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CNS Infection

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141. A NOVEL TRICYCLIC LIGAND-CONTAINING NONPEPTIDIC HIV-1 PROTEASE INHIBITOR, GRL-0739, EFFECTIVELY INHIBITS THE REPLICATION OF MULTI-DRUG-RESISTANT HIV-1 VARIANTS AND HAS A DESIRABLE CENTRAL NERVOUS SYSTEM (CNS) PENETRATION PROPERTY IN VITRO. Full Text available with Trip Pro

A NOVEL TRICYCLIC LIGAND-CONTAINING NONPEPTIDIC HIV-1 PROTEASE INHIBITOR, GRL-0739, EFFECTIVELY INHIBITS THE REPLICATION OF MULTI-DRUG-RESISTANT HIV-1 VARIANTS AND HAS A DESIRABLE CENTRAL NERVOUS SYSTEM (CNS) PENETRATION PROPERTY IN VITRO. We report here that GRL-0739, a novel nonpeptidic HIV-1 protease inhibitor containing a tricycle (cyclohexyl-bis-tetrahydrofuranylurethane [THF]) and a sulfonamide isostere, is highly active against laboratory HIV-1 strains and primary clinical isolates (50 (...) as against the HIV-2ROD variant. The development of resistance against GRL-0739 was substantially delayed compared to that of amprenavir (APV). The effects of the nonspecific binding of human serum proteins on the anti-HIV-1 activity of GRL-0739 were insignificant. In addition, GRL-0739 showed a desirable central nervous system (CNS) penetration property, as assessed using a novel in vitro blood-brain barrier model. Molecular modeling demonstrated that the tricyclic ring and methoxybenzene of GRL-0739

2015 Antimicrobial Agents and Chemotherapy

142. Adults with suspected central nervous system infection: a prospective study of diagnostic accuracy. (Abstract)

Adults with suspected central nervous system infection: a prospective study of diagnostic accuracy. To study the diagnostic accuracy of clinical and laboratory features in the diagnosis of central nervous system (CNS) infection and bacterial meningitis.We included consecutive adult episodes with suspected CNS infection who underwent cerebrospinal fluid (CSF) examination. The reference standard was the diagnosis classified into five categories: 1) CNS infection; 2) CNS inflammation without (...) infection; 3) other neurological disorder; 4) non-neurological infection; and 5) other systemic disorder.Between 2012 and 2015, 363 episodes of suspected CNS infection were included. CSF examination showed leucocyte count >5/mm3 in 47% of episodes. Overall, 89 of 363 episodes were categorized as CNS infection (25%; most commonly viral meningitis [7%], bacterial meningitis [7%], and viral encephalitis [4%]), 36 (10%) episodes as CNS inflammatory disorder, 111 (31%) as systemic infection, in 119 (33

2016 Journal of Infection

143. More Challenges From Ebola: Infection of the Central Nervous System. Full Text available with Trip Pro

More Challenges From Ebola: Infection of the Central Nervous System. Cases of relapsed Ebola virus disease involving symptoms in the central nervous system are reminiscent of our past observations with some nonhuman primates (NHPs) that survived acute Ebola virus infection. We document our findings in detail here and suggest that this phenomenon can be further investigated in NHPs.© Crown copyright 2016.

2016 Journal of Infectious Diseases

144. Role of Cytochrome P450 2B6 Pharmacogenomics in Determining Efavirenz-Mediated Central Nervous System Toxicity, Treatment Outcomes, and Dosage Adjustments in Patients with Human Immunodeficiency Virus Infection. (Abstract)

Role of Cytochrome P450 2B6 Pharmacogenomics in Determining Efavirenz-Mediated Central Nervous System Toxicity, Treatment Outcomes, and Dosage Adjustments in Patients with Human Immunodeficiency Virus Infection. For treatment-naive patients with human immunodeficiency virus infection, efavirenz (EFV), together with tenofovir and emtricitabine, was once widely prescribed given its efficacy and ease of administration in a combination pill. However, the high rate of central nervous system (CNS (...) ) toxicities from EFV prompted the U.S. Department of Health and Human Services to move the EFV-based regimen from the recommended to the alternative category. For patients who do meet the criteria for newer recommended antiretroviral treatments, EFV is a viable option and often the mainstay of treatment outside the United States because newer antiretroviral treatments are more expensive. CNS toxicity occurring with the recommended standard dose of EFV remains a challenge and may in part be attributable

2016 Pharmacotherapy

145. Tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in Kota Kinabalu, Sabah, Malaysia: an observational study. Full Text available with Trip Pro

Tuberculous meningitis is a major cause of mortality and morbidity in adults with central nervous system infections in Kota Kinabalu, Sabah, Malaysia: an observational study. Central nervous system (CNS) infections are a significant contributor to morbidity and mortality globally. However, most published studies have been conducted in developed countries where the epidemiology and aetiology differ significantly from less developed areas. Additionally, there may be regional differences due (...) to variation in the socio-economic levels, public health services and vaccination policies. Currently, no prospective studies have been conducted in Sabah, East Malaysia to define the epidemiology and aetiology of CNS infections. A better understanding of these is essential for the development of local guidelines for diagnosis and management.We conducted a prospective observational cohort study in patients aged 12 years and older with suspected central nervous system infections at Queen Elizabeth Hospital

2016 BMC Infectious Diseases

146. Comorbidities and factors associated with central nervous system infections and death in non-perinatal listeriosis: a clinical case series. Full Text available with Trip Pro

Comorbidities and factors associated with central nervous system infections and death in non-perinatal listeriosis: a clinical case series. Listeriosis is a rare disease caused by the bacterium Listeria monocytogenes and mainly affects at risk people. Listeriosis can lead to sepsis, central nervous system (CNS) infections and death. The objectives of this study were to describe and quantify comorbidities and neurological sequelae underlying non-perinatal listeriosis cases and to describe (...) the factors associated with death and CNS infections in non-perinatal listeriosis.We retrospectively collected clinical data through computerized, paper or microfilmed medical records in two Belgian university hospitals. Logistic regression models and likelihood ratio tests allowed identifying factors associated with death and CNS infections.Sixty-four cases of non-perinatal listeriosis were included in the clinical case series and 84 % were affected by at least one comorbid condition. The main

2016 BMC Infectious Diseases

147. Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal and Central Nervous System Infections. Full Text available with Trip Pro

implicated in respiratory viral, gastrointestinal, or central nervous system infections. This review summarizes the test characteristics of available assays, highlights the advantages and limitations of multiplex technology for infectious diseases, and discusses potential utilization of these new tests in clinical practice.© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com. (...) Multiplexed Molecular Diagnostics for Respiratory, Gastrointestinal and Central Nervous System Infections. The development and implementation of highly multiplexed molecular diagnostic tests have allowed clinical microbiology laboratories to more rapidly and sensitively detect a variety of pathogens directly in clinical specimens. Current US Food and Drug Administration-approved multiplex panels target multiple different organisms simultaneously and can identify the most common pathogens

2016 Clinical Infectious Diseases

148. A Rare Central Nervous System Fungal Infection Resulting from Brown Heroin Use. (Abstract)

A Rare Central Nervous System Fungal Infection Resulting from Brown Heroin Use. Fungal nervous system infection can be a difficult diagnosis to make, due to the fact that there are no specific manifestations of the disease and laboratory confirmation is difficult to confirm.We report a young male who presented to our emergency department with a variety of unilateral visual field complaints. While he initially denied recent IV drug abuse, his physical examination was highly suggestive (...) of a fungal infection known to result from brown heroin use. He was ultimately diagnosed with meningitis, ventriculitis, and endogenous endophthalmitis believed to result from a Candida species. The response to treatment with vitrectomy and broad-spectrum antimicrobials gave support to the presumed diagnosis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: We provide a rarely described report of a possible complication from the use of IV brown heroin that led to a central nervous system infection

2016 Journal of Emergency Medicine

149. Managing Atypical and Typical herpetic central nervous system infections: results of A Multinational study. Full Text available with Trip Pro

in 96.3 and 87.5% of the cases with and without encephalitic clinical presentation, respectively. Considering the subtle nature of HME, CSF HSV PCR, EEG and MRI data should be collected for all patients with a central nervous system infection. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. (...) Managing Atypical and Typical herpetic central nervous system infections: results of A Multinational study. There have been many studies pertaining to the management of herpetic meningoencephalitis (HME), but the majority of them have focussed on virologically unconfirmed cases or included only small sample sizes. We have conducted a multicentre study aimed at providing management strategies for HME. Overall, 501 adult patients with PCR-proven HME were included retrospectively from 35 referral

2016 Clinical Microbiology and Infection

150. Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant. Full Text available with Trip Pro

Mechanisms of immune escape in central nervous system infection with neurotropic JC virus variant. Symptomatic infections of the central nervous system (CNS) with JC polyomavirus (JCV) usually occur as a result of immunocompromise and manifest as progressive multifocal leukoencephalopathy (PML) or granule cell neuronopathy (GCN). After immune reconstitution, some of these cases may show long-term persistence of JCV and delayed clinical improvement despite inflammation.We followed 4 patients (...) IRIS.Our findings suggest that efficient CD4(+) T-cell recognition of neurotropic JCV variants is crucial to support CD8(+) T cells in combating JCV infection of the CNS.© 2016 American Neurological Association.

2016 Annals of Neurology

151. Immune activation in the central nervous system throughout the course of HIV infection. Full Text available with Trip Pro

Immune activation in the central nervous system throughout the course of HIV infection. Robust and dynamic innate and adaptive responses characterize the acute central nervous system (CNS) response to HIV and other viral infections. In a state of chronic infection or viral latency, persistent immune activation associates with abnormality in the CNS. Understanding this process is critical, as immune-mediated abnormality in nonrenewable CNS cells may result in long-term neurologic sequelae (...) for HIV-infected individuals.In humans, immune activation is reduced by suppressive combination antiretroviral therapy, but persists at abnormally elevated levels on treatment. CNS immune activation is initiated in acute infection and progressively increases until combination antiretroviral therapy is started. Newly identified characteristics of the CNS immune surveillance network include features of homeostasis and function of brain microglial cells, lymphatic drainage from CNS to cervical lymph

2016 Current opinion in HIV and AIDS

152. SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques Full Text available with Trip Pro

SIV Infection Impairs the Central Nervous System in Chinese Rhesus Macaques The central nervous system (CNS) impairment is a consequence seen in SIV infection of rhesus macaques of Indian-origin, which is more common in infected macaques with rapid disease progression than in those with conventional disease progression. Here, we investigated the CNS damages in SIVmac239-infected Chinese rhesus macaques. We demonstrated that SIV infection of Chinese macaques could cause neuropathological (...) ). These findings indicate that SIVmac239 infection of Chinese rhesus macaque can be used as a suitable animal model and alternative resource for nueroAIDS research.

2016 Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology

153. Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus Full Text available with Trip Pro

. It is found that HEP-Flury infection can activate the innate immunity earlier through the RIG-I/MDA-5 signaling, and the innate immunity pre-activated by HEP-Flury or Newcastle disease virus (NDV) infection can effectively prevent the CVS-11 to invade central nervous system (CNS), but fails to clear the CVS-11 after its entry into the CNS. In addition, following CVS-11 infection, genes implicated in cell adhesion, blood vessel morphogenesis and coagulation were mainly up-regulated, while the genes (...) Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus Rabies remains a major public health concern in many developing countries. The precise neuropathogenesis of rabies is unknown, though it is hypothesized to be due to neuronal death or dysfunction. Mice that received intranasal inoculation of an attenuated rabies virus (RABV) strain HEP-Flury exhibited subtle clinical signs, and eventually recovered, which is different from

2016 Frontiers in microbiology

154. Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease Full Text available with Trip Pro

Interaction between Tat and Drugs of Abuse during HIV-1 Infection and Central Nervous System Disease In many individuals, drug abuse is intimately linked with HIV-1 infection. In addition to being associated with one-third of all HIV-1 infections in the United States, drug abuse also plays a role in disease progression and severity in HIV-1-infected patients, including adverse effects on the central nervous system (CNS). Specific systems within the brain are known to be damaged in HIV-1 (...) -infected individuals and this damage is similar to that observed in drug abuse. Even in the era of anti-retroviral therapy (ART), CNS pathogenesis occurs with HIV-1 infection, with a broad range of cognitive impairment observed, collectively referred to as HIV-1-associated neurocognitive disorders (HAND). A number of HIV-1 proteins (Tat, gp120, Nef, Vpr) have been implicated in the etiology of pathogenesis and disease as a result of the biologic activity of the extracellular form of each

2016 Frontiers in microbiology

155. Neuroinvasion and Inflammation in Viral Central Nervous System Infections Full Text available with Trip Pro

Neuroinvasion and Inflammation in Viral Central Nervous System Infections Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate (...) examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators

2016 Mediators of inflammation

156. Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection Full Text available with Trip Pro

Entry Sites of Venezuelan and Western Equine Encephalitis Viruses in the Mouse Central Nervous System following Peripheral Infection Venezuelan and western equine encephalitis viruses (VEEV and WEEV; Alphavirus; Togaviridae) are mosquito-borne pathogens causing central nervous system (CNS) disease in humans and equids. Adult CD-1 mice also develop CNS disease after infection with VEEV and WEEV. Adult CD-1 mice infected by the intranasal (i.n.) route, showed that VEEV and WEEV enter the brain (...) through olfactory sensory neurons (OSNs). In this study, we injected the mouse footpad with recombinant WEEV (McMillan) or VEEV (subtype IC strain 3908) expressing firefly luciferase (fLUC) to simulate mosquito infection and examined alphavirus entry in the CNS. Luciferase expression served as a marker of infection detected as bioluminescence (BLM) by in vivo and ex vivo imaging. BLM imaging detected WEEV and VEEV at 12 h postinoculation (hpi) at the injection site (footpad) and as early as 72 hpi

2016 Journal of virology

157. West Nile Virus Spreads Transsynaptically within the Pathways of Motor Control: Anatomical and Ultrastructural Mapping of Neuronal Virus Infection in the Primate Central Nervous System Full Text available with Trip Pro

West Nile Virus Spreads Transsynaptically within the Pathways of Motor Control: Anatomical and Ultrastructural Mapping of Neuronal Virus Infection in the Primate Central Nervous System During recent West Nile virus (WNV) outbreaks in the US, half of the reported cases were classified as neuroinvasive disease. WNV neuroinvasion is proposed to follow two major routes: hematogenous and/or axonal transport along the peripheral nerves. How virus spreads once within the central nervous system (CNS (...) , respectively), strongly indicating transsynaptic spread of the virus between connected neurons. Neuronal connectivity-based reconstruction of the directionality of transsynaptic virus spread suggests that, within the CNS, WNV can utilize both anterograde and retrograde axonal transport to infect connected neurons.This study offers a new insight into the neuropathogenesis of WNV infection in a primate model that closely mimics WNV encephalomyelitis in humans. We show that within the primate CNS, WNV

2016 PLoS neglected tropical diseases

158. Safety and clinical response of intraventricular caspofungin for Scedosporium apiospermum complex central nervous system infection Full Text available with Trip Pro

Safety and clinical response of intraventricular caspofungin for Scedosporium apiospermum complex central nervous system infection We present a 71-year old woman treated with 14 days of 5 mg intraventricular caspofungin for Scedosporium apiospermum complex meningoencephalitis diagnosed after spinal fusion and instrumentation. Cerebrospinal fluid studies improved during therapy and intraventricular administration was well tolerated. Within weeks of discontinuation, the patient experienced

2016 Medical mycology case reports

159. Emerging Diagnostic and Therapeutic Tools for Central Nervous System Infections Full Text available with Trip Pro

Emerging Diagnostic and Therapeutic Tools for Central Nervous System Infections 27695862 2018 08 16 2018 11 13 2168-6157 73 12 2016 12 01 JAMA neurology JAMA Neurol Emerging Diagnostic and Therapeutic Tools for Central Nervous System Infections. 1389-1390 10.1001/jamaneurol.2016.3617 Wilson Michael M Department of Neurology, University of California, San Francisco. Tyler Kenneth L KL Departments of Neurology, Medicine, and Immunology-Microbiology, University of Colorado School of Medicine (...) , Aurora. eng R33 AI101064 AI NIAID NIH HHS United States Journal Article United States JAMA Neurol 101589536 2168-6149 2016 10 4 6 0 2016 10 4 6 1 2016 10 4 6 0 ppublish 27695862 2557233 10.1001/jamaneurol.2016.3617 PMC5154841 NIHMS824805 Neurology. 2010 Sep 7;75(10):924-32 20820004 JAMA Neurol. 2015 Feb;72(2):143-4 25485794 Clin Infect Dis. 2015 Mar 15;60(6):919-23 25572898 Ann Neurol. 2015 Nov;78(5):722-30 26290222 J Neurovirol. 2016 Jun;22(3):257-60 26903031 Clin Infect Dis. 2003 Mar 15;36(6):731

2016 JAMA neurology

160. Zika Virus Infection in the Central Nervous System and Female Genital Tract Full Text available with Trip Pro

Zika Virus Infection in the Central Nervous System and Female Genital Tract 27617352 2018 02 01 2018 11 13 1080-6059 22 12 2016 12 Emerging infectious diseases Emerging Infect. Dis. Zika Virus Infection in the Central Nervous System and Female Genital Tract. 2228-2230 10.3201/eid2212.161280 Nicastri Emanuele E Castilletti Concetta C Balestra Pietro P Galgani Simonetta S Ippolito Giuseppe G eng Case Reports Letter Research Support, Non-U.S. Gov't 2016 12 15 United States Emerg Infect Dis 9508155 (...) 1080-6040 0 Antibodies, Neutralizing 0 Antibodies, Viral 0 RNA, Viral IM Adult Antibodies, Neutralizing immunology Antibodies, Viral immunology Central Nervous System Viral Diseases diagnosis transmission virology Dominican Republic Female Genitalia, Female virology Humans Italy Neutralization Tests RNA, Viral Real-Time Polymerase Chain Reaction Travel Zika Virus classification genetics immunology isolation & purification Zika Virus Infection diagnosis transmission virology Dominican Republic Italy

2016 Emerging Infectious Diseases

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