electrode placement, analog filtering, stimulus polarity and stimulus rate on linear VsEP thresholds, latencies and amplitudes recorded from mice. Two electrode-recording montages were evaluated, rostral (forebrain) to 'mastoid' and caudal (cerebellum) to 'mastoid'. VsEP thresholds and peak latencies were identical between the two recording sites; however, peak amplitudes were larger for the caudal recording montage. VsEPs were also affected by filtering. Results suggest optimum high pass filter cutoff at 100-300 Hz, and low pass filter cutoff at 10,000 Hz. To evaluate stimulus rate, linear jerk pulses were presented at 9.2, 16, 25, 40 and 80 Hz. At 80 Hz, mean latencies were longer (0.350-0.450 ms) and mean amplitudes reduced (0.8-1.8 microV) for all response peaks. In 50% of animals, late peaks (P3, N3) disappeared at 80 Hz. The results offer options for VsEP recording protocols. Copyright 2002 Elsevier Science B.V.

Software platform for managing the classification of error- related potentials of observers

NASA Astrophysics Data System (ADS)

Asvestas, P.; Ventouras, E.-C.; Kostopoulos, S.; Sidiropoulos, K.; Korfiatis, V.; Korda, A.; Uzunolglu, A.; Karanasiou, I.; Kalatzis, I.; Matsopoulos, G.

2015-09-01

Human learning is partly based on observation. Electroencephalographic recordings of subjects who perform acts (actors) or observe actors (observers), contain a negative waveform in the Evoked Potentials (EPs) of the actors that commit errors and of observers who observe the error-committing actors. This waveform is called the Error-Related Negativity (ERN). Its detection has applications in the context of Brain-Computer Interfaces. The present work describes a software system developed for managing EPs of observers, with the aim of classifying them into observations of either correct or incorrect actions. It consists of an integrated platform for the storage, management, processing and classification of EPs recorded during error-observation experiments. The system was developed using C# and the following development tools and frameworks: MySQL, .NET Framework, Entity Framework and Emgu CV, for interfacing with the machine learning library of OpenCV. Up to six features can be computed per EP recording per electrode. The user can select among various feature selection algorithms and then proceed to train one of three types of classifiers: Artificial Neural Networks, Support Vector Machines, k-nearest neighbour. Next the classifier can be used for classifying any EP curve that has been inputted to the database.

Function of bacterial cells and their exuded extracellular polymeric substances (EPS) in virus removal by red soils.

PubMed

Zhao, Bingzi; Jiang, Yan; Jin, Yan; Zhang, Jiabao

2014-01-01

The potential influence of autochthonous microorganisms on virus fate in soil is usually determined through extreme conditions of sterilization vs. nonsterilization; however, the relative importance of microbial cells and their exudates remains unclear. In this study, bacterial cells (cell) were harvested, and their exuded extracellular polymeric substances (EPS) were extracted from three strains of bacteria, namely, Gram-negative bacteria Pseudomonas putida and Pseudomonas aeruginosa as well as Gram-positive bacterium Bacillus subtilis. This study aimed to evaluate virus removal in solutions in the presence of cell, EPS, and their combination (cell/EPS), as well as to investigate how their presence affects virus removal efficiencies by four red soils based on batch experiments. Results showed that virus removal percentage in solutions ranged from 11 to 23 in the presence of cells only and from 12 to 15 in the presence of EPS only. The removal percentage in the combined cell/EPS treatment can be estimated by summing the results achieved by the cell and EPS treatments, separately. Meanwhile, cell presence had a negligible effect on virus removal by red soils. EPS and combined cell/EPS significantly reduced virus removal by 20 to 69% and 16 to 50%, respectively, which indicated that EPS served a dominant function in reducing virus removal. This study clearly demonstrated that the prediction of virus removal by red soils must consider the effect of bacteria, especially those producing large quantities of EPS, which can be responsible for the underestimation of viral load in certain studies.

30 CFR 550.219 - What oil and hazardous substance spills information must accompany the EP?

Code of Federal Regulations, 2012 CFR

2012-07-01

...), (d), and (e)). (b) Modeling report. If you model a potential oil or hazardous substance spill in developing your EP, a modeling report or the modeling results, or a reference to such report or results if...

30 CFR 550.219 - What oil and hazardous substance spills information must accompany the EP?

Code of Federal Regulations, 2013 CFR

2013-07-01

...), (d), and (e)). (b) Modeling report. If you model a potential oil or hazardous substance spill in developing your EP, a modeling report or the modeling results, or a reference to such report or results if...

30 CFR 550.219 - What oil and hazardous substance spills information must accompany the EP?

Code of Federal Regulations, 2014 CFR

2014-07-01

...), (d), and (e)). (b) Modeling report. If you model a potential oil or hazardous substance spill in developing your EP, a modeling report or the modeling results, or a reference to such report or results if...

Antiretroviral Therapy and Pre-exposure Prophylaxis: Combined Impact on HIV Transmission and Drug Resistance in South Africa

PubMed Central

Abbas, Ume L.; Glaubius, Robert; Mubayi, Anuj; Hood, Gregory; Mellors, John W.

2013-01-01

Background. The potential impact of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) with overlapping and nonoverlapping antiretrovirals (ARVs) on human immunodeficiency virus (HIV) transmission and drug resistance is unknown. Methods. A detailed mathematical model was used to simulate the epidemiological impact of ART alone, PrEP alone, and combined ART + PrEP in South Africa. Results. ART alone initiated at a CD4 lymphocyte cell count <200 cells/µL (80% coverage and 96% effectiveness) prevents 20% of HIV infections over 10 years but increases drug resistance prevalence to 6.6%. PrEP alone (30% coverage and 75% effectiveness) also prevents 21% of infections but with lower resistance prevalence of 0.5%. The ratio of cumulative infections prevented to prevalent drug-resistant cases after 10 years is 7-fold higher for PrEP than for ART. Combined ART + PrEP with overlapping ARVs prevents 35% of infections but increases resistance prevalence to 8.2%, whereas ART + PrEP with nonoverlapping ARVs prevents slightly more infections (37%) and reduces resistance prevalence to 7.2%. Conclusions. Combined ART + PrEP is likely to prevent more HIV infections than either strategy alone, but with higher prevalence of drug resistance. ART is predicted to contribute more to resistance than is PrEP. Optimizing both ART and PrEP effectiveness and delivery are the keys to preventing HIV transmission and drug resistance. PMID:23570850

Study of interactions between anionic exopolysaccharides produced by newly isolated probiotic bacteria and sodium caseinate.

PubMed

Abid, Yousra; Joulak, Ichrak; Ben Amara, Chedia; Casillo, Angela; Attia, Hamadi; Gharsallaoui, Adem; Azabou, Samia

2018-07-01

The present study aims to evaluate the interactions between four exopolysaccharides (EPS) produced by probiotic bacteria and sodium caseinate (Cas) in order to simulate their behavior in dairy products. Complexation between the produced EPS samples and Cas was investigated as a function of polysaccharide to protein ratio. The highest turbidity and average size of complexes were formed at an EPS/Cas ratio of 3 (corresponding to 1 g/L of EPS and 0.33 g/L of Cas) as a result of the combination of individual complexes to form aggregates. Zeta potential measurements and Cas surface hydrophobicity results suggested that complex formation occurred essentially through electrostatic attractions with a possible contribution of hydrophobic interaction for EPS-GM which was produced by Bacillus tequilensis-GM. Afterwards, the effect of pH on the complexation between biopolymers was studied when EPS and Cas concentrations were maintained constant at 1 and 0.33 g/L, respectively. pH was adjusted to 3.0 and 3.5, respectively. Results showed that the highest amount and sizes of EPS/Cas complexes were formed at pH 3.5 and that EPS-GM enabled to obtain the biggest and highest amount of aggregates. Therefore, the obtained results support the fact that the simultaneous presence of EPS and Cas in dairy products results in complexes formation via electrostatic interactions depending on EPS/Cas ratio and pH of the medium. Copyright © 2018 Elsevier B.V. All rights reserved.

Effects of lubiprostone on pacemaker activity of interstitial cells of cajal from the mouse colon.

PubMed

Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok; Jun, Jae Yeoul

2014-08-01

Lubiprostone is a chloride (Cl(-)) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K(+)] channel blocker) and apamin (a calcium [Ca(2+)]-dependent K(+) channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K(+) channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K(+) channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K(+) channel through a prostanoid EP receptor-independent mechanism.

Effects of Lubiprostone on Pacemaker Activity of Interstitial Cells of Cajal from the Mouse Colon

PubMed Central

Jiao, Han-Yi; Kim, Dong Hyun; Ki, Jung Suk; Ryu, Kwon Ho; Choi, Seok

2014-01-01

Lubiprostone is a chloride (Cl-) channel activator derived from prostaglandin E1 and used for managing constipation. In addition, lubiprostone affects the activity of gastrointestinal smooth muscles. Interstitial cells of Cajal (ICCs) are pacemaker cells that generate slow-wave activity in smooth muscles. We studied the effects of lubiprostone on the pacemaker potentials of colonic ICCs. We used the whole-cell patch-clamp technique to determine the pacemaker activity in cultured colonic ICCs obtained from mice. Lubiprostone hyperpolarized the membrane and inhibited the generation of pacemaker potentials. Prostanoid EP1, EP2, EP3, and EP4 antagonists (SC-19220, PF-04418948, 6-methoxypyridine-2-boronc acid N-phenyldiethanolamine ester, and GW627368, respectively) did not block the response to lubiprostone. L-NG-nitroarginine methyl ester (L-NAME, an inhibitor of nitric oxide synthase) and 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, an inhibitor of guanylate cyclase) did not block the response to lubiprostone. In addition, tetraethylammonium (TEA, a voltage-dependent potassium [K+] channel blocker) and apamin (a calcium [Ca2+]-dependent K+ channel blocker) did not block the response to lubiprostone. However, glibenclamide (an ATP-sensitive K+ channel blocker) blocked the response to lubiprostone. Similar to lubiprostone, pinacidil (an opener of ATP-sensitive K+ channel) hyperpolarized the membrane and inhibited the generation of pacemaker potentials, and these effects were inhibited by glibenclamide. These results suggest that lubiprostone can modulate the pacemaker potentials of colonic ICCs via activation of ATP-sensitive K+ channel through a prostanoid EP receptor-independent mechanism. PMID:25177167

Epithelial-to-mesenchymal transition leads to loss of EpCAM and different physical properties in circulating tumor cells from metastatic breast cancer.

PubMed

Hyun, Kyung-A; Koo, Gi-Bang; Han, Hyunju; Sohn, Joohyuk; Choi, Wonshik; Kim, Seung-Il; Jung, Hyo-Il; Kim, You-Sun

2016-04-26

The dissemination of circulating tumor cells (CTCs) requires the Epithelial-to-Mesenchymal transition (EMT), in which cells lose their epithelial characteristics and acquire more mesenchymal-like phenotypes. Current isolation of CTCs relies on affinity-based approaches reliant on the expression of Epithelial Cell Adhesion Molecule (EpCAM). Here we show EMT-induced breast cancer cells maintained in prolonged mammosphere culture conditions possess increased EMT markers and cancer stem cell markers, as well as reduced cell mass and size by quantitative phase microscopy; however, EpCAM expression is dramatically decreased in these cells. Moreover, CTCs isolated from breast cancer patients using a label-free microfluidic flow fractionation device had differing expression patterns of EpCAM, indicating that affinity approaches reliant on EpCAM expression may underestimate CTC number and potentially miss critical subpopulations. Further characterization of CTCs, including low-EpCAM populations, using this technology may improve detection techniques and cancer diagnosis, ultimately improving cancer treatment.

Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study.

PubMed

Ware, Norma C; Pisarski, Emily E; Haberer, Jessica E; Wyatt, Monique A; Tumwesigye, Elioda; Baeten, Jared M; Celum, Connie L; Bangsberg, David R

2015-05-01

Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.

Scytonemin Plays a Potential Role in Stabilizing the Exopolysaccharidic Matrix in Terrestrial Cyanobacteria.

PubMed

Gao, Xiang

2017-02-01

Cyanobacteria are photosynthetic oxygen-evolving prokaryotes that are distributed in diverse habitats. They synthesize the ultraviolet (UV)-screening pigments, scytonemin (SCY) and mycosporine-like amino acids (MAAs), located in the exopolysaccharide (EPS) matrix. Multiple roles for both pigments have gradually been recognized, such as sunscreen ability, antioxidant activity, and heat dissipation from absorbed UV radiation. In this study, a filamentous terrestrial cyanobacterium Nostoc flagelliforme was used to evaluate the potential stabilizing role of SCY on the EPS matrix. SCY (∼3.7 %) was partially removed from N. flagelliforme filaments by rinsing with 100 % acetone for 5 s. The physiological damage to cells resulting from this treatment, in terms of photosystem II activity parameter Fv/Fm, was repaired after culturing the sample for 40 h. The physiologically recovered sample was further desiccated by natural or rapid drying and then allowed to recovery for 24 h. Compared with the normal sample, a relatively slower Fv/Fm recovery was observed in the SCY-partially removed sample, suggesting that the decreased SCY concentration in the EPS matrix caused cells to suffer further damage upon desiccation. In addition, the SCY-partially removed sample could allow the release of MAAs (∼25 %) from the EPS matrix, while the normal sample did not. Therefore, damage caused by drying of the former resulted from at least the reduction of structural stability of the EPS matrix as well as the loss of partial antioxidant compounds. Considering that an approximately 4 % loss of SCY led to this significant effect, the structurally stabilizing potential of SCY on the EPS matrix is crucial for terrestrial cyanobacteria survival in complex environments.

Potential contribution of microbial communities in technical ceramics for the improvement of rheological properties

NASA Astrophysics Data System (ADS)

Moreira, Bernardino; Miller, Ana Z.; Santos, Ricardo; Monteiro, Sílvia; Dias, Diamantino; Neves, Orquídia; Dionísio, Amélia; Saiz-Jimenez, Cesareo

2014-05-01

Several bacterial and fungal species naturally occurring in ceramic raw materials used in construction, such as Aspergillus, Penicillium and Aureobasidium, are known to produce exopolysaccharides (EPS). These polymers excreted by the cells are of widespread occurrence and may confer unique and potentially interesting properties with potential industrial uses, such as viscosity control, gelation, and flocculation, during ceramic manufacturing. In this study, the microbial communities present in clay raw materials were identified by both cultural methods and DNA-based molecular techniques in order to appraise their potential contribution to enhance the performance of technical ceramics through the use of EPS. Mineralogical identification by X- Ray Diffraction (XRD) and Fourier Transform Infrared (FTIR) spectroscopy of the clay raw materials, as well as characterization of rheological properties of ceramic slips were also performed. Microbial EPS production and its introduction into ceramic slips will be then carried out in order to evaluate their effects on the rheological properties of the ceramic slips, powders and conformed bodies. Some positive aspects related to the use of EPS are: reduction of the environmental impact caused by synthetic organic additives, reduction of production costs, as well as the costs related with operator protection systems, gaseous effluent treatments, complex landfill, among others.

A novel biosorbent for dye removal: extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1.

PubMed

Zhang, Zhiqiang; Xia, Siqing; Wang, Xuejiang; Yang, Aming; Xu, Bin; Chen, Ling; Zhu, Zhiliang; Zhao, Jianfu; Jaffrezic-Renault, Nicole; Leonard, Didier

2009-04-15

This paper deals with the extracellular polymeric substance (EPS) of Proteus mirabilis TJ-1 used as a novel biosorbent to remove dye from aqueous solution in batch systems. As a widely used and hazardous dye, basic blue 54 (BB54) was chosen as the model dye to examine the adsorption performance of the EPS. The effects of pH, initial dye concentration, contact time and temperature on the sorption of BB54 to the EPS were examined. At various initial dye concentrations (50-400 mg/L), the batch sorption equilibrium can be obtained in only 5 min. Kinetic studies suggested that the sorption followed the internal transport mechanism. According to the Langmuir model, the maximum BB54 uptake of 2.005 g/g was obtained. Chemical analysis of the EPS indicated the presence of protein (30.9%, w/w) and acid polysaccharide (63.1%, w/w). Scanning electron microscopy (SEM) images showed that the EPS with a crystal-linear structure was whole enwrapped by adsorbed dye molecules. FTIR spectrum result revealed the presence of adsorbing groups such as carboxyl, hydroxyl and amino groups in the EPS. High-molecular weight of the EPS with more binding-sites and stronger van der Waals forces together with its specific construct leads to the excellent performance of dye adsorption. The EPS shows potential board application as a biosorbent for both environmental protection and dye recovery.

A comparison of temporal Facebook networks of young men who have sex with men (MSM), differentiated by awareness and use of preexposure prophylaxis (PrEP)

PubMed Central

Khanna, Aditya S.; Schumm, Phil; Schneider, John A.

2016-01-01

Young Black men who have sex with men (YBMSM) are the only population in the U.S. who have experienced rising HIV incidence over the past decade. Consistent preexposure prophylaxis (PrEP) use can substantially reduce the risk of HIV acquisition. What differentiates those who become aware of PrEP, and those who do not, remains largely unknown. The social networks of YBMSM can impact their awareness of PrEP; to examine this impact, we used two waves of Facebook data from the “uConnect” study – a longitudinal cohort study of YBMSM in Chicago (n=266). While PrEP awareness increased from 45% at baseline to 75% at follow-up, its use remained low (4% and 6%). There were 88 PrEP-unaware individuals at baseline who became aware (BA) by follow-up, and 56 who remained persistently unaware (PU). While the PUs had a higher median number of total Facebook friends, the BAs had a higher median numbers of friends who participated in uConnect, who were PrEP-aware, and who practiced behaviors previously found to be associated with individual-level awareness of PrEP at baseline. The BAs also had substantially more “influential” friends. These findings demonstrate the potential of social networks in raising PrEP awareness and use among YBMSM. PMID:28003117

Effect of Engineered Nanoparticles on Exopolymeric Substances Release from Marine Phytoplankton

NASA Astrophysics Data System (ADS)

Chiu, Meng-Hsuen; Khan, Zafir A.; Garcia, Santiago G.; Le, Andre D.; Kagiri, Agnes; Ramos, Javier; Tsai, Shih-Ming; Drobenaire, Hunter W.; Santschi, Peter H.; Quigg, Antonietta; Chin, Wei-Chun

2017-12-01

Engineered nanoparticles (ENPs), products from modern nanotechnologies, can potentially impact the marine environment to pose serious threats to marine ecosystems. However, the cellular responses of marine phytoplankton to ENPs are still not well established. Here, we investigate four different diatom species ( Odontella mobiliensis, Skeletonema grethae, Phaeodactylum tricornutum, Thalassiosira pseudonana) and one green algae ( Dunaliella tertiolecta) for their extracellular polymeric substances (EPS) release under model ENP treatments: 25 nm titanium dioxide (TiO2), 10-20 nm silicon dioxide (SiO2), and 15-30 nm cerium dioxide (CeO2). We found SiO2 ENPs can significantly stimulate EPS release from these algae (200-800%), while TiO2 ENP exposure induced the lowest release. Furthermore, the increase of intracellular Ca2+ concentration can be triggered by ENPs, suggesting that the EPS release process is mediated through Ca2+ signal pathways. With better understanding of the cellular mechanism mediated ENP-induced EPS release, potential preventative and safety measures can be developed to mitigate negative impact on the marine ecosystem.

Microbial exopolysaccharide-mediated synthesis and stabilization of metal nanoparticles.

PubMed

Sathiyanarayanan, Ganesan; Dineshkumar, Krishnamoorthy; Yang, Yung-Hun

2017-11-01

Exopolysaccharides (EPSs) are structurally and functionally valuable biopolymer secreted by different prokaryotic and eukaryotic microorganisms in response to biotic/abiotic stresses and to survive in extreme environments. Microbial EPSs are fascinating in various industrial sectors due to their excellent material properties and less toxic, highly biodegradable, and biocompatible nature. Recently, microbial EPSs have been used as a potential template for the rapid synthesis of metallic nanoparticles and EPS-mediated metal reduction processes are emerging as simple, harmless, and environmentally benign green chemistry approaches. EPS-mediated synthesis of metal nanoparticles is a distinctive metabolism-independent bio-reduction process due to the formation of interfaces between metal cations and the polyanionic functional groups (i.e. hydroxyl, carboxyl and amino groups) of the EPS. In addition, the range of physicochemical features which facilitates the EPS as an efficient stabilizing or capping agents to protect the primary structure of the metal nanoparticles with an encapsulation film in order to separate the nanoparticle core from the mixture of composites. The EPS-capping also enables the further modification of metal nanoparticles with expected material properties for multifarious applications. The present review discusses the microbial EPS-mediated green synthesis/stabilization of metal nanoparticles, possible mechanisms involved in EPS-mediated metal reduction, and application prospects of EPS-based metal nanoparticles.

The potential impact of pre-exposure prophylaxis for HIV prevention among men who have sex with men and transwomen in Lima, Peru: a mathematical modelling study.

PubMed

Gomez, Gabriela B; Borquez, Annick; Caceres, Carlos F; Segura, Eddy R; Grant, Robert M; Garnett, Geoff P; Hallett, Timothy B

2012-01-01

HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a "conditional efficacy" parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036-US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary.

The Potential Impact of Pre-Exposure Prophylaxis for HIV Prevention among Men Who Have Sex with Men and Transwomen in Lima, Peru: A Mathematical Modelling Study

PubMed Central

Caceres, Carlos F.; Segura, Eddy R.; Grant, Robert M.; Garnett, Geoff P.; Hallett, Timothy B.

2012-01-01

Background HIV pre-exposure prophylaxis (PrEP), the use of antiretroviral drugs by uninfected individuals to prevent HIV infection, has demonstrated effectiveness in preventing acquisition in a high-risk population of men who have sex with men (MSM). Consequently, there is a need to understand if and how PrEP can be used cost-effectively to prevent HIV infection in such populations. Methods and Findings We developed a mathematical model representing the HIV epidemic among MSM and transwomen (male-to-female transgender individuals) in Lima, Peru, as a test case. PrEP effectiveness in the model is assumed to result from the combination of a “conditional efficacy” parameter and an adherence parameter. Annual operating costs from a health provider perspective were based on the US Centers for Disease Control and Prevention interim guidelines for PrEP use. The model was used to investigate the population-level impact, cost, and cost-effectiveness of PrEP under a range of implementation scenarios. The epidemiological impact of PrEP is largely driven by programme characteristics. For a modest PrEP coverage of 5%, over 8% of infections could be averted in a programme prioritising those at higher risk and attaining the adherence levels of the Pre-Exposure Prophylaxis Initiative study. Across all scenarios, the highest estimated cost per disability-adjusted life year averted (uniform strategy for a coverage level of 20%, US$1,036–US$4,254) is below the World Health Organization recommended threshold for cost-effective interventions, while only certain optimistic scenarios (low coverage of 5% and some or high prioritisation) are likely to be cost-effective using the World Bank threshold. The impact of PrEP is reduced if those on PrEP decrease condom use, but only extreme behaviour changes among non-adherers (over 80% reduction in condom use) and a low PrEP conditional efficacy (40%) would adversely impact the epidemic. However, PrEP will not arrest HIV transmission in isolation because of its incomplete effectiveness and dependence on adherence, and because the high cost of programmes limits the coverage levels that could potentially be attained. Conclusions A strategic PrEP intervention could be a cost-effective addition to existing HIV prevention strategies for MSM populations. However, despite being cost-effective, a substantial expenditure would be required to generate significant reductions in incidence. Please see later in the article for the Editors' Summary PMID:23055836

Awareness and attitudes of pre-exposure prophylaxis for HIV prevention among physicians in Guatemala: Implications for country-wide implementation.

PubMed

Ross, Ian; Mejia, Carlos; Melendez, Johanna; Chan, Philip A; Nunn, Amy C; Powderly, William; Goodenberger, Katherine; Liu, Jingxia; Mayer, Kenneth H; Patel, Rupa R

2017-01-01

HIV continues to be a major health concern with approximately 2.1 million new infections occurring worldwide in 2015. In Central America, Guatemala had the highest incident number of HIV infections (3,700) in 2015. Antiretroviral pre-exposure prophylaxis (PrEP) was recently recommended by the World Health Organization (WHO) as an efficacious intervention to prevent HIV transmission. PrEP implementation efforts are underway in Guatemala and success will require providers that are knowledgeable and willing to prescribe PrEP. We sought to explore current PrEP awareness and prescribing attitudes among Guatemalan physicians in order to inform future PrEP implementation efforts. We conducted a cross-sectional survey of adult internal medicine physicians at the main teaching hospital in Guatemala City in March 2015. The survey included demographics, medical specialty, years of HIV patient care, PrEP awareness, willingness to prescribe PrEP, previous experience with post-exposure prophylaxis, and concerns about PrEP. The primary outcome was willingness to prescribe PrEP, which was assessed using a 5-point Likert scale for different at-risk population scenarios. Univariate and multivariate logistic regression was performed to identify predictors for willingness to prescribe PrEP. Eighty-seven physicians completed the survey; 66% were male, 64% were internal medicine residency trainees, and 10% were infectious disease (ID) specialists. Sixty-nine percent of physicians were PrEP aware, of which 9% had previously prescribed PrEP. Most (87%) of respondents were willing to prescribe PrEP to men who have sex with men (MSM), sex workers, injection drug users, or HIV-uninfected persons having known HIV-positive sexual partners. Concerns regarding PrEP included development of resistance (92%), risk compensation (90%), and cost (64%). Univariate logistic regression showed that younger age, being a resident trainee, and being a non-ID specialist were significant predictors for willingness to prescribe PrEP. In multivariate logistic regression, being a non-ID specialist was a significant predictor. Guatemalan physicians at an urban public hospital were PrEP aware and willing to prescribe, but few have actually done so yet. Future education programs should address the concerns identified, including the low potential for the development of antiretroviral resistance. These findings can aid PrEP implementation efforts in Guatemala.

Chemical and rheological properties of an extracellular polysaccharide produced by the cyanobacterium Anabaena sp. ATCC 33047.

PubMed

Moreno, J; Vargas, M A; Madiedo, J M; Muñoz, J; Rivas, J; Guerrero, M G

2000-02-05

The cyanobacterium (blue-green alga) Anabaena sp. ATCC 33047 produces an exopolysaccharide (EPS) during the stationary growth phase in batch culture. Chemical analysis of EPS revealed a heteropolysaccharidic nature, with xylose, glucose, galactose, and mannose the main neutral sugars found. The infrared (IR) spectrum of EPS showed absorption bands of carboxylate groups. The average molecular mass of the polymer was 1.35 MDa. Aqueous dispersions at EPS concentrations ranging from 0.2% to 0.6% (w/w) showed marked shear-thinning properties (power-law behavior). Linear dynamic viscoelastic properties showed that the elastic component was always higher than the viscous component. Viscous and viscoelastic properties demonstrated the absence of conformational changes within the concentration range studied. Stress-growth experiments revealed that 0.4% and 0.6% (w/w) EPS dispersions showed thixotropic properties. A detailed comparison of the linear dynamic viscoelasticity, transient flow, and decreasing shear rate flow curve properties was made for 0.4% (w/w) dispersions of xanthan gum (XG), Alkemir 110 (AG), and EPS. Viscoelastic spectra demonstrated that the EPS dispersion turned out to be more "fluidlike" than the AG and XG dispersions. The flow indexes indicated that the EPS dispersion was less shear-sensitive than that of XG, showing essentially the same viscosity, that is, >50 s(-1). The fact that viscosities of EPS and AG dispersions were not substantially different within the shear-rate range covered must be emphasized, in relation to EPS potential applications. The rheological behavior of EPS dispersions indicates the formation of an intermediate structure between a random-coil polysaccharide and a weak gel. Copyright 2000 John Wiley & Sons, Inc.

Sry HMG Box Protein 9-positive (Sox9+) Epithelial Cell Adhesion Molecule-negative (EpCAM−) Biphenotypic Cells Derived from Hepatocytes Are Involved in Mouse Liver Regeneration*

PubMed Central

Tanimizu, Naoki; Nishikawa, Yuji; Ichinohe, Norihisa; Akiyama, Haruhiko; Mitaka, Toshihiro

2014-01-01

It has been shown that mature hepatocytes compensate tissue damages not only by proliferation and/or hypertrophy but also by conversion into cholangiocyte-like cells. We found that Sry HMG box protein 9-positive (Sox9+) epithelial cell adhesion molecule-negative (EpCAM−) hepatocyte nuclear factor 4α-positive (HNF4α+) biphenotypic cells showing hepatocytic morphology appeared near EpCAM+ ductular structures in the livers of mice fed 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet. When Mx1-Cre:ROSA mice, which were injected with poly(I:C) to label mature hepatocytes, were fed with the DDC diet, we found LacZ+Sox9+ cells near ductular structures. Although Sox9+EpCAM− cells adjacent to expanding ducts likely further converted into ductular cells, the incidence was rare. To know the cellular characteristics of Sox9+EpCAM− cells, we isolated them as GFP+EpCAM− cells from DDC-injured livers of Sox9-EGFP mice. Sox9+EpCAM− cells proliferated and could differentiate to functional hepatocytes in vitro. In addition, Sox9+EpCAM− cells formed cysts with a small central lumen in collagen gels containing Matrigel® without expressing EpCAM. These results suggest that Sox9+EpCAM− cells maintaining biphenotypic status can establish cholangiocyte-type polarity. Interestingly, we found that some of the Sox9+ cells surrounded luminal spaces in DDC-injured liver while they expressed HNF4α. Taken together, we consider that in addition to converting to cholangiocyte-like cells, Sox9+EpCAM− cells provide luminal space near expanded ductular structures to prevent deterioration of the injuries and potentially supply new hepatocytes to repair damaged tissues. PMID:24482234

Acceptability of microbicidal vaginal rings and oral pre-exposure prophylaxis for HIV prevention among female sex workers in a high-prevalence US city.

PubMed

Peitzmeier, Sarah M; Tomko, Catherine; Wingo, Erin; Sawyer, Anne; Sherman, Susan G; Glass, Nancy; Beyrer, Chris; Decker, Michele R

2017-11-01

Biomedical HIV prevention tools including oral pre-exposure prophylaxis (PrEP) and vaginal microbicidal rings hold unique value for high-risk women who may have limited capacity for condom negotiation, including the key populations of sex workers and drug users. Commercial sex is a PrEP indicator in CDC guidelines, yet little is known about female sex workers' (FSWs) knowledge of and attitudes toward PrEP or the recently developed monthly vaginal microbicide rings. We describe knowledge and attitudes toward PrEP and microbicide rings in a sample of 60 mostly drug-using FSWs in Baltimore, Maryland, a high HIV-prevalence US city. Just 33% had heard of PrEP, but 65% were interested in taking daily oral PrEP and 76% were interested in a microbicide vaginal ring; 87% were interested in at least one of the two methods. Results suggest method mix will be important as biomedical tools for HIV prophylaxis are implemented and scaled up in this population, as 12% were interested in PrEP but not vaginal rings, while 19% were interested in vaginal rings but not in PrEP. Self-efficacy for daily oral adherence was high (79%) and 78% were interested in using PrEP even if condoms were still necessary. Women who had experienced recent client-perpetrated violence were significantly more interested in PrEP (86% vs 53%, p = 0.009) and microbicidal rings (91% vs 65%, p = 0.028) than women who had not recently experienced violence. No differences were observed by demographics nor HIV risk behaviors, suggesting broad potential interest in daily PrEP and monthly-use vaginal microbicides in this high-risk population.

Does Pre-exposure prophylaxis (PrEP) for HIV prevention in men who have sex with men (MSM) change risk behavior? A systematic review.

PubMed

Freeborn, Kellie; Portillo, Carmen J

2017-08-03

Pre-exposure prophylaxis (PrEP) for HIV has been available since 2012. Even so, PrEP has not been widely accepted among healthcare providers and MSM some of whom are convinced that PrEP decreases condom use, and increases sexually transmitted infections (STIs). A systematic review of the state of the evidence regarding the association of PrEP with condom use, STI incidence and change in sexual risk behaviors in MSM. A structured search of databases resulted in 142 potential citations, but only ten publications met inclusion criteria and underwent data abstraction and critical appraisal. An adapted Cochrane Collaboration domain based assessment tool was used to critically appraise the methodological components of each quantitative study, and the Mixed Methods Appraisal Tool (MMAT) was used to critically appraise qualitative and mixed-methods studies. Condom use in MSM utilizing PrEP is influenced by multiple factors. Studies indicate rates of STIs in treatment and placebo groups were high. PrEP did not significantly change STI rates between baseline and follow-up. Reporting of sexual risk improved when questionnaires were completed in private by clients. Our review found that PrEP may provide an opportunity for MSM to access sexual health care, testing, treatment and counselling services. We did not find any conclusive evidence that PrEP users increase sexual risk behaviors. The perception among healthcare providers that PrEP leads to increased sexual risk behaviors has yet to be confirmed. In order to provide effective sexual health services, clinicians need to be knowledgeable about PrEP as an HIV prevention tool. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

HIV pre-exposure prophylaxis: Exploring the potential for expanding the role of pharmacists in public health.

PubMed

Okoro, Olihe; Hillman, Lisa

2018-05-19

The study objectives were to a) assess knowledge and experience; b) describe perceptions and attitudes; and c) identify training needs of community-based pharmacists regarding HIV pre-exposure prophylaxis (PrEP). This was a cross-sectional survey study. The survey was administered online to pharmacists practicing in a community setting in the state of Minnesota. Measures included knowledge of and experience with HIV PrEP, perceptions and attitudes towards pharmacists' involvement, and HIV PrEP-specific training needs for pharmacists. With a survey response rate of approximately 13% (n = 347), most respondents (76.4%) agreed that HIV PrEP can be beneficial in high-risk populations. Forty-six percent of respondents were not aware of U.S. Food and Drug Administration approval of emtricitabine and tenofovir disoproxil fumarate for PrEP. Most respondents (71.1%) were "not at all familiar" with Centers for Disease Control and Prevention guidelines for PrEP. Twenty-one percent of respondents had sufficient knowledge to counsel patients on PrEP. Experience with counseling on PrEP (21.8%), having dispensed PrEP in the last 2 years (33.1%), fewer years in practice (≤10 years), location of practice site (urban or suburban), and having received HIV continuing education in the last 2 years (33.0%) were associated with more knowledge of HIV PrEP. Top concerns with counseling were knowledge about the medication and behavior modification. The most frequently indicated primary concerns with implementing PrEP initiatives were identifying appropriate candidates and patient adherence. As pharmacists' roles continue to expand, relevant content in pharmacy education and requisite training (including continuing education) are critical to addressing knowledge gaps and competencies that will enable pharmacists engage more effectively in public health efforts such as HIV prevention. Published by Elsevier Inc.

Potentiation of epidural lidocaine by co-administering tramadol by either intramuscular or epidural route in cats

PubMed Central

Hermeto, Larissa C.; DeRossi, Rafael; Marques, Beatriz C.; Jardim, Paulo H.A.

2015-01-01

This study investigated the analgesic and systemic effects of intramuscular (IM) versus epidural (EP) administration of tramadol as an adjunct to EP injection of lidocaine in cats. Six healthy, domestic, shorthair female cats underwent general anesthesia. A prospective, randomized, crossover trial was then conducted with each cat receiving the following 3 treatments: EP injection of 2% lidocaine [LEP; 3.0 mg/kg body weight (BW)]; EP injection of a combination of lidocaine and 5% tramadol (LTEP; 3.0 and 2.0 mg/kg BW, respectively); or EP injection of lidocaine and IM injection of tramadol (LEPTIM; 3.0 and 2.0 mg/kg BW, respectively). Systemic effects, spread and duration of analgesia, behavior, and motor blockade were determined before treatment and at predetermined intervals afterwards. The duration of analgesia was 120 ± 31 min for LTEP, 71 ± 17 min for LEPTIM, and 53 ± 6 min for LEP (P < 0.05; mean ± SD). The cranial spread of analgesia obtained with LTEP was similar to that with LEP or LEPTIM, extending to dermatomic region T13–L1. Complete motor blockade was similar for the 3 treatments. It was concluded that tramadol produces similar side effects in cats after either EP or IM administration. Our findings indicate that EP and IM tramadol (2 mg/kg BW) with EP lidocaine produce satisfactory analgesia in cats. As an adjunct to lidocaine, EP tramadol provides a longer duration of analgesia than IM administration. The adverse effects produced by EP and IM administration of tramadol were not different. Further studies are needed to determine whether EP administration of tramadol could play a role in managing postoperative pain in cats when co-administered with lidocaine after painful surgical procedures. PMID:26130854

Antiviral activity of the exopolysaccharide produced by Serratia sp. strain Gsm01 against Cucumber mosaic virus.

PubMed

Ipper, Nagesh S; Cho, Saeyoull; Lee, Seon Hwa; Cho, Jun Mo; Hur, Jang Hyun; Lim, Chun Keun

2008-01-01

The potential of the exopolysaccharide (EPS) from a Serratia sp. strain Gsm01 as an antiviral agent against a yellow strain of Cucumber mosaic virus (CMV-Y) was evaluated in tobacco plants (Nicotiana tabacum cv. Xanthi-nc). The spray treatment of plants using an EPS preparation, 72 before CMV-Y inoculation, protected them against symptom appearance. Fifteen days after challenge inoculation with CMVY, 33.33% of plants showed mosaic symptoms in EPS-treated plants compared with 100% in the control plants. The EPS-treated plants, which showed mosaic symptoms, appeared three days later than the controls. The enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase polymerase chain reaction (RT-PCR) analyses of the leaves of the protected plants revealed that the EPS treatment affected virus accumulation in those plants. Analysis of phenylalanine ammonia lyase, peroxidase, and phenols in protected plants revealed enhanced accumulation of these substances. The pathogenesis-related (PR) genes expression represented by PR-1b was increased in EPS-treated plants. This is the first report of a systemic induction of protection triggered by EPS produced by Serratia sp. against CMV-Y.

Use of Pre-exposure Prophylaxis (PrEP) in Young Men Who Have Sex with Men is Associated with Race, Sexual Risk Behavior and Peer Network Size.

PubMed

Kuhns, Lisa M; Hotton, Anna L; Schneider, John; Garofalo, Robert; Fujimoto, Kayo

2017-05-01

Pre-exposure prophylaxis (PrEP) is efficacious to prevent HIV infection, however, uptake among young men who have sex with men (YMSM) is relatively low. The purpose of this study was to describe PrEP use and related factors in a representative sample of YMSM in two cities, Chicago and Houston. YMSM, ages 16-29, were recruited via respondent-driven sampling (RDS) from 2014 to 2016. Correlates of PrEP uptake were assessed in weighted multivariable logistic regression models. A total of 12.2% of participants (of 394) reported ever taking PrEP; Black YMSM had the lowest rates of uptake (4.7%) and Whites the highest (29.5%). In a multivariable regression model, having an HIV positive sex partner, reporting recent group sex, peer network size, and city (Chicago) were significantly and positively associated with use of PrEP, while Black race was negatively associated with it. Given evidence of racial/ethnic disparities in PrEP uptake in this study, further research is needed to identify potential mechanisms of action and points of intervention.

Long acting systemic HIV pre-exposure prophylaxis: an examination of the field.

PubMed

Lykins, William R; Luecke, Ellen; Johengen, Daniel; van der Straten, Ariane; Desai, Tejal A

2017-12-01

Oral pre-exposure prophylaxis for the prevention of HIV-1 transmission (HIV PrEP) has been widely successful as demonstrated by a number of clinical trials. However, studies have also demonstrated the need for patients to tightly adhere to oral dosing regimens in order to maintain protective plasma and tissue concentrations. This is especially true for women, who experience less forgiveness from dose skipping than men in clinical trials of HIV PrEP. There is increasing interest in long-acting (LA), user-independent forms of HIV PrEP that could overcome this adherence challenge. These technologies have taken multiple forms including LA injectables and implantables. Phase III efficacy trials are ongoing for a LA injectable candidate for HIV PrEP. This review will focus on the design considerations for both LA injectable and implantable platforms for HIV PrEP. Additionally, we have summarized the existing LA technologies currently in clinical and pre-clinical studies for HIV PrEP as well as other technologies that have been applied to HIV PrEP and contraceptives. Our discussion will focus on the potential application of these technologies in low resource areas, and their use in global women's health.

EpCAM-Independent Enrichment of Circulating Tumor Cells in Metastatic Breast Cancer.

PubMed

Schneck, Helen; Gierke, Berthold; Uppenkamp, Frauke; Behrens, Bianca; Niederacher, Dieter; Stoecklein, Nikolas H; Templin, Markus F; Pawlak, Michael; Fehm, Tanja; Neubauer, Hans

2015-01-01

Circulating tumor cells (CTCs) are the potential precursors of metastatic disease. Most assays established for the enumeration of CTCs so far-including the gold standard CellSearch-rely on the expression of the cell surface marker epithelial cell adhesion molecule (EpCAM). But, these approaches may not detect CTCs that express no/low levels of EpCAM, e.g. by undergoing epithelial-to-mesenchymal transition (EMT). Here we present an enrichment strategy combining different antibodies specific for surface proteins and extracellular matrix (ECM) components to capture an EpCAMlow/neg cell line and EpCAMneg CTCs from blood samples of breast cancer patients depleted for EpCAM-positive cells. The expression of respective proteins (Trop2, CD49f, c-Met, CK8, CD44, ADAM8, CD146, TEM8, CD47) was verified by immunofluorescence on EpCAMpos (e.g. MCF7, SKBR3) and EpCAMlow/neg (MDA-MB-231) breast cancer cell lines. To test antibodies and ECM proteins (e.g. hyaluronic acid (HA), collagen I, laminin) for capturing EpCAMneg cells, the capture molecules were first spotted in a single- and multi-array format onto aldehyde-coated glass slides. Tumor cell adhesion of EpCAMpos/neg cell lines was then determined and visualized by Coomassie/MitoTracker staining. In consequence, marginal binding of EpCAMlow/neg MDA-MB-231 cells to EpCAM-antibodies could be observed. However, efficient adhesion/capturing of EpCAMlow/neg cells could be achieved via HA and immobilized antibodies against CD49f and Trop2. Optimal capture conditions were then applied to immunomagnetic beads to detect EpCAMneg CTCs from clinical samples. Captured CTCs were verified/quantified by immunofluorescence staining for anti-pan-Cytokeratin (CK)-FITC/anti-CD45 AF647/DAPI. In total, in 20 out of 29 EpCAM-depleted fractions (69%) from 25 metastatic breast cancer patients additional EpCAMneg CTCs could be identified [range of 1-24 CTCs per sample] applying Trop2, CD49f, c-Met, CK8 and/or HA magnetic enrichment. EpCAMneg dual-positive (CKpos/CD45pos) cells could be traced in 28 out of 29 samples [range 1-480]. By single-cell array-based comparative genomic hybridization we were able to demonstrate the malignant nature of one EpCAMneg subpopulation. In conclusion, we established a novel enhanced CTC enrichment strategy to capture EpCAMneg CTCs from clinical blood samples by targeting various cell surface antigens with antibody mixtures and ECM components.

Production of Exopolysaccharide by Lactobacillus rhamnosus R and Analysis of Its Enzymatic Degradation during Prolonged Fermentation

PubMed Central

Pham, P. L.; Dupont, I.; Roy, D.; Lapointe, G.; Cerning, J.

2000-01-01

The potential of Lactobacillus rhamnosus R for producing exopolysaccharide (EPS) when grown on basal minimum medium supplemented with glucose or lactose was investigated. EPS production by L. rhamnosus R is partially growth associated and about 500 mg of EPS per liter was synthesized with both sugars. The product yield coefficient (YEPS/S) was 3.15 (0.0315 g of EPS [g of lactose]−1) and 2.88 (0.0288 g of EPS [g of glucose]−1). It was clearly shown that the amount of EPS produced declined upon prolonged fermentation. Degradation of EPS in fermentation processes was also assessed by measuring its molecular weights and viscosities. As these reductions might have a negative effect on the yield and viscosifying properties of EPS, it was essential to examine possible causes related to this breakdown. The decrease in viscosities and molecular weights of EPS withdrawn at different cultivation times permitted us to suspect the presence of a depolymerizing enzyme in the fermentation medium. Our study on enzymatic production profiles showed a large spectrum of glycohydrolases (α-d-glucosidase, β-d-glucosidase, α-d-galactosidase, β-d-galactosidase, β-d-glucuronidase, and some traces of α-l-rhamnosidase). These enzymes were localized, two of them (α-d-glucosidase and β-d-glucuronidase) were partially purified and characterized. When incubated with EPS, these enzymes were capable of lowering the viscosity of the polymer as well as liberating some reducing sugars. Upon prolonged incubation (27 h), the loss of viscosity was increased up to 33%. PMID:10831403

Evaluation of the Expression Profile of Extrapyramidal Symptoms Due to Antipsychotics by Data Mining of Japanese Adverse Drug Event Report (JADER) Database.

PubMed

Kose, Eiji; Uno, Kana; Hayashi, Hiroyuki

2017-01-01

 Typical antipsychotics are easily expressed as adverse events such as extrapyramidal symptom (EPS). On the other hand, incidence of adverse events due to atypical antipsychotics is low. Therefore, currently, atypical antipsychotics are widely used to treat schizophrenia. However, it has been reported that there is no difference in the frequency of EPS in atypical and typical antipsychotics. This study aimed to evaluate the expression profile of EPS in atypical and typical antipsychotics treatment using the Japanese Adverse Drug Event Report (JADER) database. We analyzed reports of EPS in the JADER database and calculated the reporting odds ratio (ROR) of antipsychotics potentially associated with EPS. We applied the Weibull shape parameter to time-to-event data in the JADER database. Consequently, there was little information to distinguish between the ROR of atypical and typical antipsychotics. A significant difference related to the time of onset of EPS in both antipsychotics was not recognized. However, when comparing each drug, Paliperidone, Perospirone, Blonanserin, and Aripiprazole were relatively developed as EPS in the early stage. On the other hand, Risperidone, Clozapine, Olanzapine, and Quetiapine were developed as EPS not only at an early stage but also after long-term use. In addition, this finding was suggested from the result of the cumulative incidence of EPS in each drug and of the time-to-onset analysis using Weibull distribution. These findings may contribute to future clinical practice because we revealed the expression profile of EPS in treatment with atypical and typical antipsychotics.

A Novel Exopolysaccharide with Metal Adsorption Capacity Produced by a Marine Bacterium Alteromonas sp. JL2810

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

Zhang, Zilian; Cai, Ruanhong; Zhang, Wenhui

Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of EPS produced by a marine bacterium, Alteromonas sp. JL2810, was characterized, and the biosorption of the EPS for heavy metals Cu 2+, Ni 2+, and Cr 6+ was also investigated. Nuclear magnetic resonance (NMR) analysis indicated that the JL2810 EPS have a novel structure consisting of the repeating unit of [-3)-α-Rhap-(1→3)-α-Manp-(1→4)-α-3OAc-GalAp-(1→]. The biosorption of the EPS formore » heavy metals was affected by a medium pH; the maximum biosorption capacities for Cu 2+ and Ni 2+ were 140.8-8.2 mg/g and 226.3-3.3 mg/g at pH 5.0; however, for Cr 6+ it was 215.2-5.1 mg/g at pH 5.5. Infrared spectrometry analysis demonstrated that the groups of O-H, C=O, and C-O-C were the main function groups for the adsorption of JL2810 EPS with the heavy metals. The adsorption equilibrium of JL2810 EPS for Ni 2+ was further analyzed, and the equilibrium data could be better represented by the Langmuir isotherm model. The novel EPS could be potentially used in industrial applications as a novel bio-resource for the removal of heavy metals.« less

A Novel Exopolysaccharide with Metal Adsorption Capacity Produced by a Marine Bacterium Alteromonas sp. JL2810

DOE PAGES

Zhang, Zilian; Cai, Ruanhong; Zhang, Wenhui; ...

2017-06-12

Most marine bacteria can produce exopolysaccharides (EPS). However, very few structures of EPS produced by marine bacteria have been determined. The characterization of EPS structure is important for the elucidation of their biological functions and ecological roles. In this study, the structure of EPS produced by a marine bacterium, Alteromonas sp. JL2810, was characterized, and the biosorption of the EPS for heavy metals Cu 2+, Ni 2+, and Cr 6+ was also investigated. Nuclear magnetic resonance (NMR) analysis indicated that the JL2810 EPS have a novel structure consisting of the repeating unit of [-3)-α-Rhap-(1→3)-α-Manp-(1→4)-α-3OAc-GalAp-(1→]. The biosorption of the EPS formore » heavy metals was affected by a medium pH; the maximum biosorption capacities for Cu 2+ and Ni 2+ were 140.8-8.2 mg/g and 226.3-3.3 mg/g at pH 5.0; however, for Cr 6+ it was 215.2-5.1 mg/g at pH 5.5. Infrared spectrometry analysis demonstrated that the groups of O-H, C=O, and C-O-C were the main function groups for the adsorption of JL2810 EPS with the heavy metals. The adsorption equilibrium of JL2810 EPS for Ni 2+ was further analyzed, and the equilibrium data could be better represented by the Langmuir isotherm model. The novel EPS could be potentially used in industrial applications as a novel bio-resource for the removal of heavy metals.« less

Limited SHIV env diversification in macaques failing oral antiretroviral pre-exposure prophylaxis.

PubMed

Zheng, Qi; Ruone, Susan; Switzer, William M; Heneine, Walid; García-Lerma, J Gerardo

2012-05-09

Pre-exposure prophylaxis (PrEP) with daily Truvada [a combination of emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF)] is a novel HIV prevention strategy recently found to prevent HIV transmission among men who have sex with men and heterosexual couples. Acute infection in adherent persons who fail PrEP will inevitably occur under concurrent antiretroviral therapy, thus raising questions regarding the potential impact of PrEP on early viral dynamics. We investigated viral evolution dynamics in a macaque model of PrEP consisting of repeated rectal exposures to SHIV162P3 in the presence of PrEP. Four macaques were infected during daily or intermittent PrEP with FTC or FTC/TDF, and five were untreated controls. SHIV env sequence evolution was monitored by single genome amplification with phylogenetic and sequence analysis. Mean nucleotide divergence from transmitted founder viruses calculated 17 weeks (range = 12-20) post peak viremia was significantly lower in PrEP failures than in control animals (7.2 × 10-3 compared to 1.6 × 10-2 nucleotide substitutions per site per year, respectively, p < 0.0001). Mean virus diversity was also lower in PrEP failures after 17 weeks (0.13% vs. 0.53% in controls, p < 0.0001). Our results in a macaque model of acute HIV infection suggest that infection during PrEP limits early virus evolution likely because of a direct antiviral effect of PrEP and/or reduced target cell availability. Reduced virus diversification during early infection might enhance immune control by slowing the selection of escape mutants.

Current understanding of auditory neuropathy.

PubMed

Boo, Nem-Yun

2008-12-01

Auditory neuropathy is defined by the presence of normal evoked otoacoustic emissions (OAE) and absent or abnormal auditory brainstem responses (ABR). The sites of lesion could be at the cochlear inner hair cells, spiral ganglion cells of the cochlea, synapse between the inner hair cells and auditory nerve, or the auditory nerve itself. Genetic, infectious or neonatal/perinatal insults are the 3 most commonly identified underlying causes. Children usually present with delay in speech and language development while adult patients present with hearing loss and disproportionately poor speech discrimination for the degree of hearing loss. Although cochlear implant is the treatment of choice, current evidence show that it benefits only those patients with endocochlear lesions, but not those with cochlear nerve deficiency or central nervous system disorders. As auditory neuropathy is a disorder with potential long-term impact on a child's development, early hearing screen using both OAE and ABR should be carried out on all newborns and infants to allow early detection and intervention.

Amino-oxyacetic acid as a palliative in tinnitus.

PubMed

Reed, H T; Meltzer, J; Crews, P; Norris, C H; Quine, D B; Guth, P S

1985-12-01

Amino-oxyacetic acid, previously shown to cause a reversible loss of hearing sensitivity and a reduction in endocochlear potential, was tried as a palliative in human tinnitus. Because the drug seemed to have a cochlear site of action, patients were selected for the study if their audiograms were indicative of cochlear lesions and if there was a reduction in tinnitus following intravenous lidocaine (lidocaine positive). Ten such patients received either 50 or 75 mg of amino-oxyacetic acid four times a day orally for one week or placebo administered in a random, crossover, double-blind design. Of these ten, three reported subjective lessening of tinnitus. One of those three and two others not reporting subjective lessening of tinnitus showed a substantial improvement in speech discrimination scores while receiving amino-oxyacetic acid but not placebo. One additional patient who did not receive lidocaine also reported a subjective lessening of tinnitus. Four patients who were lidocaine negative showed neither subjective nor objective improvement in tinnitus after treatment with amino-oxyacetic acid.

Solitomab, an epithelial cell adhesion molecule/CD3 bispecific antibody (BiTE), is highly active against primary chemotherapy-resistant ovarian cancer cell lines in vitro and fresh tumor cells ex vivo.

PubMed

English, Diana P; Bellone, Stefania; Schwab, Carlton L; Roque, Dana M; Lopez, Salvatore; Bortolomai, Ileana; Cocco, Emiliano; Bonazzoli, Elena; Chatterjee, Sudeshna; Ratner, Elena; Silasi, Dan-Arin; Azodi, Masoud; Schwartz, Peter E; Rutherford, Thomas J; Santin, Alessandro D

2015-02-01

Solitomab is a novel, bispecific, single-chain antibody that targets epithelial cell adhesion molecule (EpCAM) on tumor cells and also contains a cluster of differentiation 3 (CD3) (T-cell coreceptor) binding region. The authors evaluated the in vitro activity of solitomab against primary chemotherapy-resistant epithelial ovarian carcinoma cell lines as well as malignant cells in ascites. EpCAM expression was evaluated by flow cytometry in 5 primary ovarian cancer cell lines and in 42 fresh ovarian tumor cell cultures in ascites from patients with mainly advanced or recurrent, chemotherapy-resistant disease. The potential activity of solitomab against EpCAM-positive tumor cells was evaluated by flow cytometry, proliferation, and 4-hour chromium-release, cell-mediated cytotoxicity assays. EpCAM expression was detected by flow cytometry in approximately 80% of the fresh ovarian tumors and primary ovarian tumor cell lines tested. EpCAM-positive, chemotherapy-resistant cell lines were identified as resistant to natural killer cell-mediated or T-cell-mediated killing after exposure to peripheral blood lymphocytes in 4-hour chromium-release assays (mean±standard error of the mean, 3.6%±0.7% of cells killed after incubation of EpCAM-positive cell lines with control bispecific antibody). In contrast, after incubation with solitomab, EpCAM-positive, chemotherapy-resistant cells became highly sensitive to T-cell cytotoxicity (mean±standard error of the mean, 28.2%±2.05% of cells killed; P<.0001) after exposure to peripheral blood lymphocytes. Ex vivo incubation of autologous tumor-associated lymphocytes with EpCAM-expressing malignant cells in ascites with solitomab resulted in a significant increase in T-cell activation markers and a reduction in the number of viable ovarian tumor cells in ascites (P<.001). Solitomab may represent a novel, potentially effective agent for the treatment of chemotherapy-resistant ovarian cancers that overexpress EpCAM. © 2014 American Cancer Society.

Antibiofilm and Anti-Infection of a Marine Bacterial Exopolysaccharide Against Pseudomonas aeruginosa

PubMed Central

Wu, Shimei; Liu, Ge; Jin, Weihua; Xiu, Pengyuan; Sun, Chaomin

2016-01-01

Pseudomonas aeruginosa is a well-known pathogenic bacterium that forms biofilms and produces virulence factors, thus leading to major problems in many fields, such as clinical infection, food contamination, and marine biofouling. In this study, we report the purification and characterization of an exopolysaccharide EPS273 from the culture supernatant of marine bacterium P. stutzeri 273. The exopolysaccharide EPS273 not only effectively inhibits biofilm formation but also disperses preformed biofilm of P. aeruginosa PAO1. High performance liquid chromatography traces of the hydrolyzed polysaccharides shows that EPS273 primarily consists of glucosamine, rhamnose, glucose and mannose. Further investigation demonstrates that EPS273 reduces the production of the virulence factors pyocyanin, exoprotease, and rhamnolipid, and the virulence of P. aeruginosa PAO1 to human lung cells A549 and zebrafish embryos is also obviously attenuated by EPS273. In addition, EPS273 also greatly reduces the production of hydrogen peroxide (H2O2) and extracellular DNA (eDNA), which are important factors for biofilm formation. Furthermore, EPS273 exhibits strong antioxidant potential by quenching hydroxyl and superoxide anion radicals. Notably, the antibiofouling activity of EPS273 is observed in the marine environment up to 2 weeks according to the amounts of bacteria and diatoms in the glass slides submerged in the ocean. Taken together, the properties of EPS273 indicate that it has a promising prospect in combating bacterial biofilm-associated infection, food-processing contamination and marine biofouling. PMID:26903981

Improvement in Long-Term Memory following Chronic Administration of Eryngium planum Root Extract in Scopolamine Model: Behavioral and Molecular Study

PubMed Central

Ozarowski, Marcin; Thiem, Barbara; Mikolajczak, Przemyslaw L.; Piasecka, Anna; Kachlicki, Piotr; Szulc, Michal; Kaminska, Ewa; Kujawski, Radoslaw; Bartkowiak-Wieczorek, Joanna; Kujawska, Malgorzata; Jodynis-Liebert, Jadwiga; Budzianowski, Jaromir; Kędziora, Izabela; Seremak-Mrozikiewicz, Agnieszka; Czerny, Boguslaw; Bobkiewicz-Kozłowska, Teresa

2015-01-01

Eryngium planum L. (EP) is as a rare medicinal plant with a lot of potentials as pharmaceutical crops. The aim of our study was to assess the effect of subchronic (28-fold) administration of a 70% ethanol extract of EP roots (200 mg/kg, p.o.) on behavioral and cognitive responses in Wistar rats linked with acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and beta-secretase (BACE-1) mRNA levels and AChE and BuChE activities in the hippocampus and frontal cortex. On the last day of experiment, 30 min after the last dose of EP or Huperzine A (HU), scopolamine (SC) was given at a dose of 0.5 mg/kg b.w. intraperitoneally. The results of a passive avoidance test showed an improvement in long-term memory produced by the EP extract in both scopolamine-induced rats and control group. EP caused an insignificant inhibition of AChE and BuChE activities in the frontal cortex and the hippocampus. EP decreased mRNA AChE, BuChE, and BACE-1 levels, especially in the cortex. Our results suggest that the EP extract led to the improvement of the long-term memory in rats coupled with total saponin content. The mechanism of EP action is probably complicated, since HPLC-MS analysis showed 64 chemical compounds (phenolics, saponins) in the extract of EP roots. PMID:26483842

Antioxidant and anti-inflammatory activities of acai (euterpe precatoria) fruit pulp

USDA-ARS?s Scientific Manuscript database

Euterpe precatoria (EP), a species bearing the common name “acai”, has been rarely studied for potential health-related properties. One recent study revealed that fruit pulp of EP contained similar polyphenolic profiles but in higher concentrations than that of another well-studied “acai” Euterpe ol...

Global distribution of vertical wavenumber spectra in the lower stratosphere observed using high-vertical-resolution temperature profiles from COSMIC GPS radio occultation

NASA Astrophysics Data System (ADS)

Noersomadi; Tsuda, T.

2016-02-01

We retrieved temperature (T) profiles with a high vertical resolution using the full spectrum inversion (FSI) method from the Constellation Observing System for Meteorology, Ionosphere and Climate (COSMIC) GPS radio occultation (GPS-RO) data from January 2007 to December 2009. We studied the characteristics of temperature perturbations in the stratosphere at 20-27 km altitude. This height range does not include a sharp jump in the background Brunt-Väisälä frequency squared (N2) near the tropopause, and it was reasonably stable regardless of season and latitude. We analyzed the vertical wavenumber spectra of gravity waves (GWs) with vertical wavelengths ranging from 0.5 to 3.5 km, and we integrated the (total) potential energy EpT. Another integration of the spectra from 0.5 to 1.75 km was defined as EpS for short vertical wavelength GWs, which was not studied with the conventional geometrical optics (GO) retrievals. We also estimated the logarithmic spectral slope (p) for the saturated portion of spectra with a linear regression fitting from 0.5 to 1.75 km.Latitude and time variations in the spectral parameters were investigated in two longitudinal regions: (a) 90-150° E, where the topography was more complicated, and (b) 170-230° E, which is dominated by oceans. We compared EpT, EpS, and p, with the mean zonal winds (U) and outgoing longwave radiation (OLR). We also show a ratio of EpS to EpT and discuss the generation source of EpS. EpT and p clearly showed an annual cycle, with their maximum values in winter at 30-50° N in region (a), and 50-70° N in region (b), which was related to the topography. At 30-50° N in region (b), EpT and p exhibited some irregular variations in addition to an annual cycle. In the Southern Hemisphere, we also found an annual oscillation in EpT and p, but it showed a time lag of about 2 months relative to U. Characteristics of EpTand p in the tropical region seem to be related to convective activity. The ratio of EpT to the theoretical model value, assuming saturated GWs, became larger in the equatorial region and over mountainous regions.

Metagenomes reveal microbial structures, functional potentials, and biofouling-related genes in a membrane bioreactor.

PubMed

Ma, Jinxing; Wang, Zhiwei; Li, Huan; Park, Hee-Deung; Wu, Zhichao

2016-06-01

Metagenomic sequencing was used to investigate the microbial structures, functional potentials, and biofouling-related genes in a membrane bioreactor (MBR). The results showed that the microbial community in the MBR was highly diverse. Notably, function analysis of the dominant genera indicated that common genes from different phylotypes were identified for important functional potentials with the observation of variation of abundances of genes in a certain taxon (e.g., Dechloromonas). Despite maintaining similar metabolic functional potentials with a parallel full-scale conventional activated sludge (CAS) system due to treating the identical wastewater, the MBR had more abundant nitrification-related bacteria and coding genes of ammonia monooxygenase, which could well explain its excellent ammonia removal in the low-temperature period. Furthermore, according to quantification of the genes involved in exopolysaccharide and extracellular polymeric substance (EPS) protein metabolism, the MBR did not show a much different potential in producing EPS compared to the CAS system, and bacteria from the membrane biofilm had lower abundances of genes associated with EPS biosynthesis and transport compared to the activated sludge in the MBR.

Properties of the Eliassen-Palm flux for planetary scale motions

NASA Technical Reports Server (NTRS)

Palmer, T. N.

1982-01-01

In an investigation of the properties of the quasi-geostrophic Eliassen-Palm (EP) flux for planetary-scale motions, particular attention is given to the relation between the EP flux divergence and the meridional flux of eddy potential vorticity, and the relations between the EP flux, group velocity, and the zonal mean refractive index in the Wentzel-Kramers-Brillouin-Jeffreys limit. This latter diagnostic has appeared in a number of different forms as that quantity whose gradient determines the refraction of group velocity paths or EP flux trajectories. The question is considered which, if any, of these forms holds for planetary scale motions. In this investigation, a planetary-scale motion is formally defined to be one for which Burger's (1958) quasigeostrophic theory is appropriate.

Enhancement of therapeutic drug and DNA delivery into cells by electroporation* Enhancement of therapeutic drug and DNA delivery into cells by electroporation

NASA Astrophysics Data System (ADS)

Rabussay, Dietmar; Dev, Nagendu B.; Fewell, Jason; Smith, Louis C.; Widera, Georg; Zhang, Lei

2003-02-01

The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as `electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing `pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm-1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco-economic profile of EP compares favourably with other drug and DNA delivery methods.

Exploring strategies for PrEP adherence and dosing preferences in the context of sexualized recreational drug use among MSM: a qualitative study.

PubMed

Closson, Elizabeth F; Mitty, Jennifer A; Malone, Jowanna; Mayer, Kenneth H; Mimiaga, Matthew J

2018-02-01

The use of recreational drugs while having sex is associated with increased HIV incidence among men who have sex with men (MSM). Taking a daily antiretroviral pill, or pre-exposure prophylaxis (PrEP) is a biomedical intervention to prevent HIV. However, the efficacy of PrEP is closely tied with high levels of adherence. While PrEP has the potential to reduce HIV acquisition, the use of recreational drugs may impede adherence. We explored perceptions of PrEP utilization and regimen preferences among 40 HIV-negative, MSM who reported concurrent recreational drug use and condomless anal sex with a man. Semi-structured qualitative interviews were conducted and the data were analyzed using a qualitative descriptive approach. Participants perceived that it would be challenging to take PrEP while high on crystal meth, crack, powder cocaine, ecstasy and/or GHB. However, men identified strategies for using PrEP when they were not high on these drugs, including taking the pill when they started their day and integrating PrEP into an established routine, such as when taking other medications or preparing for sex. PrEP regimen preferences seemed to be shaped by the frequency in which participants used drugs and their ability to plan for sex. Taking PrEP everyday was appealing for those who regularly engaged in sexualized recreational drug use. Accounts depict these sexual interactions as frequent but unpredictable. A daily regimen would allow them to be prepared for sex without having to plan. An event-driven regimen was acceptable to men who occasionally used recreational drugs in the context of sex. For this group, sex usually occurred was generally prearranged. Patterns of sex and recreational drug use figured largely into participants' framings of how they would use PrEP. These behaviors will likely play a role in the uptake of and adherence to PrEP among this population.

Piracy of PGE2/EP receptor mediated signaling by Kaposi’s sarcoma associated herpes virus (KSHV/HHV-8) for latency gene expression: Strategy of a successful pathogen

PubMed Central

Paul, Arun George; Sharma-Walia, Neelam; Kerur, Nagaraj; White, Carl; Chandran, Bala

2010-01-01

KSHV is implicated in the pathogenesis of KS, a chronic inflammation associated malignancy. COX-2 and its metabolite PGE2, two pivotal proinflammatory/oncogeneic molecules, are proposed to play roles in the expression of major KSHV latency associated nuclear antigen-1 (LANA-1). Microsomal prostaglandin E2 synthase (mPGES), PGE2 and its receptors (EP1, EP2, EP3, and EP4) were detected in KS lesions with the distinct staining of EP2/EP4 in KS lesions. In latently infected endothelial TIVE-LTC cells, EP receptor antagonists down-regulated LANA-1 expression as well as Ca2+, p-Src, p-PI3K, p-PKCζ/λ, and p-NF-κB, which are also some of the signal molecules proposed to be important in KS pathogenesis. Exogenous PGE2 and EP receptor agonists induced the LANA-1 promoter in 293 cells, and YY1, Sp1, Oct-1, Oct-6, C/EBP and c-Jun transcription factors appear to be involved in this induction. PGE2/EP receptor induced LANA-1 promoter activity was down-regulated significantly by the inhibition of Ca2+, p-Src, p-PI3K, p-PKCζ/λ, and p-NF-κB. These findings implicate the inflammatory PGE2/EP receptors and the associated signal molecules in herpes virus latency and uncover a novel paradigm that demonstrates the evolution of KSHV genome plasticity to utilize inflammatory response for its survival advantage of maintaining latent gene expression. This data also suggests that potential use of anti-COX-2 and anti-EP receptor therapy may not only ameliorate the chronic inflammation associated with KS but could also lead to elimination of the KSHV latent infection and the associated KS lesions. PMID:20388794

Ultrasound diagnosis of ectopic pregnancy

PubMed Central

2015-01-01

Abstract Ectopic pregnancy (EP) remains the number one cause of first trimester maternal death. Traditionally, laparoscopy has been the gold standard for diagnosis of EP. The advent of high‐resolution transvaginal scan (TVS) means more clinically stable women with EPs are diagnosed earlier, well before surgery becomes necessary in many cases. Early diagnosis by TVS is therefore potentially life saving and can reduce surgical morbidity by allowing elective surgery or even non‐surgical conservative treatment options. Combining transabdominal and transvaginal scanning confers no benefit over transvaginal scanning alone. Reports that reads “…empty uterus, ectopic pregnancy cannot be excluded” should be a thing of the past. Diagnosis of EP should be based upon the positive identification of an adnexal mass using TVS rather than the absence of an intra‐uterine gestational sac. A systematic approach to scanning the early pregnancy pelvis will diagnose the vast majority of EPs at the initial scan. Ultrasound, and in particular TVS, is fast becoming the new gold standard for diagnosis of all types of EP. In modern management, laparoscopy should be seen as the operative tool of choice while TVS the diagnostic tool of choice. PMID:28191110

Facebook network structure and awareness of preexposure prophylaxis among young men who have sex with men.

PubMed

Khanna, Aditya S; Schumm, Phil; Schneider, John A

2017-03-01

Young Black men who have sex with men (YBMSM) are the only population in the United States who have experienced rising human immunodeficiency virus incidence over the past decade. Consistent pre-exposure prophylaxis (PrEP) use can substantially reduce the risk of human immunodeficiency virus acquisition. What differentiates those who become aware of PrEP, and those who do not, remains largely unknown. The social networks of YBMSM can impact their awareness of PrEP; to examine this impact, we used two waves of Facebook data from "uConnect"-a longitudinal cohort study of YBMSM in Chicago (n = 266). While PrEP awareness increased from 45% at baseline to 75% at follow-up, its use remained low (4% and 6%). There were 88 PrEP-unaware individuals at baseline who became aware (BA) by follow-up, and 56 who remained persistently unaware. While the persistently unawares had a higher median number of total Facebook friends, the BAs had a higher median numbers of friends who participated in uConnect, who were PrEP-aware, and who practiced behaviors previously found to be associated with individual-level awareness of PrEP at baseline. The BAs also had substantially more "influential" friends. These findings demonstrate the potential of social networks in raising PrEP awareness and use among YBMSM. Copyright © 2016 Elsevier Inc. All rights reserved.

Effects of polysaccharide isolated from Streptococcus thermophilus CRL1190 on human gastric epithelial cells.

PubMed

Marcial, Guillermo; Messing, Jutta; Menchicchi, Bianca; Goycoolea, Francisco M; Faller, Gerhard; Graciela, Font de Valdez; Hensel, Andreas

2013-11-01

EPS1190 was isolated from skim milk fermented with Stretococcus thermophilus CRL1190. The polysaccharide consisted of 33% glucose and 66% galactose with 1,4- and 1,4,6-galactose residues as main building blocks beside a high amount of 1,4-linked glucose. The polymer was characterized additionally concerning viscosity and zeta potential. EPS1190 stimulated cellular vitality and proliferation of human stomach AGS cells and human buccal KB cells significantly. EPS1190 stimulated phagocytosis rate of murine macrophages RAW264.7 significantly. NO-release or anti-inflammatory effects by inhibition of LPS-induced NO release were not observed. Confocal laser scanning microscopy revealed that EPS1190 is partially internalized into AGS cells via endosomes. The bioadhesive absorption of FITC-labeled EPS1190 into the mucus layer on the apical side of the epithelium using histological tissue sections from human stomach was observed. Specific interaction of EPS1190 with mucin can be excluded as shown by microviscosimetry studies. EPS1190 increased the adhesion of H. pylori to AGS cells, which resulted in increased secretion of proinflammatory cytokines TNFa, IL-6 and IL-8. Summarizing, EPS1190 seems to stimulate epithelial cell regeneration and immunological innate defense mechanisms, which again can rationalized the use of this polysaccharide as cytoprotective compound in probiotioc preparations. Copyright © 2013 Elsevier B.V. All rights reserved.

Revealing the characteristics of a novel bioflocculant and its flocculation performance in Microcystis aeruginosa removal

NASA Astrophysics Data System (ADS)

Sun, Pengfei; Hui, Cai; Bai, Naling; Yang, Shengmao; Wan, Li; Zhang, Qichun; Zhao, Yuhua

2015-12-01

In the present work, a novel bioflocculant, EPS-1, was prepared and used to flocculate the kaolin suspension and Microcystis aeruginosa. We focused on the characteristics and flocculation performance of EPS-1, especially with regard to its protein components. An important attribute of EPS-1 was its protein content, with 18 protein types identified that occupied a total content of 31.70% in the EPS-1. Moreover, the flocculating activity of these protein components was estimated to be no less than 33.93%. Additionally, polysaccharides that occupied 57.12% of the total EPS-1 content consisted of four monosaccharides: maltose, D-xylose, mannose, and D-fructose. In addition, carbonyl, amino, and hydroxyl groups were identified as the main functional groups. Three main elements, namely C1s, N1s, and O1s, were present in EPS-1 with relative atomic percentages of 62.63%, 24.91%, and 10.5%, respectively. Zeta potential analysis indicated that charge neutralization contributed to kaolin flocculation, but was not involved in M. aeruginosa flocculation. The flocculation conditions of EPS-1 were optimized, and the maximum flocculating efficiencies were 93.34% within 2 min for kaolin suspension and 87.98% within 10 min for M. aeruginosa. These results suggest that EPS-1 could be an alternative to chemical flocculants for treating wastewaters and cyanobacterium-polluted freshwater.

A hydrologic drying bias in water-resource impact analyses of anthropogenic climate change

USGS Publications Warehouse

Milly, Paul; Dunne, Krista A.

2017-01-01

For water-resource planning, sensitivity of freshwater availability to anthropogenic climate change (ACC) often is analyzed with “offline” hydrologic models that use precipitation and potential evapotranspiration (Ep) as inputs. Because Ep is not a climate-model output, an intermediary model of Ep must be introduced to connect the climate model to the hydrologic model. Several Ep methods are used. The suitability of each can be assessed by noting a credible Ep method for offline analyses should be able to reproduce climate models’ ACC-driven changes in actual evapotranspiration in regions and seasons of negligible water stress (Ew). We quantified this ability for seven commonly used Ep methods and for a simple proportionality with available energy (“energy-only” method). With the exception of the energy-only method, all methods tend to overestimate substantially the increase in Ep associated with ACC. In an offline hydrologic model, the Ep-change biases produce excessive increases in actual evapotranspiration (E), whether the system experiences water stress or not, and thence strong negative biases in runoff change, as compared to hydrologic fluxes in the driving climate models. The runoff biases are comparable in magnitude to the ACC-induced runoff changes themselves. These results suggest future hydrologic drying (wetting) trends likely are being systematically and substantially overestimated (underestimated) in many water-resource impact analyses.

Biosorption of Cadmium by Non-Toxic Extracellular Polymeric Substances (EPS) Synthesized by Bacteria from Marine Intertidal Biofilms

PubMed Central

Camacho-Chab, Juan Carlos; Chan-Bacab, Manuel Jesús; Aguila-Ramírez, Ruth Noemí; Bartolo-Pérez, Pascual; Tabasco-Novelo, Carolina; Gaylarde, Christine; Ortega-Morales, Benjamín Otto

2018-01-01

Cadmium is a major heavy metal found in polluted aquatic environments, mainly derived from industrial production processes. We evaluated the biosorption of solubilized Cd2+ using the extracellular polymeric substances (EPS) produced by Bacillus sp. MC3B-22 and Microbacterium sp. MC3B-10 (Microbactan); these bacteria were originally isolated from intertidal biofilms off the coast of Campeche, Mexico. EPS were incubated with different concentrations of cadmium in ultrapure water. Residual Cd2+ concentrations were determined by Inductive Coupled Plasma-Optic Emission Spectrometry and the maximum sorption capacity (Qmax) was calculated according to the Langmuir model. EPS were characterized by X-ray photoelectron spectroscopy (XPS) before and after sorption. The Qmax of Cd2+ was 97 mg g−1 for Microbactan and 141 mg g−1 for MC3B-22 EPS, these adsorption levels being significantly higher than previously reported for other microbial EPS. In addition, XPS analysis revealed changes in structure of EPS after biosorption and showed that amino functional groups contributed to the binding of Cd2+, unlike other studies that show the carbohydrate fraction is responsible for this activity. This work expands the current view of bacterial species capable of synthesizing EPS with biosorbent potential for cadmium and provides evidence that different chemical moieties, other than carbohydrates, participate in this process. PMID:29439486

Development of a fermented ice-cream as influenced by in situ exopolysaccharide production: Rheological, molecular, microstructural and sensory characterization.

PubMed

Dertli, Enes; Toker, Omer S; Durak, M Zeki; Yilmaz, Mustafa T; Tatlısu, Nevruz Berna; Sagdic, Osman; Cankurt, Hasan

2016-01-20

This study aimed to investigate the role of in situ exopolysaccharide (EPS) production by EPS(+)Streptococcus thermophilus strains on physicochemical, rheological, molecular, microstructural and sensory properties of ice cream in order to develop a fermented and consequently functional ice-cream in which no stabilizers would be required in ice-cream production. For this purpose, the effect of EPS producing strains (control, strain 1, strain 2 and mixture) and fermentation conditions (fermentation temperature; 32, 37 and 42 °C and time; 2, 3 and 4h) on pH, S. thermophilus count, EPS amount, consistency coefficient (K), and apparent viscosity (η50) were investigated and optimized using single and multiple response optimization tools of response surface methodology. Optimization analyses indicated that functional ice-cream should be fermented with strain 1 or strain mixture at 40-42 °C for 4h in order to produce the most viscous ice-cream with maximum EPS content. Optimization analysis results also revealed that strain specific conditions appeared to be more effective factor on in situ EPS production amount, K and η50 parameters than did fermentation temperature and time. The rheological analysis of the ice-cream produced by EPS(+) strains revealed its high viscous and pseudoplastic non-Newtonian fluid behavior, which demonstrates potential of S. thermophilus EPS as thickening and gelling agent in dairy industry. FTIR analysis proved that the EPS in ice-cream corresponded to a typical EPS, as revealed by the presence of carboxyl, hydroxyl and amide groups with additional α-glycosidic linkages. SEM studies demonstrated that it had a web-like compact microstructure with pores in ice-cream, revealing its application possibility in dairy products to improve their rheological properties. Copyright © 2015. Published by Elsevier Ltd.

Characterisation of the physical composition and microbial community structure of biofilms within a model full-scale drinking water distribution system.

PubMed

Fish, Katherine E; Collins, Richard; Green, Nicola H; Sharpe, Rebecca L; Douterelo, Isabel; Osborn, A Mark; Boxall, Joby B

2015-01-01

Within drinking water distribution systems (DWDS), microorganisms form multi-species biofilms on internal pipe surfaces. A matrix of extracellular polymeric substances (EPS) is produced by the attached community and provides structure and stability for the biofilm. If the EPS adhesive strength deteriorates or is overcome by external shear forces, biofilm is mobilised into the water potentially leading to degradation of water quality. However, little is known about the EPS within DWDS biofilms or how this is influenced by community composition or environmental parameters, because of the complications in obtaining biofilm samples and the difficulties in analysing EPS. Additionally, although biofilms may contain various microbial groups, research commonly focuses solely upon bacteria. This research applies an EPS analysis method based upon fluorescent confocal laser scanning microscopy (CLSM) in combination with digital image analysis (DIA), to concurrently characterize cells and EPS (carbohydrates and proteins) within drinking water biofilms from a full-scale DWDS experimental pipe loop facility with representative hydraulic conditions. Application of the EPS analysis method, alongside DNA fingerprinting of bacterial, archaeal and fungal communities, was demonstrated for biofilms sampled from different positions around the pipeline, after 28 days growth within the DWDS experimental facility. The volume of EPS was 4.9 times greater than that of the cells within biofilms, with carbohydrates present as the dominant component. Additionally, the greatest proportion of EPS was located above that of the cells. Fungi and archaea were established as important components of the biofilm community, although bacteria were more diverse. Moreover, biofilms from different positions were similar with respect to community structure and the quantity, composition and three-dimensional distribution of cells and EPS, indicating that active colonisation of the pipe wall is an important driver in material accumulation within the DWDS.

The Promise of Pre-Exposure Prophylaxis for Black Men Who Have Sex with Men: An Ecological Approach to Attitudes, Beliefs, and Barriers.

PubMed

Philbin, Morgan M; Parker, Caroline M; Parker, Richard G; Wilson, Patrick A; Garcia, Jonathan; Hirsch, Jennifer S

2016-06-01

Research has demonstrated the clinical effectiveness of pre-exposure prophylaxis (PrEP) for HIV prevention, but little is known about how factors at the individual-, interpersonal-, community-, and structural levels impact PrEP use for black men who have sex with men (BMSM). We advance existing work by examining how all levels of the ecological framework must be addressed for PrEP to be successfully implemented as an effective HIV prevention approach. We interviewed 31 BMSM three times each and 17 community stakeholders once each; interviews were taped, transcribed, and analyzed using the constant comparative method. Factors that influence how BMSM experienced PrEP emerged across all levels of the ecological framework: At the individual level, respondents were wary of giving medication to healthy people and of the potential side-effects. At the interpersonal level, BMSM believed that PrEP use would discourage condom use and that PrEP should only be one option for HIV prevention, not the main option. At the community level, men described not trusting the pharmaceutical industry and described PrEP as an option for others, not for themselves. At the structural level, BMSM talked about HIV and sexuality-related stigmas and how they must overcome those before PrEP engagement. BMSM are a key population in the US National HIV/AIDS Strategy, yet few individuals believe that PrEP would be personally helpful. Our research indicates the urgent need to raise awareness and address structural stigma and policies that could be substantial barriers to the scale-up and implementation of PrEP-related services.

The Promise of Pre-Exposure Prophylaxis for Black Men Who Have Sex with Men: An Ecological Approach to Attitudes, Beliefs, and Barriers

PubMed Central

Parker, Caroline M.; Parker, Richard G.; Wilson, Patrick A.; Garcia, Jonathan; Hirsch, Jennifer S.

2016-01-01

Abstract Research has demonstrated the clinical effectiveness of pre-exposure prophylaxis (PrEP) for HIV prevention, but little is known about how factors at the individual-, interpersonal-, community-, and structural levels impact PrEP use for black men who have sex with men (BMSM). We advance existing work by examining how all levels of the ecological framework must be addressed for PrEP to be successfully implemented as an effective HIV prevention approach. We interviewed 31 BMSM three times each and 17 community stakeholders once each; interviews were taped, transcribed, and analyzed using the constant comparative method. Factors that influence how BMSM experienced PrEP emerged across all levels of the ecological framework: At the individual level, respondents were wary of giving medication to healthy people and of the potential side-effects. At the interpersonal level, BMSM believed that PrEP use would discourage condom use and that PrEP should only be one option for HIV prevention, not the main option. At the community level, men described not trusting the pharmaceutical industry and described PrEP as an option for others, not for themselves. At the structural level, BMSM talked about HIV and sexuality-related stigmas and how they must overcome those before PrEP engagement. BMSM are a key population in the US National HIV/AIDS Strategy, yet few individuals believe that PrEP would be personally helpful. Our research indicates the urgent need to raise awareness and address structural stigma and policies that could be substantial barriers to the scale-up and implementation of PrEP-related services. PMID:27220036

Role of Bacterial Exopolysaccharides (EPS) in the Fate of the Oil Released during the Deepwater Horizon Oil Spill

PubMed Central

Gutierrez, Tony; Berry, David; Yang, Tingting; Mishamandani, Sara; McKay, Luke; Teske, Andreas; Aitken, Michael D.

2013-01-01

Halomonas species are recognized for producing exopolysaccharides (EPS) exhibiting amphiphilic properties that allow these macromolecules to interface with hydrophobic substrates, such as hydrocarbons. There remains a paucity of knowledge, however, on the potential of Halomonas EPS to influence the biodegradation of hydrocarbons. In this study, the well-characterized amphiphilic EPS produced by Halomonas species strain TG39 was shown to effectively increase the solubilization of aromatic hydrocarbons and enhance their biodegradation by an indigenous microbial community from oil-contaminated surface waters collected during the active phase of the Deepwater Horizon oil spill. Three Halomonas strains were isolated from the Deepwater Horizon site, all of which produced EPS with excellent emulsifying qualities and shared high (97-100%) 16S rRNA sequence identity with strain TG39 and other EPS-producing Halomonas strains. Analysis of pyrosequence data from surface water samples collected during the spill revealed several distinct Halomonas phylotypes, of which some shared a high sequence identity (≥97%) to strain TG39 and the Gulf spill isolates. Other bacterial groups comprising members with well-characterized EPS-producing qualities, such as Alteromonas , Colwellia and Pseudoalteromonas , were also found enriched in surface waters, suggesting that the total pool of EPS in the Gulf during the spill may have been supplemented by these organisms. Roller bottle incubations with one of the Halomonas isolates from the Deepwater Horizon spill site demonstrated its ability to effectively produce oil aggregates and emulsify the oil. The enrichment of EPS-producing bacteria during the spill coupled with their capacity to produce amphiphilic EPS is likely to have contributed to the ultimate removal of the oil and to the formation of oil aggregates, which were a dominant feature observed in contaminated surface waters. PMID:23826336

Characterisation of the Physical Composition and Microbial Community Structure of Biofilms within a Model Full-Scale Drinking Water Distribution System

PubMed Central

Fish, Katherine E.; Collins, Richard; Green, Nicola H.; Sharpe, Rebecca L.; Douterelo, Isabel; Osborn, A. Mark; Boxall, Joby B.

2015-01-01

Within drinking water distribution systems (DWDS), microorganisms form multi-species biofilms on internal pipe surfaces. A matrix of extracellular polymeric substances (EPS) is produced by the attached community and provides structure and stability for the biofilm. If the EPS adhesive strength deteriorates or is overcome by external shear forces, biofilm is mobilised into the water potentially leading to degradation of water quality. However, little is known about the EPS within DWDS biofilms or how this is influenced by community composition or environmental parameters, because of the complications in obtaining biofilm samples and the difficulties in analysing EPS. Additionally, although biofilms may contain various microbial groups, research commonly focuses solely upon bacteria. This research applies an EPS analysis method based upon fluorescent confocal laser scanning microscopy (CLSM) in combination with digital image analysis (DIA), to concurrently characterize cells and EPS (carbohydrates and proteins) within drinking water biofilms from a full-scale DWDS experimental pipe loop facility with representative hydraulic conditions. Application of the EPS analysis method, alongside DNA fingerprinting of bacterial, archaeal and fungal communities, was demonstrated for biofilms sampled from different positions around the pipeline, after 28 days growth within the DWDS experimental facility. The volume of EPS was 4.9 times greater than that of the cells within biofilms, with carbohydrates present as the dominant component. Additionally, the greatest proportion of EPS was located above that of the cells. Fungi and archaea were established as important components of the biofilm community, although bacteria were more diverse. Moreover, biofilms from different positions were similar with respect to community structure and the quantity, composition and three-dimensional distribution of cells and EPS, indicating that active colonisation of the pipe wall is an important driver in material accumulation within the DWDS. PMID:25706303

Willingness to use HIV pre-exposure prophylaxis among gay men, other men who have sex with men and transgender women in Myanmar.

PubMed

Draper, Bridget L; Fowkes, Freya J I; Oo, Zaw Min; Thein, Zaw Win; Aung, Poe Poe; Veronese, Vanessa; Ryan, Claire; Thant, Myo; Hughes, Chad; Stoové, Mark

2017-07-26

HIV pre-exposure prophylaxis (PrEP) has emerged as a key component of contemporary HIV combination prevention strategies. To explore the local suitability of PrEP, country-specific acceptability studies are needed to inform potential PrEP implementation. In the context of Myanmar, in addition to resource constraints, HIV service access by gay men, other men who have sex with men, and transgender women (GMT) continues to be constrained by legislative and community stigma and marginalization. We aimed to determine PrEP acceptability among GMT in Myanmar and explore the factors associated with willingness to use PrEP. GMT were recruited in Yangon and Mandalay through local HIV prevention outreach programmes in November and December 2014. Quantitative surveys were administered by trained peer educators and collected data on demographics, sexual risk, testing history and PrEP acceptability. A modified six-item PrEP acceptability scale classified self-reported HIV undiagnosed GMT as willing to use PrEP. Multivariable logistic regression identified factors associated with willingness to use PrEP. Among 434 HIV undiagnosed GMT, PrEP awareness was low (5%). PrEP acceptability was high, with 270 (62%) GMT classified as willing to use PrEP. GMT recruited in Mandalay (adjusted odds ratio (aOR) = 1.79; 95%CI = 1.05-3.03), who perceived themselves as likely to become HIV positive (aOR = 1.82; 95%CI = 1.10-3.02), who had more than one recent regular partner (aOR = 2.94; 95%CI = 1.41-6.14), no regular partners (aOR = 2.05; 95%CI = 1.10-3.67), more than five casual partners (aOR = 2.05; 95%CI = 1.06-3.99) or no casual partners (aOR = 2.25; 95%CI = 1.23-4.11) were more likely to be willing to use PrEP. The association between never or only occasionally using condoms with casual partners and willingness to use PrEP was marginally significant (aOR = 2.02; 95%CI = 1.00-4.10). GMT who reported concern about side effects and long-term use of PrEP were less likely (aOR = 0.35; 95%CI = 0.21-0.59) to be willing to use PrEP. This is the first study to assess PrEP acceptability in Myanmar. Findings suggest PrEP is an acceptable prevention option among GMT in Myanmar, providing they are not required to pay for it. Implementation/demonstration projects are needed to explore the feasibility and cost-effectiveness of PrEP as a prevention option for GMT in Myanmar.

Effect of Engineered Nanoparticles on Exopolymeric Substances Release from Marine Phytoplankton.

PubMed

Chiu, Meng-Hsuen; Khan, Zafir A; Garcia, Santiago G; Le, Andre D; Kagiri, Agnes; Ramos, Javier; Tsai, Shih-Ming; Drobenaire, Hunter W; Santschi, Peter H; Quigg, Antonietta; Chin, Wei-Chun

2017-12-13

Engineered nanoparticles (ENPs), products from modern nanotechnologies, can potentially impact the marine environment to pose serious threats to marine ecosystems. However, the cellular responses of marine phytoplankton to ENPs are still not well established. Here, we investigate four different diatom species (Odontella mobiliensis, Skeletonema grethae, Phaeodactylum tricornutum, Thalassiosira pseudonana) and one green algae (Dunaliella tertiolecta) for their extracellular polymeric substances (EPS) release under model ENP treatments: 25 nm titanium dioxide (TiO 2 ), 10-20 nm silicon dioxide (SiO 2 ), and 15-30 nm cerium dioxide (CeO 2 ). We found SiO 2 ENPs can significantly stimulate EPS release from these algae (200-800%), while TiO 2 ENP exposure induced the lowest release. Furthermore, the increase of intracellular Ca 2+ concentration can be triggered by ENPs, suggesting that the EPS release process is mediated through Ca 2+ signal pathways. With better understanding of the cellular mechanism mediated ENP-induced EPS release, potential preventative and safety measures can be developed to mitigate negative impact on the marine ecosystem.

Attitudes and Perceptions of Biomedical HIV Prevention Methods: Voices from Young Men who Have Sex with Men

PubMed Central

Kubicek, Katrina; Arauz-Cuadra, Cesar; Kipke, Michele D.

2015-01-01

In the third decade of the HIV/AIDS epidemic in the United States, the prevalence rates of new HIV infections among young men who have sex with men (YMSM) continue to increase. As new and emerging HIV prevention method are developed, it is important to understand the perceptions of this vulnerable population –as they may be an ideal target for these intervention methods. This pilot study provides an overview of YMSM of color’s awareness and perceptions of pre-exposure prophylaxis (PrEP) and rectal microbicides (RM). A total of 6 focus groups were convened with 53 YMSM (23 Latino/Hispanic and 30 Black/African American). Findings indicate a lack of knowledge of biomedical interventions and high perceived acceptability. Concerns regarding PrEP included potential side effects, potential for misinterpretation of its use and cost. RMs were perceived to be more acceptable than PrEP, but the limited knowledge about their potential was emphasized by YMSM. Results are discussed in relation to the need for providers to continue to provide general health education about safe sexual practices. As PrEP and other biomedical interventions are introduced into community settings, caution should be taken with regards to determining the appropriate target user and sufficient education. PMID:25633499

Attitudes and perceptions of biomedical HIV prevention methods: voices from young men who have sex with men.

PubMed

Kubicek, Katrina; Arauz-Cuadra, Cesar; Kipke, Michele D

2015-02-01

In the third decade of the HIV/AIDS epidemic in the United States, the prevalence rates of new HIV infections among young men who have sex with men (YMSM) continue to increase. As new and emerging HIV prevention methods are developed, it is important to understand the perceptions of this vulnerable population-as they may be an ideal target for these intervention methods. This pilot study provides an overview of YMSM of color's awareness and perceptions of pre-exposure prophylaxis (PrEP) and rectal microbicides (RM). A total of 6 focus groups were convened with 53 YMSM (23 Latino/Hispanic and 30 Black/African American). Findings indicate a lack of knowledge of biomedical interventions and high perceived acceptability. Concerns regarding PrEP included potential side effects, potential for misinterpretation of its use and cost. RMs were perceived to be more acceptable than PrEP, but the limited knowledge about their potential was emphasized by YMSM. Results are discussed in relation to the need for providers to continue to provide general health education about safe sexual practices. As PrEP and other biomedical interventions are introduced into community settings, caution should be taken with regards to determining the appropriate target user and sufficient education.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure.

PubMed

Roth, Caleb C; Barnes, Ronald A; Ibey, Bennett L; Beier, Hope T; Christopher Mimun, L; Maswadi, Saher M; Shadaram, Mehdi; Glickman, Randolph D

2015-10-09

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane.

Silicifying Biofilm Exopolymers on a Hot-Spring Microstromatolite: Templating Nanometer-Thick Laminae

NASA Astrophysics Data System (ADS)

Handley, Kim M.; Turner, Sue J.; Campbell, Kathleen A.; Mountain, Bruce W.

2008-08-01

Exopolymeric substances (EPS) are an integral component of microbial biofilms; however, few studies have addressed their silicification and preservation in hot-spring deposits. Through comparative analyses with the use of a range of microscopy techniques, we identified abundant EPS significant to the textural development of spicular, microstromatolitic, siliceous sinter at Champagne Pool, Waiotapu, New Zealand. Examination of biofilms coating sinter surfaces by confocal laser scanning microscopy (CLSM), environmental scanning electron microscopy (ESEM), cryo-scanning electron microscopy (cryo-SEM), and transmission electron microscopy (TEM) revealed contraction of the gelatinous EPS matrix into films (approximately 10 nm thick) or fibrillar structures, which is common in conventional SEM analyses and analogous to products of naturally occurring desiccation. Silicification of fibrillar EPS contributed to the formation of filamentous sinter. Matrix surfaces or dehydrated films templated sinter laminae (nanometers to microns thick) that, in places, preserved fenestral voids beneath. Laminae of similar thickness are, in general, common to spicular geyserites. This is the first report to demonstrate EPS templation of siliceous stromatolite laminae. Considering the ubiquity of biofilms on surfaces in hot-spring environments, EPS silicification studies are likely to be important to a better understanding of the origins of laminae in other modern and ancient stromatolitic sinters, and EPS potentially may serve as biosignatures in extraterrestrial rocks.

Designing Epidemiology Studies to Determine the Incidence and Prevalence of Encapsulating Peritoneal Sclerosis (EPS).

PubMed

Nitsch, Dorothea; Davenport, Andrew

2015-12-01

The reported incidence and prevalence of encapsulating peritoneal sclerosis (EPS) varies markedly between North America, Europe, Japan, and Australia. Although this could reflect differences in clinical practice patterns and access to transplantation as there is no current test for early detection, and some patients may present many years after discontinuation of peritoneal dialysis (PD), there are concerns about under-reporting, particularly for those with milder forms. Currently, only PD vintage has been identified as a significant risk factor for developing EPS, although some patients can develop EPS within months of starting PD. As such, there is a need for epidemiological studies to determine the incidence and prevalence of EPS to allow for patient education and counselling in terms of dialysis modality choice and length of treatment. In addition, carefully designed epidemiological studies could potentially allow for the identification of risk factors and bio-markers that could then be used to identify patients at increased risk of developing EPS in the future. Typically, studies to date have been underpowered with inadequate longitudinal follow-up. We review the different types of epidemiological studies and provide information as to the number of patients to be recruited and the duration of follow-up required to determine the incidence and prevalence of EPS. Copyright © 2015 International Society for Peritoneal Dialysis.

Comparison of Expansive Pedicle Screw and Polymethylmethacrylate-Augmented Pedicle Screw in Osteoporotic Sheep Lumbar Vertebrae: Biomechanical and Interfacial Evaluations

PubMed Central

Zhang, Bo; Xie, Qing-yun; Wang, Cai-ru; Liu, Jin-biao; Liao, Dong-fa; Jiang, Kai; Lei, Wei; Pan, Xian-ming

2013-01-01

Background It was reported that expansive pedicle screw (EPS) and polymethylmethacrylate-augmented pedicle screw (PMMA-PS) could be used to increase screw stability in osteoporosis. However, there are no studies comparing the two kinds of screws in vivo. Thus, we aimed to compare biomechanical and interfacial performances of EPS and PMMA-PS in osteoporotic sheep spine. Methodology/Principal Findings After successful induction of osteoporotic sheep, lumbar vertebrae in each sheep were randomly divided into three groups. The conventional pedicle screw (CPS) was inserted directly into vertebrae in CPS group; PMMA was injected prior to insertion of CPS in PMMA-PS group; and the EPS was inserted in EPS group. Sheep were killed and biomechanical tests, micro-CT analysis and histological observation were performed at both 6 and 12 weeks post-operation. At 6-week and 12-week, screw stabilities in EPS and PMMA-PS groups were significantly higher than that in CPS group, but there were no significant differences between EPS and PMMA-PS groups at two study periods. The screw stability in EPS group at 12-week was significantly higher than that at 6-week. The bone trabeculae around the expanding anterior part of EPS were more and denser than that in CPS group at 6-week and 12-week. PMMA was found without any degradation and absorption forming non-biological “screw-PMMA-bone” interface in PMMA-PS group, however, more and more bone trabeculae surrounded anterior part of EPS improving local bone quality and formed biological “screw-bone” interface. Conclusions/Significance EPS can markedly enhance screw stability with a similar effect to the traditional method of screw augmentation with PMMA in initial surgery in osteoporosis. EPS can form better biological interface between screw and bone than PMMA-PS. In addition, EPS have no risk of thermal injury, leakage and compression caused by PMMA. We propose EPS has a great application potential in augmentation of screw stability in osteoporosis in clinic. PMID:24086381

A Bayesian approach to estimate evoked potentials.

PubMed

Sparacino, Giovanni; Milani, Stefano; Arslan, Edoardo; Cobelli, Claudio

2002-06-01

Several approaches, based on different assumptions and with various degree of theoretical sophistication and implementation complexity, have been developed for improving the measurement of evoked potentials (EP) performed by conventional averaging (CA). In many of these methods, one of the major challenges is the exploitation of a priori knowledge. In this paper, we present a new method where the 2nd-order statistical information on the background EEG and on the unknown EP, necessary for the optimal filtering of each sweep in a Bayesian estimation framework, is, respectively, estimated from pre-stimulus data and obtained through a multiple integration of a white noise process model. The latter model is flexible (i.e. it can be employed for a large class of EP) and simple enough to be easily identifiable from the post-stimulus data thanks to a smoothing criterion. The mean EP is determined as the weighted average of the filtered sweeps, where each weight is inversely proportional to the expected value of the norm of the correspondent filter error, a quantity determinable thanks to the employment of the Bayesian approach. The performance of the new approach is shown on both simulated and real auditory EP. A signal-to-noise ratio enhancement is obtained that can allow the (possibly automatic) identification of peak latencies and amplitudes with less sweeps than those required by CA. For cochlear EP, the method also allows the audiology investigator to gather new and clinically important information. The possibility of handling single-sweep analysis with further development of the method is also addressed.

Partner Disclosure of PrEP Use and Undetectable Viral Load on Geosocial Networking Apps: Frequency of Disclosure and Decisions About Condomless Sex.

PubMed

Newcomb, Michael E; Mongrella, Melissa C; Weis, Benjamin; McMillen, Samuel J; Mustanski, Brian

2016-02-01

Recent advances in biomedical prevention strategies, including pre-exposure prophylaxis (PrEP) and achieving an undetectable viral load (UVL) among HIV-infected persons, show promise in curbing the rising incidence of HIV among men who have sex with men (MSM) in the United States. This mixed-methods study aimed to investigate the frequency with which MSM encounter potential sex partners on geosocial networking apps who disclose biomedical prevention use, and how MSM make decisions about condom use after these disclosures. Participants were recruited through advertisements placed on a large geosocial networking app for MSM. A total of 668 and 727 participants, respectively, responded to questionnaires assessing partner disclosure of PrEP use and UVL. Each questionnaire included an open-ended item assessing reasons for condomless anal sex (CAS) with partners using biomedical prevention. Across both surveys, most respondents encountered potential sex partners who disclosed PrEP use or UVL, and the majority of those who met up with these partners engaged in CAS at least once. Qualitative analyses found that most participants who reported CAS did so after making a calculated risk about HIV transmission. We also describe a novel risk reduction strategy, "biomed-matching," or having CAS only when both individuals use PrEP or have UVL. We report serostatus differences in both quantitative and qualitative findings. Disclosure of PrEP use and UVL is not uncommon among MSM. Many MSM make accurate appraisals of the risks of CAS with biomedical prevention, and mobile apps may aid with disclosing biomedical prevention use.

Evoked potential correlates of selective attention with multi-channel auditory inputs

NASA Technical Reports Server (NTRS)

Schwent, V. L.; Hillyard, S. A.

1975-01-01

Ten subjects were presented with random, rapid sequences of four auditory tones which were separated in pitch and apparent spatial position. The N1 component of the auditory vertex evoked potential (EP) measured relative to a baseline was observed to increase with attention. It was concluded that the N1 enhancement reflects a finely tuned selective attention to one stimulus channel among several concurrent, competing channels. This EP enhancement probably increases with increased information load on the subject.

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis

PubMed Central

Morelle, Johann; Sow, Amadou; Hautem, Nicolas; Bouzin, Caroline; Crott, Ralph

2015-01-01

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport. PMID:25636412

Getting PrEPared for HIV Prevention Navigation: Young Black Gay Men Talk About HIV Prevention in the Biomedical Era.

PubMed

Mutchler, Matt G; McDavitt, Bryce; Ghani, Mansur A; Nogg, Kelsey; Winder, Terrell J A; Soto, Juliana K

2015-09-01

Biomedical HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP), represent new opportunities to reduce critically high HIV infection rates among young black men who have sex with men (YBMSM). We report results of 24 dyadic qualitative interviews (N=48), conducted in Los Angeles, CA, exploring how YBMSM and their friends view PrEP and PEP. Interviews were analyzed using a grounded theory approach. Participants had widely divergent levels of knowledge about these prevention methods. Misconceptions and mistrust regarding PrEP were common, and concerns were expressed about PrEP-related stigma and the potential for gossip among peers who might assume a person on PrEP was HIV-positive. Yet participants also framed PrEP and PEP as valuable new options within an expanded "tool kit" of HIV prevention strategies that created possibilities for preventing new HIV infections, dating men with a different HIV status, and decreased anxiety about exposure to HIV. We organized themes around four main areas: (1) information and misinformation about biomedical HIV prevention; (2) expectations about PrEP, sexual behavior, and stigma; (3) gossip, disclosure, and "spreading the word" about PrEP and PEP; and (4) the roles of PrEP and PEP in an expanded HIV prevention tool kit. The findings suggest a need for guidance in navigating the increasingly complex array of HIV-prevention options available to YBMSM. Such "prevention navigation" could counter misconceptions and address barriers, such as stigma and mistrust, while helping YBMSM make informed selections from among expanded HIV prevention options.

Awareness and Willingness to Use HIV Pre-Exposure Prophylaxis amongst Gay and Bisexual Men in Scotland: Implications for Biomedical HIV Prevention

PubMed Central

Young, Ingrid; Li, Jessica; McDaid, Lisa

2013-01-01

Objectives To investigate the awareness of, and willingness to use, HIV Pre-Exposure Prophylaxis (PrEP), and willingness to take part in a PrEP study among gay and bisexual men in Scotland. Methods Cross-sectional survey of 17 gay commercial venues in Glasgow and Edinburgh in May 2011 (N = 1515, 65.2% response rate); 1393 are included in the analyses. Results Just under one-third of participants had heard of PrEP (n = 434; 31.2%), with awareness associated with being aged older than 35 years, talking to UAI partners about HIV, and with having had an HIV or STI test in the previous 12 months. Around half were willing to take part in a PrEP study (n = 695; 49.9%) or to take PrEP on a daily basis (n = 756; 54.3%). In multivariate analysis, willingness to take PrEP was associated with lower levels of education, regular gay scene attendance, ‘high-risk’ unprotected anal intercourse (UAI) and testing for HIV or STI in the previous 12 months. Reasons for not wanting to participate in a PrEP study or take PrEP included perceptions of low personal risk of HIV and concerns with using medication as an HIV prevention method. Conclusions There is a willingness to engage in new forms of HIV prevention and research amongst a significant number of gay and bisexual men in Scotland. Future biomedical HIV interventions need to consider the links between sexual risk behaviour, testing, and potential PrEP use. PMID:23691143

Sexually transmitted infections and pre-exposure prophylaxis: challenges and opportunities among men who have sex with men in the US.

PubMed

Scott, Hyman M; Klausner, Jeffrey D

2016-01-01

Pre-Exposure Prophylaxis (PrEP) has shown high efficacy in preventing human immunodeficiency virus (HIV) infection among men who have sex with men (MSM) in several large clinical trials, and more recently in "real world" reports of clinical implementation and a PrEP demonstration project. Those studies also demonstrated high bacterial sexually transmitted infection (STI) incidence and raised the discussion of how PrEP may impact STI control efforts, especially in the setting of increasing Neisseria gonorrhoeae antimicrobial resistance and the increase in syphilis cases among MSM. Here, we discuss STIs as a driver of HIV transmission risk among MSM, and the potential opportunities and challenges for STI control afforded by expanded PrEP implementation among high-risk MSM.

Misoprostol Reverse Hippocampal Neuron Cyclooxygenase-2 Downstream Signaling Imbalance in Aluminum-Overload Rats

PubMed Central

Guo, Yuanxin; Lei, Wenjuan; Wang, Jianfeng; Hu, Xinyue; Wei, Yuling; Ji, Chaonan; Yang, Junqing

2016-01-01

Although COX-2 inhibition in animal models of neurodegenerative diseases has shown neuroprotection, recent studies have revealed some serious side effects (ulcers, bleeding, fatal cerebrovascular diseases etc.) and the limited benefits of COX-2 inhibitors. A more focused approach is necessary to explore the therapeutic effect of the COX downstream signaling pathway in neurological research. The aim of this study was to explore the alterations of the PGES-PGE2-EP signal pathway and the effect of misoprostol on neurodegeneration by chronic aluminum-overload in rats. Adult rats were treated by intragastric administration of aluminum gluconate. The PGE2 content and expression of PGES and EPs in the hippocampi of rats were detected using ELISA, q-PCR and Western blot analysis, respectively. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the rat hippocampi were also detected. The misoprostol treatment dose-dependently improved spatial learning and memory function as well as healing after hippocampal neuron damage induced by chronic aluminum-overload in rats. Meanwhile, the administration of misoprostol resulted in a decrease in the PGE2 level and down-regulation of the mPGES-1, EP2 and EP4 expression levels, while there was a dose-dependent up-regulation of EP3 expression. These results suggest that misoprostol possesses a neuroprotective property, and the mechanism involves affecting the EP3 level and reducing the endogenous production of PGE2 through a negative feedback mechanism, increasing the EP3 expression level, decreasing the EP2 and EP4 expression levels, and rebuilding the mPGES-1-PGE2-EP1-4 signal pathway balance. In this way, misoprostol has a counteractive effect on oxidant stress and inflammation in the central nervous system. The PGES-PGE2-EPs signaling pathway is a potential therapeutic strategy for treating neurodegeneration in patients. PMID:27033056

Formation of microplastics by polychaetes (Marphysa sanguinea) inhabiting expanded polystyrene marine debris.

PubMed

Jang, Mi; Shim, Won Joon; Han, Gi Myung; Song, Young Kyoung; Hong, Sang Hee

2018-06-01

Fragmentation of large plastic debris into smaller particles results in increasing microplastic concentrations in the marine environment. In plastic debris fragmentation processes, the influence of biological factors remains largely unknown. This study investigated the fragmentation of expanded polystyrene (EPS) debris by polychaetes (Marphysa sanguinea) living on the debris. A large number of EPS particles (131 ± 131 particles/individual, 0.2-3.8 mm in length) were found in the digestive tracts of burrowing polychaetes living on EPS debris. To confirm the formation of microplastics by polychaetes and identify the quantity and morphology of produced microplastics, polychaetes were exposed to EPS blocks in filtered seawater under laboratory conditions. Polychaetes burrowed into the blocks and created numerous EPS microplastic particles, indicating that a single polychaete can produce hundreds of thousands of microplastic particles per year. These results reveal the potential role of marine organisms as microplastic producers in the marine environment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Imaging exciton–polariton transport in MoSe2 waveguides

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

Hu, F.; Luan, Y.; Scott, M. E.

The exciton polariton (EP), a half-light and half-matter quasiparticle, is potentially an important element for future photonic and quantum technologies1-4. It provides both strong light-matter interactions and long-distance propagation that is necessary for applications associated with energy or information transfer. Recently, strongly-coupled cavity EPs at room temperature have been demonstrated in van der Waals (vdW) materials due to their strongly-bound excitons5-9. Here we report a nano-optical imaging study of waveguide EPs in MoSe2, a prototypical vdW semiconductor. The measured propagation length of the EPs is sensitive to the excitation photon energy and reaches over 12 μm. The polariton wavelength canmore » be conveniently altered from 600 nm down to 300 nm by controlling the waveguide thickness. Furthermore, we found an intriguing back-bending polariton dispersion close to the exciton resonance. The observed EPs in vdW semiconductors could be useful in future nanophotonic circuits operating in the near-infrared to visible spectral regions.« less

Imaging exciton–polariton transport in MoSe2 waveguides

DOE PAGES

Hu, F.; Luan, Y.; Scott, M. E.; ...

2017-05-08

The exciton polariton (EP), a half-light and half-matter quasiparticle, is potentially an important element for future photonic and quantum technologies1-4. It provides both strong light-matter interactions and long-distance propagation that is necessary for applications associated with energy or information transfer. Recently, strongly-coupled cavity EPs at room temperature have been demonstrated in van der Waals (vdW) materials due to their strongly-bound excitons5-9. Here we report a nano-optical imaging study of waveguide EPs in MoSe2, a prototypical vdW semiconductor. The measured propagation length of the EPs is sensitive to the excitation photon energy and reaches over 12 μm. The polariton wavelength canmore » be conveniently altered from 600 nm down to 300 nm by controlling the waveguide thickness. Furthermore, we found an intriguing back-bending polariton dispersion close to the exciton resonance. The observed EPs in vdW semiconductors could be useful in future nanophotonic circuits operating in the near-infrared to visible spectral regions.« less

Electroporation enhances antimicrobial photodynamic therapy mediated by the hydrophobic photosensitizer, hypericin, Electroporation enhances antimicrobial photodynamic inactivation

PubMed Central

de Melo, Wanessa de Cássia Martins Antunes; Lee, Alexander N; Perussi, Janice Rodrigues; Hamblin, Michael R.

2013-01-01

The effective transport of photosensitizers (PS) across the membrane and the intracellular accumulation of PS are the most crucial elements in antimicrobial photodynamic therapy (aPDT). However, due to the morphological complexity of Gram-negative bacteria the penetration of PS is limited, especially hydrophobic PS. Electroporation (EP) could increase the effectiveness of aPDT, by promoting the formation of transient pores that enhance the permeability of the bacterial membrane to PS. In this study we evaluated the combination of aPDT mediated by the hydrophobic PS, hypericin and EP (aPDT/EP) against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. These bacteria were exposed to light (590 nm) in the presence of hypericin (4µM), following electroporation. The results showed that aPDT/EP inactivated 3.67 logs more E. coli and 2.65 logs more S. aureus than aPDT alone. Based on these results we suggest that EP can potentiate the aPDT effect. PMID:24284122

A pill for HIV prevention: déjà vu all over again?

PubMed

Myers, Julie E; Sepkowitz, Kent A

2013-06-01

Recent FDA approval of tenofovir-emtricitabine for prevention of human immunodeficiency virus (HIV) as a form of pre-exposure prophylaxis (PrEP) has led to concern about implementation of this strategy. Fifty years ago, a very similar national and international debate occurred when the oral contraceptive pill ("the Pill" or "OCP") was approved. Contentious issues included OCP safety, cost, and the potential impact on sexual behavior--many of the same concerns being voiced currently about PrEP. In this article, we review the social and medical history of OCP, drawing parallels with the current PrEP debate. We also explore the key areas where PrEP differs from its forbear: lower efficacy, presence of drug resistance, and a more circumscribed (and marginalized) target population. A thoughtful approach to PrEP implementation, bearing in mind the historical insights gained from the 1960s, might serve as well as we begin this new chapter in the control of the HIV epidemic.

Entanglement prethermalization in an interaction quench between two harmonic oscillators.

PubMed

Ikeda, Tatsuhiko N; Mori, Takashi; Kaminishi, Eriko; Ueda, Masahito

2017-02-01

Entanglement prethermalization (EP) refers to a quasi-stationary nonequilibrium state of a composite system in which each individual subsystem looks thermal but the entire system remains nonthermal due to quantum entanglement between subsystems. We theoretically study the dynamics of EP following a coherent split of a one-dimensional harmonic potential in which two interacting bosons are confined. This problem is equivalent to that of an interaction quench between two harmonic oscillators. We show that this simple model captures the bare essentials of EP; that is, each subsystem relaxes to an approximate thermal equilibrium, whereas the total system remains entangled. We find that a generalized Gibbs ensemble exactly describes the total system if we take into account nonlocal conserved quantities that act nontrivially on both subsystems. In the presence of a symmetry-breaking perturbation, the relaxation dynamics of the system exhibits a quasi-stationary EP plateau and eventually reaches thermal equilibrium. We analytically show that the lifetime of EP is inversely proportional to the magnitude of the perturbation.

Influence of fermentation liquid from waste activated sludge on anoxic/oxic- membrane bioreactor performance: Nitrogen removal, membrane fouling and microbial community.

PubMed

Han, Xiaomeng; Zhou, Zhen; Mei, Xiaojie; Ma, Yan; Xie, Zhenfang

2018-02-01

In order to investigate effects of waste activated sludge (WAS) fermentation liquid on anoxic/oxic- membrane bioreactor (A/O-MBR), two A/O-MBRs with and without WAS fermentation liquid addition were operated in parallel. Results show that addition of WAS fermentation liquid clearly improved denitrification efficiency without deterioration of nitrification, while severe membrane fouling occurred. WAS fermentation liquid resulted in an elevated production of proteins and humic acids in bound extracellular polymeric substance (EPS) and release of organic matter with high MW fractions in soluble microbial product (SMP) and loosely bound EPS (LB-EPS). Measurement of deposition rate and fluid structure confirmed increased fouling potential of SMP and LB-EPS. γ-Proteobacteria and Ferruginibacter, which can secrete and export EPS, were also found to be abundant in the MBR with WAS fermentation liquid. It is implied that when WAS fermentation liquid was applied, some operational steps to control membrane fouling should be employed. Copyright © 2017 Elsevier Ltd. All rights reserved.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm.

PubMed

Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-08

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

EP-DNN: A Deep Neural Network-Based Global Enhancer Prediction Algorithm

NASA Astrophysics Data System (ADS)

Kim, Seong Gon; Harwani, Mrudul; Grama, Ananth; Chaterji, Somali

2016-12-01

We present EP-DNN, a protocol for predicting enhancers based on chromatin features, in different cell types. Specifically, we use a deep neural network (DNN)-based architecture to extract enhancer signatures in a representative human embryonic stem cell type (H1) and a differentiated lung cell type (IMR90). We train EP-DNN using p300 binding sites, as enhancers, and TSS and random non-DHS sites, as non-enhancers. We perform same-cell and cross-cell predictions to quantify the validation rate and compare against two state-of-the-art methods, DEEP-ENCODE and RFECS. We find that EP-DNN has superior accuracy with a validation rate of 91.6%, relative to 85.3% for DEEP-ENCODE and 85.5% for RFECS, for a given number of enhancer predictions and also scales better for a larger number of enhancer predictions. Moreover, our H1 → IMR90 predictions turn out to be more accurate than IMR90 → IMR90, potentially because H1 exhibits a richer signature set and our EP-DNN model is expressive enough to extract these subtleties. Our work shows how to leverage the full expressivity of deep learning models, using multiple hidden layers, while avoiding overfitting on the training data. We also lay the foundation for exploration of cross-cell enhancer predictions, potentially reducing the need for expensive experimentation.

Analysis of extracellular polymeric substances (EPS) and ciprofloxacin-degrading microbial community in the combined Fe-C micro-electrolysis-UBAF process for the elimination of high-level ciprofloxacin.

PubMed

Zhang, Longlong; Yue, Qinyan; Yang, Kunlun; Zhao, Pin; Gao, Baoyu

2018-02-01

Extracellular polymeric substances (EPS) and ciprofloxacin-degrading microbial community in the combined Fe-C micro-electrolysis and up-flow biological aerated filter (UBAF) process for the treatment of high-level ciprofloxacin (CIP) were analyzed. The research demonstrated a great potential of Fe-C micro-electrolysis-UBAF for the elimination of high-level CIP. Above 90% of CIP removal was achieved through the combined process at 100 mg L -1 of CIP loading. In UBAF, the pollutants were mainly removed at 0-70 cm heights. Three-dimensional fluorescence spectrum (3D-EEM) was used to characterize the chemical structural of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) extracted from biofilm sample in UBAF. The results showed that the protein-like substances in LB-EPS and TB-EPS had no clear change in the study. Nevertheless, an obvious release of polysaccharides in EPSs was observed during long-term exposure to CIP, which was considered as a protective response of microbial to CIP toxic. The high-throughput sequencing results revealed that the biodiversity of bacteria community became increasingly rich with gradual ciprofloxacin biodegradation in UBAF. The ciprofloxacin-degrading microbial community was mainly dominated by Proteobacteria and Bacteroidetes. Microorganisms from genera Dechloromonas, Brevundimonas, Flavobacterium, Sphingopyxis and Bosea might take a major role in ciprofloxacin degradation. This study provides deep theoretical guidance for real CIP wastewater treatment. Copyright © 2017. Published by Elsevier Ltd.

Safety of oral tenofovir disoproxil fumarate-based HIV pre-exposure prophylaxis use in lactating HIV-uninfected women.

PubMed

Mugwanya, Kenneth K; John-Stewart, Grace; Baeten, Jared

2017-07-01

In settings where HIV is prevalent in heterosexual populations, pregnancy and postpartum breastfeeding periods can be associated with substantial HIV acquisition risk. Pre-exposure prophylaxis (PrEP) with daily oral tenofovir disoproxil fumarate (TDF)/emtricitabine is an attractive HIV prevention option for women who are lactating but data are limited on its safety during the lactation period. Areas covered: We provide a concise synthesis and summary of current evidence on the safety of TDF-based PrEP during breastfeeding. We conducted a review, searching Pubmed database and major PrEP conferences for primary studies with TDF-based PrEP exposure during postpartum breastfeeding. Expert opinion: TDF-based oral PrEP is an effective female-controlled HIV prevention option. There is evidence supporting the safety of TDF use for infant outcomes during breastfeeding in antiretroviral treatment regimens for HIV and hepatitis B virus, and more limited, but consistently safe, data from use of TDF as PrEP. The potential for risk is arguably outweighed for at-risk individuals by HIV prevention benefits, including indirect protection to the infant as a result of preventing HIV in the breastfeeding mother. As PrEP delivery is scaled up in heterosexual populations in high HIV prevalence settings and for at-risk persons in other settings, implementation science studies can provide a framework to increase the accrual of safety, acceptability, and use data related to PrEP during lactation.

Interactions of Cd and Cu in anaerobic estuarine sediments. 1: Partitioning in geochemical fractions of sediments

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

Rule, J.H.; Alden, R.W. III

1996-04-01

Partitioning of Cd and Cu between geochemical fractions of an anaerobic estuarine sediment was determined after equilibrating fine-sandy sediment with different combinations of added Cd (0, 2.5, 5 mg/kg) and Cu(0, 12.5, 25 mg/kg). Sediments were placed in aquaria with 20 ppt seawater where bioassay test organisms were exposed for 14 d. At the start and conclusion of the experimental period, sediments were sequentially extracted to determine the elemental content of the exchangeable (EP), easily reducible (ERP), organic- sulfide (OSP), moderately reducible (MRP), and acid extractable (AEP) phases. Partitioning of the metals in both the native and treated sediments was,more » for Cd: OSP {much_gt} ERP > AEP > EP (MRP was below detection) and for Cu: OSP {much_gt} AEP > ERP > MRP > EP. Cadmium extracted in all phases and Cu in the EP, RP, and OSP were proportional to the respective treatments. The EP-Cd, ERP-Cd, and OSP-Cd were affected by the Cu treatment and significant interactions occurred between Cd and Cu for the EP-Cd, ERP-Cd, OSP-Cd, EP-Cu, and ERP-Cu. Increasing levels of applied Cd and Cu resulted in greater amounts of EP-Cd and ERP-Cd, fractions that are the most bioavailable and the most readily available for desorption into the water column. A significant conclusion is that the input of nontoxic metals may affect the geochemical phase distribution, potential bioavailability, and toxicity of native sediment metals.« less

Willingness to use pre-exposure prophylaxis for HIV prevention among female sex workers: a cross-sectional study in China

PubMed Central

Peng, Bin; Yang, Xiaowei; Zhang, Yan; Dai, Jianghong; Liang, Hao; Zou, Yunfeng; Luo, Jinkun; Peng, Hongbin; Zhong, Xiaoni; Huang, Ailong

2012-01-01

Background Pre-exposure prophylaxis (PrEP) is a strategy developed to prevent individuals who are human immunodeficiency virus (HIV)-negative from developing HIV infection. In China, while conducting a clinical trial to investigate the effectiveness and safety of PrEP, we performed this survey to assess the willingness of female sex workers to use PrEP, and identify predictors of this willingness. Methods From July 2009 to April 2010, a cross-sectional study was carried out in four provinces of China. We recruited 1611 female sex workers who completed a self-administered survey to assess their awareness of and intention to use PrEP. The survey also canvassed demographic, behavioral, and psychosocial variables. Bivariate and multivariable logistic regression models were fitted to identify predictors of intent to use PrEP. Results In total, 69% of the women (95% confidence interval [CI] 66.7–71.3) reported intent to use PrEP, and 12% (95% CI 10.5–13.7) had used drugs in the past to prevent a sexually transmitted infection. Further, 16.5% (95% CI 14.7–18.4) had previously heard of PrEP, and 1.4% (95% CI 0.9–2.1) had used PrEP previously to prevent HIV infection. Multivariate analysis indicated the following significant predictors of intent to use PrEP: Han ethnicity (adjusted odds ratio [AOR] 1.446; P = 0.011), urban residence (AOR 1.302; P = 0.027), knowledge about transmission of HIV/acquired immune deficiency virus syndrome (AIDS, AOR 1.817; P = 0.0007), a history of sexually transmitted infection (AOR 1.830; P < 0.0001), a history of using medication to prevent a sexually transmitted disease (AOR 2.547; P < 0.0001), and willingness to access knowledge about HIV/AIDS (AOR 2.153; P < 0.0001). Conclusion The majority of female sex workers reported intent to use PrEP if it is safe and effective. Given that most of the participants had never heard of PrEP before, we strongly recommend that educational materials be developed with detailed introduction of PrEP. The risks and benefits of PrEP use should be fully explained to potential users when promoting PrEP in the future. PMID:23055781

Complete genome sequence of Defluviimonas alba cai42T, a microbial exopolysaccharides producer.

PubMed

Zhao, Jie-Yu; Geng, Shuang; Xu, Lian; Hu, Bing; Sun, Ji-Quan; Nie, Yong; Tang, Yue-Qin; Wu, Xiao-Lei

2016-12-10

Defluviimonas alba cai42 T , isolated from the oil-production water in Xinjiang Oilfield in China, has a strong ability to produce exopolysaccharides (EPS). We hereby present its complete genome sequence information which consists of a circular chromosome and three plasmids. The strain characteristically contains various genes encoding for enzymes involved in EPS biosynthesis, modification, and export. According to the genomic and physiochemical data, it is predicted that the strain has the potential to be utilized in industrial production of microbial EPS. Copyright © 2016 Elsevier B.V. All rights reserved.

Hyperbranched exopolysaccharide-enhanced foam properties of sodium fatty alcohol polyoxyethylene ether sulfate.

PubMed

Deng, Quanhua; Li, Haiping; Sun, Haoyang; Sun, Yange; Li, Ying

2016-05-01

The foam properties, such as the foamability, foam stability, drainage, coalescence and bulk rheology, of aqueous solutions containing an eco-friendly exopolysaccharide (EPS) secreted by a deep-sea mesophilic bacterium, Wangia profunda SM-A87, and an anionic surfactant, sodium fatty alcohol polyoxyethylene ether sulfate (AES), were studied. Both the foamability and foam stability of the EPS/AES solutions are considerably higher than those of single AES solutions, even at very low AES concentrations, although pure EPS solutions cannot foam. The improved foamability and foam stability arise from the formation of the EPS/AES complex via hydrogen bonds at the interfaces. The synergism between the EPS and AES decreases the surface tension, increases the interfacial elasticity and water-carrying capacity, and suppresses the coalescence and collapse of the foams. The EPS/AES foams are more salt-resistant than the AES foams. This work provides not only a new eco-friendly foam with great potential for use in enhanced oil recovery and health-care products but also useful guidance for designing other environmentally friendly foam systems that exhibit high performance. Copyright © 2016 Elsevier B.V. All rights reserved.

HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma.

PubMed

Pellegrini, Laura; Xue, Jiaming; Larson, David; Pastorino, Sandra; Jube, Sandro; Forest, Kelly H; Saad-Jube, Zeyana Salim; Napolitano, Andrea; Pagano, Ian; Negi, Vishal S; Bianchi, Marco E; Morris, Paul; Pass, Harvey I; Gaudino, Giovanni; Carbone, Michele; Yang, Haining

2017-04-04

Human malignant mesothelioma (MM) is an aggressive cancer linked to asbestos and erionite exposure. We previously reported that High-Mobility Group Box-1 protein (HMGB1), a prototypic damage-associated molecular pattern, drives MM development and sustains MM progression. Moreover, we demonstrated that targeting HMGB1 inhibited MM cell growth and motility in vitro, reduced tumor growth in vivo, and prolonged survival of MM-bearing mice. Ethyl pyruvate (EP), the ethyl ester of pyruvic acid, has been shown to be an effective HMGB1 inhibitor in inflammation-related diseases and several cancers. Here, we studied the effect of EP on the malignant phenotype of MM cells in tissue culture and on tumor growth in vivo using an orthotopic MM xenograft model. We found that EP impairs HMGB1 secretion by MM cells leading to reduced RAGE expression and NF-κB activation. As a consequence, EP impaired cell motility, cell proliferation, and anchorage-independent growth of MM cells. Moreover, EP reduced HMGB1 serum levels in mice and inhibited the growth of MM xenografts.Our results indicate that EP effectively hampers the malignant phenotype of MM, offering a novel potential therapeutic approach to patients afflicted with this dismal disease.

Structural characterization of the exopolysaccharide produced by Streptococcus thermophilus 05-34 and its in situ application in yogurt.

PubMed

Qin, Q Q; Xia, B S; Xiong, Y; Zhang, S X; Luo, Y B; Hao, Y L

2011-01-01

An exopolysaccharide (EPS) producing strain was isolated from Tibetan kefir grains in China, which was identified by 16S rDNA tests and designated as Streptococcus thermophilus 05-34. The high-performance liquid chromatography analysis showed that it was composed of galactose and glucose in a molar ratio of 1.0:0.8 with a molecular mass of 2.5 × 10(4) Da. EPS was further revealed to have α-d-glucose, α-d-galactose, β-d-glucose, and β-d-galactose by Fourier transform infrared spectroscopy combined with 1D (1) H nuclear magnetic resonance spectroscopy. The length of EPS ranged from 10 to 100 nm and the maximal height of lumps was 2.5 nm through atomic force micrograph analysis. Furthermore, yogurt fermented with EPS-producing S. thermophilus 05-34 exhibited lower susceptibility to whey separation, higher viscosity, and sensory scores than those made with non-EPS-producing strain in yogurt production. These results suggested that EPS-producing Streptococcus thermophilus 05-34 provided a potential application in the fermented dairy industry. © 2011 China Agricultural University © 2011 Journal of Food Science © 2011 Institute of Food Technologists®

Factors influencing access to education, decision making, and receipt of preferred dialysis modality in unplanned dialysis start patients.

PubMed

Machowska, Anna; Alscher, Mark Dominik; Reddy Vanga, Satyanarayana; Koch, Michael; Aarup, Michael; Qureshi, Abdul Rashid; Lindholm, Bengt; Rutherford, Peter A

2016-01-01

Unplanned dialysis start (UPS) leads to worse clinical outcomes than planned start, and only a minority of patients ever receive education on this topic and are able to make a modality choice, particularly for home dialysis. This study aimed to determine the predictive factors for patients receiving education, making a decision, and receiving their preferred modality choice in UPS patients following a UPS educational program (UPS-EP). The Offering Patients Therapy Options in Unplanned Start (OPTiONS) study examined the impact of the implementation of a specific UPS-EP, including decision support tools and pathway improvement on dialysis modality choice. Linear regression models were used to examine the factors predicting three key steps: referral and receipt of UPS-EP, modality decision making, and actual delivery of preferred modality choice. A simple economic assessment was performed to examine the potential benefit of implementing UPS-EP in terms of dialysis costs. The majority of UPS patients could receive UPS-EP (214/270 patients) and were able to make a decision (177/214), although not all patients received their preferred choice (159/177). Regression analysis demonstrated that the initial dialysis modality was a predictive factor for referral and receipt of UPS-EP and modality decision making. In contrast, age was a predictor for referral and receipt of UPS-EP only, and comorbidity was not a predictor for any step, except for myocardial infarction, which was a weak predictor for lower likelihood of receiving preferred modality. Country practices predicted UPS-EP receipt and decision making. Economic analysis demonstrated the potential benefit of UPS-EP implementation because dialysis modality costs were associated with modality distribution driven by patient preference. Education and decision support can allow UPS patients to understand their options and choose dialysis modality, and attention needs to be focused on ensuring equity of access to educational programs, especially for the elderly. Physician practice and culture across units/countries is an important predictor of UPS patient management and modality choice independent of patient-related factors. Additional work is required to understand and improve patient pathways to ensure that modality preference is enacted. There appears to be a cost benefit of delivering education, supporting choice, and ensuring that the choice is enacted in UPS patients.

PrEP as a feature in the optimal landscape of combination HIV prevention in sub-Saharan Africa

PubMed Central

McGillen, Jessica B; Anderson, Sarah-Jane; Hallett, Timothy B

2016-01-01

Introduction The new WHO guidelines recommend offering pre-exposure prophylaxis (PrEP) to people who are at substantial risk of HIV infection. However, where PrEP should be prioritised, and for which population groups, remains an open question. The HIV landscape in sub-Saharan Africa features limited prevention resources, multiple options for achieving cost saving, and epidemic heterogeneity. This paper examines what role PrEP should play in optimal prevention in this complex and dynamic landscape. Methods We use a model that was previously developed to capture subnational HIV transmission in sub-Saharan Africa. With this model, we can consider how prevention funds could be distributed across and within countries throughout sub-Saharan Africa to enable optimal HIV prevention (that is, avert the greatest number of infections for the lowest cost). Here, we focus on PrEP to elucidate where, and to whom, it would optimally be offered in portfolios of interventions (alongside voluntary medical male circumcision, treatment as prevention, and behaviour change communication). Over a range of continental expenditure levels, we use our model to explore prevention patterns that incorporate PrEP, exclude PrEP, or implement PrEP according to a fixed incidence threshold. Results At low-to-moderate levels of total prevention expenditure, we find that the optimal intervention portfolios would include PrEP in only a few regions and primarily for female sex workers (FSW). Prioritisation of PrEP would expand with increasing total expenditure, such that the optimal prevention portfolios would offer PrEP in more subnational regions and increasingly for men who have sex with men (MSM) and the lower incidence general population. The marginal benefit of including PrEP among the available interventions increases with overall expenditure by up to 14% (relative to excluding PrEP). The minimum baseline incidence for the optimal offer of PrEP declines for all population groups as expenditure increases. We find that using a fixed incidence benchmark to guide PrEP decisions would incur considerable losses in impact (up to 7%) compared with an approach that uses PrEP more flexibly in light of prevailing budget conditions. Conclusions Our findings suggest that, for an optimal distribution of prevention resources, choices of whether to implement PrEP in subnational regions should depend on the scope for impact of other possible interventions, local incidence in population groups, and total resources available. If prevention funding were to become restricted in the future, it may be suboptimal to use PrEP according to a fixed incidence benchmark, and other prevention modalities may be more cost-effective. In contrast, expansions in funding could permit PrEP to be used to its full potential in epidemiologically driven prevention portfolios and thereby enable a more cost-effective HIV response across Africa. PMID:27760682

Vulnerable infected populations and street markets for ARVs: Potential implications for PrEP rollout in the USA.

PubMed

Kurtz, Steven P; Buttram, Mance E; Surratt, Hilary L

2014-04-01

Widespread diversion of antiretroviral (ARV) medications to illicit markets has recently been documented among indigent patients in South Florida. The recent approval of ARVs for pre-exposure prophylaxis (PrEP) has the potential to broaden these illicit markets, as high-risk individuals seek ARVs without a prescription or medical supervision. Nonadherence among diverters and unsupervised use of ARVs for treatment or PrEP increase risks of treatment failure, drug resistance, and disease transmission. We report the scope of ARV diversion among substance-using men who have sex with men in South Florida. Structured interviews (N = 515) queried demographics, HIV status, mental distress, substance dependence, and sexual risks. HIV-positive participants answered questions about medical care, treatment, and ARV adherence and diversion. Median age was 39. Of 46.4% who were HIV-positive, 79.1% were prescribed ARVs. Of these, 27% reported selling/trading ARVs. Reasons for diversion were sharing/trading with friends, sale/trade for money/drugs, and sale/trade of unused medications. ARV diverters, compared to nondiverters, were more likely to be substance dependent (74.5% vs. 58.7%, p = 0.046) and have traded sex for money/drugs (60.8% vs. 32.6%, p < 0.001), and less likely to be adherent to ARVs (54.9% vs. 73.9%, p = 0.012). ARV diversion should be a particular concern in communities of high-risk men who have sex with men as uninfected men in such communities are likely to benefit most from PrEP but unlikely to have access to PrEP and necessary ancillary services through the health-care system. The implications of diversion for increased risks of treatment failure, disease transmission, and PrEP failure should be carefully considered in developing policy and behavioral supports to scaling up treatment as prevention and PrEP.

Pathophysiological role of prostaglandin E2-induced up-regulation of the EP2 receptor in motor neuron-like NSC-34 cells and lumbar motor neurons in ALS model mice.

PubMed

Kosuge, Yasuhiro; Miyagishi, Hiroko; Yoneoka, Yuki; Yoneda, Keiko; Nango, Hiroshi; Ishige, Kumiko; Ito, Yoshihisa

2017-07-04

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by selective degeneration of motor neurons. The primary triggers for motor neuronal death are still unknown, but inflammation is considered to be an important factor contributing to the pathophysiology of ALS both clinically and in ALS models. Prostaglandin E2 (PGE2) and its corresponding four E-prostanoid receptors play a pivotal role in the degeneration of motor neurons in human and transgenic models of ALS. It has also been shown that PGE2-EP2 signaling in glial cells (astrocytes or microglia) promotes motor neuronal death in G93A mice. The present study was designed to investigate the levels of expression of EP receptors in the spinal motor neurons of ALS model mice and to examine whether PGE2 alters the expression of EP receptors in differentiated NSC-34 cells, a motor neuron-like cell line. Immunohistochemical staining demonstrated that EP2 and EP3 immunoreactivity was localized in NeuN-positive large cells showing the typical morphology of motor neurons in mice. Semi-quantitative analysis showed that the immunoreactivity of EP2 in motor neurons was significantly increased in the early symptomatic stage in ALS model mice. In contrast, the level of EP3 expression remained constant, irrespective of age. In differentiated NSC-34 cells, bath application of PGE2 resulted in a concentration-dependent decrease of MTT reduction. Although PGE2 had no effect on cell survival at concentrations of less than 10 μM, pretreatment with 10 μM PGE2 significantly up-regulated EP2 and concomitantly potentiated cell death induced by 30 μM PGE2. These results suggest that PGE2 is an important effector for induction of the EP2 subtype in differentiated NSC-34 cells, and that not only EP2 up-regulation in glial cells but also EP2 up-regulation in motor neurons plays a pivotal role in the vulnerability of motor neurons in ALS model mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeted expression of suicide gene by tissue-specific promoter and microRNA regulation for cancer gene therapy.

PubMed

Danda, Ravikanth; Krishnan, Gopinath; Ganapathy, Kalaivani; Krishnan, Uma Maheswari; Vikas, Khetan; Elchuri, Sailaja; Chatterjee, Nivedita; Krishnakumar, Subramanian

2013-01-01

In order to realise the full potential of cancer suicide gene therapy that allows the precise expression of suicide gene in cancer cells, we used a tissue specific Epithelial cell adhesion molecule (EpCAM) promoter (EGP-2) that directs transgene Herpes simplex virus-thymidine kinase (HSV-TK) expression preferentially in EpCAM over expressing cancer cells. EpCAM levels are considerably higher in retinoblastoma (RB), a childhood eye cancer with limited expression in normal cells. Use of miRNA regulation, adjacent to the use of the tissue-specific promoter, would provide the second layer of control to the transgene expression only in the tumor cells while sparing the normal cells. To test this hypothesis we cloned let-7b miRNA targets in the 3'UTR region of HSV-TK suicide gene driven by EpCAM promoter because let-7 family miRNAs, including let-7b, were found to be down regulated in the RB tumors and cell lines. We used EpCAM over expressing and let-7 down regulated RB cell lines Y79, WERI-Rb1 (EpCAM (+ve)/let-7b(down-regulated)), EpCAM down regulated, let-7 over expressing normal retinal Müller glial cell line MIO-M1(EpCAM (-ve)/let-7b(up-regulated)), and EpCAM up regulated, let-7b up-regulated normal thyroid cell line N-Thy-Ori-3.1(EpCAM (+ve)/let-7b(up-regulated)) in the study. The cell proliferation was measured by MTT assay, apoptosis was measured by probing cleaved Caspase3, EpCAM and TK expression were quantified by Western blot. Our results showed that the EGP2-promoter HSV-TK (EGP2-TK) construct with 2 or 4 copies of let-7b miRNA targets expressed TK gene only in Y79, WERI-Rb-1, while the TK gene did not express in MIO-M1. In summary, we have developed a tissue-specific, miRNA-regulated dual control vector, which selectively expresses the suicide gene in EpCAM over expressing cells.

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

PubMed Central

Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

2014-01-01

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic application of prospective prostaglandin G-protein-coupled receptor drugs in the clinic for treatment of TBI and other acute brain injuries. PMID:25426930

Dexmedetomidine Does Not Affect Evoked Potentials During Spine Surgery.

PubMed

Rozet, Irene; Metzner, Julia; Brown, Marcia; Treggiari, Miriam M; Slimp, Jefferson C; Kinney, Greg; Sharma, Deepak; Lee, Lorri A; Vavilala, Monica S

2015-08-01

The effect of dexmedetomidine on evoked potentials (EPs) has not been elucidated. We aimed to investigate the effect of dexmedetomidine on somatosensory, motor, and visual EPs. After IRB approval, 40 adult patients scheduled for elective spine surgery using total IV anesthesia with propofol and remifentanil were randomly assigned to receive either dexmedetomidine (n = 20) or placebo (n = 20) in a double-blind, placebo-controlled trial. After obtaining informed consent, positioning, and baseline EPs recording, patients were randomly assigned to either IV dexmedetomidine 0.6 μg/kg infused over 10 minutes, followed by 0.6 μg/kg/h, or a corresponding volume of IV normal saline (placebo). EP measures at 60 ± 30 minutes after initiation of study drug were defined as T1 and at 150 ± 30 minutes were defined as T2. Changes from baseline to T1 (primary end point) and from baseline to T2 (secondary end point) in EP latencies (milliseconds) and amplitudes (microvolts) were compared between groups. Data presented as mean ± SD (95% confidence interval). Data from 40 patients (dexmedetomidine: n = 20; age, 54 ± 3 years; 10 males; placebo: n = 20; age, 52 ± 2 years; 5 males) were analyzed. There was no difference between dexmedetomidine versus placebo groups in primary end points: change of somatosensory EPs at T1, latency: 0.01 ± 1.3 (-0.64, 0.65) vs 0.01 ± 1.3 (-0.64, 0.65), P = 0.43 (-1.24, 0.45); amplitude: 0.03 ± 0.14 (-0.06, 0.02) vs -0.01 ± 0.13 (-0.07, 0.05), P = 0.76 (-0.074, 0.1); motor EPs amplitude at T1: 65.1 ± 194.8 (-35, 165; n = 18) vs 109.2 ± 241.4 (-24, 243; n = 16), P = 0.57 (-113.5, 241.57); visual EPs at T1 (right eye), amplitude: 2.3 ± 3.6 (-0.4, 5.1; n = 11) vs 0.3 ± 6.0 (-3.3, 3.9; n = 16), P = 0.38 (-6.7, 2.6); latency N1: 2.3 ± 3.6 (-0.4, 5.1) vs 0.3 ± 6.0 (-3.3, 3.9), P = 0.38 (-6.7, 2.6); latency P1: -1.6 ± 13.4 (-11.9, 8.7) vs -1.4 ± 8.1 (-6.3, 3.5), P = 0.97 (-9.3, 9.7) or secondary end points. There were no differences between right and left visual EPs either at T1 or at T2. In clinically relevant doses, dexmedetomidine as an adjunct to total IV anesthesia does not seem to alter EPs and therefore can be safely used during surgeries requiring monitoring of EPs.

Evoked potentials in multiple sclerosis.

PubMed

Kraft, George H

2013-11-01

Before the development of magnetic resonance imaging (MRI), evoked potentials (EPs)-visual evoked potentials, somatosensory evoked potentials, and brain stem auditory evoked responses-were commonly used to determine a second site of disease in patients being evaluated for possible multiple sclerosis (MS). The identification of an area of the central nervous system showing abnormal conduction was used to supplement the abnormal signs identified on the physical examination-thus identifying the "multiple" in MS. This article is a brief overview of additional ways in which central nervous system (CNS) physiology-as measured by EPs-can still contribute value in the management of MS in the era of MRIs. Copyright © 2013 Elsevier Inc. All rights reserved.

Community member perspectives from transgender women and men who have sex with men on pre-exposure prophylaxis as an HIV prevention strategy: implications for implementation

PubMed Central

2012-01-01

Background An international randomized clinical trial (RCT) on pre-exposure prophylaxis (PrEP) as an human immunodeficiency virus (HIV)-prevention intervention found that taken on a daily basis, PrEP was safe and effective among men who have sex with men (MSM) and male-to-female transgender women. Within the context of the HIV epidemic in the United States (US), MSM and transgender women are the most appropriate groups to target for PrEP implementation at the population level; however, their perspectives on evidenced-based biomedical research and the results of this large trial remain virtually unknown. In this study, we examined the acceptability of individual daily use of PrEP and assessed potential barriers to community uptake. Methods We conducted semi-structured interviews with an ethnoracially diverse sample of thirty HIV-negative and unknown status MSM (n = 24) and transgender women (n = 6) in three California metropolitan areas. Given the burden of disease among ethnoracial minorities in the US, we purposefully oversampled for these groups. Thematic coding and analysis of data was conducted utilizing an approach rooted in grounded theory. Results While participants expressed general interest in PrEP availability, results demonstrate: a lack of community awareness and confusion about PrEP; reservations about PrEP utilization, even when informed of efficacious RCT results; and concerns regarding equity and the manner in which a PrEP intervention could be packaged and marketed in their communities. Conclusions In order to effectively reduce HIV health disparities at the population level, PrEP implementation must take into account the uptake concerns of those groups who would actually access and use this biomedical intervention as a prevention strategy. Recommendations addressing these concerns are provided. PMID:23181780

Risk Perception, Sexual Behaviors, and PrEP Adherence Among Substance-Using Men Who Have Sex with Men: a Qualitative Study.

PubMed

Storholm, Erik D; Volk, Jonathan E; Marcus, Julia L; Silverberg, Michael J; Satre, Derek D

2017-08-01

The antiretroviral drug combination emtricitabine and tenofovir disoproxil fumarate (TDF/FTC) taken as pre-exposure prophylaxis (PrEP) is effective in preventing HIV infection, yet it also requires adherence and potentially decreases condom use. This study sought to examine these issues among a key population at risk of HIV infection, substance-using men who have sex with men (MSM). We conducted semi-structured interviews with an ethnically diverse sample of 30 young (aged 20-35) MSM prescribed PrEP within a large integrated healthcare system in San Francisco, who had reported recent drug use or hazardous drinking and one or more missed doses of PrEP. We explored participants' risk perception and sexual risk behavior, drug and alcohol use, and PrEP adherence in the context of substance use. Interviews were transcribed and coded using a directed content analysis approach to identify key categories and commonalities, and differences across participants. Salient subcategories included positive psychological effects of being on PrEP (e.g., decreased anxiety, feelings of empowerment), social effects (e.g., reduced HIV stigma), and reduction in overall perceptions of HIV risk. While overall reported use of condoms went down and many reported a brief period of increased condomless sex following PrEP initiation, others continued condom use with most of their sexual partners. Contextual factors influencing their decision to engage in condomless sex included how well they knew the partner and whether the partner was on PrEP or HIV antiretroviral treatment. Factors associated with poor adherence included disruptions in daily routine and use of alcohol and methamphetamine. PrEP-prescribing clinicians should support their patients in making informed decisions about condom use and identifying strategies to maximize adherence in the context of substance use.

The 17,18-epoxyeicosatetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques.

PubMed

Nagatake, Takahiro; Shiogama, Yumiko; Inoue, Asuka; Kikuta, Junichi; Honda, Tetsuya; Tiwari, Prabha; Kishi, Takayuki; Yanagisawa, Atsushi; Isobe, Yosuke; Matsumoto, Naomi; Shimojou, Michiko; Morimoto, Sakiko; Suzuki, Hidehiko; Hirata, So-Ichiro; Steneberg, Pär; Edlund, Helena; Aoki, Junken; Arita, Makoto; Kiyono, Hiroshi; Yasutomi, Yasuhiro; Ishii, Masaru; Kabashima, Kenji; Kunisawa, Jun

2017-12-27

Metabolites of eicosapentaenoic acid exert various physiologic actions. 17,18-Epoxyeicosatetraenoic acid (17,18-EpETE) is a recently identified new class of antiallergic and anti-inflammatory lipid metabolite of eicosapentaenoic acid, but its effects on skin inflammation and the underlying mechanisms remain to be investigated. We evaluated the effectiveness of 17,18-EpETE for control of contact hypersensitivity in mice and cynomolgus macaques. We further sought to reveal underlying mechanisms by identifying the responsible receptor and cellular target of 17,18-EpETE. Contact hypersensitivity was induced by topical application of 2,4-dinitrofluorobenzene. Skin inflammation and immune cell populations were analyzed by using flow cytometric, immunohistologic, and quantitative RT-PCR analyses. Neutrophil mobility was examined by means of imaging analysis in vivo and neutrophil culture in vitro. The receptor for 17,18-EpETE was identified by using the TGF-α shedding assay, and the receptor's involvement in the anti-inflammatory effects of 17,18-EpETE was examined by using KO mice and specific inhibitor treatment. We found that preventive or therapeutic treatment with 17,18-EpETE ameliorated contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques. 17,18-EpETE was recognized by G protein-coupled receptor (GPR) 40 (also known as free fatty acid receptor 1) and inhibited chemoattractant-induced Rac activation and pseudopod formation in neutrophils. Indeed, the antiallergic inflammatory effect of 17,18-EpETE was abolished in the absence or inhibition of GPR40. 17,18-EpETE inhibits neutrophil mobility through GPR40 activation, which is a potential therapeutic target to control allergic inflammatory diseases. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Roles of affinity and lipophilicity in the slow kinetics of prostanoid receptor antagonists on isolated smooth muscle preparations

PubMed Central

Jones, RL; Woodward, DF; Wang, JW; Clark, RL

2011-01-01

BACKGROUND AND PURPOSE The highly lipophilic acyl-sulphonamides L-798106 and L-826266 showed surprisingly slow antagonism of the prostanoid EP3 receptor system in guinea-pig aorta. Roles of affinity and lipophilicity in the onset kinetics of these and other prostanoid ligands were investigated. EXPERIMENTAL APPROACH Antagonist selectivity was assessed using a panel of human recombinant prostanoid receptor-fluorimetric imaging plate reader assays. Potencies/affinities and onset half-times of agonists and antagonists were obtained on guinea-pig-isolated aorta and vas deferens. n-Octanol-water partition coefficients were predicted. KEY RESULTS L-798106, L-826266 and the less lipophilic congener (DG)-3ap appear to behave as selective, competitive-reversible EP3 antagonists. For ligands of low to moderate lipophilicity, potency increments for EP3 and TP (thromboxane-like) agonism on guinea-pig aorta (above pEC50 of 8.0) were associated with progressively longer onset half-times; similar trends were found for TP and histamine H1 antagonism above a pA2 limit of 8.0. In contrast, L-798106 (EP3), L-826266 (EP3, TP) and the lipophilic H1 antagonists astemizole and terfenadine exhibited very slow onset rates despite their moderate affinities; (DG)-3ap (EP3) had a faster onset. Agonism and antagonism on the vas deferens EP3 system were overall much faster, although trends were similar. CONCLUSIONS AND IMPLICATIONS High affinity and high liphophilicity may contribute to the slow onsets of prostanoid ligands in some isolated smooth muscle preparations. Both relationships are explicable by tissue disposition under the limited diffusion model. EP3 antagonists used as research tools should have moderate lipophilicity. The influence of lipophilicity on the potential clinical use of EP3 antagonists is discussed. PMID:20973775

Short latency compound action potentials from mammalian gravity receptor organs

NASA Technical Reports Server (NTRS)

Jones, T. A.; Jones, S. M.

1999-01-01

Gravity receptor function was characterized in four mammalian species using far-field vestibular evoked potentials (VsEPs). VsEPs are compound action potentials of the vestibular nerve and central relays that are elicited by linear acceleration ramps applied to the cranium. Rats, mice, guinea pigs, and gerbils were studied. In all species, response onset occurred within 1.5 ms of the stimulus onset. Responses persisted during intense (116 dBSPL) wide-band (50 to 50 inverted question mark omitted inverted question mark000 Hz) forward masking, whereas auditory responses to intense clicks (112 dBpeSPL) were eliminated under the same conditions. VsEPs remained after cochlear extirpation but were eliminated following bilateral labyrinthectomy. Responses included a series of positive and negative peaks that occurred within 8 ms of stimulus onset (range of means at +6 dBre: 1.0 g/ms: P1=908 to 1062 micros, N1=1342 to 1475 micros, P2=1632 to 1952 micros, N2=2038 to 2387 micros). Mean response amplitudes at +6 dBre: 1.0 g/ms ranged from 0.14 to 0.99 microV. VsEP input/output functions revealed latency slopes that varied across peaks and species ranging from -19 to -51 micros/dB. Amplitude-intensity slopes also varied ranging from 0.04 to 0.08 microV/dB for rats and mice. Latency values were comparable to those of birds although amplitudes were substantially smaller in mammals. VsEP threshold values were considerably higher in mammals compared to birds and ranged from -8.1 to -10.5 dBre 1.0 g/ms across species. These results support the hypothesis that mammalian gravity receptors are less sensitive to dynamic stimuli than are those of birds.

Characterization of Pressure Transients Generated by Nanosecond Electrical Pulse (nsEP) Exposure

PubMed Central

Roth, Caleb C.; Barnes Jr., Ronald A.; Ibey, Bennett L.; Beier, Hope T.; Christopher Mimun, L.; Maswadi, Saher M.; Shadaram, Mehdi; Glickman, Randolph D.

2015-01-01

The mechanism(s) responsible for the breakdown (nanoporation) of cell plasma membranes after nanosecond pulse (nsEP) exposure remains poorly understood. Current theories focus exclusively on the electrical field, citing electrostriction, water dipole alignment and/or electrodeformation as the primary mechanisms for pore formation. However, the delivery of a high-voltage nsEP to cells by tungsten electrodes creates a multitude of biophysical phenomena, including electrohydraulic cavitation, electrochemical interactions, thermoelastic expansion, and others. To date, very limited research has investigated non-electric phenomena occurring during nsEP exposures and their potential effect on cell nanoporation. Of primary interest is the production of acoustic shock waves during nsEP exposure, as it is known that acoustic shock waves can cause membrane poration (sonoporation). Based on these observations, our group characterized the acoustic pressure transients generated by nsEP and determined if such transients played any role in nanoporation. In this paper, we show that nsEP exposures, equivalent to those used in cellular studies, are capable of generating high-frequency (2.5 MHz), high-intensity (>13 kPa) pressure transients. Using confocal microscopy to measure cell uptake of YO-PRO®-1 (indicator of nanoporation of the plasma membrane) and changing the electrode geometry, we determined that acoustic waves alone are not responsible for poration of the membrane. PMID:26450165

Functional exploration of extracellular polymeric substances (EPS) in the bioleaching of obsolete electric vehicle LiNixCoyMn1-x-yO2 Li-ion batteries.

PubMed

Wang, Jia; Tian, Bingyang; Bao, Yihui; Qian, Can; Yang, Yiran; Niu, Tianqi; Xin, Baoping

2018-07-15

As a fairly new concept, the recovery of valuable metals from urban mining by using bioleaching has become a hotspot. However, the function of extracellular polymeric substances (EPS) in the bioleaching of urban mining gains little attention. The current study used spent EV LIBs to represent urban mining products and systematically explored the function and role of EPS in the attachment of cells to the cathodes, formation of aggregates (cell-EPS-cathode), variation in the electrical and surface properties of the aggregates, concentration of both Fe 2+ and Fe 3+ surrounding the aggregates, electron transfer inside the aggregates and metals released from the aggregates. The results indicated that a strong adhesion of cells to the cathodes occurs mediated by EPS via both hydrophobic force as a main role and electrostatic force as a minor role. Second, the EPS not only adsorb Fe 3+ but also more strongly adsorb Fe 2+ to concentrate the Fe 2+ /Fe 3+ cycle inside the aggregates, witnessing stronger reductive attack on the high valence state of metals as a contact reductive mechanism. Third, the retention or addition of EPS elevated the electronic potential and reduced the electronic resistance to lift the corrosion electric current, thereby boosting the electron transfer and metal dissolution. Copyright © 2018 Elsevier B.V. All rights reserved.

Pharmacovigilance of herbal medicines: the potential contributions of ethnobotanical and ethnopharmacological studies.

PubMed

Rodrigues, Eliana; Barnes, Joanne

2013-01-01

Typically, ethnobotanical/ethnopharmacological (EB/EP) surveys are used to describe uses, doses/dosages, sources and methods of preparation of traditional herbal medicines; their application to date in examining the adverse effects, contraindications and other safety aspects of these preparations is limited. From a pharmacovigilance perspective, numerous challenges exist in applying its existing methods to studying the safety profile of herbal medicines, particularly where used by indigenous cultures. This paper aims to contribute to the methodological aspects of EB/EP field work, and to extend the reach of pharmacovigilance, by proposing a tool comprising a list of questions that could be applied during interview and observational studies. The questions focus on the collection of information on the safety profile of traditional herbal medicines as it is embedded in traditional knowledge, as well as on identifying personal experiences (spontaneous reports) of adverse or undesirable effects associated with the use of traditional herbal medicines. Questions on the precise composition of traditional prescriptions or 'recipes', their preparation, storage, administration and dosing are also included. Strengths and limitations of the tool are discussed. From this interweaving of EB/EP and pharmacovigilance arises a concept of ethnopharmacovigilance for traditional herbal medicines: the scope of EB/EP is extended to include exploration of the potential harmful effects of medicinal plants, and the incorporation of pharmacovigilance questions into EB/EP studies provides a new opportunity for collection of 'general' traditional knowledge on the safety of traditional herbal medicines and, importantly, a conduit for collection of spontaneous reports of suspected adverse effects. Whether the proposed tool can yield data sufficiently rich and of an appropriate quality for application of EB/EP (e.g. data verification and quantitative analysis tools) and pharmacovigilance techniques (e.g. causality assessment and data mining) requires field testing.

HIV-Negative Partnered Men's Willingness to Use Pre-Exposure Prophylaxis and Associated Factors Among an Internet Sample of U.S. HIV-Negative and HIV-Discordant Male Couples

PubMed Central

Stephenson, Rob

2015-01-01

Abstract Purpose: Research on male couples' willingness to use pre-exposure prophylaxis (PrEP) is critically lacking. Methods: A cross-sectional 2011 Internet survey collected dyadic data from 275 HIV-negative and 58 HIV-discordant male couples to describe 631 HIV-negative partnered mens' willingness to use PrEP and associated couple-level demographic and behavioral factors with multivariate multilevel modeling. Results: Fifty-three percent were very to extremely likely to use PrEP. Willingness was positively associated with being in a mixed race and behaviorally non-monogamous relationship, and with amyl nitrate use with sex outside the relationship. Willingness was negatively associated with having a college education. Conclusion: Prevention efforts should educate male couples about the potential benefits of PrEP. PMID:26790016

Emergency physicians' attitudes and preferences regarding computed tomography, radiation exposure, and imaging decision support.

PubMed

Griffey, Richard T; Jeffe, Donna B; Bailey, Thomas

2014-07-01

Although computerized decision support for imaging is often recommended for optimizing computed tomography (CT) use, no studies have evaluated emergency physicians' (EPs') preferences regarding computerized decision support in the emergency department (ED). In this needs assessment, the authors sought to determine if EPs view overutilization as a problem, if they want decision support, and if so, the kinds of support they prefer. A 42-item, Web-based survey of EPs was developed and used to measure EPs' attitudes, preferences, and knowledge. Key contacts at local EDs sent letters describing the study to their physicians. Exploratory principal components analysis (PCA) was used to determine the underlying factor structure of multi-item scales, Cronbach's alpha was used to measure internal consistency of items on a scale, Spearman correlations were used to describe bivariate associations, and multivariable linear regression analysis was used to identify variables independently associated with physician interest in decision support. Of 235 surveys sent, 155 (66%) EPs responded. Five factors emerged from the PCA. EPs felt that: 1) CT overutilization is a problem in the ED (α = 0.75); 2) a patient's cumulative CT study count affects decisions of whether and what type of imaging study to order only some of the time (α = 0.75); 3) knowledge that a patient has had prior CT imaging for the same indication makes EPs less likely to order a CT (α = 0.42); 4) concerns about malpractice, patient satisfaction, or insistence on CTs affect CT ordering decisions (α = 0.62); and 5) EPs want decision support before ordering CTs (α = 0.85). Performance on knowledge questions was poor, with only 18% to 39% correctly responding to each of the three multiple-choice items about effective radiation doses of chest radiograph and single-pass abdominopelvic CT, as well as estimated increased risk of cancer from a 10-mSv exposure. Although EPs wanted information on patients' cumulative exposures, they feel inadequately familiar with this information to make use of it clinically. If provided with patients' cumulative radiation exposures from CT, 87% of EPs said that they would use this information to discuss imaging options with their patients. In the multiple regression model, which included all variables associated with interest in decision support at p < 0.10 in bivariate tests, items independently associated with EPs' greater interest in all types of decision support proposed included lower total knowledge scores, greater frequency that cumulative CT study count affects EP's decision to order CTs, and greater agreement that overutilization of CT is a problem and that awareness of multiple prior CTs for a given indication affects CT ordering decisions. Emergency physicians view overutilization of CT scans as a problem with potential for improvement in the ED and would like to have more information to discuss risks with their patients. EPs are interested in all types of imaging decision support proposed to help optimize imaging ordering in the ED and to reduce radiation to their patients. Findings reveal several opportunities that could potentially affect CT utilization. © 2014 by the Society for Academic Emergency Medicine.

The Use of Online Posts to Identify Barriers to and Facilitators of HIV Pre-exposure Prophylaxis (PrEP) Among Men Who Have Sex with Men: A Comparison to a Systematic Review of the Peer-Reviewed Literature.

PubMed

Hannaford, Alisse; Lipshie-Williams, Madeleine; Starrels, Joanna L; Arnsten, Julia H; Rizzuto, Jessica; Cohen, Phillip; Jacobs, Damon; Patel, Viraj V

2018-04-01

Pre-exposure prophylaxis (PrEP) remains an under-utilized HIV prevention tool among men who have sex with men (MSM). To more comprehensively elucidate barriers and facilitators to PrEP use among US MSM, we conducted a systematic review of peer-reviewed published articles and content analysis of online posts about PrEP. We searched peer-reviewed databases (Medline, Web of Science, Google Scholar) using MESH headings and keywords about PrEP and/or HIV prevention from 2005 to 2015. We included original studies among MSM in the US that reported on barriers, facilitators, or other factors related to PrEP use. We also searched online posts and associated comments (news articles, opinion pieces, blogs and other social media posts) in diverse venues (Facebook, Slate Outward, Huffington Post Gay Voices, Queerty, and My PrEP Experience blog) to identify posts about PrEP. We used content analysis to identify themes and compare potential differences between the peer-reviewed literature and online posts. We identified 25 peer-reviewed articles and 28 online posts meeting inclusion criteria. We identified 48 unique barriers and 46 facilitators to using PrEP. These 94 themes fit into six overarching categories: (1) access (n = 14), (2) attitudes/beliefs (n = 24), (3) attributes of PrEP (n = 13), (4) behaviors (n = 11), (5) sociodemographic characteristics (n = 8), and (6) social network (n = 6). In all categories, analysis of online posts resulted in identification of a greater number of unique themes. Thirty-eight themes were identified in the online posts that were not identified in the peer-reviewed literature. We identified barriers and facilitators to PrEP in online posts that were not identified in a systematic review of the peer-reviewed literature. By incorporating data both from a systematic review of peer-reviewed articles and from online posts, we have identified salient and novel information about barriers to and facilitators of PrEP use. Traditional research approaches may not comprehensively capture current factors important for designing and implementing PrEP related interventions.

Electrophysiological changes correlated with temperature increases induced by high-intensity focused ultrasound ablation.

PubMed

Wu, Ziqi; Kumon, Ronald E; Laughner, Jacob I; Efimov, Igor R; Deng, Cheri X

2015-02-01

To gain better understanding of the detailed mechanisms of high-intensity focused ultrasound (HIFU) ablation for cardiac arrhythmias, we investigated how the cellular electrophysiological (EP) changes were correlated with temperature increases and thermal dose (cumulative equivalent minutes [CEM43]) during HIFU application using Langendorff-perfused rabbit hearts. Employing voltage-sensitive dye di-4-ANEPPS, we measured the EP and temperature during HIFU using simultaneous optical mapping and infrared imaging. Both action potential amplitude (APA) and action potential duration at 50% repolarization (APD50) decreased with temperature increases, and APD50 was more thermally sensitive than APA. EP and tissue changes were irreversible when HIFU-induced temperature increased above 52.3 ± 1.4°C and log10(CEM43) above 2.16 ± 0.51 (n = 5), but were reversible when temperature was below 50.1 ± 0.8°C and log10(CEM43) below -0.9 ± 0.3 (n = 9). EP and temperature/thermal dose changes were spatially correlated with HIFU-induced tissue necrosis surrounded by a transition zone. Copyright © 2015 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

Age-related differences in event-related potentials for early visual processing of emotional faces.

PubMed

Hilimire, Matthew R; Mienaltowski, Andrew; Blanchard-Fields, Fredda; Corballis, Paul M

2014-07-01

With advancing age, processing resources are shifted away from negative emotional stimuli and toward positive ones. Here, we explored this 'positivity effect' using event-related potentials (ERPs). Participants identified the presence or absence of a visual probe that appeared over photographs of emotional faces. The ERPs elicited by the onsets of angry, sad, happy and neutral faces were recorded. We examined the frontocentral emotional positivity (FcEP), which is defined as a positive deflection in the waveforms elicited by emotional expressions relative to neutral faces early on in the time course of the ERP. The FcEP is thought to reflect enhanced early processing of emotional expressions. The results show that within the first 130 ms young adults show an FcEP to negative emotional expressions, whereas older adults show an FcEP to positive emotional expressions. These findings provide additional evidence that the age-related positivity effect in emotion processing can be traced to automatic processes that are evident very early in the processing of emotional facial expressions. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

An evaluation of complementary relationship assumptions

NASA Astrophysics Data System (ADS)

Pettijohn, J. C.; Salvucci, G. D.

2004-12-01

Complementary relationship (CR) models, based on Bouchet's (1963) somewhat heuristic CR hypothesis, are advantageous in their sole reliance on readily available climatological data. While Bouchet's CR hypothesis requires a number of questionable assumptions, CR models have been evaluated on variable time and length scales with relative success. Bouchet's hypothesis is grounded on the assumption that a change in potential evapotranspiration (Ep}) is equal and opposite in sign to a change in actual evapotranspiration (Ea), i.e., -dEp / dEa = 1. In his mathematical rationalization of the CR, Morton (1965) similarly assumes that a change in potential sensible heat flux (Hp) is equal and opposite in sign to a change in actual sensible heat flux (Ha), i.e., -dHp / dHa = 1. CR models have maintained these assumptions while focusing on defining Ep and equilibrium evapotranspiration (Epo). We question Bouchet and Morton's aforementioned assumptions by revisiting CR derivation in light of a proposed variable, φ = -dEp/dEa. We evaluate φ in a simplified Monin Obukhov surface similarity framework and demonstrate how previous error in the application of CR models may be explained in part by previous assumptions that φ =1. Finally, we discuss the various time and length scales to which φ may be evaluated.

Potential evapotranspiration and the likelihood of future drought

NASA Technical Reports Server (NTRS)

Rind, D.; Hansen, J.; Goldberg, R.; Rosenzweig, C.; Ruedy, R.

1990-01-01

The possibility that the greenhouse warming predicted by the GISS general-circulation model and other GCMs could lead to severe droughts is investigated by means of numerical simulations, with a focus on the role of potential evapotranspiration E(P). The relationships between precipitation (P), E(P), soil moisture, and vegetation changes in GCMs are discussed; the empirically derived Palmer drought-intensity index and a new supply-demand index (SDDI) based on changes in P - E(P) are described; and simulation results for the period 1960-2060 are presented in extensive tables, graphs, and computer-generated color maps. Simulations with both drought indices predict increasing drought frequency for the U.S., with effects already apparent in the 1990s and a 50-percent frequency of severe droughts by the 2050s. Analyses of arid periods during the Mesozoic and Cenozoic are shown to support the use of the SDDI in GCM drought prediction.

A Qualitative Study of Provider Thoughts on Implementing Pre-Exposure Prophylaxis (PrEP) in Clinical Settings to Prevent HIV Infection

PubMed Central

Arnold, Emily A.; Hazelton, Patrick; Lane, Tim; Christopoulos, Katerina A.; Galindo, Gabriel R.; Steward, Wayne T.; Morin, Stephen F.

2012-01-01

Background A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States. Methods Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time. Results Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations. Conclusions While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice. PMID:22792384

A qualitative study of provider thoughts on implementing pre-exposure prophylaxis (PrEP) in clinical settings to prevent HIV infection.

PubMed

Arnold, Emily A; Hazelton, Patrick; Lane, Tim; Christopoulos, Katerina A; Galindo, Gabriel R; Steward, Wayne T; Morin, Stephen F

2012-01-01

A recent clinical trial demonstrated that a daily dose tenofovir disoproxil fumarate and emtricitabrine (TDF-FTC) can reduce HIV acquisition among men who have sex with men (MSM) and transgender (TG) women by 44%, and up to 90% if taken daily. We explored how medical and service providers understand research results and plan to develop clinical protocols to prescribe, support and monitor adherence for patients on PrEP in the United States. Using referrals from our community collaborators and snowball sampling, we recruited 22 healthcare providers in San Francisco, Oakland, and Los Angeles for in-depth interviews from May-December 2011. The providers included primary care physicians seeing high numbers of MSM and TG women, HIV specialists, community health clinic providers, and public health officials. We analyzed interviews thematically to produce recommendations for setting policy around implementing PrEP. Interview topics included: assessing clinician impressions of PrEP and CDC guidance, considerations of cost, office capacity, dosing schedules, and following patients over time. Little or no demand for PrEP from patients was reported at the time of the interviews. Providers did not agree on the most appropriate patients for PrEP and believed that current models of care, which do not involve routine frequent office visits, were not well suited for prescribing PrEP. Providers detailed the need to build capacity and were concerned about monitoring side effects and adherence. PrEP was seen as potentially having impact on the epidemic but providers also noted that community education campaigns needed to be tailored to effectively reach specific vulnerable populations. While PrEP may be a novel and clinically compelling prevention intervention for MSM and TG women, it raises a number of important implementation challenges that would need to be addressed. Nonetheless, most providers expressed optimism that they eventually could prescribe and monitor PrEP in their practice.

SIPP, a Novel Mitochondrial Phosphate Carrier, Mediates in Self-Incompatibility1[OPEN

PubMed Central

2017-01-01

In Solanaceae, the S-specific interaction between the pistil S-RNase and the pollen S-Locus F-box protein controls self-incompatibility (SI). Although this interaction defines the specificity of the pollen rejection response, the identification of three pistil essential modifier genes unlinked to the S-locus (HT-B, 120K, and NaStEP) unveils a higher degree of complexity in the pollen rejection pathway. We showed previously that NaStEP, a stigma protein with homology with Kunitz-type protease inhibitors, is essential to SI in Nicotiana spp. During pollination, NaStEP is taken up by pollen tubes, where potential interactions with pollen tube proteins might underlie its function. Here, we identified NaSIPP, a mitochondrial protein with phosphate transporter activity, as a novel NaStEP-interacting protein. Coexpression of NaStEP and NaSIPP in pollen tubes showed interaction in the mitochondria, although when expressed alone, NaStEP remains mostly cytosolic, implicating NaSIPP-mediated translocation of NaStEP into the organelle. The NaSIPP transcript is detected specifically in mature pollen of Nicotiana spp.; however, in self-compatible plants, this gene has accumulated mutations, so its coding region is unlikely to produce a functional protein. RNA interference suppression of NaSIPP in Nicotiana spp. pollen grains disrupts the SI by preventing pollen tube inhibition. Taken together, our results are consistent with a model whereby the NaStEP and NaSIPP interaction, in incompatible pollen tubes, might destabilize the mitochondria and contribute to arrest pollen tube growth. PMID:28874520

Mechanism and Parameter Optimization of Fenton’s Reagent Integrated with Surfactant Pretreatment to Improve Sludge Dewaterability

PubMed Central

Hong, Chen; Yang, Qiang; Feng, Lihui; Jia, Mengmeng; Li, Yifei

2017-01-01

Sludge dewatering can effectively reduce the volume and mass of sludge for subsequent treatment and disposal. The work validated the potential of Fenton’s reagent combined with dodecyl dimethyl benzyl ammonium chloride (DDBAC) in improving sludge dewaterability and proposed the mechanism of joint conditioning. The composite conditioner dosage was optimized using response surface methodology. Results indicated the good conditioning capability of the composite conditioners. The optimum dosages for H2O2, Fe2+, and DDBAC were 44.6, 39.6, and 71.0 mg/g, respectively, at which a sludge cake water content of 59.67% could be achieved. Moreover, a second-order polynomial equation was developed to describe the behavior of joint conditioning. Analysis of the reaction mechanism showed that Fenton oxidation effectively decomposed extracellular polymeric substance (EPS), including loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS), into dissolved organics, such as proteins and polysaccharides. The process facilitated the conversion of the bound water into free water. Furthermore, DDBAC further released the bound water through solubilization of TB-EPS and LB-EPS after the Fenton reaction. The bound water content of the sludge conditioned with Fenton’s reagent decreased from 3.15 to 1.36 g/g and further decreased to 1.08 g/g with the addition of DDBAC. High-performance liquid chromatography analysis verified that the composite conditioning could oxidize and hydrolyze EPS into low-molecular-mass organics (e.g., formic and acetic acid), thereby facilitating the release of bound water. PMID:28081203

High Willingness to Use HIV Pre-Exposure Prophylaxis Among Transgender Women in Argentina.

PubMed

Zalazar, Virginia; Arístegui, Inés; Kerr, Thomas; Marshall, Brandon D L; Romero, Marcela; Sued, Omar; Socías, M Eugenia

2016-01-01

Purpose: In Argentina, transgender women face a disproportionately high prevalence of HIV infection (34%). Although not currently approved in Argentina, pre-exposure prophylaxis (PrEP) may offer a potential effective HIV prevention tool for this population. In this study, we assessed the willingness to use PrEP among transgender women in Argentina. Methods: Data were drawn from a nationwide cross-sectional survey conducted among transgender women in 2013. Using multivariable logistic regression, we assessed the prevalence of and factors associated with willingness to use PrEP among transgender women with negative or unknown HIV status. Results: This study included 337 transgender women (278 HIV negative and 59 with unknown HIV status), most of whom had a history of sex work involvement (81.8%). Overall, 301 (89.3%) expressed willingness to use PrEP. In a multivariable analysis, having casual sexual partners was positively associated with willingness to use PrEP (adjusted odds ratio [AOR]=4.26, 95% confidence interval [CI] 1.73-10.51), while discrimination by healthcare workers was negatively associated (AOR=0.33, 95% CI 0.12-0.88). Conclusion: We found high levels of willingness to use PrEP among transgender women in Argentina, suggesting that there is high perception of HIV risk in this population. However, discrimination by healthcare workers was a strong negative correlate of willingness to use PrEP, suggesting that multilevel interventions that address gender-based stigma in healthcare settings will be critical for the success of PrEP as an HIV prevention strategy in this population.

High Willingness to Use HIV Pre-Exposure Prophylaxis Among Transgender Women in Argentina

PubMed Central

Zalazar, Virginia; Arístegui, Inés; Kerr, Thomas; Marshall, Brandon D.L.; Romero, Marcela; Sued, Omar; Socías, M. Eugenia

2016-01-01

Abstract Purpose: In Argentina, transgender women face a disproportionately high prevalence of HIV infection (34%). Although not currently approved in Argentina, pre-exposure prophylaxis (PrEP) may offer a potential effective HIV prevention tool for this population. In this study, we assessed the willingness to use PrEP among transgender women in Argentina. Methods: Data were drawn from a nationwide cross-sectional survey conducted among transgender women in 2013. Using multivariable logistic regression, we assessed the prevalence of and factors associated with willingness to use PrEP among transgender women with negative or unknown HIV status. Results: This study included 337 transgender women (278 HIV negative and 59 with unknown HIV status), most of whom had a history of sex work involvement (81.8%). Overall, 301 (89.3%) expressed willingness to use PrEP. In a multivariable analysis, having casual sexual partners was positively associated with willingness to use PrEP (adjusted odds ratio [AOR]=4.26, 95% confidence interval [CI] 1.73–10.51), while discrimination by healthcare workers was negatively associated (AOR=0.33, 95% CI 0.12–0.88). Conclusion: We found high levels of willingness to use PrEP among transgender women in Argentina, suggesting that there is high perception of HIV risk in this population. However, discrimination by healthcare workers was a strong negative correlate of willingness to use PrEP, suggesting that multilevel interventions that address gender-based stigma in healthcare settings will be critical for the success of PrEP as an HIV prevention strategy in this population. PMID:28861540

Assessment of environmental effects on Space Station Freedom Electrical Power System

NASA Technical Reports Server (NTRS)

Lu, Cheng-Yi; Nahra, Henry K.

1991-01-01

Analyses of EPS (electrical power system) interactions with the LEO (low earth orbit) environment are described. The results of these analyses will support EPS design so as to be compatible with the natural and induced environments and to meet power, lifetime, and performance requirements. The environmental impacts to the Space Station Freedom EPS include aerodynamic drag, atomic oxygen erosion, ultraviolet degradation, VXB effect, ionizing radiation dose and single event effects, electromagnetic interference, electrostatic discharge, plasma interactions (ion sputtering, arcing, and leakage current), meteoroid and orbital debris threats, thermal cycling effects, induced current and voltage potential differences in the SSF due to induced electric field, and contamination degradation.

Measure Guideline. Transitioning From Three-Coat Stucco to One-Coat Stucco With EPS

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

Brozyna, K.; Davis, G.; Rapport, A.

2012-04-01

This measure guideline has been developed to help builders transition from using a traditional three-coat stucco wall-cladding system to a one-coat stucco wall-cladding system with expanded polystyrene (EPS) insulated sheathing. The one-coat system maintains the look of a traditional stucco system but uses only a base layer and a finish coat over EPS insulation that achieves higher levels of energy efficiency. Potential risks associated with the installation of a one-coat stucco system are addressed in terms of design, installation, and warranty concerns such as cracking and delamination, along with mitigation strategies to reduce these risks.

Multimodal evoked potentials in patients with multiple sclerosis in assessment of the course of the disease.

PubMed

Łabuz-Roszak, Beata; Torbus, Magdalena; Kubicka-Bączyk, Katarzyna; Machowska-Majchrzak, Agnieszka; Kierber, Agata; Borucka, Katarzyna; Zellner, Małgorzata; Starostak-Tatar, Anna; Pierzchała, Krystyna

Multiple sclerosis (MS) is a chronic inflammatory, demyelinating disease of the central nervous system with a multifocal damage. The assessment of the MS course by multimodal evoked potentials (EP). We evaluated 95 patients (63 female, 32 male) with relapsing-remitting MS in the average age of 36.4±10.4. The average disease duration was 4.6±7.4 year. Among them, 48 patients (50.5%) were treated with immunomodulatory drugs. All patients underwent neurological examination and EP testing: VEP (visual evoked potentials), SEP (somatosensory evoked potentials), endogenous potential P300. The latencies of following waves were evaluated: P100 (VEP), N4 , N9 , N13, N20, P22 (SEP) and P300, with the reference values of the Neurophysiological Research Laboratory of the Department of Neurology in Zabrze. Abnormal VEP(I) was found in 80 patients (84.2%), SEP(I) in 9 patients (9.5%), P300(I) in 15 patients (15.8%). Abnormal result of the control research VEP (II) was found in 23 patients (82.1%), SEP(II) in 1 patient (3.6%), P300(II) in 4 patients (14.3%). The average values of the waves latencies in the control study were higher, however the statistical significance was not found. The correlation was observed between EDSS, and N20 and P22. No relationship was found between EP and age, disease duration, number of relapses and treatment. In the era of neuroimaging, usage of EP in the diagnosis and assessment of MS is limited. Electrophysiological studies may be used in addition to the clinical examination to confirm the multifocal damage.

Synthesis, microsome-mediated metabolism, and identification of major metabolites of environmental pollutant naphtho[8,1,2-ghi]chrysene.

PubMed

Sharma, Arun K; Gowdahalli, Krishnegowda; Gimbor, Melissa; Amin, Shantu

2008-05-01

Naphtho[8,1,2- ghi]chrysene, commonly known as naphtho[1,2- e]pyrene (N[1,2- e]P) is a widespread environmental pollutant, identified in coal tar extract, air borne particulate matter, marine sediment, cigarette smoke condensate, and vehicle exhaust. Herein, we determined the ability of rat liver microsomes to metabolize N[1,2- e]P and an unequivocal assignment of the metabolites by comparing them with independently synthesized standards. We developed the synthesis of both the fjord region and the K-region dihydrodiols and various phenolic derivatives for metabolite identification. The 12-OH-N[1,2- e]P, fjord region dihydrodiol 14 and diol epoxide 15 were synthesized using a Suzuki cross-coupling reaction followed by the appropriate manipulation of the functional groups. The K-region trans-4,5-dihydrodiol ( 18) was prepared by the treatment of N[1,2- e]P with OsO 4 to give cis-dihydrodiol 16, followed by pyridinium chlorochromate oxidation to quinone 17, and finally reduction with NaBH 4 to afford the dihydrodiol 18 with the desired trans stereochemistry. The 9-OH-N[1,2- e]P ( 30) and N[1,2- e]P trans-9,10-dihydrodiol ( 32) were also synthesized following a Suzuki cross-coupling approach starting from 1,2,3,6,7,8-hexahydropyrene-4-boronic acid. The metabolism of N[1,2- e]P with rat liver microsomes led to several dihydrodiol and phenolic metabolites as assessed by the HPLC trace. The 11,12-dihydrodiol and 4,5-dihydrodiol were identified as major dihydrodiol metabolites. The synthesized 9,10-dihydrodiol, on the other hand, did not match with any of the peaks in the metabolism trace. Among the phenols, only 12-OH-N[1,2- e]P was identified in the metabolism. The other phenolic derivatives synthesized, that is, the 4-/5-, 9-, 10-, and 11-hydroxy derivatives, were not detected in the metabolism trace. In summary, N[1,2- e]P trans-11,12-dihydrodiol was the major metabolite formed along with N[1,2- e]P 4,5- trans-dihydrodiol and 12-OH-N[1,2- e]P on exposure of rat liver microsomes to N[1,2- e]P. The presence of N[1,2- e]P in the environment and formation of fjord region dihydrodiol 14 as a major metabolite in in vitro metabolism studies strongly suggest the role of N[1,2- e]P as a potential health hazard.

Extracellular Polymeric Substances (EPS) of Freshwater Biofilms Stabilize and Modify CeO2 and Ag Nanoparticles

PubMed Central

Kroll, Alexandra; Behra, Renata; Kaegi, Ralf; Sigg, Laura

2014-01-01

Streams are potential receiving compartments for engineered nanoparticles (NP). In streams, NP may remain dispersed or settle to the benthic compartment. Both dispersed and settling NP can accumulate in benthic biofilms called periphyton that are essential to stream ecosystems. Periphytic organisms excrete extracellular polymeric substances (EPS) that interact with any material reaching the biofilms. To understand the interaction of NP with periphyton it is therefore crucial to study the interaction of NP with EPS. We investigated the influence of EPS on the physicochemical properties of selected NP (CeO2, Ag) under controlled conditions at pH 6, 7.6, 8.6 and light or dark exposure. We extracted EPS from five different periphyton communities, characterized the extracts, and exposed CeO2 and carbonate-stabilized Ag NP (0.5 and 5 mg/L, both 25 nm primary particle size) and AgNO3 to EPS (10 mg/L) over two weeks. We measured NP size distribution, shape, primary particle size, surface plasmon resonance, and dissolution. All EPS extracts were composed of biopolymers, building blocks of humic substances, low molecular weight (Mr) acids, and small amphiphilic or neutral compounds in varying concentrations. CeO2 NP were stabilized by EPS independent of pH and light/dark while dissolution increased over time in the dark at pH 6. EPS induced a size increase in Ag NP in the light with decreasing pH and the formation of metallic Ag NP from AgNO3 at the same conditions via EPS-enhanced photoreduction. NP transformation and formation were slower in the extract with the lowest biopolymer and low Mr acid concentrations. Periphytic EPS in combination with naturally varying pH and light/dark conditions influence the properties of the Ag and CeO2 NP tested and thus the exposure conditions within biofilms. Our results indicate that periphytic organisms may be exposed to a constantly changing mixture of engineered and naturally formed Ag NP and Ag+. PMID:25333364

Patients with encapsulating peritoneal sclerosis have increased peritoneal expression of connective tissue growth factor (CCN2), transforming growth factor-β1, and vascular endothelial growth factor.

PubMed

Abrahams, Alferso C; Habib, Sayed M; Dendooven, Amélie; Riser, Bruce L; van der Veer, Jan Willem; Toorop, Raechel J; Betjes, Michiel G H; Verhaar, Marianne C; Watson, Christopher J E; Nguyen, Tri Q; Boer, Walther H

2014-01-01

Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P < 0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P < 0.001), TGFβ1 (24-fold, P < 0.05), and VEGF (77-fold, P < 0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0 ± 4.5 vs. 0.91 ± 0.92 ng/ml, P < 0.01), while plasma CCN2 levels were not increased. Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study.

Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

PubMed Central

Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

2014-01-01

Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a locally driven response. The potential of CCN2 as biomarker and target for CCN2-inhibiting agents to prevent or treat EPS warrants further study. PMID:25384022

Effectiveness and Cost Effectiveness of Oral Pre-Exposure Prophylaxis in a Portfolio of Prevention Programs for Injection Drug Users in Mixed HIV Epidemics

PubMed Central

Alistar, Sabina S.; Owens, Douglas K.; Brandeau, Margaret L.

2014-01-01

Background Pre-exposure prophylaxis with oral antiretroviral treatment (oral PrEP) for HIV-uninfected injection drug users (IDUs) is potentially useful in controlling HIV epidemics with a significant injection drug use component. We estimated the effectiveness and cost effectiveness of strategies for using oral PrEP in various combinations with methadone maintenance treatment (MMT) and antiretroviral treatment (ART) in Ukraine, a representative case for mixed HIV epidemics. Methods and Findings We developed a dynamic compartmental model of the HIV epidemic in a population of non-IDUs, IDUs who inject opiates, and IDUs in MMT, adding an oral PrEP program (tenofovir/emtricitabine, 49% susceptibility reduction) for uninfected IDUs. We analyzed intervention portfolios consisting of oral PrEP (25% or 50% of uninfected IDUs), MMT (25% of IDUs), and ART (80% of all eligible patients). We measured health care costs, quality-adjusted life years (QALYs), HIV prevalence, HIV infections averted, and incremental cost effectiveness. A combination of PrEP for 50% of IDUs and MMT lowered HIV prevalence the most in both IDUs and the general population. ART combined with MMT and PrEP (50% access) averted the most infections (14,267). For a PrEP cost of $950, the most cost-effective strategy was MMT, at $520/QALY gained versus no intervention. The next most cost-effective strategy consisted of MMT and ART, costing $1,000/QALY gained compared to MMT alone. Further adding PrEP (25% access) was also cost effective by World Health Organization standards, at $1,700/QALY gained. PrEP alone became as cost effective as MMT at a cost of $650, and cost saving at $370 or less. Conclusions Oral PrEP for IDUs can be part of an effective and cost-effective strategy to control HIV in regions where injection drug use is a significant driver of the epidemic. Where budgets are limited, focusing on MMT and ART access should be the priority, unless PrEP has low cost. PMID:24489747

Probabilistic Storm Surge Forecast For Venice

NASA Astrophysics Data System (ADS)

Mel, Riccardo; Lionello, Piero

2013-04-01

This study describes an ensemble storm surge prediction procedure for the city of Venice, which is potentially very useful for its management, maintenance and for operating the movable barriers that are presently being built. Ensemble Prediction System (EPS) is meant to complement the existing SL forecast system by providing a probabilistic forecast and information on uncertainty of SL prediction. The procedure is applied to storm surge events in the period 2009-2010 producing for each of them an ensemble of 50 simulations. It is shown that EPS slightly increases the accuracy of SL prediction with respect to the deterministic forecast (DF) and it is more reliable than it. Though results are low biased and forecast uncertainty is underestimated, the probability distribution of maximum sea level produced by the EPS is acceptably realistic. The error of the EPS mean is shown to be correlated with the EPS spread. SL peaks correspond to maxima of uncertainty and uncertainty increases linearly with the forecast range. The quasi linear dynamics of the storm surges produces a modulation of the uncertainty after the SL peak with period corresponding to that of the main Adriatic seiche.

Evaluation of dermal wound healing activity and in vitro antibacterial and antioxidant activities of a new exopolysaccharide produced by Lactobacillus sp.Ca6.

PubMed

Trabelsi, Imen; Ktari, Naourez; Ben Slima, Sirine; Triki, Mehdi; Bardaa, Sana; Mnif, Hela; Ben Salah, Riadh

2017-10-01

The present study aimed to evaluate the in vitro antibacterial and antioxidant activities and the in vivo wound healing performance of a noval exopolysaccharides (EPS-Ca 6 ) produced by Lactobacillus sp.Ca 6 strain. The results showed that EPS-Ca 6 had a potential antioxidant activity determined through four different assays: DPPH scavenging activity, reducing power, β-carotene bleaching by linoleic acid assay, and Metal chelating activities. It also exhibited significant antibacterial activity against pathogenic bacteria Salmonella enterica and Micrococcus luteus. The wound healing activity of the EPS-Ca 6 , using excision wound model in rats, showed that this novel EPS accelerated significantly wound healing activity as compared to the control group, and a total closure was achieved after 14days of wound induction. Furthermore, histological examination of biopsies showed fully re-epithelialized wound with a complete epidermal regeneration. Overall the finding indicates that the EPS-Ca 6 might be useful as a wound healing agent in modern medicine. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular Epidemiology of HIV-1 Subtype B Reveals Heterogeneous Transmission Risk: Implications for Intervention and Control

PubMed Central

Le Vu, Stephane; Ratmann, Oliver; Tostevin, Anna; Dunn, David; Orkin, Chloe; O’Shea, Siobhan; Delpech, Valerie; Brown, Alison; Gill, Noel; Fraser, Christophe

2018-01-01

Abstract Background The impact of HIV pre-exposure prophylaxis (PrEP) depends on infections averted by protecting vulnerable individuals as well as infections averted by preventing transmission by those who would have been infected if not receiving PrEP. Analysis of HIV phylogenies reveals risk factors for transmission, which we examine as potential criteria for allocating PrEP. Methods We analyzed 6912 HIV-1 partial pol sequences from men who have sex with men (MSM) in the United Kingdom combined with global reference sequences and patient-level metadata. Population genetic models were developed that adjust for stage of infection, global migration of HIV lineages, and changing incidence of infection through time. Models were extended to simulate the effects of providing susceptible MSM with PrEP. Results We found that young age <25 years confers higher risk of HIV transmission (relative risk = 2.52 [95% confidence interval, 2.32–2.73]) and that young MSM are more likely to transmit to one another than expected by chance. Simulated interventions indicate that 4-fold more infections can be averted over 5 years by focusing PrEP on young MSM. Conclusions Concentrating PrEP doses on young individuals can avert more infections than random allocation. PMID:29506269

Effect of prostanoid EP4 receptor antagonist, CJ-042,794, in rat models of pain and inflammation.

PubMed

Murase, Akio; Okumura, Takako; Sakakibara, Ayano; Tonai-Kachi, Hiroko; Nakao, Kazunari; Takada, Junji

2008-02-02

Recent study suggests that the proinflammatory and nociceptive effects of prostaglandin E(2) are mediated by prostanoid receptor subtype EP(4) and prostanoid EP(4) receptor may be a potential target for the treatment of inflammatory pain. Here we describe pharmacological characterization of a novel prostanoid EP(4) receptor antagonist, CJ-042,794 (4-{(1S)-1-[({5-chloro-2-[(4-fluorophenyl) oxy] phenyl} carbonyl) amino] ethyl} benzoic acid) in comparison with piroxicam (non-steroidal anti-inflammatory drug) or rofecoxib (cyclooxygenase-2 inhibitor). CJ-042,794 competitively antagonized cAMP accumulation with a pA(2) value of 8.7 in HEK293 cells overexpressing rat prostanoid EP(4) receptors. Orally administered CJ-042,794 dose-dependently inhibited carrageenan-induced mechanical hyperalgesia with an ED(50) value of 4.7 mg/kg (11 micromol/kg) and its maximal activity was somewhat less effective than that of 10 mg/kg piroxicam (30 micromol/kg p.o.). When CJ-042,794 and rofecoxib were administered to adjuvant-induced arthritis rats on Days 12-22 twice daily, both compounds reversed paw swelling to normal levels. These results suggest that a pharmacological blockade of the prostanoid EP(4) receptor may represent a new therapeutic strategy in signs and symptomatic relief of osteoarthritis and/or rheumatoid arthritis.

Configuring the users of new HIV-prevention technologies: the case of HIV pre-exposure prophylaxis.

PubMed

Holt, Martin

2015-01-01

HIV pre-exposure prophylaxis (PrEP) is a prevention technology that involves prescribing antiretroviral drugs to HIV-negative people to protect them from infection. This paper considers how the development of the technology has necessitated the parallel configuration of its users, and how this process has affected the perception and uptake of the technology. In designing a technology, potential users are typically defined, enabled and constrained, partly to create a target population (or market) for the technology, but also to reassure people that it can be used safely and effectively. This process may or may not be helpful for the uptake and use of the technology. Published research on PrEP indicates that while the technology was under trial, the primary focus was on the 'at-risk' subject in need of PrEP, with little or no consideration of the other qualities necessary for successful use. Post-trial accounts of PrEP have begun to outline desirable qualities of successful PrEP use, such as caution, compliance and being organised. It appears that the PrEP user was only partially configured during the technology's development, and the initial focus on risk has done little to counter fears of the technology, which may partially account for its slow uptake.

Pre-exposure prophylaxis (PrEP) for men who have sex with men in Europe: review of evidence for a much needed prevention tool.

PubMed

Reyniers, Thijs; Hoornenborg, Elske; Vuylsteke, Bea; Wouters, Kristien; Laga, Marie

2017-08-01

In many Western countries with good coverage of antiretroviral treatment (ART) programmes the annual number of HIV infections is still high and not (yet) declining among men who have sex with men (MSM). This might indicate that antiretroviral treatment roll-out alone will not turn around the course of the epidemic and that new, additional tools are needed. Antiretrovirals used as prevention tools for people not yet infected with HIV, such as pre-exposure prophylaxis (PrEP) could be such important additional tools. PrEP is a new type of biomedical prevention, which involves the use of antiretrovirals before, during and after (periods of) sexual exposure to HIV. In this review, we will focus on PrEP as a new prevention tool for MSM at high risk in Europe, including its evidence for effectiveness, challenges for implementation, ongoing European demonstration studies; as well as how PrEP relates to other existing prevention tools. In light of European Medicines Agency's recent recommendation for approval of PrEP we briefly review the potential implications. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Preliminary evidence of HIV seroconversion among HIV-negative men who have sex with men taking non-prescribed antiretroviral medication for HIV prevention in Miami, Florida, USA.

PubMed

Buttram, Mance E; Kurtz, Steven P

2017-04-01

Background Limited information suggests that men who have sex with men (MSM) are informally obtaining antiretroviral medication (ARVs) and using them for HIV pre-exposure prophylaxis (PrEP). Data are drawn from an on-going study examining the use of non-prescribed ARVs for PrEP. To date, 24 qualitative interviews have been conducted with HIV-negative, substance-using MSM living in Miami, Florida, USA. Data are presented from two participants who reported HIV seroconversion while using non-prescribed ARVs for PrEP. Preliminary data indicate that some young MSM: (i) lack awareness of and accurate information about the efficacious use of PrEP; (ii) obtain non-prescribed ARVs from HIV-positive sex partners and use these medications for PrEP in a way that does not provide adequate protection against HIV infection or cohere with established guidelines; and (iii) engage in multiple HIV transmission risk behaviours, including condomless anal sex and injection drug use. The informal, non-prescribed and non-medically supervised use of ARVs for HIV prevention has the potential to undermine the protective benefits of PrEP and leave men unprotected against HIV transmission and at risk for ARV resistance.

Protection of silver nanoparticles using Eysenhardtia polystachya in peroxide-induced pancreatic β-Cell damage and their antidiabetic properties in zebrafish.

PubMed

Garcia Campoy, Abraham Heriberto; Perez Gutierrez, Rosa Martha; Manriquez-Alvirde, Gabriela; Muñiz Ramirez, Alethia

2018-01-01

The aim was to explore the efficacy of extract of Eysenhardtia polystachya -loaded silver nanoparticles (EP/AgNPs) on pancreatic β cells, INS-1 cells, and zebrafish as a valuable model for the study of diabetes mellitus. EP/AgNPs were synthesized using methanol/water bark extract of E. polystachya and characterized using various physicochemical techniques. Immersion of adult zebrafish in 111 mM glucose solution resulted in a sustained hyperglycemic, hyperlipidemic state, and serum insulin levels decreased. The synthesized EP/AgNPs showed an absorption peak at 413 nm on ultraviolet-visible spectroscopy, revealing the surface plasmon resonance of the nanoparticles. Transmission electron microscopy indicated that most of the particles were spherical, with a diameter of 10-12 nm, a polydispersity index of 0.197, and a zeta potential of -32.25 mV, suggesting high stability of the nanoparticles. EP/AgNPs promote pancreatic β-cell survival, insulin secretion, enhanced hyperglycemia, and hyperlipidemia in glucose-induced diabetic zebrafish. EP/AgNPs also showed protection of the pancreatic β-cell line INS-1 against hydrogen peroxide-induced oxidative injury. The results indicate that EP/AgNPs have good antidiabetic activity and therefore could be used to prevent the development of diabetes.

Improving outcome in schizophrenia: the potential importance of EPS and neuroleptic dysphoria.

PubMed

Gerlach, Jes

2002-03-01

Despite half a century of antipsychotic drug treatment, the outcome of therapy in schizophrenia remains disappointing. Relapse, rehospitalization, limited fulfilment of social roles, and suicide remain frequent, and the economic costs are high. Current relapse rates may be two to three times higher than those that could be achieved with optimal use of therapy. Poor compliance with treatment is considered to be a significant preventable cause of poor outcome and is in turn likely to be influenced by the patient's experience of drug treatment. There is some evidence that extrapyramidal symptoms (EPS), particularly akathisia and neuroleptic dysphoria, are associated with poor compliance and poor treatment outcome. Atypical antipsychotics have a lower risk of EPS than do standard antipsychotics. Some (risperidone, olanzapine, and ziprasidone) show evidence of a dose-related increase in EPS, but clozapine and quetiapine have demonstrated a placebo-level incidence of EPS across the dose range. Quetiapine does not require the regular blood monitoring mandated for clozapine, and results from a patient survey indicate a high degree of patient satisfaction with treatment. While further research is needed, it is possible that wider use of medications with low EPS and high patient acceptability could promote better compliance and improve the outcome of schizophrenia treatment.

Unidirectional reflectionless light propagation at exceptional points

NASA Astrophysics Data System (ADS)

Huang, Yin; Shen, Yuecheng; Min, Changjun; Fan, Shanhui; Veronis, Georgios

2017-05-01

In this paper, we provide a comprehensive review of unidirectional reflectionless light propagation in photonic devices at exceptional points (EPs). EPs, which are branch point singularities of the spectrum, associated with the coalescence of both eigenvalues and corresponding eigenstates, lead to interesting phenomena, such as level repulsion and crossing, bifurcation, chaos, and phase transitions in open quantum systems described by non-Hermitian Hamiltonians. Recently, it was shown that judiciously designed photonic synthetic matters could mimic the complex non-Hermitian Hamiltonians in quantum mechanics and realize unidirectional reflection at optical EPs. Unidirectional reflectionlessness is of great interest for optical invisibility. Achieving unidirectional reflectionless light propagation could also be potentially important for developing optical devices, such as optical network analyzers. Here, we discuss unidirectional reflectionlessness at EPs in both parity-time (PT)-symmetric and non-PT-symmetric optical systems. We also provide an outlook on possible future directions in this field.

Electrocochleographic analysis of the suppression of tinnitus by electrical promontory stimulation.

PubMed

Watanabe, K; Okawara, D; Baba, S; Yagi, T

1997-01-01

To investigate the origin, and evaluate the mechanism by which tinnitus is suppressed we performed electrical promontory stimulation (EPS) in 56 patients with tinnitus, and measured the compound action potential (CAP) using electrocochleography before and after EPS. In the group of patients in whom tinnitus was suppressed, the CAP amplitudes increased significantly, whereas the latencies showed no remarkable change. In the group of patients in whom tinnitus was not suppressed, both the CAP amplitudes and latencies exhibited no significant change. These data indicate that the effect on the cochlear nerve plays an important role in the suppression of tinnitus by EPS. The CAP reflects the number of the auditory nerve fibers which discharge synchronously. It is speculated that an increase of the CAP amplitudes is caused by synchronizing discharges of the auditory nerve fibers, and that the mechanism by which EPS suppresses tinnitus may be related to synchronizing these discharges.

Hearing dysfunction in heterozygous Mitf(Mi-wh) /+ mice, a model for Waardenburg syndrome type 2 and Tietz syndrome.

PubMed

Ni, Christina; Zhang, Deming; Beyer, Lisa A; Halsey, Karin E; Fukui, Hideto; Raphael, Yehoash; Dolan, David F; Hornyak, Thomas J

2013-01-01

The human deafness-pigmentation syndromes, Waardenburg syndrome (WS) type 2a, and Tietz syndrome are characterized by profound deafness but only partial cutaneous pigmentary abnormalities. Both syndromes are caused by mutations in MITF. To illuminate differences between cutaneous and otic melanocytes in these syndromes, their development and survival in heterozygous Microphthalmia-White (Mitf(Mi-wh) /+) mice were studied and hearing function of these mice characterized. Mitf(Mi-wh) /+ mice have a profound hearing deficit, characterized by elevated auditory brainstem response thresholds, reduced distortion product otoacoustic emissions, absent endocochlear potential, loss of outer hair cells, and stria vascularis abnormalities. Mitf(Mi-wh) /+ embryos have fewer melanoblasts during embryonic development than their wild-type littermates. Although cochlear melanocytes are present at birth, they disappear from the Mitf(Mi-wh) /+ cochlea between P1 and P7. These findings may provide insight into the mechanism of melanocyte and hearing loss in human deafness-pigmentation syndromes such as WS and Tietz syndrome and illustrate differences between otic and follicular melanocytes. © 2012 John Wiley & Sons A/S.

Southern African guidelines on the safe use of pre-exposure prophylaxis in persons at risk of acquiring HIV-1 infection

PubMed Central

Rebe, Kevin; Venter, Francois; Maartens, Gary; Moorhouse, Michelle; Conradie, Francesca; Wallis, Carole; Black, Vivian; Harley, Beth; Eakles, Robyn

2016-01-01

The Southern African HIV Clinicians Society published its first set of oral pre-exposure prophylaxis (PrEP) guidelines in June 2012 for men who have sex with men (MSM) who are at risk of HIV infection. With the flurry of data that has been generated in PrEP clinical research since the first guideline, it became evident that there was a need to revise and expand the PrEP guidelines with new evidence of safety and efficacy of PrEP in several populations, including MSM, transgender persons, heterosexual men and women, HIV-serodiscordant couples and people who inject drugs. This need is particularly relevant following the World Health Organization (WHO) Consolidated Treatment Guidelines released in September 2015. These guidelines advise that PrEP is a highly effective, safe, biomedical option for HIV prevention that can be incorporated with other combination prevention strategies in Southern Africa, given the high prevalence of HIV in the region. PrEP should be tailored to populations at highest risk of HIV acquisition, whilst further data from studies in the region accrue to guide optimal deployment to realise the greatest impact regionally. PrEP may be used intermittently during periods of perceived HIV acquisition risk, rather than continually and lifelong, as is the case with antiretroviral treatment. Recognition and accurate measurement of potential risk in individuals and populations also warrants discussion, but are not extensively covered in these guidelines. PMID:29568613

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions

PubMed Central

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R.; Tantucci, Claudio

2016-01-01

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions. PMID:26689993

Detection of EpCAM-positive microparticles in pleural fluid: A new approach to mini-invasively identify patients with malignant pleural effusions.

PubMed

Roca, Elisa; Lacroix, Romaric; Judicone, Coralie; Laroumagne, Sophie; Robert, Stéphane; Cointe, Sylvie; Muller, Alexandre; Kaspi, Elise; Roll, Patrice; Brisson, Alain R; Tantucci, Claudio; Astoul, Philippe; Dignat-George, Françoise

2016-01-19

Pleural biomarkers allowing to mini-invasively discriminate benign from malignant pleural effusions are needed. Among potential candidates, microparticles (MPs) are extracellular vesicles that vectorize antigen derived from the parent cell. We hypothesized that tumor-derived MPs could be present in the pleural liquid and help to identify patients with malignant pleural effusions. Using highly sensitive flow cytometry and cryo-electron microscopy, we showed that large amounts of MPs from hematopoïetic and vascular origin could be detectable in pleural fluids. Their level did not differ between benign (n = 14) and malignant (n = 71) pleural effusions. Analysis of selected tumoral associated antigens (podoplanin, mucin 1 and EpCAM, epithelial-cell-adhesion-molecule) evidenced for the first time the presence of tumor-derived MPs expressing EpCAM in malignant pleural fluids only (Specificity = 93%, Sensitivity = 49% and 45% for flow cytometry and ELISA, respectively). The detection of EpCAM-positive-MPs (EpCAM + MPs) by flow cytometry showed a better specificity and sensitivity than ELISA to distinguish between pleural carcinoma and the others malignant pleural effusions (MPE; Sp: 96% vs 89%; Se: 79% vs 66%). Combining EpCAM+ MPs and cytology improved the diagnosis of MPE compared to cytology alone. This study establishes the basis for using EpCAM+ MPs as a promising new biomarker that could be added to the armamentarium to mini-invasively identify patients with malignant pleural effusions.

Electroencephalography and analgesics

PubMed Central

Malver, Lasse Paludan; Brokjær, Anne; Staahl, Camilla; Graversen, Carina; Andresen, Trine; Drewes, Asbjørn Mohr

2014-01-01

To assess centrally mediated analgesic mechanisms in clinical trials with pain patients, objective standardized methods such as electroencephalography (EEG) has many advantages. The aim of this review is to provide the reader with an overview of present findings in analgesics assessed with spontaneous EEG and evoked brain potentials (EPs) in humans. Furthermore, EEG methodologies will be discussed with respect to translation from animals to humans and future perspectives in predicting analgesic efficacy. We searched PubMed with MeSH terms ‘analgesics’, ‘electroencephalography’ and ‘evoked potentials’ for relevant articles. Combined with a search in their reference lists 15 articles on spontaneous EEG and 55 papers on EPs were identified. Overall, opioids produced increased activity in the delta band in the spontaneous EEG, but increases in higher frequency bands were also seen. The EP amplitudes decreased in the majority of studies. Anticonvulsants used as analgesics showed inconsistent results. The N-methyl-D-aspartate receptor antagonist ketamine showed an increase in the theta band in spontaneous EEG and decreases in EP amplitudes. Tricyclic antidepressants increased the activity in the delta, theta and beta bands in the spontaneous EEG while EPs were inconsistently affected. Weak analgesics were mainly investigated with EPs and a decrease in amplitudes was generally observed. This review reveals that both spontaneous EEG and EPs are widely used as biomarkers for analgesic drug effects. Methodological differences are common and a more uniform approach will further enhance the value of such biomarkers for drug development and prediction of treatment response in individual patients. PMID:23593934

An experimental setup to characterize MR switched gradient-induced potentials.

PubMed

Fokapu, Odette; El-Tatar, Aziz

2013-06-01

We have developed an experimental setup as an in vitro research tool for studying the contamination of electrophysiological signals (EPS) by MRI environment; particularly, when due to the switched gradient-induced potentials. The system is composed of: 1) a MRI compatible module for the transmission of the EPS into the MRI tunnel, 2) a gelatin-based tissue-mimicking phantom, placed inside the tunnel, in which EPS is injected, 3) a detection module composed of a five input channel MRI compatible transmitter placed inside the tunnel, allowing an on-site pre-amplification of the bio-potentials and their transmission, via an optical fiber cable, to a four filtered output per channel receiver (350 Hz, 160 Hz, 80 Hz, and 40 Hz, for a total of 20 channels) placed in the control room, and 4) a signal processing algorithm used to analyze the generated induced potentials. A set of tests were performed to validate the electronic performances of the setup. We also present in this work an interesting application of the setup, i.e., the acquisition and analysis of the induced potentials with respect of the slice orientation for a given MRI sequence. Significant modifications of the time and frequency characteristics were observed with respect to axial, coronal or sagittal orientations.

Comparative analysis of in vitro characteristics of fresh and frozen-thawed urethral and epididymal spermatozoa from cats (Felis domesticus).

PubMed

Prochowska, Sylwia; Niżański, Wojciech; Partyka, Agnieszka

2016-11-01

The first aim of this study was to provide a comprehensive analysis of structural and functional features of spermatozoa in semen collected from the same cat by two methods: urethral catheterization and epididymis slicing. The second aim was to assess if feline urethral (CT) and epididymal (EP) spermatozoa undergo the same changes during cryopreservation and to compare the postthaw characteristics of spermatozoa collected by the two methods. In the first phase, CT and EP semen were collected from 20 cats, and sperm motility, viability, morphology, computer-assisted sperm analysis (CASA) parameters, membrane and acrosome integrity, mitochondrial potential, lipid peroxidation, and chromatin status were assessed. In the second phase, both types of semen collected from 10 cats were cryopreserved, thawed, and the same sperm parameters were assessed as in fresh semen. Fresh CT spermatozoa (phase I) showed higher (P < 0.05) motility (subjective: median 75.0% vs. 62.5%; by CASA: mean ± SD 60.2 ± 10.7% vs. 43.1 ± 16.7%), morphology (mean ± SD, 57.5 ± 9.6% vs. 45.2 ± 15.9%), and membrane integrity (median live: 89.2% vs. 79.8%). Other parameters were not different between CT and EP spermatozoa. After cryopreservation (phase II), spermatozoa from both types of semen did not differ significantly, except for lipid peroxidation of live sperm cells (median CT: 3.5%, EP: 1.7%, P < 0.05). Urethral and EP spermatozoa showed a similar, significant drop in motility (CT to 18.6 ± 10.3% and EP to 21.6 ± 12.1%, P < 0.05), progressive motility (CT to 6.8 ± 5.9% and EP to 8.3 ± 8.8%, P < 0.05), and rapid movement (from 34.3 ± 20.6% to 8.5 ± 7.0% in CT and from 26.0 ± 14.7% to 10.1 ± 10.4% in EP, P < 0.05), whereas other motion characteristics assessed by CASA were not affected (P > 0.05). The strongest change after cryopreservation was noted in high mitochondrial potential (median CT: 1.3%, EP: 2.2%). Although cryopreservation increased acrosome damage and lipid peroxidation, the level of these changes in the population of live sperm cells remained low (median acrosome damage: CT: 3.3%, EP: 4.5%, lipid peroxidation CT: 3.5%, EP: 1.7%). Cryopreservation did not affect chromatin structure (median percent DNA fragmentation index, CT: 3.3%, EP: 2.3%). In this study, we confirmed that urethral catheterization for collection of semen allows the retrieval of spermatozoa with quality equally good as in those obtained by epididymal slicing. Spermatozoa from both types of semen collected showed similar characteristics after freezing/thawing so both types can be used for semen banking. Copyright © 2016 Elsevier Inc. All rights reserved.

Polysaccharides from Epimedium koreanum Nakai with immunomodulatory activity and inhibitory effect on tumor growth in LLC-bearing mice.

PubMed

Wang, Chengcheng; Feng, Liang; Su, Jiayan; Cui, Li; Dan Liu; Yan, Jun; Ding, Chuanlin; Tan, Xiaobin; Jia, Xiaobin

2017-07-31

Epimedium koreanum Nakai is documented as tonic herbal in China for over a thousand years and has the potential to enhance the body's immunity according to the theory of traditional Chinese medicine. Polysaccharides are one of the most important effective compounds in Epimedium koreanum Nakai. Accumulating evidence indicated polysaccharides derived from traditional Chinese medicine have potent immune-enhancing properties and relatively nontoxic effects in cancer treatment. However, information about immunological regulation in tumor of Epimedium koreanum Nakai polysaccharides is limited and the reports of purification, characterization of polysaccharides have remained less. The purpose of our study was to further investigate the active polysaccharides from Epimedium koreanum Nakai by evaluating the immune-regulation activities in tumor-bearing mice and provide reasonable explanation for traditional application. We firstly purified Epimedium koreanum polysaccharide (EPS) from crude extracts and evaluated EPS in vitro using immunological experiments including maturation and Ag presentation function of DCs, CD4 T-cell differentiation and secretion of anti-cancer cytokines. In LLC-bearing mice model, we investigated its antitumor activities through evaluation of tumor cell proliferative activity, calculation of immune organ indexes and relative host immune system function tests. Results showed that EPS (180 × 10 4 Da) was composed of mannose (Man), rhamnose (Rha), glucuronic acid (GlcUA), galactosamine (GalN), glucose (Glc), galactose (Gal), arabinose (Ara) and fructose (Fuc). Chemical composition assay indicated EPS was a fraction with 28.20% uronic acid content. FT-IR suggested the presence of pyraoid ring in EPS and SEM displayed smooth surface embedded by several pores. Moreover, Our study suggested EPS could remarkably stimulate macrophages to secrete substantial anti-cancer cytokines and promote maturation as well as Ag presentation function of DCs. Strikingly, CD4 T-cell differentiation and increased INF-γ production stimulated by EPS-activated macrophages were observed in the research. Furthermore, EPS exhibited prominent antitumor activities through regulating host immune system function in LLC-bearing mice. Taken together, experimental findings suggested EPS could be regarded as a potential immune-stimulating modifier for cancer therapy. Our studies demonstrated the polysaccharide (180 × 10 4 Da) purified from Epimedium koreanum Nakai could promote maturation and Ag presentation function of DCs, increase the level of immunomodulatory cytokines and activate CD4 T-cell differentiation. Furthermore, it may inhibit the tumor growth in LLC-bearing mice through regulating host immune system function. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

[The experimental research of inner ear metabolism and electrical physiology of autoimmune sensorineural hearing loss].

PubMed

Tan, C; Cao, Y; Hu, P

1998-09-01

Inquire into the mechanism of inner ear pathological physiology in autoimmune sensorineural hearing loss (ASHL). With the auditory electric-physiological techniques and enzyme-histochemical method, the change of inner ear hearing function and enzyme activity were observed. These animals, which threshold of auditory nerve compound active potential (CAP) and cochlear microphonic potential(CM) heightening evidently, showed that the amplitude of endolymphatic potential(EP) (include-EP) bring down in various degrees, which was related to the change of the active of Na(+)-K(+)-ATPase and SDH in vascularis stria and endolymphatic sac. The abnormality of enzymes metabolism in inner ear tissues, which following autoimmune inflammation damage, is the pathological foundation of hearing dysfunction.

Alcohol-antiretroviral interactive toxicity beliefs as a potential barrier to HIV pre-exposure prophylaxis among men who have sex with men.

PubMed

Kalichman, Seth C; Eaton, Lisa

2017-07-17

Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. HIV-negative sexually active men who have sex with men ( N  = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs. A total of 118 (43%) men surveyed had two or more male sex partners and condomless anal sex in the previous six months. Alcohol use was reported by over 90% of men and it was common for participants to believe that mixing alcohol and antiretrovirals is toxic; 75% endorsed at least one interactive toxicity belief. Among the 118 men who had engaged in condomless anal sex and had multiple sex partners, one in three stated that they were not interested in PrEP and men not interested in PrEP were significantly more likely to binge drink and hold interactive toxicity beliefs. These results mirror studies that find interactive toxicity beliefs are a potent predictor of intentional antiretroviral non-adherence among people living with HIV and suggest interactive toxicity beliefs may impede PrEP uptake and adherence. Messages to increase PrEP awareness and adherence may also take steps to counter erroneous beliefs about mixing alcohol with antiretrovirals in the context of PrEP.

Facilitators and Barriers to Participation in PrEP HIV Prevention Trials Involving Transgender Male and Female Adolescents and Emerging Adults

PubMed Central

Fisher, Celia B.; Fried, Adam L.; Desmond, Margaret; Macapagal, Kathryn; Mustanski, Brian

2018-01-01

Despite the disproportionate burden of HIV facing transgender youth, they continue to be under-represented in studies designed to provide an empirical basis for pre-exposure prophylaxis (PrEP) programs that can meet the unique needs of this population. This study examined facilitators and barriers to participation in a PrEP adherence study. Ninety transgender male (TM) and 60 transgender female (TF) 14 – 21 year olds attracted to cisgender male sexual partners completed an online survey to examine (a) gender identity, age and family disclosure; (b) sexual experience, HIV/STI testing history and perceptions of HIV risk; (c) prior health services and (d) perceived PrEP research risks and benefits (e) and the relationship of these factors to the likelihood of study participation. Approximately 50% were likely to participate in the PrEP study. Participation facilitators included prior sexual and health service experiences (i.e. number of sexual partners, STI testing history, comfort discussing sexual orientation and HIV protection with health providers) and study access to PrEP and health services (i.e. daily HIV protection, not having to rely on a partner for protection, regular health check ups). Participation barriers included lack of concern about HIV, potential medication side effects, the logistics of quarterly meetings, remembering to take PrEP daily and reluctance to discuss gender identity with study staff. Requiring guardian consent was a participation barrier for youth under 18. Results suggest that successful recruitment and retention of transgender youth in PrEP prevention studies warrant protocols designed to address youth's underestimation of HIV risk, concerns regarding medical risk and study logistics, and their need for gender and sexual orientation affirming health services. PMID:28650227

The actin-binding proteins eps8 and gelsolin have complementary roles in regulating the growth and stability of mechanosensory hair bundles of mammalian cochlear outer hair cells.

PubMed

Olt, Jennifer; Mburu, Philomena; Johnson, Stuart L; Parker, Andy; Kuhn, Stephanie; Bowl, Mike; Marcotti, Walter; Brown, Steve D M

2014-01-01

Sound transduction depends upon mechanosensitive channels localized on the hair-like bundles that project from the apical surface of cochlear hair cells. Hair bundles show a stair-case structure composed of rows of stereocilia, and each stereocilium contains a core of tightly-packed and uniformly-polarized actin filaments. The growth and maintenance of the stereociliary actin core are dynamically regulated. Recently, it was shown that the actin-binding protein gelsolin is expressed in the stereocilia of outer hair cells (OHCs) and in its absence they become long and straggly. Gelsolin is part of a whirlin scaffolding protein complex at the stereocilia tip, which has been shown to interact with other actin regulatory molecules such as Eps8. Here we investigated the physiological effects associated with the absence of gelsolin and its possible overlapping role with Eps8. We found that, in contrast to Eps8, gelsolin does not affect mechanoelectrical transduction during immature stages of development. Moreover, OHCs from gelsolin knockout mice were able to mature into fully functional sensory receptors as judged by the normal resting membrane potential and basolateral membrane currents. Mechanoelectrical transducer current in gelsolin-Eps8 double knockout mice showed a profile similar to that observed in the single mutants for Eps8. We propose that gelsolin has a non-overlapping role with Eps8. While Eps8 is mainly involved in the initial growth of stereocilia in both inner hair cells (IHCs) and OHCs, gelsolin is required for the maintenance of mature hair bundles of low-frequency OHCs after the onset of hearing.

The Sequence-specific Peptide-binding Activity of the Protein Sulfide Isomerase AGR2 Directs Its Stable Binding to the Oncogenic Receptor EpCAM.

PubMed

Mohtar, M Aiman; Hernychova, Lenka; O'Neill, J Robert; Lawrence, Melanie L; Murray, Euan; Vojtesek, Borek; Hupp, Ted R

2018-04-01

AGR2 is an oncogenic endoplasmic reticulum (ER)-resident protein disulfide isomerase. AGR2 protein has a relatively unique property for a chaperone in that it can bind sequence-specifically to a specific peptide motif (TTIYY). A synthetic TTIYY-containing peptide column was used to affinity-purify AGR2 from crude lysates highlighting peptide selectivity in complex mixtures. Hydrogen-deuterium exchange mass spectrometry localized the dominant region in AGR2 that interacts with the TTIYY peptide to within a structural loop from amino acids 131-135 (VDPSL). A peptide binding site consensus of Tx[IL][YF][YF] was developed for AGR2 by measuring its activity against a mutant peptide library. Screening the human proteome for proteins harboring this motif revealed an enrichment in transmembrane proteins and we focused on validating EpCAM as a potential AGR2-interacting protein. AGR2 and EpCAM proteins formed a dose-dependent protein-protein interaction in vitro Proximity ligation assays demonstrated that endogenous AGR2 and EpCAM protein associate in cells. Introducing a single alanine mutation in EpCAM at Tyr251 attenuated its binding to AGR2 in vitro and in cells. Hydrogen-deuterium exchange mass spectrometry was used to identify a stable binding site for AGR2 on EpCAM, adjacent to the TLIYY motif and surrounding EpCAM's detergent binding site. These data define a dominant site on AGR2 that mediates its specific peptide-binding function. EpCAM forms a model client protein for AGR2 to study how an ER-resident chaperone can dock specifically to a peptide motif and regulate the trafficking a protein destined for the secretory pathway. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Endothelial E-type prostanoid 4 receptors promote barrier function and inhibit neutrophil trafficking.

PubMed

Konya, Viktoria; Üllen, Andreas; Kampitsch, Nora; Theiler, Anna; Philipose, Sonia; Parzmair, Gerald P; Marsche, Gunther; Peskar, Bernhard A; Schuligoi, Rufina; Sattler, Wolfgang; Heinemann, Akos

2013-02-01

Increased vascular permeability is a fundamental characteristic of inflammation. Substances that are released during inflammation, such as prostaglandin (PG) E(2), can counteract vascular leakage, thereby hampering tissue damage. In this study we investigated the role of PGE(2) and its receptors in the barrier function of human pulmonary microvascular endothelial cells and in neutrophil trafficking. Endothelial barrier function was determined based on electrical impedance measurements. Neutrophil recruitment was assessed based on adhesion and transendothelial migration. Morphologic alterations are shown by using immunofluorescence microscopy. We observed that activation of E-type prostanoid (EP) 4 receptor by PGE(2) or an EP4-selective agonist (ONO AE1-329) enhanced the barrier function of human microvascular lung endothelial cells. EP4 receptor activation prompted similar responses in pulmonary artery and coronary artery endothelial cells. These effects were reversed by an EP4 antagonist (ONO AE3-208), as well as by blocking actin polymerization with cytochalasin B. The EP4 receptor-induced increase in barrier function was independent of the classical cyclic AMP/protein kinase A signaling machinery, endothelial nitric oxide synthase, and Rac1. Most importantly, EP4 receptor stimulation showed potent anti-inflammatory activities by (1) facilitating wound healing of pulmonary microvascular endothelial monolayers, (2) preventing junctional and cytoskeletal reorganization of activated endothelial cells, and (3) impairing neutrophil adhesion to endothelial cells and transendothelial migration. The latter effects could be partially attributed to reduced E-selectin expression after EP4 receptor stimulation. These data indicate that EP4 agonists as anti-inflammatory agents represent a potential therapy for diseases with increased vascular permeability and neutrophil extravasation. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Non-daily pre-exposure prophylaxis for HIV prevention

PubMed Central

Anderson, Peter L.; García-Lerma, J. Gerardo; Heneine, Walid

2015-01-01

Purpose of review To discuss non-daily pre-exposure prophylaxis (PrEP) modalities that may provide advantages compared with daily PrEP in cost and cumulative toxicity, but may have lower adherence forgiveness. Recent Findings Animal models have informed our understanding of early viral transmission events, which help guide event-driven PrEP dosing strategies. These models indicate early establishment of viral replication in rectal or cervicovaginal tissues, so event-driven PrEP should rapidly deliver high mucosal drug concentrations within hours of the potential exposure event. Macaque models have demonstrated the high biological efficacy for event-driven dosing of oral tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) against both vaginal and rectal virus transmission. In humans, the IPERGAY study demonstrated 86% efficacy for event-driven oral TDF/FTC dosing among men who have sex with men (MSM), while no similar efficacy data are available on women or heterosexual men. The HPTN 067 study showed that certain MSM populations adhere well to non-daily PrEP while other populations of women adhere more poorly to non-daily versus daily regimens. Pharmacokinetic studies following oral TDF/FTC dosing in humans, indicate that TFV-diphosphate (the active form of TFV) accumulates to higher concentrations in rectal versus cervicovaginal tissue but non-adherence in trials complicates the interpretation of differential mucosal drug concentrations. Summary Event-driven dosing for TFV-based PrEP has promise for HIV prevention in MSM. Future research of event-driven PrEP in women and heterosexual men should be guided by a better understanding of the importance of mucosal drug concentrations for PrEP efficacy and its sensitivity to adherence. PMID:26633641

Willingness to Accept HIV Pre-Exposure Prophylaxis among Chinese Men Who Have Sex with Men

PubMed Central

Li, Shuming; Li, Dongliang; Zhang, Lifen; Fan, Wensheng; Yang, Xueying; Yu, Mingrun; Xiao, Dong; Yan, Li; Zhang, Zheng; Shi, Wei; Luo, Fengji; Ruan, Yuhua; Jin, Qi

2012-01-01

Objective We investigated the awareness and acceptability of pre-exposure prophylaxis (PrEP) among men who have sex with men (MSM) and potential predicting factors. Methods This study was conducted among MSM in Beijing, China. Study participants, randomly selected from an MSM cohort, completed a structured questionnaire, and provided their blood samples to test for HIV infection and syphilis. Univariate logistic regression analyses were performed to evaluate the factors associated with willingness to accept (WTA) PrEP. Factors independently associated with willingness to accept were identified by entering variables into stepwise logistic regression analysis. Results A total of 152 MSM completed the survey; 11.2% had ever heard of PrEP and 67.8% were willing to accept it. Univariate analysis showed that age, years of education, consistent condom use in the past 6 months, heterosexual behavior in the past 6 months, having ever heard of PrEP and the side effects of antiretroviral drugs, and worry about antiretroviral drugs cost were significantly associated with willingness to accept PrEP. In the multivariate logistic regression model, only consistent condom use in the past 6 months (odds ratio [OR]: 0.31; 95% confidence interval [CI]: 0.13–0.70) and having ever heard of the side effects of antiretroviral drugs (OR: 0.30; 95% CI: 0.14–0.67) were independently associated with willingness to accept PrEP. Conclusions The awareness of PrEP in the MSM population was low. Sexual behavioral characteristics and knowledge about ART drugs may have effects on willingness to accept PrEP. Comprehensive prevention strategies should be recommended in the MSM community. PMID:22479320

Alcohol-antiretroviral interactive toxicity beliefs as a potential barrier to HIV pre-exposure prophylaxis among men who have sex with men

PubMed Central

Kalichman, Seth C; Eaton, Lisa

2017-01-01

Abstract Introduction: Pre-exposure prophylaxis (PrEP) offers as much as 90% protection against HIV transmission. However, the effectiveness of PrEP depends on uptake and adherence to even intermittent dosing. Along with intoxication leading to unintentional non-adherence, believing that alcohol mixed with pharmaceuticals is harmful (i.e., interactive toxicity beliefs) may lead to poor uptake and intentional non-adherence. Methods: HIV-negative sexually active men who have sex with men (N = 272) at a large Gay Pride event in Atlanta, GA, completed anonymous surveys of demographic characteristics, sexual behaviour, alcohol use and PrEP-related alcohol interactive toxicity beliefs. Results: A total of 118 (43%) men surveyed had two or more male sex partners and condomless anal sex in the previous six months. Alcohol use was reported by over 90% of men and it was common for participants to believe that mixing alcohol and antiretrovirals is toxic; 75% endorsed at least one interactive toxicity belief. Among the 118 men who had engaged in condomless anal sex and had multiple sex partners, one in three stated that they were not interested in PrEP and men not interested in PrEP were significantly more likely to binge drink and hold interactive toxicity beliefs. Conclusions: These results mirror studies that find interactive toxicity beliefs are a potent predictor of intentional antiretroviral non-adherence among people living with HIV and suggest interactive toxicity beliefs may impede PrEP uptake and adherence. Messages to increase PrEP awareness and adherence may also take steps to counter erroneous beliefs about mixing alcohol with antiretrovirals in the context of PrEP. PMID:28715159

Electrochemistry and Spectroelectrochemistry of 1,8-Naphthalene and 1,8- Anthracene-Linked Cofacial Binuclear Metallophthalocynanines. New Mixed Valence Metallopthalocyanines

DTIC Science & Technology

1990-05-10

slope of a plot of peak current vs. sweep rate to the charge should be equal to nF/4RT, where n is the number of electrons per adsorbed species and...overlapping waves. b) Values ofAEp : (Ep. - Epe) are given at a potential sweep rate of 50 mV/s. c) data fom ref.8g. d) Potentials are approximate because...cyclic voltametry at 200, 100, 50 and 20 mV/s, Average data being E : (Eps + Epc)/2 are reported. Data in parenthesis are estimated from overlapping

Kinetic determinations of accurate relative oxidation potentials of amines with reactive radical cations.

PubMed

Gould, Ian R; Wosinska, Zofia M; Farid, Samir

2006-01-01

Accurate oxidation potentials for organic compounds are critical for the evaluation of thermodynamic and kinetic properties of their radical cations. Except when using a specialized apparatus, electrochemical oxidation of molecules with reactive radical cations is usually an irreversible process, providing peak potentials, E(p), rather than thermodynamically meaningful oxidation potentials, E(ox). In a previous study on amines with radical cations that underwent rapid decarboxylation, we estimated E(ox) by correcting the E(p) from cyclic voltammetry with rate constants for decarboxylation obtained using laser flash photolysis. Here we use redox equilibration experiments to determine accurate relative oxidation potentials for the same amines. We also describe an extension of these experiments to show how relative oxidation potentials can be obtained in the absence of equilibrium, from a complete kinetic analysis of the reversible redox kinetics. The results provide support for the previous cyclic voltammetry/laser flash photolysis method for determining oxidation potentials.

Prevalence of and Factors Associated with the Use of HIV Serosorting and Other Biomedical Prevention Strategies Among Men Who Have Sex with Men in a US Nationwide Survey.

PubMed

Grov, Christian; Jonathan Rendina, H; Patel, Viraj V; Kelvin, Elizabeth; Anastos, Kathryn; Parsons, Jeffrey T

2018-03-17

PrEP and treatment-as-prevention (TasP) are biomedical strategies to reduce HIV transmission. Some men who have sex with men (MSM) are combining biomedical strategies with HIV serosorting-termed "biomed matching" when both partners are either on PrEP or TasP, or "biomed sorting" when one partner is using PrEP and the other TasP. Nevertheless, there is limited data on the extent of biomed matching/sorting in large geographically diverse samples. In 2016-2017, 5021 MSM from across the US were surveyed about their HIV status and HIV viral load/PrEP use, as well as that of their recent casual male partners. For each participant, we calculated the proportion of his partners who were (1) HIV-positive and undetectable, (2) HIV-positive and detectable/unknown, (3) HIV unknown/undiscussed, (4) HIV-negative on PrEP, (5) HIV-negative, not on PrEP. In total, 66.6% (n = 3346) of participants were HIV-negative and not on PrEP, 11.9% (n = 599) on PrEP, 14.1% (n = 707) HIV-positive and undetectable, 1.1% (n = 55) HIV-positive and viral load detectable/unknown, and 6.2% (n = 313) HIV unsure/unknown. A participant's own HIV and PrEP status/was significantly associated with that of his partners (all p < 0.001), evincing evidence of both serosorting and biomed matching. Among men on PrEP and those who were HIV-undetectable, there was also some evidence to suggest these participants dually engaged in biomed matching as well as biomed sorting. We found evidence of biomed matching and sorting, which may compound its effectiveness for those using it (i.e., both partners bring biomedical protection). Unintended consequences of biomed matching/sorting include that men not using a biomedical strategy may be less likely to benefit from a partner's use of the strategy-potentially further driving disparities in HIV infections. Public health campaigns might be well served to highlight not only the benefits that biomedical HIV prevention strategies provide for their users (e.g., "being on PrEP protects me from getting HIV"), but also the benefits that a user brings to his partners (e.g., "my use of PrEP means my partners won't get HIV"), and the benefits of being with a partner who is using a biomedical strategy (e.g., "my partner's use of PrEP/TasP protects me from HIV").

Comparison of 2 kinds of pedicle screws in primary spinal instrumentation: biomechanical and interfacial evaluations in sheep vertebrae in vitro.

PubMed

Liu, Da; Zhang, Yi; Lei, Wei; Wang, Cai-ru; Xie, Qing-yun; Liao, Dong-fa; Jiang, Kai; Zhou, Jin-song; Zhang, Bo; Pan, Xian-ming

2014-04-01

Expansive pedicle screw (EPS) and polymethylmethacrylate-augmented pedicle screw (PMMA-PS) were inserted in sheep vertebrae in vitro and were evaluated by performing biomechanical tests, radiographic examinations and histological observations. The objective of the study was to compare the biomechanical and interfacial performances of EPS and PMMA-PS in sheep lumbar vertebrae in vitro. It is a great challenge for orthopedic surgeons performing transpedicular fixation in the osteoporotic spine. It was reported that either the EPS or PMMA-PS could increase the screw stability. However, there are no studies comparing the 2 kinds of screws especially in primary spinal instrumentation. A total of 60 sheep lumbar vertebrae were randomly divided into 3 groups. A pilot hole was made in advance in all samples using the same method. Thereafter, the conventional pedicle screw (CPS) was inserted directly into the pilot hole in the CPS group; the hole in PMMA-PS group was first filled with polymethylmethacrylate (PMMA; 1.0 mL) and then inserted with CPS; and the EPS was inserted directly into the vertebrae in EPS group. After a period of 24 hours, biomechanical tests were performed to evaluate screw stability, and x-ray examination, micro-computerized tomography analysis, and histologic observation were performed to evaluate the interface between screw and bone. Compared with the stability of CPS, those of EPS and PMMA-PS were significantly enhanced. However, no significant differences were detected between the stabilities of EPS and PMMA-PS. The PMMA surrounding the screw blocked direct contact between bone and screw and formed a "screw-PMMA-bone" interface in the PMMA-PS group. There was a "screw-bone" interface in both CPS and EPS groups. Nevertheless, the expanded anterior part of EPS formed a claw-like structure pressing the surrounding bone trabeculae, which made the local bone tissue more compacted and denser than that in the CPS group. EPS can enhance the screw stability as markedly as the traditional PMMA-PS in primary surgery, and EPS can form a better immediate interface between screw and bone compared with PMMA-PS. EPS also can effectively avoid thermal injury, leakage, and compression caused by PMMA. A great feasibility was proved in this study to perform comparisons between the 2 kinds of pedicle screws in osteoporotic sheep vertebrae in vivo in the further research. In conclusion, we propose that EPS has a great application potential in augmentation of screw stability in the clinic.

Economic evaluation of HIV pre-exposure prophylaxis strategies: protocol for a methodological systematic review and quantitative synthesis.

PubMed

Thavorn, Kednapa; Kugathasan, Howsikan; Tan, Darrell H S; Moqueet, Nasheed; Baral, Stefan D; Skidmore, Becky; MacFadden, Derek; Simkin, Anna; Mishra, Sharmistha

2018-03-15

Pre-exposure prophylaxis (PrEP) with antiretrovirals is an efficacious and effective intervention to decrease the risk of HIV (human immunodeficiency virus) acquisition. Yet drug and delivery costs prohibit access in many jurisdictions. In the absence of guidelines for the synthesis of economic evaluations, we developed a protocol for a systematic review of economic evaluation studies for PrEP by drawing on best practices in systematic reviews and the conduct and reporting of economic evaluations. We aim to estimate the incremental cost per health outcome of PrEP compared with placebo, no PrEP, or other HIV prevention strategies; assess the methodological variability in, and quality of, economic evaluations of PrEP; estimate the incremental cost per health outcome of different PrEP implementation strategies; and quantify the potential sources of heterogeneity in outcomes. We will systematically search electronic databases (MEDLINE, Embase) and the gray literature. We will include economic evaluation studies that assess both costs and health outcomes of PrEP in HIV-uninfected individuals, without restricting language or year of publication. Two reviewers will independently screen studies using predefined inclusion criteria, extract data, and assess methodological quality using the Philips checklist, Second Panel on the Cost-effectiveness of Health and Medicines, and the International Society for Pharmacoeconomics and Outcomes Research recommendations. Outcomes of interest include incremental costs and outcomes in natural units or utilities, cost-effectiveness ratios, and net monetary benefit. We will perform descriptive and quantitative syntheses using sensitivity analyses of outcomes by population subgroups, HIV epidemic settings, study designs, baseline intervention contexts, key parameter inputs and assumptions, type of outcomes, economic perspectives, and willingness to pay values. Findings will guide future economic evaluation of PrEP strategies in terms of methodological and knowledge gaps, and will inform decisions on the efficient integration of PrEP into public health programs across epidemiologic and health system contexts. PROSPERO CRD42016038440 .

Prioritizing Risk in Preparation for a Demonstration Project: A Mixed Methods Feasibility Study of Oral Pre-Exposure Prophylaxis (PREP) among Female Sex Workers in South India.

PubMed

Reza-Paul, Sushena; Lazarus, Lisa; Doshi, Monika; Hafeez Ur Rahman, Syed; Ramaiah, Manjula; Maiya, Raviprakash; Ms, Venugopal; Venukumar, K T; Sundararaman, Sundar; Becker, Marissa; Moses, Stephen; Lorway, Robert

2016-01-01

HIV prevalence among female sex workers (FSWs) in India remains well above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka. From January-April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data. Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a "double safety" in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95%) expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%), those who do not use condoms when clients offer more money (58%), who do not consistently use condoms with regular partners (57%), who drink alcohol regularly (49%), and who do not use condoms consistently with clients (48%). This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means of supporting PrEP uptake and adherence.

Technological, rheological and sensory characterizations of a yogurt containing an exopolysaccharide extract from Lactobacillus fermentum Lf2, a new food additive.

PubMed

Ale, Elisa C; Perezlindo, Marcos J; Pavón, Yanina; Peralta, Guillermo H; Costa, Silvia; Sabbag, Nora; Bergamini, Carina; Reinheimer, Jorge A; Binetti, Ana G

2016-12-01

Lactobacillus fermentum Lf2, an autochthonous strain isolated as a non starter culture in Cremoso cheese, produces high EPS levels (~1g/L) in optimized conditions (SDM broth, pH6.0, 30°C, 72h). Technological (texture profile and rheological analysis) and sensory properties of non-fat yogurts with 300 and 600mg EPS/L were studied at 3 and 25days after manufacture. Yogurts with different EPS concentrations showed higher hardness values than the control group at both periods of time, being the only significant difference that remained stable during time. The consistency index was also higher for the treated samples at both times evaluated, being significantly different for samples with 300mg/L of EPS extract, while the flow behavior index was lower for EPS-added yogurts. The thixotropic index was lower (P<0.05) for samples with the highest EPS extract concentration at the end of the storage time. Regarding the sensory analysis, those yogurts with 600mg/L of EPS extract presented the highest values of consistency at 3days of storage. No considerable differences for defects (milk powder, acid, bitter and cooked milk flavors) were perceived between treated and control samples at both times evaluated. Syneresis was also studied and samples with 600mg/L of EPS extract presented the lowest syneresis values at 25days of storage, which considerably decreased with the time of storage. In conclusion, the EPS from L. fermentum Lf2, used as an additive, provided yogurt with creamy consistency and increased hardness, without the presence of unwanted defects and improving the water holding capacity of the product. All the analysis done showed the potential of this extract to be used as a technofunctional natural ingredient, and it should be considered its positive impact on health, according to previous studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new insight to adsorption and accumulation of high lead concentration by exopolymer and whole cells of lead-resistant bacterium Acinetobacter junii L. Pb1 isolated from coal mine dump.

PubMed

Kushwaha, Anamika; Rani, Radha; Kumar, Sanjay; Thomas, Tarence; David, Arun Alfred; Ahmed, Meraz

2017-04-01

A lead-resistant bacterial strain was isolated from coal mine dump and identified as Acinetobacter junii Pb1 on basis of 16S rRNA (ribosomal ribonucleic acid) gene sequencing. The minimum inhibitory concentration of lead for the strain was 16,000 mg l -1 and it showed antibiotic and multi metal resistance. In aqueous culture, at an initial lead (Pb(II)) concentration of 100 and 500 mg l -1 , lead adsorption and accumulation by the isolate was 100 and 60%, at pH 7 at 30 °C after 48 and 120 h, respectively. The two fractions of exopolysaccharide (EPS), loosely associated EPS (laEPS) and bound EPS (bEPS), and whole cells (devoid of EPS) showed high binding affinity towards Pb(II). The binding affinity of laEPS towards Pb(II) (1071 mg Pb g -1 ) was three times higher than that of bEPS (321.5 mg Pb g -1 ) and 6.5 times higher than that of whole cells (165 mg Pb g -1 ). The binding affinity of EPS and whole cells with Pb(II), reported in the current study, is considerably higher as compared to that reported in the literature, till date. SEM analysis, showed an increase in thickness of cells on exposure to Pb(II) and TEM analysis, revealed its accumulation (interior of cell) and its adsorption (with the external cell surface). The isolate was also found to be positive for indole acetic acid (IAA) and 1-aminocyclopropane-1-carboxylate (ACC) deaminase production which helps in promoting plant growth. Thus, this study provides a new understanding towards Pb(II) uptake by A. junii Pb1, highlighting its potential on the restoration of Pb(II) contaminated repositories.

Training dedicated emergency physicians in surgical critical care: knowledge acquisition and workforce collaboration for the care of critically ill trauma/surgical patients.

PubMed

Chiu, William C; Marcolini, Evie G; Simmons, Dell E; Yeatts, Dale J; Scalea, Thomas M

2011-07-01

The Leapfrog Group initiative has led to an increasing public demand for dedicated intensivists providing critical care services. The Acute Care Surgery training initiative promotes an expansion of trauma/surgical care and operative domain, redirecting some of our focus from critical care. Will we be able to train and enforce enough intensivists to care for critically ill surgical patients? We have been training emergency physicians (EPs) alongside surgeons in our country's largest Trauma/Surgical Critical Care Fellowship Program annually for more than a decade. We reviewed our Society of Critical Care Medicine Multidisciplinary Critical Care Knowledge Assessment Program (MCCKAP, critical care in-training examination) scores from 2006 to 2009 (4 years). The MCCKAP, administered during the ninth month of a Critical Care Fellowship, is the only known standardized objective examination available in this country to compare critical care knowledge acquisition across different specialties. Subsequent workforce outcome for these Emergency Medicine Critical Care Fellowship graduates was analyzed. Over the 4-year period, we trained 42 Fellows in our Program who qualified for this study (30 surgeons and 12 EPs). Surgeons and EP performance scores on the MCCKAP examination were not different. The mean National Board Equivalent score was 419 ± 61 (mean ± standard deviation) for surgeons and 489 ± 87 for EPs. The highest score was achieved by an EP. The lowest score was not achieved by an EP. Ten of 12 (83%) EP Critical Care Fellowship graduates are practicing inpatient critical care in intensive care units with attending physician level responsibilities. EPs training in a Surgical Critical Care Fellowship can acquire critical care knowledge equivalent to that of surgeons. EPs trained in a Surgical Critical Care paradigm can potentially expand the intensive care unit workforce for Surgical Critical Care patients.

Assessment of potential probiotic properties of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains isolated from kefir.

PubMed

Sabir, Firat; Beyatli, Yavuz; Cokmus, Cumhur; Onal-Darilmaz, Derya

2010-01-01

In this study, the metabolic activities (in terms of quantities of the produced lactic acid, hydrogen peroxide, and exopolysaccharides) of 8 strains of Lactobacillus spp., Lactococcus spp., and Pediococcus spp., were determined. Lactic acid levels produced by strains were 8.1 to 17.4 mg/L. The L. acidophilus Z1L strain produced the maximum amount (3.18 μg/mL) of hydrogen peroxide. The exopolysaccharides (EPS) production by the strains was ranged between 173 and 378 mg/L. The susceptibility of 7 different antibiotics against these strains was also tested. All strains were found to be sensitive to ampicillin. The tolerance of the strains to low pH, their resistance to bile salts of strains, and their abilities to autoaggregate and coaggregate with Escherichia coli ATCC 11229 were also evaluated. High EPS-producing strains showed significant autoaggregation and coaggregation ability with test bacteria (P < 0.01). A correlation also was determined between EPS production and acid-bile tolerance (P < 0.05). EPS production possibly affects or is involved in acid-bile tolerance and aggregation of Lactobacillus spp., Lactococcus spp., and Pediococcus spp. strains and supports the potential of L. acidophilus Z1L strain as new probiotic. © 2010 Institute of Food Technologists®

Expression and characterization of a potential exopolysaccharide from a newly isolated halophilic thermotolerant bacteria Halomonas nitroreducens strain WB1

PubMed Central

Chikkanna, Arpitha; Kishore, Abhinoy

2018-01-01

The halophilic bacterial strain WB1 isolated from a hydrothermal vent was taxonomically characterized using multiple proxies, as Halomonas nitroreducens strain WB1. When grown on malt extract/yeast extract (MY) medium, it produced large quantities of exopolysaccharide (EPS). The polymer was synthesized at a higher rate during the log and early stationary phases. The anionic polysaccharide is primarily composed of glucose, mannose, and galactose. The studied EPS was highly viscous and had pseudoplastic nature. The EPS was found to be a mixture of three polysaccharides under FT-IR, which makes it less labile to environmental diagenesis. It also has emulsifying and antioxidant activity along with the binding capacity to heavy metals. The EPS has unique and interesting physical and chemical properties, which are different from earlier reported exo-polysaccharides produced by different bacterial genus. This suggests that the extreme geological niches like hypersaline, hyperthermal, hypothermal, and oligophilic environments, which are not well studied so far, can offer extensive and potential resources for medical, biotechnological and industrial applications. The study clearly showed that the thermal springs from the temperate region can be a potent source of many such industrially important microbial genera and need further detailed studies to be carried out. PMID:29707437

Two Sides of the Same Coin: ERP and Wavelet Analyses of Visual Potentials Evoked and Induced by Task-Relevant Faces.

PubMed

Van der Lubbe, Rob H J; Szumska, Izabela; Fajkowska, Małgorzata

2016-01-01

New analysis techniques of the electroencephalogram (EEG) such as wavelet analysis open the possibility to address questions that may largely improve our understanding of the EEG and clarify its relation with related potentials (ER Ps). Three issues were addressed. 1) To what extent can early ERERP components be described as transient evoked oscillations in specific frequency bands? 2) Total EEG power (TP) after a stimulus consists of pre-stimulus baseline power (BP), evoked power (EP), and induced power (IP), but what are their respective contributions? 3) The Phase Reset model proposes that BP predicts EP, while the evoked model holds that BP is unrelated to EP; which model is the most valid one? EEG results on NoGo trials for 123 individuals that took part in an experiment with emotional facial expressions were examined by computing ERPs and by performing wavelet analyses on the raw EEG and on ER Ps. After performing several multiple regression analyses, we obtained the following answers. First, the P1, N1, and P2 components can by and large be described as transient oscillations in the α and θ bands. Secondly, it appears possible to estimate the separate contributions of EP, BP, and IP to TP, and importantly, the contribution of IP is mostly larger than that of EP. Finally, no strong support was obtained for either the Phase Reset or the Evoked model. Recent models are discussed that may better explain the relation between raw EEG and ERPs.

Bacterial exopolysaccharide based magnetic nanoparticles: a versatile nanotool for cancer cell imaging, targeted drug delivery and synergistic effect of drug and hyperthermia mediated cancer therapy.

PubMed

Sivakumar, Balasubramanian; Aswathy, Ravindran Girija; Sreejith, Raveendran; Nagaoka, Yutaka; Iwai, Seiki; Suzuki, Masashi; Fukuda, Takahiro; Hasumura, Takashi; Yoshida, Yasuhiko; Maekawa, Toru; Sakthikumar, Dasappan Nair

2014-06-01

Microbial exopolysaccharides (EPSs) are highly heterogeneous polymers produced by fungi and bacteria that have garnered considerable attention and have remarkable potential in various fields, including biomedical research. The necessity of biocompatible materials to coat and stabilize nanoparticles is highly recommended for successful application of the same in biomedical regime. In our study we have coated magnetic nanoparticles (MNPs) with two bacterial EPS-mauran (MR) and gellan gum (GG). The biocompatibility of EPS coated MNPs was enhanced and we have made it multifunctional by attaching targeting moiety, folate and with encapsulation of a potent anticancerous drug, 5FU. We have conjugated an imaging moiety along with nanocomposite to study the effective uptake of nanoparticles. It was also observed that the dye labeled folate targeted nanoparticles could effectively enter into cancer cells and the fate of nanoparticles was tracked with Lysotracker. The biocompatibility of EPS coated MNPs and synergistic effect of magnetic hyperthermia and drug for enhanced antiproliferation of cancer cells was also evaluated. More than 80% of cancer cells was killed within a period of 60 min when magnetic hyperthermia (MHT) was applied along with drug loaded EPS coated MNPs, thus signifying the combined effect of drug loaded MNPs and MHT. Our results suggests that MR and GG coated MNPs exhibited excellent biocompatibility with low cell cytotoxicity, high therapeutic potential, and superparamagnetic behavior that can be employed as prospective candidates for bacterial EPS based targeted drug delivery, cancer cell imaging and for MHT for killing cancer cells within short period of time.

Two Sides of the Same Coin: ERP and Wavelet Analyses of Visual Potentials Evoked and Induced by Task-Relevant Faces

PubMed Central

Van der Lubbe, Rob H. J.; Szumska, Izabela; Fajkowska, Małgorzata

2016-01-01

New analysis techniques of the electroencephalogram (EEG) such as wavelet analysis open the possibility to address questions that may largely improve our understanding of the EEG and clarify its relation with related potentials (ER Ps). Three issues were addressed. 1) To what extent can early ERERP components be described as transient evoked oscillations in specific frequency bands? 2) Total EEG power (TP) after a stimulus consists of pre-stimulus baseline power (BP), evoked power (EP), and induced power (IP), but what are their respective contributions? 3) The Phase Reset model proposes that BP predicts EP, while the evoked model holds that BP is unrelated to EP; which model is the most valid one? EEG results on NoGo trials for 123 individuals that took part in an experiment with emotional facial expressions were examined by computing ERPs and by performing wavelet analyses on the raw EEG and on ER Ps. After performing several multiple regression analyses, we obtained the following answers. First, the P1, N1, and P2 components can by and large be described as transient oscillations in the α and θ bands. Secondly, it appears possible to estimate the separate contributions of EP, BP, and IP to TP, and importantly, the contribution of IP is mostly larger than that of EP. Finally, no strong support was obtained for either the Phase Reset or the Evoked model. Recent models are discussed that may better explain the relation between raw EEG and ERPs. PMID:28154612

Life cycle assessment of integrated solid state anaerobic digestion and composting for on-farm organic residues treatment.

PubMed

Li, Yangyang; Manandhar, Ashish; Li, Guoxue; Shah, Ajay

2018-03-20

Driven by the gradual changes in the structure of energy consumption and improvements of living standards in China, the volume of on-farm organic solid waste is increasing. If untreated, these unutilized on-farm organic solid wastes can cause environmental problems. This paper presents the results of a life cycle assessment to compare the environmental impacts of different on-farm organic waste (which includes dairy manure, corn stover and tomato residue) treatment strategies, including anaerobic digestion (AD), composting, and AD followed by composting. The input life cycle inventory data are specific to China. The potential environmental impacts of different waste management strategies were assessed based on their acidification potential (AP), eutrophication potential (EP), global warming potential (GWP), ecotoxicity potential (ETP), and resource depletion (RD). The results show that the preferred treatment strategy for dairy manure is the one that integrated corn stover and tomato residue utilization and solid state AD technologies into the system. The GWP of integrated solid state AD and composting was the least, which is -2900 kg CO 2 eq/ t of dairy manure and approximately 14.8 times less than that of current status (i.e., liquid AD of dairy manure). Solid state AD of dairy manure, corn stover and tomato residues is the most favorable option in terms of AP, EP and ETP, which are more than 40% lower than that of the current status (i.e., AP: 3.11 kg SO 2 , EP: -0.94 kg N, and ETP: -881 CTUe (Comparative Toxic Units ecotoxicity)). The results also show that there is a significant potential for AP, EP, ETP, and GWP reduction, if AD is used prior to composting. The scenario analysis for transportation distance showed that locating the AD plant and composting facility on the farm was advantageous in terms of all the life cycle impact categories. Copyright © 2018 Elsevier Ltd. All rights reserved.

Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk.

PubMed

Wilton, James; Kain, Taylor; Fowler, Shawn; Hart, Trevor A; Grennan, Troy; Maxwell, John; Tan, Darrell Hs

2016-01-01

Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify "optimal" candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify "optimal" candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were "optimal" candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3-2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2-2.3). The proportion of men who were "optimal" candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers.

Use of an HIV-risk screening tool to identify optimal candidates for PrEP scale-up among men who have sex with men in Toronto, Canada: disconnect between objective and subjective HIV risk

PubMed Central

Wilton, James; Kain, Taylor; Fowler, Shawn; Hart, Trevor A; Grennan, Troy; Maxwell, John; Tan, Darrell HS

2016-01-01

Introduction Identifying appropriate pre-exposure prophylaxis (PrEP) candidates is a challenge in planning for the safe and effective roll-out of this strategy. We explored the use of a validated HIV risk screening tool, HIV Incidence Risk Index for Men who have Sex with Men (HIRI-MSM), to identify “optimal” candidates among MSM testing at a busy sexual health clinic's community testing sites in Toronto, Canada. Methods Between November 2014 and April 2015, we surveyed MSM undergoing anonymous HIV testing at community testing sites in Toronto, Canada, to quantify “optimal” candidates for scaling up PrEP roll-out, defined as being at high objective HIV risk (scoring ≥10 on the HIRI-MSM), perceiving oneself at moderate-to-high HIV risk and being willing to use PrEP. Cascades were constructed to identify barriers to broader PrEP uptake. The association between HIRI-MSM score and both willingness to use PrEP and perceived HIV risk were explored in separate multivariable logistic regression analyses. Results Of 420 respondents, 64.4% were objectively at high risk, 52.5% were willing to use PrEP and 27.2% perceived themselves at moderate-to-high HIV risk. Only 16.4% were “optimal” candidates. Higher HIRI-MSM scores were positively associated with both willingness to use PrEP (aOR=1.7 per 10 score increase, 95%CI=1.3–2.2) and moderate-to-high perceived HIV risk (aOR=1.7 per 10 score increase, 95%CI=1.2–2.3). The proportion of men who were “optimal” candidates increased to 42.9% when the objective HIV risk cut-off was changed to top quartile of HIRI-MSM scores (≥26). In our full cascade, a very low proportion (5.3%) of MSM surveyed could potentially benefit from PrEP under current conditions. The greatest barrier in the cascade was low perception of HIV risk among high-risk men, but considerable numbers were also lost in downstream cascade steps. Of men at high objective HIV risk, 68.3% did not perceive themselves to be at moderate-to-high HIV risk, 23.6% were unaware of PrEP, 40.1% were not willing to use PrEP, 47.6% lacked a family physician with whom they felt comfortable discussing sexual health, and 31.6% had no means to cover the cost of PrEP. Conclusions A higher HIRI-MSM cut-off may be helpful for identifying candidates for PrEP scale-up. Improving engagement in the PrEP cascade will require interventions to simultaneously address multiple barriers. PMID:27265490

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

You, Guoxiang

The extended DLVO (XDLVO) theory was applied to elucidate the potential effects of CeO{sub 2} nanoparticles (CeO{sub 2} NPs) on sludge aggregation and the role of extracellular polymeric substances (EPS). In this study, seven different concentrations of CeO{sub 2} NPs were added to activated sludge cultured in sequencing batch reactors (SBRs) and compared with a control test that received no CeO{sub 2} NPs. After exposure to 50 mg/L CeO{sub 2} NPs, a negligible change (p>0.1) occurred in the sludge volume index (SVI), whereas the flocculability and aggregation of the sludge decreased by 18.8% and 11.2%, respectively, resulting in a highmore » effluent turbidity. The XDLVO theory demonstrated that the adverse effects of the CeO{sub 2} NPs on sludge aggregation were due to an enhanced barrier energy. Compared to the van der Waals energies (W{sub A}) and the electric double layer (W{sub R}), the acid-base interaction (W{sub AB}) markedly changed for the various concentrations of CeO{sub 2} NPs. The EPS played a decisive role in the sludge surface characteristics, as the removal of EPS equals to the negative effects induced by 5–10 mg/L CeO{sub 2} NPs on the sludge flocculability and aggregation. The presence of CeO{sub 2} NPs induced negative contributions to the tight boundary EPS (TB-EPS) and core bacteria while positive contributions to the total interaction energy of the loose boundary EPS (LB-EPS). - Highlights: • CeO{sub 2} NPs adversely affected the flocculability and aggregation of the sludge. • The presence of CeO{sub 2} NPs increased the energy barrier and led to a stable suspension. • The removal of EPS equals to the negative effects induced by 5–10 mg/L CeO{sub 2} NPs. • The acid-base interaction was dominate and markedly changed for the CeO{sub 2} NPs. • CeO{sub 2} NPs induced negative contributions to the TB-EPS while positive to the LB-EPS.« less

The cortical spatiotemporal correlate of otolith stimulation: Vestibular evoked potentials by body translations.

PubMed

Ertl, M; Moser, M; Boegle, R; Conrad, J; Zu Eulenburg, P; Dieterich, M

2017-07-15

The vestibular organ senses linear and rotational acceleration of the head during active and passive motion. These signals are necessary for bipedal locomotion, navigation, the coordination of eye and head movements in 3D space. The temporal dynamics of vestibular processing in cortical structures have hardly been studied in humans, let alone with natural stimulation. The aim was to investigate the cortical vestibular network related to natural otolith stimulation using a hexapod motion platform. We conducted two experiments, 1. to estimate the sources of the vestibular evoked potentials (VestEPs) by means of distributed source localization (n=49), and 2. to reveal modulations of the VestEPs through the underlying acceleration intensity (n=24). For both experiments subjects were accelerated along the main axis (left/right, up/down, fore/aft) while the EEG was recorded. We were able to identify five VestEPs (P1, N1, P2, N2, P3) with latencies between 38 and 461 ms as well as an evoked beta-band response peaking with a latency of 68 ms in all subjects and for all acceleration directions. Source localization gave the cingulate sulcus visual (CSv) area and the opercular-insular region as the main origin of the evoked potentials. No lateralization effects due to handedness could be observed. In the second experiment, area CSv was shown to be integral in the processing of acceleration intensities as sensed by the otolith organs, hinting at its potential role in ego-motion detection. These robust VestEPs could be used to investigate the mechanisms of inter-regional interaction in the natural context of vestibular processing and multisensory integration. Copyright © 2017 Elsevier Inc. All rights reserved.

An Improved Evolutionary Programming with Voting and Elitist Dispersal Scheme

NASA Astrophysics Data System (ADS)

Maity, Sayan; Gunjan, Kumar; Das, Swagatam

Although initially conceived for evolving finite state machines, Evolutionary Programming (EP), in its present form, is largely used as a powerful real parameter optimizer. For function optimization, EP mainly relies on its mutation operators. Over past few years several mutation operators have been proposed to improve the performance of EP on a wide variety of numerical benchmarks. However, unlike real-coded GAs, there has been no fitness-induced bias in parent selection for mutation in EP. That means the i-th population member is selected deterministically for mutation and creation of the i-th offspring in each generation. In this article we present an improved EP variant called Evolutionary Programming with Voting and Elitist Dispersal (EPVE). The scheme encompasses a voting process which not only gives importance to best solutions but also consider those solutions which are converging fast. By introducing Elitist Dispersal Scheme we maintain the elitism by keeping the potential solutions intact and other solutions are perturbed accordingly, so that those come out of the local minima. By applying these two techniques we can be able to explore those regions which have not been explored so far that may contain optima. Comparison with the recent and best-known versions of EP over 25 benchmark functions from the CEC (Congress on Evolutionary Computation) 2005 test-suite for real parameter optimization reflects the superiority of the new scheme in terms of final accuracy, speed, and robustness.

Ethyl pyruvate protects against blood-brain barrier damage and improves long-term neurological outcomes in a rat model of traumatic brain injury.

PubMed

Shi, Hong; Wang, Hai-Lian; Pu, Hong-Jian; Shi, Ye-Jie; Zhang, Jia; Zhang, Wen-Ting; Wang, Guo-Hua; Hu, Xiao-Ming; Leak, Rehana K; Chen, Jun; Gao, Yan-Qin

2015-04-01

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced long-term brain damage. Ethyl pyruvate (EP) has shown neuroprotection in several models of acute brain injury. The present study therefore investigated the potential beneficial effect of EP on long-term outcomes after TBI and the underlying mechanisms. Male adult rats were subjected to unilateral controlled cortical impact injury. EP was injected intraperitoneally 15 min after TBI and again at 12, 24, 36, 48, and 60 h after TBI. Neurological deficits, blood-brain barrier (BBB) integrity, and neuroinflammation were assessed. Ethyl pyruvate improved sensorimotor and cognitive functions and ameliorated brain tissue damage up to 28 day post-TBI. BBB breach and brain edema were attenuated by EP at 48 h after TBI. EP suppressed matrix metalloproteinase (MMP)-9 production from peripheral neutrophils and reduced the number of MMP-9-overproducing neutrophils in the spleen, and therefore mitigated MMP-9-mediated BBB breakdown. Moreover, EP exerted potent antiinflammatory effects in cultured microglia and inhibited the elevation of inflammatory mediators in the brain after TBI. Ethyl pyruvate confers long-term neuroprotection against TBI, possibly through breaking the vicious cycle among MMP-9-mediated BBB disruption, neuroinflammation, and long-lasting brain damage. © 2014 John Wiley & Sons Ltd.

Erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy

NASA Astrophysics Data System (ADS)

Zhu, Dao-Ming; Xie, Wei; Xiao, Yu-Sha; Suo, Meng; Zan, Ming-Hui; Liao, Qing-Quan; Hu, Xue-Jia; Chen, Li-Ben; Chen, Bei; Wu, Wen-Tao; Ji, Li-Wei; Huang, Hui-Ming; Guo, Shi-Shang; Zhao, Xing-Zhong; Liu, Quan-Yan; Liu, Wei

2018-02-01

Recently, red blood cell (RBC) membrane-coated nanoparticles have attracted much attention because of their excellent immune escapability; meanwhile, gold nanocages (AuNs) have been extensively used for cancer therapy due to their photothermal effect and drug delivery capability. The combination of the RBC membrane coating and AuNs may provide an effective approach for targeted cancer therapy. However, few reports have shown the utilization of combining these two technologies. Here, we design erythrocyte membrane-coated gold nanocages for targeted photothermal and chemical cancer therapy. First, anti-EpCam antibodies were used to modify the RBC membranes to target 4T1 cancer cells. Second, the antitumor drug paclitaxel (PTX) was encapsulated into AuNs. Then, the AuNs were coated with the modified RBC membranes. These new nanoparticles were termed EpCam-RPAuNs. We characterized the capability of the EpCam-RPAuNs for selective tumor targeting via exposure to near-infrared irradiation. The experimental results demonstrate that EpCam-RPAuNs can effectively generate hyperthermia and precisely deliver the antitumor drug PTX to targeted cells. We also validated the biocompatibility of the EpCam-RAuNs in vitro. By combining the molecularly modified targeting RBC membrane and AuNs, our approach provides a new way to design biomimetic nanoparticles to enhance the surface functionality of nanoparticles. We believe that EpCam-RPAuNs can be potentially applied for cancer diagnoses and therapies.

Different SEP recovery cycle in adolescent migraineurs with exploding or imploding pain.

PubMed

Iacovelli, Elisa; Tarantino, Samuela; Capuano, Alessandro; De Luca, Massimiliano; De Ranieri, Cristiana; Vigevano, Federico; Arendt-Nielsen, Lars; Valeriani, Massimiliano

2013-01-01

Our aim was to investigate whether migraine adolescents with pain directed inside (imploding pain--IP) and outside (exploding pain--EP) the head may have different levels of cortical excitability underlying their migraineous syndrome. Ten migraine children referring prevalent EP (mean age 14.5 ± 1.4 years, 3 girls, 7 boys), 10 patients with IP (mean age 14.1 ± 2.2 years, 4 girls, 6 boys), and 13 control subjects (mean age 13 ± 1.8 years, 6 males, 7 females) participated to the study. The recovery cycle of the somatosensory evoked potentials to electrical median nerve stimuli at interstimulus intervals of 5, 20, and 40 ms was measured. Anger expression, anxiety, and somatic concerns were investigated in migraine patients. Overall, SEP recovery cycle was shorter in migraineurs than in healthy controls. The recovery cycle of the frontal N30 SEP component was significantly shorter in IP than in EP patients. While among the EP patients those with faster N30 recovery cycle had higher Trait-Anger score, the opposite was found among the IP patients. Our results suggest that the inhibitory mechanisms within the somatosensory cortex are more impaired in IP than in EP migraine adolescents. The pathophysiological difference between IP and EP migraineurs was strengthened also by the opposite correlations between the brain excitability and the anger expression. Copyright © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

A novel technique using potassium permanganate and reflectance confocal microscopy to image biofilm extracellular polymeric matrix reveals non-eDNA networks in Pseudomonas aeruginosa biofilms

PubMed Central

Swearingen, Matthew C.; Mehta, Ajeet; Mehta, Amar; Nistico, Laura; Hill, Preston J.; Falzarano, Anthony R.; Wozniak, Daniel J.; Hall-Stoodley, Luanne; Stoodley, Paul

2015-01-01

Biofilms are etiologically important in the development of chronic medical and dental infections. The biofilm extracellular polymeric substance (EPS) determines biofilm structure and allows bacteria in biofilms to adapt to changes in mechanical loads such as fluid shear. However, EPS components are difficult to visualize microscopically because of their low density and molecular complexity. Here, we tested potassium permanganate, KMnO4, for use as a non-specific EPS contrast-enhancing stain using confocal laser scanning microscopy in reflectance mode. We demonstrate that KMnO4 reacted with EPS components of various strains of Pseudomonas, Staphylococcus and Streptococcus, yielding brown MnO2 precipitate deposition on the EPS, which was quantifiable using data from the laser reflection detector. Furthermore, the MnO2 signal could be quantified in combination with fluorescent nucleic acid staining. COMSTAT image analysis indicated that KMnO4 staining increased the estimated biovolume over that determined by nucleic acid staining alone for all strains tested, and revealed non-eDNA EPS networks in Pseudomonas aeruginosa biofilm. In vitro and in vivo testing indicated that KMnO4 reacted with poly-N-acetylglucosamine and Pseudomonas Pel polysaccharide, but did not react strongly with DNA or alginate. KMnO4 staining may have application as a research tool and for diagnostic potential for biofilms in clinical samples. PMID:26536894

Protection of silver nanoparticles using Eysenhardtia polystachya in peroxide-induced pancreatic β-Cell damage and their antidiabetic properties in zebrafish

PubMed Central

Garcia Campoy, Abraham Heriberto; Perez Gutierrez, Rosa Martha; Manriquez-Alvirde, Gabriela; Muñiz Ramirez, Alethia

2018-01-01

Background The aim was to explore the efficacy of extract of Eysenhardtia polystachya-loaded silver nanoparticles (EP/AgNPs) on pancreatic β cells, INS-1 cells, and zebrafish as a valuable model for the study of diabetes mellitus. Materials and methods EP/AgNPs were synthesized using methanol/water bark extract of E. polystachya and characterized using various physicochemical techniques. Results Immersion of adult zebrafish in 111 mM glucose solution resulted in a sustained hyperglycemic, hyperlipidemic state, and serum insulin levels decreased. The synthesized EP/AgNPs showed an absorption peak at 413 nm on ultraviolet–visible spectroscopy, revealing the surface plasmon resonance of the nanoparticles. Transmission electron microscopy indicated that most of the particles were spherical, with a diameter of 10–12 nm, a polydispersity index of 0.197, and a zeta potential of −32.25 mV, suggesting high stability of the nanoparticles. EP/AgNPs promote pancreatic β-cell survival, insulin secretion, enhanced hyperglycemia, and hyperlipidemia in glucose-induced diabetic zebrafish. EP/AgNPs also showed protection of the pancreatic β-cell line INS-1 against hydrogen peroxide-induced oxidative injury. Conclusion The results indicate that EP/AgNPs have good antidiabetic activity and therefore could be used to prevent the development of diabetes. PMID:29750032

Characterization of hepatic progenitors from human fetal liver during second trimester.

PubMed

Rao, Mekala-Subba; Khan, Aleem-Ahmed; Parveen, Nyamath; Habeeb, Mohammed-Aejaz; Habibullah, Chittoor-Mohammed; Pande, Gopal

2008-10-07

To enrich hepatic progenitors using epithelial cell adhesion molecule (EpCAM) as a marker from human fetal liver and investigate the expression of human leukocyte antigen (HLA) and their markers associated with hepatic progenitor cells. EpCAM +ve cells were isolated using magnetic cell sorting (MACS) from human fetuses (n = 10) at 15-25 wk gestation. Expression of markers for hepatic progenitors such as albumin, alpha-fetoprotein (AFP), CD29 (integrin beta1), CD49f (integrin alpha6) and CD90 (Thy 1) was studied by using flow cytometry, immunocytochemistry and RT-PCR; HLA class I (A, B, C) and class II (DR) expression was studied by flow cytometry only. FACS analysis indicated that EpCAM +ve cells were positive for CD29, CD49f, CD90, CD34, HLA class I, albumin and AFP but negative for HLA class II (DR) and CD45. RT PCR showed that EpCAM +ve cells expressed liver epithelial markers (CK18), biliary specific marker (CK19) and hepatic markers (albumin, AFP). On immunocytochemical staining, EpCAM +ve cells were shown positive signals for CK18 and albumin. Our study suggests that these EpCAM +ve cells can be used as hepatic progenitors for cell transplantation with a minimum risk of alloreactivity and these cells may serve as a potential source for enrichment of hepatic progenitor.

Présentation d'une formule pratique d'estimation de l'évaporation potentielle, conforme aux nouvelles recommandations internationales

NASA Astrophysics Data System (ADS)

Lhomme, J. P.; Monteny, B.

1982-03-01

This paper begins to recall new concepts concerning evapotranspiration as they have been specified by the round-table conference of Budapest in May 1977. The potential evaporation ( EP) is now defined as the evaporation of a crop whose all exchange surfaces (leaves, stalks,...) are saturated, i.e., covered with a thin film of water. It can be calculated by a theoretical formula of Penman type. We give the reasons why it is interesting to use grass potential evaporation ( EP g ) as reference. The empirical relationships to estimate in this case the net radiation and the aerodynamic component of the formula have been derived from measurements made in Ivory Coast (West Africa). The relationship (8) has been obtained. It gives the daily value of EP g in millimeters of water per day (mm/d). The values calculated by this formula are compared to measurements of grass maximal evapotranspiration ( ETM g ).

Pre-exposure prophylaxis of HIV: A right way to go or a long way to go?

PubMed Central

Yu, Wenya; Wang, Lu; Han, Na; Zhang, Xiayan; Mahapatra, Tanmay; Mahapatra, Sanchita; Babu, Giridhara R.; Tang, Weiming; Detels, Roger; Zhao, Jinkou

2014-01-01

Antiretroviral drugs are being tried as candidates for the pre-exposure prophylaxis (PrEP) against HIV for a considerable period, due to their potential for immediate inhibition of viral replication. Discrepancies in the findings called for a critical review of the relevant efforts and their outcomes. A systematic literature search identified 143 eligible articles of which only 5 reported complete findings while another 11 were still on-going. Observed moderate efficacy and good safety profile seemed to identify PrEP as a promising step for minimizing the spread of HIV to relatively unaffected population and controlling the epidemic among high risk population groups. But the duration of this efficacy was found to depend heavily on the availability, adherence and other related issues like cost, political commitment, ethical consideration etc. To prevent potential cultural and behavioral modifications, proper pre-administration counseling also seemed critical for the success of PrEP as a cost-effective intervention with adequate coverage. PMID:25078629

Extracellular polymer substance synthesized by a halophilic bacterium Chromohalobacter canadensis 28.

PubMed

Radchenkova, Nadja; Boyadzhieva, Ivanka; Atanasova, Nikolina; Poli, Annarita; Finore, Ilaria; Di Donato, Paola; Nicolaus, Barbara; Panchev, Ivan; Kuncheva, Margarita; Kambourova, Margarita

2018-04-03

Halophilic microorganisms are producers of a lot of new compounds whose properties suggest promising perspectives for their biotechnological exploration. Moderate halophilic bacterium Chromohalobacter canadensis 28 was isolated from Pomorie salterns as an extracellular polymer substance (EP) producer. The best carbon source for extracellular polymer production was found to be lactose, a sugar received as a by-product from the dairy industry. After optimization of the culture medium and physicochemical conditions for cultivation, polymer biosynthesis increased more than 2-fold. The highest level of extracellular polymer synthesis by C. canadensis 28 was observed in an unusually high NaCl concentration (15% w/v). Chemical analysis of the purified polymer revealed the presence of an exopolysaccharide (EPS) fraction (14.3% w/w) and protein fraction (72% w/w). HPLC analysis of the protein fraction showed the main presence of polyglutamic acid (PGA) (75.7% w/w). EPS fraction analysis revealed the following sugar composition (% w/w): glucosamine 36.7, glucose 32.3, rhamnose 25.4, xylose 1.7, and not identified sugar 3.9. The hydrogel formed by PGA and EPS fractions showed high swelling behavior, very good emulsifying and stabilizing properties, and good foaming ability. This is the first report for halophilic bacterium able to synthesize a polymer containing PGA fraction. The synthesized biopolymer shows an extremely high hydrophilicity, due to the simultaneous presence of PGA and EPS. The analysis of its functional properties and the presence of glucosamine in the highest proportion in EPS fraction clearly determine the potential of EP synthesized by C. canadensis 28 for application in the cosmetics industry.

Anti-EpCAM scFv gadolinium chelate: a novel targeted MRI contrast agent for imaging of colorectal cancer.

PubMed

Khantasup, Kannika; Saiviroonporn, Pairash; Jarussophon, Suwatchai; Chantima, Warangkana; Dharakul, Tararaj

2018-05-08

The development of targeted contrast agents for magnetic resonance imaging (MRI) facilitates enhanced cancer imaging and more accurate diagnosis. In the present study, a novel contrast agent was developed by conjugating anti-EpCAM humanized scFv with gadolinium chelate to achieve target specificity. The material design strategy involved site-specific conjugation of the chelating agent to scFv. The scFv monomer was linked to maleimide-DTPA via unpaired cysteine at the scFv C-terminus, followed by chelation with gadolinium (Gd). Successful scFv-DTPA conjugation was achieved at 1:10 molar ratio of scFv to maleimide-DTPA at pH 6.5. The developed anti-EpCAM-Gd-DTPA MRI contrast agent was evaluated for cell targeting ability, in vitro serum stability, cell cytotoxicity, relaxivity, and MR contrast enhancement. A high level of targeting efficacy of anti-EpCAM-Gd-DTPA to an EpCAM-overexpressing HT29 colorectal cell was demonstrated by confocal microscopy. Good stability of the contrast agent was obtained and no cytotoxicity was observed in HT29 cells after 48 h incubation with 25-100 µM of Gd. Favorable imaging was obtained using anti-EpCAM-Gd-DTPA, including 1.8-fold enhanced relaxivity compared with Gd-DTPA, and MR contrast enhancement observed after binding to HT29. The potential benefit of this contrast agent for in vivo MR imaging of colorectal cancer, as well as other EpCAM positive cancers, is suggested and warrants further investigation.

Chitosan and β-Cyclodextrin-epichlorohydrin Polymer Composite Film as a Plant Healthcare Material for Carbendazim-Controlled Release to Protect Rape against Sclerotinia sclerotiorum (Lib.) de Bary.

PubMed

Wang, Delong; Jia, Mingchen; Wang, Lanying; Song, Shuang; Feng, Juntao; Zhang, Xing

2017-03-26

The influence of β-cyclodextrin-epichlorohydrin (β-CD-EP) polymers on the improvement of the solubility and antifungal activity of carbendazim has been investigated. Meanwhile, the potential of the chitosan and β-CD-EP composite film used as a plant healthcare material for carbendazim-controlled release to protect rape against Sclerotinia sclerotiorum (Lib.) de Bary has been evaluated. β-CD-EP-1 and 2 (β-CD content, 750 mg/g and 440 mg/g, respectively) were found to significantly improve the solubility of the guest molecule carbendazim (17.9 and 18.5 times, respectively) and the 1:1 stoichiometry of the host-guest was confirmed by the Job's plot. A slight synergism was observed for the β-CD-EP/carbendazim complex against S. sclerotiorum (Lib.) de Bary, indicating an enhancement to the bioavailability of carbendazim. The in vitro release studies revealed that β-CD-EP polymers could efficiently modulate carbendazim release behaviors, such as the release retard and rate. The in vivo efficacy experiments demonstrated that the β-CD-EP/carbendazim and chitosan composite film could significantly prolong the effective duration of carbendazim at a concentration of 100 μg/mL compared with spraying carbendazim at 500 μg/mL. Thereby, a highly useful and strategic concept in plant disease control by a plant healthcare material-the chitosan and polymeric β-CD-EP composite film-is provided, which could also serve as a concept for related plant diseases.

The importance of polysomnography in the evaluation of prolonged disorders of consciousness: sleep recordings more adequately correlate than stimulus-related evoked potentials with patients' clinical status.

PubMed

de Biase, Stefano; Gigli, Gian Luigi; Lorenzut, Simone; Bianconi, Claudio; Sfreddo, Patrizia; Rossato, Gianluca; Basaldella, Federica; Fuccaro, Matteo; Corica, Antonio; Tonon, Davide; Barbone, Fabio; Valente, Mariarosaria

2014-04-01

The aim of our study was to evaluate the importance of sleep recordings and stimulus-related evoked potentials (EPs) in patients with prolonged disorders of consciousness (DOCs) by correlating neurophysiologic variables with clinical evaluation obtained using specific standardized scales. There were 27 vegetative state (VS) and 5 minimally conscious state (MCS) patients who were evaluated from a clinical and neurophysiologic perspective. Clinical evaluation included the Coma Recovery Scale-Revised (CRS-R), Disability Rating Scale (DRS), and Glasgow Coma Scale (GCS). Neurophysiologic evaluation included 24-h polysomnography (PSG), somatosensory EPs (SEPs), brainstem auditory EPs (BAEPs), and visual EPs (VEPs). Patients with preservation of each single sleep element (sleep-wake cycle, sleep spindles, K-complexes, and rapid eye movement [REM] sleep) always showed better clinical scores compared to those who did not have preservation. Statistical significance was only achieved for REM sleep. In 7 patients PSG showed the presence of all considered sleep elements, and they had a CRS-R score of 8.29±1.38. In contrast, 25 patients who lacked one or more of the sleep elements had a CRS-R score of 4.84±1.46 (P<.05). Our multivariate analysis clarified that concurrent presence of sleep spindles and REM sleep were associated with a much higher CRS-R score (positive interaction, P<.0001). On the other hand, no significant associations were found between EPs and CRS-R scores. PSG recordings have proved to be a reliable tool in the neurophysiologic assessment of patients with prolonged DOCs, correlating more adequately than EPs with the clinical evaluation and the level of consciousness. The main contribution to higher clinical scores was determined by the concomitant presence of REM sleep and sleep spindles. PSG recordings may be considered inexpensive, noninvasive, and easy-to-perform examinations to provide supplementary information in patients with prolonged DOCs. Copyright © 2014 Elsevier B.V. All rights reserved.

Production and properties of an exopolysaccharide synthesized by the extreme halophilic archaeon Haloterrigena turkmenica.

PubMed

Squillaci, Giuseppe; Finamore, Rosario; Diana, Paola; Restaino, Odile Francesca; Schiraldi, Chiara; Arbucci, Salvatore; Ionata, Elena; La Cara, Francesco; Morana, Alessandra

2016-01-01

We have isolated a novel exopolysaccharide (EPS) produced by the extreme halophilic archaeon Haloterrigena turkmenica. Some features, remarkable from an industrial point of view, such as emulsifying and antioxidant properties, were investigated. H. turkmenica excreted 20.68 mg of EPS per 100 ml of culture medium when grown in usual medium supplemented with glucose. The microorganism excreted the biopolymer mainly in the middle exponential growth phase and reached the maximal production in the stationary phase. Analyses by anion exchange chromatography and SEC-TDA Viscotek indicated that the EPS was composed of two main fractions of 801.7 and 206.0 kDa. It was a sulfated heteropolysaccharide containing glucose, galactose, glucosamine, galactosamine, and glucuronic acid. Studies performed utilizing the mixture of EPS anionic fractions showed that the biopolymer had emulsifying activity towards vegetable oils comparable or superior to that exhibited by the controls, moderate antioxidant power when tested with 2,2'-diphenyl-1-picrylhydrazyl (DPPH(·)), and moisture-retention ability higher than hyaluronic acid (HA). The EPS from H. turkmenica is the first exopolysaccharide produced by an archaea to be characterized in terms of properties that can have potential biotechnological applications.

Electroporation-assisted discrimination of normal, benign and cancerous human gastric tissues by OCT and diffuse reflectance spectra images

NASA Astrophysics Data System (ADS)

Li, Caiyun; Wei, Huajiang; Zhao, Yanping; Wu, Guoyong; Gu, Huaimin; Guo, Zhouyi; Yang, Hongqin; He, Yonghong; Xie, Shusen

2018-07-01

The purpose of this study is to illustrate experimentally the optical coherence tomography (OCT) signal slope and diffuse reflectance (DR) spectra of 30% and 80% glycerol combined with electroporation (EP) diffusion in normal, benign and cancerous human gastric tissues in vitro. The results of OCT showed that the permeability coefficients of 80% and 30% glycerol (both with and without EP) have the following trend: human cancerous gastric tissue  >  human benign gastric tissue  >  human normal gastric tissue under the same conditions. The permeability coefficient of the 30% glycerol group is larger than that of the 80% glycerol group under the same circumstances; the permeability coefficient of glycerol combined with the EP group is larger than that without the EP group under the same conditions. The permeability coefficient and the reduction of the DR spectra have perfect linear correlation (R2  =  0.9745). The research results suggest that OCT and the DR spectra combined with an optical clearing agent (glycerol) and the EP method can potentially become a powerful tool for the early diagnosis and monitoring of human gastric cancer.

Antiretroviral Chemoprophylaxis: State of Evidence and the Research Agenda

PubMed Central

Mayer, Kenneth H.

2014-01-01

Oral antiretroviral preexposure prophylaxis (PrEP) has been shown to decrease human immunodeficiency virus (HIV) incidence in studies of men who have sex with men, heterosexual men and women, and injecting drug users. One study of pericoital tenofovir gel demonstrated that it reduced HIV incidence in South African women. However, other studies of African women failed to demonstrate protection with either oral tenofovir or tenofovir-emtricitabine, or daily tenofovir gel. The magnitude of PrEP protection appears to be highly correlated with medication adherence. New studies are evaluating whether different antiretrovirals, including dapivirine, rilpivirine, maraviroc, and new integrase inhibitors. Different formulations are also being evaluated, including gels, films, vaginal rings, and injectable medication. Although PrEP efficacy has been demonstrated, and several normative bodies (eg, the US Food and Drug Administration) have approved PrEP for clinical use, uptake has been slow. Reasons may include lack of sufficient provider and consumer education, residual concerns about costs, potential long-term toxicities, and behavioral disinhibition. Additional work is under way to determine how to best educate consumers and providers about optimal adherence and to use PrEP in conjunction with risk mitigation. PMID:24926034

Drug-induced parkinsonism in relation to choline-containing compounds measured by 1H-MR spectroscopy in putamen of chronically medicated patients with schizophrenia.

PubMed

Yamasue, Hidenori; Fukui, Tsunehiro; Fukuda, Rin; Kasai, Kiyoto; Iwanami, Akira; Kato, Nobumasa; Kato, Tadafumi

2003-12-01

Extrapyramidal side-effects (EPS), the most frequent and severe side-effects of antipsychotics, sometimes become irreversible and cause severe psychosocial disturbance in patients with schizophrenia. However, the neurobiological basis of EPS has not yet been elucidated. In this study, neurochemical correlates of EPS were examined by 1H-MR spectroscopy (1H-MRS). Sixteen medicated patients with schizophrenia and 15 age-, gender- and parental-socioeconomic-status-matched normal controls were examined using single-voxel 1H-MRS. Absolute concentrations of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine, myo-inositol, and Glx (glutamate and glutamine) in the left putamen were evaluated. The patient group showed mild EPS and no significant metabolic abnormalities in this region. The more severe drug-induced parkinsonism assessed by the Simpson-Angus Scale, however, significantly correlated with the higher Cho concentration and tended to be correlated with the higher NAA concentration in the patient group. These results suggest a potential of 1H-MRS as a non-invasive monitoring method of neurobiological correlates of EPS associated with neuroleptic treatments in patients with schizophrenia.

Using the costs of drug therapy to screen patients for a community pharmacy-based medication review program.

PubMed

Krähenbühl, Jean-Marc; Decollogny, Anne; Bugnon, Olivier

2008-12-01

To measure the positive predictive value (PPV) of the cost of drug therapy (threshold = 2000 Swiss francs [CHF], US$1440, 1360) as a screening criterion for identifying patients who may benefit from medication review (MR). To describe identified drug-related problems (DRPs) and expense problems (EPs), and to estimate potential savings if all recommendations were accepted. Five voluntary Swiss community pharmacies. Of 12,680 patients, 592 (4.7%) had drug therapy costs exceeding 2000 CHF over a six-month period from July 1 to December 31, 2002. This threshold limit was set to identify high-risk patients for DRPs and EPs. Three pharmacists consecutively conducted a medication review based on the pharmaceutical charts of 125 sampled patients who met the inclusion criterion. The PPV of a threshold of 2000 CHF for identifying patients who might benefit from a MR: true positives were patients with at least one DRP, while false positives were patients with no DRP. The selection based on this criterion had a PPV of 86% for detecting patients with at least one DRP and 95% if EPs were also considered. There was a mean of 2.64 (SD = 2.20) DRPs per patient and a mean of 2.14 (SD = 1.39) EPs per patient. Of these patients, 90% were over 65 years old or were treated with at least five chronic medications, two common criteria for identifying patients at risk of DRPs. The main types of DRPs were drug-drug interactions, compliance problems and duplicate drugs. Mean daily drug cost per patient was CHF 14.87 (US$10.70, 10.10). A potential savings of CHF 1.67 (US$1.20, 1.14) per day (11%) was estimated if all recommendations to solve DRPs and EPs suggested herein were implemented. Further studies should investigate whether the potential benefit of medication reviews in preventing DRPs and containing costs in this patient group can be confirmed in a real practice environment.

Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.

PubMed

Haberer, Jessica E; Baeten, Jared M; Campbell, James; Wangisi, Jonathan; Katabira, Elly; Ronald, Allan; Tumwesigye, Elioda; Psaros, Christina; Safren, Steven A; Ware, Norma C; Thomas, Katherine K; Donnell, Deborah; Krows, Meighan; Kidoguchi, Lara; Celum, Connie; Bangsberg, David R

2013-01-01

Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation. Within the Partners PrEP Study (a randomized placebo-controlled trial of oral tenofovir and emtricitabine/tenofovir among HIV-uninfected members of serodiscordant couples in Kenya and Uganda), we collected objective measures of PrEP adherence using unannounced home-based pill counts and electronic pill bottle monitoring. Participants received individual and couples-based adherence counseling at PrEP initiation and throughout the study; counseling was intensified if unannounced pill count adherence fell to <80%. Participants were followed monthly to provide study medication, adherence counseling, and HIV testing. A total of 1,147 HIV-uninfected participants were enrolled: 53% were male, median age was 34 years, and median partnership duration was 8.5 years. Fourteen HIV infections occurred among adherence study participants--all of whom were assigned to placebo (PrEP efficacy = 100%, 95% confidence interval 83.7%-100%, p<0.001). Median adherence was 99.1% (interquartile range [IQR] 96.9%-100%) by unannounced pill counts and 97.2% (90.6%-100%) by electronic monitoring over 807 person-years. Report of no sex or sex with another person besides the study partner, younger age, and heavy alcohol use were associated with <80% adherence; the first 6 months of PrEP use and polygamous marriage were associated with >80% adherence. Study limitations include potential shortcomings of the adherence measures and use of a convenience sample within the substudy cohort. The high PrEP adherence achieved in the setting of active adherence monitoring and counseling support was associated with a high degree of protection from HIV acquisition by the HIV-uninfected partner in heterosexual serodiscordant couples. Low PrEP adherence was associated with sexual behavior, alcohol use, younger age, and length of PrEP use. Please see later in the article for the Editors' Summary.

Life Cycle Assessment of Bio-diesel Production—A Comparative Analysis

NASA Astrophysics Data System (ADS)

Chatterjee, R.; Sharma, V.; Mukherjee, S.; Kumar, S.

2014-04-01

This work deals with the comparative analysis of environmental impacts of bio-diesel produced from Jatropha curcas, Rapeseed and Palm oil by applying the life cycle assessment and eco-efficiency concepts. The environmental impact indicators considered in the present paper include global warming potential (GWP, CO2 equivalent), acidification potential (AP, SO2 equivalent) and eutrophication potential (EP, NO3 equivalent). Different weighting techniques have been used to present and evaluate the environmental characteristics of bio-diesel. With the assistance of normalization values, the eco-efficiency was demonstrated in this work. The results indicate that the energy consumption of bio-diesel production is lowest in Jatropha while AP and EP are more in case of Jatropha than that of Rapeseed and Palm oil.

The promise and peril of pre-exposure prophylaxis (PrEP): using social science to inform prep interventions among female sex workers.

PubMed

Syvertsen, Jennifer L; Robertson Bazzi, Angela M; Scheibe, Andrew; Adebajo, Sylvia; Strathdee, Steffanie A; Wechsberg, Wendee M

2014-09-01

Advances in biomedical interventions to prevent HIV offer great promise in reducing the number of new infections across sub- Saharan Africa, particularly among vulnerable populations such as female sex workers. Several recent trials testing pre-exposure prophylaxis (PrEP) have demonstrated efficacy, although others have been stopped early for futility. Given the importance and complexities of social and behavioural factors that influence biomedical approaches to prevention, we discuss several key areas of consideration moving forward, including trial participation, adherence strategies, social relationships, and the structural factors that shape PrEP interest, use, and potential effectiveness among female sex workers in sub-Saharan Africa. Our review highlights the importance of involving social scientists in clinical and community-based research on PrEP. We advocate for a shift away from a singular "re-medicalization" of the HIV epidemic to that of a "reintegration" of interdisciplinary approaches to prevention that could benefit female sex workers and other key populations at risk of acquiring HIV.

An improved nuclear mass model: FRDM (2012)

NASA Astrophysics Data System (ADS)

Moller, Peter

2011-10-01

We have developed an improved nuclear mass model which we plan to finalize in 2012, so we designate it FRDM(2012). Relative to our previous mass table in 1995 we do a full four-dimensional variation of the shape coordinates EPS2, EPS3, EPS4, and EPS6, we consider axial asymmetric shape degrees of freedom and we vary the density symmetry parameter L. Other additional features are also implemented. With respect to the Audi 2003 data base we now have an accuracy of 0.57 MeV. We have carefully tested the extrapolation properties of the new mass table by adjusting model parameters to limited data sets and testing on extended data sets and find it is highly reliable in new regions of nuclei. We discuss what the remaining differences between model calculations and experiment tell us about the limitations of the currently used effective single-particle potential and possible extensions. DOE No. DE-AC52-06NA25396.

Lipoic acid stimulates cAMP production via the EP2 and EP4 prostanoid receptors and inhibits IFN gamma synthesis and cellular cytotoxicity in NK cells

PubMed Central

Salinthone, Sonemany; Schillace, Robynn V.; Marracci, Gail H.; Bourdette, Dennis N.; Carr, Daniel W.

2008-01-01

The antioxidant lipoic acid (LA) treats and prevents the animal model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). In an effort to understand the therapeutic potential of LA in MS, we sought to define the cellular mechanisms that mediate the effects of LA on human natural killer (NK) cells, which are important in innate immunity as the first line of defense against invading pathogens and tumor cells. We discovered that LA stimulates cAMP production in NK cells in a dose-dependent manner. Studies using pharmacological inhibitors and receptor transfection experiments indicate that LA stimulates cAMP production via activation of the EP2 and EP4 prostanoid receptors and adenylyl cyclase. In addition, LA suppressed interleukin (IL)-12/IL-18 induced IFNγ secretion and cytotoxicity in NK cells. These novel findings suggest that LA may inhibit NK cell function via the cAMP signaling pathway. PMID:18562016

[PrEP Forum: an on-line debate on pre-exposure prophylaxis in Brazil].

PubMed

Queiroz, Artur Acelino Francisco Luz Nunes; Sousa, Alvaro Francisco Lopes de

2017-11-21

This study aimed to identify health-promoting contents focused on HIV/Aids prevention in messages posted in a Facebook group for debates on the use of pre-exposure prophylaxis (PrEP). This was a prospective observational study using systematic non-participant observation. From July 2015 to June 2016, all the posts in the group were catalogued and formed a corpus. Everything was processed in IRaMuTeQ and analyzed by descending hierarchical classification. The collected data were grouped in three classes: (1) HIV/Aids prevention: discussing prophylaxis, treatment, target public, and side effects; (2) universal access to PrEP in Brazil: discussing government responsibilities; (3) on-line purchase of truvada: exposing a situation of vulnerability. The findings call attention to a potential public health problem and provide backing for understanding facilitators and barriers to the use of PrEP in Brazil through the identification of health-promoting content linked to individual, social, and institutional markers.

Derivation of Pluripotent Stem Cells with In Vivo Embryonic and Extraembryonic Potency.

PubMed

Yang, Yang; Liu, Bei; Xu, Jun; Wang, Jinlin; Wu, Jun; Shi, Cheng; Xu, Yaxing; Dong, Jiebin; Wang, Chengyan; Lai, Weifeng; Zhu, Jialiang; Xiong, Liang; Zhu, Dicong; Li, Xiang; Yang, Weifeng; Yamauchi, Takayoshi; Sugawara, Atsushi; Li, Zhongwei; Sun, Fangyuan; Li, Xiangyun; Li, Chen; He, Aibin; Du, Yaqin; Wang, Ting; Zhao, Chaoran; Li, Haibo; Chi, Xiaochun; Zhang, Hongquan; Liu, Yifang; Li, Cheng; Duo, Shuguang; Yin, Ming; Shen, Huan; Belmonte, Juan Carlos Izpisua; Deng, Hongkui

2017-04-06

Of all known cultured stem cell types, pluripotent stem cells (PSCs) sit atop the landscape of developmental potency and are characterized by their ability to generate all cell types of an adult organism. However, PSCs show limited contribution to the extraembryonic placental tissues in vivo. Here, we show that a chemical cocktail enables the derivation of stem cells with unique functional and molecular features from mice and humans, designated as extended pluripotent stem (EPS) cells, which are capable of chimerizing both embryonic and extraembryonic tissues. Notably, a single mouse EPS cell shows widespread chimeric contribution to both embryonic and extraembryonic lineages in vivo and permits generating single-EPS-cell-derived mice by tetraploid complementation. Furthermore, human EPS cells exhibit interspecies chimeric competency in mouse conceptuses. Our findings constitute a first step toward capturing pluripotent stem cells with extraembryonic developmental potentials in culture and open new avenues for basic and translational research. VIDEO ABSTRACT. Copyright © 2017 Elsevier Inc. All rights reserved.

Evoked potential application to study of echolocation in cetaceans

NASA Astrophysics Data System (ADS)

Supin, Alexander Ya.; Nactigall, Paul E.; Pawloski, Jeffrey; Au, Whitlow W. L.

2002-05-01

The evoked-potential (EP) method is effective in studies of hearing capabilities of cetaceans. However, until now EP studies in cetaceans were performed only in conditions of passive hearing by recording EP to external stimuli. Can this method be applied to study active echolocation in odontocetes? To answer this question, auditory brainstem evoked responses (ABR) were recorded in a false killer whale while the animal echolocated a target within an experiment in which the animal reported the target present or absent. The ABR collection was triggered by echolocation clicks. In these conditions, the recorded ABR pattern contained a duplicate set of waves. A comparison of ABR wave delays recorded during echolocation with those recorded during regular external stimulation has shown that the first set of waves is a response to the emitted click whereas the second one is a response to the echo. Both responses, to the emitted click and to the echo, were of comparable amplitude in spite of the intensity difference of these two sounds of more than 40 dB near the animal's head. This finding indicates some mechanisms releasing responses to echoes from masking by loud emitted clicks. The evoked-potential method may be productive to investigate these mechanisms.

Measure Guideline: Transitioning from Three-Coat Stucco to One-Coat Stucco with EPS

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

Brozyna, K.; Davis, G.; Rapport, A.

2012-04-01

This Measure Guideline has been developed to help builders transition from using a traditional three-coat stucco wall-cladding system to a one-coat stucco wall-cladding system with expanded polystyrene (EPS) insulated sheathing. The three-coat system uses a base layer, a fill layer, and a finish layer. The one-coat system maintains the look of a traditional stucco system but uses only a base layer and a finish coat over EPS insulation that achieves higher levels of energy efficiency. Potential risks associated with the installation of a one-coat stucco system are addressed in terms of design, installation, and warranty concerns such as cracking andmore » delamination, along with mitigation strategies to reduce these risks.« less

A novel bradykinin potentiating peptide isolated from Bothrops jararacussu venom using catallytically inactive oligopeptidase EP24.15.

PubMed

Rioli, Vanessa; Prezoto, Benedito C; Konno, Katsuhiro; Melo, Robson L; Klitzke, Clécio F; Ferro, Emer S; Ferreira-Lopes, Mônica; Camargo, Antonio C M; Portaro, Fernanda C V

2008-05-01

Characterization of the peptide content of venoms has a number of potential benefits for basic research, clinical diagnosis, development of new therapeutic agents, and production of antiserum. Here, we use a substrate-capture assay that employs a catalytically inactive mutant of thimet oligopeptidase (EC 3.4.24.15; EP24.15) to identify novel bioactive peptides in Bothrops jararacussu venom. Of the peptides captured with inactive EP24.15 and identified by mass spectrometry, three were previously identified bradykinin-potentiating peptides (BPP),

Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

PubMed

Zhang, Mo; Chen, Lizhu; Yuan, Zhengwei; Yang, Zeyu; Li, Yue; Shan, Liping; Yin, Bo; Fei, Xiang; Miao, Jianing; Song, Yongsheng

2016-11-01

Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

[Evoked Potential Blind Extraction Based on Fractional Lower Order Spatial Time-Frequency Matrix].

PubMed

Long, Junbo; Wang, Haibin; Zha, Daifeng

2015-04-01

The impulsive electroencephalograph (EEG) noises in evoked potential (EP) signals is very strong, usually with a heavy tail and infinite variance characteristics like the acceleration noise impact, hypoxia and etc., as shown in other special tests. The noises can be described by a stable distribution model. In this paper, Wigner-Ville distribution (WVD) and pseudo Wigner-Ville distribution (PWVD) time-frequency distribution based on the fractional lower order moment are presented to be improved. We got fractional lower order WVD (FLO-WVD) and fractional lower order PWVD (FLO-PWVD) time-frequency distribution which could be suitable for a stable distribution process. We also proposed the fractional lower order spatial time-frequency distribution matrix (FLO-STFM) concept. Therefore, combining with time-frequency underdetermined blind source separation (TF-UBSS), we proposed a new fractional lower order spatial time-frequency underdetermined blind source separation (FLO-TF-UBSS) which can work in a stable distribution environment. We used the FLO-TF-UBSS algorithm to extract EPs. Simulations showed that the proposed method could effectively extract EPs in EEG noises, and the separated EPs and EEG signals based on FLO-TF-UBSS were almost the same as the original signal, but blind separation based on TF-UBSS had certain deviation. The correlation coefficient of the FLO-TF-UBSS algorithm was higher than the TF-UBSS algorithm when generalized signal-to-noise ratio (GSNR) changed from 10 dB to 30 dB and a varied from 1. 06 to 1. 94, and was approximately e- qual to 1. Hence, the proposed FLO-TF-UBSS method might be better than the TF-UBSS algorithm based on second order for extracting EP signal under an EEG noise environment.

Compound gravity receptor polarization vectors evidenced by linear vestibular evoked potentials

NASA Technical Reports Server (NTRS)

Jones, S. M.; Jones, T. A.; Bell, P. L.; Taylor, M. J.

2001-01-01

The utricle and saccule are gravity receptor organs of the vestibular system. These receptors rely on a high-density otoconial membrane to detect linear acceleration and the position of the cranium relative to Earth's gravitational vector. The linear vestibular evoked potential (VsEP) has been shown to be an effective non-invasive functional test specifically for otoconial gravity receptors (Jones et al., 1999). Moreover, there is some evidence that the VsEP can be used to independently test utricular and saccular function (Taylor et al., 1997; Jones et al., 1998). Here we characterize compound macular polarization vectors for the utricle and saccule in hatchling chickens. Pulsed linear acceleration stimuli were presented in two axes, the dorsoventral (DV, +/- Z axis) to isolate the saccule, and the interaural (IA, +/- Y axis) to isolate the utricle. Traditional signal averaging was used to resolve responses recorded from the surface of the skull. Latency and amplitude of eighth nerve components of the linear VsEP were measured. Gravity receptor responses exhibited clear preferences for one stimulus direction in each axis. With respect to each utricular macula, lateral translation in the IA axis produced maximum ipsilateral response amplitudes with substantially greater amplitude intensity (AI) slopes than medially directed movement. Downward caudal motions in the DV axis produced substantially larger response amplitudes and AI slopes. The results show that the macula lagena does not contribute to the VsEP compound polarization vectors of the sacculus and utricle. The findings suggest further that preferred compound vectors for the utricle depend on the pars externa (i.e. lateral hair cell field) whereas for the saccule they depend on pars interna (i.e. superior hair cell fields). These data provide evidence that maculae saccule and utricle can be selectively evaluated using the linear VsEP.

Further Insights into Metal-DOM Interaction: Consideration of Both Fluorescent and Non-Fluorescent Substances

PubMed Central

Xu, Huacheng; Zhong, Jicheng; Yu, Guanghui; Wu, Jun; Jiang, Helong; Yang, Liuyan

2014-01-01

Information on metal binding with fluorescent substances has been widely studied. By contrast, information on metal binding with non-fluorescent substances remains lacking despite the dominance of these substances in aquatic systems. In this study, the metal binding properties of both fluorescent and non-fluorescent substances were investigated by using metal titration combined with two-dimensional correlation spectroscopy (2D–COS) analysis. The organic matters in the eutrophic algae-rich lake, including natural organic matters (NOM) and algae-induced extracellular polymeric substances (EPS), both contained fluorescent and non-fluorescent substances. The peaks in the one-dimensional spectra strongly overlapped, while 2D–COS can decompose the overlapped peaks and thus enhanced the spectral resolution. Moreover, 2D FTIR COS demonstrated that the binding susceptibility of organic ligands in both NOM and algal EPS matrices followed the order: 3400>1380>1650 cm−1, indicative the significant contribution of non-fluorescent ligands in metal binding. The modified Stern-Volmer equation also revealed a substantial metal binding potential for the non-fluorescent substances (logKM: 3.57∼4.92). As for the effects of organic ligands on metal binding, EPS was characterized with higher binding ability than NOM for both fluorescent and non-fluorescent ligands. Algae-induced EPS and the non-fluorescent substances in eutrophic algae-rich lakes should not be overlooked because of their high metal binding potential. PMID:25380246

What qualities in a potential HIV pre-exposure prophylaxis service are valued by black men who have sex with men in London? A qualitative acceptability study.

PubMed

Witzel, T Charles; Nutland, Will; Bourne, Adam

2018-07-01

Black men who have sex with men (BMSM) have higher HIV incidence and prevalence when compared to other MSM, despite similar levels of condom use and testing. Pre-exposure prophylaxis (PrEP) could be a useful intervention to reduce these inequalities. This research therefore aims to understand the dimensions of acceptability of a potential PrEP service for BMSM aged 18-45 years in London. In-depth semi-structured interviews were conducted with 25 PrEP-eligible BMSM between April and August 2016. Interviews were recorded and transcribed verbatim, then subject to a thematic framework analysis, informed by intersectionality theory. BMSM had distinct preferences for sexual health services, which have implications for PrEP service development. Three primary domains emerged in our analysis: proximity and anonymity; quality, efficiency and reassurance; and understanding, empathy and identity. These relate, respectively, to preferences regarding clinic location and divisions from community, features of service delivery and staff characteristics. Due to concerns about confidentiality, community-based services may not be useful for this group. Careful consideration in regards to components used in service development will facilitate ongoing engagement. Interpersonal skills of staff are central to service acceptability, particularly when staff are perceived to be from similar cultural backgrounds as their patients.

CCCP activation of the reconstituted NaK-pump.

PubMed

Yoda, A; Yoda, S

1990-08-01

In the NaK-ATPase proteoliposomes (PLs), the NaK-pump activity, Na+ uptake, and ATP hydrolysis were apparently enhanced by carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and other ionophores without ion gradients. These ionophore effects were not cation specific. Without ionophores, the PL's ATPase activity fell to its steady-state value within 3 sec at 15 degrees C. This decrease in activity disappeared in the presence of CCCP. Since CCCP is believed to enhance proton mobility across the lipid bilayer and dissipate membrane potential (Vm), we postulated that a Vm build-up partially inhibits the PLs by changing the conformation of the NaK-pump, and that CCCP eliminated this partial inhibition. Since this activation required extracellular K+ and high ATP concentration in the PLs, CCCP must affect the conversion between the phosphorylated forms of NaK-ATPase (EP); this step has been suggested by Goldschlegger et al. (1987) to be the voltage-sensitive step (J. Physiol. (London) 387:331-355). Although cytoplasmic K+ accelerated the change of ADP- and K(+)-sensitive EP (E*P) to K(+)-sensitive ADP-insensitive EP (E2P), CCCP did not complete with cytoplasmic K+ when cytoplasmic Na+ was saturated. When the PLs were phosphorylated with 20 microM ATP and 20 microM palmitoyl CoA instead of with high concentration of ATP, CCCP increased the E*P content and decreased the ADP-sensitive K(+)-insensitive EP (E1P). The results described above suggest that CCCP affects the E1P to E*P change in the E1P----E*P----E2P conversion and that this reaction step is inhibited by Vm.

Tumour-associated circulating microparticles: A novel liquid biopsy tool for screening and therapy monitoring of colorectal carcinoma and other epithelial neoplasia.

PubMed

Willms, Arnulf; Müller, Clara; Julich, Henrike; Klein, Niklas; Schwab, Robert; Güsgen, Christoph; Richardsen, Ines; Schaaf, Sebastian; Krawczyk, Marcin; Krawczyk, Marek; Lammert, Frank; Schuppan, Detlef; Lukacs-Kornek, Veronika; Kornek, Miroslaw

2016-05-24

Up to date, novel tools for low-cost, minimal invasive cancer surveillance, cancer screening and treatment monitoring are in urgent need. Physicians consider the so-called liquid biopsy as a possible future tool successfully achieving these ultimate goals. Here, we aimed to identify circulating tumour-associated MPs (taMPs) that could aid in diagnosing minimal-invasively the presence and follow up treatment in non-small cell lung carcinoma (NSCLC), colorectal carcinoma (CRC) and pancreas carcinoma (PaCa). Tumour-associated MPs (taMPs) were quantified after isolation by centrifugation followed by flow cytometry analysis from the serum of cancer patients with CRC (n = 52), NSCLC (n = 40) and PaCa (n = 11). Healthy subjects (n = 55) or patients with struma nodosa (thyroid nodules) (n = 43) served as negative controls. In all three types of tumour entities, the presence of tumour was associated with an increase of circulating EpCAM+ and EpCAM+CD147+ taMPs. The presence of CD147+EpCAM+ taMPs were specific to tumour-bearing patients thus allowing the specific distinction of malignancies from patients with thyroid nodules. Increased level of EpCAM single positive MPs were, in turn, also detected in patients with thyroid nodules. Importantly, EpCAM+CD147+ taMPs correlated with the measured tumour-volume in CRC patients. EpCAM+ taMPs decreased at 7 days after curative R0 tumour resection suggesting a close dependence with tumour presence. AUROC values (up to 0.85 and 0.90), sensitivity/specificity scores, and positive/negative predictive values indicated a high diagnostic accuracy of EpCAM+CD147+ taMPs. Taken together, EpCAM+CD147+ double positive taMPs could potentially serve as novel promising clinical parameter for cancer screening, diagnosis, surveillance and therapy monitoring.

[Reduced zinc concentration in expressed prostatic secretion relates to the pain symptoms of types Ⅲ and Ⅳ prostatitis].

PubMed

Mo, Lin-Jian; Chen, Xi; Wang, Xiao-Ming; Li, Guang-Yu; Zhang, Xun; Huang, Shan; Xie, Zhi-Bin; Mo, Zeng-Nan

2016-06-01

To determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis. We collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type ⅢA, 69 cases of type ⅢB, and 39 cases of type Ⅳ, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects. The participants were aged 17－65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the ⅢA (［162.2±10.8］ μg/ml) and ⅢB (［171.2±12.0］ μg/ml) than in the Ⅳ (［234.6±17.9］ μg/ml) (P<0.05 ) and the control group (［259.5±14.6］ μg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=－0.248, P<0.01), quality of life score (r=－0.232, P<0.01), severity score (r=－0.270, P<0.01), total NIH-CPSI score (r=－0.281, P<0.01), and the pH value in EPS (r=－0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects. The reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.

Selective inhibition of prostaglandin E2 receptors EP2 and EP4 induces apoptosis of human endometriotic cells through suppression of ERK1/2, AKT, NFkappaB, and beta-catenin pathways and activation of intrinsic apoptotic mechanisms.

PubMed

Banu, Sakhila K; Lee, JeHoon; Speights, V O; Starzinski-Powitz, Anna; Arosh, Joe A

2009-08-01

Endometriosis is a benign chronic gynecological disease of reproductive-age women characterized by the presence of functional endometrial tissues outside the uterine cavity. It is an estrogen-dependent disease. Current treatment modalities to inhibit biosynthesis and actions of estrogen compromise menstruation, pregnancy, and the reproductive health of women and fail to prevent reoccurrence of disease. There is a critical need to identify new specific signaling modules for non-estrogen-targeted therapies for endometriosis. In our previous study, we reported that selective inhibition of cyclooxygenase-2 prevented survival, migration, and invasion of human endometriotic epithelial and stromal cells, which was due to decreased prostaglandin E(2) (PGE(2)) production. In this study, we determined mechanisms through which PGE(2) promoted survival of human endometriotic cells. Results of the present study indicate that 1) PGE(2) promotes survival of human endometriotic cells through EP2 and EP4 receptors by activating ERK1/2, AKT, nuclear factor-kappaB, and beta-catenin signaling pathways; 2) selective inhibition of EP2 and EP4 suppresses these cell survival pathways and augments interactions between proapoptotic proteins (Bax and Bad) and antiapoptotic proteins (Bcl-2/Bcl-XL), facilitates the release of cytochrome c, and thus activates caspase-3/poly (ADP-ribose) polymerase-mediated intrinsic apoptotic pathways; and 3) these PGE(2) signaling components are more abundantly expressed in ectopic endometriosis tissues compared with eutopic endometrial tissues during the menstrual cycle in women. These novel findings may provide an important molecular framework for further evaluation of selective inhibition of EP2 and EP4 as potential therapy, including nonestrogen target, to expand the spectrum of currently available treatment options for endometriosis in women.

A novel technique using potassium permanganate and reflectance confocal microscopy to image biofilm extracellular polymeric matrix reveals non-eDNA networks in Pseudomonas aeruginosa biofilms.

PubMed

Swearingen, Matthew C; Mehta, Ajeet; Mehta, Amar; Nistico, Laura; Hill, Preston J; Falzarano, Anthony R; Wozniak, Daniel J; Hall-Stoodley, Luanne; Stoodley, Paul

2016-02-01

Biofilms are etiologically important in the development of chronic medical and dental infections. The biofilm extracellular polymeric substance (EPS) determines biofilm structure and allows bacteria in biofilms to adapt to changes in mechanical loads such as fluid shear. However, EPS components are difficult to visualize microscopically because of their low density and molecular complexity. Here, we tested potassium permanganate, KMnO4, for use as a non-specific EPS contrast-enhancing stain using confocal laser scanning microscopy in reflectance mode. We demonstrate that KMnO4 reacted with EPS components of various strains of Pseudomonas, Staphylococcus and Streptococcus, yielding brown MnO2 precipitate deposition on the EPS, which was quantifiable using data from the laser reflection detector. Furthermore, the MnO2 signal could be quantified in combination with fluorescent nucleic acid staining. COMSTAT image analysis indicated that KMnO4 staining increased the estimated biovolume over that determined by nucleic acid staining alone for all strains tested, and revealed non-eDNA EPS networks in Pseudomonas aeruginosa biofilm. In vitro and in vivo testing indicated that KMnO4 reacted with poly-N-acetylglucosamine and Pseudomonas Pel polysaccharide, but did not react strongly with DNA or alginate. KMnO4 staining may have application as a research tool and for diagnostic potential for biofilms in clinical samples. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Experimental animal models of encapsulating peritoneal sclerosis.

PubMed

Hoff, Catherine M

2005-04-01

Encapsulating peritoneal sclerosis (EPS) is an infrequent, but extremely serious complication of long-term peritoneal dialysis. The cause of EPS is unclear, but the low incidence suggests that it is most likely multifactorial. The elucidation of developmental pathways and predictive markers of EPS would facilitate the identification and management of high-risk patients. Animal models are often used to define pathways of disease progression and to test strategies for treatment and prevention in the patient population. Ideally such models could help to define the cause of EPS and its developmental pathways, to facilitate the identification of contributing factors and predictive markers, and to provide a system to test therapeutic strategies. Researchers have studied several rodent models of EPS that rely on chronic chemical irritation (for example, bleach, low-pH solution, chlorhexidine gluconate) to induce peritoneal sclerosis and abdominal encapsulation. Development in all models is progressive, with inflammation giving way to peritoneal fibrosis or sclerosis with accumulating membrane damage, culminating in cocoon formation. Microscopic findings are similar to those proposed as diagnostic criteria for clinical EPS: an initial inflammatory infiltrate and submesothelial thickening, collagen deposition, and activation and proliferation of peritoneal fibroblasts. The potential to block progression of peritoneal sclerosis in these models by anti-inflammatory, antifibrotic, and anti-angiogenic agents, and by inhibitors of the renin-angiotensin system have been demonstrated. Animal models based on clinically relevant risk factors (for example, uremia, peritonitis, and long-term exposure to dialysis solutions) now represent the next step in model development.

Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

PubMed

Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

2015-11-15

Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects. Copyright © 2015 the American Physiological Society.

Tidal and seasonal effects on the short-term temporal patterns of bacteria, microphytobenthos and exopolymers in natural intertidal biofilms (Brouage, France)

NASA Astrophysics Data System (ADS)

Orvain, Francis; De Crignis, Margot; Guizien, Katell; Lefebvre, Sébastien; Mallet, Clarisse; Takahashi, Eri; Dupuy, Christine

2014-09-01

Relationships between bacteria, microphytobenthos and extracellular polymeric substances (EPS) that make up microbial biofilms over bare mudflats were investigated at an hourly frequency during two 14-day spring-neap cycles in winter and summer 2008. Bacterial abundance and total chl a concentration were lower in summer (0.78 × 108 ± SD 0.39 × 108 cell.m- 2 and 59.0 ± SD 10.42 mgchla.m- 2) than in winter (3.7 × 108 ± SD 1.9 × 108 cell.m- 2 and 106.64 ± SD 11.29 mgchla.m- 2), coinciding with a high abundance of the gastropod Peringia ulvae in summer, which subsequently impacted 1st-cm chl a concentration by intense grazing. Bound and colloidal EPS carbohydrate temporal patterns were similar in winter (5.71 ± SD 3.95 and 4.67 ± SD 3.45 μg.g- 1, respectively) but were different in summer (14.9 ± SD 4.05 and 5.60 ± SD 4.50 μg.g- 1, respectively). Carbohydrate colloidal EPS appeared to be related to light and salinity, while 1st-mm chl a concentration was negatively affected by strong salinities and predation pressure by P. ulvae. The fluctuations of colloidal carbohydrates were remarkably similar in the two seasons with peaks just after spring tides when the highest irradiance was received by microphytobenthic cells. Apparently, colloidal EPS carbohydrates can protect cells against the high salinity values ranging from 32.3 to 50.4 PSU. The presence of bound EPS carbohydrates may be linked to sediment colonization and resistance of biofilm activity. Proteins in EPS were absent in winter and represented a small proportion in summer (10%), but they appeared to be a good indicator of potential synergistic effects between MPB and bacteria in summer. Conversely, bound EPS carbohydrates reached high levels in winter, while the number of bacteria decreased simultaneously, suggesting a negative effect on bacterial growth in the absence of proteins in EPS. There was a lower proportion (31%) of low molecular weight EPS in summer than in winter (83%), possibly in relation to desiccation.

Living with encapsulating peritoneal sclerosis (EPS): the patient's perspective.

PubMed

Hurst, Helen; Summers, Angela; Beaver, Kinta; Caress, Ann-Louise

2014-01-01

Although relatively rare, encapsulating peritoneal sclerosis (EPS) is nonetheless a major concern within the renal community. Risk of developing EPS is associated with long-term peritoneal dialysis (PD). High mortality was previously reported, although surgery has since improved outcomes. Research into EPS focuses on imaging and early detection methods, genetics, biomarkers and preventive strategies. No previous studies have examined patients' experiences of EPS. The aim of the present study was to explore the experience of patients who have undergone surgery for EPS in one center in the North of England. A qualitative phenomenological approach, involving in-depth interviews, was adopted. Nine participants were recruited out of a total of 18 eligible. Most participants were interviewed twice over a 12-month period (October 2009 to October 2010). Interpretive data analysis was conducted, following the philosophical tradition of hermeneutics, to draw out themes from the data. Data collection and analysis took place concurrently and participants were sent a summary of their first interview to allow a period of reflection prior to the subsequent interview. EPS presented the most serious challenge participants had faced since developing chronic kidney disease (CKD). Three major themes were identified, each with subcategories. The key issues for patients were related to identification of early symptoms and lack of understanding. The patients' sense of 'not being heard' by health care professionals led to a loss of trust and enhanced their feelings of uncertainty. The enormity of the surgery, the suffering, and what they had to endure had an enormous impact, but an overriding aspect of this experience was also the loss they felt for their independence and for the PD therapy over which they had control. The findings of this study highlight a number of important issues relevant to clinical practice, including lack of information and understanding of EPS, particularly its early symptoms At the time patients transfer from peritoneal to hemodialysis, the provision of adequate information about the risks and potential early signs of EPS may not only improve their experiences, but may also assist in early detection. Copyright © 2014 International Society for Peritoneal Dialysis.

Aircraft-Based Satellite Navigation Augmentation to Enable Automated Landing and Movement on the Airport Surface

NASA Astrophysics Data System (ADS)

Obeidat, Qasem Turki

A brain-computer interface (BCI) enables a paralyzed user to interact with an external device through brain signals. A BCI measures identifies patterns within these measured signals, translating such patterns into commands. The P300 is a pattern of a scalp potentials elicited by a luminance increment of an attended target rather than a non-target character of an alphanumeric matrix. The Row-Column Paradigm (RCP) can utilize responses to series of illuminations of matrix target and non-target characters to spell out alphanumeric strings of P300-eliciting target characters, yet this popular RCP speller faces three challenges. Theadjacent problem concerns the proximity of neighboring characters, the crowding problem concerns their number. Both adjacent and crowding problems concern how these factors impede BCI performance. The fatigue problem concerns how RCP use is tiring. This dissertation addressed these challenges for both desktop and mobile platforms. A new P300 speller interface, the Zigzag Paradigm (ZP), reduced the adjacent problem by increasing the distance between adjacent characters, as well as the crowding problem, by reducing the number neighboring characters. In desktop study, the classification accuracy was significantly improved 91% with the ZP VS 80.6% with the RCP. Since the ZP is not suitable for mobile P300 spellers with a small screen size, a new P300 speller interface was developed in this study, the Edges Paradigm (EP). The EP reduced the adjacent and crowding problems by adding flashing squares located upon the outer edges of the character matrix in the EP. The classification accuracy of the EP (i.e., 93.3%) was significantly higher than the RCP (i.e., 82.1%). We further compared three speller paradigms (i.e., RCP, ZP, and EP), and the result indicated that the EP produced the highest accuracy and caused less fatigue. Later, the EP is implemented in a simulator of a Samsung galaxy smart phone on the Microsoft Surface Pro 2. The mobile EP was compared with the RCP under the mobility situation when a user is moving on a wheelchair. The results showed that the EP significantly improved the online classification accuracy and user experience over the RCP.

Prioritizing Risk in Preparation for a Demonstration Project: A Mixed Methods Feasibility Study of Oral Pre-Exposure Prophylaxis (PREP) among Female Sex Workers in South India

PubMed Central

Reza-Paul, Sushena; Lazarus, Lisa; Doshi, Monika; Hafeez Ur Rahman, Syed; Ramaiah, Manjula; Maiya, Raviprakash; MS, Venugopal; Venukumar, K. T.; Sundararaman, Sundar; Becker, Marissa; Moses, Stephen; Lorway, Robert

2016-01-01

Background HIV prevalence among female sex workers (FSWs) in India remains well above the national average. Pre-exposure prophylaxis (PrEP), a new HIV prevention technology, may help to reduce HIV incidence, but there is a dearth of research that can inform the potential scale-up of PrEP in India. In partnership with Ashodaya Samithi, a local sex worker collective, we conducted a feasibility study to assess acceptance of a planned PrEP demonstration project, willingness to use PrEP, and recommendations for project roll-out among FSWs in southern Karnataka. Methods From January–April 2015, 6 focus group discussions, 47 in-depth interviews, and 427 interviewer-administered questionnaires were completed by female sex workers. All participants were 18 years of age or older and practiced sex work. Qualitative data were coded for key themes and emergent categories. Univariate descriptive analysis was employed to summarise the quantitative data. Results Qualitative. PrEP was described as an exciting new prevention technology that places control in the hands of FSWs and provides a “double safety” in combination with condom use. Participants expressed agreement that women who may experience more HIV risk in their occupational environments should be prioritized for enrollment into a demonstration project. Quantitative. 406 participants (95%) expressed interest in PrEP. Participants prioritized the inclusion of FSWs under the age of 25 (79%), those who do not use condoms when clients offer more money (58%), who do not consistently use condoms with regular partners (57%), who drink alcohol regularly (49%), and who do not use condoms consistently with clients (48%). Discussion This feasibility study indicated strong interest in PrEP and a desire to move forward with the demonstration project. Participants expressed their responses in terms of public health discourses surrounding risk, pointing to the importance of situating PrEP scale up within the trusted spaces of community-based organizations as a means of supporting PrEP uptake and adherence. PMID:27880833

EPS composition and calcification potential of tufa-dominating cyanobacteria investigated by Scanning Transmission X-ray Microscopy (STXM) and Laser Scanning Microscopy (LSM)

NASA Astrophysics Data System (ADS)

Zippel, Barbara; Dynes, James J.; Obst, Martin; Lawrence, John R.; Neu, Thomas R.

2010-05-01

Tufa deposits in freshwater habitats are the result of calcium carbonate precipitation within interfacial microbial ecosystems. Calcite precipitation is influenced by the saturation index and the occurrence of extracellular polymeric substances (EPS) which are produced by a variety of microorganisms. In theory, the first important step of biologically induced calcification processes is the adsorption of calcium ions by extracellular polymeric substances (EPS) produced by cyanobacteria. In the present study we take advantage of Laser Scanning Microscopy (LSM) and combine it with Synchrotron imaging using Scanning Transmission X-ray Microscopy (STXM). STXM represents a technique that allows simultaneous analysis of inorganic and organic constituents as a scale of 50 nm. By means of STXM it is possible to differentiate between calcium carbonate phases at the Ca L-edge. Furthermore, STXM has also been used at the C K-edge to map the major biomolecules (proteins, lipids, and polysaccharides). The purpose of this study is to find out if there are differences in calcium adsorption depending on specific composition of the EPS produced by filamentous cyanobacteria isolated from a German hard water creek (Westerhöfer Bach, Harz Mountains). The goal was to elucidate the potential of biofilms constituents, including microbial cell surfaces as well as extracellular polymeric substances, in triggering the formation of calcium carbonate in tufa systems. For this purpose three filamentous cyanobacteria (Pseudanabaena sp., Leptolyngbya sp. and Nostoc sp.) were cultivated in creek-adapted as well as standard media (BG11) on polycarbonate slides. In situ EPS composition was detected by means of fluorescence lectin-binding approach (FLBA) using 23 commercially available lectins with different specificities for mono- and disaccharides and amino sugars. For CaCO3 nucleation experiments cyanobacterial biofilms grown on polycarbonate slides were deposited in NaHCO3/CaCl2 solutions supersaturated 10 times with respect to calcite for 48, 72 and 144 hours. For the STXM experiment on beamline 10-ID1 at the Canadian Light Source (CLS), the biofilm samples were scrapped off, suspended in a slurry and deposited carefully on a Si3N4 window. In order to obtain quantitative speciation maps of cyanobacterial sheath EPS, image sequences (stacks) were recorded at the C-1s (280-320 eV) and Ca-2p (340-360 eV) edges. Data analysis was done by using the software aXis2000, and energy spectra were fitted with available reference spectra. Nearly the same lectins specific for fucose, mannose, N-acetylgalactosamine and N-acetylglucosamine, as well as sialic acid bound preferentially to the EPS of cyanobacterial sheaths of Pseudanabaena sp. and Leptolyngbya sp. Surprisingly, in case of Nostoc sp. only two lectins specific for fucose, and N-acetylgalactosamine showed a clear binding to the EPS of sheaths. Qualitative, lectin-specific EPS composition was not influenced by nutrient concentrations within the medium during cultivation. In order to biochemically characterize the CaCO3 nucleation sites within the sheaths of the cyanobacteria investigated, carbon maps of the most abundant organic components were derived from C-1s image sequences. The sheaths of the cyanobacteria contained mainly polysaccharides followed by proteins, and a small amount of lipids. The highest amount of polysaccharides was detected in EPS produced by Pseudanabaena sp., whereas in Nostoc sp. only one-fifth was found. All samples investigated contained spectral signatures of Ca2+ adsorbed to EPS. Aragonite-like CaCO3 was detected in close association with the cell surface of Leptolyngbya sp. only. Highest amount of adsorbed Ca to EPS was found in Pseudanabaena sp., whereas only one-third was detected within the EPS of sheaths in Leptolyngbya sp. and Nostoc sp. Results of this combined approach show that the cyanobacteria investigated are may be involved in calcification processes to different degrees.

EPS (Electric Particulate Suspension) Microgravity Technology Provides NASA with New Tools

NASA Technical Reports Server (NTRS)

Colver, Gerald M.; Greene, Nate; Xu, Hua

2004-01-01

The Electric Particulate Suspension is a fire safety ignition test system being developed at Iowa State University with NASA support for evaluating combustion properties of powders, powder-gas mixtures, and pure gases in microgravity and gravitational atmospheres (quenching distance, ignition energy, flammability limits). A separate application is the use of EPS technology to control heat transfer in vacuum and space environment enclosures. In combustion testing, ignitable powders (aluminum, magnesium) are introduced in the EPS test cell and ignited by spark, while the addition of inert particles act as quenching media. As a combustion research tool, the EPS method has potential as a benchmark design for quenching powder flames that would provide NASA with a new fire safety standard for powder ignition testing. The EPS method also supports combustion modeling by providing accurate measurement of flame-quenching distance as an important parameter in laminar flame theory since it is closely related to characteristic flame thickness and flame structure. In heat transfer applications, inert powder suspensions (copper, steel) driven by electric fields regulate heat flow between adjacent surfaces enclosures both in vacuum (or gas) and microgravity. This simple E-field control can be particularly useful in space environments where physical separation is a requirement between heat exchange surfaces.

Partial characterization of an extracellular polysaccharide produced by the moderately halophilic bacterium Halomonas xianhensis SUR308.

PubMed

Biswas, Jhuma; Ganguly, J; Paul, A K

2015-01-01

A moderately halophilic bacterium, Halomonas xianhensis SUR308 (Genbank Accession No. KJ933394) was isolated from a multi-pond solar saltern at Surala, Ganjam district, Odisha, India. The isolate produced a significant amount (7.87 g l(-1)) of extracellular polysaccharides (EPS) when grown in malt extract-yeast extract medium supplemented with 2.5% NaCl, 0.5% casein hydrolysate and 3% glucose. The EPS was isolated and purified following the conventional method of precipitation and dialysis. Chromatographic analysis (paper, GC and GC-MS) of the hydrolyzed EPS confirmed its heteropolymeric nature and showed that it is composed mainly of glucose (45.74 mol%), galactose (33.67 mol %) and mannose (17.83 mol%). Fourier-transform infrared spectroscopy indicated the presence of methylene and carboxyl groups as characteristic functional groups. In addition, its proton nuclear magnetic resonance spectrum revealed functional groups specific for extracellular polysaccharides. X-ray diffraction analysis revealed the amorphous nature (CIxrd, 0.56) of the EPS. It was thermostable up to 250 °C and displayed pseudoplastic rheology and remarkable stability against pH and salts. These unique properties of the EPS produced by H. xianhensis indicate its potential to act as an agent for detoxification, emulsification and diverse biological activities.

Mechanical and thermal properties of biocomposites from nonwoven industrial Fique fiber mats with Epoxy Resin and Linear Low Density Polyethylene

NASA Astrophysics Data System (ADS)

Hidalgo-Salazar, Miguel A.; Correa, Juan P.

2018-03-01

In this work Linear Low Density Polyethylene-nonwoven industrial Fique fiber mat (LLDPE-Fique) and Epoxy Resin-nonwoven industrial Fique fiber mat (EP-Fique) biocomposites were prepared using thermocompression and resin film infusion processes. Neat polymeric matrices and its biocomposites were tested following ASTM standards in order to evaluate tensile and flexural mechanical properties. Also, thermal behavior of these materials has been studied by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Tensile and flexural test revealed that nonwoven Fique reinforced composites exhibited higher modulus and strength but lower deformation capability as compared with LLDPE and EP neat matrices. TG thermograms showed that nonwoven Fique fibers incorporation has an effect on the thermal stability of the composites. On the other hand, Fique fibers did not change the crystallization and melting processes of the LLDPE matrix but restricts the motion of EP macromolecules chains thus increases the Tg of the EP-Fique composite. Finally, this work opens the possibility of considering non-woven Fique fibers as a reinforcement material with a high potential for the manufacture of biocomposites for automotive applications. In addition to the processing test specimens, it was also possible to manufacture a part of LLDPE-Fique, and one part of EP-Fique.

The effectiveness of three home products in cleaning and disinfection of Staphylococcus aureus and Escherichia coli on home environmental surfaces.

PubMed

Goodyear, N; Brouillette, N; Tenaglia, K; Gore, R; Marshall, J

2015-11-01

The objectives of this study were to investigate three products for: (i) cleaning effectiveness on two common household surfaces, and (ii) disinfection effectiveness against two common bacteria. Products included conventional ('bleach'), environmentally preferable (EP), do-it-yourself (DIY: distilled white vinegar, club soda, tea tree oil), 24-h old DIY, and individual DIY components in dilution. For cleaning ceramic, no product was effective (≥85% removal of Hucker's soil), however, DIY performed better than EP and bleach. On stainless, only DIY failed to meet the standard. For disinfection, bleach and EP achieved ≥5·00 log10 reductions under all conditions. DIY and components were more active against Escherichia coli than Staphylococcus aureus but only fresh DIY and 50% vinegar achieved ≥5·00 log10 reductions. EP is an effective alternative to bleach. DIY may be an adequate alternative for cleaning ceramic and for household use, where complete elimination of micro-organisms is unnecessary; however, it must be freshly prepared each day. This is the first report of performance of purportedly safer alternatives for both cleaning and disinfection for use in home health care. The EP product and DIY are potential alternatives for some household uses. © 2015 The Society for Applied Microbiology.

Chemical and rheological properties of exopolysaccharides produced by four isolates of rhizobia.

PubMed

Moretto, Cristiane; Castellane, Tereza Cristina Luque; Lopes, Erica Mendes; Omori, Wellington Pine; Sacco, Laís Postai; Lemos, Eliana Gertrudes de Macedo

2015-11-01

The rheological, physicochemical properties, emulsification and stability of exopolysaccharides (EPSs) from four rhizobia isolates (LBMP-C01, LBMP-C02, LBMP-C03 and LBMP-C04) were studied. The EPS yields of isolates under these experimental conditions were in the range of 1.5-6.63gL(-1). The LBMP-C04 isolate, which presented the highest EPS production (6.63gL(-1)), was isolated from Arachis pintoi and was identified as a Rhizobium sp. strain that could be explored as a possible potential source for the production of extracellular heteropolysaccharides. All polymers showed a pseudoplastic non-Newtonian fluid behavior or shear thinning property in aqueous solutions. Among the four EPS tested against hydrocarbons, EPS LBMP-C01 was found to be more effective against hexane, olive and soybean oils (89.94%, 82.75% and 81.15%, respectively). Importantly, we found that changes in pH (2-11) and salinity (0-30%) influenced the emulsification of diesel oil by the EPSs. EPSLBMP-C04 presented optimal emulsification capacity at pH 10 (E24=53%) and 30% salinity (E24=27%). These findings contribute to the understanding of the influence of the chemical composition, physical properties and biotechnology applications of rhizobial EPS solutions their bioemulsifying properties. Copyright © 2015 Elsevier B.V. All rights reserved.

Transition Metal-Oxide Free Perovskite Solar Cells Enabled by a New Organic Charge Transport Layer.

PubMed

Chang, Sehoon; Han, Ggoch Ddeul; Weis, Jonathan G; Park, Hyoungwon; Hentz, Olivia; Zhao, Zhibo; Swager, Timothy M; Gradečak, Silvija

2016-04-06

Various electron and hole transport layers have been used to develop high-efficiency perovskite solar cells. To achieve low-temperature solution processing of perovskite solar cells, organic n-type materials are employed to replace the metal oxide electron transport layer (ETL). Although PCBM (phenyl-C61-butyric acid methyl ester) has been widely used for this application, its morphological instability in films (i.e., aggregation) is detrimental. Herein, we demonstrate the synthesis of a new fullerene derivative (isobenzofulvene-C60-epoxide, IBF-Ep) that serves as an electron transporting material for methylammonium mixed lead halide-based perovskite (CH3NH3PbI(3-x)Cl(x)) solar cells, both in the normal and inverted device configurations. We demonstrate that IBF-Ep has superior morphological stability compared to the conventional acceptor, PCBM. IBF-Ep provides higher photovoltaic device performance as compared to PCBM (6.9% vs 2.5% in the normal and 9.0% vs 5.3% in the inverted device configuration). Moreover, IBF-Ep devices show superior tolerance to high humidity (90%) in air. By reaching power conversion efficiencies up to 9.0% for the inverted devices with IBF-Ep as the ETL, we demonstrate the potential of this new material as an alternative to metal oxides for perovskite solar cells processed in air.

Molecular bases of K+ secretory cells in the inner ear: shared and distinct features between birds and mammals

PubMed Central

Wilms, Viviane; Köppl, Christine; Söffgen, Chris; Hartmann, Anna-Maria; Nothwang, Hans Gerd

2016-01-01

In the cochlea, mammals maintain a uniquely high endolymphatic potential (EP), which is not observed in other vertebrate groups. However, a high [K+] is always present in the inner ear endolymph. Here, we show that Kir4.1, which is required in the mammalian stria vascularis to generate the highly positive EP, is absent in the functionally equivalent avian tegmentum vasculosum. In contrast, the molecular repertoire required for K+ secretion, specifically NKCC1, KCNQ1, KCNE1, BSND and CLC-K, is shared between the tegmentum vasculosum, the vestibular dark cells and the marginal cells of the stria vascularis. We further show that in barn owls, the tegmentum vasculosum is enlarged and a higher EP (~+34 mV) maintained, compared to other birds. Our data suggest that both the tegmentum vasculosum and the stratified stria vascularis evolved from an ancestral vestibular epithelium that already featured the major cell types of the auditory epithelia. Genetic recruitment of Kir4.1 specifically to strial melanocytes was then a crucial step in mammalian evolution enabling an increase in the cochlear EP. An increased EP may be related to high-frequency hearing, as this is a hallmark of barn owls among birds and mammals among amniotes. PMID:27680950

High pre-exposure prophylaxis uptake and early adherence among men who have sex with men and transgender women at risk for HIV Infection: the PrEP Brasil demonstration project.

PubMed

Hoagland, Brenda; Moreira, Ronaldo I; De Boni, Raquel B; Kallas, Esper G; Madruga, José Valdez; Vasconcelos, Ricardo; Goulart, Silvia; Torres, Thiago S; Marins, Luana M S; Anderson, Peter L; Luz, Paula M; Costa Leite, Iuri da; Liu, Albert Y; Veloso, Valdilea G; Grinsztejn, Beatriz

2017-04-06

The efficacy of pre-exposure prophylaxis (PrEP) in preventing sexual acquisition of human immunodeficiency virus (HIV) is well established. Little is known about the feasibility of PrEP implementation in middle-income settings with concentrated epidemics among men who have sex with men (MSM) and transgender women (TGW). PrEP Brasil is a prospective, multicentre, open-label demonstration project assessing PrEP delivery in the context of the Brazilian Public Health System. HIV-uninfected MSM and TGW in 3 referral centres in Rio de Janeiro and São Paulo were evaluated for eligibility and offered 48 weeks of daily emtricitabine/tenofovir for PrEP. Concentrations of tenofovir diphosphate in dried blood spot samples (DBS) at week 4 after enrolment (early adherence) were measured. Predictors of drug levels were assessed using ordinal logistic regression models considering the DBS drug level as a 3 level variable (<350 fmol/punch, ≥350-699 fmol/punch and ≥700 fmol/punch). 1,270 individuals were assessed for participation; n = 738 were potentially eligible and n = 450 were offered PrEP (PrEP uptake was 60.9%). Eligible but not enrolled individuals were younger, had lower HIV risk perception and had lower PrEP awareness. At week 4, 424 participants (of the 450 enrolled) had DBS TFV-DP concentrations, 94.1% in the protective range (≥350 fmol/punch, consistent with ≥2 pills per week), and 78% were in the highly protective range (≥700 fmol/punch, ≥4 pills per week). Participants with ≥12 years of schooling had 1.9 times the odds (95%CI 1.10-3.29) of a higher versus lower drug level than participants with <12 years of schooling. Condomless receptive anal intercourse in the prior 3 months was also associated with higher drug levels (adjusted OR = 1.78; 95% CI 1.08-2.94). The high uptake and early adherence indicate that PrEP for high-risk MSM and TGW can be successfully delivered in the context of the Brazilian Public Health System. Interventions to address disparities on PrEP awareness and HIV risk perception among the younger and less educated are urgently needed in order to maximize the impact of this prevention strategy on the reduction of HIV infection among MSM and TGW in Brazil.

Consensus Conference Follow-up: Inter-rater Reliability Assessment of the Best Evidence in Emergency Medicine (BEEM) Rater Scale, a Medical Literature Rating Tool for Emergency Physicians

PubMed Central

Worster, Andrew; Kulasegaram, Kulamakan; Carpenter, Christopher R.; Vallera, Teresa; Upadhye, Suneel; Sherbino, Jonathan; Haynes, R. Brian

2011-01-01

Background Studies published in general and specialty medical journals have the potential to improve emergency medicine (EM) practice, but there can be delayed awareness of this evidence because emergency physicians (EPs) are unlikely to read most of these journals. Also, not all published studies are intended for or ready for clinical practice application. The authors developed “Best Evidence in Emergency Medicine” (BEEM) to ameliorate these problems by searching for, identifying, appraising, and translating potentially practice-changing studies for EPs. An initial step in the BEEM process is the BEEM rater scale, a novel tool for EPs to collectively evaluate the relative clinical relevance of EM-related studies found in more than 120 journals. The BEEM rater process was designed to serve as a clinical relevance filter to identify those studies with the greatest potential to affect EM practice. Therefore, only those studies identified by BEEM raters as having the highest clinical relevance are selected for the subsequent critical appraisal process and, if found methodologically sound, are promoted as the best evidence in EM. Objectives The primary objective was to measure inter-rater reliability (IRR) of the BEEM rater scale. Secondary objectives were to determine the minimum number of EP raters needed for the BEEM rater scale to achieve acceptable reliability and to compare performance of the scale against a previously published evidence rating system, the McMaster Online Rating of Evidence (MORE), in an EP population. Methods The authors electronically distributed the title, conclusion, and a PubMed link for 23 recently published studies related to EM to a volunteer group of 134 EPs. The volunteers answered two demographic questions and rated the articles using one of two randomly assigned seven-point Likert scales, the BEEM rater scale (n = 68) or the MORE scale (n = 66), over two separate administrations. The IRR of each scale was measured using generalizability theory. Results The IRR of the BEEM rater scale ranged between 0.90 (95% confidence interval [CI] = 0.86 to 0.93) to 0.92 (95% CI = 0.89 to 0.94) across administrations. Decision studies showed a minimum of 12 raters is required for acceptable reliability of the BEEM rater scale. The IRR of the MORE scale was 0.82 to 0.84. Conclusions The BEEM rater scale is a highly reliable, single-question tool for a small number of EPs to collectively rate the relative clinical relevance within the specialty of EM of recently published studies from a variety of medical journals. It compares favorably with the MORE system because it achieves a high IRR despite simply requiring raters to read each article’s title and conclusion. PMID:22092904

A case study of chewed Truvada® for PrEP maintaining protective drug levels as measured by a novel urine tenofovir assay.

PubMed

Lalley-Chareczko, Linden; Clark, Devon; Zuppa, Athena F; Moorthy, Ganesh; Conyngham, Caitlin; Mounzer, Karam; Koenig, Helen

2017-01-01

Emtricitabine/tenofovir disoproxil fumarate (FTC/TDF; Truvada ® ) given as pre-exposure prophylaxis (PrEP) successfully blocks HIV when taken once daily prior to potential HIV exposure. A 22-year-old male reported difficulty swallowing FTC/TDF for PrEP and subsequently began chewing the FTC/TDF tablets. Monthly urine samples assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) indicated tenofovir levels >1,000 ng/ml, indicative of protection from HIV acquisition, over a 48-week period. Data from observational studies of HIV-positive patients details the successful treatment of HIV using crushed FTC/TDF delivered via feeding and gastronomy tubes while small, randomized trials of healthy volunteers demonstrate bioequivalence between whole and crushed FTC/TDF.

Corrosion protection of low-carbon steel using exopolysaccharide coatings from Leuconostoc mesenteroides.

PubMed

Finkenstadt, Victoria L; Côté, Gregory L; Willett, J L

2011-06-01

Corrosion of metals is a serious and challenging problem faced worldwide by industry. Purified Leuconostoc mesenteroides exopolysaccharide (EPS) coatings, cast from aqueous solution, inhibited the corrosion of low-carbon steel as determined by electrochemical impedance spectroscopy (EIS). There were two different corrosion behaviors exhibited when EPS films from different strains were cast onto the steel. One EPS coating reacted immediately with the steel substrate to form an iron (III) oxide layer ("rust") during the drying process while another did not. The samples that did not flash corrode had higher corrosion inhibition and formed an iron (II) passivation layer during EIS testing that persisted after the cells were disassembled. Corrosion inhibition was strain-specific as polysaccharides with similar structure did not have the same corrosion potential.

A novel Online-to-Offline (O2O) model for pre-exposure prophylaxis and HIV testing scale up.

PubMed

Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya

2017-03-13

PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam's Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. The O2O model was piloted by Adam's Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam's Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant's socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Between January 10th and April 11th, 2016, Adam's Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0-7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14-4.66; p  = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19-3.54; p  = 0.009), being aware of sexual partners' HIV status (OR 2.37, 95%CI 1.29-4.35; p  = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19-5.09; p  = 0.01), and enrolment at Adam's Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06-6.95; p  < 0.001) were independently associated with PrEP uptake. Adam's Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations.

77 FR 65935 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-31

... NS Port Road Branch from Perrysburg, MD, Milepost (MP) PD-0.3, to Enola, PA, MP EP-68.2. The discontinuance would include automatic signals: PD 1.9, PD 6.4, PD 9.7, PD 15.7, PD 18.7, PD 23.6, PD 28.8, PD 35.7, EP 35.2, EP 40.0, EP 42.4, EP 47.6, EP 49.5, EP 53.6, EP 54.0, EP 58.3, EP 62.8, EP 67.1. The...

EEG, evoked potentials and pulsed Doppler in asphyxiated term infants.

PubMed

Julkunen, Mia K; Himanen, Sari-Leena; Eriksson, Kai; Janas, Martti; Luukkaala, Tiina; Tammela, Outi

2014-09-01

To evaluate electroencephalograms (EEG), evoked potentials (EPs) and Doppler findings in the cerebral arteries as predictors of a 1-year outcome in asphyxiated newborn infants. EEG and EPs (brain stem auditory (BAEP), somatosensory (SEP), visual (VEP) evoked potentials) were assessed in 30 asphyxiated and 30 healthy term infants during the first days (range 1-8). Cerebral blood flow velocities (CBFV) were measured from the cerebral arteries using pulsed Doppler at ∼24h of age. EEG, EPs, Doppler findings, symptoms of hypoxic ischemic encephalopathy (HIE) and their combination were evaluated in predicting a 1-year outcome. An abnormal EEG background predicted poor outcome in the asphyxia group with a sensitivity of 67% and 81% specificity, and an abnormal SEP with 75% and 79%, respectively. Combining increased systolic CBFV (mean+3SD) with abnormal EEG or SEP improved the specificity, but not the sensitivity. The predictive values of abnormal BAEP and VEP were poor. Normal EEG and SEP predicted good outcome in the asphyxia group with sensitivities from 79% to 81%. The combination of normal EEG, normal SEP and systolic CBFV<3SD predicted good outcome with a sensitivity of 74% and 100% specificity. Combining abnormal EEG or EPs findings with increased systolic CBFV did not improve prediction of a poor 1-year outcome of asphyxiated infants. Normal EEG and normal SEP combined with systolic CBFV<3SD at about 24 h can be valuable in the prediction of normal 1-year outcome. Combining systolic CBFV at 24 h with EEG and SEP examinations can be of use in the prediction of normal 1-year outcome among asphyxiated infants. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Prediction of long-term disability in multiple sclerosis.

PubMed

Schlaeger, R; D'Souza, M; Schindler, C; Grize, L; Dellas, S; Radue, E W; Kappos, L; Fuhr, P

2012-01-01

Little is known about the predictive value of neurophysiological measures for the long-term course of multiple sclerosis (MS). To prospectively investigate whether combined visual (VEP) and motor evoked potentials (MEP) allow prediction of disability over 14 years. A total of 30 patients with relapsing-remitting and secondary progressive MS were prospectively investigated with VEPs, MEPs and the Expanded Disability Status Scale (EDSS) at entry (T0) and after 6, 12 and 24 months, and with cranial MRI scans at entry (T2-weighted and gadolinium-enhanced T1-weighted images). EDSS was again assessed at year 14 (T4). The association between evoked potential (EP), magnetic resonance (MR) data and EDSS was measured using Spearman's rank correlation. Multivariable linear regression was performed to predict EDSS(T4) as a function of z-transformed EP-latencies(T0). The model was validated using a jack-knife procedure and the potential for improving it by inclusion of additional baseline variables was examined. EDSS values(T4) correlated with the sum of z-transformed EP-latencies(T0) (rho = 0.68, p < 0.0001), but not with MR-parameters(T0). EDSS(T4) as predicted by the formula EDSS(T4) = 4.194 + 0.088 * z-score P100(T0) + 0.071 * z-score CMCT(UE, T0) correlated with the observed values (rho = 0.69, p < 0.0001). Combined EPs allow prediction of long-term disability in small groups of patients with MS. This may have implications for the choice of monitoring methods in clinical trials and for daily practice decisions.

Functional and bioinformatics analysis of an exopolysaccharide-related gene (epsN) from Lactobacillus kefiranofaciens ZW3.

PubMed

Wang, Jingrui; Tang, Wei; Zheng, Yongna; Xing, Zhuqing; Wang, Yanping

2016-09-01

A novel lactic acid bacteria strain Lactobacillus kefiranofaciens ZW3 exhibited the characteristics of high production of exopolysaccharide (EPS). The epsN gene, located in the eps gene cluster of this strain, is associated with EPS biosynthesis. Bioinformatics analysis of this gene was performed. The conserved domain analysis showed that the EpsN protein contained MATE-Wzx-like domains. Then the epsN gene was amplified to construct the recombinant expression vector pMG36e-epsN. The results showed that the EPS yields of the recombinants were significantly improved. By determining the yields of EPS and intracellular polysaccharide, it was considered that epsN gene could play its Wzx flippase role in the EPS biosynthesis. This is the first time to prove the effect of EpsN on L. kefiranofaciens EPS biosynthesis and further prove its functional property.

Effect of dietary protein concentration on ammonia and greenhouse gas emitting potential of dairy manure.

PubMed

Lee, C; Hristov, A N; Dell, C J; Feyereisen, G W; Kaye, J; Beegle, D

2012-04-01

Two experiments were conducted to investigate the effect of dietary crude protein concentration on ammonia (NH(3)) and greenhouse gas (GHG; nitrous oxide, methane, and carbon dioxide) emissions from fresh dairy cow manure incubated in a controlled environment (experiment 1) and from manure-amended soil (experiment 2). Manure was prepared from feces and urine collected from lactating Holstein cows fed diets with 16.7% (DM basis; HCP) or 14.8% CP (LCP). High-CP manure had higher N content and proportion of NH(3)- and urea-N in total manure N than LCP manure (DM basis: 4.4 vs. 2.8% and 51.4 vs. 30.5%, respectively). In experiment 1, NH(3) emitting potential (EP) was greater for HCP compared with LCP manure (9.20 vs. 4.88 mg/m(2) per min, respectively). The 122-h cumulative NH(3) emission tended to be decreased 47% (P=0.09) using LCP compared with HCP manure. The EP and cumulative emissions of GHG were not different between HCP and LCP manure. In experiment 2, urine and feces from cows fed LCP or HCP diets were mixed and immediately applied to lysimeters (61×61×61 cm; Hagerstown silt loam; fine, mixed, mesic Typic Hapludalf) at 277 kg of N/ha application rate. The average NH(3) EP (1.53 vs. 1.03 mg/m(2) per min, respectively) and the area under the EP curve were greater for lysimeters amended with HCP than with LCP manure. The largest difference in the NH(3) EP occurred approximately 24 h after manure application (approximately 3.5 times greater for HCP than LCP manure). The 100-h cumulative NH(3) emission was 98% greater for HCP compared with LCP manure (7,415 vs. 3,745 mg/m(2), respectively). The EP of methane was increased and that of carbon dioxide tended to be increased by LCP compared with HCP manure. The cumulative methane emission was not different between treatments, whereas the cumulative carbon dioxide emission was increased with manure from the LCP diet. Nitrous oxide emissions were low in this experiment and did not differ between treatments. In the conditions of these experiments, fresh manure from dairy cows fed a LCP diet had substantially lower NH(3) EP, compared with manure from cows fed a HCP diet. The LCP manure increased soil methane EP due to a larger mass of manure added to meet plant N requirements compared with HCP manure. These results represent effects of dietary protein on NH(3) and GHG EP of manure in controlled laboratory conditions and do not account for environmental factors affecting gaseous emissions from manure on the farm. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Accounting for uncertainty in the quantification of the environmental impacts of Canadian pig farming systems.

PubMed

Mackenzie, S G; Leinonen, I; Ferguson, N; Kyriazakis, I

2015-06-01

The objective of the study was to develop a life cycle assessment (LCA) for pig farming systems that would account for uncertainty and variability in input data and allow systematic environmental impact comparisons between production systems. The environmental impacts of commercial pig production for 2 regions in Canada (Eastern and Western) were compared using a cradle-to-farm gate LCA. These systems had important contrasting characteristics such as typical feed ingredients used, herd performance, and expected emission factors from manure management. The study used detailed production data supplied by the industry and incorporated uncertainty/variation in all major aspects of the system including life cycle inventory data for feed ingredients, animal performance, energy inputs, and emission factors. The impacts were defined using 5 metrics-global warming potential, acidification potential, eutrophication potential (EP), abiotic resource use, and nonrenewable energy use-and were expressed per kilogram carcass weight at farm gate. Eutrophication potential was further separated into marine EP (MEP) and freshwater EP (FEP). Uncertainties in the model inputs were separated into 2 types: uncertainty in the data used to describe the system (α uncertainties) and uncertainty in impact calculations or background data that affects all systems equally (β uncertainties). The impacts of pig production in the 2 regions were systematically compared based on the differences in the systems (α uncertainties). The method of ascribing uncertainty influenced the outcomes. In eastern systems, EP, MEP, and FEP were lower (P < 0.05) when assuming that all uncertainty in the emission factors for leaching from manure application was β. This was mainly due to increased EP resulting from field emissions for typical ingredients in western diets. When uncertainty in these emission factors was assumed to be α, only FEP was lower in eastern systems (P < 0.05). The environmental impacts for the other impact categories were not significantly different between the 2 systems, despite their aforementioned differences. In conclusion, a probabilistic approach was used to develop an LCA that systematically dealt with uncertainty in the data when comparing multiple environmental impacts measures in pig farming systems for the first time. The method was used to identify differences between Canadian pig production systems but can also be applied for comparisons between other agricultural systems that include inherent variation.

Effects of Acute Administration of Ketorolac on Mammalian Vestibular Sensory Evoked Potentials

PubMed Central

Gaines, G Christopher; Jones, Timothy A

2013-01-01

The nonsteroidal antiinflammatory drug (NSAID) ketorolac is a candidate for use as a supplemental analgesic during major surgery in anesthetized rodents. The use of ketorolac during surgery is believed to reduce the anesthetic dose required to achieve and maintain an adequate surgical plane, thus improving the physiologic condition and survival of animals during long experimental procedures. Ketorolac has reported side effects that include dizziness, ear pain, hearing loss, tinnitus, and vertigo in humans, but ketorolac has not been reported to affect the vestibular system in animals. To investigate this possibility, we evaluated the acute effects of ketorolac on vestibular compound action potentials in C57BL/6 mice. Linear vestibular sensory-evoked potentials (VsEP) were recorded during the administration of ketorolac at doses 3 to 14 times the effective analgesic dose. VsEP results for ketorolac were compared with those from a control group maintained under anesthesia for the same period. Ketorolac did not significantly affect the temporal profiles of response latencies and amplitudes or the rate of change in response measures over time between controls and ketorolac-treated mice. These findings demonstrate that ketorolac can be used as an analgesic to supplement anesthesia in mice without concerns of modifying the amplitudes and latencies of the linear VsEP. PMID:23562034

EpsA is an essential gene in exopolysaccharide production in Lactobacillus johnsonii FI9785.

PubMed

Dertli, Enes; Mayer, Melinda J; Colquhoun, Ian J; Narbad, Arjan

2016-07-01

Lactobacillus johnsonii FI9785 has an eps gene cluster which is required for the biosynthesis of homopolymeric exopolysaccharides (EPS)-1 and heteropolymeric EPS-2 as a capsular layer. The first gene of the cluster, epsA, is the putative transcriptional regulator. In this study we showed the crucial role of epsA in EPS biosynthesis by demonstrating that deletion of epsA resulted in complete loss of both EPS-1 and EPS-2 on the cell surface. Plasmid complementation of the epsA gene fully restored EPS production, as confirmed by transmission electron microscopy and nuclear magnetic resonance (NMR) analysis. Furthermore, this complementation resulted in a twofold increase in the expression levels of this gene, which almost doubled amounts of EPS production in comparison with the wild-type strain. Analysis of EPS by NMR showed an increased ratio of the heteropolysaccharide to homopolysaccharide in the complemented strain and allowed identification of the acetylated residue in EPS-2 as the (1,4)-linked βGlcp unit, with the acetyl group located at O-6. These findings indicate that epsA is a positive regulator of EPS production and that EPS production can be manipulated by altering its expression. © 2015 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.

Equilibrium Passive Sampling of POP in Lipid-Rich and Lean Fish Tissue: Quality Control Using Performance Reference Compounds.

PubMed

Rusina, Tatsiana P; Carlsson, Pernilla; Vrana, Branislav; Smedes, Foppe

2017-10-03

Passive sampling is widely used to measure levels of contaminants in various environmental matrices, including fish tissue. Equilibrium passive sampling (EPS) of persistent organic pollutants (POP) in fish tissue has been hitherto limited to application in lipid-rich tissue. We tested several exposure methods to extend EPS applicability to lean tissue. Thin-film polydimethylsiloxane (PDMS) passive samplers were exposed statically to intact fillet and fish homogenate and dynamically by rolling with cut fillet cubes. The release of performance reference compounds (PRC) dosed to passive samplers prior to exposure was used to monitor the exchange process. The sampler-tissue exchange was isotropic, and PRC were shown to be good indicators of sampler-tissue equilibration status. The dynamic exposures demonstrated equilibrium attainment in less than 2 days for all three tested fish species, including lean fish containing 1% lipid. Lipid-based concentrations derived from EPS were in good agreement with lipid-normalized concentrations obtained using conventional solvent extraction. The developed in-tissue EPS method is robust and has potential for application in chemical monitoring of biota and bioaccumulation studies.

Identifying oil/marine snow associations in mesocosm simulations of the Deepwater Horizon oil spill event using solid-state 13C NMR spectroscopy.

PubMed

Hatcher, Patrick G; Obeid, Wassim; Wozniak, Andrew S; Xu, Chen; Zhang, Saijin; Santschi, Peter H; Quigg, Antonietta

2018-01-01

The Deepwater Horizon oil spill stimulated the release of marine snow made up of dead/living plankton/bacteria and their exopolymeric polysaccharide substances (EPS), termed marine oil snow (MOS), promoting rapid removal of oil from the water column into sediments near the well site. Mesocosm simulations showed that Macondo surrogate oil readily associates with the marine snow. Quantitative solid-state 13 C NMR readily distinguishes this oil from naturally formed marine snow and reveals that adding the dispersant Corexit enhances the amount of oil associated with the MOS, thus contributing to rapid removal from the water column. Solvent extraction of MOS removes the oil-derived compounds for analysis by one and two-dimensional GC/MS and evaluation of potential transformations they undergo when associated with the EPS. The results reveal that the oil associated with EPS is subjected to rapid transformation, in a matter of days, presumably by bacteria and fungi associated with EPS. Copyright © 2017 Elsevier Ltd. All rights reserved.

LBM-EP: Lattice-Boltzmann method for fast cardiac electrophysiology simulation from 3D images.

PubMed

Rapaka, S; Mansi, T; Georgescu, B; Pop, M; Wright, G A; Kamen, A; Comaniciu, Dorin

2012-01-01

Current treatments of heart rhythm troubles require careful planning and guidance for optimal outcomes. Computational models of cardiac electrophysiology are being proposed for therapy planning but current approaches are either too simplified or too computationally intensive for patient-specific simulations in clinical practice. This paper presents a novel approach, LBM-EP, to solve any type of mono-domain cardiac electrophysiology models at near real-time that is especially tailored for patient-specific simulations. The domain is discretized on a Cartesian grid with a level-set representation of patient's heart geometry, previously estimated from images automatically. The cell model is calculated node-wise, while the transmembrane potential is diffused using Lattice-Boltzmann method within the domain defined by the level-set. Experiments on synthetic cases, on a data set from CESC'10 and on one patient with myocardium scar showed that LBM-EP provides results comparable to an FEM implementation, while being 10 - 45 times faster. Fast, accurate, scalable and requiring no specific meshing, LBM-EP paves the way to efficient and detailed models of cardiac electrophysiology for therapy planning.

[Effect of polymeric aluminum-iron on EPS and bio-flocculation in A2/O system].

PubMed

Wen, Qin-Xue; Liu, Ai-Cui; Chen, Zhi-Qiang; Shi, Han-Chang; Lü, Bing-Nan

2012-04-01

Polymeric aluminum-iron (PAFC) was added at the end of aeration tank to enhance phosphorus removal, so that the phosphorus concentration in the effluent could meet the calss A standard in municipal sewage treatment plant pollutant discharge standard (GB 18918-2002). The characteristics of extracellular polymer substances (EPS) and bio-flocculation for the activated sludge in the A2/O system were analyzed in the experiment. The results showed that, the gross of EPS varied little with the increase in PAFC dosage, while, the ratio of albumen to polysaccharide declined from 3.30 to 2.30. When the PAFC dosage increased, the concentration of Al3+ in EPS increased during the whole anaerobic-anoxic-aerobic cycle. The flocs of activated sludge became larger after PAFC addition, Zeta potential of the effluent dropped significantly from - 15.83 mV to -21.20 mV and sludge yield increased. Therefore, bio-flocculation of the activated sludge in the A2/O system improved when a proper amount of PAFC was added, subsequently improve the water quality of the effluent.

Measuring the relative hydrogen-bonding strengths of alcohols in aprotic organic solvents.

PubMed

Tessensohn, Malcolm E; Lee, Melvyn; Hirao, Hajime; Webster, Richard D

2015-01-12

Voltammetric experiments with 9,10-anthraquinone and 1,4-benzoquinone performed under controlled moisture conditions indicate that the hydrogen-bond strengths of alcohols in aprotic organic solvents can be differentiated by the electrochemical parameter ΔEp (red) =|Ep (red(1)) -Ep (red(2)) |, which is the potential separation between the two one-electron reduction processes. This electrochemical parameter is inversely related to the strength of the interactions and can be used to differentiate between primary, secondary, tertiary alcohols, and even diols, as it is sensitive to both their steric and electronic properties. The results are highly reproducible across two solvents with substantially different hydrogen-bonding properties (CH3 CN and CH2 Cl2 ) and are supported by density functional theory calculations. This indicates that the numerous solvent-alcohol interactions are less significant than the quinone-alcohol hydrogen-bonding interactions. The utility of ΔEp (red) was illustrated by comparisons between 1) 3,3,3-trifluoro-n-propanol and 1,3-difluoroisopropanol and 2) ethylene glycol and 2,2,2-trifluoroethanol. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prevotella intermedia induces prostaglandin E2 via multiple signaling pathways.

PubMed

Guan, S-M; Fu, S-M; He, J-J; Zhang, M

2011-01-01

Prostaglandin E(2) (PGE(2)) plays important roles in the bone resorption of inflammatory diseases such as rheumatoid arthritis and periodontitis via specific prostaglandin receptors (i.e., EP1-EP4). In this study, the authors examined whether Prevotella intermedia regulates PGE(2) production and EP expression in human periodontal ligament fibroblasts (hPDLs); they also explored the potential signaling pathways involved in PGE(2) production. P. intermedia induced PGE(2) production and cyclooxygenase-2 (COX-2) expression in a dose- and time-dependent manner. Indomethacin and NS-398 completely abrogated the P. intermedia-induced PGE(2) production without modulating COX-2 expression. Specific inhibitors of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, phosphatidylinositol 3-kinase, and protein kinase C--but not c-AMP and protein kinase A--significantly attenuated the P. intermedia-induced COX-2 and PGE(2) expression. P. intermedia reduced EP1 expression in a concentration- and time-dependent manner. The results indicate that the COX-2-dependent induction of PGE(2) by P. intermedia in hPDLs is mediated by multiple signaling pathways.

Identifying grasslands suitable for cellulosic feedstock crops in the Greater Platte River Basin: dynamic modeling of ecosystem performance with 250 m eMODIS

USGS Publications Warehouse

Gu, Yingxin; Boyte, Stephen P.; Wylie, Bruce K.; Tieszen, Larry L.

2012-01-01

This study dynamically monitors ecosystem performance (EP) to identify grasslands potentially suitable for cellulosic feedstock crops (e.g., switchgrass) within the Greater Platte River Basin (GPRB). We computed grassland site potential and EP anomalies using 9-year (2000–2008) time series of 250 m expedited moderate resolution imaging spectroradiometer Normalized Difference Vegetation Index data, geophysical and biophysical data, weather and climate data, and EP models. We hypothesize that areas with fairly consistent high grassland productivity (i.e., high grassland site potential) in fair to good range condition (i.e., persistent ecosystem overperformance or normal performance, indicating a lack of severe ecological disturbance) are potentially suitable for cellulosic feedstock crop development. Unproductive (i.e., low grassland site potential) or degraded grasslands (i.e., persistent ecosystem underperformance with poor range condition) are not appropriate for cellulosic feedstock development. Grassland pixels with high or moderate ecosystem site potential and with more than 7 years ecosystem normal performance or overperformance during 2000–2008 are identified as possible regions for future cellulosic feedstock crop development (ca. 68 000 km2 within the GPRB, mostly in the eastern areas). Long-term climate conditions, elevation, soil organic carbon, and yearly seasonal precipitation and temperature are important performance variables to determine the suitable areas in this study. The final map delineating the suitable areas within the GPRB provides a new monitoring and modeling approach that can contribute to decision support tools to help land managers and decision makers make optimal land use decisions regarding cellulosic feedstock crop development and sustainability.

Bacterial Exopolysaccharide mediated heavy metal removal: A Review on biosynthesis, mechanism and remediation strategies.

PubMed

Gupta, Pratima; Diwan, Batul

2017-03-01

Heavy metal contamination has been recognized as a major public health risk, particularly in developing countries and their toxicological manifestations are well known. Conventional remediation strategies are either expensive or they generate toxic by-products, which adversely affect the environment. Therefore, necessity for an environmentally safe strategy motivates interest towards biological techniques. One of such most profoundly driven approach in recent times is biosorption through microbial biomass and their products. Extracellular polymeric substances are such complex blend of high molecular weight microbial (prokaryotic and eukaryotic) biopolymers. They are mainly composed of proteins, polysaccharides, uronic acids, humic substances, lipids etc. One of its essential constituent is the exopolysaccharide (EPS) released out of self defense against harsh conditions of starvation, pH and temperature, hence it displays exemplary physiological, rheological and physio-chemical properties. Its net anionic makeup allows the biopolymer to effectively sequester positively charged heavy metal ions. The polysaccharide has been expounded deeply in this article with reference to its biosynthesis and emphasizes heavy metal sorption abilities of polymer in terms of mechanism of action and remediation. It reports current investigation and strategic advancements in dealing bacterial cells and their EPS in diverse forms - mixed culture EPS, single cell EPS, live, dead or immobilized EPS. A significant scrutiny is also involved highlighting the existing challenges that still lie in the path of commercialization. The article enlightens the potential of EPS to bring about bio-detoxification of heavy metal contaminated terrestrial and aquatic systems in highly sustainable, economic and eco-friendly manner.

Pterocarpus santalinus L. Regulated Ultraviolet B Irradiation-induced Procollagen Reduction and Matrix Metalloproteinases Expression Through Activation of TGF-β/Smad and Inhibition of the MAPK/AP-1 Pathway in Normal Human Dermal Fibroblasts.

PubMed

Gao, Wei; Lin, Pei; Hwang, Eunson; Wang, Yushuai; Yan, Zhengfei; Ngo, Hien T T; Yi, Tae-Hoo

2018-01-01

Ultraviolet light-induced reactive oxygen species (ROS) damage human skin and prematurely cause aging. A growing body of research is focusing on considering plants and plant-derived compounds as antiphotoaging therapeutic material. Pterocarpus santalinus L., as an Indian traditional medicine, possesses antidiabetic, anti-inflammatory and antioxidative effects. Here, we studied the antiphotoaging effects of ethanolic extract of P. santalinus L. heartwood (EPS) on ultraviolet radiation B (UVB)-irradiated normal human dermal fibroblasts (NHDFs). Results showed that EPS significantly inhibited the upregulation of matrix metalloproteinases and IL-6 caused by UVB irradiation, and suppressed UVB-induced phosphorylation of extracellular signal-regulated kinase, Jun N-terminal kinase and p38, as well as the activation of AP-1 transcription factors. Further study indicated that UVB-induced production of MMP-1 and IL-6 could be inhibited by PD 98059 (an ERK inhibitor) and SP600125 (A JNK inhibitor), implied that EPS inhibited UVB-induced MMP-1 and IL-6 secretion by inactivating MAPK signaling pathway. In addition, EPS possessed an excellent antioxidant activity, which could increase cytoprotective antioxidants such as HO-1, NQ-O1 expression by facilitating the nuclear accumulation of Nrf2. Treatment of NHDFs with EPS also recovered UVB-induced procollagen type I reduction by activating TGF-β/Smad pathway. These findings demonstrated that EPS had a potential effect against UVB-induced skin photoaging. © 2017 The American Society of Photobiology.

Mixed biofilm formation by Shiga toxin-producing Escherichia coli and Salmonella enterica serovar Typhimurium enhanced bacterial resistance to sanitization due to extracellular polymeric substances.

PubMed

Wang, Rong; Kalchayanand, Norasak; Schmidt, John W; Harhay, Dayna M

2013-09-01

Shiga toxin-producing Escherichia coli O157:H7 and Salmonella enterica serovar Typhimurium are important foodborne pathogens capable of forming single-species biofilms or coexisting in multispecies biofilm communities. Bacterial biofilm cells are usually more resistant to sanitization than their planktonic counterparts, so these foodborne pathogens in biofilms pose a serious food safety concern. We investigated how the coexistence of E. coli O157:H7 and Salmonella Typhimurium strains would affect bacterial planktonic growth competition and mixed biofilm composition. Furthermore, we also investigated how mixed biofilm formation would affect bacterial resistance to common sanitizers. Salmonella Typhimurium strains were able to outcompete E. coli strains in the planktonic growth phase; however, mixed biofilm development was highly dependent upon companion strain properties in terms of the expression of bacterial extracellular polymeric substances (EPS), including curli fimbriae and exopolysaccharide cellulose. The EPS-producing strains with higher biofilm-forming abilities were able to establish themselves in mixed biofilms more efficiently. In comparison to single-strain biofilms, Salmonella or E. coli strains with negative EPS expression obtained significantly enhanced resistance to sanitization by forming mixed biofilms with an EPS-producing companion strain of the other species. These observations indicate that the bacterial EPS components not only enhance the sanitizer resistance of the EPS-producing strains but also render protections to their companion strains, regardless of species, in mixed biofilms. Our study highlights the potential risk of cross-contamination by multispecies biofilms in food safety and the need for increased attention to proper sanitization practices in food processing facilities.

Prostanoid receptor antagonists: development strategies and therapeutic applications

PubMed Central

Jones, RL; Giembycz, MA; Woodward, DF

2009-01-01

Identification of the primary products of cyclo-oxygenase (COX)/prostaglandin synthase(s), which occurred between 1958 and 1976, was followed by a classification system for prostanoid receptors (DP, EP1, EP2 …) based mainly on the pharmacological actions of natural and synthetic agonists and a few antagonists. The design of potent selective antagonists was rapid for certain prostanoid receptors (EP1, TP), slow for others (FP, IP) and has yet to be achieved in certain cases (EP2). While some antagonists are structurally related to the natural agonist, most recent compounds are ‘non-prostanoid’ (often acyl-sulphonamides) and have emerged from high-throughput screening of compound libraries, made possible by the development of (functional) assays involving single recombinant prostanoid receptors. Selective antagonists have been crucial to defining the roles of PGD2 (acting on DP1 and DP2 receptors) and PGE2 (on EP1 and EP4 receptors) in various inflammatory conditions; there are clear opportunities for therapeutic intervention. The vast endeavour on TP (thromboxane) antagonists is considered in relation to their limited pharmaceutical success in the cardiovascular area. Correspondingly, the clinical utility of IP (prostacyclin) antagonists is assessed in relation to the cloud hanging over the long-term safety of selective COX-2 inhibitors. Aspirin apart, COX inhibitors broadly suppress all prostanoid pathways, while high selectivity has been a major goal in receptor antagonist development; more targeted therapy may require an intermediate position with defined antagonist selectivity profiles. This review is intended to provide overviews of each antagonist class (including prostamide antagonists), covering major development strategies and current and potential clinical usage. PMID:19624532

Using Discrete Event Simulation to Model the Economic Value of Shorter Procedure Times on EP Lab Efficiency in the VALUE PVI Study.

PubMed

Kowalski, Marcin; DeVille, J Brian; Svinarich, J Thomas; Dan, Dan; Wickliffe, Andrew; Kantipudi, Charan; Foell, Jason D; Filardo, Giovanni; Holbrook, Reece; Baker, James; Baydoun, Hassan; Jenkins, Mark; Chang-Sing, Peter

2016-05-01

The VALUE PVI study demonstrated that atrial fibrillation (AF) ablation procedures and electrophysiology laboratory (EP lab) occupancy times were reduced for the cryoballoon compared with focal radiofrequency (RF) ablation. However, the economic impact associated with the cryoballoon procedure for hospitals has not been determined. Assess the economic value associated with shorter AF ablation procedure times based on VALUE PVI data. A model was formulated from data from the VALUE PVI study. This model used a discrete event simulation to translate procedural efficiencies into metrics utilized by hospital administrators. A 1000-day period was simulated to determine the accrued impact of procedure time on an institution's EP lab when considering staff and hospital resources. The simulation demonstrated that procedures performed with the cryoballoon catheter resulted in several efficiencies, including: (1) a reduction of 36.2% in days with overtime (422 days RF vs 60 days cryoballoon); (2) 92.7% less cumulative overtime hours (370 hours RF vs 27 hours cryoballoon); and (3) an increase of 46.7% in days with time for an additional EP lab usage (186 days RF vs 653 days cryoballoon). Importantly, the added EP lab utilization could not support the time required for an additional AF ablation procedure. The discrete event simulation of the VALUE PVI data demonstrates the potential positive economic value of AF ablation procedures using the cryoballoon. These benefits include more days where overtime is avoided, fewer cumulative overtime hours, and more days with time left for additional usage of EP lab resources.

Adaptive regularization network based neural modeling paradigm for nonlinear adaptive estimation of cerebral evoked potentials.

PubMed

Zhang, Jian-Hua; Böhme, Johann F

2007-11-01

In this paper we report an adaptive regularization network (ARN) approach to realizing fast blind separation of cerebral evoked potentials (EPs) from background electroencephalogram (EEG) activity with no need to make any explicit assumption on the statistical (or deterministic) signal model. The ARNs are proposed to construct nonlinear EEG and EP signal models. A novel adaptive regularization training (ART) algorithm is proposed to improve the generalization performance of the ARN. Two adaptive neural modeling methods based on the ARN are developed and their implementation and performance analysis are also presented. The computer experiments using simulated and measured visual evoked potential (VEP) data have shown that the proposed ARN modeling paradigm yields computationally efficient and more accurate VEP signal estimation owing to its intrinsic model-free and nonlinear processing characteristics.

Production of extracellular polymeric substances (EPS) by Serratia sp.1 using wastewater sludge as raw material and flocculation activity of the EPS produced.

PubMed

Bezawada, J; Hoang, N V; More, T T; Yan, S; Tyagi, N; Tyagi, R D; Surampalli, R Y

2013-10-15

Growth profile and extracellular polymeric substances (EPS) production of Serratia sp.1 was studied in shake flask fermentation for 72 h using wastewater sludge as raw material. Maximum cell concentration of 6.7 × 10(9) cfu/mL was obtained at 48 h fermentation time. EPS dry weight, flocculation activity and dewaterability of different EPS (tightly bound or TB-EPS, loosely bound or LB-EPS and broth-EPS or B-EPS) were also measured. The highest concentration of LB-EPS (2.45 g/L) and TB-EPS (0.99 g/L) were attained at 48 h of fermentation. Maximum flocculation activity and dewaterability (ΔCST) of TB-EPS (76.4%, 14.5s and 76.5%, 15.5s), LB-EPS (67.8%, 8.1s and 64.7%, 7.6s) and broth EPS (61%, 6.1s and 70.4%, 6.8s) were obtained at 36 and 48 h of growth. Higher flocculation activity and dewaterability were achieved with TB-EPS than with the two other EPS. Characterization of TB-EPS and LB-EPS was done in terms of their protein and carbohydrate content. Protein content was much higher in TB-EPS where as carbohydrate content was only slightly higher in TB-EPS than LB-EPS. Morphology of the Serratia strain after fermentation in sludge and TSB was observed under a scanning electron microscope and the cell size was found to be bigger in the sludge medium than the TSB medium. Copyright © 2013 Elsevier Ltd. All rights reserved.

Increased Evoked Potentials and Behavioral Indices in Response to Pain Among Individuals with Intellectual Disability.

PubMed

Benromano, Tali; Pick, Chaim G; Granovsky, Yelena; Defrin, Ruth

2017-09-01

Previous studies on the sensitivity and reactivity to pain of individuals with intellectual disability (ID) are inconsistent. The inconsistency may result from the reliance on self-reports and facial expressions of pain that are subject to internal and external biases. The aim was therefore to evaluate the reactivity to pain of individuals with ID by recording pain-evoked potentials (EPs), here for the first time, and testing their association with behavioral pain indices. Forty-one healthy adults, 16 with mild-moderate ID and 25 controls. Subjects received series of phasic heat stimuli and rated their pain on self-report scales. Changes in facial expressions and in pain EPs were recorded and analyzed offline. Pain self-reports, facial expressions, and the N2P2 amplitudes of the EPs exhibited stimulus-response relationship with stimulation intensity in both groups. The facial expressions and N2P2 amplitudes of individuals with ID were increased and N2P2 latency prolonged compared with controls. N2P2 amplitudes correlated with self-reports only in controls. Individuals with ID are hypersensitive/reactive to pain, a finding bearing clinical implications. Although pain EPs may reflect a somewhat different aspect of pain than the behavioral indices do, there is evidence to support their use to record pain in noncommunicative individuals, pending further validation. © 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

The effects of piracetam on heroin-induced CPP and neuronal apoptosis in rats.

PubMed

Xu, Peng; Li, Min; Bai, Yanping; Lu, Wei; Ling, Xiaomei; Li, Weidong

2015-05-01

Piracetam is a positive allosteric modulator of the AMPA receptor that has been used in the treatment of cognitive disorders for decades. Recent surveys and drug analyses have demonstrated that a heroin mixture adulterated with piracetam has spread rapidly in heroin addicts in China, but its addictive properties and the damage it causes to the central neural system are currently unknown. The effect of piracetam on the reward properties of heroin was assessed by conditioned place preference (CPP). Electron microscopy and radioimmunoassay were used to compare the effects of heroin mixed with equivalent piracetam (HP) and heroin alone on neuronal apoptosis and the levels of beta-endorphin (β-EP) in different brain subregions within the corticolimbic system, respectively. Piracetam significantly enhanced heroin-induced CPP expression while piracetam itself didn't induce CPP. Morphological observations showed that HP-treated rats had less neuronal apoptosis than heroin-treated group. Interestingly, HP normalized the levels of β-EP in the medial prefrontal cortex (mPFC) and core of the nucleus accumbens (AcbC) subregions, in where heroin-treated rats showed decreased levels of β-EP. These results indicate that piracetam potentiate the heroin-induced CPP and protect neurons from heroin-induced apoptosis. The protective role of HP might be related to the restoration of β-EP levels by piracetam. Our findings may provide a potential interpretation for the growing trend of HP abuse in addicts in China. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Successful treatment algorithm for evaluation of early pregnancy after in vitro fertilization.

PubMed

Cookingham, Lisa Marii; Goossen, Rachel P; Sparks, Amy E T; Van Voorhis, Bradley J; Duran, Eyup Hakan

2015-10-01

To evaluate a prospectively implemented clinical algorithm for early identification of ectopic pregnancy (EP) and heterotopic pregnancy (HP) after assisted reproductive technology (ART). Analysis of prospectively collected data. Academic medical center. All ART-conceived pregnancies between January 1995 and June 2013. Early pregnancy monitoring via clinical algorithm with all pregnancies screened using human chorionic gonadotropin (hCG) levels and reported symptoms, with subsequent early ultrasound evaluation if hCG levels were abnormal or if the patient reported pain or vaginal bleeding. Algorithmic efficiency for diagnosis of EP and HP and their subsequent clinical outcomes using a binary forward stepwise logistic regression model built to determine predictors of early pregnancy failure. Of the 3,904 pregnancies included, the incidence of EP and HP was 0.77% and 0.46%, respectively. The algorithm selected 96.7% and 83.3% of pregnancies diagnosed with EP and HP, respectively, for early ultrasound evaluation, leading to earlier treatment and resolution. Logistic regression revealed that first hCG, second hCG, hCG slope, age, pain, and vaginal bleeding were all independent predictors of early pregnancy failure after ART. Our clinical algorithm for early pregnancy evaluation after ART is effective for identification and prompt intervention of EP and HP without significant over- or misdiagnosis, and avoids the potential catastrophic morbidity associated with delayed diagnosis. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Compensating for Electrode Polarization in Dielectric Spectroscopy Studies of Colloidal Suspensions: Theoretical Assessment of Existing Methods

PubMed Central

Chassagne, Claire; Dubois, Emmanuelle; Jiménez, María L.; van der Ploeg, J. P. M; van Turnhout, Jan

2016-01-01

Dielectric spectroscopy can be used to determine the dipole moment of colloidal particles from which important interfacial electrokinetic properties, for instance their zeta potential, can be deduced. Unfortunately, dielectric spectroscopy measurements are hampered by electrode polarization (EP). In this article, we review several procedures to compensate for this effect. First EP in electrolyte solutions is described: the complex conductivity is derived as function of frequency, for two cell geometries (planar and cylindrical) with blocking electrodes. The corresponding equivalent circuit for the electrolyte solution is given for each geometry. This equivalent circuit model is extended to suspensions. The complex conductivity of a suspension, in the presence of EP, is then calculated from the impedance. Different methods for compensating for EP are critically assessed, with the help of the theoretical findings. Their limit of validity is given in terms of characteristic frequencies. We can identify with one of these frequencies the frequency range within which data uncorrected for EP may be used to assess the dipole moment of colloidal particles. In order to extract this dipole moment from the measured data, two methods are reviewed: one is based on the use of existing models for the complex conductivity of suspensions, the other is the logarithmic derivative method. An extension to multiple relaxations of the logarithmic derivative method is proposed. PMID:27486575

Characterization of extracellular polymeric substances in biofilms under long-term exposure to ciprofloxacin antibiotic using fluorescence excitation-emission matrix and parallel factor analysis.

PubMed

Gu, Chaochao; Gao, Pin; Yang, Fan; An, Dongxuan; Munir, Mariya; Jia, Hanzhong; Xue, Gang; Ma, Chunyan

2017-05-01

The presence of antibiotic residues in the environment has been regarded as an emerging concern due to their potential adverse environmental consequences such as antibiotic resistance. However, the interaction between antibiotics and extracellular polymeric substances (EPSs) of biofilms in wastewater treatment systems is not entirely clear. In this study, the effect of ciprofloxacin (CIP) antibiotic on biofilm EPS matrix was investigated and characterized using fluorescence excitation-emission matrix (EEM) and parallel factor (PARAFAC) analysis. Physicochemical analysis showed that the proteins were the major EPS fraction, and their contents increased gradually with an increase in CIP concentration (0-300 μg/L). Based on the characterization of biofilm tightly bound EPS (TB-EPS) by EEM, three fluorescent components were identified by PARAFAC analysis. Component C1 was associated with protein-like substances, and components C2 and C3 belonged to humic-like substances. Component C1 exhibited an increasing trend as the CIP addition increased. Pearson's correlation results showed that CIP correlated significantly with the protein contents and component C1, while strong correlations were also found among UV 254 , dissolved organic carbon, humic acids, and component C3. A combined use of EEM-PARAFAC analysis and chemical measurements was demonstrated as a favorable approach for the characterization of variations in biofilm EPS in the presence of CIP antibiotic.

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients

PubMed Central

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J.; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-01-01

Background Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. Methods This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Results Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. Conclusions The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression. PMID:29113403

A phase 2, open-label, multi-center study of amuvatinib in combination with platinum etoposide chemotherapy in platinum-refractory small cell lung cancer patients.

PubMed

Byers, Lauren Averett; Horn, Leora; Ghandi, Jitendra; Kloecker, Goetz; Owonikoko, Taofeek; Waqar, Saiama Naheed; Krzakowski, Maciej; Cardnell, Robert J; Fujimoto, Junya; Taverna, Pietro; Azab, Mohammad; Camidge, David Ross

2017-10-06

Amuvatinib (MP-470) is a multi-targeted kinase inhibitor with potent activity against c-Kit, synergistic with DNA-damaging agents. We evaluated amuvatinib in combination with platinum-etoposide (EP) chemotherapy by objective response rate, survival, and tolerability in platinum-refractory small cell lung cancer (SCLC) patients. This study used a Simon 2-stage design requiring ≥3 centrally confirmed responses in the first 21 subjects. Subjects received EP with 300 mg amuvatinib orally three times daily in cycles of 21 days. A three-day amuvatinib run-in period before EP occurred in Cycle 1. Subjects received the same EP chemotherapy regimen given prior to progression/relapse. Among 23 subjects treated, we observed four PRs (17.4%) per RECIST 1.1, only two of which were centrally confirmed (8.7%, response duration 119, 151 days). Three subjects (13%) had confirmed stable disease. c-Kit H-score was ≥100 in two subjects whose respective durations of disease control were 151 and 256 days. The addition of amuvatinib to EP chemotherapy in unselected, platinum-refractory SCLC did not meet the primary endpoint of ≥3 confirmed responses in stage 1. However, high c-Kit expression in two subjects with durable disease control suggests the potential for further study of amuvatinib in SCLC patients with high c-Kit expression.

Brachybacterium sp. CH-KOV3 isolated from an oil-polluted environment-a new producer of levan.

PubMed

Djurić, Aleksandra; Gojgić-Cvijović, Gordana; Jakovljević, Dragica; Kekez, Branka; Kojić, Jovana Stefanović; Mattinen, Maija-Liisa; Harju, Inka Elina; Vrvić, Miroslav M; Beškoski, Vladimir P

2017-11-01

Various microorganisms isolated from polluted environments, such as Pseudomonas sp. and Micrococcus sp. can synthesize exopolysaccharides (EPSs) which are natural, non-toxic and biodegradable polymers. EPSs play a key role in protection of microbial cells under various external influences. For humans, these substances have potential use in many industries. EPSs can be applied as a flavor or a fragrance carrier, an emulsifier, a stabilizer, a prebiotic, an antioxidant or an antitumor agent. In this study, we characterized an environmental microorganism that produces EPS, optimized EPS production by this strain and characterized the EPS produced. Isolate CH-KOV3 was identified as Brachybacterium paraconglomeratum. The sucrose level in the growth medium greatly influenced EPS production, and the highest yield was when the microorganism was incubated in media with 500g/L of sucrose. The optimal temperature and pH were 28°C and 7.0, respectively. The nuclear magnetic resonance (NMR) results and GC-MS analysis confirmed that the residues were d-fructofuranosyl residues with β-configuration, where fructose units are linked by β-2,6-glycosidic bonds, with β-2,1-linked branches. All these data indicate that the investigated EPS is a levan-type polysaccharide. Thus, it was concluded that Brachybacterium sp. CH-KOV3 could constitute a new source for production of the bioactive polysaccharide, levan. Copyright © 2017 Elsevier B.V. All rights reserved.

Prostaglandin E2 modulates dendritic cell function via EP2 and EP4 receptor subtypes.

PubMed

Harizi, Hedi; Grosset, Christophe; Gualde, Norbert

2003-06-01

We have reported previously that PGE(2) inhibits dendritic cells (DC) functions. Because E prostanoid receptor (EPR) subtypes involved in this action are unknown, expression and functions of these receptors were examined in DC. Western blot and flow cytometry analyses showed that all EPRs were coexpressed in DC. In a dose-dependent manner, lipopolysaccharide (LPS) enhanced EP(2)R/EP(4)R but not EP(1)R/EP(3)R expressions. NS-398, a cyclooxygenase (COX)-2-selective inhibitor, suppressed LPS-enhanced EP(2)R/EP(4)R expression, suggesting that COX-2-issued prostaglandin E(2) (PGE(2)) modulates DC function through stimulation of specific EPR subtypes. Using selective agonists, we found that butaprost, an EP(2)R agonist, and PGE(1) alcohol, an EP(2)R and EP(2)R/EP(4)R agonist, inhibited major histocompatibility complex class II expression and enhanced interleukin-10 production from DC. However, no effect was observed with sulprostone and 17-phenyl-omega-trinor-PGE(2), selective agonists for EP(1)R and EP(1)R/EP(3)R, respectively. Treatment of DC with dibutyryl cyclic adenosine monophosphate (cAMP), an analog of cAMP, mimics PGE(2)-induced, inhibitory effects. Taken together, our data demonstrate that EP(2)R/EP(4)R are efficient for mediating PGE(2)-induced modulation of DC functions.

Potential impact of pre-exposure prophylaxis for female sex workers and men who have sex with men in Bangalore, India: a mathematical modelling study.

PubMed

Mitchell, Kate M; Prudden, Holly J; Washington, Reynold; Isac, Shajy; Rajaram, Subramanian P; Foss, Anna M; Terris-Prestholt, Fern; Boily, Marie-Claude; Vickerman, Peter

2016-01-01

In Bangalore, new HIV infections of female sex workers and men who have sex with men continue to occur, despite high condom use. Pre-exposure prophylaxis (PrEP) has high anti-HIV efficacy for men who have sex with men. PrEP demonstration projects are underway amongst Indian female sex workers. We estimated the impact and efficiency of prioritizing PrEP to female sex workers and/or men who have sex with men in Bangalore. A mathematical model of HIV transmission and treatment for female sex workers, clients, men who have sex with men and low-risk groups was parameterized and fitted to Bangalore data. The proportion of transmission attributable (population attributable fraction) to commercial sex and sex between men was calculated. PrEP impact (infections averted, life-years gained) and efficiency (life-years gained/infections averted per 100 person-years on PrEP) were estimated for different levels of PrEP adherence, coverage and prioritization strategies (female sex workers, high-risk men who have sex with men, both female sex workers and high-risk men who have sex with men, or female sex workers with lower condom use), under current conditions and in a scenario with lower baseline condom use amongst key populations. Population attributable fractions for commercial sex and sex between men have declined over time, and they are predicted to account for 19% of all new infections between 2016 and 2025. PrEP could prevent a substantial proportion of infections amongst female sex workers and men who have sex with men in this setting (23%/27% over 5/10 years, with 60% coverage and 50% adherence), which could avert 2.9%/4.3% of infections over 5/10 years in the whole Bangalore population. Impact and efficiency in the whole population was greater if female sex workers were prioritized. Efficiency increased, but impact decreased, if only female sex workers with lower condom use were given PrEP. Greater impact and efficiency was predicted for the scenario with lower condom use. PrEP could be beneficial for female sex workers and men who have sex with men in Bangalore, and give some benefits in the general population, especially in similar settings with lower condom use levels.

Entanglement Potential Versus Negativity of Wigner Function for SUP-Operated Quantum States

NASA Astrophysics Data System (ADS)

Chatterjee, Arpita

2018-02-01

We construct a distinct category of nonclassical quantum states by applying a superposition of products (SUP) of field annihilation (\\hat {a}) and creation (\\hat {a}^{\\dagger }) operators of the type (s\\hat {a}\\hat {a}^{\\dagger }+t\\hat {a}^{\\dagger }\\hat {a}), with s2+t2=1, upon thermal and even coherent states. We allow these SUP operated states to undergo a decoherence process and then describe the nonclassical features of the resulted field by using the entanglement potential (EP) and the negativity of the Wigner distribution function. Our analysis reveals that both the measures are reduced in the linear loss process. The partial negativity of the Wigner function disappears when losses exceed 50% but EP exists always.

Evaluation of solar electric propulsion technologies for discovery class missions

NASA Technical Reports Server (NTRS)

Oh, David Y.

2005-01-01

A detailed study examines the potential benefits that advanced electric propulsion (EP) technologies offer to the cost-capped missions in NASA's Discovery program. The study looks at potential cost and performance benefits provided by three EP technologies that are currently in development: NASA's Evolutionary Xenon Thruster (NEXT), an Enhanced NSTAR system, and a Low Power Hall effect thruster. These systems are analyzed on three straw man Discovery class missions and their performance is compared to a state of the art system using the NSTAR ion thruster. An electric propulsion subsystem cost model is used to conduct a cost-benefit analysis for each option. The results show that each proposed technology offers a different degree of performance and/or cost benefit for Discovery class missions.

The Cost and Impact of Scaling Up Pre-exposure Prophylaxis for HIV Prevention: A Systematic Review of Cost-Effectiveness Modelling Studies

PubMed Central

Gomez, Gabriela B.; Borquez, Annick; Case, Kelsey K.; Wheelock, Ana; Vassall, Anna; Hankins, Catherine

2013-01-01

Background Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions. Methods and Findings We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP. Conclusions Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention—cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary PMID:23554579

English community pharmacists’ experiences of using electronic transmission of prescriptions: a qualitative study

PubMed Central

2013-01-01

Background The Electronic Prescription Service Release 2 (EPS2) in England has been designed to provide electronic transmission of digitally-signed prescriptions between primary care providers, with the intent on removing the large amounts of paper currently exchanged. As part of a wider evaluation of the EPS service, we wished to explore pharmacists’ experience with the new system and their perceptions of its benefits and any associated problems. Methods We conducted semi-structured telephone interviews with community pharmacists using EPS2. We used a purposive sampling technique to obtain views from pharmacists working in pharmacies with a range of sizes and locations and to include both independent pharmacies and multiples. Interviews were transcribed verbatim and coded using grounded theory to identify the main factors that have influenced deployment and implementation in the eyes of respondents. QSR Nvivo was used as to aid in this process. Results It became apparent from the analysis that respondents perceived a wide range of advantages of EPS including improved safety, stock control, time management and improved relationships between pharmacy and General Practice staff. Respondents did not perceive a large difference in terms of work processes or development of their professional role. A large number of problems had been experienced in relation to both the technology itself and the way it was used by General Practices. It became apparent that work-around procedures had been developed for dealing with these issues but that not all these problems were perceived as having been addressed sufficiently at source. This sometimes had implications for the extent of EPS2 use and also limited some of the potential advantages of the EPS2 system, such as reduced effort in the management of prescription reimbursement. Respondents made suggestions for future improvements to EPS2. While interview data demonstrated that there were some feedback procedures in place, these were not regarded as being sufficient by the majority of respondents. Conclusions Whilst pharmacists perceived a wide range of benefits of EPS, a large number of problems had been experienced. Despite these difficulties, no pharmacists expressed an overall negative view. PMID:24152293

The cost and impact of scaling up pre-exposure prophylaxis for HIV prevention: a systematic review of cost-effectiveness modelling studies.

PubMed

Gomez, Gabriela B; Borquez, Annick; Case, Kelsey K; Wheelock, Ana; Vassall, Anna; Hankins, Catherine

2013-01-01

Cost-effectiveness studies inform resource allocation, strategy, and policy development. However, due to their complexity, dependence on assumptions made, and inherent uncertainty, synthesising, and generalising the results can be difficult. We assess cost-effectiveness models evaluating expected health gains and costs of HIV pre-exposure prophylaxis (PrEP) interventions. We conducted a systematic review comparing epidemiological and economic assumptions of cost-effectiveness studies using various modelling approaches. The following databases were searched (until January 2013): PubMed/Medline, ISI Web of Knowledge, Centre for Reviews and Dissemination databases, EconLIT, and region-specific databases. We included modelling studies reporting both cost and expected impact of a PrEP roll-out. We explored five issues: prioritisation strategies, adherence, behaviour change, toxicity, and resistance. Of 961 studies retrieved, 13 were included. Studies modelled populations (heterosexual couples, men who have sex with men, people who inject drugs) in generalised and concentrated epidemics from Southern Africa (including South Africa), Ukraine, USA, and Peru. PrEP was found to have the potential to be a cost-effective addition to HIV prevention programmes in specific settings. The extent of the impact of PrEP depended upon assumptions made concerning cost, epidemic context, programme coverage, prioritisation strategies, and individual-level adherence. Delivery of PrEP to key populations at highest risk of HIV exposure appears the most cost-effective strategy. Limitations of this review include the partial geographical coverage, our inability to perform a meta-analysis, and the paucity of information available exploring trade-offs between early treatment and PrEP. Our review identifies the main considerations to address in assessing cost-effectiveness analyses of a PrEP intervention--cost, epidemic context, individual adherence level, PrEP programme coverage, and prioritisation strategy. Cost-effectiveness studies indicating where resources can be applied for greatest impact are essential to guide resource allocation decisions; however, the results of such analyses must be considered within the context of the underlying assumptions made. Please see later in the article for the Editors' Summary.

English community pharmacists' experiences of using electronic transmission of prescriptions: a qualitative study.

PubMed

Garfield, Sara; Hibberd, Ralph; Barber, Nick

2013-10-23

The Electronic Prescription Service Release 2 (EPS2) in England has been designed to provide electronic transmission of digitally-signed prescriptions between primary care providers, with the intent on removing the large amounts of paper currently exchanged. As part of a wider evaluation of the EPS service, we wished to explore pharmacists' experience with the new system and their perceptions of its benefits and any associated problems. We conducted semi-structured telephone interviews with community pharmacists using EPS2. We used a purposive sampling technique to obtain views from pharmacists working in pharmacies with a range of sizes and locations and to include both independent pharmacies and multiples. Interviews were transcribed verbatim and coded using grounded theory to identify the main factors that have influenced deployment and implementation in the eyes of respondents. QSR Nvivo was used as to aid in this process. It became apparent from the analysis that respondents perceived a wide range of advantages of EPS including improved safety, stock control, time management and improved relationships between pharmacy and General Practice staff. Respondents did not perceive a large difference in terms of work processes or development of their professional role. A large number of problems had been experienced in relation to both the technology itself and the way it was used by General Practices. It became apparent that work-around procedures had been developed for dealing with these issues but that not all these problems were perceived as having been addressed sufficiently at source. This sometimes had implications for the extent of EPS2 use and also limited some of the potential advantages of the EPS2 system, such as reduced effort in the management of prescription reimbursement. Respondents made suggestions for future improvements to EPS2. While interview data demonstrated that there were some feedback procedures in place, these were not regarded as being sufficient by the majority of respondents. Whilst pharmacists perceived a wide range of benefits of EPS, a large number of problems had been experienced. Despite these difficulties, no pharmacists expressed an overall negative view.

A novel Online-to-Offline (O2O) model for pre-exposure prophylaxis and HIV testing scale up

PubMed Central

Anand, Tarandeep; Nitpolprasert, Chattiya; Trachunthong, Deondara; Kerr, Stephen J; Janyam, Surang; Linjongrat, Danai; Hightow-Weidman, Lisa B; Phanuphak, Praphan; Ananworanich, Jintanat; Phanuphak, Nittaya

2017-01-01

Abstract Introduction: PrEP awareness and uptake among men who have sex with men (MSM) and transgender women (TG) in Thailand remains low. Finding ways to increase HIV testing and PrEP uptake among high-risk groups is a critical priority. This study evaluates the effect of a novel Adam’s Love Online-to-Offline (O2O) model on PrEP and HIV testing uptake among Thai MSM and TG and identifies factors associated with PrEP uptake. Methods: The O2O model was piloted by Adam’s Love (www.adamslove.org) HIV educational and counselling website. MSM and TG reached online by PrEP promotions and interested in free PrEP and/or HIV testing services contacted Adam’s Love online staff, received real-time PrEP eCounseling, and completed online bookings for receiving services at one of the four sites in Bangkok based on their preference. Auto-generated site- and service-specific e-tickets and Quick Response (QR) codes were sent to their mobile devices enabling monitoring and check-in by offline site staff. Service uptake and participant’s socio-demographic and risk behaviour characteristics were analyzed. Factors associated with PrEP uptake were assessed using multiple logistic regression. Results: Between January 10th and April 11th, 2016, Adam’s Love reached 272,568 people online via the PrEP O2O promotions. 425 MSM and TG received eCounseling and e-tickets. There were 325 (76.5%) MSM and TG who checked-in at clinics and received HIV testing. Nine (2.8%) were diagnosed with HIV infection. Median (IQR) time between receiving the e-ticket and checking-in was 3 (0–7) days. Of 316 HIV-negative MSM and TG, 168 (53.2%) started PrEP. In a multivariate model, higher education (OR 2.30, 95%CI 1.14–4.66; p = 0.02), seeking sex partners online (OR 2.05, 95%CI 1.19–3.54; p = 0.009), being aware of sexual partners’ HIV status (OR 2.37, 95%CI 1.29–4.35; p = 0.008), ever previously using post-exposure prophylaxis (PEP) (OR 2.46, 95%CI 1.19–5.09; p = 0.01), and enrolment at Adam’s Love clinic compared to the other three sites (OR 3.79, 95%CI 2.06–6.95; p < 0.001) were independently associated with PrEP uptake. Conclusions: Adam’s Love O2O model is highly effective in linking online at-risk MSM and TG to PrEP and HIV testing services, and has high potential to be replicated and scaled up in other settings with high Internet penetration among key populations. PMID:28362062

Computerized follow-up of discrepancies in image interpretation between emergency and radiology departments.

PubMed

Siegel, E; Groleau, G; Reiner, B; Stair, T

1998-08-01

Radiographs are ordered and interpreted for immediate clinical decisions 24 hours a day by emergency physicians (EP's). The Joint Commission for Accreditation of Health Care Organizations requires that all these images be reviewed by radiologists and that there be some mechanism for quality improvement (QI) for discrepant readings. There must be a log of discrepancies and documentation of follow up activities, but this alone does not guarantee effective Q.I. Radiologists reviewing images from the previous day and night often must guess at the preliminary interpretation of the EP and whether follow up action is necessary. EP's may remain ignorant of the final reading and falsely assume the initial diagnosis and treatment were correct. Some hospitals use a paper system in which the EP writes a preliminary interpretation on the requisition slip, which will be available when the radiologist dictates the final reading. Some hospitals use a classification of discrepancies based on clinical import and urgency, and communicated to the EP on duty at the time of the official reading, but may not communicate discrepancies to the EP's who initial read the images. Our computerized radiology department and picture archiving and communications system have increased technologist and radiologist productivity, and decreased retakes and lost films. There are fewer face-to-face consultants of radiologists and clinicians, but more communication by telephone and electronic annotation of PACS images. We have integrated the QI process for emergency department (ED) images into the PACS, and gained advantages over the traditional discrepancy log. Requisitions including clinical indications are entered into the Hospital Information System and then appear on the PACS along with images on readings. The initial impression, time of review, and the initials of the EP are available to the radiologist dictating the official report. The radiologist decides if there is a discrepancy, and whether it is category I (potentially serious, needs immediate follow-up), category II (moderate risk, follow-up in one day), or category III (low risk, follow-up in several days). During the working day, the radiologist calls immediately for category I discrepancies. Those noted from the evening, night, or weekend before are called to the EP the next morning. All discrepancies with the preliminary interpretation are communicated to the EP and are kept in a computerized log for review by a radiologist at a weekly ED teaching conference. This system has reduced the need for the radiologist to ask or guess what the impression was in the ED the night before. It has reduced the variability in recording of impressions by EP's, in communication back from radiologists, in the clinical] follow-up made, and in the documentation of the whole QI process. This system ensures that EP's receive notification of their discrepant readings, and provides continuing education to all the EP's on interpreting images on their patients.

Innovative combination of electrolysis and Fe(II)-activated persulfate oxidation for improving the dewaterability of waste activated sludge.

PubMed

Zhen, Guang-Yin; Lu, Xue-Qin; Li, Yu-You; Zhao, You-Cai

2013-05-01

The feasibility of electrolysis integrated with Fe(II)-activated persulfate (S2O8(2-)) oxidation to improve waste activated sludge (WAS) dewaterability was evaluated. The physicochemical properties (sludge volume (SV), total suspended solids (TSS) and volatile suspended solids (VSS)) and extracellular polymeric substances (EPS), including slime EPS, loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) were characterized to identify their exact roles in sludge dewatering. While dewaterability negatively corresponded to LB-EPS, TB-EPS, protein (PN) and polysaccharide (PS) in LB-EPS and TB-EPS, it was independent of SV, TSS, VSS, slime EPS and PN/PS. Further study through scanning electron microscope (SEM) verified the entrapment of bacterial cells by TB-EPS, protecting them against electrolysis disruption. Comparatively, electrolysis integrated with S2O8(2-)/Fe(II) oxidation was able to effectively disrupt the protective barrier and crack the entrapped cells, releasing the water inside EPS and cells. Therefore, the destruction of both TB-EPS and cells is the fundamental reason for the enhanced dewaterability. Copyright © 2013 Elsevier Ltd. All rights reserved.

Intimate Partner Violence and Adherence to HIV Pre-exposure Prophylaxis (PrEP) in African Women in HIV Serodiscordant Relationships: A Prospective Cohort Study

PubMed Central

Haberer, Jessica; Celum, Connie; Mugo, Nelly; Ware, Norma C.; Cohen, Craig R.; Tappero, Jordan W.; Kiarie, James; Ronald, Allan; Mujugira, Andrew; Tumwesigye, Elioda; Were, Edwin; Irungu, Elizabeth; Baeten, Jared M.

2016-01-01

Background: Intimate partner violence (IPV) is associated with higher HIV incidence, reduced condom use, and poor adherence to antiretroviral therapy and other medications. IPV may also affect adherence to pre-exposure prophylaxis (PrEP). Methods: We analyzed data from 1785 HIV-uninfected women enrolled in a clinical trial of PrEP among African HIV serodiscordant couples. Experience of verbal, physical, or economic IPV was assessed at monthly visits by face-to-face interviews. Low PrEP adherence was defined as clinic-based pill count coverage <80% or plasma tenofovir levels <40 ng/mL. The association between IPV and low adherence was analyzed using generalized estimating equations, adjusting for potential confounders. In-depth interview transcripts were examined to explain how IPV could impact adherence. Results: Sixteen percent of women reported IPV during a median of 34.8 months of follow-up (interquartile range 27.0–35.0). Overall, 7% of visits had pill count coverage <80%, and 32% had plasma tenofovir <40 ng/mL. Women reporting IPV in the past 3 months had increased risk of low adherence by pill count (adjusted risk ratio 1.49, 95% confidence interval: 1.17 to 1.89) and by plasma tenofovir (adjusted risk ratio 1.51, 95% confidence interval: 1.06 to 2.15). Verbal, economic, and physical IPV were all associated with low adherence. However, the impact of IPV diminished and was not statistically significant 3 months after the reported exposure. In qualitative interviews, women identified several ways in which IPV affected adherence, including stress and forgetting, leaving home without pills, and partners throwing pills away. Conclusions: Women who reported recent IPV in the Partners PrEP Study were at increased risk of low PrEP adherence. Strategies to mitigate PrEP nonadherence in the context of IPV should be evaluated. PMID:27243900

Identification of Differentially Expressed Proteins in Direct Expressed Prostatic Secretions of Men with Organ-confined Versus Extracapsular Prostate Cancer*

PubMed Central

Kim, Yunee; Ignatchenko, Vladimir; Yao, Cindy Q.; Kalatskaya, Irina; Nyalwidhe, Julius O.; Lance, Raymond S.; Gramolini, Anthony O.; Troyer, Dean A.; Stein, Lincoln D.; Boutros, Paul C.; Medin, Jeffrey A.; Semmes, O. John; Drake, Richard R.; Kislinger, Thomas

2012-01-01

Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients. Fluids that are proximal to the prostate, such as expressed prostatic secretions (EPS), are attractive sources of potential prostate cancer biomarkers as these fluids likely bathe the tumor. Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ-confined (n = 8) prostate cancer were used as a discovery cohort, and were analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass spectrometer. A total of 624 unique proteins were identified by at least two unique peptides with a 0.2% false discovery rate. A semiquantitative spectral counting algorithm identified 133 significantly differentially expressed proteins in the discovery cohort. Integrative data mining prioritized 14 candidates, including two known prostate cancer biomarkers: prostate-specific antigen and prostatic acid phosphatase, which were significantly elevated in the direct-EPS from the organ-confined cancer group. These and five other candidates (SFN, MME, PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set of direct-EPS from patients with biochemically recurrent disease (n = 5) versus patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we performed proof-of-concept SRM-MS-based relative quantification of the five candidates using unpurified heavy isotope-labeled synthetic peptides spiked into pools of EPS-urines from men with extracapsular and organ-confined prostate tumors. This study represents the first efforts to define the direct-EPS proteome from two major subclasses of prostate cancer using shotgun proteomics and verification in EPS-urine by SRM-MS. PMID:22986220

The novel EpCAM-targeting monoclonal antibody 3–17I linked to saporin is highly cytotoxic after photochemical internalization in breast, pancreas and colon cancer cell lines

PubMed Central

Lund, Kaja; Bostad, Monica; Skarpen, Ellen; Braunagel, Michael; Kiprijanov, Sergej; Krauss, Stefan; Duncan, Alex; Høgset, Anders; Selbo, Pål K.

2014-01-01

The epithelial cell adhesion molecule (EpCAM) is expressed by a wide range of human carcinomas, making it an attractive diagnostic and therapeutic target in oncology. Its recent identification on cancer stem cells has raised further interest in its use for tumor targeting and therapy. Here, we present the characterization and therapeutic potential of 3–17I, a novel human EpCAM-targeting monoclonal antibody. Strong reaction of 3–17I was observed in all lung, colon, and breast human tumor biopsies evaluated. By flow cytometry and confocal fluorescence microscopy, we demonstrate that 3–17I specifically targets EpCAM-positive cell lines. We also show evidence for mAb-sequestration in endo-/lysosomes, suggesting internalization of 3–17I by receptor-mediated endocytosis. The ribosomal-inactivating toxin saporin was linked to 3–17I, creating the per se non-toxic immunotoxin 3–17I-saporin, a promising candidate for the drug delivery technology photochemical internalization (PCI). PCI is based on a light-controlled destruction of endolysosomal membranes and subsequent cytosolic release of the sequestered payload upon light exposure. EpCAM-positive human cancer cell lines MCF7 (breast), BxPC-3 (pancreas), WiDr (colon), and the EpCAM-negative COLO320DM (colon), were treated with 3–17I-saporin in combination with the clinically relevant photosensitizer TPCS2a (Amphinex), followed by exposure to light. No cytotoxicity was observed after treatment with 3–17I-saporin without light exposure. However, cell viability, proliferation and colony-forming capacity was strongly reduced in a light-dependent manner after PCI of 3–17I. Our results show that 3–17I is an excellent candidate for diagnosis of EpCAM-positive tumors and for development of clinically relevant antibody-drug conjugates, using PCI for the treatment of localized tumors. PMID:24525727

Microbial Activity and Depositional System Dynamics: Linking Scales With The Aid of New Technology

NASA Astrophysics Data System (ADS)

Defew, E. C.; Hagerthey, S. E.; Honeywill, C.; Perkins, R. G.; Black, K. S.; Paterson, D. M.

The dynamics of estuarine depositional systems are influenced by sediment-dwelling microphytobenthic assemblages. These assemblages produce extracellular polymeric substances (EPS), which are known to be important in the process of sediment biosta- bilisation. However, these communities are generally studied on very small spatial scales making the prediction of primary productivity and their importance in terms of sediment stability over large areas uncertain. Recent advances in our knowledge of the biostabilisation process have allowed the establishment of links between EPS produc- tion, spatial distribution of algal biomass and their primary productivity over much larger spatial scales. For example, during the multidisciplinary BIOPTIS project, re- mote sensing (RS) was combined with ground-truthing measurements of physical and biological parameters to produce synoptic maps leading to a better understanding of system dynamics and the potential effects of environmental perturbations such as cli- mate change. Recent work using low-temperature scanning electron microscopy (LT- SEM) and in-line laser holography has measured the influence of EPS on the erosional behaviour of sediment flocs and particles and has shown that an increase in the con- centration of EPS determines the nature of the eroded floc material and the critical threshold for sediment erosion. This provides the mechanistic link required between EPS concentration and sediment stability. Whilst it is not yet possible to discern EPS concentration directly by RS studies, we know that EPS concentrations in sediments co-vary with chlorophyll a content, and are closely related to algal productivity. There- fore, RS studies which provide large-scale spatial information of chlorophyll a distri- bution may be used to model the stability and productivity of intertidal depositional systems. This paper introduces the basis of these linkages from the cellular level (in situ chlorophyll fluorescence), the ground-truthing approach (sediment stability, struc- ture, pigment distribution, in situ chlorophyll fluorescence) and investigates the poten- tial of a RS approach in a case study of a Scottish Estuary.

Circulating miR-323-3p as a Biomarker of Ectopic Pregnancy

PubMed Central

Zhao, Zhen; Zhao, Qiuhong; Warrick, Joshua; Lockwood, Christina M.; Woodworth, Alison; Moley, Kelle H.; Gronowski, Ann M.

2013-01-01

BACKGROUND The use of serum human chorionic gonadotropin (hCG) and progesterone to identify patients with ectopic pregnancy (EP) has been shown to have poor clinical utility. Pregnancy-associated circulating microRNAs (miRNAs) have been proposed as potential biomarkers for the diagnosis of pregnancy-associated complications. This proof-of concept study examined the diagnostic accuracy of various miRNAs to detect EP in an emergency department (ED) setting. METHODS This was a retrospective case-control analysis of 89 women who presented to the ED with vaginal bleeding and/or abdominal pain/cramping, and were diagnosed with viable intrauterine pregnancy (VIP), spontaneous abortion (SA), or EP. Serum hCG and progesterone concentrations were determined by immunoassays. Serum miR-323-3p, miR-517a, miR-519d, and miR-525-3p concentrations were measured using TaqMan real-time PCR. Statistical analysis was performed to determine the clinical utility of these biomarkers as single markers and as multimarker panels for EP. RESULTS Concentrations of serum hCG, progesterone, miR-517a, miR-519d, and miR-525-3p were significantly lower in EP and SA than in VIP. In contrast, the concentration of miR-323-3p was significantly elevated in EP as compared to SA and VIP. As a single marker, miR-323-3p had the highest sensitivity of 37.0% (at a fixed-specificity of 90%). Comparatively, combined hCG, progesterone, and miR-323-3p panel yielded the highest sensitivity of 77.8% (at a fixed-specificity of 90%). A stepwise analysis using hCG, then progesterone, and then miR-323-3p resulted in 96.3% sensitivity and 72.6% specificity. CONCLUSIONS Pregnancy-associated miRNAs, especially miR-323-3p, added significant diagnostic accuracy to a panel including hCG and progesterone for the diagnosis of EP. PMID:22395025

Pre-exposure Prophylaxis With Tenofovir Disoproxil Fumarate/Emtricitabine and Kidney Tubular Dysfunction in HIV-Uninfected Individuals.

PubMed

Jotwani, Vasantha; Scherzer, Rebecca; Glidden, David V; Mehrotra, Megha; Defechereux, Patricia; Liu, Albert; Gandhi, Monica; Bennett, Michael; Coca, Steven G; Parikh, Chirag R; Grant, Robert M; Shlipak, Michael G

2018-06-01

Pre-exposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) is becoming increasingly adopted for HIV prevention. Tenofovir can cause proximal tubular damage and chronic kidney disease in HIV-infected persons, but little is known regarding its nephrotoxic potential among HIV-uninfected persons. In this study, we evaluated the effects of PrEP on urine levels of the following: α1-microglobulin (α1m), a marker of impaired tubular reabsorption; albuminuria, a measure of glomerular injury; and total proteinuria. The Iniciativa Profilaxis Pre-Exposicion (iPrEx) study randomized HIV-seronegative men and transgender women who have sex with men to oral TDF/FTC or placebo. The iPrEx open-label extension (iPrEx-OLE) study enrolled former PrEP trial participants to receive open-label TDF/FTC. A cross-sectional analysis compared urine biomarker levels by study arm in iPrEx (N = 100 treatment arm, N = 100 placebo arm). Then, urine biomarker levels were compared before and after PrEP initiation in 109 participants of iPrEx-OLE. In iPrEx, there were no significant differences in urine α1m, albuminuria, or proteinuria by treatment arm. In iPrEx-OLE, after 24 weeks on PrEP, urine α1m and proteinuria increased by 21% [95% confidence interval (CI): 10 to 33] and 18% (95% CI: 8 to 28), respectively. The prevalence of detectable α1m increased from 44% to 65% (P < 0.001) and estimated glomerular filtration rate declined by 4 mL/min/1.73 m (P < 0.001). There was no significant change in albuminuria (6%; 95% CI: -7% to 20%). PrEP with TDF/FTC was associated with a statistically significant rise in urine α1m and proteinuria after 6 months, suggesting that PrEP may result in subclinical tubule dysfunction.

The contribution of visual processing to academic achievement in adolescents born extremely preterm or extremely low birth weight.

PubMed

Molloy, Carly S; Di Battista, Ashley M; Anderson, Vicki A; Burnett, Alice; Lee, Katherine J; Roberts, Gehan; Cheong, Jeanie Ly; Anderson, Peter J; Doyle, Lex W

2017-04-01

Children born extremely preterm (EP, <28 weeks) and/or extremely low birth weight (ELBW, <1000 g) have more academic deficiencies than their term-born peers, which may be due to problems with visual processing. The aim of this study is to determine (1) if visual processing is related to poor academic outcomes in EP/ELBW adolescents, and (2) how much of the variance in academic achievement in EP/ELBW adolescents is explained by visual processing ability after controlling for perinatal risk factors and other known contributors to academic performance, particularly attention and working memory. A geographically determined cohort of 228 surviving EP/ELBW adolescents (mean age 17 years) was studied. The relationships between measures of visual processing (visual acuity, binocular stereopsis, eye convergence, and visual perception) and academic achievement were explored within the EP/ELBW group. Analyses were repeated controlling for perinatal and social risk, and measures of attention and working memory. It was found that visual acuity, convergence and visual perception are related to scores for academic achievement on univariable regression analyses. After controlling for potential confounds (perinatal and social risk, working memory and attention), visual acuity, convergence and visual perception remained associated with reading and math computation, but only convergence and visual perception are related to spelling. The additional variance explained by visual processing is up to 6.6% for reading, 2.7% for spelling, and 2.2% for math computation. None of the visual processing variables or visual motor integration are associated with handwriting on multivariable analysis. Working memory is generally a stronger predictor of reading, spelling, and math computation than visual processing. It was concluded that visual processing difficulties are significantly related to academic outcomes in EP/ELBW adolescents; therefore, specific attention should be paid to academic remediation strategies incorporating the management of working memory and visual processing in EP/ELBW children.

Influence of loosely bound extracellular polymeric substances (EPS) on the flocculation, sedimentation and dewaterability of activated sludge.

PubMed

Li, X Y; Yang, S F

2007-03-01

Laboratory experiments on the activated sludge (AS) process were carried out to investigate the influence of microbial extracellular polymeric substances (EPS), including loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS), on biomass flocculation, sludge settlement and dewaterability. The heat EPS extraction method was modified to include a mild step and a harsh step for extracting the LB-EPS and TB-EPS, respectively, from the sludge suspension. Six lab-scale AS reactors were used to grow AS with different carbon sources of glucose and sodium acetate, and different sludge retention times (SRTs) of 5, 10 and 20 days. The variation in the bioreactor condition produced sludge with different abundances of EPS and different flocculation and separation characteristics. The sludge that was fed on glucose had more EPS than the sludge that was fed on acetate. For any of the feeding substrates, the sludge had a nearly consistent TB-EPS value regardless of the SRT, and an LB-EPS content that decreased with the SRT. The acetate-fed sludge performed better than the glucose-fed sludge in terms of bioflocculation, sludge sedimentation and compression, and sludge dewaterability. The sludge flocculation and separation improved considerably as the SRT lengthened. The results demonstrate that the LB-EPS had a negative effect on bioflocculation and sludge-water separation. The parameters for the performance of sludge-water separation were much more closely correlated with the amount of LB-EPS than with the amount of TB-EPS. It is argued that although EPS is essential to sludge floc formation, excessive EPS in the form of LB-EPS could weaken cell attachment and the floc structure, resulting in poor bioflocculation, greater cell erosion and retarded sludge-water separation.

Pharmacological characterization of the inhibitory activity of beta h-endorphin (beta h-EP), [Arg9,19,24,28,29]-beta h-EP, [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens.

PubMed

Valenzuela, R; Li, C H; Huidobro-Toro, J P

1991-08-01

The inhibitory opioid activities of beta h-endorphin (beta h-EP), its structurally related peptide analogues [Gln8,Gly31]-beta h-EP-Gly-Gly-NH2 (Gly-Gly-beta h-EP), [Arg9,19,24,28,29]-beta h-EP (Arg-beta h-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-beta h-EP, beta h-EP and Gly-Gly-beta h-EP. Neither Gly-Gly-beta h-EP nor Arg-beta h-EP antagonized the inhibitory action of beta h-EP or methionine enkephalin. An hour of tissue exposure to 30 nM beta-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of beta h-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for beta h-EP and Arg-beta h-EP, it was only about 3-fold for Gly-Gly-beta h-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9.4; its potency as an antagonist of beta h-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8.5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7.8.

The Crystal Structure of a Binary Complex of Two Pseudopilins: EpsI And EpsJ From the Type 2 Secretion System of Vibrio Vulnificus

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

Yanez, M.E.; Korotkov, K.V.; Abendroth, J.

2009-05-28

Type II secretion systems (T2SS) translocate virulence factors from the periplasmic space of many pathogenic bacteria into the extracellular environment. The T2SS of Vibrio cholerae and related species is called the extracellular protein secretion (Eps) system that consists of a core of multiple copies of 11 different proteins. The pseudopilins, EpsG, EpsH, EpsI, EpsJ and EpsK, are five T2SS proteins that are thought to assemble into a pseudopilus, which is assumed to interact with the outer membrane pore, and may actively participate in the export of proteins. We report here biochemical evidence that the minor pseudopilins EpsI and EpsJ frommore » Vibrio species interact directly with one another. Moreover, the 2.3 {angstrom} resolution crystal structure of a complex of EspI and EpsJ from Vibrio vulnificus represents the first atomic resolution structure of a complex of two different pseudopilin components from the T2SS. Both EpsI and EpsJ appear to be structural extremes within the family of type 4a pilin structures solved to date, with EpsI having the smallest, and EpsJ the largest, 'variable pilin segment' seen thus far. A high degree of sequence conservation in the EpsI:EpsJ interface indicates that this heterodimer occurs in the T2SS of a large number of bacteria. The arrangement of EpsI and EpsJ in the heterodimer would correspond to a right-handed helical character of proteins assembled into a pseudopilus.« less

Adolescent Human Immunodeficiency Virus Care Providers’ Attitudes Toward the Use of Oral Pre-Exposure Prophylaxis in Youth

PubMed Central

Zimet, Gregory; Lally, Michelle; Kahn, Jessica A.

2016-01-01

Abstract Oral pre-exposure prophylaxis (PrEP) for human immunodeficiency virus (HIV) prevention is currently indicated for use in adults in the United States and may soon be indicated for minor adolescents. However, implementation of PrEP use among minors may present unique barriers. We conducted 15 individual, semi-structured interviews among US clinicians caring for HIV-infected and at-risk youth. The theory-driven interview guide assessed demographics, perceived role of oral PrEP in HIV prevention among adolescents, perceived barriers to and facilitating factors for use of PrEP in adolescents, and clinician-reported likelihood of prescribing PrEP. Transcripts were analyzed using framework analysis. Overall, clinicians viewed PrEP as a time-limited intervention that is one part of a comprehensive approach to HIV prevention among adolescents. Perceived barriers to prescribing to minors included concerns about: confidentiality, legality of minors consenting to PrEP without parental involvement, ability of minors to understand the risks/benefits of PrEP, the possible impact of PrEP on bone accrual, off-label use of PrEP medication in minors, and the high costs associated with PrEP use. Clinician-reported facilitating factors for prescribing PrEP to youth included educating communities and other clinicians about PrEP, ensuring adequate financial resources and infrastructure for delivering PrEP, developing formal guidance on effective behavioral interventions that should be delivered with PrEP, and gaining personal experience with prescribing PrEP. Clinicians indicated greater comfort with prescribing PrEP to adults versus minors. For PrEP to become more widely available to youth at risk for HIV infection, barriers that are unique to PrEP use in minors must be addressed. PMID:27410497

“Support Your Client at the Space That They're in”: HIV Pre-Exposure Prophylaxis (PrEP) Prescribers' Perspectives on PrEP-Related Risk Compensation

PubMed Central

Magnus, Manya; Mayer, Kenneth H.; Krakower, Douglas S.; Eldahan, Adam I.; Hawkins, Lauren A. Gaston; Underhill, Kristen; Hansen, Nathan B.; Kershaw, Trace S.; Betancourt, Joseph R.; Dovidio, John F.

2017-01-01

Abstract Despite the demonstrated effectiveness of HIV pre-exposure prophylaxis (PrEP) and evidence that most PrEP users do not engage in risk compensation (i.e., increased risk behavior due to a perceived decrease in HIV susceptibility), some healthcare providers report patient risk compensation to be a deterrent to prescribing PrEP. Overcoming this barrier is essential to supporting PrEP access and uptake among people at risk for HIV. To inform such efforts, this qualitative study explored PrEP-related risk compensation attitudes among providers with firsthand experience prescribing PrEP. US-based PrEP providers (n = 18), most of whom were HIV specialists, were recruited through direct outreach and referral from colleagues and other participants. Individual 90-min semistructured interviews were conducted by phone or in person from September 2014 through February 2015, transcribed, and thematically analyzed. Three attitudinal themes emerged: (1) providers' role is to support patients in making informed decisions, (2) risk behavior while taking PrEP does not fully offset PrEP's protective benefit (i.e., PrEP confers net protection, even with added behavioral risk), and (3) PrEP-related risk compensation is unduly stigmatized within and beyond the healthcare community. Participants were critical of other healthcare providers' negative judgment of patients and reluctance to prescribe PrEP due to anticipated risk compensation. Several providers also acknowledged an evolution in their thinking from initial ambivalence toward greater acceptance of PrEP and PrEP-related behavior change. PrEP providers' insights about risk compensation may help to address unsubstantiated concerns about PrEP-related risk compensation and challenge the acceptability of withholding PrEP on these grounds. PMID:28414261

An intercomparison of stratospheric gravity wave potential energy densities from METOP GPS radio occultation measurements and ECMWF model data

NASA Astrophysics Data System (ADS)

Rapp, Markus; Dörnbrack, Andreas; Kaifler, Bernd

2018-02-01

Temperature profiles based on radio occultation (RO) measurements with the operational European METOP satellites are used to derive monthly mean global distributions of stratospheric (20-40 km) gravity wave (GW) potential energy densities (EP) for the period July 2014-December 2016. In order to test whether the sampling and data quality of this data set is sufficient for scientific analysis, we investigate to what degree the METOP observations agree quantitatively with ECMWF operational analysis (IFS data) and reanalysis (ERA-Interim) data. A systematic comparison between corresponding monthly mean temperature fields determined for a latitude-longitude-altitude grid of 5° by 10° by 1 km is carried out. This yields very low systematic differences between RO and model data below 30 km (i.e., median temperature differences is between -0.2 and +0.3 K), which increases with height to yield median differences of +1.0 K at 34 km and +2.2 K at 40 km. Comparing EP values for three selected locations at which also ground-based lidar measurements are available yields excellent agreement between RO and IFS data below 35 km. ERA-Interim underestimates EP under conditions of strong local mountain wave forcing over northern Scandinavia which is apparently not resolved by the model. Above 35 km, RO values are consistently much larger than model values, which is likely caused by the model sponge layer, which damps small-scale fluctuations above ˜ 32 km altitude. Another reason is the well-known significant increase of noise in RO measurements above 35 km. The comparison between RO and lidar data reveals very good qualitative agreement in terms of the seasonal variation of EP, but RO values are consistently smaller than lidar values by about a factor of 2. This discrepancy is likely caused by the very different sampling characteristics of RO and lidar observations. Direct comparison of the global data set of RO and model EP fields shows large correlation coefficients (0.4-1.0) with a general degradation with increasing altitude. Concerning absolute differences between observed and modeled EP values, the median difference is relatively small at all altitudes (but increasing with altitude) with an exception between 20 and 25 km, where the median difference between RO and model data is increased and the corresponding variability is also found to be very large. The reason for this is identified as an artifact of the EP algorithm: this erroneously interprets the pronounced climatological feature of the tropical tropopause inversion layer (TTIL) as GW activity, hence yielding very large EP values in this area and also large differences between model and observations. This is because the RO data show a more pronounced TTIL than IFS and ERA-Interim. We suggest a correction for this effect based on an estimate of this artificial EP using monthly mean zonal mean temperature profiles. This correction may be recommended for application to data sets that can only be analyzed using a vertical background determination method such as the METOP data with relatively scarce sampling statistics. However, if the sampling statistics allows, our analysis also shows that in general a horizontal background determination is advantageous in that it better avoids contributions to EP that are not caused by gravity waves.

Novel nanoporous sorbent for solid-phase extraction in petroleum fingerprinting

NASA Astrophysics Data System (ADS)

Alayande, S. Oluwagbemiga; Hlengilizwe, Nyoni; Dare, E. Olugbenga; Msagati, Titus A. M.; Akinlabi, A. Kehinde; Aiyedun, P. O.

2016-04-01

Sample preparation is crucial in the analysis of petroleum and its derivatives. In this study, developing affordable sorbent for petroleum fingerprinting analysis using polymer waste such expanded polystyrene was explored. The potential of electrospun expanded polystyrene (EPS) as a sorbent for the solid-phase extraction (SPE) technique was investigated, and its efficiency was compared with commercial cartridges such as alumina, silica and alumina/silica hybrid commercial for petroleum fingerprinting analysis. The chromatograms showed that the packed electrospun EPS fibre demonstrated excellent properties for SPE applications relative to the hybrid cartridges.

Inhibition of microsomal prostaglandin E synthase-1 facilitates liver repair after hepatic injury in mice.

PubMed

Nishizawa, Nobuyuki; Ito, Yoshiya; Eshima, Koji; Ohkubo, Hirotoki; Kojo, Ken; Inoue, Tomoyoshi; Raouf, Joan; Jakobsson, Per-Johan; Uematsu, Satoshi; Akira, Shizuo; Narumiya, Shuh; Watanabe, Masahiko; Majima, Masataka

2018-07-01

Liver repair following hepatic ischemia/reperfusion (I/R) injury is crucial to survival. This study aims to examine the role of endogenous prostaglandin E 2 (PGE 2 ) produced by inducible microsomal PGE synthase-1 (mPGES-1), a terminal enzyme of PGE 2 generation, in liver injury and repair following hepatic I/R. mPGES-1 deficient (Ptges -/- ) mice or their wild-type (WT) counterparts were subjected to partial hepatic ischemia followed by reperfusion. The role of E prostanoid receptor 4 (EP4) was then studied using a genetic knockout model and a selective antagonist. Compared with WT mice, Ptges -/- mice exhibited reductions in alanine aminotransferase (ALT), necrotic area, neutrophil infiltration, chemokines, and proinflammatory cytokine levels. Ptges -/- mice also showed promoted liver repair and increased Ly6C low macrophages (Ly6C low /CD11b high /F4/80 high -cells) with expression of anti-inflammatory and reparative genes, while WT mice exhibited delayed liver repair and increased Ly6C high macrophages (Ly6C high /CD11b high /F4/80 low -cells) with expression of proinflammatory genes. Bone marrow (BM)-derived mPGES-1-deficient macrophages facilitated liver repair with increases in Ly6C low macrophages. In vitro, mPGES-1 was expressed in macrophages polarized toward the proinflammatory profile. Mice treated with the mPGES-1 inhibitor Compound III displayed increased liver protection and repair. Hepatic I/R enhanced the hepatic expression of PGE receptor subtype, EP4, in WT mice, which was reduced in Ptges -/- mice. A selective EP4 antagonist and genetic deletion of Ptger4, which codes for EP4, accelerated liver repair. The proinflammatory gene expression was upregulated by stimulation of EP4 agonist in WT macrophages but not in EP4-deficient macrophages. These results indicate that mPGES-1 regulates macrophage polarization as well as liver protection and repair through EP4 signaling during hepatic I/R. Inhibition of mPGES-1 could have therapeutic potential by promoting liver repair after acute liver injury. Hepatic ischemia/reperfusion injury is a serious complication that occurs in liver surgery. Herein, we demonstrated that inducible prostaglandin E 2 synthase (mPGES-1), an enzyme involved in synthesizing prostaglandin E 2 , worsens the injury and delays liver repair through accumulation of proinflammatory macrophages. Inhibition of mPGES-1 offers a potential therapy for both liver protection and repair in hepatic ischemia/reperfusion injury. Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Use of plant woody species electrical potential for irrigation scheduling

PubMed Central

Ríos-Rojas, Liliana; Morales-Moraga, David; Alcalde, José A; Gurovich, Luis A

2015-01-01

The electrical response of plants to environmental stimuli can be measured and quantitatively related to the intensity of several stimulating sources, like temperature, solar radiation, soil water content, evapotranspiration rates, sap flow and dendrometric cycles. These relations can be used to assess the influence of different environmental situations on soil water availability to plants, defined as a steady state condition between leaf transpirative flow and soil water flow to plant roots. A restricted soil water flow due to soil dryness can trigger water stress in plants, if the atmospheric evaporative demand is high, causing partial stomata closure as a physiological response to avoid plant dehydration; water stressed and unstressed plants manifest a differential electrical response. Real time plant electrical response measurements can anticipate actions that prevent the plant reaching actual stress conditions, optimizing stomata gas exchange and photosynthetic rates. An electrophysiological sensor developed in this work, allows remote real-time recording information on plant electrical potential (EP) in the field, which is highly related to EP measurements obtained with a laboratory Keithley voltmeter sensor used in an highly controlled experimental setup. Our electrophysiological sensor is a wireless, autonomous devise, which transmits EP information via Internet to a data server. Using both types of sensors (EP electrodes with a Keithley voltmeter and the electrophysiological sensor), we measured in real time the electrical responses of Persea americana and Prunus domestica plants, to induced water deficits. The differential response for 2 scenarios: irrigation and water restriction is identified by a progressive change in slope on the daily maximal and minimal electric signal values in stressed plants, and a zero-slope for similar signals for well-watered plants. Results show a correspondence between measured signals obtained by our electrophysiological sensor and the EP electrodes connected to the Keithley voltmeter in each irrigation stage. Also, both sensors show a daily cyclical signal (circadian cycle). PMID:25826257

Improved antimicrobial activities of synthetic-hybrid bacteriocins designed from enterocin E50-52 and pediocin PA-1.

PubMed

Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L; Chikindas, Michael L

2015-03-01

Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Improved Antimicrobial Activities of Synthetic-Hybrid Bacteriocins Designed from Enterocin E50-52 and Pediocin PA-1

PubMed Central

Tiwari, Santosh Kumar; Sutyak Noll, Katia; Cavera, Veronica L.

2014-01-01

Two hybrid bacteriocins, enterocin E50-52/pediocin PA-1 (EP) and pediocin PA-1/enterocin E50-52 (PE), were designed by combining the N terminus of enterocin E50-52 and the C terminus of pediocin PA-1 and by combining the C terminus of pediocin PA-1 and the N terminus of enterocin E50-52, respectively. Both hybrid bacteriocins showed reduced MICs compared to those of their natural counterparts. The MICs of hybrid PE and EP were 64- and 32-fold lower, respectively, than the MIC of pediocin PA-1 and 8- and 4-fold lower, respectively, than the MIC of enterocin E50-52. In this study, the effect of hybrid as well as wild-type (WT) bacteriocins on the transmembrane electrical potential (ΔΨ) and their ability to induce the efflux of intracellular ATP were investigated. Enterocin E50-52, pediocin PA-1, and hybrid bacteriocin PE were able to dissipate ΔΨ, but EP was unable to deplete this component. Both hybrid bacteriocins caused a loss of the intracellular concentration of ATP. EP, however, caused a faster efflux than PE and enterocin E50-52. Enterocin E50-52 and hybrids PE and EP were active against the Gram-positive and Gram-negative bacteria tested, such as Micrococcus luteus, Salmonella enterica serovar Enteritidis 20E1090, and Escherichia coli O157:H7. The hybrid bacteriocins designed and described herein are antimicrobial peptides with MICs lower those of their natural counterparts. Both hybrid peptides induce the loss of intracellular ATP and are capable of inhibiting Gram-negative bacteria, and PE dissipates the electrical potential. In this study, the MIC of hybrid bacteriocin PE decreased 64-fold compared to the MIC of its natural peptide counterpart, pediocin PA-1. Inhibition of Gram-negative pathogens confers an additional advantage for the application of these peptides in therapeutics. PMID:25527560

The Efficacy of Intraoperative Neurophysiological Monitoring Using Transcranial Electrically Stimulated Muscle-evoked Potentials (TcE-MsEPs) for Predicting Postoperative Segmental Upper Extremity Motor Paresis After Cervical Laminoplasty.

PubMed

Fujiwara, Yasushi; Manabe, Hideki; Izumi, Bunichiro; Tanaka, Hiroyuki; Kawai, Kazumi; Tanaka, Nobuhiro

2016-05-01

Prospective study. To investigate the efficacy of transcranial electrically stimulated muscle-evoked potentials (TcE-MsEPs) for predicting postoperative segmental upper extremity palsy following cervical laminoplasty. Postoperative segmental upper extremity palsy, especially in the deltoid and biceps (so-called C5 palsy), is the most common complication following cervical laminoplasty. Some papers have reported that postoperative C5 palsy cannot be predicted by TcE-MsEPs, although others have reported that it can be predicted. This study included 160 consecutive cases that underwent open-door laminoplasty, and TcE-MsEP monitoring was performed in the biceps brachii, triceps brachii, abductor digiti minimi, tibialis anterior, and abductor hallucis. A >50% decrease in the wave amplitude was defined as an alarm point. According to the monitoring alarm, interventions were performed, which include steroid administration, foraminotomies, etc. Postoperative deltoid and biceps palsy occurred in 5 cases. Among the 155 cases without segmental upper extremity palsy, there were no monitoring alarms. Among the 5 deltoid and biceps palsy cases, 3 had significant wave amplitude decreases in the biceps during surgery, and palsy occurred when the patients awoke from anesthesia (acute type). In the other 2 cases in which the palsy occurred 2 days after the operation (delayed type), there were no significant wave decreases. In all of the cases, the palsy was completely resolved within 6 months. The majority of C5 palsies have been reported to occur several days after surgery, but some of them have been reported to occur immediately after surgery. Our results demonstrated that TcE-MsEPs can predict the acute type, whereas the delayed type cannot be predicted. A >50% wave amplitude decrease in the biceps is useful to predict acute-type segmental upper extremity palsy. Further examination about the interventions for monitoring alarm will be essential for preventing palsy.

Use of plant woody species electrical potential for irrigation scheduling.

PubMed

Ríos-Rojas, Liliana; Morales-Moraga, David; Alcalde, José A; Gurovich, Luis A

2015-01-01

The electrical response of plants to environmental stimuli can be measured and quantitatively related to the intensity of several stimulating sources, like temperature, solar radiation, soil water content, evapotranspiration rates, sap flow and dendrometric cycles. These relations can be used to assess the influence of different environmental situations on soil water availability to plants, defined as a steady state condition between leaf transpirative flow and soil water flow to plant roots. A restricted soil water flow due to soil dryness can trigger water stress in plants, if the atmospheric evaporative demand is high, causing partial stomata closure as a physiological response to avoid plant dehydration; water stressed and unstressed plants manifest a differential electrical response. Real time plant electrical response measurements can anticipate actions that prevent the plant reaching actual stress conditions, optimizing stomata gas exchange and photosynthetic rates. An electrophysiological sensor developed in this work, allows remote real-time recording information on plant electrical potential (EP) in the field, which is highly related to EP measurements obtained with a laboratory Keithley voltmeter sensor used in an highly controlled experimental setup. Our electrophysiological sensor is a wireless, autonomous devise, which transmits EP information via Internet to a data server. Using both types of sensors (EP electrodes with a Keithley voltmeter and the electrophysiological sensor), we measured in real time the electrical responses of Persea americana and Prunus domestica plants, to induced water deficits. The differential response for 2 scenarios: irrigation and water restriction is identified by a progressive change in slope on the daily maximal and minimal electric signal values in stressed plants, and a zero-slope for similar signals for well-watered plants. Results show a correspondence between measured signals obtained by our electrophysiological sensor and the EP electrodes connected to the Keithley voltmeter in each irrigation stage. Also, both sensors show a daily cyclical signal (circadian cycle).

Risk perception and sex behaviour in pregnancy and breastfeeding in high HIV prevalence settings: Programmatic implications for PrEP delivery

PubMed Central

Farley, Elise; Towriss, Catriona; Gomba, Yolanda; Bekker, Linda-Gail; Gorbach, Pamina; Shoptaw, Steven; Coates, Thomas; Myer, Landon

2018-01-01

HIV acquisition during pregnancy and breastfeeding significantly contributes toward paediatric HIV infection; however, little is known about risk behaviours in HIV-uninfected pregnant and postpartum women. We conducted twenty-six in-depth-interviews between July and December 2016 using a semi-structured interview guide among HIV-uninfected pregnant and recently postpartum women at-risk of HIV acquisition (defined as reporting ≥1 of the following: partner’s serostatus unknown or HIV-infected, recent condomless sex in pregnancy, and/or alcohol use during pregnancy) who attended primary healthcare services. Our study contextualizes factors related to risky sexual behaviours during pregnancy and postpartum periods and assesses knowledge and hypothetical acceptability of pre-exposure prophylaxis (PrEP) in pregnancy. Translated and transcribed data were coded and analysed by three researchers using a thematic analysis approach. In interviews with HIV-uninfected pregnant/postpartum women at-risk of HIV acquisition, we identified common themes associated with sexual risk behaviours during pregnancy, including: lack of control over decisions in sex and condom use in pregnancy, low perceived risk (e.g. beliefs that their partner has the same HIV-negative serostatus), and socio-cultural beliefs around condom use during pregnancy (e.g. contact with sperm is essential for baby’s development). PrEP knowledge was low among HIV-uninfected pregnant and breastfeeding women, and potential acceptability was good, though primary concerns were around the potential impact on the infant. While mothers presented a clear desire to protect themselves from HIV acquisition once pregnant, they also reported lack of control, and socio-cultural beliefs, like sex is good for the baby, that increased their risk of seroconversion. Mothers had limited PrEP awareness but reported hypothetical willingness to use PrEP because of concerns over HIV acquisition and onward mother to child transmission. PMID:29758064

Effect of salinity on extracellular polymeric substances of activated sludge from an anoxic-aerobic sequencing batch reactor.

PubMed

Wang, Zichao; Gao, Mengchun; Wang, Zhe; She, Zonglian; Chang, Qingbo; Sun, Changqing; Zhang, Jian; Ren, Yun; Yang, Ning

2013-11-01

The effect of salinity on extracellular polymeric substances (EPS) of activated sludge was investigated in an anoxic-aerobic sequencing batch reactor (SBR). The contents of loosely bound EPS (LB-EPS) and tightly bound EPS (TB-EPS) were positively correlated with the salinity. The polysaccharide (PS) and protein (PN) contents in both LB-EPS and TB-EPS increased with the increase of salinity. With the increase of salinity from 0.5% to 6%, the PN/PS ratios in LB-EPS and TB-EPS decreased from 4.8 to 0.9 and from 2.9 to 1.4, respectively. The four fluorescence peaks in both LB-EPS and TB-EPS identified by three-dimensional excitation-emission matrix fluorescence spectroscopy are attributed to PN-like substances and humic acid-like substances. The Fourier transform infrared spectra of the LB-EPS and TB-EPS appeared to be very similar, but the differences across the spectra were apparent in terms of the relative intensity of some bands with the increase of salinity. The sludge volume index showed a linear correlation with LB-EPS (R(2)=0.9479) and TB-EPS (R(2)=0.9355) at different salinities, respectively. Copyright © 2013 Elsevier Ltd. All rights reserved.