Introduction. Candidiasis is the most commonly encountered opportunistic infection among HIV-positive subjects. The purpose of this study was to assess specific keratinocyte immune parameters in the pseudomembranous and erythematous forms of HIV-associated oral candidiasis.Material\\/Methods. This collaborative study from three centers analyzed 25 HIV-positive and 10 HIV-negative subjects with either pseudomembranous or erythematous candidiasis. Oral biopsy specimens from lesional tissues were
L. R Eversole; Peter A Reichart; Giuseppe Ficarra; A Schmidt-Westhausen; Paolo Romagnoli; Nicola Pimpinelli
Only some patients with HIV-infection receive an adequate pain therapy. In later stages of HIV-infection up to 50% 6 of patients perform extraordinary doctor visits because of pain. Principally primary and secondary neuromanifestations of HIV-infection have to be differentiated. Rare forms of HIV-associated polyneuropathies represent mononeuropathy or mononeuritis multiple acute and chronic inflammatory demyelinating polyneuropathy and polyneuropathy caused by opportunistic infections. HIV-associated distal-symmetric polyneuropathy represents the most common form during HIV-infection with a prevalence up to 50%. Typical clinical symptoms and signs are pain, hyp- and dysaesthesia, diminuted deep tendon reflexes, motor deficits and autonomic disturbances. Always neurological examination and neurophysiologic investigation on the sural and peronaeal nerve are necessary for monitoring progression of polyneuropathy and as basics before starting antiretroviral therapy with neurotoxic substances. According to momentary opinion, HIV-associated distal-symmetric polyneuropathy represents no indication for antiretroviral therapy. Symptomatic therapy includes antiepileptic medication as gabapentine, antidepressive drugs as amitiptyline and additionally retarded opiates. Depressive disorders ma y accentuate pain problems a n d need psychotherapeutic and thymoleptic therapy. Special problems occur when neurotoxic substances evoke or deteriorate polyneuropathy. In these cases an individual therapeutic proceeding about continuation or discontinuation of neurotoxic medication is necessary. Symptoms of myopathy during HIV-infection are muscle pain, elevation of CK and typical changes of motor units detected by electromyography. In most cases biopsy is necessary for diagnosis of specific forms of HN-associated myopathy. HIV-associated polymyositis is treated by non-steroid analgetics, corticoids, immunoglobulines and plasmapheresis, myopathy induced by neurotoxic medication analogous to polyneuropathy. PMID:11810345
Husstedt, I W; Böckenholt, S; Kammer-Suhr, B; Evers, S
Background Human Immunodeficiency Virus-1 (HIV) infection frequently results in neurocognitive impairment. While the cause remains unclear, recent gene expression studies have identified genes whose transcription is dysregulated in individuals with HIV-association neurocognitive disorder (HAND). However, the methods for interpretation of such data have lagged behind the technical advances allowing the decoding genetic material. Here, we employ systems biology methods novel to the field of NeuroAIDS to further interrogate extant transcriptome data derived from brains of HIV?+?patients in order to further elucidate the neuropathogenesis of HAND. Additionally, we compare these data to those derived from brains of individuals with Alzheimer’s disease (AD) in order to identify common pathways of neuropathogenesis. Methods In Study 1, using data from three brain regions in 6 HIV-seronegative and 15 HIV?+?cases, we first employed weighted gene co-expression network analysis (WGCNA) to further explore transcriptome networks specific to HAND with HIV-encephalitis (HIVE) and HAND without HIVE. We then used a symptomatic approach, employing standard expression analysis and WGCNA to identify networks associated with neurocognitive impairment (NCI), regardless of HIVE or HAND diagnosis. Finally, we examined the association between the CNS penetration effectiveness (CPE) of antiretroviral regimens and brain transcriptome. In Study 2, we identified common gene networks associated with NCI in both HIV and AD by correlating gene expression with pre-mortem neurocognitive functioning. Results Study 1: WGCNA largely corroborated findings from standard differential gene expression analyses, but also identified possible meta-networks composed of multiple gene ontology categories and oligodendrocyte dysfunction. Differential expression analysis identified hub genes highly correlated with NCI, including genes implicated in gliosis, inflammation, and dopaminergic tone. Enrichment analysis identified gene ontology categories that varied across the three brain regions, the most notable being downregulation of genes involved in mitochondrial functioning. Finally, WGCNA identified dysregulated networks associated with NCI, including oligodendrocyte and mitochondrial functioning. Study 2: Common gene networks dysregulated in relation to NCI in AD and HIV included mitochondrial genes, whereas upregulation of various cancer-related genes was found. Conclusions While under-powered, this study identified possible biologically-relevant networks correlated with NCI in HIV, and common networks shared with AD, opening new avenues for inquiry in the investigation of HAND neuropathogenesis. These results suggest that further interrogation of existing transcriptome data using systems biology methods can yield important information.
Human immunodeficiency virus type 1 is associated with the development of neurocognitive disorders in many infected individuals, including a broad spectrum of motor impairments and cognitive deficits. Despite extensive research, the pathogenesis of HIV-associated neurocognitive disorders (HAND) is still not clear. This review provides a comprehensive view of HAND, including HIV neuroinvasion, HAND diagnosis and different level of disturbances, influence of highly-active antiretroviral therapy to HIV-associated dementia (HAD), possible pathogenesis of HAD, etc. Together, this review will give a thorough and clear understanding of HAND, especially HAD, which will be vital for future research, diagnosis and treatment.
Zhou, Li; Saksena, Nitin K.
Chronic diarrhoea and weight loss commonly complicate the course of HIV infection and AIDS. The broad range of potential aetiological agents in HIV-infected patients with diarrhoea, the cost of the various tests required to detect these agents, and the variable response to treatment in these patients make the approach to HIV-associated diarrhoea complex and confusing. Weight loss and cachexia may
H. L. DuPont; G. D. Marshall
Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features. Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies. Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.
Flepisi, Brian Thabile; Bouic, Patrick; Sissolak, Gerhard; Rosenkranz, Bernd
The introduction of combined antiretroviral therapy (cART) has dramatically reduced the risk of central nervous system opportunistic infection and severe dementia secondary to HIV infection in the last two decades. However, a milder form of HIV-associated neurocognitive disorder (HAND) remains prevalent in the cART era and has a significant impact on patients' quality of life. In this review, we outline updated research findings on investigating and monitoring cognitive impairment in HAND patients. The outcomes of recent research on the pathogenesis of HAND and how it overlaps with neurodegenerative diseases are discussed. Lastly, there is a brief discussion of the results of clinical trials using a brain-penetrating cART regimen. PMID:24938216
Brew, Bruce J; Chan, Phillip
Neurological involvement in HIV is often associated with cognitive impairment. Although severe and progressive neurocognitive impairment has become rare in HIV clinics in the era of potent antiretroviral therapy, most patients with HIV worldwide have poor outcomes on formal neurocognitive tests. In this Review, we describe the manifestations of HIV-associated neurocognitive disorder in the era of effective HIV therapy, outline diagnosis and treatment recommendations, and explore the research questions that remain. Although comorbid disorders, such as hepatitis C infection or epilepsy, might cause some impairment, their prevalence is insufficient to explain the frequency with which it is encountered. HIV disease markers, such as viral load and CD4 cell counts, are not strongly associated with ongoing impairment on treatment, whereas cardiovascular disease markers and inflammatory markers are. New cerebrospinal fluid and neuroimaging biomarkers are needed to detect and follow impairment. Ongoing research efforts to optimise HIV therapy within the CNS, and potentially to intervene in downstream mechanisms of neurotoxicity, remain important avenues for future investigation. Ultimately, the full control of virus in the brain is a necessary step in the goal of HIV eradication. PMID:24156898
Clifford, David B; Ances, Beau M
This review presents an up-to-date assessment of the role of the tryptophan metabolic and catabolic pathways in neurodegenerative disease and HIV-associated neurocognitive disorder. The kynurenine pathway and the effects of each of its enzymes and products are reviewed. The differential expression of the kynurenine pathway in cells within the brain, including inflammatory cells, is explored given the increasing recognition of the importance of inflammation in neurodegenerative disease. An overview of common mechanisms of neurodegeneration is presented before a review and discussion of the evidence for a pathogenetic role of the kynurenine pathway in Alzheimer’s disease, HIV-associated neurocognitive disorder, Huntington’s disease, motor neurone disease, and Parkinson’s disease.
Davies, Nicholas W.S.; Guillemin, Gilles; Brew, Bruce J.
The last decade has witnessed major advances in our understanding of the epidemiology and pathophysiology of HIV-related cardiovascular disease in sub-Saharan Africa. In this review, we summarise these and discuss clinically relevant advances in diagnosis and treatment. In the Heart of Soweto Study, 10% of patients with newly diagnosed cardiovascular disease were HIV positive, and the most common HIV-related presentations were cardiomyopathy (38%), pericardial disease (13%) and pulmonary arterial hypertension (8%). HIV-related cardiomyopathy is more common with increased immunosuppression and HIV viraemia. With adequate antiretroviral therapy, the prevalence is low. Contributing factors such as malnutrition and genetic predisposition are under investigation. In other settings, pericardial disease is the most common presentation of HIV-related cardiovascular disease (over 40%), and over 90% of pericardial effusions are due to Mycobacterium tuberculosis (TB) pericarditis. HIV-associated TB pericarditis is associated with a greater prevalence of myopericarditis, a lower rate of progression to constriction, and markedly increased mortality. The role of steroids is currently under investigation in the form of a randomised controlled trial. HIV-associated pulmonary hypertension is significantly more common in sub-Saharan Africa than in developed countries, possibly as a result of interactions between HIV and other infectious agents, with very limited treatment options. It has recently been recognised that patients with HIV are at increased risk of sudden death. Infection with HIV is independently associated with QT prolongation, which is more marked with hepatitis C co-infection and associated with a 4.5-fold higher than expected rate of sudden death. The contribution of coronary disease to the overall burden of HIV-associated cardiovascular disease is still low in sub-Saharan Africa. PMID:23680889
Syed, Faisal F; Sani, Mahmoud Umar
HIV-associated sensory neuropathy remains an important complication of combination antiretroviral therapy (CART) and HIV infection. Mitochondrial DNA haplogroups and single nucleotide polymorphisms (SNPs) have previously been associated with symptomatic neuropathy in clinical trial participants. We examined associations between mitochondrial DNA variation and HIV-associated sensory neuropathy in CHARTER. CHARTER is a U.S. based longitudinal observational study of HIV-infected adults who underwent a structured interview and standardized examination. HIV-associated sensory neuropathy was determined by trained examiners as ?1 sign (diminished vibratory and sharp-dull discrimination or ankle reflexes) bilaterally. Mitochondrial DNA sequencing was performed and haplogroups were assigned by published algorithms. Multivariable logistic regression of associations between mitochondrial DNA SNPs, haplogroups and HIV-associated sensory neuropathy were performed. In analyses of associations of each mitochondrial DNA SNP with HIV-associated sensory neuropathy, the two most significant SNPs were at positions A12810G (odds ratio [95% confidence interval] = 0.27 [0.11-0.65]; p = 0.004) and T489C (odds ratio [95% confidence interval] = 0.41 [0.21-0.80]; p = 0.009). These synonymous changes are known to define African haplogroup L1c and European haplogroup J, respectively. Both haplogroups are associated with decreased prevalence of HIV-associated sensory neuropathy compared with all other haplogroups (odds ratio [95% confidence interval] = 0.29 [0.12-0.71]; p = 0.007 and odds ratio [95% confidence interval] = 0.42 [0.18-1.0]; p = 0.05, respectively). In conclusion, in this cohort of mostly combination antiretroviral therapy-treated subjects, two common mitochondrial DNA SNPs and their corresponding haplogroups were associated with a markedly decreased prevalence of HIV-associated sensory neuropathy.
Holzinger, Emily R.; Hulgan, Todd; Ellis, Ronald J.; Samuels, David C.; Ritchie, Marylyn D.; Haas, David W.; Kallianpur, Asha R.; Bloss, Cinnamon S.; Clifford, David B.; Collier, Ann C.; Gelman, Benjamin B.; Marra, Christina M.; McArthur, Justin C.; McCutchan, J. Allen; Morgello, Susan; Simpson, David M.; Franklin, Donald R.; Rosario, Debralee; Selph, Doug; Letendre, Scott; Grant, Igor
HIV associated dementia (HAD), is a neuronal complication of HIV infection and causes cognitive and motor impairment. The cognitive decline in HAD is due to widespread synaptic loss than neuronal loss. The neurotoxicity in HAD is caused by activation of NMDA receptors by HIV-proteins but the exact mechanism of the synaptic loss is yet to be determined. This article explores a novel pathomechanism for the observed synaptic loss. The HIV-proteins augment NMDA mediated increase of intracellular Ca(2+) in neurons which activates nNOs for Nitric Oxide (NO) synthesis. The NO activates MAPK and phosphorylates Microtubule-associated protein-2(MAP2) at specific sites causing conformational changes, microtubular disassembly and promote MAP2 degradation by the ubiquitin-proteosome pathway. Under physiological conditions Ca(2+) signaling increases cholesterol transport into mitochondria for steroidogenesis by the CYP11A1. The neurosteroid pregnenolone binds to MAP2 and causes inhibition of phosphorylation, increase in microtubule assembly and decrease MAP2 degradation. The NO can inhibits CYP11A1 in a concentration dependent manner and reduces steroidogeneisis. There is a upregulation of NO production in HAD from HIV infected microglia and astrocytes which cross neuronal membrane and increase intracellular NO. This can cause profound inhibition of steroidogenesis in the brain, increase MAP2 degradation and synaptic loss in presence of HIV-proteins. PMID:22386322
Perumal, Madhusoothanan Bhagavathi; Dhanasekaran, Saranya
Background: Painful HIV-associated sensory neuropathies (HIV-SN) are a common complication of HIV infection. The pathogenesis is unknown and the treatment very limited. Gabapentin (GBP) is effective in painful diabetic neuropathy and postherpetic neuralgia and its effectiveness on painful HIV-SN has been reported anecdotally. Design: Multicenter, prospective, randomised, double-blind, placebo-controlled study. Methods: Patients were followed for a 1-week screening, a 4-week
K. Hahn; G. Arendt; J. S. Braun; H.-J von Giesen; I. W. Husstedt; M. Maschke; M. E. Straube; E. Schielke
HIV-associated neurocognitive disorders (HAND) are the most common preventable and treatable cause of dementia. While the incidence of the most severe form of HAND, HIV-associated dementia, has decreased since the introduction of combination antiretroviral therapy (cART), the prevalence of less severe forms of HAND has continued to rise. HAND leads to a subcortical dementia consisting of a triad of cognitive, behavior, and motor dysfunction. No single laboratory test can establish HAND, but ancillary studies including neuropsychological testing, neuroimaging studies, and cerebrospinal fluid (CSF) analysis are useful for supporting or refuting the diagnosis. More recent evidence has suggested that higher central nervous system-penetrating cART may lead to greater suppression of CSF HIV viral loads and improved cognition. Because viral control generally has been successful without eliminating cognitive dysfunction, further clinical studies that assess adjunctive neuroprotective drugs are likely to be required. PMID:18957181
Ances, Beau M; Clifford, David B
Human Immunodeficiency Virus (HIV) infection causes progressive damage to both limbs of the immune system, which results in a plethora of opportunistic infections. Among the various opportunistic infections, gastrointestinal infections are very common in HIV / Acquired Immunodeficiency Syndrome (AIDS). Opportunistic spore-forming protozoal parasites, namely, Cryptosporidium parvum, Isospora belli, Cyclospora cayetanensis, and Microsporidia, play a major role in causing chronic diarrhea, accompanied with weight loss, in patients with HIV / AIDS. The purpose of this review is to discuss the salient microbiological, clinical, and diagnostic aspects of important enteric spore-forming opportunistic parasites in HIV / AIDS. PMID:23507985
Chawla, Rohit; Ichhpujani, R L
Objectives: This is a cross-sectional, observational study to determine the frequency and associated features of HIV-associated neurocognitive disorders (HAND) in a large, diverse sample of infected individuals in the era of combination antiretroviral therapy (CART). Methods: A total of 1,555 HIV-infected adults were recruited from 6 university clinics across the United States, with minimal exclusions. We used standardized neuromedical, psychiatric, and neuropsychological (NP) examinations, and recently published criteria for diagnosing HAND and classifying 3 levels of comorbidity (minimal to severe non-HIV risks for NP impairment). Results: Fifty-two percent of the total sample had NP impairment, with higher rates in groups with greater comorbidity burden (40%, 59%, and 83%). Prevalence estimates for specific HAND diagnoses (excluding severely confounded cases) were 33% for asymptomatic neurocognitive impairment, 12% for mild neurocognitive disorder, and only 2% for HIV-associated dementia (HAD). Among participants with minimal comorbidities (n = 843), history of low nadir CD4 was a strong predictor of impairment, and the lowest impairment rate on CART occurred in the subset with suppressed plasma viral loads and nadir CD4 ?200 cells/mm3 (30% vs 47% in remaining subgroups). Conclusions: The most severe HAND diagnosis (HAD) was rare, but milder forms of impairment remained common, even among those receiving CART who had minimal comorbidities. Future studies should clarify whether early disease events (e.g., profound CD4 decline) may trigger chronic CNS changes, and whether early CART prevents or reverses these changes. GLOSSARY ANI = asymptomatic neurocognitive impairment; CART = combination antiretroviral therapy; CHARTER = CNS HIV Antiretroviral Therapy Effects Research; CIDI = Composite International Diagnostic Interview; CLIA = Clinical Laboratory Improvement Amendments; CPE = CNS penetration effectiveness; HAD = HIV-associated dementia; HAND = HIV-associated neurocognitive disorder; IADL = instrumental activities of daily living; LP = lumbar puncture; MND = mild neurocognitive disorder; NP = neuropsychological; PAOFI = Patient's Assessment of Own Functioning Inventory.
Heaton, R.K.; Clifford, D.B.; Franklin, D.R.; Woods, S.P.; Ake, C.; Vaida, F.; Ellis, R.J.; Letendre, S.L.; Marcotte, T.D.; Atkinson, J.H.; Rivera-Mindt, M.; Vigil, O.R.; Taylor, M.J.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Jernigan, T.L.; Wong, J.; Grant, I.
HIV-associated neurologic disease continues to be a significant complication in the era of highly active antiretroviral therapy. A substantial subset of the HIV-infected population shows impaired neuropsychological performance as a result of HIV-mediated neuroinflammation and eventual central nervous system (CNS) injury. CNS compartmentalization of HIV, coupled with the evolution of genetically isolated populations in the CNS, is responsible for poor prognosis in patients with AIDS, warranting further investigation and possible additions to the current therapeutic strategy. This chapter reviews key advances in the field of neuropathogenesis and studies that have highlighted how molecular diversity within the HIV genome may impact HIV-associated neurologic disease. We also discuss the possible functional implications of genetic variation within the viral promoter and possibly other regions of the viral genome, especially in the cells of monocyte–macrophage lineage, which are arguably key cellular players in HIV-associated CNS disease.
Nonnemacher, Michael R.; Wigdahl, Brian
Bosco is a software project developed by the Open Science Grid to help scientists better utilize their on-campus computing resources. Instead of submitting jobs through a dedicated gatekeeper, as most remote submission mechanisms use, it uses the built-in SSH protocol to gain access to the cluster. By using a common access method, SSH, we are able to simplify the interaction with the cluster, making the submission process more user friendly. Additionally, it does not add any extra software to be installed on the cluster making Bosco an attractive option for the cluster administrator. In this paper, we will describe Bosco, the personal supercomputing assistant, and how Bosco is used by researchers across the U.S. to manage their computing workflows. In addition, we will also talk about how researchers are using it, including an unique use of Bosco to submit CMS reconstruction jobs to an opportunistic XSEDE resource.
Weitzel, D.; Sfiligoi, I.; Bockelman, B.; Frey, J.; Wuerthwein, F.; Fraser, D.; Swanson, D.
The term HIV-associated eosinophilic folliculitis (EF) designates an idiopathic dermatitis that appears in HIV-infected patients with different clinical manifestations but with a distinctive histological feature characterized by a predominantly eosinophilic infiltrate in the follicular infundibula. On the other side, follicular mucinosis (FM) is a reaction pattern in the follicular epithelium, characterized by a mucinous degeneration of the outer sheath of
G. F. Buezo; J. Fraga; P. Abajo; L. Ríos; E. Daudén; A. García-Díez
The pathogenesis of immune reconstitution disease (IRD) is not well understood and it can be difficult to manage. Leukotrienes exert proinflammatory effects, have an important role in the innate immune response, and are relatively deficient in HIV infection. Montelukast is a leukotriene receptor antagonist (LTRA) currently licensed for the treatment of asthma. We report a series of three patients with severe HIV associated IRD (cases 1 and 2 associated with starting HAART and unresponsive to steroids), who obtained clinically dramatic responses to treatment with montelukast. The first case is of IRD to secondary syphilis and the second and third to tuberculosis. Cases 1 and 3 both relapsed after a temporary break from montelukast and resolved on restarting. Montelukast should be considered in HIV associated IRD as an alternative to steroids and where these are not effective. Leukotriene overactivity may be implicated in IRD.
Hardwick, C; White, D; Morris, E; Monteiro, E F; Breen, R A; Lipman, M
Potent combination antiretroviral therapy (ART) has resulted in dramatic improvement in AIDS associated morbidity and mortality. Although combination ART has resulted in a significant reduction in HIV associated dementia, the most severe form of HIV associated neurocognitive disorders (HAND), the overall prevalence of HAND among this population is estimated at 40%. It has been recognized that the central nervous system (CNS) serves as a reservoir for HIV, and neuronal damage begins at the time of acute infection and persists due to chronic infection of microglial and perivascular macrophages. Although combination ART has resulted in virologic control in the plasma compartment, virologic breakthrough can potentially ensue within the CNS compartment due to limited ART drug exposure. The purpose of this review is to discuss the definition, clinical spectrum and risk factors associated with HAND, review the pathogenesis of HAND, and address the pharmacologic challenges associated with ART drug exposure in the CNS compartment.
Nabha, Linda; Duong, Lan; Timpone, Joseph
Human immunodeficiency virus type 1 (HIV) infection presently affects more that 40 million people worldwide, and is associated with central nervous system (CNS) disruption in at least 30% of infected individuals. The use of highly active antiretroviral therapy has lessened the incidence, but not the prevalence of mild impairment of higher cognitive and cortical functions (HIV-associated neurocognitive disorders) as well as substantially reduced a more severe form dementia (HIV-associated dementia). Furthermore, improving neurological outcomes will require novel, adjunctive therapies that are targeted towards mechanisms of HIV-induced neurodegeneration. Identifying such molecular and pharmacological targets requires an understanding of the events preceding irreversible neuronal damage in the CNS, such as actions of neurotoxins (HIV proteins and cellular factors), disruption of ion channel properties, synaptic damage, and loss of adult neurogenesis. By considering the specific mechanisms and consequences of HIV neuropathogenesis, unified approaches for neuroprotection will likely emerge using a tailored, combined, and non-invasive approach.
Lindl, Kathryn A.; Marks, David R.; Kolson, Dennis L.
Human herpesvirus (HHV)-8 associated oncogenesis, a state of immune impairment, a local inflammatory environment, angiogenesis and HIV infection occurring concurrently are important factors for the development of HIV-associated Kaposi sarcoma (KS). Activation of the interleukin (IL)-6 receptor signalling pathway and constitutive signalling of viral G protein-coupled receptor (vGPCR) play an important role in the activation, proliferation and transformation of HHV-8
Neil H Wood; Liviu Feller
This review focuses on the “real world” implications of infection with HIV\\/AIDS from a neuropsychological perspective. Relevant\\u000a literature is reviewed which examines the relationships between HIV-associated neuropsychological impairment and employment,\\u000a driving, medication adherence, mood, fatigue, and interpersonal functioning. Specifically, the relative contributions of medical,\\u000a cognitive, psychosocial, and psychiatric issues on whether someone with HIV\\/AIDS will be able to return to
Ashley A. Gorman; Jessica M. Foley; Mark L. Ettenhofer; Charles H. Hinkin; Wilfred G. van Gorp
Advances in the treatment of the human immunodeficiency virus (HIV) have dramatically improved survival rates over the past\\u000a 10 years, but HIV-associated neurocognitive disorders (HAND) remain highly prevalent and continue to represent a significant\\u000a public health problem. This review provides an update on the nature, extent, and diagnosis of HAND. Particular emphasis is\\u000a placed on critically evaluating research within the realm
Steven Paul Woods; David J. Moore; Erica Weber; Igor Grant
The commonest opportunistic parasites causing morbidity and/or mortality in the immuno-compromised subjects are mainly the gastro-intestinal ones. This study clarified the prevalence of the opportunistic parasites among a group of immunocompromised patients selected from Al Azhar University Hospitals. One hundred immunocompromised patients (GI) were divided into GIa: 40 malignancy patients. GIb: 30 with diabetes mellitus. GIc: 30 with chronic renal failure. GII: included 20 cross-matched healthy subjects as controls. Sheets were filled out on each subject including all personal and medical history. Both groups were subjected to stool and blood examinations for parasites. The results showed opportunistic parasites in 30% of patients and in 10% of healthy controls. The highest group had parasitosis was patients suffering from malignancy (18%). The patients suffering from chronic renal failure or from diabetes mellitus were equally affected (6% each group). There was significant relation between malignant patients and diabetic or chronic renal failure ones, but without significant relation between diabetic and chronic renal failure patients. Giardia lamblia was the most common parasite found in the patients (10%) of which 5% were among patients suffering from malignancy. Others were Cryptospotidium parvum (7%) Cyclospora cayetanensis (3%) and Microsporidia species (2%). Mixed infection was detected in 2 cases that had C. parvum and Cyclospora. But, neither Isospora belli nor Strongyloides stercoralis were detected. Also, ELISA showed antibodies against Toxoplasma gondii in sex patients but none against Leishmania d. infantum. PMID:21268546
Baiomy, Ahmed M Said; Mohamed, Khairy Abd Al-Hamid; Ghannam, Mohamed A Mosaad; Shahat, Samir Abd Al-Razek; Al-Saadawy, Ahmed Saad Kamel
HIV-associated dementia (HAD) is widely considered a “subcortical” dementia that involves a disruption of frontal-basal ganglia circuits. Deficits in verbal fluency are common in HAD; however, the cognitive underpinnings of these deficits are not well understood. To elucidate the cognitive mechanisms underlying the diminished verbal fluency output in HAD, we examined several qualitative aspects of letter fluency in 21 individuals
Steven Paul Woods; Emily Conover; Julie D. Rippeth; Catherine L. Carey; Raul Gonzalez; Thomas D. Marcotte; Robert K. Heaton; Igor Grant
Abstract Human immunodeficiency virus (HIV) infection has altered both the epidemiology and outcome of enteric opportunistic parasitic infections. This study was done to determine the prevalence and species/genotypes of intestinal coccidian and microsporidial infections among HIV/AIDS patients with diarrhea and/or a history of diarrhea alternately with an asymptomatic interval, and their association with CD4 T cell count. This cross-sectional study was done from May 2010 to May 2011 in Shiraz University of Medical Sciences, South of Iran. A blood sample was obtained from HIV-positive patients for a CD4 T cell count upon enrollment. Sociodemographic data and a history of diarrhea were collected by interviewing 356 consecutive participants (273 males and 83 females). Whenever possible more than a fecal sample was collected from all the participants and examined for parasites using direct, physiological saline solution ethyl acetate, an acid-fast trichrome stain, nested polymerase chain reaction, and sequencing techniques for the detection, confirmation, and genotyping of Cryptosporidium spp., Cyclospora cayetanensis, Isospora belli, and intestinal microsporidia (Enterocytozoon bieneusi). The most common opportunistic and nonopportunistic pathogens were Cryptosporidium spp. (C. parvum and C. andersoni), E. bieneusi, Giardia lamblia, Sarcocystis spp., and Blastocystis homonis affecting 34, 8, 23, 1, and 14 patients, respectively. C. cayetanensis, I. belli, Enterobius vermicularis, and Hymenolepis nana were observed in few patients. A CD4 count <200 cells/?l was significantly associated with the presence of opportunistic parasites and diarrhea (p<0.05). Opportunistic intestinal parasites should be suspected in any HIV/AIDS patient with chronic diarrhea. Tropical epidemic nonopportunistic enteric parasitic infections among such patients should not be neglected in Iran.
Agholi, Mahmoud; Motazedian, Mohammad Hossein
HIV-1 infection can lead to neurocognitive impairment collectively known as HIV-associated neurocognitive disorders (HAND). Although combined antiretroviral treatment (cART) has significantly ameliorated HIV's morbidity and mortality, persistent neuroinflammation and neurocognitive dysfunction continue. This review focuses on the current clinical and molecular evidence of the viral and host factors that influence glutamate-mediated neurotoxicity and neuropathogenesis as an important underlying mechanism during the course of HAND development. In addition, discusses potential pharmacological strategies targeting the glutamatergic system that may help prevent and improve neurological outcomes in HIV-1-infected subjects. PMID:24867611
Vázquez-Santiago, Fabián J; Noel, Richard J; Porter, James T; Rivera-Amill, Vanessa
Background: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor- (TNF) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. Objective: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. Methods: Sixty-four subjects with
D. B. Clifford; J. C. McArthur; G. Schifitto; K. Kieburtz; M. P. McDermott; S. Letendre; B. A. Cohen; K. Marder; R. J. Ellis; C. M. Marra
Human immunodeficiency virus (HIV) enters the brain soon after seroconversion and can cause HIV-associated neurocognitive disorders (HAND). Although the more severe and progressive forms of HAND are less prevalent due to combination antiretroviral therapy (cART), ? 40% of HIV-infected (HIV+) patients continue to have cognitive impairment. Some HIV+ individuals who have effective plasma HIV-1 RNA suppression with cART still develop HAND. It is often difficult to diagnose HAND in the outpatient setting as detailed neuropsychological performance testing is required. Additional biomarkers that are relatively easy to obtain and clinically relevant are needed for assessing HIV-associated neuropathologic changes. Recently developed noninvasive magnetic resonance imaging (MRI) techniques have great potential to serve as biomarkers. The authors review the application of some of these neuroimaging techniques, magnetic resonance spectroscopy (MRS), volumetric MRI, diffusion tensor imaging (DTI), functional MRI (fMRI), in HIV+ individuals. Each of the neuroimaging methods offers unique insight into mechanisms underlying neuroHIV, could monitor disease progression, and may assist in evaluating the efficacy of particular cART regimens. It is hoped that considerable progress will continue to occur such that some of these neuroimaging methods will be incorporated across multiple sites and included in future HAND guidelines. PMID:24715492
Masters, Mary C; Ances, Beau M
FK506 binding protein (FKBP)-51 and FKBP52 act as molecular chaperones to control glucocorticoid receptor (GR) sensitivity. Dysregulation of proteins involved in GR-mediated signaling can lead to maladaptive stress response and aging-related cognitive decline. As HIV infection is related to chronic stress, we hypothesized that altered cortical expression of these proteins was associated with HIV-associated neurocognitive disorders (HAND). We used quantitative immunohistochemistry to assess expression levels of these proteins in the mid-frontal gyrus of 55 HIV-infected subjects free of cerebral opportunistic diseases compared to 20 age-matched non-HIV controls. The immunoreactivity normalized to the neuroanatomic area measured (IRn) for FKBP51 was increased in HIV subjects both in the cortex and subcortical white matter (p<0.0001, U test), while no significant alterations were observed for GR or FKBP52. Notably, the cortical FKBP51 IRn was higher in HAND subjects than in cognitively normal HIV subjects (p=0.02, U test). There was also a trend for increasing cortical FKBP51 IRn with the increasing severity of HAND (p=0.08, Kruskal-Wallis test). No significant changes in FKBP51 IRn were found with respect to hepatitis C virus infection, lifetime methamphetamine use, or antiretroviral treatment in HIV subjects. In conclusion, the increased cortical expression of FKBP51 (an inhibitor for GR activity) might represent negative feedback in an attempt to reduce GR sensitivity in the setting of chronic stress-induced elevation of GR-mediated signaling inherent in HIV infection. The further increased FKBP51 expression might lead to maladaptive stress response and HAND.
Soontornniyomkij, Virawudh; Everall, Ian P.; Moore, David J.; Gouaux, Ben; Tatro, Erick T.; Gospodarev, Vadim; Masliah, Eliezer; Yin, Nicole S.; Vinters, Harry V.; Achim, Cristian L.
Plantar fasciitis is diagnosed based on a pathognomonic clinical presentation and physical examination including plantar heel pain with the initial few steps after a period of inactivity. People living with HIV/AIDS, who are taking anti-retroviral medications, often have an associated redistribution of body fat (lipodystrophy). Lipoatrophy of the extremities may involve the heel fat-pad in this population and result in the signs and symptoms of plantar fasciitis. Two cases of plantar heel pain in HIV-associated lipodystrophy are presented to discuss the possible clinical association between the two conditions. Although conservative therapies have limited evidence, they are commonly used and have been seen, clinically, to result in a resolution of symptoms. In the presented cases, the individuals benefited from soft tissue therapy, modalities, activity modification and education on proper footwear. Clinicians should be aware that the association between these two conditions may be a significant cause of morbidity in a population of patients with HIV.
Stupar, Maja; Tibbles, Anthony
Script generation describes one’s ability to produce complex, sequential action plans derived from mental representations of everyday activities. The aim of this study was to assess the effect of HIV infection on script generation performance. Sixty HIV+ individuals (48% of whom had HIV-associated neurocognitive disorders [HAND]) and 26 demographically comparable HIV? participants were administered a novel, standardized test of script generation, which required participants to verbally generate and organize the necessary steps for completing six daily activities. HAND participants evidenced significantly more total errors, intrusions, and script boundary errors compared to the HIV-sample, indicating difficulties inhibiting irrelevant actions and staying within the prescribed boundaries of scripts, but had adequate knowledge of the relevant actions required for each script. These findings are generally consistent with the executive dysfunction and slowing common in HAND and suggest that script generation may play a role in everyday functioning problems in HIV.
Scott, J. Cobb; Woods, Steven Paul; Vigil, Ofilio; Heaton, Robert K.; Grant, Igor; Ellis, Ronald J.; Marcotte, Thomas D.
CMS is using a tiered setup of dedicated computing resources provided by sites distributed over the world and organized in WLCG. These sites pledge resources to CMS and are preparing them especially for CMS to run the experiment's applications. But there are more resources available opportunistically both on the GRID and in local university and research clusters which can be used for CMS applications. We will present CMS' strategy to use opportunistic resources and prepare them dynamically to run CMS applications. CMS is able to run its applications on resources that can be reached through the GRID, through EC2 compliant cloud interfaces. Even resources that can be used through ssh login nodes can be harnessed. All of these usage modes are integrated transparently into the GlideIn WMS submission infrastructure, which is the basis of CMS' opportunistic resource usage strategy. Technologies like Parrot to mount the software distribution via CVMFS and xrootd for access to data and simulation samples via the WAN are used and will be described. We will summarize the experience with opportunistic resource usage and give an outlook for the restart of LHC data taking in 2015.
Kreuzer, Peter; Hufnagel, Dirk; Dykstra, D.; Gutsche, O.; Tadel, M.; Sfiligoi, I.; Letts, J.; Wuerthwein, F.; McCrea, A.; Bockelman, B.; Fajardo, E.; Linares, L.; Wagner, R.; Konstantinov, P.; Blumenfeld, B.; Bradley, D.; Cms Collaboration
Abstract. Many organizations use opportunistic reuse as a low-cost mechanism to improve the efficiency of development. Scrapheap reuse is a particular form of opportunistic development that we explore in this paper with the aid of an experimental study.
Gerald Kotonya; Simon Lock; John Mariani
The goal of this thesis is to combine computerized vision and artificial intelligence programming in an application of robotic assembly that will use opportunistic scheduling. Opportunistic scheduling is making a schedule based on current opportunities. A...
A. W. Butler
HIV associated nephropathy syndrome ( HIVAN Syndrome ) is a recently identified entity and no study has been done in Senegal. So we report this observation. A 40 years old black patient was admitted for renal oedema syndrome and immunosuppressive signs. The biological investigations noticed a non-pur nephrotic syndrome and severe renal failure. Ultrasonography showed quite normal kidney sizes with hyper echogenicity and dediferenciation. HIV research was positive with 45 CD4 lymphocytes / mm3. This patient had no known causes of nephrotic syndrome ( diabetis, lupus ,amyloidosis.). So the diagnosis of HIVAN syndrome was determined with the clinical features and the bad outcome. We emphasize on the necessity to think about HIVAN in every black patient presenting a quickly progressive non-pur nephrotic syndrome. We expect prospectives studies to describe the clinical signs and the frequency of HIVAN syndrome in Senegal. PMID:15782480
Dia, D; Fall, K; Niang, A; Guibal, A; Fall, S; Dieng, M; Diallo, I; Debonne, J M
We address opportunistic use of RF spectrum for communication among frequency-agile nodes composing a network, under the assumptions that the network and its environment are time-varying and users external to the network may have precedence in access and use of certain frequencies under certain conditions. We consider three different frequency assignment problems: (1) finding a common broadcast frequency for a
M. E. Steenstrup
Coastal wetlands are among the most fragmented and disturbed ecosystems and the Great Lakes are no exception. One possible result is the observed increase in the presence and dominance of invasive and other opportunistic plant species, such as the common reed (Phragmites australi...
Cooperative communications has emerged as one of the most efficient way of exploiting spatial diversity in wire- less communications. Cooperative communications is a strategy where users, besides transmitting their own information, also relay re-encoded version of other users' information to a common destination. In this paper, we investigate a scheme called space- time (ST) coded cooperation with opportunistic network coding,
Gordhan Das Menghwar; Bujar Krasniqi; Asif Ali Shah; Christoph F. Mecklenbrauker
Summary: Stenotrophomonas maltophilia is an emerging multidrug-resistant global opportunistic pathogen. The increasing incidence of nosocomial and community-acquired S. maltophilia infections is of particular concern for immunocompromised individuals, as this bacterial pathogen is associated with a significant fatality/case ratio. S. maltophilia is an environmental bacterium found in aqueous habitats, including plant rhizospheres, animals, foods, and water sources. Infections of S. maltophilia can occur in a range of organs and tissues; the organism is commonly found in respiratory tract infections. This review summarizes the current literature and presents S. maltophilia as an organism with various molecular mechanisms used for colonization and infection. S. maltophilia can be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients, as a cocolonizer with Pseudomonas aeruginosa. Recent evidence of cell-cell communication between these pathogens has implications for the development of novel pharmacological therapies. Animal models of S. maltophilia infection have provided useful information about the type of host immune response induced by this opportunistic pathogen. Current and emerging treatments for patients infected with S. maltophilia are discussed.
AT1R has been reported to play an important role in the progression of HIV-associated nephropathy (HIVAN); however, the effect of AT2R has not been studied. Age and sex matched control (FVB/N) and Tg26 mice aged 4, 8, and 16 weeks were studied for renal tissue expression of AT1R and AT2R (Protocol A). Renal tissue mRNA expression of AT2R was lower in Tg26 mice when compared with control mice. In protocol B, Tg26 mice were treated with either saline, telmisartan (TEL, AT1 blocker), PD123319 (PD, AT2R blocker), or TEL + PD for two weeks. TEL-receiving Tg26 (TRTg) displayed less advanced glomerular and tubular lesions when compared with saline-receiving Tg26 (SRTg). TRTgs displayed enhanced renal tissue AT2R expression when compared to SRTgs. Diminution of renal tissue AT2R expression was associated with advanced renal lesions in SRTgs; whereas, upregulation of AT2R expression in TRTgs was associated with attenuated renal lesions. PD-receiving Tg 26 mice (PDRTg) did not show any alteration in the course of HIVAN; whereas, PD + TEL-receiving Tg26 (PD-TRTg) showed worsening of renal lesions when compared to TRTgs. Interestingly, plasma as well as renal tissues of Tg26 mice displayed several fold higher concentration of Ang III, a ligand of AT2R.
Salhan, Divya; Sagar, Ankita; Kumar, Dileep; Rattanavich, Rungwasee; Rai, Partab; Maheshwari, Subani; Adabala, Madhuri; Husain, Mohammad; Ding, Guohua; Malhotra, Ashwani; Chander, Praveen N.; Singhal, Pravin C.
In the present study, we hypothesized that HIV-1-induced occult HIV-associated nephropathy (HIVAN) would become apparent in the presence of adverse host factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent Vpr expression in podocytes) with two, three, and four copies of the angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered doxycycline for 3 weeks (to develop clinically occult HIVAN) followed by doxycycline-free water during the next 3 weeks. Subsequently, renal biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt-2 developed neither proteinuria nor elevated blood pressure, and displayed minimal glomerular and tubular lesions only, without any microcyst formation. Vpr-Agt-3 showed mild glomerular and tubular lesions and microcyst formation, whereas Vpr-Agt-4 showed moderate proteinuria, hypertension, glomerular sclerosis, tubular dilation, microcysts, and expression of epithelial mesenchymal transition markers. Vpr-Agt-4 not only displayed enhanced renal tissue expression of Agt, renin, and angiotensin-converting enzyme, but also had higher renal tissue concentrations of angiotensin II. Moreover, renal cells in Vpr-Agt-4 showed enhanced expression of transforming growth factor-?, connective tissue growth factor, and vascular endothelial growth factor. These findings indicate that adverse host factors, such as the activation of the renin-angiotensin system, promote the progression of occult HIVAN to apparent HIVAN. PMID:21871425
Kumar, Dileep; Salhan, Divya; Magoon, Sandeep; Torri, Deepti D; Sayeneni, Swapna; Sagar, Ankita; Bandhlish, Anshu; Malhotra, Ashwani; Chander, Praveen N; Singhal, Pravin C
In the present study, we hypothesized that HIV-1–induced occult HIV-associated nephropathy (HIVAN) would become apparent in the presence of adverse host factors. To test our hypothesis, Vpr mice (which display doxycycline-dependent Vpr expression in podocytes) with two, three, and four copies of the angiotensinogen (Agt) gene (Vpr-Agt-2, Vpr-Agt-3, and Vpr-Agt-4) were administered doxycycline for 3 weeks (to develop clinically occult HIVAN) followed by doxycycline-free water during the next 3 weeks. Subsequently, renal biomarkers were measured, and kidneys were harvested for renal histology. Vpr-Agt-2 developed neither proteinuria nor elevated blood pressure, and displayed minimal glomerular and tubular lesions only, without any microcyst formation. Vpr-Agt-3 showed mild glomerular and tubular lesions and microcyst formation, whereas Vpr-Agt-4 showed moderate proteinuria, hypertension, glomerular sclerosis, tubular dilation, microcysts, and expression of epithelial mesenchymal transition markers. Vpr-Agt-4 not only displayed enhanced renal tissue expression of Agt, renin, and angiotensin-converting enzyme, but also had higher renal tissue concentrations of angiotensin II. Moreover, renal cells in Vpr-Agt-4 showed enhanced expression of transforming growth factor-?, connective tissue growth factor, and vascular endothelial growth factor. These findings indicate that adverse host factors, such as the activation of the renin-angiotensin system, promote the progression of occult HIVAN to apparent HIVAN.
Kumar, Dileep; Salhan, Divya; Magoon, Sandeep; Torri, Deepti D.; Sayeneni, Swapna; Sagar, Ankita; Bandhlish, Anshu; Malhotra, Ashwani; Chander, Praveen N.; Singhal, Pravin C.
Sensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated neurocognitive disorders (HAND). Thirty-seven HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, although the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated. PMID:23552464
Minassian, Arpi; Henry, Brook L; Woods, Steven Paul; Vaida, Florin; Grant, Igor; Geyer, Mark A; Perry, William
Sensorimotor inhibition, or the ability to filter out excessive or irrelevant information, theoretically supports a variety of higher-level cognitive functions. Impaired inhibition may be associated with increased impulsive and risky behavior in everyday life. Individuals infected with HIV frequently show impairment on tests of neurocognitive function, but sensorimotor inhibition in this population has not been studied and may be a contributor to the profile of HIV-associated Neurocognitive Disorders (HAND). 37 HIV-infected individuals (15 with HAND) and 48 non-infected comparison subjects were assessed for prepulse inhibition (PPI), an eyeblink startle paradigm measuring sensorimotor gating. Although HIV status alone was not associated with PPI deficits, HIV-positive participants meeting criteria for HAND showed impaired PPI compared to cognitively intact HIV-positive subjects. In HIV-positive subjects, PPI was correlated with working memory but was not associated with antiretroviral therapy or illness factors. In conclusion, sensorimotor disinhibition in HIV accompanies deficits in higher-order cognitive functions, though the causal direction of this relationship requires investigation. Subsequent research on the role of sensorimotor gating on decision-making and risk behaviors in HIV may be indicated.
Minassian, Arpi; Henry, Brook L.; Woods, Steven Paul; Vaida, Florin; Grant, Igor; Geyer, Mark A.; Perry, William
The prognosis of human immunodeficiency virus (HIV)-infected individuals has dramatically improved worldwide since the introduction of highly antiretroviral therapy. Nevertheless, along with the decrease in mortality, several body modifications not initially related to HIV infection have been reported. Disorders in lipid and glucose metabolism, accompanied by body shape abnormalities and alterations in fat distribution, began to be described. A syndrome, named “HIV-associated lipodystrophy syndrome”, was coined to classify these clinical spectrum aspects. This syndrome involves not only metabolic alterations but also fat redistribution, with lipoatrophy due to subcutaneous fat loss (predominantly in the face and lower limbs) and lipohypertrophy related to central fat gain. These changes in body shape are very important to be recognized, as they are associated with worse morbidity and mortality. Self-esteem difficulties related to body alterations might lead to treatment failures due to medication adherence problems. Moreover, these alterations have been associated with an increased risk of cardiovascular events. Therefore, it is extremely important to identify this syndrome early in order to provide an even better quality of life for this population, as the clinical approach is not easy. Treatment change, medications to treat dyslipidemia, and surgical intervention are instruments to be used to try to correct these abnormalities. The aim of this study is to review clinical presentation, diagnosis, and management of body shape and metabolic complications of HIV infection from a Brazilian perspective, a medium income country with a large number of patients on antiretroviral therapy.
Alves, Marcelle D; Brites, Carlos; Sprinz, Eduardo
HIV infection of the central nervous system leads to HIV-associated dementia (HAD) in a substantial subset of infected individuals. The pathogenesis of neuronal dysfunction in HAD is not well understood, but previous studies have demonstrated evidence for activation of apoptotic pathways. The tumor suppressor transcription factor p53 is an apical mediator of neuronal apoptosis following a variety of injurious stimuli. To determine whether p53 participates in HAD, we exposed cerebrocortical cultures from wild-type and p53 deficient mice to the neurotoxic HIV envelope protein gp120. Using neuron/microglia co-culture of mixed p53 genotype, we observed that both neurons and microglia require p53 for gp120 induced neuronal apoptosis. Additionally, accumulation of p53 protein in neurons was recently reported in post-mortem cortical tissue from a small group of HAD patients. Using a much larger cohort of HAD cases, we extend this finding and report that p53 protein also increases in non-neuronal cells, including microglia. Taken together these findings demonstrate a novel role for p53 in the microglial response to gp120. Additionally, these findings, in conjunction with a recent report that monocytes expressing HIV-Tat also secrete neurotoxins that promote p53 activation, suggest that distinct HIV proteins may converge on the p53 pathway to promote neurotoxicity. PMID:15155568
Garden, Gwenn A; Guo, Weiqun; Jayadev, Suman; Tun, Christina; Balcaitis, Stephanie; Choi, Jo; Montine, Thomas J; Möller, Thomas; Morrison, Richard S
Trimethoprim, an antifolate commonly prescribed in combination with sulfamethoxazole, potently inhibits several prokaryotic species of dihydrofolate reductase (DHFR). However, several eukaryotic pathogenic organisms are resistant to trimethoprim, preventing its effective use as a therapeutic for those infections. We have been building a program to reengineer trimethoprim to more potently and selectively inhibit eukaryotic species of DHFR as a viable strategy for new drug discovery targeting several opportunistic pathogens. We have developed a series of compounds that exhibit potent and selective inhibition of DHFR from the parasitic protozoa Cryptosporidium and Toxoplasma as well as the fungus Candida glabrata. A comparison of the structures of DHFR from the fungal species Candida glabrata and Pneumocystis suggests that the compounds may also potently inhibit Pneumocystis DHFR.
Liu, J.; Bolstad, D; Bolstad, E; Wright, D; Anderson, A
The human immunodeficiency virus (HIV) invades the central nervous system early in the course of infection and establishes a protected viral reservoir. However, neurocognitive consequences of HIV infection, known collectively as HIV-associated neurocognitive disorders (HAND), develop in only a small portion of infected patients. The precise mechanisms of pathogenesis involved in HIV-induced central nervous system injury are still not completely understood. In particular, most theories of HAND pathogenesis cannot account for either the selective vulnerability of specific neuronal populations to HIV-induced neurodegeneration or why only a subset of patients develop clinically detectable nervous system disease. Epidemiological and virological studies have identified a variety of host and viral factors that are associated with increased risk of developing HAND. Some host factors that predispose HIV-infected patients to HAND overlap with those associated with Alzheimer's disease (AD), suggesting the possibility that common pathogenic mechanisms may participate in both diseases. Here, we will review reports of host and viral factors associated with HAND and place these studies in the context of the data employed to support current theories regarding the molecular and cellular mechanisms that lead to HIV-induced neurodegeneration with additional focus on mechanisms common to AD pathogenesis. PMID:19373562
Jayadev, Suman; Garden, Gwenn A
The human immunodeficiency virus (HIV) invades the central nervous system early in the course of infection and establishes a protected viral reservoir. However, neurocognitive consequences of HIV infection, known collectively as HIV-associated neurocognitive disorders (HAND), develop in only a small portion of infected patients. The precise mechanisms of pathogenesis involved in HIV-induced central nervous system injury are still not completely understood. In particular, most theories of HAND pathogenesis cannot account for either the selective vulnerability of specific neuronal populations to HIV-induced neurodegeneration or why only a subset of patients develop clinically detectable nervous system disease. Epidemiological and virological studies have identified a variety of host and viral factors that are associated with increased risk of developing HAND. Some host factors that predispose HIV-infected patients to HAND overlap with those associated with Alzheimer’s disease (AD), suggesting the possibility that common pathogenic mechanisms may participate in both diseases. Here, we will review reports of host and viral factors associated with HAND and place these studies in the context of the data employed to support current theories regarding the molecular and cellular mechanisms that lead to HIV-induced neurodegeneration with additional focus on mechanisms common to AD pathogenesis.
Jayadev, Suman; Garden, Gwenn A.
Objective. HIV-associated diarrhoea occurs in nearly all patients with acquired immunodeficiency syndrome (AIDS) in the developing countries. Diarrhoea is caused by the HIV-related immune dysfunction and is pivotal in the decrease of the helper T-cell (CD4? \\/) population. Enteric pathogens in HIV-associated diarrhoea are, for example, Cryptosporidium, Amoeba and Campylobacter species. Bovine colostrum is the first milk the suckling calf
Claes-Henrik Florén; Sonny Chinenye; Lidia Elfstrand; Conny Hagman; Ingemar Ihse
Objective: To determine the effect of smoked cannabis on the neuropathic pain of HIV-associated sensory neuropathy and an experimental pain model. Methods: Prospective randomized placebo-controlled trial conducted in the inpatient General Clinical Research Center between May 2003 and May 2005 involving adults with painful HIV- associated sensory neuropathy. Patients were randomly assigned to smoke either cannabis (3.56% tetrahydrocannabinol) or identical
D. I. Abrams; C. A. Jay; S. B. Shade; H. Vizoso; H. Reda; M. E. Kelly; M. C. Rowbotham; K. L. Petersen
Background There is an urgent need to more accurately diagnose HIV-associated neurocognitive disorder (HAND) in Africa. Rapid screening tests for HIV-associated dementia are of limited utility due to variable sensitivity and specificity. The use of selected neuropsychological tests is more appropriate, but norms for HIV seronegative people are not readily available for sub-Saharan African populations. We sought to derive normative scores for two commonly used neuropsychological tests that generate four test scores -- namely the Trail-Making Test (Parts A and B) and the Digit Span Test [Forward (DSF) and Backward (DSB)]. To assess memory and recall, we used the memory item of the International HIV Dementia Scale (IHDS). Findings One hundred and ten HIV seronegative participants were assessed at McCord Hospital, Durban, South Africa between March 3rd and October 31st, 2008. We excluded people with major depressive disorder, substance use abuse and dependence and head injuries (with or without loss of consciousness). All the participants in this study were African and predominantly female with an average age of 28.5 years and 10 years of education. Age and gender influenced neuropsychological functioning, with older people performing worse. The effect of gender was not uniform across all the tests. Conclusion These two neuropsychological tests can be administered with the IHDS in busy antiretroviral clinics. Their performance can be measured against these norms to more accurately diagnose the spectrum and progression of HAND.
Introduction. The most commonly seen glomerular disease in HIV infected patients is HIV-associated nephropathy (HIVAN); however, a multitude of other nephropathies can occur in HIV infection with an almost equal cumulative frequency. We report an unusual case of a patient with clinical and histological evidence of HIVAN in which the diagnosis was initially confounded by the finding of an elevated serum anti-glomerular basement membrane (anti-GBM) antibody. Case Presentation. We present a case of a 27-year-old African American female with a history of schizophrenia, cocaine abuse, and HIV infection who upon admission to our hospital was found to have severe acute kidney injury requiring hemodialysis. Urine studies revealed nephrotic range proteinuria and a serological workup was positive for anti-GBM antibody elevation with a value of 91 units (normal: 0–20 units). A renal biopsy revealed HIVAN with no evidence of crescentic glomerulonephritis or anti-GBM disease. Conclusion. This case highlights the need for careful interpretation of anti-GBM antibody tests in HIV infected patients with kidney disease and, in particular, the need for biopsy confirmation of the diagnosis prior to starting therapy. More research is needed to study the prognostic correlation between the degree of anti-GBM antibody elevation in HIVAN and disease severity.
Makary, Raafat; Poenariu, Andreea
Opportunistic practices can accelerate and simplify ubiquitous computing systems design. Such practices may include copying and pasting code from online forums into one's own scripts or reappropriating components from consumer electronics for design prototypes. The authors introduce a framework that links opportunistic design for ubiquitous computing to hardware and software practices. They interview 14 professional and hobbyist \\
Björn Hartmann; Scott Doorley; Scott R. Klemmer
This review focuses on free-living amoebae, widely distributed in soil and water, causing opportunistic and non-opportunistic infections in humans: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. Diseases include primary amoebic meningoencephalitis (N. fowleri), granulomatous amoebic encephalitis, cutaneous and nasopharyngeal infections (Acanthamoeba spp., Balamuthia mandrillaris, S. diploidea), and amoebic keratitis (Acanthamoeba spp). Acanthamoeba, Balamuthia, and Naegleria have been repeatedly
Frederick L. Schuster; Govinda S. Visvesvara
We analyze the performance of an opportunistic transmission strategy for Wireless Sensor Networks (WSNs). We consider a transmission strategy called Binary Decision-Based Transmission (BDT), which is a common form of opportunistic transmission. The BDT scheme initiates transmission only when the channel quality exceeds the optimum threshold to avoid unsuccessful transmissions that waste energy. We formulate the Markov Decision Process (MDP) to identify an optimum threshold for transmission decisions in the BDT scheme.
Kim, Jeong Geun; Phan, Ca Van; Kim, Wonha
The Mars Exploration Rover Spirit recently set a record for the furthest distance traveled in a single sol on Mars. Future planetary exploration missions are expected to use even longer drives to position rovers in areas of high scientific interest. This increase provides the potential for a large rise in the number of new science collection opportunities as the rover traverses the Martian surface. In this paper, we describe the OASIS system, which provides autonomous capabilities for dynamically identifying and pursuing these science opportunities during longrange traverses. OASIS uses machine learning and planning and scheduling techniques to address this goal. Machine learning techniques are applied to analyze data as it is collected and quickly determine new science gods and priorities on these goals. Planning and scheduling techniques are used to alter the behavior of the rover so that new science measurements can be performed while still obeying resource and other mission constraints. We will introduce OASIS and describe how planning and scheduling algorithms support opportunistic science.
Gaines, Daniel M.; Estlin, Tara; Forest, Fisher; Chouinard, Caroline; Castano, Rebecca; Anderson, Robert C.
Background The mitochondrial DNA (mtDNA) T16189C polymorphism, with a homopolymeric C-tract of 10–12 cytosines, is a putative genetic risk factor for idiopathic dilated cardiomyopathy in the African and British populations. We hypothesized that this variant may predispose to dilated cardiomyopathy in people who are infected with the human immunodeficiency virus (HIV). Methods A case-control study of 30 HIV-positive cases with dilated cardiomyopathy and 37 HIV-positive controls without dilated cardiomyopathy was conducted. The study was confined to persons of black African ancestry to minimize confounding of results by population admixture. HIV-positive patients with an echocardiographically confirmed diagnosis of dilated cardiomyopathy and HIV-positive controls with echocardiographically normal hearts were studied. Patients with secondary causes of cardiomyopathy (such as hypertension, diabetes, pregnancy, alcoholism, valvular heart disease, and opportunistic infection) were excluded from the study. DNA samples were sequenced for the mtDNA T16189C polymorphism with a homopolymeric C-tract in the forward and reverse directions on an ABI3100 sequencer. Results The cases and controls were well matched for age (median 35 years versus 34 years, P = 0.93), gender (males 60% vs 53%, P = 0.54), and stage of HIV disease (mean CD4 T cell count 260.7/?L vs. 176/?L, P = 0.21). The mtDNA T16189C variant with a homopolymeric C-tract was detected at a frequency of 26.7% (8/30) in the HIV-associated cardiomyopathy cases and 13.5% (5/37) in the HIV-positive controls. There was no significant difference between cases and controls (Odds Ratio 2.33, 95% Confidence Interval 0.67–8.06, p = 0.11). Conclusion The mtDNA T16189C variant with a homopolymeric C-tract is not associated with dilated cardiomyopathy in black African people infected with HIV.
Shaboodien, Gasnat; Engel, Mark E; Syed, Faisal F; Poulton, Joanna; Badri, Motasim; Mayosi, Bongani M
Up to 50% of long-term HIV infected patients, including those with systemically well-controlled infection, commonly experience memory problems and slowness, difficulties in concentration, planning, and multitasking. Deposition of A? plaques is also a common pathological feature of HIV infection. However, it is not clear whether this accumulation is due to AD-like processes, HIV-associated immunosuppression, Tat protein-induced A? elevations, and/or the effects of single highly active antiretroviral therapy (ART). Here we evaluated the effects of several ART medications (Zidovudine, Lamivudine, Indinavir, and Abacavir) alone and in combination on: 1) A?1-40, 42 generation in murine N2a cells transfected with the human "Swedish" mutant form of APP; 2) microglial phagocytosis of FITC-A?1-42 peptides in cultured murine N9 microglia. We report for the first time that these antiretroviral compounds (10 ?M) generally increase A? generation (~50-200%) in SweAPP N2a cells and markedly inhibit microglial phagocytosis of FITC-A?1-42 peptides in murine microglia. The most significant amyloidogenic effects were observed with combined ART (p < 0.05); suggesting certain ART medications may have additive amyloidogenic effects when combined. As these antiretroviral compounds are capable of penetrating the blood brain barrier and reaching the concentrations employed in the in vitro studies, these findings raise the possibility that ART may play a casual role in the elevated A? found in the brains of those infected with HIV. Therefore these compounds may consequently contribute to cognitive decline observed in HIV associated neurocognitive disorders (HAND).
Psoriasis is a chronic inflammatory skin disease that involves immune-mediated cutaneous inflammation and keratinocyte hyperproliferation. Psoriasis in patients with HIV responds poorly to treatment and has a high morbidity rate, thus posing a challenge to clinicians. Until now, there have been no documented cases of acitretin therapy for HIV-associated psoriasis in Korea. Here, we report a case of safe and successful therapy with acitretin in a 52-year-old man with HIV-associated psoriasis that responded poorly to previous treatments including steroids and ultraviolet B phototherapy. We also review the relevant literature.
Kim, Min Sung; Shin, Jin Ho; Cho, Jin Kyung; Lee, Hyang Im; Kim, Hyun Jung
One strategy for disinflation prescribes a deliberate path towards low inflation. A contrasting opportunistic approach eschews deliberate action and instead waits for unforeseen shocks to reduce inflation. This paper compares the ability of these two appr...
A. N. Bomfim G. D. Rudebusch
Prior research provides evidence that insiders generate significant abnormal returns by trading on private information. We use the cross sectional variations of insidersÆ ability to trade opportunistically to gauge managerial opportunism at the company level. Using U.S. top executivesÆ insider trades data; we develop a proxy for managerial opportunism, referred to as opportunistic insider trade (OIT). We first show companies
Katherine Gunny; Bin Ke; Tracey Chunqi Zhang
The pathogenesis of the HIV associated Kaposi's sarcoma is still unclear, but it appears to be a multifactorial process. Different investigations have shown, that cytokines and growth factors influence the development of KS. Several cases with tumor manifestation after irritation of the skin are demonstrated. Therefore a mechanism of development comparable with the Koebner Phenomenon can be postulated. PMID:2399758
Plettenberg, A; Engelmann, L; Meigel, W
Background: HIV-associated neurologic disorders (HAND) continue to develop in many patients with HIV. CSF amyloid measurements in HAND have been reported to be similar to those in de- mentia of the Alzheimer type (DAT). Confirmatory evaluation of this finding in carefully evaluated subjects is needed. Methods: CSF specimens were obtained from subjects clinically categorized with normal cogni- tion from the
D. B. Clifford; A. M. Fagan; D. M. Holtzman; J. C. Morris; M. Teshome; A. R. Shah; J. S. K. Kauwe
Long-term cancer risks are uncertain in HIV-infected persons, particularly those using highly active antiretroviral therapy (HAART). Timely, population-based surveillance of HIV-associated malignancies in the United States has been challenging because of various data inadequacies. Cancer registries represent a resource for this surveillance, if uncertainties around accurate differentiation of HIV-associated and unassociated cancers can be resolved. To inform the utility of cancer registry data for classifying and monitoring HIV-associated cancers, the completeness and quality of cancer registry-available information about patient HIV status was assessed. For all 10,126 non-Hodgkin lymphomas (NHLs), 1497 Hodgkin lymphomas (HLs), and 895 anal cancers reported to the Greater San Francisco Bay Area registry during 1990-1998, 6 indicators of patient HIV status were retrieved from 2 cancer registry-available sources (cancer registry records, death records) and from linkage with the California AIDS registry. Cross-tabulations were used to examine the distributions of patients with evidence of positive HIV status by indicator and source. Together, 5 cancer registry-available HIV indicators identified 25% more presumed HIV-positive NHL patients and nearly 50% more HL and anal cancer patients than were detected by AIDS registry linkage. Eighty-three percent of NHL patients and at least half of HL and anal cancer patients were identified by multiple sources of HIV indicators, and most individual indicators agreed acceptably with others. However, optimal strategies for classifying HIV-associated patients differed by cancer site. At least in this region, cancer registry data represent a useful resource for monitoring HIV-associated lymphomas and anal cancer and may offer benefits over linkage-based means in the age of HAART. PMID:15247562
Clarke, Christina A; Glaser, Sally L
Immunodeficiency associated Burkitt's lymphoma is the most common in patients with HIV/AIDS. It accounts for 30-40% of Non-Hodgkin's lymphomas and may be the first sign of underlying immunosuppression. This report illustrates a case of Burkitt's lymphoma of maxillary alveolar ridge, which was the first manifestation in an HIV positive patient, with a brief discussion on clinicopathologic features, aetiopathogenesis and treatment. PMID:24551737
Pinisetti, Soujanya; Nalabolu, Govind Raj Kumar; Uvr, Chowdary; Tadi, Durga Prasad
In recent years, technological advances have lead to a society with communication platforms like iPhone and Kinect Xbox that are able to inject sensing presence into online social networks (OSNs). Thus, it is possible to create large- scale opportunistic networks by integrating sensors, applications and social networks and this development could also promote innovative collaborative cyber security models. In this
Henric Johnson; Niklas Lavesson; Daniela Oliveira; S. Felix Wu
HIV-associated neurocognitive disorders (HAND) are one of major comorbidities in patients with HIV-1 infection. There are currently no standardized tests for screening HAND in such patients. The sensitivity of the cognitive function tests routinely used in clinical practice, such as the Mini-Mental State Examination and the Revised Hasegawa's Dementia Scale, is inadequate to rule out HAND, even in patients with clear abnormal behavior. We report a 41-year-old man with HIV-associated dementia, the most severe form of HAND, in whom the simplified methods did not show abnormal results, and a comprehensive battery of neuropsychological tests which covering several cognitive domains was needed to detect cognitive impairment. PMID:24462448
Nakazato, Ai; Tominaga, Daisuke; Tasato, Daisuke; Miyagi, Kyoko; Nakamura, Hideta; Haranaga, Shusaku; Higa, Futoshi; Tateyama, Masao; Fujita, Jiro
BackgroundHLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess
Rachel D. Schrier; Saurabh Gupta; Patricia Riggs; Lucette A. Cysique; Scott Letendre; Hua Jin; Stephen A. Spector; Kumud K. Singh; Tanya Wolfson; Zunyou Wu; Kun Xue Hong; Xin Yu; Chuan Shi; Robert K. Heaton
SUMMARY The human immunodeficiency virus (HIV) associated tuberculosis (TB) epidemic remains an enormous challenge to TB control in countries with a high prevalence of HIV. In their 1999 article entitled ‘Will DOTS do it?’, De Cock and Chaisson questioned whether the World Health Organization’s DOTS Strategy could control this epidemic. Data over the past 10 years have clearly shown that DOTS is insufficient as a single TB control intervention in such settings because it does not address the fundamental epidemiological interactions between TB and HIV. Immunodeficiency is a principal river of this epidemic, and the solution must therefore include immune recovery using antiretroviral therapy (ART). Thus, in the era of global ART scale-up, we now ask the question, ‘Will ART do it?’ ART reduces the risk of TB by 67% (95%CI 61–73), halves TB recurrence rates, reduces mortality risk by 64–95% in cohorts and prolongs survival in patients with HIV-associated drug-resistant TB. However, the cumulative lifetime risk of TB in HIV infected individuals is a function of time spent at various CD4-defined levels of risk, both before and during ART. Current initiation of ART at low CD4 cell counts (by which time much HIV-associated TB has already occurred) and low effective coverage greatly undermine the potential impact of ART at a population level. Thus, while ART has proven a critical intervention for case management of HIV-associated TB, much of its preventive potential for TB control is currently being squandered. Much earlier ART initiation with high coverage is required if ART is to substantially influence the incidence of TB.
Lawn, S. D.; Harries, A. D.; Williams, B. G.; Chaisson, R. E.; Losina, E.; De Cock, K. M.; Wood, R.
The collapsing glomerulopathy of HIV- associated nephropathy (HIVAN) is characterized by podocyte dedifferentiation and proliferation. In af- fected glomeruli, proliferating podocytes adhere in aggregates to form glomerular pseudocrescents and fill an enlarged Bowman's space. Previously, we reported that sidekick-1 (sdk-1), an adhesion molecule of the immunoglobulin superfamily, was highly up-regulated in HIV-1 transgenic podocytes. In the current work, we explore
Lewis Kaufman; Guozhe Yang; Kayo Hayashi; James R. Ashby; Li Huang; Michael J. Ross; Mary E. Klotman; Paul E. Klotman
HIV-1 infection can be associated with neuropsychological (NP) deficits ranging from subtle to severe. The purpose of this study was to evaluate the functional, or “real-world” impact of HIV-associated NP impairment in a group of 267 HIV-infected participants. All participants received comprehensive NP, neuromedical, and standardized functional evaluations that included laboratory measures of shopping, cooking, financial management, medication management and
ROBERT K. HEATON; THOMAS D. MARCOTTE; Monica Rivera-Mindt; Joseph Sadek; DAVID J. MOORE; Heather Bentley; J. ALLEN MCCUTCHAN; Carla Reicks; Igor Grant
The aim of the present study was to investigate the nature and cognitive mechanisms of serial position learning effects in HIV-associated dementia (HAD). Participants were 16 persons with HAD, 50 non-demented persons with HIV-infection, and 50 demographically comparable HIV-seronegative participants. HAD participants, relative to both comparison groups, exhibited reduced middle region (p<0.01) and elevated recency region (p<0.05) recall on the
J. Cobb Scott; Steven Paul Woods; Katherine A. Patterson; Erin E. Morgan; Robert K. Heaton; Igor Grant; Thomas D. Marcotte
Single-center studies have reported that HIV-associated nephropathy (HIVAN) can occur in children and may have a clinical course and prognosis similar to that of adults. However, the prevalence and survival has not been reported for a national sample of children with HIVAN and end-stage renal disease (ESRD) on dialysis in the United States. We utilized the United States Renal Data
Tejinder S. Ahuja; Kevin C. Abbott; Laura Pack; Yong-Fang Kuo
Considerable attention has been focused on how the APOL1/MYH9 locus determines susceptibility to focal segmental glomerulosclerosis, including HIV-associated nephropathy (HIVAN). Atta and colleagues found that homozygosity for APOL1 risk alleles was associated with many, but not all, HIVAN cases, and that APOL1 variation failed to predict characteristics of disease. Their work gives important impetus to identify other genetic and environmental factors that may provide a 'second hit' linking HIV infection to HIVAN. PMID:22791322
Hays, Thomas; Wyatt, Christina M
HIV infection is associated with impairments in prospective memory (ProM), an aspect of episodic memory that refers to the ability to execute a future intention, such as remembering to take a medication at a specific time. The current study sought to examine the relationship between HIV-associated ProM impairment and the successful management of instrumental activities of daily living (IADLs). In
Steven Paul Woods; Jennifer E. Iudicello; Lisa M. Moran; Catherine L. Carey; Matthew S. Dawson; Igor Grant
Recurrent aphthous stomatitis (RAS) is the most common oral mucosal disorder found in men and women of all ages, races, and geographic regions. There are three forms of the lesions (minor, major, and herpetiform), with major aphthous ulcers causing significant pain and potential for scarring. In HIV-infected individuals, these ulcers occur more frequently, last longer, and produce more painful symptoms than in immunocompetent persons. In addition, they may be associated with similar ulcerations involving the esophagus, rectum, anus, and genitals. The diagnosis of HIV-induced RAS requires a careful history of the condition, and a thorough extra- and intra-oral examination. Oral mucosal biopsies are required for non-healing ulcers in order to exclude the possibility of deep fungal infections, viral infections, and neoplasms. The cause of the ulcers in HIV-positive persons has not been elucidated--local diseases, genetic, immunologic, and infectious factors all probably play a role. The goals of current treatments are to promote ulcer healing, to reduce ulcer duration and pain while maintaining nutritional intake, and to prevent or diminish the frequency of recurrence. Initial therapy for infrequent RAS recurrences includes over-the-counter topical protective and analgesic products. Initial therapy for frequent RAS outbreaks requires topical anesthetics, binding agents, and corticosteroids. Major RAS and non-healing minor or herpetiform RAS may require intralesional corticosteroids and systemic prednisone. Second-line immunomodulators for frequent and non-healing ulcers includes thalidomide and other immunomodulators. PMID:14507229
Kerr, A Ross; Ship, Jonathan A
This article reviews the clinical aspects and diagnosis of HIV-associated tuberculosis in developing countries, and summarizes WHO's recommendations for treatment. According to WHO estimates (early 1992) over 4 million persons worldwide have been infected with HIV and tuberculosis; 95% of them are in the developing countries. Clinical features of HIV-associated pulmonary tuberculosis in adults are frequently atypical, particularly in the late stage of HIV infection, with non-cavitary disease, lower lobe infiltrates, hilar lymphadenopathy and pleural effusion. More typical post-primary tuberculosis with upper lobe infiltrates and cavitations is seen in the earlier stages of HIV infection. Extrapulmonary tuberculosis is reported more frequently, despite the difficulties in diagnosing it. WHO's recent guidelines recommend 6-month short-course chemotherapy with isoniazid, rifampicin, pyrazinamide and ethambutol for patients with HIV-associated tuberculosis. The older 12-month regimen without rifampicin is much less effective. Streptomycin should not be used, because of the risk of transmitting blood-borne pathogens through contaminated needles. Thioacetazone should be abandoned, because of severe adverse reactions observed among HIV-infected patients. The roles of preventive chemotherapy and BCG vaccination for prevention of tuberculosis are also briefly discussed.
Raviglione, M. C.; Narain, J. P.; Kochi, A.
Objectives Sensory neuropathy (SN) is a common peripheral nerve complication of HIV infection and highly active antiretroviral therapy. Metabolic syndrome (MetS), a cluster of risk factors for atherosclerosis and microvascular disease, is associated with SN in HIV-uninfected (HIV?) persons. We examined if MetS or its components predispose individuals to HIV-SN. Design From a prospective multicenter cohort of 1,556 HIV+ subjects, a subgroup (n=130) with fasting laboratory tests and SN assessment was selected. Methods SN was defined by symmetrically decreased reflexes or sensation loss in the legs. MetS was defined by presence of ?3 risk factors: mean arterial pressure (MAP) ?100 mm Hg; triglycerides (TRG) ?150 mg/dl and high-density lipoprotein cholesterol (HDL-C) <40 mg/dL for males, <50 mg/dL for females; body mass index (BMI) >25 kg/m2; plasma glucose (GLU) ?100 mg/dl and self-reported diabetes (DM II). Multivariate logistic regression examined the association between HIV-SN and MetS. Results After controlling for HIV-SN risk factors- age, CD4 current, length of HIV infection, use of dideoxynucleoside reverse transcriptase inhibitors and protease inhibitors; MetS was not associated with HIV-SN (p=0.72). However, when each MetS component was assessed, elevated TRG was a significant risk factor for HIV-SN. From the larger cohort, both DM II (OR=1.4, p<0.01) and elevated TRG (OR=1.4, p=0.01) were risk factors for HIV-SN. Conclusion The risk of HIV-SN was increased for DM II and elevated TRG, but not other MetS components. Both increase the risk of SN in HIV- populations, but the mechanism(s) remains unclear.
Ances, Beau M.; Vaida, Florin; Rosario, Debralee; Marquie-Beck, Jennifer; Ellis, Ronald J.; Simpson, David M.; Clifford, David B.; McArthur, Justin C.; Grant, Igor; McCutchan, J. Allen
Both practitioners and academics often frown on pragmatic and opportunistic reuse. Large organizations report that structured reuse methods and software product lines are often the way to go when it comes to efficient software reuse. However, opportunistic that is, nonstructured reuse has proven profitable for small to medium-sized organizations. Here, we describe two start-ups that have opportunistically and pragmatically developed
Slinger Jansen; Sjaak Brinkkemper; Ivo Hunink; Cetin Demir
We investigated the prevalence of HIV-associated periodontal disease in an AIDS clinic in San Francisco. Patient recruitment occurred over 6 months with 90% patient participation. In 136 patients, three forms of periodontal disease were recorded: HIV-associated gingivitis (HIV-G), HIV-associated periodontitis (HIV-P), and conventional non-HIV-associated periodontal disease. Diagnosis was based on defined clinical criteria established before the study began. For the HIV-associated diseases, two sets of diagnostic criteria were used. One consisted of clinical signs that included bleeding on probing, pocket depth, and attachment loss; and the other consisted of the same signs but did not require probing (the measurement of the depth of the gingival sulcus). Using the first set of these criteria, HIV-G was diagnosed in 42 patients [31%; 95% confidence interval (CI) 23 to 39%] and HIV-P in 5 (4%; 95% CI 1 to 7%). Using the second set, 68 patients were diagnosed with HIV-G (50%; 95% CI 42 to 58%) and 8 with HIV-P (6%; 95% CI 2 to 10%). All other categories of periodontal disease that were non-HIV-associated were diagnosed in 60 (44%) of patients. These results indicate that while the prevalence of HIV-P is low, the prevalence of HIV-G and conventional periodontal disease among HIV-infected individuals is high and should be considered in the dental care of these patients. PMID:1560345
Masouredis, C M; Katz, M H; Greenspan, D; Herrera, C; Hollander, H; Greenspan, J S; Winkler, J R
Background & Aim. Liver disease is commonly present in human immunodeficiency virus (HIV) infection. The aim was to determine the frequency of liver enlargement and its association with opportunistic infections in patients with HIV infection. Patients and methods. A total of 400 HIV-infected patients were investigated. Commercial kits (Ortho EIA; BioRad, ELISA) were used for detection of serum specific antibodies
Dragica Terzic; Branko Brmbolic; Djordje Jevtovic; Brankica Dupanovic; Milos Kora; Dubravka Selemovic; Neda Svirtlih; Nenad Draskovic; Boban Mugosa; Ivan Boricic; Zoran Terzic
We are developing technologies to increase the autonomous capabilities of future rover missions. Our objectives are to make rovers easier to command and to enable them to make more effective use of rover resources when problems arise or when things go better than expected. We will demonstrate OASIS (Onboard Analysis Science Investigation System) which combined planning and scheduling techniques with machine learning to enable rovers to perform robust and opportunistic science operations.
Gaines, Daniel M.; Estlin, Tara; Chouinard, Caroline; Castano, Rebecca; Castano, Andres; Bornstein, Ben; Anderson, Robert C.; Judd, Michele; Nesnas, Issa; Rabideau, Gregg
Background: HIV-associated lipodystrophy syndrome (LDS) as a long-term side effect of HAART is becoming increasingly important and negatively\\u000a affects adherence to medication. Currently, an effective therapy is not available. There is some evidence that the drug class\\u000a of thiazolidindiones might be effective in the treatment of LDS.\\u000a \\u000a \\u000a \\u000a Patients and Methods: Prospective open-label study with 20 HIV-infected patients suffering from severe LDS. Patients
T. Feldt; M. Oette; A. Kroidl; K. Goebels; R. Fritzen; J. Kambergs; G. Kappert; C. Vogt; M. Wettstein; D. Häussinger
Neurocognitive assessment plays a central role in the diagnosis of human immunodeficiency virus- (HIV) associated neurocognitive disorders (HAND). The history of diagnostic categories and labeling of HIV-related neurological disorders is briefly presented. The current diagnostic nomenclature of HAND and the role of neurocognitive assessment is examined. Though neurocognitive testing is sensitive in assessing a broad range of cognitive impairments, neurocognitive testing is not specific to HAND without consideration of the impact on functional status, as well as confounding factors, including premorbid status. PMID:24715485
Robertson, Kevin; Yosief, Sarah
Following the publication of the Chief Medical Officer's report on chlamydial screening, we identified the sexual health of young women as an area for concern. As part of our review we decided to opportunistically search for chlamydial genital infections using a non-invasive technique. Sexually active women under 25 years of age were invited to submit a first void urine sample for polymerase chain reaction analysis. Over the period of a year we found out that 10.9% of sexually active young women tested positive for chlamydia in our practice.
Tobin, C; Aggarwal, R; Clarke, J; Chown, R; King, D
With the present progress in transplantation procedures, there is an improvement in patient and allograft survival. However, the immunosuppression necessary to sustain the allograft predisposes these transplant recipients to infection, which is now a significant cause of morbidity and mortality. We describe a case of a 30-year-old renal transplant recipient with two opportunistic infections, namely, primary cutaneous aspergillosis and intestinal tuberculosis, with terminal enterococcal pleuritis and peritonitis. Control of the degree of immunosuppression, and prompt recognition and treatment of infection are vital for successful organ transplantation.
Mysorekar, Vijaya V.; Eshwarappa, Mahesh; Lingaraj, Umesh
Women account for half of the global human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) infections. Heterosexual contact is the leading risk factor in women. Over 50% of patients are significantly immunosuppressed at the time of diagnosis. Women with advanced HIV infection are at a risk for opportunistic infections (OIs). OIs lead to significant morbidity and cost. Some of OIs may impact women more significantly than men, that is, human papillomavirus infection and cervical cancer. OIs during pregnancy can increase the risk of maternal-to-child transmission of HIV and some OIs, such as Hepatitis C. This chapter will review of OIs that are most important in women's health. PMID:23090461
Lazenby, Gweneth B
This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated Neurocognitive Disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consisting of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with CSF amyloid.
Morgan, E.E.; Woods, S.P.; Letendre, S.L.; Franklin, D.R.; Bloss, C.; Goate, A.; Heaton, R.K.; Collier, A.C.; Marra, C.M.; Gelman, B.B.; McArthur, J.C.; Morgello, S.; Simpson, D.M.; McCutchan, J.A.; Ellis, R.J.; Abramson, I.; Gamst, A.; Fennema-Notestine, C.; Smith, D.M.; Grant, I.; Vaida, F.; Clifford, D.B.
Strategic monitoring during a delay interval is theorized to be an essential feature of time-based prospective memory (TB PM), the cognitive architecture of which is thought to rely heavily on frontostriatal systems and executive functions. This hypothesis was examined in 55 individuals with HIV-associated neurocognitive disorders (HAND) and 108 seronegative comparison participants who were administered the Memory for Intentions Screening Test (MIST), during which time monitoring (clock checking) behavior was measured. Results revealed a significant interaction between HAND group and the frequency of clock checking, in which individuals with HAND monitored checked the clock significantly less often than the comparison group across the TB PM retention intervals of the MIST. Subsequent analyses in the HAND sample revealed that the frequency of clocking checking was positively related to overall TB performance, as well as to standard clinical measures of retrospective memory and verbal fluency. These findings add support to a growing body of research elucidating TB PM’s reliance on strategic monitoring processes dependent upon intact frontostriatal systems. HIV-associated TB strategic time monitoring deficits may manifest in poorer functioning outcomes, including medication non-adherence and dependence in activities of daily living. Future research is needed to further delineate the cognitive mechanisms underlying strategic time monitoring in order to advise rehabilitation strategies for reducing HAND related TB PM deficits.
Doyle, Katie L.; Loft, Shayne; Morgan, Erin E.; Weber, Erica; Cushman, Clint; Johnston, Elaine; Grant, Igor; Woods, Steven Paul
HIV infection is associated with impairments in prospective memory (ProM), an aspect of episodic memory that refers to the ability to execute a future intention, such as remembering to take a medication at a specific time. The current study sought to examine the relationship between HIV-associated ProM impairment and the successful management of independent activities of daily living (IADLs). In a cohort of 66 HIV-infected individuals, ProM accounted for a significant proportion of variance in self-reported IADL dependence over and above that which was explained by retrospective memory and current affective distress. Analysis of component cognitive processes revealed that the relationship between HIV-associated ProM deficits and IADL dependence was driven by impaired cue detection and self-initiated intention retrieval. Results were not better explained by demographic factors, HIV disease severity, psychiatric comorbidity, or substance use. Collectively, these data support the potential incremental ecological validity of ProM as a predictor of dependence in IADLs among persons living with HIV infection.
Woods, Steven Paul; Iudicello, Jennifer E.; Moran, Lisa M.; Carey, Catherine L.; Dawson, Matthew S.; Grant, Igor
Abstract Given the detrimental effects of HIV-associated anemia on morbidity, we determined factors associated with anemia after 96 weeks of antiretroviral therapy (ART) across age groups. An HIV-positive cohort (n=3,580) of children age 5-14, reproductive age adults 18-49, and older adults ?50 from two randomized trials in Uganda and Zimbabwe were evaluated from initiation of therapy through 96 weeks. We conducted logistic and multinomial regression to evaluate common and differential determinants for anemia at 96 weeks on therapy. Prior to initiation of ART, the prevalence of anemia (age 5-11 <10.5?g/dl, 12-14 <11?g/dl, adult females <11?g/dl, adult males <12?g/dl) was 43%, which decreased to 13% at week 96 (p<0.001). Older adults had a significantly higher likelihood of anemia compared to reproductive age adults (OR 2.60, 95% CI 1.44-4.70, p=0.002). Reproductive age females had a significantly higher odds of anemia compared to men at week 96 (OR 2.56, 95% CI 1.92-3.40, p<0.001), and particularly a greater odds for microcytic anemia compared to males in the same age group (p=0.001). Other common factors associated with anemia included low body mass index (BMI) and microcytosis; greater increases in CD4 count to week 96 were protective. Thus, while ART significantly reduced the prevalence of anemia at 96 weeks, 13% of the population continued to be anemic. Specific groups, such as reproductive age females and older adults, have a greater odds of anemia and may guide clinicians to pursue further evaluation and management. PMID:24506102
Jaganath, Devan; Walker, A Sarah; Ssali, Francis; Musiime, Victor; Kiweewa, Francis; Kityo, Cissy; Salata, Robert; Mugyenyi, Peter
In this paper, we study an opportunistic scheduling scheme for the TDMA wireless network with relay stations. We model the time-varying channel condition of a wireless link as a stochastic process. Based on this model, we formulate an optimization problem for the opportunistic scheduling scheme that maximizes the expected system throughput while satisfying the QoS constraint of each user. In the opportunistic scheduling scheme for the system without relay stations, each user has only one communication path between the base station and itself, and thus only user selection is considered. However, in our opportunistic scheduling scheme for the system with relay stations, since there may exist multiple paths between the base station and a user, not only user selection but also path selection for the scheduled user is considered. In addition, we also propose an opportunistic time-sharing method for time-slot sharing between base station and relay stations. With the opportunistic time-sharing method, our opportunistic scheduling provides opportunistic resource sharing in three places in the system: user selection in a time-slot, path selection for the selected user, and time-slot sharing between base station and relay stations. Simulation results show that as the number of places that opportunistic resource sharing is applied to increases, the performance improvement also increases.
Kwon, Jeong-Ahn; Lee, Jang-Won
Diarrhea is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. Opportunistic enteric parasitic infections are encountered in 30-60% of HIV seropositive patients in developed countries and in 90% of patients in developing countries. Once the CD4+ cell count drops below 200 cells/?l, patients are considered to have developed acquired immunodeficiency syndrome (AIDS), with the risk of an AIDS-defining illness or opportunistic infection significantly increasing. Opportunistic enteric parasites encountered in these patients are Cryptosporidium, Isospora, Cyclospora, and microsporidia; as well as those more commonly associated with gastrointestinal disease, for example, Giardia intestinalis, Entamoeba histolytica, Strongyloides stercoralis, and also rarely Balantidium coli. In view of AIDS explosion in India, opportunistic enteric parasites are becoming increasingly important and it has to be identified properly. Apart from wet mounts, concentration methods for stool samples and special staining techniques for identification of these parasites, commercially available fecal immunoassays are widely available for the majority of enteric protozoa. Molecular methods such as polymerase chain reaction (PCR), PCR-restriction fragment length polymorphism, flow cytometry, and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE), have also come in the pipeline for early diagnosis of these infections. Proper disposal of the feces to prevent contamination of the soil and water, boiling/filtering drinking water along with improved personal hygiene might go a long way in preventing these enteric parasitic infections.
This review focuses on free-living amoebae, widely distributed in soil and water, causing opportunistic and non-opportunistic infections in humans: Acanthamoeba spp., Balamuthia mandrillaris, Naegleria fowleri, and Sappinia diploidea. Diseases include primary amoebic meningoencephalitis (N. fowleri), granulomatous amoebic encephalitis, cutaneous and nasopharyngeal infections (Acanthamoeba spp., Balamuthia mandrillaris, S. diploidea), and amoebic keratitis (Acanthamoeba spp). Acanthamoeba, Balamuthia, and Naegleria have been repeatedly isolated; S. diploidea has been reported only once, from a brain infection. Antimicrobial therapy for these infections is generally empirical and patient recovery often problematic. N. fowleri is highly sensitive to the antifungal agent amphotericin B, but delay in diagnosis and the fulminant nature of the disease result in few survivors. Encephalitis and other infections caused by Acanthamoeba and Balamuthia have been treated, more or less successfully, with antimicrobial combinations including sterol-targeting azoles (clotrimazole, miconazole, ketoconazole, fluconazole, itraconazole), pentamidine isethionate, 5-fluorocytosine, and sulfadiazine. The use of drug combinations addresses resistance patterns that may exist or develop during treatment, ensuring that at least one of the drugs may be effective against the amoebae. Favorable drug interactions (additive or synergistic) are another potential benefit. In vitro drug testing of clinical isolates points up strain and species differences in sensitivity, so that no single drug can be assumed effective against all amoebae. Another complication is risk of activation of dormant cysts that form in situ in Acanthamoeba and Balamuthia infections, and which can lead to patient relapse following apparently effective treatment. This is particularly true in Acanthamoeba keratitis, a non-opportunistic infection of the cornea, which responds well to treatment with chlorhexidine gluconate and polyhexamethylene biguanide, in combination with propamidine isothionate (Brolene), hexamidine (Désomodine), or neomycin. Acanthamoeba spp. may also be carriers of endosymbiotic bacteria (Legionella and Legionella-like pathogens) and have been implicated in outbreaks of pneumonias in debilitated hosts. As with other infectious diseases, recovery is dependent not only on antimicrobial therapy, but also on patient's immune status, infective dose and virulence of the ameba strain, and on how early the disease is diagnosed and drug therapy initiated. PMID:15072770
Schuster, Frederick L; Visvesvara, Govinda S
Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected (HIV?) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed the prevalence, nature, and clinical correlates of HAND. We used comparable methods of subject screening and assessments to classify neurocognitive impairment (NCI) in large groups of HIV + and HIV ? participants from the pre-CART era (1988–1995; N?=?857) and CART era (2000–2007; N?=?937). Impairment rate increased with successive disease stages (CDC stages A, B, and C) in both eras: 25%, 42%, and 52% in pre-CART era and 36%, 40%, and 45% in CART era. In the medically asymptomatic stage (CDC-A), NCI was significantly more common in the CART era. Low nadir CD4 predicted NCI in both eras, whereas degree of current immunosuppression, estimated duration of infection, and viral suppression in CSF (on treatment) were related to impairment only pre-CART. Pattern of NCI also differed: pre-CART had more impairment in motor skills, cognitive speed, and verbal fluency, whereas CART era involved more memory (learning) and executive function impairment. High rates of mild NCI persist at all stages of HIV infection, despite improved viral suppression and immune reconstitution with CART. The consistent association of NCI with nadir CD4 across eras suggests that earlier treatment to prevent severe immunosuppression may also help prevent HAND. Clinical trials targeting HAND prevention should specifically examine timing of ART initiation.
Franklin, Donald R.; Ellis, Ronald J.; McCutchan, J. Allen; Letendre, Scott L.; LeBlanc, Shannon; Corkran, Stephanie H.; Duarte, Nichole A.; Clifford, David B.; Woods, Steven P.; Collier, Ann C.; Marra, Christina M.; Morgello, Susan; Mindt, Monica Rivera; Taylor, Michael J.; Marcotte, Thomas D.; Atkinson, J. Hampton; Wolfson, Tanya; Gelman, Benjamin B.; McArthur, Justin C.; Simpson, David M.; Abramson, Ian; Gamst, Anthony; Fennema-Notestine, Christine; Jernigan, Terry L.; Wong, Joseph; Grant, Igor
Opportunistic networks are characterized by inter- mittent connectivity among mobile devices that occurs during their opportunistic contacts. With the increasing number of ca- pable wireless devices and hence increasing potential formation of opportunistic networks, enabling applications over opportunistic networks has become critical. In this paper, we design and analyze a mobile file sharing system over opportunistic networks using Bluetooth technology.
Shanshan Lu; Gautam Chavan; Yanliang Liu; Yonghe Liu
In this issue of Clinical and Vaccine Immunology, Siev and colleagues present an evaluation of antibody responses to four immunodominant proteins of Mycobacterium tuberculosis in patients with HIV-associated pulmonary tuberculosis (TB) in South Africa (M. Siev, D. Wilson, S. Kainth, V. O. Kasprowicz, C. M. Feintuch, E. Jenny-Avital, and J. J. Achkar, 21:791-798, 2014, doi:http://dx.doi.org/10.1128/CVI.00805-13). This commentary discusses the enormous need for simple point-of-care assays for tuberculosis (TB) diagnosis in patients with and without HIV coinfection in high-burden settings and considers the potential role of serological assays and the huge challenges inherent in developing and validating such assays. PMID:24739979
Lawn, Stephen D
In this paper, performance of wireless opportunistic schedulers in multiuser systems is studied under a dynamic data arrival setting. Different from the previous studies which mostly focus on the network stability and the worst case scenarios, we emphasize on the average performance of wireless opportunistic schedulers. We first develop a framework based on Markov queueing model and then analyze it
Lei Lei; Chuang Lin; Jun Cai; Xuemin Shen
Recently, the idea of opportunistic routing has been widely explored to improve the performance of multi-hop wireless mesh networks. Most of the previous studies use simulations or empirical measurements to evaluate the performance gain of opportunistic routing and therefore are limited to relatively few types of scenarios. In this paper, we take an analytical approach to study the potential gain
Chun-pong Luk; Wing-Cheong Lau; On-ching Yue
In this paper, a new opportunistic source selection (OSS) protocol is studied in bidirectional cooperative networks. Unlike existing protocols, this protocol exploits multiuser nature of the bidirectional cooperative networks and it opportunistically supports two traffic flows based on instantaneous channel conditions. This makes the OSS protocol much more reliable than existing protocols. We derive a lower bound of the outage
Zhihang Yi; Il-Min Kim
In this paper, a new opportunistic source selection (OSS) protocol is studied in bidirectional cooperative networks. Unlike existing protocols, this protocol exploits multiuser nature of the bidirectional cooperative networks and it opportunistically supports two traffic flows based on instantaneous channel conditions. This makes the OSS protocol much more reliable than existing protocols. In order to show the performance improvement, we
Zhihang Yi; Il-Min Kim
Opportunistic networks are one of the most interesting evolutions of MANETs. In opportunistic networks, mobile nodes are enabled to communicate with each other even if a route connecting them never exists. Furthermore, nodes are not supposed to possess or acquire any knowledge about the network topology, which (instead) is necessary in traditional MANET routing protocols. Routes are built dynamically, while
Luciana Pelusi; Andrea Passarella; Marco Conti
Objective: To evaluate the efficacy and safety of minocycline in the management of HIV-associated cognitive impairment. Methods: We enrolled HIV-positive participants with a CD4 count of 250 to 500 cells/?L in a randomized, double-blind, placebo-controlled study. They received 100 mg of minocycline or matching placebo orally every 12 hours for 24 weeks. Cognitive function was measured using the Uganda Neuropsychological Test Battery Summary Measure (U NP Sum) and the Memorial Sloan-Kettering (MSK) scale. The primary efficacy measure was the 24-week change in an average of 9 standardized U NP Sum z scores. Results: Seventy-three participants were enrolled. Of these, 90% were female, 49% were between the ages 30 and 39 years, and 74% had 6 or more years of education. One participant had MSK score of stage 1 (i.e., mild HIV dementia), and 72 participants had MSK stage 0.5 (i.e., equivocal or subclinical dementia) at the baseline evaluation. The minocycline effect on the 24-week change of the U NP Sum compared with placebo was 0.03 (95% confidence interval ?0.51, 0.46; p = 0.37). Conclusion: Minocycline was safe and well tolerated in HIV-positive individuals. However, it did not improve HIV-associated cognitive impairment. Classification of evidence: This study provides Class II evidence that 100 mg of minocycline given orally every 12 hours for 24 weeks had no significant effect compared with placebo in the improvement of cognitive function in antiretroviral therapy–naive, HIV-positive patients.
Miyahara, Sachiko; Evans, Scott; Lee, Anthony; Musisi, Seggane; Katabira, Elly; Robertson, Kevin; Ronald, Allan; Clifford, David B.; Sacktor, Ned
This is a cross-sectional, observational study to evaluate the hypothesis that HIV-seropositive (HIV+) apolipoprotein E4 (APOE4) carriers are at increased risk for HIV-associated neurocognitive disorders (HAND) compared to APOE4 noncarriers with HIV in the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) Group sample. APOE genotype was determined in 466 CHARTER participants with varying disease stages and histories of antiretroviral treatment who did not have severe psychiatric or medical comorbid conditions that preclude diagnosis of HAND. HAND diagnoses were based on results of comprehensive neurobehavioral evaluation and use of current neuroAIDS diagnostic criteria. HAND status consists of two levels: neuropsychologically normal status (i.e., no HAND) and any HAND diagnosis (i.e., asymptomatic neurocognitive impairment, minor neurocognitive disorder, HIV-associated dementia). Logistic regression analyses revealed no association between APOE4 carrier status and HAND, and there were no interactions between APOE4 carrier status and ethnicity, age, substance use disorders, duration of infection, or nadir CD4. Results did not differ when analysis was restricted to symptomatic HAND, and no APOE4 gene dose-dependent relationship to HAND emerged. APOE4 status was not associated with concurrent HAND in this large, well-characterized sample. This does not preclude emergence of an association between APOE4 status and HAND as this population ages. Prospective, longitudinal studies are needed to examine APOE4 as a risk factor for neurocognitive decline, incident HAND at older ages, and potential associations with cerebrospinal fluid amyloid. PMID:23408335
Morgan, E E; Woods, S P; Letendre, S L; Franklin, D R; Bloss, C; Goate, A; Heaton, R K; Collier, A C; Marra, C M; Gelman, B B; McArthur, J C; Morgello, S; Simpson, D M; McCutchan, J A; Ellis, R J; Abramson, I; Gamst, A; Fennema-Notestine, C; Smith, D M; Grant, I; Vaida, F; Clifford, D B
Executive dysfunction remains among the most prevalent cognitive domains impaired in persons with HIV-associated neurocognitive disorders (HAND). However, little is known specifically about the cognitive architecture or everyday functioning implications of planning, which is an aspect of executive functions involving the identification, organization, and completion of sequential behaviours toward the accomplishment of a goal. The current study examined these issues
Jordan E. Cattie; Katie Doyle; Erica Weber; Igor Grant; Steven Paul Woods
Microglial dysfunction is associated with the pathogenesis and progression of a number of neurodegenerative disorders including HIV associated dementia (HAD). HIV promotion of an M1 antigen presenting cell (APC) - like microglial phenotype, through the promotion of CD40 activity, may impair endogenous mechanisms important for amyloid- beta (A?) protein clearance. Further, a chronic pro-inflammatory cycle is established in this manner.
Jon Salemi; Demian F Obregon; Anthony Cobb; Spenser Reed; Edin Sadic; Jingji Jin; Francisco Fernandez; Jun Tan; Brian Giunta
Invasive fungal infections are a significant health problem in immunocompromised patients. The clinical manifestations vary and can range from colonization in allergic bronchopulmonary disease to active infection in local aetiologic agents. Many factors influence the virulence and pathogenic capacity of the microorganisms, such as enzymes including extracellular phospholipases, lipases and proteinases, dimorphic growth in some Candida species, melanin production, mannitol secretion, superoxide dismutase, rapid growth and affinity to the blood stream, heat tolerance and toxin production. Infection is confirmed when histopathologic examination with special stains demonstrates fungal tissue involvement or when the aetiologic agent is isolated from sterile clinical specimens by culture. Both acquired and congenital immunodeficiency may be associated with increased susceptibility to systemic infections. Fungal infection is difficult to treat because antifungal therapy for Candida infections is still controversial and based on clinical grounds, and for molds, the clinician must assume that the species isolated from the culture medium is the pathogen. Timely initiation of antifungal treatment is a critical component affecting the outcome. Disseminated infection requires the use of systemic agents with or without surgical debridement, and in some cases immunotherapy is also advisable. Preclinical and clinical studies have shown an association between drug dose and treatment outcome. Drug dose monitoring is necessary to ensure that therapeutic levels are achieved for optimal clinical efficacy. The objectives of this review are to discuss opportunistic fungal infections, diagnostic methods and the management of these infections.
Badiee, Parisa; Hashemizadeh, Zahra
Majority of countries don’t have an organized screening program.It is not conducted or is in form of opportunistic screening. An organized screening for cervical cancer in developed countries is resulted in significant decrease of incidence and mortality. In our country there is no an organized screening program. Even it is carried out,it is in form of opportunistic screening. Consequently,the number of cervical carcinoma (Ca PVU) is the largest in Europe. The goal of this research is accomplishing possibilities and limits of opportunistic screening in Velika Plana.
We design opportunistic spectrum access strategies for improving spectrum efficiency. In each slot, a secondary user chooses a subset of channels to sense and decides whether to access based on the sensing outcomes. Incorporating the secondary user's resi...
A. Swami Q. Zhao Y. Chen
Despite modern antiretroviral therapy, HIV-associated sensory neuropathy affects over 50 % of HIV patients. The clinical expression of HIV neuropathy is highly variable: many individuals report few symptoms, but about half report distal neuropathic pain (DNP), making it one of the most prevalent, disabling, and treatment-resistant complications of HIV disease. The presence and intensity of pain is not fully explained by the degree of peripheral nerve damage, making it unclear why some patients do, and others do not, report pain. To better understand central nervous system contributions to HIV DNP, we performed a cross-sectional analysis of structural magnetic resonance imaging volumes in 241 HIV-infected participants from an observational multi-site cohort study at five US sites (CNS HIV Anti-Retroviral Treatment Effects Research Study, CHARTER). The association between DNP and the structural imaging outcomes was investigated using both linear and nonlinear (Gaussian Kernel support vector) multivariable regression, controlling for key demographic and clinical variables. Severity of DNP symptoms was correlated with smaller total cerebral cortical gray matter volume (r?=?-0.24; p?=?0.004). Understanding the mechanisms for this association between smaller total cortical volumes and DNP may provide insight into HIV DNP chronicity and treatment-resistance. PMID:24549970
Keltner, John R; Fennema-Notestine, Christine; Vaida, Florin; Wang, Dongzhe; Franklin, Donald R; Dworkin, Robert H; Sanders, Chelsea; McCutchan, J Allen; Archibald, Sarah L; Miller, David J; Kesidis, George; Cushman, Clint; Kim, Sung Min; Abramson, Ian; Taylor, Michael J; Theilmann, Rebecca J; Julaton, Michelle D; Notestine, Randy J; Corkran, Stephanie; Cherner, Mariana; Duarte, Nichole A; Alexander, Terry; Robinson-Papp, Jessica; Gelman, Benjamin B; Simpson, David M; Collier, Ann C; Marra, Christina M; Morgello, Susan; Brown, Greg; Grant, Igor; Atkinson, J Hampton; Jernigan, Terry L; Ellis, Ronald J
Progranulin (PGRN) is a highly unusual molecule with both neuronal and microglial expression with two seemingly unrelated functions, i.e., as a neuronal growth factor and a modulator of neuroinflammation. Haploinsufficiency due to loss of function mutations lead to a fatal presenile dementing illness (frontotemporal lobar degeneration), indicating that adequate expression of PGRN is essential for successful aging. PGRN might be a particularly relevant factor in the pathogenesis of HIVencephalitis (HIVE) and HIV-associated neurocognitive disorders (HAND). We present emerging data and a review of the literature which show that cells of myeloid lineage such as macrophages and microglia are the primary sources of PGRN and that PGRN expression contributes to pathogenesis of CNS diseases. We also present evidence that PGRN is a macrophage antiviral cytokine. For example, PGRN mRNA and protein expression are significantly upregulated in brain specimens with HIVE, and in HIV infected microglia in vitro. Paradoxically, our preliminary CHARTER data analyses indicate that lower PGRN levels in CSF trended towards an association with HAND, particularly in those without detectable virus. Based upon these findings, we introduce the hypothesis that PGRN plays dual roles in modulating antiviral immunity and neuronal dysfunction in the context of HIV infection. In the presence of active viral replication, PGRN expression is increased functioning as an anti-viral factor as well as a neuroprotectant. In the absence of active HIV replication, ongoing inflammation or other stressors suppress PGRN production from macrophages/microglia contributing to neurocognitive dysfunction. We propose. PMID:23959579
Suh, Hyeon-Sook; Gelman, Benjamin B; Lee, Sunhee C
Serology data are limited for patients with sputum smear-negative HIV-associated active tuberculosis (TB). We evaluated the serum antibody responses against the mycobacterial proteins MPT51, MS, and echA1 and the 38-kDa protein via enzyme-linked immunosorbent assay (ELISA) in South African (S.A.) HIV-positive (HIV(+)) smear-negative TB patients (n = 56), U.S. HIV(+) controls with a positive tuberculin skin test (TST(+); n = 21), and S.A. HIV-negative (HIV(-)) (n = 18) and HIV(+) (n = 24) controls. TB patients had positive antibody reactivity against MPT51 (73%), echA1 (59%), MS (36%), and the 38-kDa protein (11%). Little reactivity against MPT51 and echA1 was observed in control groups at low risk for TB, i.e., S.A. HIV(-) (0% and 6%, respectively), and at moderate risk for TB development, i.e., U.S. HIV(+) TST(+) controls (14% and 10%, respectively). By contrast, more reactivity was detected in the S.A. HIV(+) control group at higher risk for TB (25% and 45%, respectively). Our data hold promise that antibody detection against MPT51 and echA1 might have adjunctive value in the detection of HIV(+) smear-negative TB and might reflect increasing Mycobacterium tuberculosis infection activity in asymptomatic HIV(+) individuals. PMID:24671553
Siev, Michael; Wilson, Douglas; Kainth, Supreet; Kasprowicz, Victoria O; Feintuch, Catherine M; Jenny-Avital, Elizabeth R; Achkar, Jacqueline M
Although HIV-associated multicentric Castleman disease (HIV-MCD) is not classified as an AIDS-defining illness, mortality is high and progression to lymphoma occurs frequently. At present, there is no widely accepted recommendation for the treatment of HIV-MCD. In this retrospective (1998-2010), multicentric analysis of 52 histologically proven cases, outcome was analyzed with respect to the use of different MCD therapies and potential prognostic factors. After a mean follow-up of 2.26 years, 19 of 52 patients died. Median estimated overall survival (OS) was 6.2 years. Potential risk factors, such as older age, previous AIDS, or lower CD4 T cells had no impact on OS. Treatment was heterogeneous, consisting of cytostatic and/or antiviral agents, rituximab, or combinations of these modalities. There were marked differences in the outcome when patients were grouped according to MCD treatment. Patients receiving rituximab-based regimens had higher complete remission rates than patients receiving chemotherapy only. The mean estimated OS in patients receiving rituximab alone or in combination with cytostatic agents was not reached, compared with 5.1 years (P = .03). Clinical outcome and overall survival of HIV-MCD have markedly improved with rituximab-based therapies, considering rituximab-based therapies (with or without cytostatic agents) to be among the preferred first-line options in patients with HIV-MCD. PMID:21778341
Hoffmann, Christian; Schmid, Holger; Müller, Markus; Teutsch, Christian; van Lunzen, Jan; Esser, Stefan; Wolf, Timo; Wyen, Christoph; Sabranski, Michael; Horst, Heinz-August; Reuter, Stefan; Vogel, Martin; Jäger, Hans; Bogner, Johannes; Arasteh, Keikawus
Human immunodeficiency virus (HIV) infection started in Africa circa 1930. South Africa has the highest prevalence rate in the world. Although reports of HIV-associated nephropathy (HIVAN) appeared in the early 1980s, the earliest report from sub-Saharan Africa (SSA) came in 1994. Geographical, socioeconomic, political, and ethical factors have worked in concert to shape the character of HIV disease as it is seen in SSA. Political leaders within SSA have, through their actions, significantly contributed to the incidence of HIV infection. Black females, who often face cultural suppression and disadvantage, have a higher prevalence of HIV than males. Too few studies and outcomes data have bedeviled the statistics in SSA in relation to HIVAN prevalence and its management. Much of what is written is approximation and anecdotal. The largest reliable biopsy series comes from the University of Cape Town, where a workable classification of HIVAN has been developed to enable standardization of terminology. Histologic and clinical prognostic indicators with outcomes have been evaluated using this classification. Patients with HIV who present with acute kidney injury appear to have mainly acute tubular necrosis due to sepsis, dehydration, and nephrotoxic drugs. Since the rollout of combination antiretroviral therapy, the extent of HIV infection and kidney disease continues to be modified and possibly retarded. PMID:22901595
Swanepoel, Charles R; Wearne, Nicola; Duffield, Maureen S; Okpechi, Ikechi G
Compared with healthy controls, HIV patients already have abnormal lipoprotein concentrations before the initiation of highly active antiretroviral therapy (HAART), which worsen with the therapy. HAART-associated dyslipidaemia features fundamental proatherogenic changes such as increased plasma triglycerides (TGs), increased total cholesterol and low-density lipoprotein cholesterol as well as decreased high-density lipoprotein cholesterol (HDL-C). The current guidelines for managing HIV-associated dyslipidaemia recommend diet and exercise counselling, alteration of HAART regimen or addition of lipid-lowering medications such as statins, fibrates and omega-3 (OM-3) fatty acids. Given that cardiovascular risk significantly increases with elevated lipid levels, selecting a drug to manage dyslipidaemia is particularly important. A case is described of an HIV patient who had severe hypertriglyceridaemia and bad metabolic parameters treated with rosuvastatin and OM-3 fatty acids. So we obtained a more marked reduction of TG levels than has never been described before in the literature, associated with a significant increase in HDL-C levels. PMID:19625595
Falasca, K; Ucciferri, C; Mancino, P; Pizzigallo, E; Calza, L; Vecchiet, J
Individuals infected with HIV show moderate deficits in decision-making, but the ecological relevance of such deficits on everyday functioning has not previously been described. This study sought to examine the magnitude, cognitive correlates, and everyday functioning impact of risky decision-making impairment in HIV-associated neurocognitive disorders (HAND). Participants included 68 HIV+ individuals with HAND, 78 HIV+ individuals without HAND, and 51 HIV- comparison participants, who were administered the Iowa Gambling Task (IGT) alongside a comprehensive neuropsychological test battery and self-report measures assessing aspects of everyday functioning. HIV+ individuals with HAND performed more poorly on the IGT relative to the other two groups, most notably during the last three trial blocks. Within the HIV+ group, IGT performance during the last three trial blocks was most strongly associated with cognitive flexibility, but was not significantly related to declines in instrumental activities of daily living (IADLs), unemployment, or medication non-adherence. While overall IGT performance across the last three trial blocks may be helpful diagnostically in identifying decision-making impairment in HAND, examination of alternate, more specific metrics (e.g., individual deck selections across trial blocks) may be more useful in delineating the role of poor decision-making in HIV-related disability, and should be examined in future research.
Iudicello, Jennifer E.; Woods, Steven Paul; Cattie, Jordan E.; Doyle, Katie; Grant, Igor
HIV-seropositive individuals with low cognitive reserve are at high risk for developing HIV-associated neurocognitive disorders (HAND). The present study evaluated the hypothesis that cognitive reserve would also play a unique role in the expression of everyday functioning complications among those with HAND (i.e., syndromic versus subsyndromic impairment). Eighty-six individuals with HIV infection were evaluated; 53 individuals evidenced normal neurocognitive performance, 16 had subsyndromic HAND (i.e., Asymptomatic Neurocognitive Impairment), and 17 were diagnosed with a syndromic HAND based on a comprehensive neurobehavioral evaluation. Cognitive reserve represented a combined score including years of education, estimated verbal IQ, and highest occupational attainment. The groups were comparable (e.g. demographics), and the HAND groups had similar rates of global neurocognitive impairment. The Syndromic HAND group evidenced lower reserve scores relative to both other groups, suggesting that HIV-infected individuals with high cognitive reserve more effectively counteract their neurocognitive impairment to maintain independence in daily living activities.
Morgan, Erin E.; Woods, Steven Paul; Smith, Christine; Weber, Erica; Scott, J. Cobb; Grant, Igor
BACKGROUND AND PURPOSE Quantitative MR imaging strategies may have considerable potential for in vivo assessment of neuropathologic changes associated with HIV. This investigation evaluated the prognostic significance of whole brain histogram-derived diffusion tensor imaging indices with respect to severity of cognitive impairment and measures of clinical status in cases of HIV. METHODS Quantitative indices derived with diffusion tensor imaging, including whole brain fractional anisotropy and the apparent diffusion coefficient, were compared for six patients with HIV and eight control volunteers. Relationships between whole brain indices and specific measures of dementia severity and clinical status were examined. RESULTS Whole brain fractional anisotropy was reduced in patients with HIV and was significantly associated with severity of dementia, as indicated by several widely used clinical and functional status measures. Summary fractional anisotropy measures were more prognostic of dementia status than were apparent diffusion coefficient measures. CONCLUSION Findings from this investigation support the use of diffusion tensor imaging for noninvasive MR imaging measurement of neuropathologic changes in studies of HIV-associated cognitive impairment.
Ragin, Ann B.; Storey, Pippa; Cohen, Bruce A.; Epstein, Leon G.; Edelman, Robert R.
The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments included the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND. PMID:21437751
Gandhi, Nishiena S; Skolasky, Richard L; Peters, Katherine B; Moxley, Richard T; Creighton, Jason; Roosa, Heidi Vornbrock; Selnes, Ola A; McArthur, Justin; Sacktor, Ned
The objectives of this study are to compare the results of newer performance-based functional assessments in the study of HIV-associated neurocognitive disorders (HAND) and to correlate these functional assessments with specific levels of severity of HAND. One hundred fourteen HIV+ subjects in an existing cohort were evaluated with a medical history, neurological exam, neuropsychological test battery as well as subjective and novel objective measures of functional abilities. Self-reported measures of functional performance included the Karnofsky Performance Scale, a questionnaire for instrumental activities of daily living, and a questionnaire for physical quality of life measures. The newer objective functional performance assessments in cluded the Columbia Medication Management and the San Diego Finances tests. These newer performance-based measures of function were assessed for their ability to predict level of HAND. The two objective measures of functional performance, The Columbia Medication Management Scale and the San Diego Finances Test, were both associated with levels of severity of HAND. The Karnofsky Performance Scale and the questionnaires for role and physical quality of life were subjective measures that were also associated with specific levels of HAND. Newer measures of functional performance can be used to objectively evaluate functional impairment in HAND and validate different levels of HAND.
Gandhi, Nishiena S.; Skolasky, Richard L.; Peters, Katherine B.; Moxley, Richard T.; Creighton, Jason; Roosa, Heidi Vornbrock; Selnes, Ola A.; McArthur, Justin; Sacktor, Ned
Interaction of the chemokine CXCL12 with its receptor CXCR4 promotes neuronal function and survival during embryonic development and throughout adulthood. Previous studies indicated that ?-opioid agonists specifically elevate neuronal levels of the protein ferritin heavy chain (FHC), which negatively regulates CXCR4 signaling and affects the neuroprotective function of the CXCL12/CXCR4 axis. Here, we determined that CXCL12/CXCR4 activity increased dendritic spine density, and also examined FHC expression and CXCR4 status in opiate abusers and patients with HIV-associated neurocognitive disorders (HAND), which is typically exacerbated by illicit drug use. Drug abusers and HIV patients with HAND had increased levels of FHC, which correlated with reduced CXCR4 activation, within cortical neurons. We confirmed these findings in a nonhuman primate model of SIV infection with morphine administration. Transfection of a CXCR4-expressing human cell line with an iron-deficient FHC mutant confirmed that increased FHC expression deregulated CXCR4 signaling and that this function of FHC was independent of iron binding. Furthermore, examination of morphine-treated rodents and isolated neurons expressing FHC shRNA revealed that FHC contributed to morphine-induced dendritic spine loss. Together, these data implicate FHC-dependent deregulation of CXCL12/CXCR4 as a contributing factor to cognitive dysfunction in neuroAIDS.
Pitcher, Jonathan; Abt, Anna; Myers, Jaclyn; Han, Rachel; Snyder, Melissa; Graziano, Alessandro; Festa, Lindsay; Kutzler, Michele; Garcia, Fernando; Gao, Wen-Jun; Fischer-Smith, Tracy; Rappaport, Jay; Meucci, Olimpia
With an emerging array of rapid diagnostic tests for tuberculosis, cost-effectiveness analyses are needed to inform scale-up in various populations and settings. Human immunodeficiency virus (HIV)-associated tuberculosis poses unique challenges in estimating and interpreting the cost-effectiveness of novel diagnostic tools. First, gains in sensitivity and specificity do not directly correlate with impact on clinical outcomes. Second, the cost-effectiveness of implementing tuberculosis diagnostics in HIV-infected populations is heavily influenced by downstream costs of HIV care. As a result, tuberculosis diagnostics may appear less cost-effective in this population than among HIV-uninfected individuals, raising important ethical and policy questions about the design and interpretation of cost-effectiveness analyses in this setting. Third, conventional cost-effectiveness benchmarks may be inadequate for making decisions about whether to adopt new diagnostics. If we are to appropriately deploy novel diagnostics for tuberculosis to people living with HIV in resource-constrained settings, these challenges in measuring cost-effectiveness must be more widely recognized and addressed. PMID:23788239
Andrews, Jason R; Lawn, Stephen D; Dowdy, David W; Walensky, Rochelle P
Background. Combination antiretroviral therapy (cART) has progressively decreased mortality of HIV-associated tuberculosis .To date, however, limited data on tuberculosis treatment outcomes among coinfected patients who are not ART-naive at the time of tuberculosis diagnosis are available. Methods. A multicenter, observational study enrolled 246 HIV-infected patients diagnosed with tuberculosis, in 96 Italian infectious diseases hospital units, who started tuberculosis treatment. A polytomous logistic regression model was used to identify baseline factors associated with the outcome. A Poisson regression model was used to explain the effect of ART during tuberculosis treatment on mortality, as a time-varying covariate, adjusting for baseline characteristics. Results. Outcomes of tuberculosis treatment were as follows: 130 (52.8%) were successfully treated, 36 (14.6%) patients died in a median time of 2 months (range: 0–16), and 80 (32.6%) had an unsuccessful outcome. Being foreign born or injecting drug users was associated with unsuccessful outcomes. In multivariable Poisson regression, cART during tuberculosis treatment decreased the risk of death, while this risk increased for those who were not ART-naive at tuberculosis diagnosis. Conclusions. ART during tuberculosis treatment is associated with a substantial reduction of death rate among HIV-infected patients. However, patients who are not ART-naive when they develop tuberculosis remain at elevated risk of death.
Girardi, Enrico; Palmieri, Fabrizio; Angeletti, Claudio; Vanacore, Paola; Matteelli, Alberto; Gori, Andrea; Carbonara, Sergio; Ippolito, Giuseppe
With the widespread use of combination antiretroviral therapy (cART), the incidence of central nervous system (CNS) opportunistic infections and coinfections has significantly decreased. This review focuses on the clinical presentation, diagnostic laboratory and radiologic findings, as well as the treatment of neurosyphilis, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and toxoplasmosis, which are CNS opportunistic infections and coinfections that are most relevant to clinicians in North America. PMID:24715489
Ho, Emily L; Marra, Christina M
Opportunistic yeast infections are diseases caused by fungi which normally are saprophytic and do not cause disease in humans or animals. The prevalence of these diseases has been increasing due to immunosuppressive, corticosteroid, and long-term antibiotic treatment following organ transplantation or after serious metabolic, hematological, or immunological diseases. We review epidemiological, clinical, diagnostic, and therapeutic aspects of the four "big" opportunistic yeast infections: candidiasis, cryptococcosis, trichosporonosis, and geotrichosis. PMID:23621330
Vázquez-González, Denisse; Perusquía-Ortiz, Ana María; Hundeiker, Max; Bonifaz, Alexandro
We study cyclic evolutionary games in a spatial diluted grid environment in which agents strategically interact locally but can also opportunistically move to other positions within a given migration radius. We find that opportunistic migration can inverse the cyclic prevalence between the strategies when the frequency of random imitation is large enough compared to the payoff-driven imitation. At the transition the average size of the patterns diverges and this threatens diversity of strategies.
Buesser, Pierre; Tomassini, Marco
Therapy of HIV-associated lymphoma-recommendations of the oncology working group of the German Study Group of Physicians in Private Practice Treating HIV-Infected Patients (DAGNÄ), in cooperation with the German AIDS Society (DAIG).
AIDS-related aggressive B cell lymphoma (HIV-NHL) is the second most common HIV-associated malignancy. In contrast, Hodgkin-lymphoma (HL) is one of the most common non-AIDS-defining malignancies. Current evidence-based recommendations for the treatment of HIV-associated lymphoma (HIV-lymphoma) are not available. A panel of experts in the field of HIV-related lymphoma performed literature searches of the PubMed, Medline, and Cochrane databases. The consensus process was carried out as an e-mail and meeting-based discussion group. Six cycles of R-CHOP or R-EPOCH are standard of care for patients (pts) with diffuse large B cell lymphoma (DLBCL). Pts with Burkitt lymphoma and good performance status should receive dose-intensive regimens such as the GMALL B-ALL/NHL protocol. Standard therapy has not been defined for pts with plasmablastic and primary effusion lymphoma. Pts with lymphoma in sensitive relapse should receive high-dose chemotherapy followed by autologous stem cell transplantation. Stage- and risk adapted treatment yields high remission and survival rates in pts with HIV-HL similar to those achieved in HIV-negative HL pts. Combination antiretroviral therapy (cART) should be applied concurrently to chemotherapy provided that pharmacokinetic interactions are being considered. Pts with HIV-lymphoma should usually be treated in an identical manner to HIV-negative patients. PMID:24807241
Hentrich, Marcus; Hoffmann, Christian; Mosthaf, Franz; Müller, Markus; Siehl, Jan; Wyen, Christoph; Hensel, Manfred
Combination antiretroviral therapy (CART) has greatly reduced medical morbidity and mortality with HIV infection, but high\\u000a rates of HIV-associated neurocognitive disorders (HAND) continue to be reported. Because large HIV-infected (HIV+) and uninfected\\u000a (HIV?) groups have not been studied with similar methods in the pre-CART and CART eras, it is unclear whether CART has changed\\u000a the prevalence, nature, and clinical correlates
Robert K. Heaton; Donald R. Franklin; Ronald J. Ellis; J. Allen McCutchan; Scott L. Letendre; Shannon LeBlanc; Stephanie H. Corkran; Nichole A. Duarte; David B. Clifford; Steven P. Woods; Ann C. Collier; Christina M. Marra; Susan Morgello; Monica Rivera Mindt; Michael J. Taylor; Thomas D. Marcotte; J. Hampton Atkinson; Tanya Wolfson; Benjamin B. Gelman; Justin C. McArthur; David M. Simpson; Ian Abramson; Anthony Gamst; Christine Fennema-Notestine; Terry L. Jernigan; Joseph Wong; Igor Grant
Background. Renal cellular HIV infection has been linked to the pathogenesis of HIV-associated nephro- pathy (HIVAN), but mediators of its development are unknown. HIV infection is associated with dis- ordered cytokine metabolism, and chemokine receptors are coreceptors for HIV immune cellular infection. Chemokines such as interleukin (IL)-8, monocyte chemoattractant protein-1 (MCP-1) and RANTES, and interferons (IFNs) have been implicated in
Paul L. Kimmel; David J. Cohen; A. Andrew Abraham; Istvan Bodi; Arnold M. Schwartz; Terry M. Phillips
BackgroundMortality is high in HIV-infected TB patients, but few studies from Southeast Asia have documented the benefits of interventions, such as co-trimoxazole (CTX), in reducing mortality during TB treatment. To help guide policy in Vietnam, we studied the epidemiology of HIV-associated TB in one province and examined factors associated with outcomes, including the impact of CTX use.Methodology\\/Principal FindingsWe retrospectively abstracted
Trinh Thanh Thuy; N. Sarita Shah; Mai Hoang Anh; Do Trong Nghia; Duong Thom; Truong Linh; Dinh Ngoc Sy; Bui Duc Duong; Luu Thi Minh Chau; Phung Thi Phuong Mai; Charles D. Wells; Kayla F. Laserson; Jay K. Varma; Maurizio Del Poeta
Background: Because of the risk of performing renal biopsies in children with co-morbid conditions, we carried out this study to identify candidate protein biomarkers in the urine of HIV-infected children with renal disease. Design, setting, participants & measurements: Urine samples from HIV-infected children with biopsy proven HIV-nephropathy (HIVAN; n = 4), HIV-associated Hemolytic Uremic Syndrome (HIV-HUS; n = 2), or no renal disease (n = 3) were analyzed by two-dimensional electrophoresis (2-DE) and proteomic methods. Positive findings were confirmed in HIV-infected children with (n = 20) and without (n = 10) proteinuria using commercially available assays. Results: By 2-DE analysis, a single urine marker was not sufficient to distinguish children with HIVAN from the others. High urine levels of ?2-microglobulin and retinol-binding protein (RBP) suggested the presence of tubular injury. In addition, we found elevated urine levels of iron and the iron-related proteins, transferrin, hemopexin, haptoglobin, lactoferrin, and neutrophil gelatinase-associated lipocalin (NGAL), in children with HIVAN and HIV-HUS. Furthermore, we detected a significant accumulation of iron in the urine and kidneys of HIV-transgenic (Tg) rats with renal disease. Conclusion: These findings suggest that iron and iron-related proteins might be promising candidate urine biomarkers to identify HIV-infected children at risk of developing HIVAN and HIV-HUS. Moreover, based on the results of previous studies, we speculate that the release or accumulation of iron in the kidney of HIV-infected children may contribute to the rapid progression of their renal disease, and could become a new therapeutic target against HIVAN and HIV-HUS.
Soler-Garcia, Angel A.; Johnson, Douglas; Hathout, Yetrib; Ray, Patricio E.
Pulmonary arterial hypertension (PAH) is increased in HIV, but its pathogenesis is not fully understood. Nonhuman primates infected with simian immunodeficiency virus (SIV) or SIV-HIV chimeric virus (SHIV) exhibit histologic changes characteristic of human PAH, but whether hemodynamic changes accompany this pathology is unknown. Repeated measurements of pulmonary artery pressures would permit longitudinal assessments of disease development and provide insights into pathogenesis. We tested the hypothesis that SIV-infected and SHIV-infected macaques develop physiologic manifestations of PAH. We performed right heart catheterizations, echocardiography, and computed tomography (CT) scans in macaques infected with either SIV (?B670) or SHIV (89.6P), and compared right heart and pulmonary artery pressures, as well as pulmonary vascular changes on CT scans, with those in uninfected control animals. Right atrial, right ventricular systolic, and pulmonary artery pressures (PAPs) were significantly elevated in 100% of macaques infected with either SIV or SHIV compared with control animals, with no difference in pulmonary capillary wedge pressure. PAPs increased as early as 3 months after SIV infection. Radiographic evidence of pulmonary vascular pruning was also found. Both SIV-infected and SHIV-infected macaques exhibited histologic changes in pulmonary arteries, predominantly consisting of intimal and medial hyperplasia. This report is the first to demonstrate SHIV-infected and SIV-infected macaques develop pulmonary hypertension at a high frequency, with physiologic changes occurring as early as 3 months after infection. These studies establish an important nonhuman primate model of HIV-associated PAH that will be useful in studies of disease pathogenesis and the efficacy of interventions. PMID:23239493
George, M Patricia; Champion, Hunter C; Simon, Marc; Guyach, Siobhan; Tarantelli, Rebecca; Kling, Heather M; Brower, Alexandra; Janssen, Christopher; Murphy, Jessica; Carney, Jonathan P; Morris, Alison; Gladwin, Mark T; Norris, Karen A
Pulmonary arterial hypertension (PAH) is increased in HIV, but its pathogenesis is not fully understood. Nonhuman primates infected with simian immunodeficiency virus (SIV) or SIV-HIV chimeric virus (SHIV) exhibit histologic changes characteristic of human PAH, but whether hemodynamic changes accompany this pathology is unknown. Repeated measurements of pulmonary artery pressures would permit longitudinal assessments of disease development and provide insights into pathogenesis. We tested the hypothesis that SIV-infected and SHIV-infected macaques develop physiologic manifestations of PAH. We performed right heart catheterizations, echocardiography, and computed tomography (CT) scans in macaques infected with either SIV (?B670) or SHIV (89.6P), and compared right heart and pulmonary artery pressures, as well as pulmonary vascular changes on CT scans, with those in uninfected control animals. Right atrial, right ventricular systolic, and pulmonary artery pressures (PAPs) were significantly elevated in 100% of macaques infected with either SIV or SHIV compared with control animals, with no difference in pulmonary capillary wedge pressure. PAPs increased as early as 3 months after SIV infection. Radiographic evidence of pulmonary vascular pruning was also found. Both SIV-infected and SHIV-infected macaques exhibited histologic changes in pulmonary arteries, predominantly consisting of intimal and medial hyperplasia. This report is the first to demonstrate SHIV-infected and SIV-infected macaques develop pulmonary hypertension at a high frequency, with physiologic changes occurring as early as 3 months after infection. These studies establish an important nonhuman primate model of HIV-associated PAH that will be useful in studies of disease pathogenesis and the efficacy of interventions.
George, M. Patricia; Champion, Hunter C.; Simon, Marc; Guyach, Siobhan; Tarantelli, Rebecca; Kling, Heather M.; Brower, Alexandra; Janssen, Christopher; Murphy, Jessica; Carney, Jonathan P.; Morris, Alison; Gladwin, Mark T.
Background Interferon-? is of key importance in the immune response to Cryptococcus neoformans. Mortality related to cryptococcal meningitis (CM) remains high, and novel treatment strategies are needed. We performed an RCT to determine whether addition of IFN? to standard therapy increased the rate of clearance of cryptococcal infection in HIV-associated CM. Methods Patients were randomized to: (1) Amphotericin-B 1mg/kg/day plus 5-FC 100mg/kg/day for 2-weeks (Standard therapy), (2) Standard therapy plus IFN?1b 100?g days 1 and 3 (IFN? 2-doses), or (3) Standard therapy plus IFN?1b 100?g days 1, 3, 5, 8, 10 and 12 (IFN? 6-doses). Primary outcome was rate of clearance of cryptococcus from the CSF (early fungicidal activity, EFA) calculated from serial quantitative cultures, previously shown to be independently associated with survival. Results Rate of fungal clearance was significantly faster in IFN? containing groups than with standard treatment. Mean EFA (logCFU/ml/day) was ?0.49 with standard treatment, ?0.64 with IFN? 2-doses, and ?0.64 with IFN? 6-doses. Difference in EFA was ?0.15 (95%CI ?0.02- ?0.27, p=0.02) between standard treatment and IFN? 2-doses, and ?0.15 (95%CI-0.05- ?0.26, p=0.006) between standard treatment and IFN? 6-doses. Mortality was 16% (14/88) at 2 weeks and 31% (27/87) at 10 weeks, with no significant difference between groups. All treatments were well tolerated. Conclusions Addition of short-course IFN? to standard treatment significantly increased the rate of clearance of cryptococcal infection from the CSF, and was not associated with any increase in adverse events. Two doses of IFN? are as effective as 6 doses.
Jarvis, Joseph N; Meintjes, Graeme; Rebe, Kevin; Williams, Gertrude Ntombomzi; Bicanic, Tihana; Williams, Anthony; Schutz, Charlotte; Bekker, Linda-Gail; Wood, Robin; Harrison, Thomas S
Objective: To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study. Methods: In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55). Results: NCI (global impairment rating ?5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for. Conclusions: As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.
Marquie-Beck, J.A.; FitzSimons, C.A.; Letendre, S.L.; Ellis, R.J.; Heaton, R.K.; Wolfson, T.; Rosario, D.; Alexander, T.J.; Marra, C.; Ances, B.M.; Grant, I.
The delay interval between encoding a future intention and detection of the retrieval cue is an essential feature of prospective memory (PM). McDaniel and Einstein’s (2000) multi-process theory posits that greater demands are placed on strategic monitoring processes as the delay interval lengthens. This hypothesis was examined in HIV-associated neurocognitive disorders (HAND), which are associated with strategic dyscontrol of PM likely secondary to prefrontostriatal circuit pathology. Seventy-eight seronegative adults and 49 individuals with HAND comprised the study groups, which were comparable with regard to demographic, psychiatric, and substance use factors. As part of a comprehensive neuropsychological evaluation, participants were administered a well-validated PM measure that included short (2-minute) and long- (15-min) task delay interval scales that utilized a standardized word search as the ongoing task. Results revealed a significant interaction of group and delay interval, with significant effects of HAND on PM at long, but not short delay. The long delay PM effect in HAND was driven primarily by deficits in time-based PM and was most strongly associated with markers of executive dysfunction. In concordance with the multi-process theory, individuals with HAND were disproportionately vulnerable to PM deficits at longer ongoing task delay intervals, which appear to be driven by strategic dyscontrol of PM that is consistent with the preferential disruption of prefrontal systems in neuroAIDS. Difficulty with successfully completing PM tasks following a longer delay could manifest in real-world problems, such as medication nonadherence and unemployment, and characterizing this specific deficit may inform remediation strategies.
Morgan, Erin E.; Weber, Erica; Rooney, Alexandra S.; Grant, Igor; Woods, Steven Paul
Background Chronic human immunodeficiency virus (HIV) infection is associated with an increased incidence of Non-Acquired Immunodeficiency Syndrome (non-AIDS) defining cancers. To date, only a limited number of cases of bladder cancer have been linked with HIV infection. We sought to describe the clinical characteristics of HIV-associated bladder cancer. Methods A retrospective study was performed involving HIV-positive patients with bladder cancer, combining cases from multiple institutions with published case reports. Data regarding patient demographics, HIV status, clinical presentation, pathology, cancer treatment, and outcome were analyzed using descriptive statistics. Results Eleven patients were identified with a median age of 55 years (range, 33 - 67). The median CD4+ count at cancer diagnosis was 280 cells/mm3 (range, 106 - 572 cells/mm3). Six patients (55%) had a known risk factor for bladder cancer, and nine (82%) presented with hematuria. Ten patients had transitional cell carcinoma, and most had superficial disease at presentation. Treatment included mainly transurethral resection of bladder tumor followed by a combination of local and systemic therapies. One patient received intravesical bacillus Calmette-Guèrin (BCG) without complication. Several patients (55%) were alive following therapy, although many (64%) suffered from local relapse and metastatic disease. Conclusion Bladder cancer is part of the growing list of cancers that may be encountered in patients living longer with chronic HIV-infection. Our patients presented at a younger age and with only mild immunosuppression, however, they experienced an expected course for their bladder cancer. Hematuria in an HIV-infected patient warrants a complete evaluation.
Gaughan, Elizabeth M; Dezube, Bruce J; Bower, Mark; Aboulafia, David M; Bohac, Gerry; Cooley, Timothy P; Pantanowitz, Liron
HIV-associated neurocognitive disorders (HAND) persist despite great advancements in combination antiretroviral therapy (cART). The gold standard for diagnosing cognitive impairment consists of a time-consuming neuropsychological battery of tests given by a trained neuropsychologist, however in the outpatient HIV clinic this is not feasible. The International HIV Dementia Scale (IHDS) was developed to help identify individuals with cognitive impairment in the outpatient setting. The IHDS is moderately sensitive for detecting more symptomatic forms of HAND but sensitivity has been shown to be poor in mild impairment. The IHDS has not been evaluated in developed countries in large cohort populations. We conducted a prospective cross-sectional study of only HIV+ individuals in an urban clinic and evaluated the prevalence of HAND and associated risk factors for cognitive impairment using the IHDS. A total of 507 HIV+ individuals participated in the study of which the majority were male (65%) and African American (68%); and 41% had cognitive impairment. On multivariate analysis, African American race (p=2.21), older age (p=1.03), high school education or less (p=2.03) and depression (p=1.05) were associated with cognitive impairment. The high prevalence of HAND in this group suggests that more severe forms of HAND persist despite cART. Identified risk factors were non-HIV-related and suggest that environmental and sociodemographic factors have a significant impact on cognitive functioning and should be given more attention. The IHDS should be further evaluated in large cohort HIV+ and HIV? populations in the United States, as there remains a significant need to identify an effective brief screening tool for cognitive impairment.
Cross, Sara; Onen, Nur; Gase, Amber; Overton, Edgar Turner; Ances, Beau M.
AIM: First, to compare the characterization of neurocognitive deficits in milder stages of HIV-associated neurocognitive disorder (HAND) derived from existing dementia rating scales of the American Academy of Neurology (AAN) and Memorial Sloan Kettering (MSK) with the 2007 consensus ('Frascati') classification. Second, to identify potential sociodemographic and clinical predictors of HAND progression during 1-year follow-up. METHODS: 104 HIV-infected subjects in an existing cohort system were evaluated with a medical history, exam, neuropsychological test battery and functional assessments. The degree of HAND was rated using the AAN, MSK and Frascati scales. The degree of concordance among these scales was determined. In addition, 45 subjects were reassessed for changes in their neurocognitive status at 1-year follow-up. Associations between age, education, sex, depression ratings, substance abuse, race, hepatitis C serostatus, CD4 count and progression of HAND were examined. RESULTS: There was excellent concordance (gamma > 0.8) among the Frascati, MSK and AAN ratings. Subjects rated as having minor cognitive motor disorder on the AAN scale (n = 45) were evenly split between Frascati rating of asymptomatic neurocognitive impairment (n = 24) and mild neurocognitive disorder (n = 21). At 1-year follow-up of 45 subjects, 31% had worsened, 13% had improved and 56% were stable. Predictors of progression included age older than 50 years (odds ratio: 5.57; p = 0.013) and female gender (odds ratio: 3.13; p = 0.036). CONCLUSION: The Frascati HAND rating scale has excellent concordance with previous neurocognitive rating scales and can be used to better characterize milder stages of cognitive impairment. Older individuals and women appeared to be more likely to show neurocognitive progression. PMID:20824119
Gandhi, Nishiena S; Moxley, Richard T; Creighton, Jason; Roosa, Heidi Vornbrock; Skolasky, Richard L; Selnes, Ola A; McArthur, Justin; Sacktor, Ned
Aim First, to compare the characterization of neurocognitive deficits in milder stages of HIV-associated neurocognitive disorder (HAND) derived from existing dementia rating scales of the American Academy of Neurology (AAN) and Memorial Sloan Kettering (MSK) with the 2007 consensus (‘Frascati’) classification. Second, to identify potential sociodemographic and clinical predictors of HAND progression during 1-year follow-up. Methods 104 HIV-infected subjects in an existing cohort system were evaluated with a medical history, exam, neuropsychological test battery and functional assessments. The degree of HAND was rated using the AAN, MSK and Frascati scales. The degree of concordance among these scales was determined. In addition, 45 subjects were reassessed for changes in their neurocognitive status at 1-year follow-up. Associations between age, education, sex, depression ratings, substance abuse, race, hepatitis C serostatus, CD4 count and progression of HAND were examined. Results There was excellent concordance (? > 0.8) among the Frascati, MSK and AAN ratings. Subjects rated as having minor cognitive motor disorder on the AAN scale (n = 45) were evenly split between Frascati rating of asymptomatic neurocognitive impairment (n = 24) and mild neurocognitive disorder (n = 21). At 1-year follow-up of 45 subjects, 31% had worsened, 13% had improved and 56% were stable. Predictors of progression included age older than 50 years (odds ratio: 5.57; p = 0.013) and female gender (odds ratio: 3.13; p = 0.036). Conclusion The Frascati HAND rating scale has excellent concordance with previous neurocognitive rating scales and can be used to better characterize milder stages of cognitive impairment. Older individuals and women appeared to be more likely to show neurocognitive progression.
Gandhi, Nishiena S; Moxley, Richard T; Creighton, Jason; Roosa, Heidi Vornbrock; Skolasky, Richard L; Selnes, Ola A; McArthur, Justin; Sacktor, Ned
Objective The apolipoprotein E (APOE) ?4 allele enhances cerebral accumulation of ?-amyloid (A?) and is a major risk factor for sporadic Alzheimer’s disease (AD). We hypothesized that HIV-associated neurocognitive disorders (HAND) would be associated with the APOE ?4 genotype and cerebral A? deposition. Design Clinico-pathological study of HIV-infected adults from four prospective cohorts in the U.S. National NeuroAIDS Tissue Consortium. Methods We used multivariable logistic regressions to model outcomes (A? plaques [immunohistochemistry] and HAND [standard criteria]) on predictors (APOE ?4 [allelic discrimination assay], older age [? 50 years], A? plaques, and their two-way interactions) and co-morbid factors. Results Isocortical A? deposits generally occurred as diffuse plaques and mild to moderate amyloid angiopathy. Isocortical phospho-Tau-immunoreactive neurofibrillary lesions were sparse. The APOE ?4 and older age were independently associated with the presence of A? plaques (adjusted odds ratio [OR] 10.16 and 5.77 [95% confidence interval (CI) 2.89–35.76 and 1.91–17.48], P=0.0003 and 0.0019, respectively, n=96). The probability of HAND was increased in the presence of A? plaques among APOE ?4 carriers (adjusted OR 30.00 [95% CI 1.41–638.63], P=0.029, n=15), but not in non-?4 carriers (n=57). Conclusion The APOE ?4 and older age increased the likelihood of cerebral A? plaque deposition in HIV-infected adults. Generally A? plaques in HIV brains were immunohistologically different from those in symptomatic AD brains. Nonetheless, A? plaques were associated with HAND among APOE ?4 carriers. The detection of APOE ?4 genotype and cerebral A? deposition biomarkers may be useful in identifying living HAND subjects who could benefit from A?-targeted therapies.
Soontornniyomkij, Virawudh; Moore, David J.; Gouaux, Ben; Soontornniyomkij, Benchawanna; Tatro, Erick T.; Umlauf, Anya; Masliah, Eliezer; Levine, Andrew J.; Singer, Elyse J.; Vinters, Harry V.; Gelman, Benjamin B.; Morgello, Susan; Cherner, Mariana; Grant, Igor; Achim, Cristian L.
Objective Replicating HIV-1 in the brain is present in HIV encephalitis (HIVE) and microglial nodule encephalitis (MGNE) and is putatively linked with HIV-associated neurocognitive disorders (HAND). A clinico-neurovirological correlation was conducted to elucidate the relationship between brain viral load and clinical phenotype. Subjects and assays HIV gag/pol RNA and DNA copies were quantified with RT-PCR or PCR in 148 HAART-era brain specimens. Comparison to HAND, HIVE and MGNE and correlation with neuropsychological (NP) test scores were done using one-way ANOVA with Tukey-Kramer and Spearman’s tests respectively. Results Brain HIV RNA was higher in subjects with HAND plus HIVE vs without HAND (delta = 2.48 log10 units, n = 27 vs 36, p < 0.001). In HAND without HIVE or MGNE, brain HIV RNA was not significantly different vs without HAND (p = 0.314). Worse NP scores correlated significantly with higher HIV RNA and interferon responses in brain specimens (p<0.001), but not with HIV RNA levels in premortem blood plasma (n = 114) or cerebrospinal fluid (n = 104). In subjects with MGNE, brain HIV RNA was slightly higher versus without MGNE (p<0.01), and much lower versus with HIVE (p<0.001). Conclusion Brain HIV RNA and to a lesser extent HIV DNA are correlated with worse NP performance in the 6 months before death. Linkage occurs primarily in patients with HIVE and MGNE; while on HAART these patients could obtain added NP improvement by further reducing brain HIV. Patients not in those groups are less certain to obtain added NP benefit.
Gelman, Benjamin B.; Lisinicchia, Joshua G.; Morgello, Susan; Masliah, Eliezer; Commins, Deborah; Achim, Cristian L.; Fox, Howard S.; Kolson, Dennis L.; Grant, Igor; Singer, Elyse; Yiannoutsos, Constantin T.; Sherman, Seth; Gensler, Gary; Moore, David J.; Chen, Tiansheng; Soukup, Vicki M.
HIV-associated neurocognitive impairment, particularly in the domain of prospective memory (ProM), increases the risk of poor everyday functioning outcomes, including medication non-adherence. However, whether ProM plays a role in health care compliance outside of the realm of medication adherence remains to be determined. This study evaluated the hypothesis that ProM is an independent predictor of failure to comply with non-medication related instructions akin to those commonly given by health care providers. Participants were 139 HIV-infected adults who underwent medical, psychiatric, and neuropsychological assessments, including a laboratory-based measure of ProM. To assess real-world compliance, participants were instructed to call the examiner 24 hours after the evaluation and report how many hours they had slept. Individuals who failed to correctly comply with these instructions (n=104) demonstrated significantly lower performance on both time- and event-based ProM at baseline than the compliant group (n=35), an effect that was primarily driven by errors of omission. ProM remained a significant predictor of noncompliance after controlling for potential confounders, including demographics (e.g., education), traditional cognitive measures of retrospective memory and executive functions, and psychiatric factors (e.g., depression). Results support the hypothesis that ProM plays a unique role in compliance with health care instructions for HIV disease management and may inform interventions designed to improve treatment outcomes.
Zogg, Jennifer B.; Woods, Steven Paul; Weber, Erica; Iudicello, Jennifer E.; Dawson, Matthew S.; Grant, Igor
A man aged 57 years who had lived most of his life in London, suffered from asthma which had begun during army service in Burma 37 years previously. Latterly he was treated with increasing doses of corticosteroids but his symptoms continued to worsen and he died of asthma. Necropsy revealed a heavy opportunistic infection of the bronchi and lungs by the nematode Strongyloides stercoralis which he had presumably acquired while on service abroad. The case illustrates the need, even in non-endemic areas, to suspect opportunistic pulmonary strongyloidiasis when a patient's asthma worsens despite treatment with increasing doses of corticosteroids. Although it is a potentially lethal iatrogenic opportunistic infection, it is amenable to treatment with anthelminthic agents if recognized in time. Images
Higenbottam, T W; Heard, B E
Background HLA-DR*04 was identified as a predictor of HIV-Associated neurocognitive disorder (HAND), low CD4 T-cell responses to HIV, and low plasma HIV RNA levels in a U.S. cohort. We hypothesized that low CD4 T-cell activation leads to poor immune control of HIV in the CNS, predisposing to HAND, but also provided fewer target (activated CD4 T-cells) for HIV replication. To assess the consistency of these HLA Class II associations in a new cohort and extend analysis to HLA Class I, HLA types, neurocognitive, and virologic status were examined in a cohort of former plasma donors in China. Methods 178 HIV infected individuals in Anhui China, were HLA typed and underwent neurocognitive evaluations (using locally standardized norms), neuromedical, treatment and virologic assessments at baseline and at 12 months. Results HLA DR*04 was associated with a higher rate of baseline neurocognitive impairment (p?=?0.04), neurocognitive decline (p?=?0.04), and lower levels of HIV RNA in plasma (p?=?0.05). HLA Class I alleles (B*27,57,58,A*03,33) that specify a CD8 T-cell response to conserved HIV sequences were neuroprotective, associated with less impairment at baseline (p?=?0.037), at month 012 (p?=?0.013) and less neurocognitive decline (p?=?0.023) in the interval. Consistent with the theory that effective CD8 T-cell responses require CD4 T-cell support, the HLA DR*04 allele reduced the neuroprotective effect of the Class I alleles. The presence of HLA-DR*04 and the Alzheimer associated allele ApoE4 in the same individual had a synergistic negative effect on cognition (p?=?0.003). Conclusions Despite major background differences between U.S. and Anhui China cohorts, HLA DR*04 predicted neurocognitive impairment and lower plasma HIV RNA levels in both populations. HLA Class I alleles associated with CD8 T-cell control of HIV were associated with protection from HAND, but protection was reduced in the presence of HLA-DR*04.
Schrier, Rachel D.; Gupta, Saurabh; Riggs, Patricia; Cysique, Lucette A.; Letendre, Scott; Jin, Hua; Spector, Stephen A.; Singh, Kumud K.; Wolfson, Tanya; Wu, Zunyou; Hong, Kun Xue; Yu, Xin; Shi, Chuan; Heaton, Robert K.
Background. Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis and poor fungal clearance during treatment are recognized adverse prognostic markers; however, the underlying pathogenic factors that drive these clinical manifestations are incompletely understood. We profiled a large set of clinical isolates for established cryptococcal virulence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentation and outcome in human cryptococcosis. Methods. Sixty-five C. neoformans isolates from clinical trial patients with matched clinical data were assayed in vitro to determine murine macrophage uptake, intracellular proliferation rate (IPR), capsule induction, and laccase activity. Analysis of the correlation between prognostic clinical and host immune parameters and fungal phenotypes was performed using Spearman's r, while the fungal-dependent impact on long-term survival was determined by Cox regression analysis. Results. High levels of fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio [HR] 2.6, 95% CI 1.2-5.5, P = 0.012). High-uptake strains were hypocapsular (r = -0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003). Fungal isolates with greater laccase activity exhibited heightened survival ex vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following patient antifungal treatment (r = 0.39, P = 0.003). Conclusion. These findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependent melanin pathways to human clinical presentation and outcome. Furthermore, characterization of fungal-specific pathways that drive clinical manifestation provide potential targets for the development of therapeutics and the management of CM. Funding. This work was made possible by funding from the Wellcome Trust (WT088148MF), the Medical Research Council (MR/J008176/1), the NIHR Surgical Reconstruction and Microbiology Research Centre and the Lister Institute for Preventive Medicine (to R.C. May), and a Wellcome Trust Intermediate fellowship (089966, to T. Bicanic). The C. neoformans isolates were collected within clinical trials funded by the British Infection Society (fellowship to T. Bicanic), the Wellcome Trust (research training fellowships WT069991, to A.E. Brouwer and WT081794, to J.N. Jarvis), and the Medical Research Council, United Kingdom (76201). The funding sources had no role in the design or conduct of this study, nor in preparation of the manuscript. PMID:24743149
Sabiiti, Wilber; Robertson, Emma; Beale, Mathew A; Johnston, Simon A; Brouwer, Annemarie E; Loyse, Angela; Jarvis, Joseph N; Gilbert, Andrew S; Fisher, Matthew C; Harrison, Thomas S; May, Robin C; Bicanic, Tihana
Background. Cryptococcal meningitis (CM) is a leading cause of HIV-associated mortality globally. High fungal burden in cerebrospinal fluid (CSF) at diagnosis and poor fungal clearance during treatment are recognized adverse prognostic markers; however, the underlying pathogenic factors that drive these clinical manifestations are incompletely understood. We profiled a large set of clinical isolates for established cryptococcal virulence traits to evaluate the contribution of C. neoformans phenotypic diversity to clinical presentation and outcome in human cryptococcosis. Methods. Sixty-five C. neoformans isolates from clinical trial patients with matched clinical data were assayed in vitro to determine murine macrophage uptake, intracellular proliferation rate (IPR), capsule induction, and laccase activity. Analysis of the correlation between prognostic clinical and host immune parameters and fungal phenotypes was performed using Spearman’s r, while the fungal-dependent impact on long-term survival was determined by Cox regression analysis. Results. High levels of fungal uptake by macrophages in vitro, but not the IPR, were associated with CSF fungal burden (r = 0.38, P = 0.002) and long-term patient survival (hazard ratio [HR] 2.6, 95% CI 1.2–5.5, P = 0.012). High-uptake strains were hypocapsular (r = –0.28, P = 0.05) and exhibited enhanced laccase activity (r = 0.36, P = 0.003). Fungal isolates with greater laccase activity exhibited heightened survival ex vivo in purified CSF (r = 0.49, P < 0.0001) and resistance to clearance following patient antifungal treatment (r = 0.39, P = 0.003). Conclusion. These findings underscore the contribution of cryptococcal-phagocyte interactions and laccase-dependent melanin pathways to human clinical presentation and outcome. Furthermore, characterization of fungal-specific pathways that drive clinical manifestation provide potential targets for the development of therapeutics and the management of CM. Funding. This work was made possible by funding from the Wellcome Trust (WT088148MF), the Medical Research Council (MR/J008176/1), the NIHR Surgical Reconstruction and Microbiology Research Centre and the Lister Institute for Preventive Medicine (to R.C. May), and a Wellcome Trust Intermediate fellowship (089966, to T. Bicanic). The C. neoformans isolates were collected within clinical trials funded by the British Infection Society (fellowship to T. Bicanic), the Wellcome Trust (research training fellowships WT069991, to A.E. Brouwer and WT081794, to J.N. Jarvis), and the Medical Research Council, United Kingdom (76201). The funding sources had no role in the design or conduct of this study, nor in preparation of the manuscript.
Sabiiti, Wilber; Robertson, Emma; Beale, Mathew A.; Johnston, Simon A.; Brouwer, Annemarie E.; Loyse, Angela; Jarvis, Joseph N.; Gilbert, Andrew S.; Fisher, Matthew C.; Harrison, Thomas S.; May, Robin C.; Bicanic, Tihana
The insertion of implants and medical devices has emerged as a common and often life-saving procedure. A current estimate of the rate of total hip replacement in the world is approximately one million a year, and knee replacements more than 250000. More than 30% of hospitalized patients have one or more vascular catheters in place. More than 10% of hospitalized
J. M. Schierholz; J. Beuth
The IEEE 802.11 wireless media access standard supports multiple data rates at the physical layer. Moreover, vari- ous auto rate adaptation mechanisms at the medium access layer have been proposed to utilize this multi-rate capabil- ity by automatically adapting the transmission rate to best match the channel conditions. In this paper, we introduce the Opportunistic Auto Rate (OAR) protocol to
B. Sadeghi; V. Kanodia; A. Sabharwal; E. Knightly
The IEEE 802.11 wireless media access standard supports multiple data rates at the physical layer. Moreover, various auto rate adaptation mechanisms at the medium access layer have been proposed to utilize this multi-rate capability by automatically adapting the transmission rate to best match the channel conditions. In this paper, we introduce the Opportunistic Auto Rate (OAR) protocol to better exploit
Bahareh Sadeghi; Vikram Kanodia; Ashutosh Sabharwal; Edward W. Knightly
Shewanella putrefaciens and Shewanella algae are Gram negative, nonfermentative and oxidative bacilli whose the main phenotypic feature is the production of hydrogen sulfide gas. Widespread in the environment, both S. putrefaciens and S. algae species are rare human bacteria although they are reported with increasing frequency as a cause of opportunistic infection in humans, such as skin and soft tissue
H. Pagniez; P. Berche
Relative to a centralized operation, opportunistic medium access capitalizing on decentralized multiuser diversity in a channel-aware homogeneous slotted Aloha system with analog-amplitude channels has been shown to incur only partial loss in throughput due to contention. In this context, we provide sufficient conditions for stability as well as upper bounds on average queue sizes, and address three equally important ques-
Yingqun Yu; Georgios B. Giannakis
Abstract Inthis paper we investigate ,the impact ,of board characteristics on opportunistic, earnings management in the context of a large emerging economy, India. While the role of company boards in earnings management has been examined in developed markets setting, particularly the US and UK, understanding their effectiveness in emerging markets like India is particularly important due to differences ,that exist
Jayati Sarkar; Subrata Sarkar; Kaustav Sen
The HIV-associated tuberculosis (TB) epidemic remains a huge challenge to public health in resource-limited settings. Reducing the nearly 0.5 million deaths that result each year has been identified as a key priority. Major progress has been made over the past 10 years in defining appropriate strategies and policy guidelines for early diagnosis and effective case management. Ascertainment of cases has been improved through a twofold strategy of provider-initiated HIV testing and counseling in TB patients and intensified TB case finding among those living with HIV. Outcomes of rifampicin-based TB treatment are greatly enhanced by concurrent co-trimoxazole prophylaxis and antiretroviral therapy (ART). ART reduces mortality across a spectrum of CD4 counts and randomized controlled trials have defined the optimum time to start ART. Good outcomes can be achieved when combining TB treatment with first-line ART, but use with second-line ART remains challenging due to pharmacokinetic drug interactions and cotoxicity. We review the frequency and spectrum of adverse drug reactions and immune reconstitution inflammatory syndrome (IRIS) resulting from combined treatment, and highlight the challenges of managing HIV-associated drug-resistant TB. PMID:24295487
Lawn, Stephen D; Meintjes, Graeme; McIlleron, Helen; Harries, Anthony D; Wood, Robin
Rituximab plus intravenous bolus chemotherapy is a standard treatment for immunocompetent patients with B-cell non-Hodgkin lymphoma (NHL). Some studies have suggested that rituximab is associated with excessive toxicity in HIVassociated NHL, and that infusional chemotherapy may be more effective. We performed a randomized phase 2 trial of rituximab (375 mg/m2) given either concurrently before each infusional etoposide, vincristine, doxorubicin, cyclophosphamide, and prednisone (EPOCH) chemotherapy cycle or sequentially (weekly for 6 weeks) after completion of all chemotherapy in HIV-associated NHL. EPOCH consisted of a 96-hour intravenous infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by intravenous bolus cyclophosphamide given every 21 days for 4 to 6 cycles. In the concurrent arm, 35 of 48 evaluable patients (73%; 95% confidence interval, 58%-85%) had a complete response. In the sequential arm, 29 of 53 evaluable patients (55%; 95% confidence interval, 41%-68%) had a complete response. The primary efficacy endpoint was met for the concurrent arm only. Toxicity was comparable in the 2 arms, although patients with a baseline CD4 count less than 50/?L had a high infectious death rate in the concurrent arm. We conclude that concurrent rituximab plus infusional EPOCH is an effective regimen for HIV-associated lymphoma. This study is registered at http://clinicaltrials.gov as NCT00049036.
Lee, Jeannette Y.; Kaplan, Lawrence D.; Levine, Alexandra M.; Ramos, Juan Carlos; Ambinder, Richard F.; Wachsman, William; Aboulafia, David; Noy, Ariela; Henry, David H.; Von Roenn, Jamie; Dezube, Bruce J.; Remick, Scot C.; Shah, Manisha H.; Leichman, Lawrence; Ratner, Lee; Cesarman, Ethel; Chadburn, Amy; Mitsuyasu, Ronald
Contributory factors to HIV-associated neurocognitive disorders (HAND) have been shown to include age, co-morbid infections, medication toxicity, virological, genetic and vascular mechanisms, as well as microbial translocation of lipopolysaccharide (LPS), which is suspected to trigger monocyte activation and increase trafficking of infected cells into the brain. In this study, our aim was to assess the degree of neurocognitive impairment in a group of randomly selected HIV-infected patients and investigate potential risk factors, including LPS plasma levels. Furthermore, we evaluated the relevance of LPS as a potential marker for screening patients with mild neurocognitive impairment. LPS plasma levels were compared among patients with HAND and those with no HAND. As LPS has also been shown to be elevated in hepatitis C co-infection, the analysis was stratified according to the presence or not of hepatitis C virus (HCV) co-infection. Differences between groups were evaluated using chi-square tests and Kruskal-Wallis non-parametric tests. Stepwise logistic regression was performed to identify independent risk factors for HAND in the subgroups of HCV-positive and negative patients. A p value <0.05 was considered significant. Analyses were conducted using SPSS® software. From December 2007 to July 2009, 179 patients were tested (mean age 44, 73 % male, 87 % on treatment, 30 % HCV co-infected, median CD4 504/ml and 67 % with viral load below 40 copies/ml). HAND was identified in 40/179 patients (22 %), the majority displaying asymptomatic neurocognitive impairment or mild neurocognitive disorder. Univariate analysis showed that age, illicit drug use, hepatitis C co-infection, prior AIDS-defining events, CD4/CD8 ratio and LPS plasma levels were significantly associated with HAND. The median LPS level was 98.2 pg/ml in the non-HAND group versus 116.1 pg/ml in the HAND group (p < 0.014). No differences were found in LPS values between subgroups of impairment. There was a clear association between LPS levels and HAND in the HCV-positive group (p = 0.036), while there was none in the HCV-negative group (p = 0.502). No difference in degree of hepatic fibrosis was found between the HAND and non-HAND groups. In conclusion, LPS levels were associated with HAND in the HCV-positive group, while, in the HCV-negative group, age and pro-viral DNA were the only variables independently associated with HAND. There was no difference in degree of liver disease as predicted by score of fibrosis between HAND and non-HAND groups. The role of HCV co-infection and higher LPS levels in the pathogenesis of HAND in patients with viral suppression on treatment requires further investigation. PMID:23846287
Vassallo, Matteo; Dunais, Brigitte; Durant, Jacques; Carsenti-Dellamonica, Helene; Harvey-Langton, Alexandra; Cottalorda, Jacqueline; Ticchioni, Michel; Laffon, Muriel; Lebrun-Frenay, Christine; Dellamonica, Pierre; Pradier, Christian
Efavirenz (EFV) is among the most commonly used antiretroviral drugs globally, causes neurological symptoms that interfere with adherence and reduce tolerability, and may have central nervous system (CNS) effects that contribute in part to HIV associated neurocognitive disorders (HAND) in patients on combination antiretroviral therapy (cART). Thus we evaluated a commonly used EFV containing regimen: EFV/zidovudine (AZT)/lamivudine (3TC) in murine N2a cells transfected with the human “Swedish” mutant form of amyloid precursor protein (SweAPP N2a cells) to assess for promotion of amyloid-beta (A?) production. Treatment with EFV or the EFV containing regimen generated significantly increased soluble amyloid beta (A?), and promoted increased ?-secretase-1 (BACE-1) expression while 3TC, AZT, or, vehicle control did not significantly alter these endpoints. Further, EFV or the EFV containing regimen promoted significantly more mitochondrial stress in SweAPP N2a cells as compared to 3TC, AZT, or vehicle control. We next tested the EFV containing regimen in A? - producing Tg2576 mice combined or singly using clinically relevant doses. EFV or the EFV containing regimen promoted significantly more BACE-1 expression and soluble A? generation while 3TC, AZT, or vehicle control did not. Finally, microglial A? phagocytosis was significantly reduced by EFV or the EFV containing regimen but not by AZT, 3TC, or vehicle control alone. These data suggest the majority of A? promoting effects of this cART regimen are dependent upon EFV as it promotes both increased production, and decreased clearance of A? peptide.
Brown, Lecia A. M.; Jin, Jingji; Ferrell, Darren; Sadic, Edin; Obregon, Demian; Smith, Adam J.; Tan, Jun; Giunta, Brian
The performance of opportunistic beamforming might be degraded if the number of users is small. This paper proposes an adaptive opportunistic beamforming technique for orthogonal frequency division multiple access systems, which can produce good results even with a small number of users. This paper also proposes a modified proportional fairness scheduling algorithm, which can further improve the performance of the proposed opportunistic beamforming technique.
Persons co-infected with HTLV-1 and HIV are at increased risk for neurologic disease. These patients may develop HAM\\/TSP and\\/or\\u000a HIV-associated dementia. In this study, we localized cells infected with retrovirus in the central nervous system (CNS) of\\u000a a patient with both HAM\\/TSP and HIV-associated dementia. HTLV-1 was localized to astrocytes and HIV to macrophage\\/microglia.\\u000a There was no co-infection of a
Michael C. Levin; Marc K. Rosenblum; Cecil H. Fox; Steven Jacobson
We report a challenging case of HIV-associated neurocognitive disorder with superimposed Epstein-Barr virus (EBV) encephalitis. The patient presented with an abnormal MRI brain scan, and EBV DNA that was detected in the cerebrospinal fluid and brain biopsy, which also demonstrated histopathological findings consistent with the diagnosis. This occurred on the background of a 12-month period of gradual cognitive decrease secondary to HIV-associated dementia. Invasive testing was required to reach the diagnosis in this case, highlighting the importance of thorough investigation of neurological impairment in HIV-positive patients. Clinicopathological recovery was achieved through optimization of antiretroviral therapy and use of valganciclovir. PMID:23475078
Trevillyan, Janine M; Mahony, Andrew A; McLean, Catriona; Hoy, Jennifer F
The gastrointestinal (GI) tract is a major site of disease in HIV infection: almost half of HIV-infected patients present with GI symptoms, and almost all patients develop GI complications. GI symptoms such as anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea are frequent and usually nonspecific among these patients. Endoscopy is the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic and histopathologic evaluation can render diagnoses in patients with non-specific symptoms. In the past three decades, studies have elucidated a variety of HIV-associated inflammatory, infectious, and neoplastic GI diseases, often with specific predilection for various sites. HIV-associated esophageal disease, for example, commonly includes candidiasis, cytomegalovirus (CMV) and herpes simplex virus (HSV) infection, Kaposi's sarcoma (KS), and idiopathic ulceration. Gastric disease, though less common than esophageal disease, frequently involves CMV, Mycobacterium avium-intracellulare (MAI), and neoplasia (KS, lymphoma). Small bowel biopsies and intestinal aspirates from HIV-infected patients often show HIV enteropathy, MAI, protozoa (Giardia, Isospora, Cryptosporidia, amebae, Microsporidia), and helminths (Strongyloides stercoralis). Colorectal biopsies demonstrate viral (CMV, HSV), bacterial (Clostridia, Salmonella, Shigella, Campylobacter), fungal (cryptococcosis, histoplasmosis), and neoplastic (KS, lymphoma) processes. Herein, we review HIV-associated GI pathology, with emphasis on common endoscopic biopsy diagnoses.
Bhaijee, Feriyl; Subramony, Charu; Tang, Shou-Jiang; Pepper, Dominique J.
THE GASTROINTESTINAL (GI) TRACT IS A MAJOR SITE OF DISEASE IN HIV INFECTION: almost half of HIV-infected patients present with GI symptoms, and almost all patients develop GI complications. GI symptoms such as anorexia, weight loss, dysphagia, odynophagia, abdominal pain, and diarrhea are frequent and usually nonspecific among these patients. Endoscopy is the diagnostic test of choice for most HIV-associated GI diseases, as endoscopic and histopathologic evaluation can render diagnoses in patients with non-specific symptoms. In the past three decades, studies have elucidated a variety of HIV-associated inflammatory, infectious, and neoplastic GI diseases, often with specific predilection for various sites. HIV-associated esophageal disease, for example, commonly includes candidiasis, cytomegalovirus (CMV) and herpes simplex virus (HSV) infection, Kaposi's sarcoma (KS), and idiopathic ulceration. Gastric disease, though less common than esophageal disease, frequently involves CMV, Mycobacterium avium-intracellulare (MAI), and neoplasia (KS, lymphoma). Small bowel biopsies and intestinal aspirates from HIV-infected patients often show HIV enteropathy, MAI, protozoa (Giardia, Isospora, Cryptosporidia, amebae, Microsporidia), and helminths (Strongyloides stercoralis). Colorectal biopsies demonstrate viral (CMV, HSV), bacterial (Clostridia, Salmonella, Shigella, Campylobacter), fungal (cryptococcosis, histoplasmosis), and neoplastic (KS, lymphoma) processes. Herein, we review HIV-associated GI pathology, with emphasis on common endoscopic biopsy diagnoses. PMID:21559197
Bhaijee, Feriyl; Subramony, Charu; Tang, Shou-Jiang; Pepper, Dominique J
One vision of an opportunistic sensor network (OSN) uses sensor access points (SAPs) to assign mobile sensors with sensing tasks submitted by applications that could be running anywhere. Tasked mobile sensors might upload sensed data back to these applications via subsequent encounters with this SAP tier. In a people-centric OSN, node mobility is uncontrolled and the architecture relies on opportunistic rendezvous between human-carried sensors and SAPs to provide tasking/uploading opportunities. However, in many reasonable scenarios application queries have a degree of time sensitivity such that the sensing target must be sampled and/or the resulting sensed data must be uploaded within a certain time window to be of greatest value. Halo efficiently, in terms of packet overhead and mobile sensor energy, provides improved delay performance in OSNs by: (i) managing tasking/uploading opportunity, and (ii) using mobility-informed scheduling at the SAP.
Eisenman, Shane B.; Lu, Hong; Campbell, Andrew T.
Bordetella holmesii is an emerging opportunistic pathogen that causes respiratory disease in healthy individuals and invasive infections among patients lacking splenic function. We used 16S rRNA analysis to confirm B. holmesii as the cause of bacteremia in a child with sickle cell disease. Semiconductor-based draft genome sequencing provided insight into B. holmesii phylogeny and potential virulence mechanisms and also identified a toluene-4-monoxygenase locus unique among bordetellae.
Planet, Paul J.; Narechania, Apurva; Hymes, Saul R.; Gagliardo, Christina; Huard, Richard C.; Whittier, Susan; Della-Latta, Phyllis; Ratner, Adam J.
\\u000a This study was undertaken to examine quantitatively the risks to human health posed by heterotrophic plate count (HPC) bacteria\\u000a found naturally in ambient and potable waters. There is no clear-cut evidence that the HPC bacteria as a whole pose a public\\u000a health risk. Only certain members are opportunistic pathogens. Using the four-tiered approach for risk assessment from the\\u000a National Academy
Patricia A. Rusin; Joan B. Rose; Charles N. Haas; Charles P. Gerba
In this paper we address the replication versus redundancy optimisation problem for a class of intermittently-connected ad hoc networks with the following three characteristics: routing is performed by a store-carry-forward mechanism in an opportunistic manner, replication of custodian messages is used to increase the delivery ratio, and fragmentation combined with redundancy in the form of erasure coding is used to
Gabriel Sandulescu; Simin Nadjm-Tehrani
Background Ultrasound can rapidly identify abnormal signs, which in high prevalence settings, are highly suggestive of extra-pulmonary tuberculosis (EPTB). Unfortunately experienced sonographers are often scarce in these settings. Methods A protocol for focused assessment with sonography for HIV-associated tuberculosis (FASH) which can be used by physicians who are relatively inexperienced in ultrasound was developed. Results The technique as well as normal and pathological findings are described and the diagnostic and possible therapeutic reasoning explained. The protocol is intended for settings where the prevalence of HIV/TB co-infected patients is high. Conclusion FASH is suitable for more rapid identification of EPTB even at the peripheral hospital level where other imaging modalities are scarce and most of the HIV and TB care will be delivered in the future.
Various screening tools have been proposed to identify HIV-Associated Neurocognitive Disorder (HAND). However, there has been no systematic review of their strengths and weaknesses in detecting HAND when compared to gold standard neuropsychological testing. Thirty-five studies assessing HAND screens that were conducted in the era of combination antiretroviral therapy were retrieved using standard search procedures. Of those, 19 (54 %) compared their screen to standard neuropsychological testing. Studies were characterised by a wide variation in criterion validity primarily due to non-standard definition of neurocognitive impairment, and to the demographic and clinical heterogeneity of samples. Assessment of construct validity was lacking, and longitudinal useability was not established. To address these limitations, the current review proposed a summary of the most sensitive and specific studies (>70 %), as well as providing explicit caution regarding their weaknesses, and recommendations for their use in HIV primary care settings. PMID:24072534
Kamminga, Jody; Cysique, Lucette A; Lu, Grace; Batchelor, Jennifer; Brew, Bruce J
Aims Combined anti-retroviral therapy (cART) has led to a reduction in the incidence of HIV-associated dementia (HAD), a severe motor/cognitive disorder afflicting HIV(+) patients. However, the prevalence of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/ microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients. The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1? and ATF6. Methods To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2? and ATF4, in cortical tissue from HIV-infected patients. Results The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. Conclusion These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease.
Akay, C.; Lindl, K. A.; Shyam, N.; Nabet, B.; Goenaga-Vazquez, Y.; Ruzbarsky, J.; Wang, Y.; Kolson, D. L.; Jordan-Sciutto, K. L.
The long-term safety and efficacy of products used in the correction of HIV-associated facial lipoatrophy (FLA) are largely unknown. The purpose of this study was to describe the long-term efficacy and safety of polyalkylimide gel (PAIG) in the treatment of HIV-associated FLA. In this open-label, randomized, single-center study, 31 HIV-positive individuals (median age 48 years (interquartile ranges (IQR) 45, 55, 97% male) with FLA were randomized to immediate (week 0 and six) or delayed (week 12 and 18) PAIG injections. Week 96 endpoints included change in FLA severity scores (FLSS) (five-point scale), proportion of patients with adverse events, and changes in quality of life, depression and anxiety using validated surveys. Results at week 96 were available for 28 patients. Adverse events, including swelling, redness, bruising and pain, were mild, and resolved after a median of three days following the injection. At week 96, median changes in physician and patient FLSS scores were -2 (IQR -3, -1; p<0.001 vs. baseline) and -2 (IQR -2, -1; p<0.001 vs. baseline), respectively. Physician and patient FLSS scores were not significantly different between the groups at week 96. Significant improvements in patient's anxiety (p<0.001), depression (p<0.001) and mental health (p=0.01) were observed from baseline to week 96. In conclusion, treatment with PAIG was associated with sustained improvements in both the physical and psychological components of FLA through 96 weeks of follow-up. PMID:20024700
Antoniou, Tony; Raboud, Janet M; Kovacs, Colin; Diong, Christina; Brunetta, Jason; Smith, Graham; Halpenny, Roberta; Beninger, Francis; Loutfy, Mona R
Background.?Cryptococcal meningitis (CM) is a leading cause of death in individuals infected with human immunodeficiency virus (HIV). Identifying factors associated with mortality informs strategies to improve outcomes. Methods.?Five hundred one patients with HIV-associated CM were followed prospectively for 10 weeks during trials in Thailand, Uganda, Malawi, and South Africa. South African patients (n = 266) were followed for 1 year. Similar inclusion/exclusion criteria were applied at all sites. Logistic regression identified baseline variables independently associated with mortality. Results.?Mortality was 17% at 2 weeks and 34% at 10 weeks. Altered mental status (odds ratio [OR], 3.1; 95% confidence interval [CI], 1.7–5.9), high cerebrospinal fluid (CSF) fungal burden (OR, 1.4 per log10 colony-forming units/mL increase; 95% CI, 1.0–1.8), older age (>50 years; OR, 3.9; 95% CI, 1.4–11.1), high peripheral white blood cell count (>10 × 109 cells/L; OR, 8.7; 95% CI, 2.5–30.2), fluconazole-based induction treatment, and slow clearance of CSF infection were independently associated with 2-week mortality. Low body weight, anemia (hemoglobin <7.5 g/dL), and low CSF opening pressure were independently associated with mortality at 10 weeks in addition to altered mental status, high fungal burden, high peripheral white cell count, and older age. In those followed for 1 year, overall mortality was 41%. Immune reconstitution inflammatory syndrome occurred in 13% of patients and was associated with 2-week CSF fungal burden (P = .007), but not with time to initiation of antiretroviral therapy (ART). Conclusions.?CSF fungal burden, altered mental status, and rate of clearance of infection predict acute mortality in HIV-associated CM. The results suggest that earlier diagnosis, more rapidly fungicidal amphotericin-based regimens, and prompt immune reconstitution with ART are priorities for improving outcomes.
Jarvis, Joseph N.; Bicanic, Tihana; Loyse, Angela; Namarika, Daniel; Jackson, Arthur; Nussbaum, Jesse C.; Longley, Nicky; Muzoora, Conrad; Phulusa, Jacob; Taseera, Kabanda; Kanyembe, Creto; Wilson, Douglas; Hosseinipour, Mina C.; Brouwer, Annemarie E.; Limmathurotsakul, Direk; White, Nicholas; van der Horst, Charles; Wood, Robin; Meintjes, Graeme; Bradley, John; Jaffar, Shabbar; Harrison, Thomas
HIV and AIDS patients often suffer from various skin infections of viral, bacterial, and fungal origin. In addition, parasitic infestations are prevalent. Common inflammatory dermatoses include seborrheic dermatitis, psoriasis, photodermatitis, and pruritic papular eruptions. This article discusses some of these conditions with an emphasis on clinical presentation. In patients with pigmented skin, diagnosis maybe challenging and complicated by dyspigmentation. PMID:24680007
Motswaledi, Mojakgomo Hendrick; Visser, Willie
Flavobacterium meningosepticum, Chromobacterium violaceum and Listeria monocytogenes are opportunistic pathogens of man and are occasional but important causes of infections in neonates, infants and adults in Papua New Guinea. Mortality is high. Flavobacterium meningosepticum should be suspected when a weak indole producing oxidase positive Gram-negative bacillus producing a discrete yellow non-diffusing pigment at room temperature and showing a resistant antibiotic sensitivity pattern is isolated from the blood and/or C.S.F. of a neonate. Chromobacterium violaceum can be presumptively identified if a Gram-negative bacillus producing an intense non-diffusing violet pigment is cultured, commonly in associated with multiple abscess formation in the host. The isolation of a slender Gram-positive bacillus from C.S.F. or blood which produces catalase and acetylmethylcarbinol is consistent with Listeria monocytogenes. This organism forms discretely beta haemolytic colonies on blood agar and attacks the carbohydrates salicin and trehalose. PMID:6951339
The 12th International Workshops on Opportunistic Protists (IWOP-12) was held in August 2012 in Tarrytown, New York. The objectives of the IWOP meetings are to: (1) serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency-associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS and (2) foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists, e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference that brings together research groups working on these opportunistic pathogens. Slow but steady progress is being achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune-deficient and immune-competent hosts, and is providing critical insights into these emerging and reemerging pathogens. This IWOP meeting demonstrated the importance of newly developed genomic level information for many of these pathogens and how analysis of such large data sets is providing key insights into the basic biology of these organisms. A great concern is the loss of scientific expertise and diversity in the research community due to the ongoing decline in research funding. This loss of researchers is due to the small size of many of these research communities and a lack of appreciation by the larger scientific community concerning the state of art and challenges faced by researchers working on these organisms. PMID:23560871
Weiss, Louis M; Cushion, Melanie T; Didier, Elizabeth; Xiao, Lihua; Marciano-Cabral, Francine; Sinai, Anthony P; Matos, Olga; Calderon, Enrique J; Kaneshiro, Edna S
The 12th International Workshops on Opportunistic Protists (IWOP-12) was held in August 2012 in Tarrytown, New York. The objectives of the IWOP meetings are to: (1) serve as a forum for exchange of new information among active researchers concerning the basic biology, molecular genetics, immunology, biochemistry, pathogenesis, drug development, therapy, and epidemiology of these immunodeficiency-associated pathogenic eukaryotic microorganisms that are seen in patients with AIDS and (2) foster the entry of new and young investigators into these underserved research areas. The IWOP meeting focuses on opportunistic protists, e.g. the free-living amoebae, Pneumocystis, Cryptosporidium, Toxoplasma, the Microsporidia, and kinetoplastid flagellates. This conference represents the major conference that brings together research groups working on these opportunistic pathogens. Slow but steady progress is being achieved on understanding the biology of these pathogenic organisms, their involvement in disease causation in both immune-deficient and immune-competent hosts, and is providing critical insights into these emerging and reemerging pathogens. This IWOP meeting demonstrated the importance of newly developed genomic level information for many of these pathogens and how analysis of such large data sets is providing key insights into the basic biology of these organisms. A great concern is the loss of scientific expertise and diversity in the research community due to the ongoing decline in research funding. This loss of researchers is due to the small size of many of these research communities and a lack of appreciation by the larger scientific community concerning the state of art and challenges faced by researchers working on these organisms.
Weiss, Louis M.; Cushion, Melanie T.; Didier, Elizabeth; Xiao, Lihua; Marciano-Cabral, Francine; Sinai, Anthony P.; Matos, Olga; Calderon, Enrique J.; Kaneshiro, Edna S.
It is significant to develop a method to realize efficient broadcast retransmission in wireless networks. Network coding is a promising technique for this purpose. In this paper, we propose a novel Wireless Broadcast Retransmission scheme based on Opportunistic Network Coding (WBRONC) aiming at reducing the number of transmissions, as well as improving the transmission efficiency. This scheme employs a new packet scheduling algorithm which uses Packet Distribution Matrix (PDM) directly to select coded packets. Thus, low computational complexity is obtained by it. It is denoted from the analysis and simulation results that the WBRONC scheme provides a substantial improvement both in transmission efficiency and computational overhead.
Gou, Liang; Zhang, Gengxin; Sun, Wei; Bian, Dongming
Ports served not only as interfaces between land and sea, but as central gathering spaces for economic and cultural exchange. Drawing on case studies from the eastern Mediterranean island of Cyprus, this paper situates opportunistic ports lacking built facilities within a broader socioeconomic context of diverse maritime communications, expanding rural settlement, and increased agricultural productivity during late antiquity. Though simple, these sites served as active agents in the development of new maritime networks as well as local markets throughout their hinterlands, adding flexibility and dynamism to the economic ties between city, countryside, and the wider late Roman world.
Immunomodulatory antibodies that enhance the immune system to fight cancer are revolutionizing the treatment of patients with an expanding variety of malignancies. There is a unique spectrum of side effects associated with immunomodulatory antibodies, termed immune-related adverse events (irAEs), which include colitis and hepatitis among others. The treatment of refractory or severe irAEs can occasionally require significant immunosuppression, involving steroids or tumor necrosis factor-alpha antagonists, placing these patients at risk for infections. We present the first reported case to our knowledge of an opportunistic infection in a patient treated with an immunomodulatory antibody. As the use of immunomodulatory antibodies expands and more patients develop irAEs that require treatment with immunosuppression, recognition of the potential for opportunistic infections in this emerging patient population will be critical. Prospective trials are needed to define the optimal immunosuppressive management of irAEs and determine whether prophylactic antiviral, antibacterial, or antifungal therapies are beneficial in this unique population.
Methamphetamine (METH) abuse in conjunction with human immunodeficiency virus (HIV) exacerbates neuropathogenesis and accelerates neurocognitive impairments in the central nervous system (CNS), collectively termed HIV Associated Neurocognitive Disorders (HAND). Since both HIV and METH have been implicated in altering the synaptic architecture, this study focused on investigating alterations in synaptic proteins. Employing a quantitative proteomics approach on synaptosomes isolated from the caudate nucleus from two groups of rhesus monkeys chronically infected with simian immunodeficiency virus (SIV) differing by one regimen, METH treatment, we identified the neuron specific Na+/K+-ATPase alpha 1 isoform 3 (ATP1A3) to be up regulated after METH treatment, and validated its up regulation by METH in vitro. Further studies on signaling mechanisms revealed that the activation of ATP1A3 involves the extracellular regulated kinase (ERK) pathway. Given its function in maintaining ionic gradients and emerging role as a signaling molecule, changes in ATP1A3 yields insights into the mechanisms associated with HAND and interactions with drugs of abuse.
Pendyala, Gurudutt; Buescher, James L.; Fox, Howard S.
Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable. PMID:24014242
Barta, Stefan K; Xue, Xiaonan; Wang, Dan; Tamari, Roni; Lee, Jeannette Y; Mounier, Nicolas; Kaplan, Lawrence D; Ribera, Josep-Maria; Spina, Michele; Tirelli, Umberto; Weiss, Rudolf; Galicier, Lionel; Boue, Francois; Wilson, Wyndham H; Wyen, Christoph; Oriol, Albert; Navarro, José-Tomás; Dunleavy, Kieron; Little, Richard F; Ratner, Lee; Garcia, Olga; Morgades, Mireia; Remick, Scot C; Noy, Ariela; Sparano, Joseph A
It is well established that infection with the human immunodeficiency virus (HIV) leads to immune suppression. Less well known is the fact that long-term, progressive HIV disease is associated with the development of cognitive deficits. Since the introduction of combined antiretroviral therapy (cART), the clinical presentation of HIV infection has evolved into a chronic illness with very low levels of viral replication and chronic immune activation, with compliant affected individuals surviving for decades with a high quality of life. Despite these advances, many HIV-infected individuals develop some degree of neurodegeneration and cognitive impairment. The underlying pathophysiological mechanisms are not well understood, and there are no effective treatments. Thus, there is an unmet need for animal models that enable the study of HIV-associated neurocognitive disorders (HAND) and the testing of new therapeutic approaches to combat them. Here, we review the pros and cons of existing mouse models of HIV infection for addressing these aims and propose a detailed strategy for developing a new mouse model of HIV infection.
Jaeger, Laura B.; Nath, Avindra
Although the introduction of highly active antiretroviral therapy (HAART) has led to a strong reduction of HIV-associated dementia (HAD) incidence, the prevalence of minor HIV-1 associated neurocognitive disorder (HAND) is rising among AIDS patients. HAART medication has shifted neuropathology from a subacute encephalitic condition to a subtle neurodegenerative process involving synaptic and dendritic degeneration, particularly of hippocampal neurons that are spared prior to HAART medication. Considerable neuroinflammation coupled with mononuclear phagocyte activation is present in HAART-medicated brains, particularly in the hippocampus. Accumulating evidence suggests that the resultant elevated secretion of pro-inflammatory cytokines such as interferon-? (IFN-?), tumor necrosis factor-? (TNF-?), and interleukin-1? (IL-1?) can increase amyloid-? peptide (A?) generation and reduce A? clearance. Recent advancements in Alzheimer’s disease (AD) research identified A? biogenesis and clearance venues that are potentially influenced by HIV viral infection, providing new insights into beta-amyloidosis segregation in HIV patients. Our study suggests enhanced beta-amyloidosis in ART-treated HAD and HIVE brains, and suppression of A? clearance by viral infection of human primary macrophages. A growing awareness of potential convergent mechanisms leading to neurodegeneration shared by HIV and A? points to a significant chance of comorbidity of AD and HAND in senile HIV patients, which calls for a need of basic studies.
Xu, Jiqing; Ikezu, Tsuneya
Background The HIV Dementia Scale (HDS) was developed to screen for HIV-associated Neurocognitive Disorders (HAND), but concerns have persisted regarding its substandard sensitivity. This study aimed to examine the classification accuracy of the HDS using raw and norm-based cutpoints, and to evaluate the contribution of the HDS subtests to predicting HAND. Methods 1,580 HIV-infected participants from 6 U.S. sites completed the HDS, and a gold standard neuropsychological battery, on which 51% of participants were impaired. Results: Sensitivity and specificity to HAND using the standard raw HDS cutpoint were 24% and 92%, respectively. The raw HDS subtests of attention, recall, and psychomotor speed significantly contributed to classification of HAND, while visuomotor construction contributed the least. A modified raw cutpoint of 14 yielded sensitivity of 66% and specificity of 61%, with cross-validation. Using norms also significantly improved sensitivity to 69% with a concomitant reduction of specificity to 56%, while the positive predictive value declined from 75% to 62% and negative predictive value improved from 54% to 64%. The HDS showed similarly modest rates of sensitivity and specificity among subpopulations of individuals with minimal comorbidity and successful viral suppression. Conclusions Findings indicate that while the HDS is a statistically significant predictor of HAND, particularly when adjusted for demographic factors, its relatively low diagnostic classification accuracy continues to hinder its clinical utility. A raw cutpoint of 14 greatly improved the sensitivity of the previously established raw cutscore, but may be subject to ceiling effects, particularly on repeat assessments.
Sakamoto, Maiko; Marcotte, Thomas D.; Umlauf, Anya; Franklin, Donald; Heaton, Robert K.; Ellis, Ronald J.; Letendre, Scott; Alexander, Terry; McCutchan, J. Allen; Morgan, Erin E.; Woods, Steven Paul; Collier, Ann C.; Marra, Christina M.; Clifford, David B.; Gelman, Benjamin B.; McArthur, Justin C.; Morgello, Susan; Simpson, David; Grant, Igor
Many practical clinical questions regarding the management of human immunodeficiency virus (HIV)–associated neurocognitive disorder (HAND) remain unanswered. We sought to identify and develop practical answers to key clinical questions in HAND management. Sixty-six specialists from 30 countries provided input into the program, which was overseen by a steering committee. Fourteen questions were rated as being of greatest clinical importance. Answers were drafted by an expert group based on a comprehensive literature review. Sixty-three experts convened to determine consensus and level of evidence for the answers. Consensus was reached on all answers. For instance, good practice suggests that all HIV patients should be screened for HAND early in disease using standardized tools. Follow-up frequency depends on whether HAND is already present or whether clinical data suggest risk for developing HAND. Worsening neurocognitive impairment may trigger consideration of antiretroviral modification when other causes have been excluded. The Mind Exchange program provides practical guidance in the diagnosis, monitoring, and treatment of HAND.
Antinori, Andrea; Arendt, Gabriele; Grant, Igor; Letendre, Scott; Chair; Munoz-Moreno, Jose A.; Eggers, Christian; Brew, Bruce; Brouillette, Marie-Josee; Bernal-Cano, Francisco; Carvalhal, Adriana; Christo, Paulo Pereira; Cinque, Paola; Cysique, Lucette; Ellis, Ronald; Everall, Ian; Gasnault, Jacques; Husstedt, Ingo; Korten, Volkan; Machala, Ladislav; Obermann, Mark; Ouakinin, Silvia; Podzamczer, Daniel; Portegies, Peter; Rackstraw, Simon; Rourke, Sean; Sherr, Lorraine; Streinu-Cercel, Adrian; Winston, Alan; Wojna, Valerie; Yazdanpannah, Yazdan; Arbess, Gordon; Baril, Jean-Guy; Begovac, Josip; Bergin, Colm; Bonfanti, Paolo; Bonora, Stefano; Brinkman, Kees; Canestri, Ana; Cholewinska-Szymanska, Grazyna; Chowers, Michal; Cooney, John; Corti, Marcelo; Doherty, Colin; Elbirt, Daniel; Esser, Stefan; Florence, Eric; Force, Gilles; Gill, John; Goffard, Jean-Christophe; Harrer, Thomas; Li, Patrick; de Kerckhove, Linos Van; Knecht, Gaby; Matsushita, Shuzo; Matulionyte, Raimonda; McConkey, Sam; Mouglignier, Antoine; Oka, Shinichi; Penalva, Augusto; Riesenberg, Klaris; Sambatakou, Helen; Tozzi, Valerio; Vassallo, Matteo; Wetterberg, Peter; Drapato, Alicia Wiercinska
Executive dysfunction remains among the most prevalent cognitive domains impaired in persons with HIV-associated neurocognitive disorders (HAND). However, little is known specifically about the cognitive architecture or everyday functioning implications of planning, which is an aspect of executive functions involving the identification, organization, and completion of sequential behaviors toward the accomplishment of a goal. The current study examined these issues using the Tower of LondonDX in 53 individuals with HAND, 109 HIV-infected persons without HAND, and 82 seronegative participants. The HAND+ group performed significantly more poorly than HIV-infected individuals without HAND on number of correct moves, total moves, execution time, time violations, and rule violations. Within the HIV+ group as a whole, greater total move scores and rule violations were most strongly associated with executive dysfunction. Of clinical relevance, elevated total moves and rule violations were significant, independent predictors of self-reported declines in instrumental activities of daily living and unemployment status in HIV. These results suggest that planning accuracy, efficiency, and rule-bound control are impaired in HAND, and may meaningfully affect more cognitively complex aspects of everyday living.
Cattie, Jordan E.; Doyle, Katie; Weber, Erica; Grant, Igor; Woods, Steven Paul
Background HIV-associated neurocognitive disorders (HAND) include both “asymptomatic” and “symptomatic” neurocognitive impairment. Asymptomatic diagnoses indicate HAND without demonstrable functional impairment. The present study compares three approaches to assess functional decline: 1) self-report measures only (SR); 2) performance-based measures only (PB); and 3) combining SR and PB measures (SR+PB). Methods We assessed 674 HIV-infected research volunteers with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via SR and PB measures. HAND diagnoses in these 233 cognitively impaired individuals were determined according to published criteria, which allow for both SR and PB methods in establishing functional decline. Results The dual-method diagnosed the most symptomatic (53%; 124/233) HAND conditions, compared to either singular method, which were only 59% concordant. Participants classified as functionally-impaired via PB were more likely to be unemployed, more immunosuppressed, and had more hepatitis-C co-infection, whereas those classified via singular SR were more depressed. Conclusions Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. PB-based classification was associated with objective functional status (i.e., employment) and important disease-related factors, whereas the typical SR singular classifications may be biased by depressed mood.
Blackstone, K.; Moore, D. J.; Heaton, R. K.; Franklin, D. R.; Woods, S. P.; Clifford, D. B.; Collier, A. C.; Marra, C. M.; Gelman, B. B.; McArthur, J. C.; Morgello, S.; Simpson, D. M.; Rivera-Mindt, M.; Deutsch, R.; Ellis, R. J.; Atkinson, J. Hampton; Grant, I.
Chronic immune activation in HIV-infected individuals leads to accumulation of exhausted tissue-like memory B cells. Exhausted lymphocytes display increased expression of multiple inhibitory receptors, which may contribute to the inefficiency of HIV-specific antibody responses. Here, we show that downregulation of B cell inhibitory receptors in primary human B cells led to increased tissue-like memory B cell proliferation and responsiveness against HIV. In human B cells, siRNA knockdown of 9 known and putative B cell inhibitory receptors led to enhanced B cell receptor–mediated (BCR-mediated) proliferation of tissue-like memory but not other B cell subpopulations. The strongest effects were observed with the putative inhibitory receptors Fc receptor–like–4 (FCRL4) and sialic acid–binding Ig-like lectin 6 (Siglec-6). Inhibitory receptor downregulation also led to increased levels of HIV-specific antibody-secreting cells and B cell–associated chemokines and cytokines. The absence of known ligands for FCRL4 and Siglec-6 suggests these receptors may regulate BCR signaling through their own constitutive or tonic signaling. Furthermore, the extent of FCLR4 knockdown effects on BCR-mediated proliferation varied depending on the costimulatory ligand, suggesting that inhibitory receptors may engage specific pathways in inhibiting B cell proliferation. These findings on HIV-associated B cell exhaustion define potential targets for reversing the deleterious effect of inhibitory receptors on immune responses against persistent viral infections.
Kardava, Lela; Moir, Susan; Wang, Wei; Ho, Jason; Buckner, Clarisa M.; Posada, Jacqueline G.; O'Shea, Marie A.; Roby, Gregg; Chen, Jenny; Sohn, Hae Won; Chun, Tae-Wook; Pierce, Susan K.; Fauci, Anthony S.
Background HIV-associated distal sensory polyneuropathy (HIV-DSP) is the most frequently reported neurologic complication associated with HIV infection. NGX-4010 is a capsaicin 8% dermal patch with demonstrated efficacy in the treatment of HIV-DSP. Data from two phase III, double-blind studies were integrated to further analyze the efficacy and safety of NGX-4010 and explore the effect of demographic and baseline factors on NGX-4010 treatment in HIV-DSP. Methods Data from two similarly designed studies in which patients with HIV-DSP received NGX-4010 or a low-concentration control patch (capsaicin 0.04% w/w) for 30 or 60 minutes were integrated. Efficacy assessments included the mean percent change from baseline in Numeric Pain Rating Scale (NPRS) scores to Weeks 2–12. Safety and tolerability assessments included adverse events (AEs) and pain during and after treatment. Results Patients (n = 239) treated with NGX-4010 for 30 minutes demonstrated significantly (p = 0.0026) greater pain relief compared with controls (n = 100); the mean percent change in NPRS scores from baseline to Weeks 2–12 was ?27.0% versus ?15.7%, respectively. Patients who received a 60-minute application of NGX-4010 (n = 243) showed comparable pain reductions (?27.5%) to patients treated for 30 minutes, but this was not statistically superior to controls (n = 115). NGX-4010 was effective regardless of gender, baseline pain score, duration of HIV-DSP, or use of concomitant neuropathic pain medication, although NGX-4010 efficacy was greater in patients not receiving concomitant neuropathic pain medications. NGX-4010 was well tolerated; the most common AEs were application-site pain and erythema, and most AEs were mild to moderate. The transient increase in pain associated with NGX-4010 treatment decreased the day after treatment and returned to baseline by Day 2. Conclusions A single 30-minute application of NGX-4010 provides significant pain relief for at least 12 weeks in patients with HIV-DSP and is well tolerated. Trial registration C107 = NCT00064623; C119 = NCT00321672
HIV-associated neurocognitive impairment, particularly in the domain of prospective memory (ProM), increases the risk of poor everyday functioning outcomes, including medication non-adherence. However, whether ProM plays a role in health care compliance outside of the realm of medication adherence remains to be determined. This study evaluated the hypothesis that ProM is an independent predictor of failure to comply with non-medication-related
Jennifer B. Zogg; Steven Paul Woods; Erica Weber; Jennifer E. Iudicello; Matthew S. Dawson; Igor Grant
Lipodystrophy (LD) is a common adverse effect of HIV treatment with highly active antiretroviral therapy, which comprises morphological and metabolic changes. The underlying mechanisms for LD are thought to be due to mitochondrial toxicity and insulin resistance, which results from derangements in levels of adipose tissue-derived proteins (adipocytokines) that are actively involved in energy homeostasis. Several management strategies for combating this syndrome are available, but they all have limitations. They include: switching from thymidine analogues to tenofovir or abacavir in lipoatrophy, or switching from protease inhibitors associated with hyperlipidaemia to a protease-sparing option; injection into the face with either biodegradable fillers such as poly-L-lactic acid and hyaluronic acid (a temporary measure requiring re-treatment) or permanent fillers such as bio-alcamid (with the risk of foreign body reaction or granuloma formation); and structured treatment interruption with the risk of loss of virological control and disease progression. There is therefore a need to explore alternative therapeutic options. Some new approaches including adipocytokines, uridine supplementation, glitazones, growth hormone (or growth hormone-releasing hormone analogues), metformin and statins (used alone or in combination) merit further investigation. PMID:18565973
Mallewa, Jane E; Wilkins, Edmund; Vilar, Javier; Mallewa, Macpherson; Doran, Dominic; Back, David; Pirmohamed, Munir
HIV retinopathy is the most common non-infectious complication in the eyes of HIV-positive individuals. Oncotic lesions in the retinal nerve fiber layer, referred to as cotton wool spots (CWS), and intraretinal (IR) hemorrhages are frequently observed but are not unique to this pathology. HIV-positive patients have impaired color vision and contrast sensitivity, which worsens with age. Evidence of inner–retinal lesions and damage have been documented ophthalmoscopically, however their long term structural effect has not been investigated. It has been hypothesized that they may be partially responsible for loss of visual function and visual field. In this study we utilized clinical data, retinal imaging and transcriptomics approaches to comprehensively interrogate non-infectious HIV retinopathy. The methods employed encompassed clinical examinations, fundus photography, indirect ophthalmoscopy, Farmsworth-Munsell 100 hue discrimination testing and Illumina BeadChip analyses. Here we show that changes in the outer retina, specifically in the retinal pigment epithelium (RPE) and photoreceptor outer segments (POS) contribute to vision changes in non-infectious HIV retinopathy. We find that in HIV-positive retinae there is an induction of rhodopsin and other transcripts (including PDE6A, PDE6B, PDE6G, CNGA1, CNGB1, CRX, NRL) involved in visual transduction, as well as structural components of the rod photoreceptors (ABCA4 and ROM1). This is consistent with an increased rate of renewal of rod outer segments induced via increased phagocytosis by HIV-infected RPE previously reported in culture. Cone-specific transcripts (OPN1SW, OPN1LW, PDE6C, PDE6H and GRK7) are uniformly downregulated in HIV positive retina, likely due to a partial loss of cone photoreceptors. Active cotton wool spots and intraretinal hemorrhages (IRH) may not affect photoreceptors directly and the interaction of photoreceptors with the aging RPE may be the key to the progressive vision changes in HIV-positive patients.
Freeman, William R.; Sprague, L. James; Gomez, Maria Laura; Cheng, Lingyun; El-Emam, Sharif; Mojana, Francesca; Bartsch, Dirk-Uwe; Bosten, Jenny; Ayyagari, Radha; Hardiman, Gary
Shewanella putrefaciens and Shewanella algae are Gram negative, nonfermentative and oxidative bacilli whose the main phenotypic feature is the production of hydrogen sulfide gas. Widespread in the environment, both S. putrefaciens and S. algae species are rare human bacteria although they are reported with increasing frequency as a cause of opportunistic infection in humans, such as skin and soft tissue infections and bacteremia. Chronic infections of the lower limbs and liver disease have been identified as risk factors for bloodstream infection, with a faster course and a poorer prognosis in the last case. S. algae appears to be more virulent than S. putrefaciens. Most human S. putrefaciens strains are isolated from bacterial flora, which puts to question its clinical significance. Molecular biology must be used for an adequate identification because S. algae can easily be mistaken for S. putrefaciens with usual tests. PMID:15914286
Pagniez, H; Berche, P
The aim of this study was to isolate, quantify, identify, and compare opportunistic microorganisms (Candida and Staphylococcus genera and Enterobacteriaceae/Pseudomonadaceae families) from prosthesis-fitting surfaces, the hard palate, and mouth rinses of individuals wearing removable maxillary prosthesis with (50) and without (50) lesions of denture stomatitis (DS). The strains were collected and identified using phenotypic, biochemical and molecular tests. The counts of microorganisms were significantly higher in the group of individuals with DS (P < 0.05). C. albicans was the most frequently isolated yeast species in both groups, following by C. tropicalis and C. glabrata. Six isolates were identified as C. dubliniensis. S. aureus and S. epidermidis were the most frequent Staphylococcus species in both groups. Klebsiella pneumoniae was the predominant species in both groups. The association between Candida spp. and bacteria isolated in this study with DS suggests that these microorganisms may play important roles in the establishment and persistence of this disease. PMID:23747028
Pereira, Cristiane Aparecida; Toledo, Bruna Costa; Santos, Camila Teles; Pereira Costa, Anna Carolina Borges; Back-Brito, Graziella Nuernberg; Kaminagakura, Estela; Jorge, Antonio Olavo Cardoso
This report summarises clinical and pathological observations on Fell pony foals with a range of signs that included ill thrift, anaemia, respiratory infection, glossal hyperkeratosis and diarrhoea. Some of the foals had normochromic, normocytic anaemia and some had low levels of plasma proteins, including immunoglobulin G. Antibiotic and supportive treatment was ineffective and all affected foals died or were killed on humane grounds. Postmortem examination of 12 foals and tissues from 2 other foals revealed a range of lesions that included glossal hyperkeratosis, typhlocolitis, intestinal cryptosporidiosis, granulomatous enteritis, proliferative and necrotising bronchiolitis consistent with adenovirus infection; lesions similar to those in the respiratory tract were present in the salivary gland and pancreas of individual foals. Lymphoid tissue was judged to be smaller than expected. These observations suggest the possibility of opportunistic infections secondary to some form of undefined immunocompromised state. PMID:11037259
Richards, A J; Kelly, D F; Knottenbelt, D C; Cheeseman, M T; Dixon, J B
Antimicrobial therapy may cause changes in the resident oral microbiota, with the increase of opportunistic pathogens. The aim of this study was to compare the prevalence of Candida, Staphylococcus, Pseudomonas and Enterobacteriaceae in the oral cavity of fifty patients undergoing antibiotic therapy for pulmonary tuberculosis and systemically healthy controls. Oral rinsing and subgingival samples were obtained, plated in Sabouraud dextrose agar with chloramphenicol, mannitol agar and MacConkey agar, and incubated for 48 h at 37°C. Candida spp. and coagulase-positive staphylococci were identified by phenotypic tests, C. dubliniensis, by multiplex PCR, and coagulase-negative staphylococci, Enterobacteriaceae and Pseudomonas spp., by the API systems. The number of Candida spp. was significantly higher in tuberculosis patients, and C. albicans was the most prevalent specie. No significant differences in the prevalence of other microorganisms were observed. In conclusion, the antimicrobial therapy for pulmonary tuberculosis induced significant increase only in the amounts of Candida spp.
Querido, Silvia Maria Rodrigues; Back-Brito, Graziella Nuernberg; dos Santos, Silvana Soleo Ferreira; Leao, Mariella Vieira Pereira; Koga-Ito, Cristiane Yumi; Jorge, Antonio Olavo Cardoso
Hedeoma drummondii is a medicinal plant with diverse properties; however, validations of its medicinal uses are scarce. To evaluate its antimicrobial properties H. drummondii, was tested against opportunistic pathogens of medical importance. Antimicrobial tests were performed by the microdilution method in order to determine the Minimal Inhibitory Concentration (MIC) for each extract. Extracts of this plant showed relevant antimicrobial activity, results revealed that the hexanic extract has stronger activity and broader spectrum compared to acetone and methanol extracts. The activity of hexanic extract may be attributed mainly to the presence of the monoterpenes pulegone and menthol. In conclusion, the hexanic extract possess relevant antibacterial properties which suggests that H. drummondii have bioactive principles; these new data provide scientific support for the use of this plant in traditional medicine, particularly for gastrointestinal diseases. PMID:21870634
Viveros-Valdez, E; Rivas-Morales, C; Oranday-Cardenas, A; Verde-Star, M J; Carranza-Rosales, P
Microorganisms are likely to develop an organic film on pipes, water reservoirs and filters used for waste water reclamation during extended missions in space. These biofilms can serve to protect and concentrate potentially pathogenic microorganisms. Our investigation has emphasized the survival strategy of opportunistic pathogenic bacteria in distilled water. Pseudomonas aeruginosa and Staphylococcus aureus were used as test organisms. Cultures were incubated at 10 degrees, 25 degrees, and 37 degrees C. No viable Staphylococcus cells were detected after the first week of incubation. P. aeruginosa, however, survived in distilled water up to 5 months at all three temperatures tested. The starved cells were able to form a biofilm layer on stainless steel. The cells exhibited a negative surface charge. The charge may be involved in the adhesion of this bacterium to metal substrata. We are currently investigating the importance of adhesion in the survival of this and other potential human pathogens found in water recycling systems.
Boyle, M.; Ford, T.; Maki, J. S.; Mitchell, R.
Freshwater fouling invertebrate zebra mussels (Dreissena polymorpha) harbor a diverse population of microorganisms in the Great Lakes of North America. Among the indigenous microorganisms, selective species are opportunistic pathogens to zebra mussels. Pathogenicity to zebra mussels by opportunistic bacteria isolated from the mussels was investigated in this study. Among the more than 30 bacteria isolated from temperature-stressed mussels, Aeromonas media,
Ji-Dong Gu; Ralph Mitchell
Opportunistic routing significantly increases unicast throughput in wireless mesh networks by effectively utilizing the wireless broadcast medium. With network coding, opportunistic routing can be implemented in a simple and practical way without resorting to a complicated scheduling protocol. Due to constraints of computational complexity, a protocol utilizing network coding needs to perform segmented network coding, which partitions the data into
Yunfeng Lin; Baochun Li; Ben Liang
Understanding the natural history of human immunodeficiency virus type 1 (HIV-1) and opportunistic infections in sub- Saharan Africa is necessary to optimize strategies for the prophylaxis and treatment of opportunistic infections and to understand the likely impact of antiretroviral therapy. We undertook a systematic review of the literature on HIV-1 infection in sub-Saharan Africa to assess data from recent cohorts
Charles B. Holmes; Elena Losina; Rochelle P. Walensky; Yazdan Yazdanpanah; Kenneth A. Freedberg
Because of the increasing use of immunosuppressive and biological drugs, the occurrence of opportunistic infections has become a key safety issue for patients with inflammatory bowel disease (IBD). Consequently, improvement of healthcare workers' knowledge of this domain is urgent. In this review, the preventive measures that would help to reduce the rate of opportunistic infections in patients with IBD are
N Viget; G Vernier-Massouille; D Salmon-Ceron; Y Yazdanpanah; J-F Colombel
In this paper, we consider a cognitive radio system in fading wireless channels and propose an opportunistic power control strategy for the cognitive users, which serves as an alternative way to protect the primary user's transmission and to realize spectrum sharing between the primary user and the cognitive users. The key feature of the proposed strategy is that, via opportunistically
Yan Chen; Guanding Yu; Zhaoyang Zhang; Hsiao-hwa Chen; Peiliang Qiu
Wireless sensor networks are designed for a plethora of applications, such as unattended event monitoring and tracking. Source-privacy is one of the looming challenges that threaten successful deployment of these sensor networks, especially when they are used to monitor sensitive objects. In order to enhance source-location privacy in wireless sensor networks, we propose the use opportunistic routing schemes. In opportunistic
Petros Spachos; Liang Song; Dimitrios Hatzinakos
We analyzed RNA gene expression in neurons from 16 cases in four categories, HIV associated dementia with HIV encephalitis (HAD/HIVE), HAD alone, HIVE alone, and HIV-1-positive (HIV+)with neither HAD nor HIVE. We produced the neurons by laser capture microdissection (LCM) from cryopreserved globus pallidus. Of 55,000 gene fragments analyzed, expression of 197 genes was identified with significance (p = 0.005).We examined each gene for its position in the human genome and found a non-stochastic occurrence for only seven genes, on chromosome 22. Six of the seven genes were identified, CSNK1E (casein kinase 1 epsilon), DGCR8 (Di George syndrome critical region 8), GGA1 (Golgi associated gamma adaptin ear containing ARF binding protein 1), MAPK11 (mitogen activated protein kinase 11), SMCR7L (Smith-Magenis syndrome chromosome region candidate 7-like), andTBC1D22A (TBC1 domain family member 22A). Six genes (CSNK1E, DGCR8, GGA1, MAPK11, SMCR7L, and one unidentified gene) had similar expression profiles across HAD/HIVE, HAD, and HIVE vs. HIV+ whereas one gene (TBC1D22A) had a differing gene expression profile across these patient categories. There are several mental disease-related genes including miRNAs on chromosome 22 and two of the genes (DGCR8 and SMCR7L) identified here are mental disease-related. We speculate that dysregulation of gene expression may occur through mechanisms involving chromatin damage and remodeling. We conclude that the pathogenesis of NeuroAIDS involves dysregulation of expression of mental disease-related genes on chromosome 22 as well as additional genes on other chromosomes. The involvement of these genes as well as miRNA requires additional investigation since numerous genes appear to be involved. PMID:21738310
Shapshak, Paul; Duncan, Robert; Kangueane, Pandajarasamme; Somboonwit, Charurut; Sinnott, John; Commins, Deborah; Singer, Elyse; Levine, Andrew
HIV-associated neurocognitive disorders (HAND) continue to be a neurological complication of HIV infection in the era of combined antiretroviral therapy (cART). Hippocampal neurodegeneration and dysfunction occurs as a result of HIV infection, but few studies to date have assesses spatial learning and memory function in patients with HAND. We used the Memory Island (MI) Test to study the effects of HIV infection, Apolipoprotein E (ApoE) allele status, and CSF ApoE protein levels on spatial learning and memory in our cohort of Hispanic women. The MI Test is a virtual reality-based computer program that tests spatial learning and memory, and was designed to resemble the Morris Water Maze (MWM) test of hippocampal function widely used in rodent studies. In the current study, HIV-seropositive women (n=20) and controls (n=16) were evaluated with neuropsychological (NP) tests, the MI Test, ApoE, and CSF ApoE assays. On the MI, the HIV-seropositive group showed significant reduced learning and delayed memory performance compared with HIV-seronegative controls. When stratified by cognitive performance on NP tests, the HIV-seropositive, cognitively impaired group performed worse than HIV-seronegative controls in ability to learn and in the delayed memory trial. Interestingly, differences were observed in the results obtained by the NP tests and the MI Test for ?4 carriers and non-carriers: NP tests showed effects of the ?4 allele in HIV-seronegative women but not HIV-seropositive ones, whereas as the converse was true for the MI Test. Our findings suggest that the MI test is sensitive in detecting spatial deficits in HIV-seropositive women, and that these deficits may arise relatively early in the course of HAND.
Morales, Diana; Acevedo, Summer F.; Skolasky, Richard L.; Hechavarria, Rosa; Santiago, Sharon; De La Torre, Tania; Maldonado, Elizabeth; Wojna, Valerie
Despite the use of anti-retroviral therapies, a majority of HIV-infected individuals still develop HIV-Associated Neurocognitive Disorders (HAND), indicating that host inflammatory mediators, in addition to viral proteins, may be contributing to these disorders. Consistently, we have previously shown that levels of the inflammatory mediator soluble CD40L (sCD40L) are elevated in the circulation of HIV-infected, cognitively impaired individuals as compared to their infected, non-impaired counterparts. Recent studies from our group suggest a role for the CD40/CD40L dyad in blood brain barrier (BBB) permeability and interestingly, sCD40L is thought to regulate BBB permeability in other inflammatory disorders of the CNS. Using complementary multiphoton microscopy and quantitative analyses in wild-type and CD40L deficient mice, we now reveal that the HIV transactivator of transcription (Tat) can induce BBB permeability in a CD40L-dependent manner. This permeability of the BBB was found to be the result of aberrant platelet activation induced by Tat, since depletion of platelets prior to treatment reversed Tat-induced BBB permeability. Furthermore, Tat treatment led to an increase in granulocyte antigen 1 (Gr1) positive monocytes, indicating an expansion of the inflammatory subset of cells in these mice, which were found to adhere more readily to the brain microvasculature in Tat treated animals. Exploring the mechanisms by which the BBB becomes compromised during HIV infection has the potential to reveal novel therapeutic targets, thereby aiding in the development of adjunct therapies for the management of HAND, which are currently lacking. PMID:23251626
Davidson, Donna C; Hirschman, Michael P; Sun, Anita; Singh, Meera V; Kasischke, Karl; Maggirwar, Sanjay B
BACKGROUND Rapid means to identify or rule-out tuberculosis (TB) would permit more efficient management of HIV-infected patients starting antiretroviral treatment (ART). SETTING South African township ART clinic. OBJECTIVE To assess the diagnostic and prognostic utility of C-reactive protein (CRP) among patients being screened for TB pre-ART. DESIGN Patients were enrolled regardless of symptoms and characterized clinically. Serum CRP was measured and sputum and urine samples were subject to multiple assays for TB. Mortality at three months was assessed. RESULTS Among 496 patients (median CD4 count, 171 cells/?L), culture-positive TB was diagnosed in 81 (16.3%) patients. CRP concentrations were much higher among TB cases (median, 57.8mg/L; IQR,20.0-202.7) compared to those without TB (6.4mg/L; IQR,2.1-21.8; P<0.001). Very low (<1.5 mg/L) CRP concentrations excluded TB (100% negative predictive value) whereas very high concentrations (>400 mg/L) were strongly predictive of TB (100% positive predictive value). However, these thresholds encompassed only 14.3% and 2.0% of all patients screened, respectively, and only 12.3% of TB cases. TB patients with CRP concentrations ?50 mg/L were substantially more likely to have poor prognostic characteristics, higher mycobacterial load, disseminated disease and greater mortality risk. CONCLUSION CRP concentrations can be used pre-ART to identify groups of patients with very high or very low TB risk, but only in an unacceptably small minority of patients screened. However, CRP concentrations have useful prognostic value in those with HIV-associated TB.
Lawn, Stephen D.; Kerkhoff, Andrew D.; Vogt, Monica; Wood, Robin
Grids currently in production can be broadly classified as either service Grids, composed of dedicated resources, or opportunistic Grids that harvest the computing power of non-dedicated resources when they are idle. While a service Grid provides high and well defined levels of quality of service, an opportunistic Grid provides only a best-effort service. Nevertheless, since opportunistic Grids do not require
Francisco Vilar Brasileiro; Matheus Gaudencio; Rafael Silva; Alexandre Duarte; Diego Scardaci; Leandro Neumann Ciuffo; Rafael Mayo; Herbert Hoeger; Michael Stanton; Raul Ramos; Roberto Barbera; Bernard Marechal; Philippe Gavillet; Diego Carvalho
An opportunistic experiment is a type of randomized controlled trial that studies the effects of a planned intervention or policy change with minimal added disruption and cost. This guide defines opportunistic experiments and provides examples, discusses issues to consider when identifying potential opportunistic experiments, and outlines the…
Resch, Alexandra; Berk, Jillian; Akers, Lauren
Objectives To assess the temporal trends in incidence of AIDS-defining opportunistic illnesses in an urban cohort of a middle-income country. Methods HIV infected patients aged ?18 years at cohort entry were included in this analysis. We calculated incidence rates per 1000 persons-years of observation for the first opportunistic illness presented after cohort enrollment, from 1987 to 2012. Trends for overall and specific opportunistic illnesses were tested and incidence rate ratios for the most recent calendar period were calculated as the ratio between the incidence rate observed in the most recent period of the study (2009–2012) and the incidence rate observed in first period of the study (1987–1990). Results Overall, 3378 patients were included in this analysis; of which 1119 (33%) patients presented an opportunistic illness during follow up. Incidence rates of all opportunistic illnesses decreased over time, and the overall opportunistic illness incidence rates fell from 295.4/1000 persons-years in 1987–1990 to 34.6/1000 persons-years in 2009–2012. Tuberculosis, esophageal candidiasis, cerebral toxoplasmosis and Pneumocystis jirovecii pneumonia were the most incident opportunistic illnesses in the cohort. Tuberculosis had the highest incidence rate in the study period. The peak in tuberculosis incidence occurred in 1991–1993 (80.8/1000 persons-years). Cerebral toxoplasmosis was the third most incident opportunistic illness in the study, with a peak of incidence of 43.6/1000 persons-year in 1987–1990. Conclusions All opportunistic illnesses incidence rates decreased over the years but they still occur in an unacceptable frequency. Tuberculosis co-infection among HIV-infected persists as an important challenge for health care professionals and policy makers in our setting. Impressively high rates of cerebral toxoplasmosis were found suggesting that its incidence among HIV-infected is linked to the high prevalence of Toxoplasma gondii infection in the general population.
Coelho, Lara; Cardoso, Sandra Wagner; Amancio, Rodrigo Teixeira; Moreira, Ronaldo Ismerio; Campos, Dayse Pereira; Veloso, Valdilea Goncalves; Grinsztejn, Beatriz; Luz, Paula Mendes
This article presents two cases of opportunistic mycoses (OMs) of the central nervous system (CNS) caused by Cryptococcus neoformans and Aspergillus nidulans, respectively. The patients were hospitalised in local hospitals between 2009 and 2011 because of unspecific symptoms (fever, headache, and/or weight lost). Duration of symptoms varied from 4 days to over 2 weeks. The patients were treated with antibiotics and symptomatically. OM was not suspected in any of them. The patients became critically ill with symptoms of CNS involvement and were transferred to the Intensive Care Unit (ICU) of the University Hospital for Infectious diseases (UHID) in Zagreb. None of the patients belonged to the high-risk population for developing OMs. They were not HIV-infected, had no transplantation of bone marrow or solid organ, and were not on severe immunosuppressive chemotherapy. Fungi were isolated from cerebrospinal fluid (CSF) samples and, in one patient, from aspirate of cerebral abscess. Isolation and mycological identification of all fungal isolates and in vitro antifungal susceptibility testing of these isolates were done at the Reference Centre for Mycological Diagnostics of Systemic and Disseminated Infections (RCMDSDI) in Zagreb. The patient with cryptococcal meningitis was treated with amphotericin B and fluconazole and the patient with cerebral aspergilloma with voriconazole. PMID:23334046
Mlinari? Missoni, Emilija; Barši?, Bruno
Finegoldia magna (formerly Peptostreptococcus magnus), a member of the Gram-positive anaerobic cocci (GPAC), is a commensal bacterium colonizing human skin and mucous membranes. Moreover, it is also recognized as an opportunistic pathogen responsible for various infectious diseases. Here, we report the complete genome sequence of F. magna ATCC 29328. The genome consists of a 1 797 577 bp circular chromosome and an 189 163 bp plasmid (pPEP1). The metabolic maps constructed based on the genome information confirmed that most F. magna strains cannot ferment most sugars, except fructose, and have various aminopeptidase activities. Three homologs of albumin-binding protein, a known virulence factor useful for antiphagocytosis, are encoded on the chromosome, and one albumin-binding protein homolog is encoded on the plasmid. A unique feature of the genome is that F. magna encodes many sortase genes, of which substrates may be involved in bacterial pathogenesis, such as antiphagocytosis and adherence to the host cell. The plasmid pPEP1 encodes seven sortase and seven substrate genes, whereas the chromosome encodes four sortase and 19 substrate genes. These plasmid-encoded sortases may play important roles in the pathogenesis of F. magna by enriching the variety of cell wall anchored surface proteins.
Goto, Takatsugu; Yamashita, Atsushi; Hirakawa, Hideki; Matsutani, Minenosuke; Todo, Kozo; Ohshima, Kenshiro; Toh, Hidehiro; Miyamoto, Kazuaki; Kuhara, Satoru; Hattori, Masahira; Shimizu, Tohru; Akimoto, Shigeru
The ubiquity of portable wireless-enabled computing and communications devices has stimulated the emergence of malicious codes (wireless worms) that are capable of spreading between spatially proximal devices. The potential exists for worms to be opportunistically transmitted between devices as they move around, so human mobility patterns will have an impact on epidemic spread. The scenario we address in this paper is proximity attacks from fleetingly in-contact wireless devices with short-range communication range, such as Bluetooth-enabled smart phones. An individual-based model of mobile devices is introduced and the effect of population characteristics and device behaviour on the outbreak dynamics is investigated. The model uses straight-line motion to achieve population, though it is recognised that this is a highly simplified representation of human mobility patterns. We show that the contact rate can be derived from the underlying mobility model and, through extensive simulation, that mass-action epidemic models remain applicable to worm spreading in the low density regime studied here. The model gives useful analytical expressions against which more refined simulations of worm spread can be developed and tested.
Rhodes, C. J.; Nekovee, M.
We are developing onboard planning and execution technologies to provide robust and opportunistic mission operations for a potential Titan aerobot. Aerobot have the potential for collecting a vast amount of high priority science data. However, to be effective, an aerobot must address several challenges including communication constraints, extended periods without contact with Earth, uncertain and changing environmental conditions, maneuverability constraints and potentially short-lived science opportunities. We are developing the AerOASIS system to develop and test technology to support autonomous science operations for a potential Titan Aerobot. The planning and execution component of AerOASIS is able to generate mission operations plans that achieve science and engineering objectives while respecting mission and resource constraints as well as adapting the plan to respond to new science opportunities. Our technology leverages prior work on the OASIS system for autonomous rover exploration. In this paper we describe how the OASIS planning component was adapted to address the unique challenges of a Titan Aerobot and we describe a field demonstration of the system with the JPL prototype aerobot.
Gaines, Daniel M.; Estlin, Tara; Schaffer, Steve; Castano, Rebecca; Elfes, Alberto
Free-living amebas are widely distributed in soil and water, particularly members of the genera Acanthamoeba and NAEGLERIA: Since the early 1960s, they have been recognized as opportunistic human pathogens, capable of causing infections of the central nervous system (CNS) in both immunocompetent and immunocompromised hosts. Naegleria is the causal agent of a fulminant CNS condition, primary amebic meningoencephalitis; Acanthamoeba is responsible for a more chronic and insidious infection of the CNS termed granulomatous amebic encephalitis, as well as amebic keratitis. Balamuthia sp. has been recognized in the past decade as another ameba implicated in CNS infections. Cultivation of these organisms in vitro provides the basis for a better understanding of the biology of these amebas, as well as an important means of isolating and identifying them from clinical samples. Naegleria and Acanthamoeba can be cultured axenically in cell-free media or on tissue culture cells as feeder layers and in cultures with bacteria as a food source. Balamuthia, which has yet to be isolated from the environment, will not grow on bacteria. Instead, it requires tissue culture cells as feeder layers or an enriched cell-free medium. The recent identification of another ameba, Sappinia diploidea, suggests that other free-living forms may also be involved as causal agents of human infections. PMID:12097243
Schuster, Frederick L
Background Sub-Saharan Africa cancer registries are beset by an increasing cancer burden further exacerbated by the AIDS epidemic where there are limited capabilities for cancer-AIDS match co-registration. We undertook a pilot study based on a “strength-of-evidence” approach using clinical data that is abstracted at the time of cancer registration for purposes of linking cancer diagnosis to AIDS diagnosis. Methods/Findings The standard Nairobi Cancer Registry form was modified for registrars to abstract the following clinical data from medical records regarding HIV infection/AIDS in a hierarchal approach at time of cancer registration from highest-to-lowest strength-of-evidence: 1) documentation of positive HIV serology; 2) antiretroviral drug prescription; 3) CD4+ lymphocyte count; and 4) WHO HIV clinical stage or immune suppression syndrome (ISS), which is Kenyan terminology for AIDS. Between August 1 and October 31, 2011 a total of 1,200 cancer cases were registered. Of these, 171 cases (14.3%) met clinical strength-of-evidence criteria for association with HIV infection/AIDS; 69% (118 cases were tumor types with known HIV association – Kaposi’s sarcoma, cervical cancer, non-Hodgkin’s and Hodgkin’s lymphoma, and conjunctiva carcinoma) and 31% (53) were consistent with non-AIDS defining cancers. Verifiable positive HIV serology was identified in 47 (27%) cases for an absolute seroprevalence rate of 4% among the cancer registered cases with an upper boundary of 14% among those meeting at least one of strength-of-evidence criteria. Conclusions/Significance This pilot demonstration of a hierarchal, clinical strength-of-evidence approach for cancer-AIDS registration in Kenya establishes feasibility, is readily adaptable, pragmatic, and does not require additional resources for critically under staffed cancer registries. Cancer is an emerging public health challenge, and African nations need to develop well designed population-based studies in order to better define the impact and spectrum of malignant disease in the backdrop of HIV infection.
Moats, Pamela; Gurka, Matthew J.; Mutuma, Geoffrey; Metheny, Christine; Mwamba, Peter M.; Oyiro, Peter O.; Fisher, Melanie; Ayers, Leona W.; Rochford, Rosemary; Mwanda, Walter O.; Remick, Scot C.
Cryptococcosis, a significant opportunistic infection, has become a global concern since the advent of immunosuppressive chemotherapy or in immunodeficient patients. Host responses range from a harmless colonization to disseminated disease. An accurate or definitive diagnosis in patients with cryptococcal meningitis is often delayed because of the similar clinical presentation and biochemical or cerebrospinal fluid findings to those of a variety of infectious and non-infectious aetiologies, most of which are also especially prevalent in developing countries. Rarely, patients with cryptococcal meningitis can develop immune reconstitution inflammatory syndrome (IRIS) when initiated on combination antiretroviral therapy (cART) the diagnosis which is often missed and can be fatal. Due to the similar presentation of infection and IRIS, it is often confused with the relapse of cryptococcal meningitis. We report a case of paradoxical recurrent meningitis in response to the initiation of cART in a patient diagnosed with cryptococcal meningitis and propose that the recurrent symptoms resulted from a therapy-induced reconstitution of the immune response against residual Cryptococcus neoformans. PMID:24108453
Jhamb, Rajat; Kashyap, Bineeta; Das, Shukla; Berry, Neha; Garg, Arun
Pseudomonas aeruginosa is a major life-threatening opportunistic pathogen that commonly infects immunocompromised patients. This bacterium owes its success as a pathogen largely to its metabolic versatility and flexibility. A thorough understanding of P. aeruginosa's metabolism is thus pivotal for the design of effective intervention strategies. Here we aim to provide, through systems analysis, a basis for the characterization of the genome-scale properties of this pathogen's versatile metabolic network. To this end, we reconstructed a genome-scale metabolic network of Pseudomonas aeruginosa PAO1. This reconstruction accounts for 1,056 genes (19% of the genome), 1,030 proteins, and 883 reactions. Flux balance analysis was used to identify key features of P. aeruginosa metabolism, such as growth yield, under defined conditions and with defined knowledge gaps within the network. BIOLOG substrate oxidation data were used in model expansion, and a genome-scale transposon knockout set was compared against in silico knockout predictions to validate the model. Ultimately, this genome-scale model provides a basic modeling framework with which to explore the metabolism of P. aeruginosa in the context of its environmental and genetic constraints, thereby contributing to a more thorough understanding of the genotype-phenotype relationships in this resourceful and dangerous pathogen.
Oberhardt, Matthew A.; Puchalka, Jacek; Fryer, Kimberly E.; Martins dos Santos, Vitor A. P.; Papin, Jason A.
The objective of this study is to determine the main opportunistic infections (OI) and those strongly linked to high death rate in hospital settings in Togo. It is a descriptive study conducted from June to November 2008 in 22 public and private settings of all medical specialties throughout the entire Togolese territory. Hospitalized patients with OI and HIV positive data were collected. The study was started after getting patient approval. Of 7,361 hospitalized patients, 1,764 were tested, giving a screening rate of 23.7%. We registered 714 HIV-infected patients (HIVIP), 40.5% of the patients tested. The most common OI encountered were buccal candidiasis (49.7% of HIVIP), genital candidiasis (9.1%), meningeal cryptococcosis (2.9%), bacterial infections (48.2%), cerebral toxoplasmosis (11.2%) and pulmonary tuberculosis (11.3%). OI strongly linked to a high death rate were meningeal cryptococcosis (61.9%) and cerebral toxoplasmosis (46.3%). OI constitute a major reason of hospitalization for HIVIP in Togo. This study allows a better orientation of strategies for screening and taking care of HIVIP in Togo. PMID:21359831
Apetse, K; Assogba, K; Kevi, K; Balogou, A A K; Pitche, P; Grunitzky, E
Airbome hyperspectral data were used to detect dense patches of Phragmites australis, a native opportunist plant species, at the Pointe Mouillee coastal wetland complex (Wayne and Monroe Counties, Michigan). This study provides initial results from one of thirteen coastal wetland...
Airbome hyperspectral data were used to detect dense patches of Phragmites australis, a native opportunist plant species, at the Pointe Mouillee coastal wetland complex (Wayne and Monroe Counties, Michigan). This study provides initial results from one of thirteen coastal wetland...
OFDMA is an attractive multiple access technique for packet-based mobile broadband wireless access for beyond 3G and 4G systems. Radio resource allocation in OFDMA can exploit multiuser diversity to increase system capacity by implementing opportunistic scheduling techniques. This paper presents a new opportunistic scheduling scheme for OFDMA-based wireless multimedia networks. We focus the scheduling algorithm on the class of delay-sensitive
Ahmed K. F. Khattab; Khaled M. F. Elsayed
There is a strong need in South Africa for neuropsychological tests that can help detect HIV-associated neurocognitive disorder (HAND) in the country’s 5.6 million people living with HIV. Yet, South African neuropsychologists are challenged to do so, as few neuropsychological tests or batteries have been developed or adapted for, and normed on, South Africa’s linguistically, culturally, educationally, and economically diverse population. The purpose of this study was to explore the utility of the Montreal Cognitive Assessment to detect HIV-associated neurocognitive impairment among a sample of HIV+ and HIV-Black, Xhosa-speaking South Africans. HIV+ participants performed significantly worse overall and specifically in the domains of visuospatial, executive, attention, and language (confrontation naming). Regression analysis indicated that HIV status and education were the strongest predictors of total scores. Floor effects were observed on cube drawing, rhinoceros naming, serial 7’s, and one abstraction item, suggesting those items might not be useful in this population. While the Montreal Cognitive Assessment holds promise to help detect HAND in South Africa, it will likely need modification before it can be normed and validated for this population. Findings from this study may help neuropsychologists working with similar populations.
Robbins, Reuben N.; Joska, John A.; Thomas, Kevin G.F.; Stein, Dan J.; Linda, Teboho; Mellins, Claude A.; Remien, Robert H.
Solid-organ transplant recipients rely on pharmacological immunosuppression to prevent allograft rejection. The effect of such chronic immunosuppression on the microflora at mucosal surfaces is not known. We evaluated the salivary bacterial microbiome of 20 transplant recipients and 19 nonimmunosuppressed controls via 454 pyrosequencing of 16S rRNA gene amplicons. Alpha-diversity and global community structure did not differ between transplant and control subjects. However, principal coordinate analysis showed differences in community membership. Taxa more prevalent in transplant subjects included operational taxonomic units (OTUs) of potentially opportunistic Gammaproteobacteria such as Klebsiella pneumoniae, Pseudomonas fluorescens, Acinetobacter species, Vibrio species, Enterobacteriaceae species, and the genera Acinetobacter and Klebsiella. Transplant subjects also had increased proportions of Pseudomonas aeruginosa, Acinetobacter species, Enterobacteriaceae species, and Enterococcus faecalis, among other OTUs, while genera with increased proportions included Klebsiella, Acinetobacter, Staphylococcus, and Enterococcus. Furthermore, in transplant subjects, the dose of the immunosuppressant prednisone positively correlated with bacterial richness, while prednisone and mycophenolate mofetil doses positively correlated with the prevalence and proportions of transplant-associated taxa. Correlation network analysis of OTU relative abundance revealed a cluster containing potentially opportunistic pathogens as transplant associated. This cluster positively correlated with serum levels of C-reactive protein, suggesting a link between the resident flora at mucosal compartments and systemic inflammation. Network connectivity analysis revealed opportunistic pathogens as highly connected to each other and to common oral commensals, pointing to bacterial interactions that may influence colonization. This work demonstrates that immunosuppression aimed at limiting T-cell-mediated responses creates a more permissive oral environment for potentially opportunistic pathogens without affecting other members of the salivary bacteriome. PMID:23616410
Diaz, Patricia I; Hong, Bo-Young; Frias-Lopez, Jorge; Dupuy, Amanda K; Angeloni, Mark; Abusleme, Loreto; Terzi, Evimaria; Ioannidou, Effie; Strausbaugh, Linda D; Dongari-Bagtzoglou, Anna
Abstract Opportunistic and other infections have declined since the introduction of highly active antiretroviral therapy (HAART) in developed countries but few studies have addressed the impact of HAART in HIV-infected children from developing countries. This study examines the prevalence and incidence of opportunistic and other infections in Latin America during the HAART era. Vertically HIV-infected children enrolled in a cohort study between 2002 and 2007 were followed for the occurrence of 29 targeted infections. Cross-sectional and longitudinal analyses were performed to calculate the prevalence of infections before enrollment and the incidence rates of opportunistic and other infections after enrollment. Comparisons were made with data from a U.S. cohort (PACTG 219C). Of the 731 vertically HIV-infected children 568 (78%) had at least one opportunistic or other infection prior to enrollment. The most prevalent infections were bacterial pneumonia, oral candidiasis, varicella, tuberculosis, herpes zoster, and Pneumocystis jiroveci pneumonia. After enrollment, the overall incidence was 23.5 per 100 person-years; the most common infections (per 100 person-years) were bacterial pneumonia (7.8), varicella (3.0), dermatophyte infections (2.9), herpes simplex (2.5), and herpes zoster (1.8). All of these incidence rates were higher than those reported in PACTG 219C. The types and relative distribution of infections among HIV-infected children in Latin America in this study are similar to those seen in the United States but the incidence rates are higher. Further research is necessary to determine the reasons for these higher rates.
Alarcon, Jorge O.; Freimanis-Hance, Laura; Krauss, Margot; Reyes, Mary F.; Cardoso, Claudete Aparecida Araujo; Mussi-Pinhata, Marisa M.; Cardoso, Edmundo
Background Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa. Methods and Findings 498 adults initiating ART in Durban, South Africa were followed prospectively for 24 weeks. IRIS diagnosis was based on consensus expert opinion, and classified by mode of presentation (paradoxical worsening of known opportunistic infection [OI] or unmasking of subclinical disease). 114 patients (22.9%) developed IRIS (36% paradoxical, 64% unmasking). Mucocutaneous conditions accounted for 68% of IRIS events, mainly folliculitis, warts, genital ulcers and herpes zoster. Tuberculosis (TB) accounted for 25% of IRIS events. 18/135 (13.3%) patients with major pre-ART OIs (e.g. TB, cryptococcosis) developed paradoxical IRIS related to the same OI. Risk factors for this type of IRIS were baseline viral load >5.5 vs. <4.5 log10 (adjusted hazard ratio 7.23; 95% confidence interval 1.35–38.76) and ?30 vs. >30 days of OI treatment prior to ART (2.66; 1.16–6.09). Unmasking IRIS related to major OIs occurred in 25/498 patients (5.0%), and risk factors for this type of IRIS were baseline C-reactive protein ?25 vs. <25 mg/L (2.77; 1.31–5.85), haemoglobin <10 vs. >12 g/dL (3.36; 1.32–8.52), ?10% vs. <10% weight loss prior to ART (2.31; 1.05–5.11) and mediastinal lymphadenopathy on pre-ART chest x-ray (9.15; 4.10–20.42). IRIS accounted for 6/25 (24%) deaths, 13/65 (20%) hospitalizations and 10/35 (29%) ART interruptions or discontinuations. Conclusion IRIS occurred in almost one quarter of patients initiating ART, and accounted for one quarter of deaths in the first 6 months. Priority strategies to reduce IRIS-associated morbidity and mortality in ART programmes include earlier ART initiation before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of OI therapy prior to ART initiation, more intensive clinical monitoring in initial weeks of ART, and education of health care workers and patients about IRIS.
Haddow, Lewis John; Moosa, Mahomed-Yunus Suleman; Mosam, Anisa; Moodley, Pravi; Parboosing, Raveen; Easterbrook, Philippa Jane
We evaluated the overall coverage, frequency and costs of Pap testing by screening modality and health care provider in Finland. Information about Pap testing in the Finnish female population of 2.7 million was obtained from nationwide population-based registry data. Among women aged 25-69 years, 87% had had a Pap test taken within or outside the organised programme at least once during the last 5 years and half of those screened in the organised programme had also had at least one Pap test taken outside the programme. Of the annual average of 530,000 Pap tests taken, 84% were taken for screening purposes and 16% as follow-up. Forty percent of the 446,000 annual screening tests were taken in the organised programme, 55% as opportunistic tests in public primary or student health care or by private providers and 5% in public secondary health care. One-fifth of all opportunistic screening Pap tests were taken from women aged <25. The voluminous opportunistic Pap testing in public primary health care was concentrated in young women aged 25-29 whereas the bulk of opportunistic testing in private health occurred in age groups eligible for organised screening. The total cost of all screening Pap tests was €22.4 million, of which 71% incurred in opportunistic screening. Of the 84,000 annual follow-up Pap tests and their €8.3 million total costs, ?60% incurred in organised screening or in secondary health care. PMID:24347441
Salo, Heini; Nieminen, Pekka; Kilpi, Terhi; Auranen, Kari; Leino, Tuija; Vänskä, Simopekka; Tiihonen, Petri; Lehtinen, Matti; Anttila, Ahti
Background The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed. Result Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue proteome, 76 differentially expressed proteins (p < 0.05; fold change>1.25) were identified between HAD and HIV non-dementia patients, of which 36 protein spots (based on 3D appearance of spots on the images) were chosen for the mass spectrometry analysis. The large majority of identified proteins were represented in the energy metabolic (mitochondria) and signal transduction pathways. Furthermore, over 90% of the protein candidates are common to both HAD and other non-viral neurodegenerative disease, such as Alzheimer's disease. The data was further validated using specific antibodies to 4 proteins (CA2, GS, CKMT and CRMP2) by western blot (WB) in the same samples used for 2D-DIGE, with additional confirmation by immunohistochemitsry (IHC) using frontal lobe tissue from different HAD and HIV+ non-dementia patients. The validation for all 4 antibodies by WB and IHC was in concordance with the DIGE results, lending further credence to the current findings. Conclusion These results suggest not only convergent pathogenetic pathways for the two diseases but also the possibility of increased Alzheimer's disease (AD) susceptibility in HAD patients whose life expectancy has been significantly increased by highly active antiretroviral therapy.
The aim of this study was to identify the feeding habits of the European intertidal crab Pachygrapsus marmoratus . Since this species is widely distributed in southern Europe, four south-western European sites far apart from each other were selected: southern Portugal, central Portugal, central Tyrrhenian coast, Italy, and northern Adriatic coast, Istria. In summer, crabs were collected and the contents of their stomachs were assessed in the laboratory. In parallel, at each collection site the relative abundance of algae species and of sessile and slow-moving animals was assessed for comparison with the relative frequency of the same items in the P. marmoratus diet. The detailed analysis of its feeding habits showed that this species is omnivorous but that it cannot simply be considered an opportunistic feeder. In all populations, algal and animal diet components were almost equally abundant; thus these crabs actively regulate their feeding to cope with the dietary needs of their fast-moving, semi-terrestrial life-style. Descriptive and quantitative analyses showed that P. marmoratus has definite preferences for animal prey and algae. Limpets and mussels proved to be the commonest prey, followed by conspecific crabs. The highly preferred plant item was filamentous algae, although corticated macroalgae and articulated calcareous algae were also common in the diet. Cyanobacteria were preferred only at the Atlantic sites and crustose algae were represented only by Ralfsia sp., a species with high protein and lipid contents. Both univariate and multivariate statistical methods confirmed that the different populations of P. marmoratus were minimally influenced by the relative abundance of the food items within their environment and their diet composition was constant throughout the sampled area. In conclusion, the relative abundance of different ingested foods can best be explained by considering the diet of P. marmoratus to be related mainly to its population structure and, for some food items, to the feeding physiology of the crab itself.
Cannicci, S.; Gomei, M.; Boddi, B.; Vannini, M.
The evidence base and theoretical frameworks for mass media HIV-prevention campaigns in the United States are not well-developed. We describe an intervention approach using culturally sensitive mass media messages to enhance protective beliefs and behavior of African American adolescents at risk for HIV. This approach exploits the potential that mass media messages have, not only to reach a large segment of the adolescent population and thereby support normative change, but also to engage the most vulnerable segments of this audience to reduce HIV-associated risk behaviors. The results from an ongoing HIV-prevention trial implemented in 2 medium-sized cities in the United States illustrate the effectiveness of this intervention approach.
Sznitman, Sharon; DiClemente, Ralph; Salazar, Laura F.; Vanable, Peter A.; Carey, Michael P.; Hennessy, Michael; Brown, Larry K.; Valois, Robert F.; Stanton, Bonita F.; Fortune, Thierry; Juzang, Ivan
Treatment guidelines recommend combination antifungal therapy with amphotericin B (AmB) as an induction therapy for cryptococcal meningitis. The objective of this study was to compare the survival benefit between 5-FC (flucytosine) and fluconazole as second-line drugs given in combination with AmB. We carried out a systematic review and meta-analysis of prospective controlled studies reporting early combination treatment for human immunodeficiency virus (HIV)-associated cryptococcal meningitis. We searched MEDLINE, EMBASE and the Cochrane Library up to October 2013. Randomised trials and prospective cohort studies were selected. The primary outcome was mortality in the first 14 and 70 days. The secondary outcome was early fungicidal activity (EFA) in the first 2 weeks. Four trials were included in our study. All included studies could be considered to be of fair quality in their methodology. The meta-analysis suggested that mortality was lower in patients who were given AmB and 5-FC at the 2 weeks point (Fig. 2); the overall reduction in mortality with the 5-FC combination group was 44 % [risk ratio (RR) 0.56, 95 % confidence interval (CI) 0.33-0.95, p?=?0.03]. EFA was significantly shorter in patients receiving AmB plus 5-FC [mean difference (MD) -0.10 log10 colony-forming units (CFU) per day, 95 % CI -0.11-0.09, p?0.00001]. Mortality was no different between the 5-FC and fluconazole groups at the 3 months time point (p?= 0.15) (Fig. 4). Adverse events occurred with similar frequency between the two treatment groups. There was no statistically significant difference in the survival rate between AmB in combination with high-dose fluconazole and the current standard of AmB plus 5-FC therapy for HIV-associated cryptococcal meningitis. PMID:24550039
Yao, Z-W; Lu, X; Shen, C; Lin, D-F
Strong statistical associations between polymorphisms in HIV-1 population sequences and carriage of HLA class I alleles have been widely used to identify possible sites of CD8 T cell immune selection in vivo. However, there have been few attempts to prospectively and systematically test these genetic “hypotheses” arising from population-based studies at a cellular, functional level. We assayed CD8 T cell epitope-specific IFN? responses in 290 individuals from the same cohort which gave rise to 874 HLA-HIV associations in genetic analyses, taking into account autologous viral sequences and individual HLA genotypes. We found immunological evidence for 58% of 374 associations tested as sites of primary immune selection and identified up to 50 novel HIV-1 epitopes using this “reverse genomics” approach. Many HLA adapted epitopes elicited equivalent or higher magnitude IFN? responses than the non-adapted epitopes, particularly in Nef. At a population level, inclusion of all the immunoreactive variant CD8 T cell epitopes in Gag, Pol, Nef and Env suggested that HIV adaptation leads to an inflation of Nef-directed immune responses relative to other proteins. We conclude that HLA-HIV associations do mark viral epitopes subject to CD8 T cell selection. These results can be used to guide functional studies of specific epitopes and escape mutations as well as test, train and evaluate analytical models of viral escape and fitness. The inflation of Nef and HLA adapted variant responses may have negative effects on natural and vaccine immunity against HIV, and therefore has implications for diversity coverage approaches in HIV vaccine design.
Almeida, Coral-Ann M; Bronke, Corine; Roberts, Steven G; McKinnon, Elizabeth; Keane, Niamh M; Chopra, Abha; Kadie, Carl; Carlson, Jonathan; Haas, David W; Riddler, Sharon A; Haubrich, Richard; Heckerman, David; Mallal, Simon; John, Mina
A web resource that contains Chemical Abstracts Service (CAS) Registry Numbers for approximately 7,800 chemicals of widespread general public interest. Common Chemistry is helpful to non-chemists who know either a name or CAS Registry NumberÂ® of a common chemical and want to pair both pieces of information.
Chemical Abstracts Service (CAS)
The multiplication of opportunistic pathogens in drinking water supplies might pose a threat to public health. In this study, distributed unchlorinated drinking water from eight treatment plants in the Netherlands was sampled and analyzed for fungi, nontuberculous mycobacteria (NTM), and several opportunistic pathogens by using selective quantitative PCR methods. Fungi and NTM were detected in all drinking water samples, whereas Legionella pneumophila, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, and Aspergillus fumigatus were sporadically observed. Mycobacterium avium complex and Acanthamoeba spp. were not detected. Season had no influence on the occurrence of these organisms, except for NTM and S. maltophilia, which were present in higher numbers in the summer. Opportunistic pathogens were more often observed in premise plumbing water samples than in samples from the distribution system. The lowest number of these organisms was observed in the finished water at the plant. Thus, fungi, NTM, and some of the studied opportunistic pathogens can multiply in the distribution and premise plumbing systems. Assimilable organic carbon (AOC) and/or total organic carbon (TOC) had no clear effects on fungal and NTM numbers or on P. aeruginosa- and S. maltophilia-positive samples. However, L. pneumophila was detected more often in water with AOC concentrations above 10 ?g C liter?1 than in water with AOC levels below 5 ?g C liter?1. Finally, samples that contained L. pneumophila, P. aeruginosa, or S. maltophilia were more frequently positive for a second opportunistic pathogen, which shows that certain drinking water types and/or sampling locations promote the growth of multiple opportunistic pathogens.
van der Kooij, Dick
Several bacterial species that are natural inhabitants of potable water distribution system biofilms are opportunistic pathogens important to sensitive patients in healthcare facilities. Waterborne healthcare-associated infections (HAI) may occur during the many uses of potable water in the healthcare environment. Prevention of infection is made more challenging by lack of data on infection rate and gaps in understanding of the ecology, virulence, and infectious dose of these opportunistic pathogens. Some healthcare facilities have been successful in reducing infections by following current water safety guidelines. This review describes several infections, and remediation steps that have been implemented to reduce waterborne HAIs. PMID:23327332
Williams, Margaret M; Armbruster, Catherine R; Arduino, Matthew J
Background: Both HIV-1 RNA and absolute CD4 cell counts have been identified as important predictors of HIV-1 disease progression and mortality. The independent impact of opportunistic infections on the risk of chronic mortality, defined as death beyond 30 days of an opportunistic infection, has not been studied when controlling for HIV-1 RNA. Our objective was to determine the relationship between
George R. Seage; Elena Losina; Sue J. Goldie; A. David Paltiel; April D. Kimmel; Kenneth A. Freedberg
In this paper, we propose and analyze two opportunistic power allocation (OPA) schemes suitable for decentralized parameter estimation in wireless sensor networks. In these schemes, only sensors for which some locally obtained quality measure exceeds a threshold computed and then broadcasted by the FC, can actually participate in the estimation process. Subsequently, the sensors adjust their transmit power in such
Javier Matamoros; Carles Antón-Haro
We describe FATCOP 2.0, a new parallel mixed integer program solver that works in an opportunistic computing environment provided by the Condor resource management system. We outline changes to the search strategy of FATCOP 1.0 that are necessary to improve re- source utilization, together with new techniques to exploit heteroge- neous resources. We detail several advanced features in the code
Qun Chen; Michael C. Ferris; Jeff Linderoth
Purpose: To review a small specialist repository's strategic and opportunistic approach to utilising collaborative regional and national digital initiatives to increase access. The Birmingham Institute of Art and Design (BIAD) Archives activity is evaluated to determine whether a project-based approach recognises and meets the needs of historians,…
Subcontractor selection strategies employed by contractors can significantly impact the success of individual organizations and the overall efficiency of the market. Long-term partnerships are promoted by experts from both academia and industry as a means of achieving improved project network productivity; however, opportunistic bidding behaviour that may accompany its implementation might negate the benefits of close collaboration. We conducted a
Hakan I. Unsal; John E. Taylor
In the Sznajd model, a democratic community with two parties is simulated. A large drawback of this model is that it always ends up in non-democratic states. Here I give two examples how the additional introduction of contrarian and opportunistic behaviors of individuals can keep a democracy alive.
Schneider, Johannes J.
In cognitive radio (CR) networks, there are scenarios where the secondary (lower priority) users intend to communicate with each other by opportunistically utilizing the transmit spectrum originally allocated to the existing primary (higher priority) users. For such a scenario, a secondary user usually has to tradeoff between two conflicting goals at the same time: one is to maximize its own
Rui Zhang; Ying-Chang Liang
In this paper, we exploit the heterogeneity of wire- less channels and propose an efficient opportunistic cognitive routing (OCR) scheme for dynamic spectrum access (DSA) networks. We first introduce a novel routing metric by jointly considering physical characteristics of spectrum bands and di- verse activities of primary users (PU) in each band. To effectively explore the spectrum opportunities, a proper
Yongkang Liu; Lin X. Cai; Xuemin Shen; Jon W. Mark
Detecting and dealing with congestion in delay tolerant opportunistic networks is an important and challenging problem. In this paper we describe CAFREP, a unified congestion control framework for routing in such networks that adapts both data sending rates and data forwarding policies through a novel reactive fully distributed approach. CAFREP enables congestion control by detecting and reacting to congested nodes
Milena Radenkovic; Andrew Grundy
Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka-Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens. PMID:24244752
Anttila, Jani; Ruokolainen, Lasse; Kaitala, Veijo; Laakso, Jouni
Environmentally transmitted pathogens face ecological interactions (e.g., competition, predation, parasitism) in the outside-host environment and host immune system during infection. Despite the ubiquitousness of environmental opportunist pathogens, traditional epidemiology focuses on obligatory pathogens incapable of environmental growth. Here we ask how competitive interactions in the outside-host environment affect the dynamics of an opportunist pathogen. We present a model coupling the classical SI and Lotka–Volterra competition models. In this model we compare a linear infectivity response and a sigmoidal infectivity response. An important assumption is that pathogen virulence is traded off with competitive ability in the environment. Removing this trade-off easily results in host extinction. The sigmoidal response is associated with catastrophic appearances of disease outbreaks when outside-host species richness, or overall competition pressure, decreases. This indicates that alleviating outside-host competition with antibacterial substances that also target the competitors can have unexpected outcomes by providing benefits for opportunist pathogens. These findings may help in developing alternative ways of controlling environmental opportunist pathogens.
Anttila, Jani; Ruokolainen, Lasse; Kaitala, Veijo; Laakso, Jouni
Relay selection (RS) has widely been studied in the literature, and an opportunistic source selection (OSS) protocol with a single relay has recently been proposed. Since RS and OSS could individually improve the performance of cooperative diversity networks, optimum combining of RS and OSS is an interesting topic. In this paper, we optimally combine RS and OSS in the sense
MinChul Ju; Il-Min Kim
The population of the Top End of the Northern Territory has a high incidence of several infections of particular signifi cance in the immunosuppressed. The following protocol for evaluation and treatment of patients prior to immunosuppression was developed in order to reduce the incidence of serious opportunistic infections. The infections discussed are Strongyloides stercoralis, tuberculosis, scabies, chronic hepatitis B, melioidosis
Joshua S Davis; Bart J Currie; Dale A Fisher; Sarah E Huffam; Nicholas M Anstey; Richard N Price; Vicki L Krause; Nathan Zweck; Paul D Lawton; Paul L Snelling; Sid Selva-nayagam
We report a case of Cryptococcus neoformans pneumonia in a patient taking ruxolitinib, a janus kinase 1,2 inhibitor approved for the treatment of myelofibrosis. We hypothesize that ruxolitinib contributed to this infection through its effects on cell-mediated immunity. Clinicians should be aware of the potential for intracellular or opportunistic infections associated with this novel drug class. PMID:23648912
Wysham, Nicholas G; Sullivan, Donald R; Allada, Gopal
BACKGROUND: The aim of this study was to analyse breast cancer incidence and mortality in Tyrol from 1970 to 2006, namely after performing more than a decade of opportunistic mammography screening and just before piloting an organised screening programme. Our investigation was conducted on a population level. METHODS: To study time trends in breast cancer incidence and mortality, we applied
Willi Oberaigner; Wolfgang Buchberger; Thomas Frede; Rudolf Knapp; Christian Marth; Uwe Siebert
Opportunistic scheduling has been recognized as an effective method that significantly outperforms fixed TDMA scheduling in both channel capacity and communication reliability. Nevertheless the superior system performance comes at a price of high computational complexity, large signaling overhead, and unfairness among users. In this paper, we find that in relay-assisted next-generation wireless networks, fixed TDMA scheduling achieves the same diversity
Suzhi Bi; Ying Jun Zhang
Recent work has shown that distributed (or cooperative) beamforming can achieve cooperative gain, such as throughput gain and diversity gain, with no need for extra spectral holes in Cognitive Wireless Networks (CWNs). However, how to efficiently schedule cooperative beamforming to improve the quality of service of unlicensed secondary users has not been well addressed. In this paper, a simple opportunistic
Juan Liu; Wei Chen; Zhigang Cao; Ying Jun Zhang
Cognitive radio is a powerful solution that can significantly improve the utilization of the precious limited radio spectrum. It allows secondary users (SUs) to opportunistically access spectral holes in the licensed spectrum without causing harmful interference to primary users (PUs). However, the secondary communication opportunity becomes extremely poor when primary systems are heavily loaded. In this paper, a distributed beamforming
Juan Liu; Wei Chen; Zhigang Cao; Ying Jun Zhang
Cognitive radio (CR) is a powerful solution that can significantly improve the utilization of the precious limited radio spectrum. It allows secondary users (SUs) to opportunistically access spectral holes of the licensed spectrum without causing harmful interference to primary users (PUs). However, waiting for idle timeslots may induce very poor quality of service (QoS) for SUs. To alleviate this, an
Juan Liu; Wei Chen; Zhigang Cao; Ying Jun Zhang
We report here the first complete genome sequence of Staphylococcus xylosus strain HKUOPL8, isolated from giant panda feces. The whole genome sequence of this strain will provide an important framework for investigating the genes responsible for potential opportunistic infections with this species, as well as its survival in various environments.
Ma, Angel Po Yee; Jiang, Jingwei; Tun, Hein Min; Mauroo, Nathalie France; Yuen, Chan San
In this paper, we analyze the outage probability and diversity order of opportunistic relay selection in a scenario based on decode and forward and where the available channel state in- formation (CSI) is outdated. The study is conducted analytically by obtaining a closed-form expression for the outage probability, which is de?ned as the probability that the instantaneous capacity is below
Jose Lopez Vicario; Albert Bel; Jose A. Lopez-Salcedo; Gonzalo Seco-granados
We introduce a new paradigm and a new technology, which we call opportunistic networks or oppnets . An oppnet grows from its seed —the original set of nodes employed together at the time of the initial oppnet deployment. The seed grows into a larger network by extending invitations to join the oppnet to foreign devices, node clusters, or networks that
Leszek Lilien; Zille Huma Kamal; Vijay Bhuse; Ajay Gupta
Aureobasidium pullulans AY4 is an opportunistic pathogen that was isolated from the skin of an immunocompromised patient. We present here the draft genome of strain AY4, which reveals an abundance of genes relevant to bioindustrial applications, including biocontrol and biodegradation. Putative genes responsible for the pathogenicity of strain AY4 were also identified.
Bamadhaj, Hasima Mustafa; Gan, Han Ming; Rashid, Noor Aini Abdul
Background: Cognitive impairment is a common con- sequence of human immunodeficiency virus (HIV) in- fection, and dementia is one of the diseases that defines the acquired immunodeficiency syndrome. Peptide T (d-ala-peptide-T-amide) has been reported to block the binding of gp120 to brain tissue and to protect neurons from the toxic effects of gp120 in vitro. In pilot studies, administration of
Peter N. R. Heseltine; Karl Goodkin; J. Hampton Atkinson; Benedetto Vitiello; James Rochon; Robert K. Heaton; Elaine M. Eaton; Frances L. Wilkie; Eugene Sobel; Stephen J. Brown; Dan Feaster; Lon Schneider; Walter L. Goldschmidts; Ellen S. Stover
A total of 450 stool samples were collected from inpatient and outpatient clinics of Pediatric Department, Minia University Hospital, Minia District, Egypt. Two groups of patients were studied, including 200 immunosuppressed and 250 immunocompetent children. Stool samples were subjected to wet saline and iodine mounts. A concentration technique (formol-ether sedimentation method) was carried out for stool samples diagnosed negative by wet saline and iodine mounts. Samples were stained by 2 different methods; acid fast stain (modified Ziehl-Neelsen stain) and Giemsa stain. Total 188 cases (94%) were diagnosed positive for parasitic infections among immunosuppressed children, whereas 150 cases (60%) were positive in immunocompetent children (P<0.0001). The most common protozoan infection in immunosuppressed group was Cryptosporidium parvum (60.2%), followed by Blastocystis hominis (12.1%), Isospora belli (9.7%), and Cyclospora caytenensis (7.8%). On the other hand, Entamoeba histolytica (24.6%) and Giardia lamblia (17.6%) were more common than other protozoans in immunocompetent children.
Ahmad, Azza K.; Ali, Basma A.; Moslam, Fadia A.
A total of 450 stool samples were collected from inpatient and outpatient clinics of Pediatric Department, Minia University Hospital, Minia District, Egypt. Two groups of patients were studied, including 200 immunosuppressed and 250 immunocompetent children. Stool samples were subjected to wet saline and iodine mounts. A concentration technique (formol-ether sedimentation method) was carried out for stool samples diagnosed negative by wet saline and iodine mounts. Samples were stained by 2 different methods; acid fast stain (modified Ziehl-Neelsen stain) and Giemsa stain. Total 188 cases (94%) were diagnosed positive for parasitic infections among immunosuppressed children, whereas 150 cases (60%) were positive in immunocompetent children (P<0.0001). The most common protozoan infection in immunosuppressed group was Cryptosporidium parvum (60.2%), followed by Blastocystis hominis (12.1%), Isospora belli (9.7%), and Cyclospora caytenensis (7.8%). On the other hand, Entamoeba histolytica (24.6%) and Giardia lamblia (17.6%) were more common than other protozoans in immunocompetent children. PMID:22451735
Abdel-Hafeez, Ekhlas H; Ahmad, Azza K; Ali, Basma A; Moslam, Fadia A
The Stanford Linear Accelerator Center (SLAC) uses a maintenance management philosophy that is best described as opportunistic or event-driven. Opportunistic maintenance can be defined as a systematic method of collecting, investigating, pre-planning, and publishing a set of proposed maintenance tasks and acting on them when there is an unscheduled failure or repair ``opportunity``. Opportunistic maintenance can be thought of as a modification of the run-to-fail maintenance management philosophy. This maintenance plan was adopted and developed to improve the overall availability of SLAC`s linear accelerator, beam delivery systems, and associated controls, power systems, and utilities. In the late 1980`s, as the technical complexity of the accelerator facility increased, variations on a conventional maintenance plan were used with mixed results. These variations typically included some type of regular periodic interruption to operations. The periodic shutdowns and unscheduled failures were additive and resulted in unsatisfactory availability. Maintenance issues are evaluated in a daily meeting that includes the accelerator managers, maintenance supervisors and managers, safety office personnel, program managers, and accelerator operators. Lists of pending maintenance tasks are made available to the general SLAC population by a World Wide Web site on a local internet. A conventional information system which pre-dates the WWW site is still being used to provide paper copies to groups that are not yet integrated into the WWW system. The local internet provides real time maintenance information, allowing people throughout the facility to track progress on tasks with essentially real-time status updates. With the introduction of opportunistic maintenance, the accelerator`s availability has been measurably better. This paper will discuss processes, rolls and responsibilities of key maintenance groups, and management tools developed to support opportunistic maintenance.
Allen, C.W.; Anderson, S.; Erickson, R.; Linebarger, W.; Sheppard, J.C.; Stanek, M.
Because the International Space Station is a closed environment with rotations of astronauts and equipment that each introduce their own microbial flora, it is necessary to monitor the air, surfaces, and water for microbial contamination. Current microbia...
A. Singhal A. S. Johnston C. M. Ott C. M. Oubre D. X. Jett K. J. Venkateswaran K. U. Jones M. C. Roman M. N. Birmele M. S. Roberts P. A. Vaishampayan T. A. Ozbolt V. A. Castro
Current methods for microbial detection: a) Labor & time intensive cultivation-based approaches that can fail to detect or characterize all cells present. b) Requires collection of samples on orbit and transportation back to ground for analysis. Disadvantages to current detection methods: a) Unable to perform quick and reliable detection on orbit. b) Lengthy sampling intervals. c) No microbe identification.
Roman, Monserrate C.; Jones, Kathy U.; Oubre, Cherie M.; Castro, Victoria; Ott, Mark C.; Birmele, Michele; Venkateswaran, Kasthuri J.; Vaishampayan, Parag A.
Because the International Space Station is a closed environment with rotations of astronauts and equipment that each introduce their own microbial flora, it is necessary to monitor the air, surfaces, and water for microbial contamination. Current microbial monitoring includes labor- and time-intensive methods to enumerate total bacterial and fungal cells, with limited characterization, during in-flight testing. Although this culture-based method is sufficient for monitoring the International Space Station, on future long-duration missions more detailed characterization will need to be performed during flight, as sample return and ground characterization may not be available. At a workshop held in 2011 at NASA's Johnson Space Center to discuss alternative methodologies and technologies suitable for microbial monitoring for these long-term exploration missions, molecular-based methodologies such as polymerase chain reaction (PCR) were recommended. In response, a multi-center (Marshall Space Flight Center, Johnson Space Center, Jet Propulsion Laboratory, and Kennedy Space Center) collaborative research effort was initiated to explore novel commercial-off-the-shelf hardware options for space flight environmental monitoring. The goal was to evaluate quantitative or semi-quantitative PCR approaches for low-cost in-flight rapid identification of microorganisms that could affect crew safety. The initial phase of this project identified commercially available platforms that could be minimally modified to perform nominally in microgravity. This phase was followed by proof-of-concept testing of the highest qualifying candidates with a universally available challenge organism, Salmonella enterica. The analysis identified two technologies that were able to perform sample-to-answer testing with initial cell sample concentrations between 50 and 400 cells. In addition, the commercial systems were evaluated for initial flight safety and readiness.
Oubre, Cherie M.; Birmele, Michele N.; Castro, Victoria A.; Venkateswaran, Kasthuri J.; Vaishampayan, Parag A.; Jones, Kathy U.; Singhal, Adesh; Johnston, Angela S.; Roman, Monserrate C.; Ozbolt, Tamra A.; Jett, Daniel X.; Roberts, Michael S.; Ott, C. Mark
Presents K-12 and college common areas considered outstanding in a competition, which judged the most outstanding learning environments at educational institutions nationwide. Jurors spent two days reviewing projects, highlighting concepts and ideas that made them exceptional. For each citation, the article offers information on the firm, client,…
American School & University, 2003
Invasive fungal infections are a major cause of morbidity and mortality among organ transplant recipients, despite many progresses concerning diagnosis, preventions and treatment. Risk factors for invasive fungal infections in transplanted recipients include type and severity of immunosuppression, especially in life-saving organs as lung or liver, older age at transplantation, and technical complexity of surgery, living in endemic areas or exposure to a contaminated environment. Superficial fungal infections are caused by Candida, Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a consequence of the systemic dissemination of invasive mycoses, or after direct inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould infections, fusariosis and infections attributable to Scedosporium and Pseudallescheria species are the most common etiological agents. Cutaneous manifestations of fungal infection are not specific, and a high degree of suspicion is required, and prompt biopsy for histology and culture is needed. Therapy with lyposomal amphotericin B and new triazoles are effective. PMID:24938725
Tessari, G; Cagalli, A; Girolomoni, G
Invasive fungal infections are a major cause of morbidity and mortality among organ transplant recipients, despite many progresses concerning diagnosis, preventions and treatment. Risk factors for invasive fungal infections in transplanted recipients include type and severity of immunosuppression, especially in life-saving organs as lung or liver, older age at transplantation, and technical complexity of surgery, living in endemic areas or exposure to a contaminated environment. Superficial fungal infections are caused by Candida, Dermatophytes, and Malassezia. In invasive mycoses, skin lesions may occur as a consequence of the systemic dissemination of invasive mycoses, or after direct inoculation in the skin. Aspergillosis, cryptococcosis, Zygomycoses, dark mould infections, fusariosis and infections attributable to Scedosporium and Pseudallescheria species are the most common etiological agents. Cutaneous manifestations of fungal infection are not specific, and a high degree of suspicion is required, and prompt biopsy for histology and culture is needed. Therapy with lyposomal amphotericin B and new triazoles are effective. PMID:25068229
Tessari, G; Cagalli, A; Girolomoni, G
Background Little is known about the prevalence and burden of HIV associated neurocognitive disorder (HAND) among patients on combination antiretroviral therapy (cART) in sub-Saharan Africa. We estimated the prevalence of HAND in adult Malawians on cART and investigated the relationship between HAND and adherence to cART. Methods HIV positive adults in Blantyre, Malawi underwent a full medical history, neurocognitive test battery, depression score, Karnofsky Performance Score and adherence assessment. The Frascati criteria were used to diagnose HAND and the Global Deficit Score (GDS) was also assessed. Blood was drawn for CD4 count and plasma nevirapine and efavirenz concentrations. HIV negative adults were recruited from the HIV testing clinic to provide normative scores for the neurocognitive battery. Results One hundred and six HIV positive patients, with median (range) age 39 (18–71) years, 73% female and median (range) CD4 count 323.5 (68–1039) cells/µl were studied. Symptomatic neurocognitive impairment was present in 15% (12% mild neurocognitive disorder [MND], 3% HIV associated dementia [HAD]). A further 55% fulfilled Frascati criteria for asymptomatic neurocognitive impairment (ANI); however factors other than neurocognitive impairment could have confounded this estimate. Neither the symptomatic (MND and HAD) nor asymptomatic (ANI) forms of HAND were associated with subtherapeutic nevirapine/efavirenz concentrations, adjusted odds ratio 1.44 (CI. 0.234, 8.798; p?=?0.696) and aOR 0.577 (CI. 0.09, 3.605; p?=?0.556) respectively. All patients with subtherapeutic nevirapine/efavirenz levels had a GDS of less than 0.6, consistent with normal neurocognition. Discussion/Conclusion Fifteen percent of adult Malawians on cART had a diagnosis of MND or HAD. Subtherapeutic drug concentrations were found exclusively in patients with normal neurocognitive function suggesting HAND did not affect cART adherence. Further study of HAND requires more robust locally derived normative neurocognitive values and determination of the clinical relevance of ANI.
Kelly, Christine M.; van Oosterhout, Joep J.; Ngwalo, Chisomo; Stewart, Robert C.; Benjamin, Laura; Robertson, Kevin R.; Khoo, Saye; Allain, Theresa J.; Solomon, Tom
Burkholderia cepacia complex is a group of 17 closely related species. For a long time B.cepacia complex is believed to be only a plant pathogen but later it has emerged as an important opportunistic pathogen causing morbidity and mortality in hospitalized patients. B.cepacia complex particularly causes bacteraemia/sepsis, septic arthritis, osteomyelitis, meningitis, peritonitis, urinary and respiratory tract infections. Patients with cystic fibrosis or chronic granulomatous disease are predisposed to B.cepacia complex infections. B.cepacia complex can survive for a long period of time and can easily multiply in aqueous environments such as disinfectant agents and intravenous fluids used in hospitals. Patients may acquire B.cepacia complex either from the environment or through patient-to-patient transmission. It has always been a tedious task for routine microbiology laboratory to identify B.cepacia complex. In these laboratories, the identification of B.cepacia complex isolates is generally performed using a combination of selective media, conventional biochemical analysis and/or commercial systems. Three media commonly used for isolation of B.cepacia complex are as follows: the Pseudomonas cepacia agar, the oxidation-fermentation based polymyxin bacitracin lactose agar, and more recently the B.cepacia selective agar. Members of the B.cepacia complex can be identified by available commercial tests, such as API 20NE, Phoenix, MicroScan or VITEK. Molecular techniques are useful for confirmation of phenotypic identification and discrimination beyond the species-level. B.cepacia complex is intrinsically resistant to antimicrobial agents such as aminoglycosides, first- and second-generation cephalosporins, antipseudomonal penicillins and polymyxins. B.cepacia complex bacteria often develop resistance to beta-lactams due to presence of inducible chromosomal beta-lactamases and altered penicillin- binding proteins. Antibiotic efflux pumps in B.cepacia complex bacteria mediate resistance to chloramphenicol, trimethoprim and fluoroquinolones. Under antimicrobial pressure, resistance can quickly develop to all susceptible antimicrobials. In this review, the classification and microbiological features of B.cepacia complex, mechanisms of virulence and pathogenesis, epidemiological properties, clinical spectrum, laboratory diagnosis, antimicrobial resistance and treatment, prevention and control measures were summarized. PMID:22639321
How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…
Two experiments were conducted to examine the effects of task importance on event-based prospective memory (PM) in separate samples of adults with HIV-associated neurocognitive disorders (HAND) and HIV-infected young adults with substance use disorders (SUD). All participants completed three conditions of an ongoing lexical decision task: (1) without PM task requirements; (2) with PM task requirements that emphasized the importance of the ongoing task; and (3) with PM task requirements that emphasized the importance of the PM task. In both experiments, all HIV+ groups showed the expected increase in response costs to the ongoing task when the PM task's importance was emphasized. In Experiment 1, individuals with HAND showed significantly lower PM accuracy as compared to HIV+ subjects without HAND when the importance of the ongoing task was emphasized, but improved significantly and no longer differed from HIV+ subjects without HAND when the PM task was emphasized. A similar pattern of findings emerged in Experiment 2, whereby HIV+ young adults with SUD (especially cannabis) showed significant improvements in PM accuracy when the PM task was emphasized. Findings suggest that both HAND and SUD may increase the amount of cognitive attentional resources that need to be allocated to support PM performance in persons living with HIV infection. (JINS, 2014, 21, 1-11). PMID:24834469
Woods, Steven Paul; Doyle, Katie L; Morgan, Erin E; Naar-King, Sylvie; Outlaw, Angulique Y; Nichols, Sharon L; Loft, Shayne
Although HIV-associated neurocognitive disorders (HAND) are the strong predictors of everyday functioning difficulties, approximately half of all functionally impaired individuals are labeled “neurocognitively normal” according to the standard neuropsychological measures, suggesting that novel predictors of functional problems in this prevalent subgroup are needed. The present study hypothesized that increased neurocognitive intra-individual variability as indexed by dispersion would be associated with poor daily functioning among 82 persons with HIV infection who did not meet research criteria for HAND. An intra-individual standard deviation was calculated across the demographically adjusted T-scores of 13 standard neuropsychological tests to represent dispersion, and functional outcomes included self-reported declines in basic and instrumental activities of daily functioning (basic activity of daily living [BADL] and instrumental activity of daily living [IADL], respectively) and medication management. Dispersion was a significant predictor of medication adherence and dependence in both BADL and IADL, even when other known predictors of functional status (i.e., age, affective distress, and indices of disease severity) were included in the models. As a significant and unique predictor of a performance on the range of daily functioning activities, neurocognitive dispersion may be indicative of deficient cognitive control expressed as inefficient regulation of neurocognitive resources in the context of competing functional demands. As such, dispersion may have clinical utility in detecting risk for functional problems among HIV-infected individuals without HAND.
Morgan, Erin E.; Woods, Steven Paul; Grant, Igor
The widespread use of highly active antiretroviral therapy (HAART) has dramatically reduced HIV-associated morbidity and mortality where treatment has been made available. Very high levels of adherence to HAART are a prerequisite for a successful virological and immunological response. Low adherence increases the risk of treatment failure and disease progression. It is also likely to lead to further transmission of resistant viruses, and to have a negative impact on the cost effectiveness of HAART. Low adherence is difficult to predict, and this has two key implications for service provision. Firstly, HAART should not be withheld on the basis of assumptions about adherence. Secondly, support with adherence should be provided to all patients prescribed HAART. Our understanding of barriers to and enablers of high adherence, and the evidence base regarding effective interventions, is limited. Meta-analysis of randomized controlled trials available from the general literature suggests multiple interventions are required to maintain high adherence to chronic therapy. This document recommends a series of measures for adoption within HIV clinical care settings, based on evaluation of existing data. High adherence is a process, not a single event, and therefore adherence support must be integrated into clinical follow up. Every prescribing unit should have a written policy on provision of adherence support, and ensure that staff are appropriately trained to make delivery of such services possible. PMID:15239716
Poppa, A; Davidson, O; Deutsch, J; Godfrey, D; Fisher, M; Head, S; Horne, R; Sherr, L
BACKGROUND: The pathogenesis of HIV-associated dementia (HAD) is poorly understood. To date, detailed proteomic fingerprinting directly from autopsied brain tissues of HAD and HIV non-dementia patients has not been performed. RESULT: Here, we have analyzed total proteins from the frontal cortex of 9 HAD and 5 HIV non-dementia patients. Using 2-Dimensional differential in-gel electrophoresis (2-DIGE) to analyze the brain tissue
Li Zhou; Eve Diefenbach; Ben Crossett; Sieu L Tran; Thomas Ng; Helen Rizos; Rejane Rua; Bin Wang; Amit Kapur; Kaushal Gandhi; Bruce J Brew; Nitin K Saksena
Opportunistic pathogens in potable water systems are an emerging health concern; however, the factors influencing their proliferation are poorly understood. Here we investigated the effects of prior granular activated carbon (GAC) biofiltration [GAC-filtered water, unfiltered water, and a blend (30% GAC filtered and 70% unfiltered water)] and disinfectant type (chlorine, chloramine) on opportunistic pathogen occurrence using five annular reactors (ARs) to simulate water distribution systems, particularly premise plumbing. GAC pre-treatment effectively reduced total organic carbon (TOC), resulting in three levels of influent TOC investigated. Quantitative polymerase chain reaction (q-PCR) provided molecular evidence of natural colonization of Legionella spp., Mycobacterium spp., Acanthamoeba spp., Hartmannella vermiformis and Mycobacterium avium on AR coupons. Cultivable mycobacteria and amoeba, including pathogenic species, were also found in bulk water and biofilm samples. While q-PCR tends to overestimate live cells, it provided a quantitative comparison of target organisms colonizing the AR biofilms in terms of gene copy numbers. In most cases, total bacteria and opportunistic pathogens were higher in the three undisinfected ARs, but the levels were not proportional to the level of GAC pre-treatment/TOC. Chlorine was more effective for controlling mycobacteria and Acanthamoeba, whereas chloramine was more effective for controlling Legionella. Both chlorine and chloramine effectively inhibited M. avium and H. vermiformis colonization. Pyrosequencing of 16S rRNA genes in coupon biofilms revealed a significant effect of GAC pre-treatment and disinfectant type on the microbial community structure. Overall, this study provides insights into the potential of different disinfectants and GAC biofilters at the treatment plant and in buildings to control downstream opportunistic pathogens and broader drinking water microbial communities. PMID:23906775
Wang, Hong; Pryor, Marsha A; Edwards, Marc A; Falkinham, Joseph O; Pruden, Amy
In this paper, a system concept is proposed and investigated for the downlink of a cellular network which combines a self-organised beamforming approach with an opportunistic scheduling concept. In the considered OFDM-based system, different beams or grids of beams are formed in time and frequency and the available space-time-frequency resources are allocated by intelligent scheduling algorithms to those mobile terminals
Rainer Gruinheid; Hermann Rohling; Karsten Brüninghaus; Uwe Schwark
This study examined the role of criminal fantasy in premeditated and repetitive sex offending. Forty-eight males participated in two experimental groups, predatory sex offenders and opportunist sex offenders, and two control groups, non-sex offenders and a group of non-offenders living in the community. The offenders were Special Hospital patients. All participants completed a measure of impulsivity and a task designed
NASHATER DEU; ROBERT J. EDELMANN
It is expected that the wireless world will need to encompass more local\\/temporary structures which can be created for exploiting dynamically appearing opportunities. Such structures, which can be called Opportunistic Networks (ONs), may comprise various terminals\\/devices, potentially organized in an infrastructure-less (ad-hoc) network mode, and be terminated at a set of access points of the infrastructure-based network. In this context,
Marios Logothetis; Kostas Tsagkaris; Panagiotis Demestichas
Particle swarm optimization (PSO) is one of the most important biological swarm intelligence paradigms. However, the standard\\u000a PSO algorithm can easily get trapped in the local optima when solving complex multimodal problems. In this paper, an improved\\u000a adaptive particle swarm optimization (IAPSO) is presented. Based on IAPSO, a joint opportunistic power and rate allocation\\u000a (JOPRA) algorithm is proposed to maximize
Defang Liu; Bochu Wang
In this paper, a dual-hop wireless cooperative network with opportunistic amplify-and-forward (AF) relaying is investigated over independent and non-identically distributed Nakagami-m fading channels. Due to the complicated form of the probability density function of the instantaneous dual-hop link signal-to-noise ratio (SNR), the symbol error rate and outage probability expressions are difficult to obtain in closed form. Taking advantage of Maclaurin
Runping Yuan; Taiyi Zhang; Jianxiong Huang; Jing Zhang; Zhenjie Feng
Sensory neuropathy (HIV-SN) is a common cause of pain in HIV-infected people. Establishing a diagnosis of HIV-SN is important, especially when contemplating opioid use in high risk populations. However physical findings of HIV-SN may be subtle, and sensitive diagnostic tools require specialized expertise. We investigated the association between self-report of distal neuropathic pain and/or paresthesias (DNPP) and objective signs of HIV-SN. Data were obtained from the Central Nervous System HIV Antiretroviral Therapy Effects Research (CHARTER) study. Out of 237 participants, 101 (43%) reported DNPP. Signs of HIV-SN were measured by a modified Total Neuropathy Score (TNS), composed of 6 objective sensory subscores (pin sensibility, vibration sensibility, deep tendon reflexes, quantitative sensory testing for cooling and vibration, and sural sensory amplitude). Self-report of DNPP was associated with all 6 TNS items in univariate analysis and with 4 TNS items in multivariate analysis. The sensitivity and specificity of self-report of DNPP in detecting the presence of a sensory abnormality was 52% and 92% respectively with a PPV of 96% and a NPV of 34%. Increasing intensity of pain measured on a visual analog scale was associated with increasing severity of sensory abnormality. In summary, our results suggest that HIV-infected patients reporting symptoms consistent with HIV-SN, such as tingling, pins and needles, or aching or stabbing pain in the distal lower extremities, usually have objective evidence of HIV-SN on neurologic examination or with neurophysiologic testing. This finding holds true regardless of demographic factors, depression or substance use history.
Robinson-Papp, J.; Morgello, S.; Vaida, F.; Fitzsimons, C.; Simpson, D.M.; Elliott, K.J.; Al-Lozi, M.; Gelman, B.B.; Clifford, D.; Marra, C.M.; McCutchan, J.A.; Atkinson, J.H.; Dworkin, R.H.; Grant, I.; Ellis, R.
There is a paucity of HIV autopsy data from South America and none that document the postmortem findings in patients with HIV/AIDS in Peru. The purpose of this autopsy study was to determine the spectrum of opportunistic infections and the causes of mortality in HIV-positive patients at a public hospital in Lima. Clinico-epidemiological information regarding HIV infection in Peru is also reviewed. Sixteen HIV-related hospital postmortems, performed between 1999 and 2004, were included in this retrospective analysis. The primary cause of death was established in 12 patients: one died of neoplasia and 11 of infectious diseases, including 3 from pulmonary infection, 7 from disseminated infection, and 2 from central nervous system infection (one case had dual pathology). Opportunistic infections were identified in 14 cases, comprising cytomegalovirus, histoplasmosis, cryptococcosis, toxoplasmosis, Pneumocystis pneumonia, aspergillosis, tuberculosis, varicella zoster virus, and cryptosporidiosis. Fourteen patients had at least one AIDS-related disease that had been neither clinically suspected nor diagnosed premortem. Moreover, 82% of the diagnoses considered to be of important clinical significance had not been suspected antemortem. The spectrum and frequency of certain opportunistic infections differed from other South American autopsy studies, highlighting the importance of performing HIV/AIDS postmortems in resource-limited countries where locally specific disease patterns may be observed.
Eza, Dominique; Cerrillo, Gustavo; Moore, David A.J.; Castro, Cecilia; Ticona, Eduardo; Morales, Domingo; Cabanillas, Jose; Barrantes, Fernando; Alfaro, Alejandro; Benavides, Alejandro; Rafael, Arturo; Valladares, Gilberto; Arevalo, Fernando; Evans, Carlton A.; Gilman, Robert H.
This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5–28 ?g/mL) and Cryptococcus spp. (3–5 ?g/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane.
Coral reefs are under increasing stress caused by global and local environmental changes, which are thought to increase the susceptibility of corals to opportunistic pathogens. In the absence of an easily culturable model animal, the understanding of the mechanisms of disease progression in corals remains fairly limited. In the present study, we tested the susceptibility of the tropical sea anemone Aiptasia pallida to an opportunistic coral pathogen (Serratia marcescens). A.?pallida was susceptible to S. marcescens?PDL100 and responded to this opportunistic coral pathogen with darkening of the tissues and retraction of tentacles, followed by complete disintegration of polyp tissues. Histological observations revealed loss of zooxanthellae and structural changes in eosinophilic granular cells in response to pathogen infection. A screen of S.?marcescens mutants identified a motility and tetrathionate reductase mutants as defective in virulence in the A.?pallida infection model. In co-infections with the wild-type strain, the tetrathionate reductase mutant was less fit within the surface mucopolysaccharide layer of the host coral Acropora palmata. PMID:24983533
Krediet, Cory J; Meyer, Julie L; Gimbrone, Nicholas; Yanong, Roy; Berzins, Ilze; Alagely, Ali; Castro, Herman; Ritchie, Kim B; Paul, Valerie J; Teplitski, Max
This study evaluated the antifungal activities of synthetic naphthoquinones against opportunistic and dermatophytic fungi and their preliminary mechanisms of action. The minimum inhibitory concentrations (MICs) of four synthetic naphthoquinones for 89 microorganisms, including opportunistic yeast agents, dermatophytes and opportunistic filamentous fungi, were determined. The compound that exhibited the best activity was assessed for its action against the cell wall (sorbitol test), for interference associated with ergosterol interaction, for osmotic balance (K+ efflux) and for membrane leakage of substances that absorb at the wavelength of 260 nm. All tested naphthoquinones exhibited antifungal activity, and compound IVS320 (3a,10b-dihydro-1H-cyclopenta [b] naphtho [2,3-d] furan-5,10-dione)-dione) demonstrated the lowest MICs across the tested species. The MIC of IVS320 was particularly low for dermatophytes (values ranging from 5-28 ?g/mL) and Cryptococcus spp. (3-5 ?g/mL). In preliminary mechanism-of-action tests, IVS320 did not alter the fungal cell wall but did cause problems in terms of cell membrane permeability (efflux of K+ and leakage of substances that absorb at 260 nm). This last effect was unrelated to ergosterol interactions with the membrane. PMID:24998949
Ferreira, Maria do Perpetuo Socorro Borges Carriço; Cardoso, Mariana Filomena do Carmo; da Silva, Fernando de Carvalho; Ferreira, Vitor Francisco; Lima, Emerson Silva; Souza, João Vicente Braga
Background. Kaposi sarcoma (KS) is one of the most common neoplasms diagnosed in HIV-seropositive subjects. Oral involvement is frequent and is associated with a poor prognosis. The aim of this study was to characterize the features of oral HIV-KS in patients from Ga-Rankuwa, South Africa. Methods. All cases with confirmed oral HIV-KS treated at the oral medicine clinic in Ga-Rankuwa from 2004 to 2010 were included in this retrospective study. Differences between males and females with oral HIV-KS in relation to HIV infection status, to oral KS presentation and to survival rates were statistically analysed. Results. Twenty (54%) of the 37 patients in the study were females and 17 (46%) were males. In 21 patients (57%), the initial presentation of HIV-KS was in the mouth. Other than the fact that females presented with larger (?10?mm) oral KS lesions (P = 0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions (P = 0.0003). Nine patients (24%) developed concomitant facial lymphoedema, and these patients had a significantly lower CD4+ T-cell count (28?cells/mm3) compared to the rest of the group (130?cells/mm3) (P = 0.01). The average CD4+ T-cell count of the patients who died (64?cells/mm3) was significantly lower (P = 0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions (P = 0.016) at the time of oral-KS presentation than of those who survived (166 ?cells/mm3). Conclusions: In Ga-Rankuwa, South Africa where HIV-KS is prevalent, oral KS affects similarly males and females. A low CD4+ T-cell count at the time of oral HIV-KS diagnosis and the development of facial lymphoedema during the course of HIV-KS disease portends a poor prognosis.
Khammissa, Razia A. G.; Pantanowitz, Liron; Feller, Liviu
Katima Mulilo has the highest burden of HIV\\/AIDS in Namibia. Due to several constraints of the antiretroviral therapy programme, HIV-infected persons still use ethnomedicines to manage AIDS-related opportunistic infections. Despite the reliance on plants to manage HIV\\/AIDS in Katima Mulilo, there have been no empirical studies to document the specific plant species used by traditional healers to treat AIDS-related opportunistic
Kazhila C Chinsembu; Marius Hedimbi
Introduction Each year, children suffer up to 5 colds and adults have 2-3 infections, leading to time off school or work, and considerable discomfort. Most symptoms resolve within a week, but coughs often persist for longer. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for common cold? We searched: Medline, Embase, The Cochrane Library and other important databases up to May 2007 (BMJ Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 19 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics or anti-inflammatory drugs, antibiotics, antihistamines, decongestants (norephedrine, oxymetazoline, or pseudoephedrine), decongestants plus antihistamine, echinacea, steam inhalation, vitamin C, and zinc (intranasal gel or lozenges).
Introduction Each year, children suffer up to 5 colds and adults have two to three infections, leading to time off school or work, and considerable discomfort. Most symptoms resolve within 1 week, but coughs often persist for longer. Methods and outcomes We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for common cold? We searched: Medline, Embase, The Cochrane Library, and other important databases up to January 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). Results We found 21 systematic reviews and RCTs that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. Conclusions In this systematic review we present information relating to the effectiveness and safety of the following interventions: analgesics or anti-inflammatory drugs, antibiotics, antihistamines, decongestants for short-term and for long-term relief, decongestants plus antihistamines, echinacea, steam inhalation, vitamin C, and zinc (intranasal gel or lozenges).
HIV-associated neurocognitive disorders (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occur in approximately 50% of HIV infected individuals. Our current understanding of HAND emanates mainly from HIV-1 subtype B (clade B), which is prevalent in USA and Western countries. However very little information is available on neuropathogenesis of HIV-1 subtype C (clade C) that exists in Sub-Saharan Africa and Asia. Therefore, studies to identify specific neuropathogenic mechanisms associated with HAND are worth pursuing to dissect the mechanisms underlying this modulation and to prevent HAND particularly in clade B infection. In this study, we have investigated 84 key human synaptic plasticity genes differential expression profile in clade B and clade C infected primary human astrocytes by using RT(2) Profile PCR Array human Synaptic Plasticity kit. Among these, 31 and 21 synaptic genes were significantly (?3 fold) down-regulated and 5 genes were significantly (?3 fold) up-regulated in clade B and clade C infected cells, respectively compared to the uninfected control astrocytes. In flow-cytometry analysis, down-regulation of postsynaptic density and dendrite spine morphology regulatory proteins (ARC, NMDAR1 and GRM1) was confirmed in both clade B and C infected primary human astrocytes and SK-N-MC neuroblastoma cells. Further, spine density and dendrite morphology changes by confocal microscopic analysis indicates significantly decreased spine density, loss of spines and decreased dendrite diameter, total dendrite and spine area in clade B infected SK-N-MC neuroblastoma cells compared to uninfected and clade C infected cells. We have also observed that, in clade B infected astrocytes, induction of apoptosis was significantly higher than in the clade C infected astrocytes. In conclusion, this study suggests that down-regulation of synaptic plasticity genes, decreased dendritic spine density and induction of apoptosis in astrocytes may contribute to the severe neuropathogenesis in clade B infection. PMID:23620748
Atluri, Venkata Subba Rao; Kanthikeel, Sudheesh P; Reddy, Pichili V B; Yndart, Adriana; Nair, Madhavan P N
Mononuclear phagocytes (monocytes, macrophages, and dendritic cells) play major roles in human immunodeficiency virus (HIV) persistence and disease pathogenesis. Macrophage antigen presentation and effector cell functions are impaired by HIV-1 infection. Abnormalities of macrophage effector cell function in bone marrow, lung, and brain likely result as a direct consequence of cellular activation and HIV replication. To further elucidate the extent of macrophage dysfunction in HIV-1 disease, a critical activation-specific regulatory molecule, nitric oxide (NO.), which may contribute to diverse pathology, was studied. Little, if any, NO. is produced by uninfected human monocytes. In contrast, infection with HIV-1 increases NO. production to modest, but significant levels (2-5 microM). Monocyte activation (with lipopolysaccharide, tumor necrosis factor alpha, or through interactions with astroglial cells) further enhances NO. production in HIV-infected cells, whereas its levels are diminished by interleukin 4. These results suggest a possible role for NO. in HIV-associated pathology where virus-infected macrophages are found. In support of this hypothesis, RNA encoding the inducible NO synthase (iNOS) was detected in postmortem brain tissue from one pediatric AIDS patient with advanced HIV encephalitis. Corresponding iNOS mRNA was not detected in brain tissue from five AIDS patients who died with less significant brain disease. These results demonstrate that HIV-1 can influence the expression of NOS in both cultured human monocytes and brain tissue. This newly described feature of HIV-macrophage interactions suggests previously unappreciated mechanisms of tissue pathology that result from productive viral replication.
Detection of Mycobacterium tuberculosis antigens in urine is attractive as a potential means of diagnosing tuberculosis (TB) regardless of the anatomical site of disease. The most promising candidate antigen is the cell wall lipopolysaccharide antigen lipoarabinomannan (LAM), which has been used to develop commercially available enzyme-linked immunosorbent assays. Although highly variable diagnostic accuracy has been observed in different clinical populations, it is now clear that this assay has useful sensitivity for diagnosis of HIV-associated TB in patients with advanced immunodeficiency and low CD4 cell counts. Thus, this assay is particularly useful when selectively used among patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards. These are the very patients who have the highest mortality risk and who stand to gain the most from rapid diagnosis, permitting immediate initiation of TB treatment. A recently developed low-cost, lateral-flow (urine ‘dip-stick’) format of the assay provides a result within 30 minutes and is potentially a major step forward as it can be used at the point-of-care, making the possibility of immediate diagnosis and treatment a reality. This paper discusses the likely utility of this point-of-care assay and how it might best be used in combination with other diagnostic assays for TB. The many further research studies that are needed on this assay are described. Consideration is particularly given to potential reasons for the variable specificity observed in existing field evaluations of LAM ELISAs. Whether this might be related to the assay itself or to the challenges associated with study design is discussed.
We report a first case of HIV-associated lymphoma (HAL) presenting with acute kidney injury (AKI) and inflammatory immune reconstitution syndrome (IRIS). A 39-year-old male, treated with nonsteroidal anti-inflammatory drugs (NSAIDs) for one month prior to admission, developed AKI, left testicular tumor, and recurrent swelling of the right parotid gland. A resected testicular tumor exhibited features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma. Renal biopsy showed hydro-degeneration of renal tubules, interstitial inflammatory cells, and a small number of lymphoma cells in the sub-capsule, compatible with acute interstitial nephritis. His renal dysfunction rapidly recovered following chemotherapy and combination antiretroviral therapy (cART). He developed pneumonia concomitantly with a decrease in HIV-RNA level and an increase in CD4+ cells after the first cycle of chemotherapy, which spontaneously resolved after the second cycle of chemotherapy without additional anti-infection drugs; thus, his pneumonia fulfilled the diagnostic criteria for IRIS. We suggest that IRIS may frequently develop during chemotherapy for HAL, but may be overlooked. He was coinfected with hepatitis B virus (HBV), which genotypes known as is associated with liver-related mortality and response to antiviral therapy; recently, an intimate interplay between HIV and HBV in the onset of lymphoma has been reported. Therefore, we addressed the HBV genotype in the patient. The analysis revealed that he exhibited a mixed genotype (A/E) not native to Japan and primarily found in Europe and North America or West Africa. These findings suggest that universal vaccination for juveniles against HBV is warranted in Japan. PMID:23411777
Tajima, Katsushi; Kohno, Kei; Shiono, Yosuke; Suzuki, Ikuko; Kato, Yuichi; Hiroshima, Yuki; Yamamoto, Masakazu; Ohtake, Hiroya; Iwaba, Akiko; Yamakawa, Mitsunori; Kato, Takeo
Detection of Mycobacterium tuberculosis antigens in urine is attractive as a potential means of diagnosing tuberculosis (TB) regardless of the anatomical site of disease. The most promising candidate antigen is the cell wall lipopolysaccharide antigen lipoarabinomannan (LAM), which has been used to develop commercially available enzyme-linked immunosorbent assays. Although highly variable diagnostic accuracy has been observed in different clinical populations, it is now clear that this assay has useful sensitivity for diagnosis of HIV-associated TB in patients with advanced immunodeficiency and low CD4 cell counts. Thus, this assay is particularly useful when selectively used among patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards. These are the very patients who have the highest mortality risk and who stand to gain the most from rapid diagnosis, permitting immediate initiation of TB treatment. A recently developed low-cost, lateral-flow (urine 'dip-stick') format of the assay provides a result within 30 minutes and is potentially a major step forward as it can be used at the point-of-care, making the possibility of immediate diagnosis and treatment a reality. This paper discusses the likely utility of this point-of-care assay and how it might best be used in combination with other diagnostic assays for TB. The many further research studies that are needed on this assay are described. Consideration is particularly given to potential reasons for the variable specificity observed in existing field evaluations of LAM ELISAs. Whether this might be related to the assay itself or to the challenges associated with study design is discussed. PMID:22536883
Lawn, Stephen D
Background HIV-associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral treatment (ART), and it is essential to have a sensitive and specific HAND screening tool. Methods Participants were 200 HIV-infected US military beneficiaries, managed early in the course of HIV infection, had few comorbidities, and had open access to ART. Participants completed a comprehensive, seven-domain (16-test), neuropsychological battery (?120 min); neurocognitive impairment (NCI) was determined using a standardized score derived from demographically adjusted T-scores (global deficit score ?0.5). Restricting the estimated administration time of the screening battery to =?20 minutes, we examined the sensitivity and specificity of detecting NCI for all possible combinations of 2-, 3-, and 4- tests from the comprehensive battery. Results Participants were relatively healthy (median CD4 count: 546 cells/mm3) with 64% receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min; sensitivity?=?73%; specificity?=?83%); the best 3-test screener included the above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min; sensitivity?=?86%; specificity?=?75%). The addition of Action Fluency to the above three tests improved specificity (18 min; sensitivity?=?86%; specificity?=?87%). Conclusions Combinations of widely accepted neuropsychological tests with brief implementation time demonstrated good sensitivity and specificity compared to a time intensive neuropsychological test battery. Tests of verbal learning, attention/working memory, and processing speed are particularly useful in detecting NCI. Utilizing validated, easy to administer, traditional neuropsychological tests with established normative data may represent an excellent approach to screening for NCI in HIV.
Moore, David J.; Roediger, Mollie J. P.; Eberly, Lynn E.; Blackstone, Kaitlin; Hale, Braden; Weintrob, Amy; Ganesan, Anuradha; Agan, Brian K.; Letendre, Scott L.; Crum-Cianflone, Nancy F.
Background HIV-associated neurocognitive disorder (HAND) is characterized by development of cognitive, behavioral and motor abnormalities, and occurs in approximately 50% of HIV infected individuals. In the United States, the prevalence of cigarette smoking ranges from 35-70% in HIV-infected individuals compared to 20% in general population. Cognitive impairment in heavy cigarette smokers has been well reported. However, the synergistic effects of nicotine and HIV infection and the underlying mechanisms in the development of HAND are unknown. Results In this study, we explored the role of nicotine in the progression of HAND using SK-N-MC, a neuronal cell line. SK-N-MC cells were infected with HIV-1 in the presence or absence of nicotine for 7 days. We observed significant increase in HIV infectivity in SK-N-MC treated with nicotine compared to untreated HIV-infected neuronal cells. HIV and nicotine synergize to significantly dysregulate the expression of synaptic plasticity genes and spine density; with a concomitant increase of HDAC2 levels in SK-N-MC cells. In addition, inhibition of HDAC2 up-regulation with the use of vorinostat resulted in HIV latency breakdown and recovery of synaptic plasticity genes expression and spine density in nicotine/HIV alone and in co-treated SK-N-MC cells. Furthermore, increased eIF2 alpha phosphorylation, which negatively regulates eukaryotic translational process, was observed in HIV alone and in co-treatment with nicotine compared to untreated control and nicotine alone treated SK-N-MC cells. Conclusions These results suggest that nicotine and HIV synergize to negatively regulate the synaptic plasticity gene expression and spine density and this may contribute to the increased risk of HAND in HIV infected smokers. Apart from disrupting latency, vorinostat may be a useful therapeutic to inhibit the negative regulatory effects on synaptic plasticity in HIV infected nicotine abusers.
Species' assessments must frequently be derived from opportunistic observations made by volunteers (i.e., citizen scientists). Interpretation of the resulting data to estimate population trends is plagued with problems, including teasing apart genuine population trends from variations in observation effort. We devised a way to correct for annual variation in effort when estimating trends in occupancy (species distribution) from faunal or floral databases of opportunistic observations. First, for all surveyed sites, detection histories (i.e., strings of detection-nondetection records) are generated. Within-season replicate surveys provide information on the detectability of an occupied site. Detectability directly represents observation effort; hence, estimating detectability means correcting for observation effort. Second, site-occupancy models are applied directly to the detection-history data set (i.e., without aggregation by site and year) to estimate detectability and species distribution (occupancy, i.e., the true proportion of sites where a species occurs). Site-occupancy models also provide unbiased estimators of components of distributional change (i.e., colonization and extinction rates). We illustrate our method with data from a large citizen-science project in Switzerland in which field ornithologists record opportunistic observations. We analyzed data collected on four species: the widespread Kingfisher (Alcedo atthis) and Sparrowhawk (Accipiter nisus) and the scarce Rock Thrush (Monticola saxatilis) and Wallcreeper (Tichodroma muraria). Our method requires that all observed species are recorded. Detectability was <1 and varied over the years. Simulations suggested some robustness, but we advocate recording complete species lists (checklists), rather than recording individual records of single species. The representation of observation effort with its effect on detectability provides a solution to the problem of differences in effort encountered when extracting trend information from haphazard observations. We expect our method is widely applicable for global biodiversity monitoring and modeling of species distributions. PMID:20337672
Kéry, Marc; Royle, J Andrew; Schmid, Hans; Schaub, Michael; Volet, Bernard; Häfliger, Guido; Zbinden, Niklaus
Summary Distance sampling is widely used to estimate the abundance or density of wildlife populations. Methods to estimate wildlife mortality rates have developed largely independently from distance sampling, despite the conceptual similarities between estimation of cumulative mortality and the population density of living animals. Conventional distance sampling analyses rely on the assumption that animals are distributed uniformly with respect to transects and thus require randomized placement of transects during survey design. Because mortality events are rare, however, it is often not possible to obtain precise estimates in this way without infeasible levels of effort. A great deal of wildlife data, including mortality data, is available via road-based surveys. Interpreting these data in a distance sampling framework requires accounting for the non-uniformity sampling. Additionally, analyses of opportunistic mortality data must account for the decline in carcass detectability through time. We develop several extensions to distance sampling theory to address these problems.We build mortality estimators in a hierarchical framework that integrates animal movement data, surveillance effort data, and motion-sensor camera trap data, respectively, to relax the uniformity assumption, account for spatiotemporal variation in surveillance effort, and explicitly model carcass detection and disappearance as competing ongoing processes.Analysis of simulated data showed that our estimators were unbiased and that their confidence intervals had good coverage.We also illustrate our approach on opportunistic carcass surveillance data acquired in 2010 during an anthrax outbreak in the plains zebra of Etosha National Park, Namibia.The methods developed here will allow researchers and managers to infer mortality rates from opportunistic surveillance data.
Bellan, Steve E.; Gimenez, Olivier; Choquet, Remi; Getz, Wayne M.
A monophyletic group of black yeast-like fungi containing opportunistic pathogens around Exophiala spinifera is analyzed using sequences of the small-subunit (SSU) and internal transcribed spacer (ITS) domains of ribosomal DNA. The group contains yeast-like and annellidic species (anamorph genus Exophiala) in addition to sympodial taxa (anamorph genera Ramichloridium and Rhinocladiella). The new species Exophiala oligosperma, Ramichloridium basitonum, and Rhinocladiella similis are introduced and compared with their morphologically similar counterparts at larger phylogenetic distances outside the E. spinifera clade. Exophiala jeanselmei is redefined. New combinations are proposed in EXOPHIALA: Exophiala exophialae for Phaeococcomyces exophialae and Exophiala heteromorpha for E. jeanselmei var. heteromorpha. PMID:14532218
de Hoog, G S; Vicente, V; Caligiorne, R B; Kantarcioglu, S; Tintelnot, K; Gerrits van den Ende, A H G; Haase, G
A monophyletic group of black yeast-like fungi containing opportunistic pathogens around Exophiala spinifera is analyzed using sequences of the small-subunit (SSU) and internal transcribed spacer (ITS) domains of ribosomal DNA. The group contains yeast-like and annellidic species (anamorph genus Exophiala) in addition to sympodial taxa (anamorph genera Ramichloridium and Rhinocladiella). The new species Exophiala oligosperma, Ramichloridium basitonum, and Rhinocladiella similis are introduced and compared with their morphologically similar counterparts at larger phylogenetic distances outside the E. spinifera clade. Exophiala jeanselmei is redefined. New combinations are proposed in Exophiala: Exophiala exophialae for Phaeococcomyces exophialae and Exophiala heteromorpha for E. jeanselmei var. heteromorpha.
de Hoog, G. S.; Vicente, V.; Caligiorne, R. B.; Kantarcioglu, S.; Tintelnot, K.; Gerrits van den Ende, A. H. G.; Haase, G.
Stenotrophomonas maltophilia is a worldwide human opportunistic pathogen associated with serious infections in humans, and is most often recovered from respiratory tract infections. In addition to its intrinsic drug resistance, this organism may acquire resistance via multiple molecular mechanisms. New antimicrobial strategies are needed to combat S. maltophilia infections, particularly in immunocompromised patients, cystic fibrosis patients with polymicrobial infections of the lung, and in patients with chronic infections. This editorial reports on newer drugs and antimicrobial strategies and their potential for use in treatment of S. maltophilia infections, the development of new technologies to detect this organism, and identifies strategies currently in use to reduce transmission of this pathogen. PMID:24308713
Brooke, Joanna S
This report covers the execution of and results from the activities proposed and approved in Exploration Analogs and Mission Development (EAMD) Field Test Protocol HMP2010: Evaluation of Robotic Systems to carry out Traverse Execution, Opportunistic Science, and Landing Site Evaluation Tasks. The field tests documented in this report examine one facet of a larger program of planetary surface exploration. This program has been evolving and maturing for several years, growing from a broad policy statement with a few specified milestones for NASA to an international effort with much higher fidelity descriptions of systems and operations necessary to accomplish this type of exploration.
Hoffman, Stephen J.; Leonard, Matther J.; Pacal, Lee
Background CXCL13 and CXCR5 are a chemokine and receptor pair whose interaction is critical for naïve B cell trafficking and activation within germinal centers. We sought to determine whether CXCL13 levels are elevated prior to HIV-associated non-Hodgkin B-cell lymphoma (AIDS-NHL), and whether polymorphisms in CXCL13 or CXCR5 are associated with AIDS-NHL risk and CXCL13 levels in a large cohort of HIV-infected men. Methods CXCL13 levels were measured in sera from 179 AIDS-NHL cases and 179 controls at three time-points. TagSNPs in CXCL13 (n=16) and CXCR5 (n=11) were genotyped in 183 AIDS-NHL cases and 533 controls. Odds ratios (OR) and 95% confidence intervals (CIs) for the associations between one unit increase in log CXCL13 levels and AIDS-NHL, as well as tagSNP genotypes and AIDS-NHL, were computed using logistic regression. Mixed linear regression was used to estimate mean ratios (MR) for the association between tagSNPs and CXCL13 levels. Results CXCL13 levels were elevated >3 years (OR=3.24, 95% CI=1.90–5.54), 1–3 years (OR=3.39, 95% CI=1.94–5.94) and 0–1 year (OR=3.94, 95% CI=1.98–7.81) prior to an AIDS-NHL diagnosis. The minor allele of CXCL13 rs355689 was associated with reduced AIDS-NHL risk (ORTCvsTT=0.65; 95% CI=0.45–0.96) and reduced CXCL13 levels (MRCCvsTT=0.82, 95% CI=0.68–0.99). The minor allele of CXCR5 rs630923 was associated with increased CXCL13 levels (MRAAvsTT=2.40, 95% CI=1.43–4.50). Conclusions CXCL13 levels were elevated preceding an AIDS-NHL diagnosis, genetic variation in CXCL13 may contribute to AIDS-NHL risk, and CXCL13 levels may be associated with genetic variation in CXCL13 and CXCR5. Impact CXCL13 may serve as a biomarker for early AIDS-NHL detection.
Hussain, Shehnaz K.; Zhu, Weiming; Chang, Shen-Chih; Breen, Elizabeth Crabb; Vendrame, Elena; Magpantay, Larry; Widney, Dan; Conn, Daniel; Sehl, Mary; Jacobson, Lisa P.; Bream, Jay H.; Wolinsky, Steven; Rinaldo, Charles R.; Ambinder, Richard F.; Detels, Roger; Zhang, Zuo-Feng; Martinez-Maza, Otoniel
Chemokine (C-C motif) ligand 2, also known as monocyte chemoattractant protein 1 (MCP-1) is an important factor for the pathogenesis of HIV-associated neurocognitive disorders (HAND). The mechanisms of MCP-1-mediated neuropathogenesis, in part, revolve around its neuroinflammatory role and the recruitment of monocytes into the central nervous system (CNS) via the disrupted blood-brain barrier (BBB). We have previously demonstrated that HIV-1/HIV-1 Tat upregulate platelet-derived growth factor (PDGF)-BB, a known cerebrovascular permeant; subsequently, the present study was aimed at exploring the regulation of MCP-1 by PDGF-BB in astrocytes with implications in HAND. Specifically, the data herein demonstrate that exposure of human astrocytes to HIV-1 LAI elevated PDGF-B and MCP-1 levels. Furthermore, treating astrocytes with the human recombinant PDGF-BB protein significantly increased the production and release of MCP-1 at both the RNA and protein levels. MCP-1 induction was regulated by activation of extracellular-signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinases and phosphatidylinositol 3-kinase (PI3K)/Akt pathways and the downstream transcription factor, nuclear factor ?B (NF?B). Chromatin immunoprecipitation (ChIP) assays demonstrated increased binding of NF?B to the human MCP-1 promoter following PDGF-BB exposure. Conditioned media from PDGF-BB-treated astrocytes increased monocyte transmigration through human brain microvascular endothelial cells (HBMECs), an effect that was blocked by STI-571, a tyrosine kinase inhibitor (PDGF receptor (PDGF-R) blocker). PDGF-BB-mediated release of MCP-1 was critical for increased permeability in an in vitro BBB model as evidenced by blocking antibody assays. Since MCP-1 is linked to disease severity, understanding its modulation by PDGF-BB could aid in understanding the proinflammatory responses in HAND. These results suggest that astrocyte activation by PDGF-BB exaggerates monocyte recruitment into the brain via MCP-1 and underscores the critical role astrocytes play in HAND.
Background: Invasive fungal infections cause considerable morbidity and mortality in immunocompromised hosts. Pigeon droppings could especially be a potential carrier in the spread of pathogenic yeasts and mold fungi into the environment. The objective of this study was to isolation of Cryptococcus neoformans and other opportunistic fungi from pigeon droppings. Materials and Methods: One hundred twenty samples of pigeon droppings were suspended 1:10 in saline solution and then cultured. Identification of C. neoformans was performed on bird seed agar, presence of a capsule on India ink preparation, urease production on urea agar medium and RapID yeast plus system. The identification of candida species was based on micro-morphological analysis on corn meal-Tween 80 agar, RapID yeast plus system and growth in CHROMagar candida. The identification of other fungi was based on macromorphologic, microscopic, biochemical and physiological characteristics. Results: The highest frequency of yeasts and mold fungi were observed in Candida albicans 6.6% and Penicillium spp. 25%. The frequency rate of C. neoformans isolation was 2.5%. Conclusion: Several types of fungi are present in pigeon droppings that can spread in environment and transmit to children and elderly as well as immunocompromised patients who are at increased risk of contracting opportunistic diseases.
Soltani, Maryam; Bayat, Mansour; Hashemi, Seyed J.; Zia, Mohammadali; Pestechian, Nader
The 11th in the series of International Workshops on Opportunistic Protists (IWOP-11) was held in August 2010 on the Big Island of Hawaii. These meetings are devoted to agents of infections that cause serious problems in AIDS patients and other individuals with defective immune systems. International Workshops on Opportunistic Protists serves as a forum for exchange of current research information on Pneumocystis, Cryptosporidium and the Microsporidia, Toxoplasma, free-living amoebae, kinetoplastid flagellates and other pathogens that are particularly pathogenic in immunodeficient hosts. Studies on interactions between host and pathogen, especially host responses, were highlighted in this year's symposium. The lack of in vitro cultivation methods for luxuriant growth of Pneumocystis, Cryptosporidium and the Enterocytozoon bieneusi remains a major hindrance to understanding the basic biology of these organisms and precludes genetic manipulations. However, slow but steady progress is being achieved by hard work including data mining of some completed or partially completed genome sequencing of several IWOP organisms. Of great concern is evidence for dramatic decline in research funding for these pathogens and the lack of appreciation by the larger scientific community concerning the state of art and challenges faced by researchers working on these organisms that can provide critical insight into emerging and reemerging pathogens. PMID:21129083
Kaneshiro, Edna S; Cushion, Melanie T; Marciano-Cabral, Francine; Weiss, Louis M; Xiao, Lihua
Capitella sp. I, an enrichment opportunist (Pearson and Resenberg, 1978) is a dominant inhabitant of hypoxic organic-rich marine sediments. Forbes (1988; Forbes and Lopez, in press) has demonstrated that environmental oxygen tension and the interaction between oxygen and food availability have a profound influence on the growth of this infaunal deposit feeder. Capitella sp. I, feeding on natural sediment, exhibits more rapid growth rates at high (130 mm Hg) relative to low (20 mm Hg) oxygen tensions. As part of an ongoing investigation of environmental hypoxia and heavy metal toxicity on marine benthic organisms, we investigated the effect of environmental oxygen tension on volume-loss rates of Capitella sp. I. We also examined the effect of exposure to cadmium (200 [mu]g/L) and its interaction with pO[sub 2] on volume- and carbon-loss rates. In contrast to fed worms, Capitella sp. I lost volume more rapidly at high (156 mm Hg) compared to low (12 mm Hg) oxygen tensions. Exposure to cadmium increased volume-loss rate, and the negative effect to cadmium was independent of pO[sub 2]. These results suggest that enrichment opportunists, such as Capitella, have evolved under conditions in which the availability of oxygen, rather than food, limits growth.
Forbes, V.E.; Forbes, T.L. (Odense Univ. (Denmark))
Allelopathy, one type of direct plant competition, can be a potent mechanism through which plant communities are structured. The aim of this study was to determine whether allelopathic interactions occur between the opportunistic green tide-forming species Ulva prolifera and the native macroalga Gracilaria lichvoides, both of which were collected from the coastline of East China sea. In laboratory experiments, the presence of G. lichvoides at 1.25 g wet weight L?1 significantly inhibited growth and photosynthesis of U. prolifera at concentrations of 1.25, 2.50, and 3.75 g wet weight L?1 (p<0.05) in both semi-continuous co-culture assays and in co-culture assays without nutrient supplementation. In contrast, although U. prolifera had a density effect on G. lichvoides, the differences among treatments were not significant (p>0.05). Culture medium experiments further confirmed that some allelochemicals may be released by both of the tested macroalgae, and these could account for the observed physiological inhibition of growth and photosynthesis. Moreover, the native macroalgae G. lichvoides was a stronger competitor than the opportunistic species U. prolifera. Collectively, the results of the present study represent a significant advance in exploring ecological questions about the effects of green tide blooms on the macroalgal community.
Zhang, Xiaowen; Fan, Xiao; Wang, Yitao; Li, Demao; Wang, Wei; Zhuang, Zhimeng; Ye, Naihao
Allelopathy, one type of direct plant competition, can be a potent mechanism through which plant communities are structured. The aim of this study was to determine whether allelopathic interactions occur between the opportunistic green tide-forming species Ulva prolifera and the native macroalga Gracilaria lichvoides, both of which were collected from the coastline of East China sea. In laboratory experiments, the presence of G. lichvoides at 1.25 g wet weight L(-1) significantly inhibited growth and photosynthesis of U. prolifera at concentrations of 1.25, 2.50, and 3.75 g wet weight L(-1) (p<0.05) in both semi-continuous co-culture assays and in co-culture assays without nutrient supplementation. In contrast, although U. prolifera had a density effect on G. lichvoides, the differences among treatments were not significant (p>0.05). Culture medium experiments further confirmed that some allelochemicals may be released by both of the tested macroalgae, and these could account for the observed physiological inhibition of growth and photosynthesis. Moreover, the native macroalgae G. lichvoides was a stronger competitor than the opportunistic species U. prolifera. Collectively, the results of the present study represent a significant advance in exploring ecological questions about the effects of green tide blooms on the macroalgal community. PMID:22496758
Xu, Dong; Gao, Zhengquan; Zhang, Xiaowen; Fan, Xiao; Wang, Yitao; Li, Demao; Wang, Wei; Zhuang, Zhimeng; Ye, Naihao
To examine the distribution of AIDS-defining illnesses among Danish AIDS patients, data on 687 AIDS patients diagnosed in the period from 1980 to 1990 (93% of all reported cases in the period) were collected. The most frequent AIDS-defining illness was Pneumocystis carinii pneumonia followed by candida oesophagitis and Kaposis sarcoma. The proportion of homo/bisexual men presenting with Kaposis sarcoma as the initial AIDS-defining illness declined over time. Patients with extrapulmonary tuberculosis had higher CD4 cell counts than patients presenting with other illnesses. Cytomegalovirus chorioretinitis and atypical mycobacteriosis were seen more frequently after the time of the AIDS diagnosis, and a low CD4 cell count at time of the AIDS diagnosis was a significant predictor for the development of these opportunistic infections during follow-up. Danish AIDS patients present with a wide spectrum of HIV-related illnesses, reflecting their exposure to opportunistic microorganisms and the degree of immune deficiency. The pattern of HIV-related illnesses is changing over time, and therefore continuous surveillance is needed to optimize therapeutic and prophylactic regimens. PMID:7709482
Lundgren, J D; Bentsen, K D; Pedersen, C; Gerstoft, J; Seefeldt-Nielsen, T; Nielsen, T L; Jensen, G F
Acetic acid bacteria (AAB) are broadly used in industrial food processing. Among them, members of the genera Asaia, Acetobacter, and Granulibacter were recently reported to be human opportunistic pathogens. We isolated AAB from clinical samples from three patients and describe here the clinical and bacteriological features of these cases. We report for the first time (i) the isolation of a Gluconobacter sp. from human clinical samples; (ii) the successive isolation of different AAB, i.e., an Asaia sp. and two unrelated Gluconobacter spp., from a cystic fibrosis patient; and (iii) persistent colonization of the respiratory tract by a Gluconobacter sp. in this patient. We reviewed the main clinical features associated with AAB isolation identified in the 10 documented reports currently available in the literature. Albeit rare, infections as well as colonization with AAB are increasingly reported in patients with underlying chronic diseases and/or indwelling devices. Clinicians as well as medical microbiologists should be aware of these unusual opportunistic pathogens, which are difficult to detect during standard medical microbiological investigations and which are multiresistant to antimicrobial agents. Molecular methods are required for identification of genera of AAB, but the results may remain inconclusive for identification to the species level.
Alauzet, Corentine; Teyssier, Corinne; Jumas-Bilak, Estelle; Gouby, Anne; Chiron, Raphael; Rabaud, Christian; Counil, Francois; Lozniewski, Alain; Marchandin, Helene
Climate change may cause increased microbial growth in water sources and more knowledge is required on how this may affect the hygienic water quality, i.e., whether increased occurrence of cyanobacteria and algae may stimulate the growth rate of opportunistic pathogenic bacteria. Laboratory experiments were performed to investigate if the presence of the cyanobacteria Anabanea lemmermannii and Microcystis aeruginosa affected the survival and growth rate of the opportunistic pathogenic bacteria Aeromonas hydrophila and Pseudomonas aeruginosa, and the faecal indicators Escherichia coli and coliforms. Cyanobacteria were cultured in bottles containing the nutrient-poor medium 02. Sewage, A. hydrophila or P. aeruginosa was added to cyanobacterial cultures and the bacterial growth and survival was followed. E. coli and coliforms from sewage died within few days and the decay rate was not affected by the presence of cyanobacteria. The presence of Anabaena stimulated the growth rate of P. aeruginosa, but had no effect on the growth rate of A. hydrophila. Microcystis had no effect on the growth rate of P. aeruginosa and an inhibiting effect on the growth rate of A. hydrophila. PMID:22097011
Bomo, Anne-Marie; Tryland, Ingun; Haande, Sigrid; Hagman, Camilla H C; Utkilen, Hans
Satellite communications have been rapidly developed due to its advantageous of wide coverage and large capacity. However, an efficient and robust transmission scheme still needs carefully designed due to the time-varying and unreliable nature of links of the satellite networks. In this paper, we consider cooperative communications by selecting relays dynamically via setting an appropriate threshold according to the real-time channel conditions to avoid error propagation and then apply opportunistic network coding (ONC) to further enhance network throughput. Considering the sparse representation of natural images, block based compressive sensing (BCS) and the proposed ONC are combined in a novel way forming an energy-efficient image processing system which is easy to be implemented. Simulation results show that the scheme we proposed can gain better performances compared with traditional cooperative and network coding methods.
Niu, Hui; Xiao, Song; Quan, Lei; Du, Jianchao
Members of the genus Cronobacter are an emerging group of opportunist Gram-negative pathogens. This genus was previously thought to be a single species, called Enterobacter sakazakii. Cronobacter spp. typically affect low-birth-weight neonates, causing life-threatening meningitis, sepsis and necrotizing enterocolitis. Outbreaks of disease have been associated with contaminated infant formula, although the primary environmental source remains elusive. Advanced understanding of these bacteria and better classification has been obtained by improved detection techniques and genomic analysis. Research has begun to characterize the virulence factors and pathogenic potential of Cronobacter. Investigations into sterilization techniques and protocols for minimizing the risk of contamination have been reviewed at national and international forums. In this review, we explore the clinical impact of Cronobacter neonatal and pediatric infections, discuss virulence and pathogenesis, and review prevention and treatment strategies. PMID:23538645
Hunter, C J; Bean, J F
This article studies the discrete-time queuing dynamics of opportunistic spectrum access (OSA) systems, in which the secondary user seeks spectrum vacancies between bursty transmissions of the primary user to communicate. Since spectrum sensing and data transmission can not be performed simultaneously, the secondary user employs a sensing-then-transmission strategy to detect the presence of the primary user before accessing the licensed channel. Consequently, the transmission of the secondary user is periodically suspended for spectrum sensing. To capture the discontinuous transmission nature of the secondary user, we introduce a discrete-time queuing subjected to bursty preemption to describe the behavior of the secondary user. Specifically, we derive some important metrics of the secondary user, including secondary spectrum utilization ratio, buffer length, packet delay and packet dropping ratio. Finally, simulation results validate the proposed theoretical model and reveal that the theoretical results fit the simulated results well.
Wang, Jin-long; Xu, Yu-hua; Gao, Zhan; Wu, Qi-hui
The American College of Medical Genetics and Genomics released recommendations for reporting incidental findings (IFs) in clinical exome and genome sequencing. These suggest 'opportunistic genomic screening' should be available to both adults and children each time a sequence is done and would be undertaken without seeking preferences from the patient first. Should opportunistic genomic screening be implemented in the United Kingdom, the Association of Genetic Nurses and Counsellors (AGNC), which represents British and Irish genetic counsellors and nurses, feels strongly that the following must be considered (see article for complete list): (1) Following appropriate genetic counselling, patients should be allowed to consent to or opt out of opportunistic genomic screening. (2) If true IFs are discovered the AGNC are guided by the report from the Joint Committee on Medical Genetics about the sharing of genetic testing results. (3) Children should not be routinely tested for adult-onset conditions. (4) The formation of a list of variants should involve a representative from the AGNC as well as a patient support group. (5) The variants should be for serious or life-threatening conditions for which there are treatments or preventative strategies available. (6) There needs to be robust evidence that the benefits of opportunistic screening outweigh the potential harms. (7) The clinical validity and utility of variants should be known. (8) There must be a quality assurance framework that operates to International standards for laboratory testing. (9) Psychosocial research is urgently needed in this area to understand the impact on patients. PMID:24398792
Middleton, Anna; Patch, Chris; Wiggins, Jennifer; Barnes, Kathy; Crawford, Gill; Benjamin, Caroline; Bruce, Anita
We propose the cross-layer based opportunistic multi-channel medium access control (MAC) protocols, which integrate the spectrum sensing at physical (PHY) layer with the packets scheduling at MAC layer, for the wireless ad hoc networks. Specifically, the MAC protocols enable the secondary users to identify and utilize the leftover frequency spectrum in a way that constrains the level of interference to
Hang Su; Xi Zhang
Background: We aimed to evaluate and quantify the risk of serious opportunistic infections after induction with polyclonal antibodies versus IL-2 receptor antagonists (IL-2RAs) in randomized clinical trials. Methods: PRISMA guidelines were followed and random-effects models were performed. Results: 70 randomized clinical trials (10,106 patients) were selected: 36 polyclonal antibodies (n = 3377), and 34 IL-2RAs (n = 6729). Compared to controls, polyclonal antibodies showed higher risk of serious opportunistic infections (OR: 1.93, 95% CI: 1.34-2.80; p < 0.0001); IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.80, 95% CI: 0.68-0.94; p = 0.009). Polyclonal antibodies were associated with higher risk of bacterial (OR: 1.58, 95% CI: 1.00-2.50; p = 0.049) and viral infections (OR: 2.37, 95% CI: 1.60-3.49; p < 0.0001), while IL-2RAs were associated with lower risk of cytomegalovirus (CMV) disease (OR: 0.73, 95% CI: 0.56-0.97; p = 0.032). Adjusted indirect comparison: compared to polyclonal antibodies, IL-2RAs were associated with lower risk of serious opportunistic infections (OR: 0.41, 95% CI: 0.34-0.49; p < 0.0001), bacterial infections (OR: 0.51, 95% CI: 0.39-0.67; p < 0.0001) and CMV disease (OR: 0.58, 95% CI: 0.34-0.98; p = 0.043). Results remained consistent across allografts. Conclusion: The risk of serious opportunistic infections, bacterial infections and CMV disease were all significantly decreased with IL-2RAs compared to polyclonal antibodies. PMID:24869718
Kalil, Andre C; Florescu, Marius C; Grant, Wendy; Miles, Clifford; Morris, Michael; Stevens, R Brian; Langnas, Alan N; Florescu, Diana F
Background The invasive Chondrostoma nasus nasus has colonized part of the distribution area of the protected endemic species Chondrostoma toxostoma toxostoma. This hybrid zone is a complex system where multiple effects such as inter-species competition, bi-directional introgression, strong environmental pressure and so on are combined. Why do sympatric Chondrostoma fish present a unidirectional change in body shape? Is this the result of inter-species interactions and/or a response to environmental effects or the result of trade-offs? Studies focusing on the understanding of a trade-off between multiple parameters are still rare. Although this has previously been done for Cichlid species flock and for Darwin finches, where mouth or beak morphology were coupled to diet and genetic identification, no similar studies have been done for a fish hybrid zone in a river. We tested the correlation between morphology (body and mouth morphology), diet (stable carbon and nitrogen isotopes) and genomic combinations in different allopatric and sympatric populations for a global data set of 1330 specimens. To separate the species interaction effect from the environmental effect in sympatry, we distinguished two data sets: the first one was obtained from a highly regulated part of the river and the second was obtained from specimens coming from the less regulated part. Results The distribution of the hybrid combinations was different in the two part of the sympatric zone, whereas all the specimens presented similar overall changes in body shape and in mouth morphology. Sympatric specimens were also characterized by a larger diet behavior variance than reference populations, characteristic of an opportunistic diet. No correlation was established between the body shape (or mouth deformation) and the stable isotope signature. Conclusion The Durance River is an untamed Mediterranean river despite the presence of numerous dams that split the river from upstream to downstream. The sympatric effect on morphology and the large diet behavior range can be explained by a tendency toward an opportunistic behavior of the sympatric specimens. Indeed, the similar response of the two species and their hybrids implied an adaptation that could be defined as an alternative trade-off that underline the importance of epigenetics mechanisms for potential success in a novel environment.
Corse, Emmanuel; Costedoat, Caroline; Pech, Nicolas; Chappaz, Remi; Grey, Jonathan; Gilles, Andre
Idiopathic CD4 lymphocytopenia (ICL) was first defined in 1992 by the US Centers for Disease Control and Prevention (CDC) as the repeated presence of a CD4+ T lymphocyte count of fewer than 300 cells per cubic millimeter or of less than 20% of total T cells with no evidence of human immunodeficiency virus (HIV) infection and no condition that might cause depressed CD4 counts. Most of our knowledge about ICL comes from scattered case reports. The aim of this study was to collect comprehensive data from the previously published cases to understand the characteristics of this rare condition. We searched the PubMed database and Science Direct for case reports since 1989 for Idiopathic CD4 lymphocytopenia cases. We found 258 cases diagnosed with ICL in 143 published papers. We collected data about age, sex, pathogens, site of infections, CD4 count, CD8 count, CD4:CD8 ratio, presence of HIV risk factors, malignancies, autoimmune diseases and whether the patients survived or died. The mean age at diagnosis of first opportunistic infection (or ICL if no opportunistic infection reported) was 40.7 ± 19.2 years (standard deviation), with a range of 1 to 85. One-sixty (62%) patients were males, 91 (35.2%) were females, and 7 (2.7%) patients were not identified whether males or females. Risk factors for HIV were documented in 36 (13.9%) patients. The mean initial CD4 count was 142.6 ± 103.9/mm3 (standard deviation). The mean initial CD8 count was 295 ± 273.6/mm3 (standard deviation). The mean initial CD4:CD8 ratio was 0.6 ± 0.7 (standard deviation). The mean lowest CD4 count was 115.4 ± 87.1/mm3 (standard deviation). The majority of patients 226 (87.6%) had at least one infection. Cryptococcal infections were the most prevalent infections in ICL patients (26.6%), followed by mycobacterial infections (17%), candidal infections (16.2%), and VZV infections (13.1%). Malignancies were reported in 47 (18.1%) patients. Autoimmune diseases were reported in 37 (14.2%) patients.
Ahmad, Dina S.; Esmadi, Mohammad; Steinmann, William C.
Serial monitoring of peripheral blood lymphocyte subpopulations (PBLSs) counts might be useful in predicting post-transplant opportunistic infection (OI) after kidney transplantation (KT). PBLSs were prospectively measured in 304 KT recipients at baseline and post-transplant months 1 and 6. Areas under receiver operating characteristic curves were used to evaluate the accuracy of different subpopulations in predicting the occurrence of overall OI and, specifically, cytomegalovirus (CMV) disease. We separately analyzed patients not receiving (n = 164) or receiving (n = 140) antithymocyte globulin (ATG) as induction therapy. In the non-ATG group, a CD8(+) T-cell count at month 1 <0.100 × 10(3) cells/?l had negative predictive values of 0.84 and 0.86 for the subsequent occurrence of overall OI and CMV disease, respectively. In the multivariate Cox model, a CD8(+) T-cell count <0.100 × 10(3) cells/?l was an independent risk factor for OI (adjusted hazard ratio: 3.55; P-value = 0.002). In the ATG group, a CD4(+) T-cell count at month 1 <0.050 × 10(3) cells/?l showed negative predictive values of 0.92 for the subsequent occurrence of overall OI and CMV disease. PBLSs monitoring effectively identify KT recipients at low risk of OI, providing an opportunity for individualizing post-transplant prophylaxis practices. PMID:24650360
Fernández-Ruiz, Mario; López-Medrano, Francisco; Allende, Luis M; Andrés, Amado; García-Reyne, Ana; Lumbreras, Carlos; San-Juan, Rafael; Morales, José M; Paz-Artal, Estela; Aguado, José M
Clinical-grade T cells are genetically modified ex vivo to express chimeric antigen receptors (CARs) to redirect their specificity to target tumor-associated antigens in vivo. We now have developed this molecular strategy to render cytotoxic T cells specific for fungi. We adapted the pattern-recognition receptor Dectin-1 to activate T cells via chimeric CD28 and CD3-? (designated "D-CAR") upon binding with carbohydrate in the cell wall of Aspergillus germlings. T cells genetically modified with the Sleeping Beauty system to express D-CAR stably were propagated selectively on artificial activating and propagating cells using an approach similar to that approved by the Food and Drug Administration for manufacturing CD19-specific CAR(+) T cells for clinical trials. The D-CAR(+) T cells exhibited specificity for ?-glucan which led to damage and inhibition of hyphal growth of Aspergillus in vitro and in vivo. Treatment of D-CAR(+) T cells with steroids did not compromise antifungal activity significantly. These data support the targeting of carbohydrate antigens by CAR(+) T cells and provide a clinically appealing strategy to enhance immunity for opportunistic fungal infections using T-cell gene therapy. PMID:25002471
Kumaresan, Pappanaicken R; Manuri, Pallavi R; Albert, Nathaniel D; Maiti, Sourindra; Singh, Harjeet; Mi, Tiejuan; Roszik, Jason; Rabinovich, Brian; Olivares, Simon; Krishnamurthy, Janani; Zhang, Ling; Najjar, Amer M; Huls, M Helen; Lee, Dean A; Champlin, Richard E; Kontoyiannis, Dimitrios P; Cooper, Laurence J N
Bacteria persistence is a well-known phenomenon, where a small fraction of cells in an isogenic population are able to survive high doses of antibiotic treatment. Since the persistence is often associated with single cell behaviour, the ability to study the dynamic response of individual cells to antibiotics is critical. In this work, we developed a gradient microfluidic system that enables long-term tracking of single cell morphology under a wide range of inhibitor concentrations. From time-lapse images, we calculated bacterial growth rates based on the variations in cell mass and in cell number. Using E. coli and Comamonas denitrificans to amoxicillin inhibition as model systems, we found the IC50 determined via both methods are in a good agreement. Importantly, the growth rates together with morphological dynamics of individual cells has led to the discovery of a new form of persistence to amoxicillin. Normal cells that are sensitive to amoxicillin gain persistence or recover from the killing process, if they have had an opportunity to utilise the cytoplasm released from lysed cells close-by. We term this acquired persistence in normal growing cells "opportunistic persistence". This finding might shed new insights into biofilm resistance and the effect of antibiotics on environmental microbes. PMID:24733150
Li, Bing; Qiu, Yong; Glidle, Andrew; Cooper, Jon; Shi, HanChang; Yin, HuaBing
We studied factors that affect prey selection by a generalist predator that opportunistically attacks prey species, and the associated inter- and intra-specific responses of prey to this type of predation. Our model system was a guild of ground-foraging birds that are preyed upon by magpies ( Pica pica) during the breeding season. We found that magpies attacked up to 12 species during three consecutive breeding seasons. The overall capture success was estimated to be 4.9%. Magpies tended to attack from the air, targeting solitary prey, either on the ground or flying. Inter-specific prey responses to the risk of magpie predation included a reduction in the mean number of species occupying a foraging patch when magpies were present and a decrease in the distance between heterospecific neighbours. Intra-specific responses to magpie predation varied between species that were subject to different attack rates. Preferentially attacked prey enhanced their risk responses (increase in scanning time and scanning rate in the presence of magpies) relative to those species attacked in proportion to their abundance (increase only in scanning rate with magpies). Species attacked infrequently, relative to their abundance, showed no antipredator response. The probability of being attacked, rather than mortality rate, appears to be the factor to which prey species respond. PMID:15133731
Fernández-Juricic, Esteban; Jokimäki, Jukka; McDonald, J Chase; Melado, Francisco; Toledano, Adolfo; Mayo, Carolina; Martín, Beatriz; Fresneda, Isabel; Martín, Verónica
Hfq is an RNA-binding protein known to regulate a variety of cellular processes by interacting with small RNAs (sRNAs) and mRNAs in prokaryotes. Stenotrophomonas maltophilia is an important opportunistic pathogen affecting primarily hospitalized and immunocompromised hosts. We constructed an hfq deletion mutant (?hfq) of S. maltophilia and compared the behaviors of wild-type and ?hfq S. maltophilia cells in a variety of assays. This revealed that S. maltophilia Hfq plays a role in biofilm formation and cell motility, as well as susceptibility to antimicrobial agents. Moreover, Hfq is crucial for adhesion to bronchial epithelial cells and is required for the replication of S. maltophilia in macrophages. Differential RNA sequencing analysis (dRNA-seq) of RNA isolated from S. maltophilia wild-type and ?hfq strains showed that Hfq regulates the expression of genes encoding flagellar and fimbrial components, transmembrane proteins, and enzymes involved in different metabolic pathways. Moreover, we analyzed the expression of several sRNAs identified by dRNA-seq in wild-type and ?hfq S. maltophilia cells grown in different conditions on Northern blots. The accumulation of two sRNAs was strongly reduced in the absence of Hfq. Furthermore, based on our dRNA-seq analysis we provide a genome-wide map of transcriptional start sites in S. maltophilia.
Roscetto, Emanuela; Angrisano, Tiziana; Costa, Valerio; Casalino, Mariassunta; Forstner, Konrad U.; Sharma, Cynthia M.; Di Nocera, Pier Paolo
Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three reported prior cases in the English-language literature. We describe a case of OL-HED-ID in a male infant who initially presented with congenital lymphedema, leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He subsequently developed gram-negative sepsis and multiple opportunistic infections including high-level cytomegalovirus viremia and Pneumocystis jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine sparse hair, and periorbital wrinkling, all features suggestive of ectodermal dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell dysfunction. Genetic testing revealed a novel mutation in the nuclear factor kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of OL-HED-ID. Mutations in the NEMO gene have been reported in association with hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and incontinentia pigmenti. In this case, we report a novel mutation in the NEMO gene associated with OL-HED-ID. This article highlights the dermatologic manifestations of a rare disorder, OL-HED-ID, and underscores the importance of early recognition and prompt intervention to prevent life-threatening infections. PMID:23405946
Carlberg, Valerie M; Lofgren, Sabra M; Mann, Julianne A; Austin, Jared P; Nolt, Dawn; Shereck, Evan B; Davila-Saldana, Blachy; Zonana, Jonathan; Krol, Alfons L
Mucormycosis is a rare and opportunistic infection caused by fungi belonging to the order Mucorales. Recent reports have demonstrated an increasing incidence of mucormycosis, which is frequently lethal, especially in patients suffering from severe underlying conditions such as immunodeficiency. In addition, even though conventional mycology and histopathology assays allow for the identification of Mucorales, they often fail in offering a species-specific diagnosis. Due to the lack of other laboratory tests, a precise identification of these molds is thus notoriously difficult. In this study we aimed to develop a molecular biology tool to identify the main Mucorales involved in human pathology. A PCR strategy selectively amplifies genomic DNA from molds belonging to the genera Absidia, Mucor, Rhizopus, and Rhizomucor, excluding human DNA and DNA from other filamentous fungi and yeasts. A subsequent digestion step identified the Mucorales at genus and species level. This technique was validated using both fungal cultures and retrospective analyses of clinical samples. By enabling a rapid and precise identification of Mucorales strains in infected patients, this PCR-restriction fragment length polymorphism-based method should help clinicians to decide on the appropriate treatment, consequently decreasing the mortality of mucormycosis.
Machouart, M.; Larche, J.; Burton, K.; Collomb, J.; Maurer, P.; Cintrat, A.; Biava, M. F.; Greciano, S.; Kuijpers, A. F. A.; Contet-Audonneau, N.; de Hoog, G. S.; Gerard, A.; Fortier, B.
Environmental populations of the opportunistic pathogen Aspergillus fumigatus have been shown to be genotypically diverse and to contain a range of isolates with varying pathogenic potential. In this study, we combined two RAPD primers to investigate the genetic diversity of environmental isolates from Manchester collected monthly over 1 year alongside Dublin environmental isolates and clinical isolates from patients. RAPD analysis revealed a diverse genotype, but with three major clinical isolate clusters. When the pathogenicity of clinical and Dublin isolates was compared with a random selection of Manchester isolates in a Galleria mellonella larvae model, as a group, clinical isolates were significantly more pathogenic than environmental isolates. Moreover, when relative pathogenicity of individual isolates was compared, clinical isolates were the most pathogenic, Dublin isolates were the least pathogenic and Manchester isolates showed a range in pathogenicity. Overall, this suggests that the environmental population is genetically diverse, displaying a range in pathogenicity, and that the most pathogenic strains from the environment are selected during patient infection. PMID:24464798
Alshareef, Fadwa; Robson, Geoffrey D
During the 2010-11 summer outbreak of ostreid herpesvirus 1 (OsHV-1) in New Zealand, an opportunistic longitudinal field study was conducted. OsHV-1 PCR-negative oyster spat (Crassostrea gigas) were relocated to an OsHV-1 PCR-positive area of the North Island of New Zealand that was experiencing juvenile oyster mortalities. Over a period of 13 d, spat were monitored for mortality, sampled for histopathology, and tested for the presence of OsHV-1 using real time PCR and Vibrio culture. Histopathology showed some evidence of tissue pathology; however, no consistent progressive pathology was apparent. Field mortalities were evident from Day 6 on. After 5 and 7 d of exposure, 83 and 100% of spat, respectively, tested positive for the virus by real time PCR. Vibrio species recovered during the longitudinal study included V. splendidus and V. aestuarianus. This study offers insight into the rapidity of onset and virulence of the virus in naïve oyster spat in New Zealand waters. PMID:24991849
Keeling, S E; Brosnahan, C L; Williams, R; Gias, E; Hannah, M; Bueno, R; McDonald, W L; Johnston, C
Infection rate among intravenous drug users (IDU) is higher than the general public, and is the major cause of morbidity and hospitalization in the IDU population. Epidemiologic studies provide data on increased prevalence of opportunistic bacterial infections such as TB and pneumonia, and viral infections such as HIV-1 and hepatitis in the IDU population. An important component in the intravenous drug abuse population and in patients receiving medically indicated chronic opioid treatment is opioid withdrawal. Data on bacterial virulence in the context of opioid withdrawal suggest that mice undergoing withdrawal had shortened survival and increased bacterial load in response to Salmonella infection. As the body of evidence in support of opioid dependency and its immunosuppressive effects is growing, it is imperative to understand the mechanisms by which opioids exert these effects and identify the populations at risk that would benefit the most from the interventions to counteract opioid immunosuppressive effects. Thus, it is important to refine the existing animal model to closely match human conditions and to cross-validate these findings through carefully controlled human studies. Better understanding of the mechanisms will facilitate the search for new therapeutic modalities to counteract adverse effects including increased infection rates. This review will summarize the effects of morphine on innate and adaptive immunity, identify the role of the mu opioid receptor in these functions and the signal transduction activated in the process. The role of opioid withdrawal in immunosuppression and the clinical relevance of these findings will also be discussed. PMID:21789507
Roy, Sabita; Ninkovic, Jana; Banerjee, Santanu; Charboneau, Richard Gene; Das, Subhas; Dutta, Raini; Kirchner, Varvara A; Koodie, Lisa; Ma, Jing; Meng, Jingjing; Barke, Roderick A
Certain species of the genus Cronobacter are considered opportunistic pathogens, but their detection in milk products according to ISO/TS 22964 may take up to six days. The aim of this study was to develop a fast and sensitive PCR-based detection system for these species including enrichment, DNA-isolation and detection by real-time PCR, using the outer membrane protein gene ompA as a target. The assay was successfully validated using type strains of the genus Cronobacter, as well as 18 strains of closely related genera as controls. A total of 40 Cronobacter spp. food isolates yielded positive results, while the food matrix itself did not influence the PCR reaction. An equal detection limit as achieved with the ISO/TS 22964 method was established in this study, when 0.01 CFU Cronobacter sakazakii DSM 4485(T) per gram powdered infant formula were successfully detected after 28 days of storage at ambient temperature. In comparison to the ISO/TS 22964 method, the method described here has an equal detection limit, but offers a specific detection at the genus level in an analysis time of 24 h. PMID:24929712
Zimmermann, Jennifer; Schmidt, Herbert; Loessner, Martin J; Weiss, Agnes
Infection rate among intravenous drug users (IDU) is higher than the general public, and is the major cause of morbidity and hospitalization in the IDU population. Epidemiologic studies provide data on increased prevalence of opportunistic bacterial infections such as TB and pneumonia, and viral infections such as HIV-1 and hepatitis in the IDU population. An important component in the intravenous drug abuse population and in patients receiving medically indicated chronic opioid treatment is opioid withdrawal. Data on bacterial virulence in the context of opioid withdrawal suggest that mice undergoing withdrawal had shortened survival and increased bacterial load in response to Salmonella infection. As the body of evidence in support of opioid dependency and its immunosuppressive effects is growing, it is imperative to understand the mechanisms by which opioids exert these effects and identify the populations at risk that would benefit the most from the interventions to counteract opioid immunosuppressive effects. Thus, it is important to refine the existing animal model to closely match human conditions and to cross-validate these findings through carefully controlled human studies. Better understanding of the mechanisms will facilitate the search for new therapeutic modalities to counteract adverse effects including increased infection rates. This review will summarize the effects of morphine on innate and adaptive immunity, identify the role of the mu opioid receptor in these functions and the signal transduction activated in the process. The role of opioid withdrawal in immunosuppression and the clinical relevance of these findings will also be discussed.
Roy, Sabita; Ninkovic, Jana; Banerjee, Santanu; Charboneau, Richard; Das, Subhas; Dutta, Raini; Kirchner, Varvara; Koodie, Lisa; Ma, Jing; Meng, Jingjing
Acinetobacter baumannii is an opportunistic pathogen that causes nosocomial infections. Due to the ability to persist in the clinical environment and rapidly acquire antibiotic resistance, multidrug-resistant A. baumannii clones have spread in medical units in many countries in the last decade. The molecular basis of the emergence and spread of the successful multidrug-resistant A. baumannii clones is not understood. Bacterial toxin-antitoxin (TA) systems are abundant genetic loci harbored in low-copy-number plasmids and chromosomes and have been proposed to fulfill numerous functions, from plasmid stabilization to regulation of growth and death under stress conditions. In this study, we have performed a thorough bioinformatic search for type II TA systems in genomes of A. baumannii strains and estimated at least 15 possible TA gene pairs, 5 of which have been shown to be functional TA systems. Three of them were orthologs of bacterial and archaeal RelB/RelE, HicA/HicB, and HigB/HigA systems, and others were the unique SplT/SplA and CheT/CheA TA modules. The toxins of all five TA systems, when expressed in Escherichia coli, inhibited translation, causing RNA degradation. The HigB/HigA and SplT/SplA TA pairs of plasmid origin were highly prevalent in clinical multidrug-resistant A. baumannii isolates from Lithuanian hospitals belonging to the international clonal lineages known as European clone I (ECI) and ECII.
Jurenaite, Milda; Markuckas, Arvydas
Acinetobacter baumannii is an opportunistic pathogen that causes nosocomial infections. Due to the ability to persist in the clinical environment and rapidly acquire antibiotic resistance, multidrug-resistant A. baumannii clones have spread in medical units in many countries in the last decade. The molecular basis of the emergence and spread of the successful multidrug-resistant A. baumannii clones is not understood. Bacterial toxin-antitoxin (TA) systems are abundant genetic loci harbored in low-copy-number plasmids and chromosomes and have been proposed to fulfill numerous functions, from plasmid stabilization to regulation of growth and death under stress conditions. In this study, we have performed a thorough bioinformatic search for type II TA systems in genomes of A. baumannii strains and estimated at least 15 possible TA gene pairs, 5 of which have been shown to be functional TA systems. Three of them were orthologs of bacterial and archaeal RelB/RelE, HicA/HicB, and HigB/HigA systems, and others were the unique SplT/SplA and CheT/CheA TA modules. The toxins of all five TA systems, when expressed in Escherichia coli, inhibited translation, causing RNA degradation. The HigB/HigA and SplT/SplA TA pairs of plasmid origin were highly prevalent in clinical multidrug-resistant A. baumannii isolates from Lithuanian hospitals belonging to the international clonal lineages known as European clone I (ECI) and ECII. PMID:23667234
Jurenaite, Milda; Markuckas, Arvydas; Suziedeliene, Edita
Coastal wetlands are among the most fragmented and disturbed ecosystems and the Great Lakes are no exception. One possible result is the observed increase in the presence and dominance of invasive and other opportunistic plant species, such as the common reed (Phragmites australi...
In this contribution we exploit the benefits of combining the diversity gains arising from cooperation, multiple propagation paths and from the opportunistic scheduling of multiple users, for the sake of supporting a power-efficient single-relay assisted single-carrier frequency-division multiple-access uplink, where each relay supports a single user communicating over dispersive channels subject to large-scale fading. Based on the proposed joint frequency-domain
Jiayi Zhang; Lie-Liang Yang; Lajos Hanzo
We use partisan and opportunistic political business cycle (“PBC”) considerations to develop a framework for explaining election-period decisions by credit rating agencies (“agencies”) publishing developing country sovereign risk-ratings (“ratings”). We test six hypotheses derived from the framework with 482 agency ratings for 19 countries holding 39 presidential elections from 1987-2000. We find that ratings are linked to the partisan orientation
Steven Block; Burkhard N. Schrage; Paul M. Vaaler
The sensitivity of 23 isolates of opportunistic fungi, Aspergillus fumigatus (5), A. flavus (5), A. niger (5), Pseudallescheria boydii (5), Alternaria alternata (2) and Xylohypha bantiana (1), was investigated against fluconazole and itraconazole, using Sabouraud’s dextrose broth (SD) and a high-resolution (HR) medium (Pfizer, Inc.). The procedure followed was a standard tube dilution (1 ml\\/tube) method. Candida albicans Y01 09
A. S. Sekhon; A. A. Padhye; A. K. Garg; Z. Hamir
A regional field study of ichnocoenoses in the Griesbachian Dinwoody Formation and the Smithian Sinbad Limestone Member revealed that benthic invertebrate tracemaking populations exhibited aspects of opportunistic behaviour following the end-Permian mass extinction. This study represents the first documentation of population strategies of ichnocoenoses following a mass extinction event. These trace fossil assemblages are characterised by low-to-moderate ichnodiversity, low-to-moderate bioturbation,
M. L. Fraiser; D. J. Bottjer
Background Opportunistic infections and malignancies such as malignant lymphoma and Kaposi sarcoma are significant complications of human immunodeficiency virus (HIV) infection. However, following the introduction of antiretroviral therapy in Japan in 1997, the incidence of clinical complications has decreased. In the present study, autopsy cases of HIV infection in Japan were retrospectively investigated to reveal the prevalence of opportunistic infections and malignancies. Methods A total of 225 autopsy cases of HIV infection identified at 4 Japanese hospitals from 1985–2012 were retrospectively reviewed. Clinical data were collected from patient medical records. Results Mean CD4 counts of patients were 77.0 cells/?L in patients who received any antiretroviral therapy during their lives (ART (+) patients) and 39.6 cells/?L in naïve patients (ART (?) patients). Cytomegalovirus infection (142 cases, 63.1%) and pneumocystis pneumonia (66 cases, 29.3%) were the most frequent opportunistic infections, and their prevalence was significantly lower in ART (+) patients than ART (?) patients. Non-Hodgkin lymphoma and Kaposi sarcoma were observed in 30.1% and 16.2% of ART (?) patients, and 37.9% and 15.2% of ART (+) patients, respectively. Malignant lymphoma was the most frequent cause of death, followed by cytomegalovirus infection regardless of ART. Non-acquired immunodeficiency syndrome (AIDS)-defining cancers such as liver and lung cancer caused death more frequently in ART (+) patients (9.1%) than in ART (?) patients (1.5%; P?=?0.026). Conclusions The prevalence of infectious diseases and malignancies were revealed in autopsy cases of HIV infection in Japan. The prevalence of cytomegalovirus infection and pneumocystis pneumonia at autopsy were lower in ART (+) patients than ART (?) patients. Higher prevalence of non-AIDS defining malignancies among ART (+) patients than ART (?) patients suggests that onsets of various opportunistic infections and malignancies should be carefully monitored regardless of whether the patient is receiving ART.
Katima Mulilo has the highest burden of HIV/AIDS in Namibia. Due to several constraints of the antiretroviral therapy programme, HIV-infected persons still use ethnomedicines to manage AIDS-related opportunistic infections. Despite the reliance on plants to manage HIV/AIDS in Katima Mulilo, there have been no empirical studies to document the specific plant species used by traditional healers to treat AIDS-related opportunistic infections. In this study, an ethnobotanical survey was conducted to record the various plant families, species, and plant parts used to manage different HIV/AIDS-related opportunistic infections in Katima Mulilo, Caprivi region, Namibia. The results showed that a total of 71 plant species from 28 families, mostly the Combretaceae (14%), Anacardiaceae (8%), Mimosaceae (8%), and Ebanaceae (7%), were used to treat conditions such as herpes zoster, diarrhoea, coughing, malaria, meningitis, and tuberculosis. The most plant parts used were leaves (33%), bark (32%), and roots (28%) while the least used plant parts were fruits/seeds (4%). Further research is needed to isolate the plants' active chemical compounds and understand their modes of action.
We lack a deep understanding of genetic and metabolic attributes specializing in microbial consortia for initial and subsequent waves of colonization of our body habitats. Here we show that phylogenetically interspersed bacteria in Clostridium cluster XIVa, an abundant group of bacteria in the adult human gut also known as the Clostridium coccoides or Eubacterium rectale group, contains species that have evolved distribution patterns consistent with either early successional or stable gut communities. The species that specialize to the infant gut are more likely to associate with systemic infections and can reach high abundances in individuals with Inflammatory Bowel Disease (IBD), indicating that a subset of the microbiota that have adapted to pioneer/opportunistic lifestyles may do well in both early development and with disease. We identified genes likely selected during adaptation to pioneer/opportunistic lifestyles as those for which early succession association and not phylogenetic relationships explain genomic abundance. These genes reveal potential mechanisms by which opportunistic gut bacteria tolerate osmotic and oxidative stress and potentially important aspects of their metabolism. These genes may not only be biomarkers of properties associated with adaptation to early succession and disturbance, but also leads for developing therapies aimed at promoting reestablishment of stable gut communities following physiologic or pathologic disturbances.
Lozupone, Catherine; Faust, Karoline; Raes, Jeroen; Faith, Jeremiah J.; Frank, Daniel N.; Zaneveld, Jesse; Gordon, Jeffrey I.; Knight, Rob
This article provides an overview of the National Association of State Directors of Career Technical Education Consortium's (NASDCTEc) Common Career Technical Core (CCTC), a state-led initiative that was created to ensure that career and technical education (CTE) programs are consistent and high quality across the United States. Forty-two states,…
Background Limited evidence exists on the utilization of surveillance colonoscopy in colorectal cancer (CRC) screening programs. We assessed adherence to physician recommendations for surveillance in opportunistic CRC screening in Germany. Methods A follow-up study of screening colonoscopy participants in 2007-2009 in Saarland, Germany, was conducted using health insurance claims data. Utilization of additional colonoscopies through to 2011 was ascertained. Adherence to surveillance intervals of 3, 6, 12 and 36 months, defined as having had colonoscopy at 2.5 to 4, 5 to 8, 10.5 to 16 and 33 to 48 months, respectively (i.e., tolerating a delay of 33% of each interval) was assessed. Potential predictors of non-adherence were investigated using logistic regression analysis. Results A total of 20,058 screening colonoscopy participants were included in the study. Of those with recommended surveillance intervals of 3, 6, 12 and 36 months, 46.5% (95%-confidence interval [CI]: 37.3-55.7%), 38.5% (95%-CI: 29.6-47.3%), 25.4% (95%-CI: 21.2-29.6%) and 28.0% (95%-CI: 25.5-30.5%), respectively, had a subsequent colonoscopy within the specified margins. Old age, longer recommended surveillance interval, not having had polypectomy at screening and negative colonoscopy were statistically significant predictors of non-adherence. Conclusion This study suggests frequent non-adherence to physician recommendations for surveillance colonoscopy in community practice. Increased efforts to improve adherence, including introduction of more elements of an organized screening program, seem necessary to assure a high-quality CRC screening process.
Stock, Christian; Holleczek, Bernd; Hoffmeister, Michael; Stolz, Thomas; Stegmaier, Christa; Brenner, Hermann
The opportunistic human pathogenic fungus Aspergillus fumigatus causes severe systemic infections and is a major cause of fungal infections in immunocompromised patients. A. fumigatus conidia activate the alternative pathway of the complement system. In order to assess the mechanisms by which A. fumigatus evades the activated complement system, we analyzed the binding of host complement regulators to A. fumigatus. The binding of factor H and factor H-like protein 1 (FHL-1) from human sera to A. fumigatus conidia was shown by adsorption assays and immunostaining. In addition, factor H-related protein 1 (FHR-1) bound to conidia. Adsorption assays with recombinant factor H mutants were used to localize the binding domains. One binding region was identified within N-terminal short consensus repeats (SCRs) 1 to 7 and a second one within C-terminal SCR 20. Plasminogen was identified as the fourth host regulatory molecule that binds to A. fumigatus conidia. In contrast to conidia, other developmental stages of A. fumigatus, like swollen conidia or hyphae, did not bind to factor H, FHR-1, FHL-1, and plasminogen, thus indicating the developmentally regulated expression of A. fumigatus surface ligands. Both factor H and plasminogen maintained regulating activity when they were bound to the conidial surface. Bound factor H acted as a cofactor to the factor I-mediated cleavage of C3b. Plasminogen showed proteolytic activity when activated to plasmin by urokinase-type plasminogen activator. These data show that A. fumigatus conidia bind to complement regulators, and these bound host regulators may contribute to evasion of a host complement attack. PMID:18039838
Behnsen, Judith; Hartmann, Andrea; Schmaler, Jeannette; Gehrke, Alexander; Brakhage, Axel A; Zipfel, Peter F
Polyoma middle T (PmT)-transformed endothelial cells may represent a unique murine model for human opportunistic vascular tumors. The present study was designed to evaluate the anti-tumor potential of a panel of 13 cytokines against murine PmT-transformed endothelial cells. Interferon gamma (IFNgamma) and transforming growth factor beta 1 (TGFbeta1) substantially decreased in a dose-dependent manner the proliferation of a panel of 6 PmT-transformed cell lines. IFNalpha and tumor necrosis factor alpha(TNFalpha) had marginal anti-proliferative activity, whereas other molecules (interleukins-1, -2, -4, -6 and -13, IFNbeta, leukemia inhibitory factor, oncostatin M, granulocyte-macrophage colony-stimulating factor) caused no growth inhibition. IFNgamma and TGFbeta1 were therefore selected for further analysis of their mechanism of action and in vivo relevance. IFNgamma and TGFbeta1 reduced the activity of phosphatidylinositol-3-kinase and the production of phosphatidylinositol 3,4-biphosphate, without modifying the tyrosine kinase(s) activity associated with PmT. IFNgamma and TGFbeta1 were also tested for their ability to modify the in vivo growth of the PmT-transformed endothelial cells H5V in syngeneic C57B1/6 mice. Treatment with IFNnu and TGFbeta1 significantly delayed tumor growth and increased survival time. In contrast, treatment with IFNalpha and TNFalpha failed to prolong survival. In nude mice, IFNgamma and TGFbeta1 had a transient effect on tumor growth but no effect on survival, suggesting a contribution of T cells to the in vivo anti-tumor activity of these cytokines. PMID:8598325
Dong, Q G; Graziani, A; Garlanda, C; De Calmanovici, R W; Arese, M; Soldi, R; Vecchi, A; Mantovani, A; Bussolino, F
Transient receptor potential channels (TRPs) form a large family of ubiquitous non-selective cation channels that function as cellular sensors and in many cases regulate intracellular calcium. Identification of the endogenous ligands that activate these TRP receptors is still under intense investigation with the majority of these channels still remaining “orphans”. That these channels respond to a variety of external stimuli (e.g. plant-derived lipids, changes in temperature, and changes in pH) provides a framework for their abilities as cellular sensors, however, the mechanism of direct activation is still under much debate and research. In the cases where endogenous ligands (predominately lipids) have shown direct activation of a channel, multiple ligands have been shown to activate the same channel suggesting that these receptors are “promiscuous” in nature. Lipidomics of a growing class of endogenous lipids, N-acyl amides, the most famous of which is N-arachidonoyl ethanolamine (the endogenous cannabinoid, Anandamide) is providing a novel set of ligands that have been shown to activate some members of the TRP family and have the potential to deorphanize many more. Here it is argued that activation of TRPV receptors, a subset of the larger family of TRPs, by multiple endogenous lipids that are structurally analogous is a model system to drive our understanding that many TRP receptors are not promiscuous, but are more characteristically “opportunistic” in nature; exploiting the structural similarity and biosynthesis of a narrow range of analogous endogenous lipids. In addition, this manuscript will compare the activation properties of TRPC5 to the activity profile of an “orphan” lipid, N-palmitoyl glycine; further demonstrating that lipidomics aimed at expanding our knowledge of the family of N-acyl amides has the potential to provide novel avenues of research for TRP receptors.
Bradshaw, Heather B.; Raboune, Siham; Hollis, Jennifer L.
Solving the key issue of sustainability of battery-powered sensors continues to attract significant research attention. The prevailing theme of this research is to address this concern using energy-efficient protocols based on a form of simple cooperative transmission (CT) called the opportunistic large arrays (OLAs), and intelligent exploitation of energy harvesting and hybrid energy storage systems (HESSs). The two key contributions of this research, namely, OLA with transmission threshold (OLA-T) and alternating OLA-T (A-OLA-T), offer an signal-to-noise ratio (SNR) advantage (i.e., benefits of diversity and array (power) gains) in a multi-path fading environment, thereby reducing transmit powers or extending range. Because these protocols do not address nodes individually, the network overhead remains constant for high density networks or nodes with mobility. During broadcasting across energy-constrained networks, while OLA-T saves energy by limiting node participation within a single broadcast, A-OLA-T optimizes over multiple broadcasts and drains the nodes in an equitable fashion. A major bottleneck for network sustainability is the ability of a rechargeable battery (RB) to store energy, which is limited by the number of charge-discharge cycles. Energy harvesting using a HESS that comprises a RB and a supercapacitor (SC) will minimize the RB usage, thereby preserving the charge-discharge cycles. Studying the HESS is important, rather than the SC-alone because while an SC with harvested energy may be sufficient for routine monitoring, if there is an alert, the RB could be used as necessary to support the heavier reporting requirements. Therefore, another key contribution of this research is the design and analysis of a novel routing metric called communications using HESS (CHESS), which extends the RB-life by relaying exclusively with SC energy.
Background Fern Distortion Syndrome (FDS) is a serious disease of Leatherleaf fern (Rumohra adiantiformis). The main symptom of FDS is distortion of fronds, making them unmarketable. Additional symptoms include stunting, irregular sporulation, decreased rhizome diameter, and internal discoloration of rhizomes. We previously reported an association of symptoms with increased endophytic rhizome populations of fluorescent pseudomonads (FPs). The aim of the current study was to determine if FPs from ferns in Costa Rica with typical FDS symptoms would recreate symptoms of FDS. Methodology and Findings Greenhouse tests were conducted over a 29-month period. Micro-propagated ferns derived from tissue culture were first grown one year to produce rhizomes. Then, using an 8×9 randomized complete block experimental design, 8 replicate rhizomes were inoculated by dipping into 9 different treatments before planting. Treatments included water without bacteria (control), and four different groups of FPs, each at a two concentrations. The four groups of FPs included one group from healthy ferns without symptoms (another control treatment), two groups isolated from inside rhizomes of symptomatic ferns, and one group isolated from inside roots of symptomatic ferns. Symptoms were assessed 12 and 17 months later, and populations of FPs inside newly formed rhizomes were determined after 17 months. Results showed that inoculation with mixtures of FPs from ferns with FDS symptoms, but not from healthy ferns, recreated the primary symptom of frond deformities and also the secondary symptoms of irregular sporulation, decreased rhizome diameter, and internal discoloration of rhizomes. Conclusions These results suggest a model of causation of FDS in which symptoms result from latent infections by multiple species of opportunistic endophytic bacteria containing virulence genes that are expressed when populations inside the plant reach a minimum level.
Kloepper, Joseph W.; McInroy, John A.; Liu, Ke; Hu, Chia-Hui
Small RNA molecules (sRNAs) are key mediators of virulence and stress inducible gene expressions in some pathogens. In this work we identify sRNAs in the gram positive opportunistic pathogen Enterococcus faecalis. We characterized 11 sRNAs by tiling microarray analysis, 5' and 3' RACE-PCR, and Northern blot analysis. Six sRNAs were specifically expressed at exponential phase, two sRNAs were observed at stationary phase, and three were detected during both phases. Searches of putative functions revealed that three of them (EFA0080_EFA0081 and EFB0062_EFB0063 on pTF1 and pTF2 plasmids, respectively, and EF0408_EF04092 located on the chromosome) are similar to antisense RNA involved in plasmid addiction modules. Moreover, EF1097_EF1098 shares strong homologies with tmRNA (bi-functional RNA acting as both a tRNA and an mRNA) and EF2205_EF2206 appears homologous to 4.5S RNA member of the Signal Recognition Particle (SRP) ribonucleoprotein complex. In addition, proteomic analysis of the ?EF3314_EF3315 sRNA mutant suggests that it may be involved in the turnover of some abundant proteins. The expression patterns of these transcripts were evaluated by tiling array hybridizations performed with samples from cells grown under eleven different conditions some of which may be encountered during infection. Finally, distribution of these sRNAs among genome sequences of 54 E. faecalis strains was assessed. This is the first experimental genome-wide identification of sRNAs in E. faecalis and provides impetus to the understanding of gene regulation in this important human pathogen. PMID:21912655
Shioya, Kouki; Michaux, Charlotte; Kuenne, Carsten; Hain, Torsten; Verneuil, Nicolas; Budin-Verneuil, Aurélie; Hartsch, Thomas; Hartke, Axel; Giard, Jean-Christophe
Background.?The incidence of immune reconstitution inflammatory syndrome (IRIS) when antiretroviral therapy (ART) is initiated after an AIDS-defining opportunistic infection (OI) is uncertain and understudied for the most common OIs. Methods.?We examined patients in the University of Washington Human Immunodeficiency Virus Cohort initiating potent ART subsequent to an AIDS-defining OI. IRIS was determined through retrospective medical record review and adjudication using a standardized data collection process and clinical case definition. We compared demographic and clinical characteristics, and immunologic changes in patients with and without IRIS. Results.?Among 196 patients with 260 OIs, 21 (11%; 95% confidence interval, 7%–16%) developed paradoxical IRIS in the first year on ART. The 3 most common OIs among study patients were Pneumocystis pneumonia (PCP, 28%), Candida esophagitis (23%), and Kaposi sarcoma (KS, 16%). Cumulative 1-year incidence of IRIS was 29% (12/41) for KS, 16% (4/25) for tuberculosis, 14% (1/7) for Cryptococcus, 10% (1/10) for Mycobacterium avium complex, and 4% (3/72) for PCP. Morbidity and mortality were highest in those with visceral KS-IRIS compared with other types of IRIS (100% [6/6] vs 7% [1/15], P?.01). Patients with mucocutaneous KS and tuberculosis-IRIS experienced greater median increase in CD4+ cell count during the first 6 months of ART compared with those without IRIS (+158 vs +53?cells/?L, P?=?.04, mucocutaneous KS; +261 vs +113, P?=?.04, tuberculosis). Conclusions.?Cumulative incidence and features of IRIS varied depending on the OI. IRIS occurred in >10% of patients with KS, tuberculosis, or Cryptococcus. Visceral KS-IRIS led to considerable morbidity and mortality.
Harrington, Robert D.; Dhanireddy, Shireesha; Crane, Heidi M.; Casper, Corey; Kitahata, Mari M.
Domain-specific knowledge necessary for commonality analysis falls into two general classes: commonality constraints and costing information. Notations for encoding such knowledge should be powerful and flexible and should appeal to the domain expert. The...
D. P. Yeager
Background Although Aspergillus fumigatus is an important human fungal pathogen there are few expression systems available to study the contribution of specific genes to the growth and virulence of this opportunistic mould. Regulatable promoter systems based upon prokaryotic regulatory elements in the E. coli tetracycline-resistance operon have been successfully used to manipulate gene expression in several organisms, including mice, flies, plants, and yeast. However, the system has not yet been adapted for Aspergillus spp. Results Here we describe the construction of plasmid vectors that can be used to regulate gene expression in A. fumigatus using a simple co-transfection approach. Vectors were generated in which the tetracycline transactivator (tTA) or the reverse tetracycline transactivator (rtTA2s-M2) are controlled by the A. nidulans gpdA promoter. Dominant selectable cassettes were introduced into each plasmid, allowing for selection following gene transfer into A. fumigatus by incorporating phleomycin or hygromycin into the medium. To model an essential gene under tetracycline regulation, the E. coli hygromycin resistance gene, hph, was placed under the control of seven copies of the TetR binding site (tetO7) in a plasmid vector and co-transfected into A. fumigatus protoplasts together with one of the two transactivator plasmids. Since the hph gene is essential to A. fumigatus in the presence of hygromycin, resistance to hygromycin was used as a marker of hph reporter gene expression. Transformants were identified in which the expression of tTA conferred hygromycin resistance by activating expression of the tetO7-hph reporter gene, and the addition of doxycycline to the medium suppressed hygromycin resistance in a dose-dependent manner. Similarly, transformants were identified in which expression of rtTA2s-M2 conferred hygromycin resistance only in the presence of doxycycline. The levels of doxycycline required to regulate expression of the tetO7-hph reporter gene were within non-toxic ranges for this organism, and low-iron medium was shown to reduce the amount of doxycycline required to accomplish regulation. Conclusions The vectors described in this report provide a new set of options to experimentally manipulate the level of specific gene products in A. fumigatus
Vogt, Keith; Bhabhra, Ruchi; Rhodes, Judith C; Askew, David S
Background The resident skin microbiota plays an important role in restricting pathogenic bacteria, thereby protecting the host. Scabies mites (Sarcoptes scabiei) are thought to promote bacterial infections by breaching the skin barrier and excreting molecules that inhibit host innate immune responses. Epidemiological studies in humans confirm increased incidence of impetigo, generally caused by Staphylococcus aureus and Streptococcus pyogenes, secondary to the epidermal infestation with the parasitic mite. It is therefore possible that mite infestation could alter the healthy skin microbiota making way for the opportunistic pathogens. A longitudinal study to test this hypothesis in humans is near impossible due to ethical reasons. In a porcine model we generated scabies infestations closely resembling the disease manifestation in humans and investigated the scabies associated changes in the skin microbiota over the course of a mite infestation. Methodology/Principal Findings In a 21 week trial, skin scrapings were collected from pigs infected with S. scabies var. suis and scabies-free control animals. A total of 96 skin scrapings were collected before, during infection and after acaricide treatment, and analyzed by bacterial 16S rDNA tag-encoded FLX-titanium amplicon pyrosequencing. We found significant changes in the epidermal microbiota, in particular a dramatic increase in Staphylococcus correlating with the onset of mite infestation in animals challenged with scabies mites. This increase persisted beyond treatment from mite infection and healing of skin. Furthermore, the staphylococci population shifted from the commensal S. hominis on the healthy skin prior to scabies mite challenge to S. chromogenes, which is increasingly recognized as being pathogenic, coinciding with scabies infection in pigs. In contrast, all animals in the scabies-free cohort remained relatively free of Staphylococcus throughout the trial. Conclusions/Significance This is the first experimental in vivo evidence supporting previous assumptions that establishment of pathogens follow scabies infection. Our findings provide an explanation for a biologically important aspect of the disease pathogenesis. The methods developed from this pig trial will serve as a guide to analyze human clinical samples. Studies building on this will offer implications for development of novel intervention strategies against the mites and the secondary infections.
Swe, Pearl M.; Zakrzewski, Martha; Kelly, Andrew; Krause, Lutz; Fischer, Katja
Acidic glycosphingolipid components were extracted from the opportunistic mycopathogen Aspergillus fumigatus and identified as inositol phosphorylceramide and glycosylinositol phosphorylceramides (GIPCs). Using nuclear magnetic resonance sppectroscopy, mass spectrometry, and other techniques, the structures of six major components were elucidated as Ins-P-Cer (Af-0), Manp(alpha1-->3)Manp(alpha1-->2)Ins-P-Cer (Af-2), Manp(alpha1-->2)Manp(alpha1-->3)Manp(alpha1-->2)Ins-P-Cer (Af-3a), Manp(alpha1-->3)[Galf(beta1-->6)]Manp(alpha1-->2)-Ins-P-Cer (Af-3b), Manp(alpha1-->2)-Manp(alpha1-->3)[Galf(beta1-->6)]Manp(alpha1-->2)Ins-P-Cer (Af-4), and Manp(alpha1-->3)Manp(alpha1-->6)GlcpN(alpha1-->2)Ins-P-Cer (Af-3c) (where Ins = myo-inositol and P = phosphodiester). A minor A. fumigatus GIPC was also identified as the N-acetylated version of Af-3c (Af-3c*), which suggests that formation of the GlcNalpha1-->2Ins linkage may proceed by a two-step process, similar to the GlcNalpha1-->6Ins linkage in glycosylphosphatidylinositol (GPI) anchors (transfer of GlcNAc, followed by enzymatic de-N-acetylation). The glycosylinositol of Af-3b, which bears a distinctive branching Galf(beta1-->6) residue, is identical to that of a GIPC isolated previously from the dimorphic mycopathogen Paracoccidioides brasiliensis (designated Pb-3), but components Af-3a and Af-4 have novel structures. Overlay immunostaining of A. fumigatus GIPCs separated on thin-layer chromatograms was used to assess their reactivity against sera from a patient with aspergillosis and against a murine monoclonal antibody (MEST-1) shown previously to react with the Galf(beta1-->6) residue in Pb-3. These results are discussed in relation to pathogenicity and potential approaches to the immunodiagnosis of A. fumigatus. PMID:17488996
Toledo, Marcos S; Levery, Steven B; Bennion, Beau; Guimaraes, Luciana L; Castle, Sherry A; Lindsey, Rebecca; Momany, Michelle; Park, Chaeho; Straus, Anita H; Takahashi, Helio K
Commonality analysis is a method of partitioning variance that has advantages over more traditional "OVA" methods. Commonality analysis indicates the amount of explanatory power that is "unique" to a given predictor variable and the amount of explanatory power that is "common" to or shared with at least one predictor variable. This paper outlines…
Leister, K. Dawn
Domain-specific knowledge necessary for commonality analysis falls into two general classes: commonality constraints and costing information. Notations for encoding such knowledge should be powerful and flexible and should appeal to the domain expert. The notations employed by the Commonality Analysis Problem Solver (CAPS) analysis tool are described. Examples are given to illustrate the main concepts.
Yeager, Dorian P.
Proposes the subsuming theory criterion for experiments on common ground in mutual knowledge (i.e., the design must keep common information constant and only vary whether or not it is common). Demonstrates how doing so makes stronger claims. Illustrates how experiments can be designed to satisfy the criterion by evaluating some earlier studies…
The outcome of the interactions between native commensal microorganisms and opportunistic pathogens is crucial to the health of the coral holobiont. During the establishment within the coral surface mucus layer, opportunistic pathogens, including a white pox pathogen Serratia marcescens PDL100, compete with native bacteria for available nutrients. Both commensals and pathogens employ glycosidases and N-acetyl-glucosaminidase to utilize components of coral mucus. This study tested the hypothesis that specific glycosidases were critical for the growth of S. marcescens on mucus and that their inhibition by native coral microbiota reduces fitness of the pathogen. Consistent with this hypothesis, a S. marcescens transposon mutant with reduced glycosidase and N-acetyl-glucosaminidase activities was unable to compete with the wild type on the mucus of the host coral Acropora palmata, although it was at least as competitive as the wild type on a minimal medium with glycerol and casamino acids. Virulence of the mutant was modestly reduced in the Aiptasia model. A survey revealed that ?8% of culturable coral commensal bacteria have the ability to inhibit glycosidases in the pathogen. A small molecular weight, ethanol-soluble substance(s) produced by the coral commensal Exiguobacterium sp. was capable of the inhibition of the induction of catabolic enzymes in S. marcescens. This inhibition was in part responsible for the 10-100-fold reduction in the ability of the pathogen to grow on coral mucus. These results provide insight into potential mechanisms of commensal interference with early colonization and infection behaviors in opportunistic pathogens and highlight an important function for the native microbiota in coral health. PMID:23254513
Krediet, Cory J; Ritchie, Kim B; Alagely, Ali; Teplitski, Max
The outcome of the interactions between native commensal microorganisms and opportunistic pathogens is crucial to the health of the coral holobiont. During the establishment within the coral surface mucus layer, opportunistic pathogens, including a white pox pathogen Serratia marcescens PDL100, compete with native bacteria for available nutrients. Both commensals and pathogens employ glycosidases and N-acetyl-glucosaminidase to utilize components of coral mucus. This study tested the hypothesis that specific glycosidases were critical for the growth of S. marcescens on mucus and that their inhibition by native coral microbiota reduces fitness of the pathogen. Consistent with this hypothesis, a S. marcescens transposon mutant with reduced glycosidase and N-acetyl-glucosaminidase activities was unable to compete with the wild type on the mucus of the host coral Acropora palmata, although it was at least as competitive as the wild type on a minimal medium with glycerol and casamino acids. Virulence of the mutant was modestly reduced in the Aiptasia model. A survey revealed that ?8% of culturable coral commensal bacteria have the ability to inhibit glycosidases in the pathogen. A small molecular weight, ethanol-soluble substance(s) produced by the coral commensal Exiguobacterium sp. was capable of the inhibition of the induction of catabolic enzymes in S. marcescens. This inhibition was in part responsible for the 10–100-fold reduction in the ability of the pathogen to grow on coral mucus. These results provide insight into potential mechanisms of commensal interference with early colonization and infection behaviors in opportunistic pathogens and highlight an important function for the native microbiota in coral health.
Krediet, Cory J; Ritchie, Kim B; Alagely, Ali; Teplitski, Max
In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antimicrobial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml respectively; corresponding data for chloramphenicol were 2 ug/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 ug/ml and 0.98 ug/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients. PMID:1468110
Crockett, C O; Guede-Guina, F; Pugh, D; Vangah-Manda, M; Robinson, T J; Olubadewo, J O; Ochillo, R F
In our search for therapeutic agents from natural sources with potential for the treatment of opportunistic infections in patients afflicted with acquired immunodeficiency syndrome (AIDS), we investigated antibacterial and antifungal activities of water extracts of Cassia alata (C. alata). The extracts are traditionally used in Ivory Coast, West Africa to treat bacterial infections caused by Escherichia coli (E. coli), and fungal infections caused by Candida albicans (C. albicans) and dermatophytes. Our working hypothesis was that the extract contains active ingredient(s) which can be isolated, identified and developed into useful antibacterial/antifungal agents for the treatment of opportunistic infections in patients with AIDS. We used the broth dilution and agar dilution methods. Specifically, we focused on E. coli and C. albicans and the effectiveness of the extracts was evaluated relative to those of standard antibacterial agent chloramphenicol and antifungal agent amphotericin B. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for the water extract of C. alata against E. coli were 1.6 mg/ml and 60 mg/ml, respectively; corresponding data for chloramphenicol were 2 micrograms/ml and 10 micrograms/ml. Similarly, the MIC and minimum fungicidal concentration (MFC) for the extract against C. albicans were 0.39 mg/ml and 60 mg/ml in contrast to 0.58 micrograms/ml and 0.98 micrograms/ml for amphotericin B. From the dose-response curve plots, the extract had an IC50 of 31 mg/ml for E. coli and 28 mg/ml for C. albicans. The data suggest that C. alata extracts contain agent(s) which have therapeutic potential and might be useful if isolated and developed for the treatment of opportunistic infections of AIDS patients. PMID:1472906
Crockett, C O; Guede-Guina, F; Pugh, D; Vangah-Manda, M; Robinson, T J; Olubadewo, J O; Ochillo, R F
. \\u000a \\u000a Background: Stenotrophomonas (Xanthomonas) maltophilia has been increasingly reported as a nosocomial opportunistic pathogen, responsible for serious infectious complications\\u000a in immunocompromised patients. At present very limited information is available concerning its clinical significance in the\\u000a setting of HIV infection.\\u000a \\u000a \\u000a \\u000a \\u000a Patients and Methods: A retrospective survey of clinical and microbiological records of 1,374 HIV-infected patients referring to our tertiary care\\u000a center
L. Calza; R. Manfredi; F. Chiodo
How can an incomplete and uncertain model of the environment be used to perceive, infer, decide and act efficiently? This is the challenge that both living and artificial cognitive systems have to face. Symbolic logic is, by its nature, unable to deal with this question. The subjectivist approach to probability is an extension to logic that is designed specifically to face this challenge. In this paper, we review a number of frequently encountered cognitive issues and cast them into a common Bayesian formalism. The concepts we review are ambiguities, fusion, multimodality, conflicts, modularity, hierarchies and loops. First, each of these concepts is introduced briefly using some examples from the neuroscience, psychophysics or robotics literature. Then, the concept is formalized using a template Bayesian model. The assumptions and common features of these models, as well as their major differences, are outlined and discussed. PMID:20658175
Colas, Francis; Diard, Julien; Bessière, Pierre
Background Depression causes a large burden of disease worldwide. Effective prevention has the potential to reduce that burden considerably. This study aimed to investigate the cost-effectiveness of minimal contact psychotherapy, based on Lewinsohn's ‘Coping with depression’ course, targeted at opportunistically screened individuals with sub-threshold depression. Methods and Results Using a Markov model, future health effects and costs of an intervention scenario and a current practice scenario were estimated. The time horizon was five years. Incremental cost-effectiveness ratios were expressed in euro per Disability Adjusted Life Year (DALY) averted. Probabilistic sensitivity analysis was employed to study the effect of uncertainty in the model parameters. From the health care perspective the incremental cost-effectiveness ratio was € 1,400 per DALY, and from the societal perspective the intervention was cost-saving. Although the estimated incremental costs and effects were surrounded with large uncertainty, given a willingness to pay of € 20,000 per DALY, the probability that the intervention is cost-effective was around 80%. Conclusion This modelling study showed that opportunistic screening in primary care for sub-threshold depression in combination with minimal contact psychotherapy may be cost-effective in the prevention of major depression.
van den Berg, Matthijs; Smit, Filip; Vos, Theo; van Baal, Pieter H. M.
Opportunistic parasitosis and mycosis are becoming ever more widespread, mainly under the influence of major immunodeficiencies, either acquired (AIDS) or therapeutic. In this general overview, their main aspects, both clinical and epidemiological, are underlined. In terms of epidemiology, three types of phenomena have been observed: 1) emergence of human parasitosis unknown before (microsporidiosis due to Enterocytozoon bieneusi, Encephalitozoom hellem or Septata intestinalis); 2) among the human parasites already known, identification of very pathogenic strains (Toxoplasma gondii, Aspergillus fumigatus, Cryptococcus neoformans); 3) origin probably or certainly nosocomial of certain infections (pneumocystosis; toxoplasmosis and visceral leishmaniasis transmitted during bone-marrow or organ transplantations). The development of deep mycosis (invasive aspergillosis) is particularly promoted by granulopenia and alterations in the phagocytosis. On the other hand, opportunistic protozoosis (toxoplasmosis and leishmaniasis) and helminthiasis (strongyloidosis due to Strongyloides stercolaris) are related, above all, to disorders in cellular immunity (deficit of CD4+, mainly). Finally, several of these infections may be characterised by a variety of clinical pictures and outcome, depending on the contributory factors (immunodeficit or not) which led to the development of the infection. PMID:7648314
Ambroise-Thomas, P; Grillot, R
This study employed the Geographic Information System (GIS) to correlate total mercury levels in liver tissue with post-mortem findings of aspergillosis in common loons (Gavia immer) in the northeast United States of America (USA). Aspergillosis is an opportunistic fungal infecti...
This study was conducted on the basis of a modification to Contract NAS8-36413, Space Station Commonality Analysis, which was initiated in December, 1987 and completed in July, 1988. The objective was to investigate the commonality aspects of subsystems a...
The NSDL Math Common Core collection provides quick and easy access to high-quality math resources that have been related to one or more standard statements within the Math Common Core. These resources are selected from the larger NSDL collection and other trusted providers, and organized by grade level and domain area.
Family physicians working in the emergency room or assessing acutely injured patients in the office often must assess radiographs of suspected fractures. Many common fractures are difficult to diagnose with plain film radiography. This article focuses on some commonly undiagnosed fractures, with illustrations. ImagesFigures 1-2Figures 3-5Figures 6-7Figures 8-9Figure 10
McLennan, Michael K.; Rubenstein, Joel; Howard, Brian
Concepts from Strategic Alignment, a technology-management theory, are used to discuss the Information Commons as a new service-delivery model in academic libraries. The Information Commons, as a conceptual, physical, and instructional space, involves an organizational realignment from print to the digital environment. (Author)
Cointegrated multiple time series share at least one common trend. Two tests are developed for the number of common stochastic trends (i.e., for the order of cointegration) in a multiple time series with and without drift. Both tests involve the roots of the ordinary least squares coefficient matrix obtained by regressing the series onto its first lag. Critical values for
James H. Stock; Mark W. Watson
Explaining the maintenance of communicative behavior in the face of incentives to deceive, conceal information, or exaggerate is an important problem in behavioral biology. When the interests of agents diverge, some form of signal cost is often seen as essential to maintaining honesty. Here, novel computational methods are used to investigate the role of common interest between the sender and receiver of messages in maintaining cost-free informative signaling in a signaling game. Two measures of common interest are defined. These quantify the divergence between sender and receiver in their preference orderings over acts the receiver might perform in each state of the world. Sampling from a large space of signaling games finds that informative signaling is possible at equilibrium with zero common interest in both senses. Games of this kind are rare, however, and the proportion of games that include at least one equilibrium in which informative signals are used increases monotonically with common interest. Common interest as a predictor of informative signaling also interacts with the extent to which agents' preferences vary with the state of the world. Our findings provide a quantitative description of the relation between common interest and informative signaling, employing exact measures of common interest, information use, and contingency of payoff under environmental variation that may be applied to a wide range of models and empirical systems. PMID:24244116
Godfrey-Smith, Peter; Martínez, Manolo
Common variable immunodeficiency (CVID) is a common primary immunodeficiency characterized by a failure in B-cell differentiation with defective immunoglobulin production. Affected patients are uniquely susceptible to recurrent infection with encapsulated organisms and have an increased propensity for the development of inflammatory and autoimmune manifestations. The diagnosis of CVID is commonly delayed and the underlying cause of the disorder is not understood. Replacement antibody therapy reduces the risk of serious infections. However, optimal treatment regimens for the uncommon manifestations associated with this disease, such as granulomatous lymphocytic interstitial lung disease, require further research.
Tam, Jonathan S.
The NCCLS proposed standard M38-P describes standard parameters for testing the fungistatic antifungal activities (MICs) of established agents against filamentous fungi (molds); however, standard conditions are not available for testing their fungicidal activities (minimum fungicidal or lethal concentrations (MFCs)). This study evaluated the in vitro fungistatic and fungicidal activities of voriconazole, itraconazole, and amphotericin B against 260 common and emerging
Objectives Internalised homonegativity (IH) is hypothesised to be associated with HIV risk behaviour and HIV testing in men who have sex with men (MSM). We sought to determine the social and individual variables associated with IH and the associations between IH and HIV-related behaviours. Design and setting We examined IH and its predictors as part of a larger Internet-delivered, cross-sectional study on HIV and health in MSM in 38 European countries. Participants 181?495 MSM, IH data analysis subsample 144?177. All participants were male, over the age of consent for homosexual activity in their country of domicile, and have had at least one homosexual contact in the past 6?months. Methodology An anonymous Internet-based questionnaire was disseminated in 25 languages through MSM social media, websites and organisations and responses saved to a UK-based server. IH was measured using a standardised, cross-culturally appropriate scale. Results Three clusters of European countries based on the level of experienced discrimination emerged. IH was predicted by country LGB (lesbian, gay and bisexual) legal climate, Gini coefficient and size of place of settlement. Lower IH was associated with degree the respondent was ‘out’ as gay to others and older age. ‘Outness’ was associated with ever having an HIV test and age, education and number of gay friends, while IH (controlling for the number of non-steady unprotected sex partners and perceived lack of control over safe sex) was associated with condom use for anal intercourse. Conclusions IH is associated with LGB legal climate, economic development indices and urbanisation. It is also associated with ‘outness’ and with HIV risk and preventive behaviours including HIV testing, perceived control over sexual risk and condom use. Homonegative climate is associated with IH and higher levels of HIV-associated risk in MSM. Reducing IH through attention to LGB human rights may be appropriate HIV reduction intervention for MSM.
Ross, Michael W; Berg, Rigmor C; Schmidt, Axel J; Hospers, Harm J; Breveglieri, Michele; Furegato, Martina; Weatherburn, Peter
This article explains how solar energy is the energy source for almost all living systems on earth. Photosynthesis, catabolic reactions, and anabolic reactions are briefly discussed. Lastly, common questions are answered about converting food to energy.
Discusses Commoner's ideas on the social value of the petrochemical industry and his suggestions for curtailment or elimination of its productive operation to produce a higher environmental quality for mankind at a relatively low loss in social benefit. (CC)
Chemical and Engineering News, 1973
This effort researched, developed and demonstrated a Common Mobile Ad-hoc Networking (MANET) framework (CMF) to provide a uniform abstraction for wireless discovery, communication, and routing of network traffic over heterogeneous transmission technologie...
Four common conditions: acne, psoriasis, eczema and urticaria are considered. Guidance is given on appropriate topical and systematic treatment for the different types and degrees of these conditions, with notes on management in general and criteria for referral to hospital outpatient departments. Where there are different types of the condition, with varying aetiology, for example in urticaria and eczema, management of the common types is outlined.
Ridley, M.; Safranek, M.
Opportunistic infections, especially reactivation with M. tuberculosis, are major complications during treatment with anti-TNF agents. Infections with atypical mycobacteria like Mycobacterium marinum are rare and tend to turn into a difficult and prolonged course due to delayed diagnosis. This is the first case of M. marinum infection during adalimumab therapy in a patient with Crohn's disease. The most important diagnostic step was a detailed medical history as PCR tested for M. tuberculosis and for atypical subspecies was false negative. Up to now a discontinuation of anti-TNF therapy has been recommended, however, there is no consensus about the reintroduction of biologicals after sufficient anti-infective therapy. In this patient anti-TNF therapy had to be reintroduced because of increasing activity with no relapse of M. marinum after a follow-up of 12 months. PMID:22770648
Kump, Patrizia K; Högenauer, Christoph; Wenzl, Heimo H; Petritsch, Wolfgang
Cryptococcal infection of the central nervous system (CNS) typically affects patients with HIV infection. In addition, opportunistic infections can also occur during immunosuppressive therapies. Some patients develop cryptococcal meningitis. Cryptococcomas, however, are rarely observed. A 42-year-old patient with sarcoidosis known for 2½ years presented with a cerebral mass lesion primarily thought to be CNS sarcoidosis. Stereotactic biopsy and extensive micro- and macrobiological investigations revealed a cryptococcoma which had emerged from cryptococcal meningitis despite 3 months of treatment. Differential diagnosis of cerebral cryptococcoma is difficult due to the unspecific findings in the CSF analysis if C. neoformans fails to be detected using Indian ink staining or PCR studies. In this case, stereotactic biopsy and pathohistological examination revealed C. neoformans causing intracerebral mass lesion. Intensive treatment with antifungal drugs was followed by remission of all symptoms. In conclusion, cryptococcoma of the CNS represents a very important indication of mass lesions in patients suffering from sarcoidosis and treated with corticosteroids. PMID:22434163
Jung, Alexander; Korsukewitz, Catharina; Kuhlmann, Tanja; Richters, Malte; Fischer, Bernhard; Niederstadt, Thomas; Fegeler, Wolfgang; Minnerup, Jens; Young, Peter; Husstedt, Ingo W
Bacillary angiomatosis (BA) presents most commonly as a cutaneous disease and is caused by two organisms. Bartonella (Rochalimaea) henselae and Bartonella (Rochalimaea) quintana. Biopsy confirmation of cutaneous BA is essential because lesions can mimic nodular Kaposi's sarcoma in appearance. Although the vast majority of human immunodeficiency virus (HIV)-infected patients with BA have CD4 lymphocyte counts of less than 100 cells per mm3, the disease responds well to antimicrobial therapy. Staphylococcus aureus is the most common bacterial skin pathogen affecting HIV-infected patients. The prevalence of skin disease due to S. aureus may be explained by high nasal carriage rates for the organism ( > or = 50%) and altered immune function in conjunction with an impaired cutaneous barrier. Herpes simplex virus causes mucocutaneous disease early in the course HIV infection and ulcerative lesions at any site in advanced HIV infection. Herpes zoster is common early in the course of HIV infection; recurrent and disseminated herpes zoster infections are characteristic of patients with advanced HIV disease. Acyclovir resistance is usually seen in patients with large, untreated, ulcerative lesions of herpes simplex virus and in patients with chronic, verrucous lesions of varicella-zoster virus. Cutaneous cryptococcosis, histoplasmosis, and coccidiomycosis are markers of disseminated disease and require biopsy confirmation. Scabies is easily diagnosed but may be atypical in presentation and difficult to eradicate in advanced HIV disease.
Tappero, J W; Perkins, B A; Wenger, J D; Berger, T G
Allosuckling is a situation when a female nurses a non-filial offspring. It was described in various ungulate species; however for camels this is the first description of this behaviour. The aim of the study was to assess the occurrence of allosuckling in captive camels (Camelus bactrianus) and to test whether it can be explained as a ‘milk-theft’ (opportunistic behaviour of calves) or alternatively as an altruistic behaviour of females. During 2005 and 2007, nine camel females and ten calves in four zoological gardens in the Czech Republic were observed. In total, 373 sucking bouts were recorded, from which 32 were non-filial (the calf sucked from the non-maternal female). Allosuckling regularly appeared in captive camel herds. As predicted for the milk-theft explanation, the non-filial calves sucked more often in the lateral position and even did not suck in the antiparallel position at all. The non-filial calves preferably joined the filial calf when sucking but in five cases (15.6% of non-filial sucking bouts) the calves sucked from non-maternal dam without the presence of filial calf. We then expected the differences in terminations of sucking bouts by females but did not find any difference in sucking terminations for filial and non-filial calves. As the calves were getting older, the incidence of allosucking increased. This was probably because skills of the calf to outwit the non-maternal dam increased and/or the older calves might be more motivated for allosucking due to the weaning process. Finally, duration of a sucking bout was shorter with non-filial than filial calves. The results of the study support the hypothesis of ‘milk theft’, being mostly performed by calves behaving as opportunistic parasites, but we cannot reject certain level of altruism from the allonursing females or their increased degree of tolerance to non-filial calves.
Brandlova, Karolina; Bartos, Ludek; Haberova, Tamara
The indigenous bacteria create natural cohabitation niches together with mucosal Abs in the gastrointestinal (GI) tract. Here we report that opportunistic bacteria, largely Alcaligenes species, specifically inhabit host Peyer's patches (PPs) and isolated lymphoid follicles, with the associated preferential induction of antigen-specific mucosal IgA Abs in the GI tract. Alcaligenes were identified as the dominant bacteria on the interior of PPs from naïve, specific-pathogen-free but not from germ-free mice. Oral transfer of intratissue uncultured Alcaligenes into germ-free mice resulted in the presence of Alcaligenes inside the PPs of recipients. This result was further supported by the induction of antigen-specific Ab-producing cells in the mucosal (e.g., PPs) but not systemic compartment (e.g., spleen). The preferential presence of Alcaligenes inside PPs and the associated induction of intestinal secretory IgA Abs were also observed in both monkeys and humans. Localized mucosal Ab-mediated symbiotic immune responses were supported by Alcaligenes-stimulated CD11c+ dendritic cells (DCs) producing the Ab-enhancing cytokines TGF-?, B-cell-activating factor belonging to the TNF family, and IL-6 in PPs. These CD11c+ DCs did not migrate beyond the draining mesenteric lymph nodes. In the absence of antigen-specific mucosal Abs, the presence of Alcaligenes in PPs was greatly diminished. Thus, indigenous opportunistic bacteria uniquely inhabit PPs, leading to PP-DCs-initiated, local antigen-specific Ab production; this may involve the creation of an optimal symbiotic environment on the interior of the PPs.
Obata, Takashi; Goto, Yoshiyuki; Kunisawa, Jun; Sato, Shintaro; Sakamoto, Mitsuo; Setoyama, Hiromi; Matsuki, Takahiro; Nonaka, Kazuhiko; Shibata, Naoko; Gohda, Masashi; Kagiyama, Yuki; Nochi, Tomonori; Yuki, Yoshikazu; Fukuyama, Yoshiko; Mukai, Akira; Shinzaki, Shinichiro; Fujihashi, Kohtaro; Sasakawa, Chihiro; Iijima, Hideki; Goto, Masatoshi; Umesaki, Yoshinori; Benno, Yoshimi; Kiyono, Hiroshi
During deteriorated prey availability, purely pelagic, specialised seabird species have to alter their feeding strategy by extending foraging radii and/or time spent at sea or reducing feeding intervals of chicks. In contrast, more generalised species such as the opportunistic black-headed gull ( Larus ridibundus) breeding at the German North Sea coast, can be assumed to react on prey shortages by switching foraging habitats. The coastal zone of the German North Sea provides a rich habitat mosaic consisting of the offshore zone, tidal flats and terrestrial habitats. Thus, we expected distinct temporal and spatial patterns of habitat switch in accordance with prey availability and environmental constraints. We carried out ship-based and aerial surveys as well as dietary analyses and observations on flight activity. We found a significant switch from terrestrial to marine feeding sites both on a daily basis (related to tidal cycle) and over the whole breeding season. Most likely, the latter switch is the result of lower prey availability in the terrestrial habitats and an increasing quality (in terms of prey abundance and energy intake) of the marine area. While there was only moderate variability in habitat use among different years, we revealed significant differences in the diet of birds from different colonies. The high dietary plasticity and flexible feeding strategy, switching between terrestrial and marine prey is certainly of major importance for the success of an opportunistic avian top predator in a complex coastal zone. It is suggested that - compared to situations elsewhere - the number of breeding pairs of black-headed gulls in the German North Sea coast are still stable due to the switch of foraging habitats performed by individuals in this region.
Schwemmer, Philipp; Garthe, Stefan
The activity of both cytotoxic T lymphocyte (CTL) and natural killer (NK) cells were measured cross-sectionally in 43 subjects seropositive for HIV, in 27 HIV- blood donors and in 24 HIV- persons from the Outpatients Clinic for sexually transmitted diseases. CTL activity was evaluated using the HL-60 cells coated with OKT3 as the targets and freshly separated peripheral blood lymphocytes as the effectors. In 20 out of 43 HIV+ subjects, CTL activity was significantly enhanced in comparison to the HIV- subjects. This lytic activity correlated positively with the percentages of CD3+ HLA-DR+, of CD8+ CR3- and of CD57+ CD16- lymphocytes, and was greatly reduced after elimination of CD8+, of HLA-DR+ or of CD57+ cells. The median CTL activity seemed to increase from CDC group II to CDC group IV (Centers for Disease Control classification), but to return back to control levels in those patients with a history of opportunistic infections. NK function in HIV+ subjects was not significantly different from that in the blood donors. In seropositive patients, NK activity correlated positively with the percentages of both CD16+ CD57+ and of CD8+ CR3+ cells and was strongly diminished after elimination of CD16+ or of CD57+ cells. There was no significant change in NK function according to the clinical stage. The data show that circulating CD8+ HLA-DR+ CD57+ T cells in HIV+ subjects are activated cytotoxic T cells and point to progressive (over) activation of this T cell compartment until the onset of opportunistic infections.
Vanham, G; Kestens, L; Gigase, P; Colebunders, R; Vandenbruaene, M; Brijs, L; Ceuppens, J L
Twenty-five AIDS patients were treated with HE2000, a synthetic adrenal hormone. The drug was well tolerated and safe and reduced both the incidence of tuberculosis coinfection by 42.2% (P < 0.05) and the cumulative incidence of opportunistic infections (P < 0.05). These results warrant further clinical investigation of HE2000. PMID:17470653
Stickney, Dwight R; Noveljic, Zoja; Garsd, Armando; Destiche, Daniel A; Frincke, James M
Twenty-five AIDS patients were treated with HE2000, a synthetic adrenal hormone. The drug was well tolerated and safe and reduced both the incidence of tuberculosis coinfection by 42.2% (P < 0.05) and the cumulative incidence of opportunistic infections (P < 0.05). These results warrant further clinical investigation of HE2000.
Stickney, Dwight R.; Noveljic, Zoja; Garsd, Armando; Destiche, Daniel A.; Frincke, James M.
This product consists of SAS 9 files containing data from a randomized strategy trial of Immediate (in 2 weeks of start OI treatment) vs. Deferred antiretroviral treatment (in 6 weeks) in HIV-infected adults with acute opportunistic infections, included i...
Over a period of a year, samples of water, foam, microbial mat, soil and air were obtained from areas associated with the cooling canal of a nuclear power station. The seventeen sample sites included water in the cooling canal that was thermally enriched and soil and water adjacent to, upstream, downstream and at a distance from the generator. Air samples were taken at the plant and at various distances from the plant. Fifty-two species of thermotolerant and thermophilic fungi were isolated. Of these, eleven species are grouped as opportunistic Mucorales or opportunistic Aspergillus sp. One veterinary pathogen was also isolated (Dactylaria gallopava). The opportunistic/pathogenic fungi were found primarily in the intake bay, the discharge bay and the cooling canal. Smaller numbers were obtained at both upstream and downstream locations. Soil samples near the cooling canal reflected an enrichment of thermophilous organisms, the previously mentioned opportunistic Mucorales and Aspergillus spp. Their numbers were found to be greater than that usually encountered in a mesophilic environment. However, air and soil samples taken at various distances from the power station indicated no greater abundance of these thermophilous fungi than would be expected from a thermal enriched environment. Our results indicate that there was no significant dissemination of thermophilous fungi from the thermal enriched effluents to the adjacent environment. These findings are consistent with the results of other investigators. PMID:7374746
Rippon, J W; Gerhold, R; Heath, M
BACKGROUND: GPs often lack time to provide intensive cessation advice for patients who smoke. This study aimed to determine the effectiveness of opportunistic referral of smokers by their GP for telephone cessation counselling by a trained nurse. METHODS: Adult smokers (n = 318) attending 30 GPs in South Western Sydney, Australia were randomly allocated to usual care or referral to
Jane M Young; Seham Girgis; Tracey A Bruce; Melissa Hobbs; Jeanette E Ward
In 1999, the Federal Financial Assistance Management Improvement Act was passed in order to force the development of federal electronic grant processing. A result of the legislation, the Federal Commons portal gives "grantees (state and local governments, universities, small businesses, etc.) full service grants processing across all functions in the grant life cycle." While providing only an entrance to various grant institutions and services, the Federal Commons helps to eliminate the maze-like trail that multi-grant projects sometimes must travel to get to grant proposal Web sites. Most physical sciences researchers will find relevant federal departments listed under the Science and Technology link.
This promising new quarterly online publication situates itself somewhere between a popular magazine and scholarly journal, offering a common place for a variety of readers "to explore and exchange ideas about American history." Similar in some ways to the UK-based popular history magazine History Today, Common-place offers a mix of articles, short features, and reviews aimed at an interested and informed, but not necessarily academic, audience. A discussion board is planned for the near future, and users may subscribe for email notification of new issues.