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https://www.readbyqxmd.com/read/28447399/genome-wide-association-study-of-hiv-associated-neurocognitive-disorder-hand-a-charter-group-study
#1
Peilin Jia, Zhongming Zhao, Todd Hulgan, William S Bush, David C Samuels, Cinnamon S Bloss, Robert K Heaton, Ronald J Ellis, Nicholas Schork, Christina M Marra, Ann C Collier, David B Clifford, Benjamin B Gelman, Ned Sacktor, Susan Morgello, David M Simpson, J Allen McCutchan, Jill S Barnholtz-Sloan, Donald R Franklin, Debralee Rosario, Scott L Letendre, Igor Grant, Asha R Kallianpur
HIV-associated neurocognitive disorder (HAND) often complicates HIV infection despite combination antiretroviral therapy (ART) and may be influenced by host genomics. We performed a genome-wide association study (GWAS) of HAND in 1,050 CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) Study participants. All participants underwent standardized, comprehensive neurocognitive, and neuromedical assessments to determine if they had cognitive impairment as assessed by the Global Deficit Score (GDS), and individuals with comorbidities that could confound diagnosis of HAND were excluded...
April 26, 2017: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
https://www.readbyqxmd.com/read/28446263/spectrum-and-predictors-of-refractory-status-epilepticus-in-a-developing-country
#2
Deepanshu Dubey, Sanjeev K Bhoi, Jayantee Kalita, Usha K Misra
OBJECTIVE: Refractory status epilepticus (RSE) can influence the outcome of status epilepticus (SE). In the present study, we report the aetiology and predictors of outcomes of RSE in a developing country. METHODS: This is a prospective hospital-based study of SE patients (continuous seizures for five minutes or more). Those who had SE persisting after two antiepileptic drugs were defined as having RSE. We present the demographic information, duration, and type of SE, and we note its severity using the status epilepticus severity score (STESS), its aetiology, comorbidities and imaging findings...
April 27, 2017: Canadian Journal of Neurological Sciences. le Journal Canadien des Sciences Neurologiques
https://www.readbyqxmd.com/read/28446152/differential-host-gene-responses-from-infection-with-neurovirulent-and-partially-neurovirulent-strains-of-venezuelan-equine-encephalitis-virus
#3
Paridhi Gupta, Anuj Sharma, Jing Han, Amy Yang, Manish Bhomia, Barbara Knollmann-Ritschel, Raj K Puri, Radha K Maheshwari
BACKGROUND: Venezuelan equine encephalitis virus (VEEV) is an alphavirus in the family Togaviridae. VEEV causes a bi-phasic illness in mice where primary replication in lymphoid organs is followed by entry into the central nervous system (CNS). The CNS phase of infection is marked by encephalitis and large scale neuronal death ultimately resulting in death. Molecular determinants of VEEV neurovirulence are not well understood. In this study, host gene expression response to highly neurovirulent VEEV (V3000 strain) infection was compared with that of a partially neurovirulent VEEV (V3034 strain) to identify host factors associated with VEEV neurovirulence...
April 26, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28445497/prostaglandin-e2-produced-following-infection-with-theiler-s-virus-promotes-the-pathogenesis-of-demyelinating-disease
#4
Seung Jae Kim, Young-Hee Jin, Byung S Kim
Infection of various cells with Theiler's murine encephalomyelitis virus (TMEV) activates the TLR- and melanoma differentiation-associated gene 5 (MDA5)-dependent pathways, resulting in the production of IL-1β via the activation of caspase-1 upon assembly of the node-like receptor protein 3 (NLRP3) inflammasome. The role of IL-1β in the pathogenesis of TMEV-induced demyelinating disease was previously investigated. However, the signaling effects of prostaglandin E2 (PGE2) downstream of the NLRP3 inflammasome on the immune responses to viral determinants and the pathogenesis of demyelinating disease are unknown...
2017: PloS One
https://www.readbyqxmd.com/read/28443985/zika-puzzle-in-brazil-peculiar-conditions-of-viral-introduction-and-dissemination-a-review
#5
Cristina Possas, Patricia Brasil, Mauro Ca Marzochi, Amilcar Tanuri, Reinaldo M Martins, Ernesto Ta Marques, Myrna C Bonaldo, Antonio Gp Ferreira, Ricardo Lourenço-de-Oliveira, Rita Maria R Nogueira, Patricia C Sequeira, Keyla Bf Marzochi, Akira Homma
This article discusses the peculiar conditions that favoured the unexpected introduction of Zika virus into the poorest northeastern region of Brazil in 2015, its speed of transmission to other Brazilian states, other Latin American countries and other regions, and the severity of related neurological disorders in newborns and adults. Contrasting with evidence that Zika had so far caused only mild cases in humans in the last six decades, the epidemiological scenario of this outbreak in Brazil indicates dramatic health effects: in 2015, an increase of 20-fold in notified cases of microcephaly and/or central nervous system (CNS) alterations suggestive of Zika congenital infection, followed by an exponential increase in 2016, with 2366 cumulative cases confirmed in the country by the end of December 2016...
May 2017: Memórias do Instituto Oswaldo Cruz
https://www.readbyqxmd.com/read/28435899/hematologic-parameters-to-predict-negative-cerebrospinal-fluid-examination-results-among-neurologically-intact-patients-who-underwent-lumbar-puncture-on-suspicion-of-central-nervous-system-infection
#6
Ji Hwan Kim, Hong-Jik Kim, Ji Ung Na, Sang Kuk Han, Pil Cho Choi, Dong Hyuk Shin
OBJECTIVE: Cerebrospinal fluid (CSF) examination is mandatory whenever central nervous system (CNS) infection is suspected. However, pleocytosis is not detected in a substantial number of suspected patients who undergo CSF examination. This study aimed to identify parameters that can aid in predicting negative CSF examination results (defined as a white blood cell count of <5 cells/high-power field). METHODS: The study included 101 neurologically intact patients who underwent lumbar puncture because of suspicion of CNS infection...
March 2017: Clinical and Experimental Emergency Medicine
https://www.readbyqxmd.com/read/28435763/toxoplasma-infection-in-an-immunocompetent-host-possible-risk-of-living-with-multiple-cats
#7
Halis Kaan Akturk, David Sotello, Allen Ameri, Ahmed S Abuzaid, Ana Marcella Rivas, Priyanka Vashisht
A 32-year-old man presented with agitation, headache, and confusion. He was immunocompetent and had been living with multiple cats for many years. His vital signs were stable. He was afebrile. Multiple blood tests did not show any serious problem. Brain magnetic resonance imaging (MRI) revealed multiple ring-enhancing white matter lesions. Cerebrospinal fluid analysis did not show any signs of infection. Based on a presumptive diagnosis of multiple sclerosis, high-dose corticosteroid treatment was started. However, this caused worsening of the symptoms and increased the size of the lesions...
March 19, 2017: Curēus
https://www.readbyqxmd.com/read/28435078/preformulation-studies-of-ceftriaxone-for-pediatric-non-parenteral-administration-as-an-alternative-to-existing-injectable-formulations
#8
Tina Kauss, Mathieu Marchivie, Thida Phoeung, Alexandra Gaubert, Amélie Désiré, Giovanni Tonelli, Chantal Boyer, Marie-Hélène Langlois, Anthony Cartwright, Melba Gomes, Nicholas White, Karen Gaudin
Ceftriaxone, a third generation cephalosporin, has a wide antibacterial spectrum that has good CNS penetration, which makes it potentially suitable for initial treatment of severe neonatal pediatric infections providing suitable formulation. We evaluated its physicochemical and technical characteristics to assess its potential for development as a non-parenteral dosage form. As ceftriaxone is marked only for injectable use, these data are not available. Using HPLC and Karl Fischer titration, sensitivity of ceftriaxone to water, feasibility and impact of pharmaceutical processes and compatibility with common pharmaceutical excipients were assessed...
April 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28435023/the-clinical-significance-of-neutrophilic-pleocytosis-in-cerebrospinal-fluid-in-patients-with-viral-central-nervous-system-infections
#9
Siraya Jaijakul, Lucrecia Salazar, Susan H Wootton, Elizabeth Aguilera, Rodrigo Hasbun
BACKGROUND: Viral central nervous system infections are typically characterized by a cerebrospinal fluid (CSF) lymphocytic pleocytosis. A CSF neutrophilic pleocytosis presentation has been described but its prognostic and clinical significance is unknown. The objectives of our study were to 1) compare the clinical and laboratory characteristics of viral CNS infections with CSF neutrophilic pleocytosis to those with a lymphocytic pleocytosis and 2) evaluate factors associated with an adverse clinical outcome...
April 20, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28428210/proton-chemical-shift-imaging-study-of-the-combined-antiretroviral-therapy-impact-on-neurometabolic-parameters-in-chronic-hiv-infection
#10
J Boban, D Kozic, V Turkulov, D Lendak, M Bjelan, M Semnic, S Brkic
BACKGROUND AND PURPOSE: The introduction of combination antiretroviral therapy has failed to reduce the high prevalence of mild forms of HIV-associated neurocognitive disorders. The aim of this study was to test the effect of combined antiretroviral therapy on brain metabolite ratios in chronic HIV infection by using proton chemical shift imaging. MATERIALS AND METHODS: We performed 2D chemical shift imaging in 91 subjects (31 HIV+ patients with chronic infection on combination antiretroviral therapy, 19 combination antiretroviral therapy-na|fkve HIV+ subjects with chronic infection, and 41 healthy controls), covering frontal and parietal subcortical white and cingulate gyrus gray matter, analyzing ratios of NAA/Cr and Cho/Cr on long-TE and mIns/Cr on short-TE MR spectroscopy...
April 20, 2017: AJNR. American Journal of Neuroradiology
https://www.readbyqxmd.com/read/28427421/cerebrospinal-fluid-csf-biomarkers-of-iron-status-are-associated-with-csf-viral-load-antiretroviral-therapy-and-demographic-factors-in-hiv-infected-adults
#11
Stephanie M Patton, Quan Wang, Todd Hulgan, James R Connor, Peilin Jia, Zhongming Zhao, Scott L Letendre, Ronald J Ellis, William S Bush, David C Samuels, Donald R Franklin, Harpreet Kaur, Jennifer Iudicello, Igor Grant, Asha R Kallianpur
BACKGROUND: HIV-associated neurocognitive disorder (HAND) remains common, despite antiretroviral therapy (ART). HIV dysregulates iron metabolism, but cerebrospinal fluid (CSF) levels of iron and iron-transport proteins in HIV-infected (HIV+) persons are largely unknown. The objectives of this study were to characterize CSF iron-related biomarkers in HIV+ adults and explore their relationships to known predictors of HAND. METHODS: We quantified total iron, transferrin and heavy-chain (H)-ferritin by immunoassay in CSF sampled by lumbar puncture in 403 HIV+ participants in a multi-center, observational study and evaluated biomarker associations with demographic and HIV-related correlates of HAND [e...
April 21, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28424694/immune-responses-in-the-central-nervous-system-are-anatomically-segregated-in-a-non-human-primate-model-of-human-immunodeficiency-virus-infection
#12
Barbara Tavano, Vicky Tsipouri, Gareth A D Hardy, Caroline M Royle, Michael R Keegan, Dietmar Fuchs, Steven Patterson, Neil Almond, Neil Berry, Claire Ham, Deborah Ferguson, Adriano Boasso
The human immunodeficiency virus (HIV) accesses the central nervous system (CNS) early during infection, leading to HIV-associated cognitive impairment and establishment of a viral reservoir. Here, we describe a dichotomy in inflammatory responses in different CNS regions in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. We found increased expression of inflammatory genes and perivascular leukocyte infiltration in the midbrain of SIV-infected macaques. Conversely, the frontal lobe showed downregulation of inflammatory genes associated with interferon-γ and interleukin-6 pathways, and absence of perivascular cuffing...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28424687/cd103-cd8-t-cells-in-the-toxoplasma-infected-brain-exhibit-a-tissue-resident-memory-transcriptional-profile
#13
Tyler A Landrith, Suhas Sureshchandra, Andrea Rivera, Jessica C Jang, Maham Rais, Meera G Nair, Ilhem Messaoudi, Emma H Wilson
During chronic infection, memory T cells acquire a unique phenotype and become dependent on different survival signals than those needed for memory T cells generated during an acute infection. The distinction between the role of effector and memory T cells in an environment of persistent antigen remains unclear. Here, in the context of chronic Toxoplasma gondii infection, we demonstrate that a population of CD8 T cells exhibiting a tissue-resident memory (TRM) phenotype accumulates within the brain. We show that this population is distributed throughout the brain in both parenchymal and extraparenchymal spaces...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28423529/pif-promotes-brain-re-myelination-locally-while-regulating-systemic-inflammation-clinically-relevant-multiple-sclerosis-m-smegmatis-model
#14
Giuseppe Migliara, Martin Mueller, Alessia Piermattei, Chaya Brodie, Michael J Paidas, Eytan R Barnea, Francesco Ria
Neurologic disease diagnosis and treatment is challenging. Multiple Sclerosis (MS) is a demyelinating autoimmune disease with few clinical forms and uncertain etiology. Current studies suggest that it is likely caused by infection(s) triggering a systemic immune response resulting in antigen/non-antigen-related autoimmune response in central nervous system (CNS). New therapeutic approaches are needed. Secreted by viable embryos, PreImplantation Factor (PIF) possesses a local and systemic immunity regulatory role...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419136/occurrence-of-leishmania-infantum-in-the-central-nervous-system-of-naturally-infected-dogs-parasite-load-viability-co-infections-and-histological-alterations
#15
Valéria da Costa Oliveira, Viviane Cardoso Boechat, Artur Augusto Velho Mendes Junior, Maria de Fátima Madeira, Luiz Claudio Ferreira, Fabiano Borges Figueiredo, Monique Paiva Campos, Francisco das Chagas de Carvalho Rodrigues, Raquel de Vasconcellos Carvalhaes de Oliveira, Maria Regina Reis Amendoeira, Rodrigo Caldas Menezes
Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined...
2017: PloS One
https://www.readbyqxmd.com/read/28417331/use-of-high-dose-oral-valacyclovir-during-an-intravenous-acyclovir-shortage-a-retrospective-analysis-of-tolerability-and-drug-shortage-management
#16
Milena M McLaughlin, Sarah H Sutton, Ashley O Jensen, John S Esterly
INTRODUCTION: In late 2011, a shortage of IV acyclovir led to the need to empirically substitute high-dose oral valacyclovir (HDVA) to conserve IV acyclovir for patients with confirmed herpes simplex virus (HSV) meningitis or encephalitis. This report describes the management of the most recent national IV acyclovir shortage by the Antimicrobial Stewardship Program (ASP) at Northwestern Memorial Hospital (NMH), Chicago, IL, USA, and the use of HDVA. Secondarily, we assessed the safety and tolerability of HDVA as an alternate to IV acyclovir during this shortage...
April 17, 2017: Infectious Diseases and Therapy
https://www.readbyqxmd.com/read/28410692/treatment-outcome-of-extrapulmonary-tuberculosis-under-revised-national-tuberculosis-control-programme
#17
J J Cherian, I Lobo, A Sukhlecha, U Chawan, N A Kshirsagar, B L Nair, L Sawardekar
BACKGROUND: Extrapulmonary tuberculosis (EPTB) constitutes 15-20% of tuberculosis cases in India. Earlier studies have evaluated treatment outcomes of EPTB with little information on outcomes of individual site of EPTB. AIMS: The objective was to study the outcome of Directly Observed Treatment Short course (DOTS) treatment of EPTB in different organ systems under Revised National Tuberculosis Control Programme. METHODS: Multi-centric retrospectives record review was carried out in three states in India...
April 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#18
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28407743/new-drugs-new-toxicities-severe-side-effects-of-modern-targeted-and-immunotherapy-of-cancer-and-their-management
#19
REVIEW
Frank Kroschinsky, Friedrich Stölzel, Simone von Bonin, Gernot Beutel, Matthias Kochanek, Michael Kiehl, Peter Schellongowski
Pharmacological and cellular treatment of cancer is changing dramatically with benefits for patient outcome and comfort, but also with new toxicity profiles. The majority of adverse events can be classified as mild or moderate, but severe and life-threatening complications requiring ICU admission also occur. This review will focus on pathophysiology, symptoms, and management of these events based on the available literature.While standard antineoplastic therapy is associated with immunosuppression and infections, some of the recent approaches induce overwhelming inflammation and autoimmunity...
April 14, 2017: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/28407741/the-pd-1-pd-l1-pathway-promotes-development-of-brain-resident-memory-t-cells-following-acute-viral-encephalitis
#20
Sujata Prasad, Shuxian Hu, Wen S Sheng, Priyanka Chauhan, Amar Singh, James R Lokensgard
BACKGROUND: Previous work from our laboratory has demonstrated that during acute viral brain infection, glial cells modulate antiviral T cell effector responses through the PD-1: PD-L1 pathway, thereby limiting the deleterious consequences of unrestrained neuroinflammation. Here, we evaluated the PD-1: PD-L1 pathway in development of brain-resident memory T cells (bTRM) following murine cytomegalovirus (MCMV) infection. METHODS: Flow cytometric analysis of immune cells was performed at 7, 14, and 30 days post-infection (dpi) to assess the shift of brain-infiltrating CD8(+) T cell populations from short-lived effector cells (SLEC) to memory precursor effector cells (MPEC), as well as generation of bTRMs...
April 13, 2017: Journal of Neuroinflammation
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