Viral Reservoirs in Lymph Nodes of FIV-Infected Progressor and Long-Term Non-Progressor Cats during the Asymptomatic Phase.

BackgroundExamination of a cohort of cats experimentally infected with feline immunodeficiency virus (FIV) for 5.75 years revealed detectable proviral DNA in peripheral blood mononuclear cells (PBMCs) harvested during the asymptomatic phase, undetectable plasma viral RNA (FIV gag), and rarely detectable cell-associated viral RNA. Despite apparent viral latency in peripheral CD4+ T cells, circulating CD4+ T cell numbers progressively declined in progressor animals. The aim of this study was to explore this dichotomy of peripheral blood viral latency in the face of progressive immunopathology. The viral replication status, cellular immunophenotypes, and histopathologic features were compared between popliteal lymph nodes (PLNs) and peripheral blood. Also, we identified and further characterized one of the FIV-infected cats identified as a long-term non-progressor (LTNP).ResultsPLN-derived leukocytes from FIV-infected cats during the chronic asymptomatic phase demonstrated active viral gag transcription and FIV protein translation as determined by real-time RT-PCR, Western blot and in situ immunohistochemistry, whereas viral RNA in blood leukocytes was either undetectable or intermittently detectable and viral protein was not detected. Active transcription of viral RNA was detectable in PLN-derived CD4+ and CD21+ leukocytes. Replication competent provirus was reactivated ex vivo from PLN-derived leukocytes from three of four FIV-infected cats. Progressor cats showed a persistent and dramatically decreased proportion and absolute count of CD4+ T cells in blood, and a decreased proportion of CD4+ T cells in PLNs. A single long-term non-progressor (LTNP) cat persistently demonstrated an absolute peripheral blood CD4+ T cell count indistinguishable from uninfected animals, a lower proviral load in unfractionated blood and PLN leukocytes, and very low amounts of viral RNA in the PLN.ConclusionCollectively our data indicates that PLNs harbor important reservoirs of ongoing viral replication during the asymptomatic phase of infection, in spite of undetectable viral activity in peripheral blood. A thorough understanding of tissue-based lentiviral reservoirs is fundamental to medical interventions to eliminate virus or prolong the asymptomatic phase of FIV infection

Reduction of the size of datasets by using evolutionary feature selection: the case of noise in a modern city

Smart city initiatives have emerged to mitigate the negative effects of a very fast growth of urban areas. Most of the population in our cities are exposed to high levels of noise that generate discomfort and different health problems. These issues may be mitigated by applying different smart cities solutions, some of them require high accurate noise information to provide the best quality of serve possible. In this study, we have designed a machine learning approach based on genetic algorithms to analyze noise data captured in the university campus. This method reduces the amount of data required to classify the noise by addressing a feature selection optimization problem. The experimental results have shown that our approach improved the accuracy in 20% (achieving an accuracy of 87% with a reduction of up to 85% on the original dataset).Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This research has been partially funded by the Spanish MINECO and FEDER projects TIN2016-81766-REDT (http://cirti.es), and TIN2017-88213-R (http://6city.lcc.uma.es)

The health profile of people living with Parkinson\u27s Disease managed in a comprehensive care setting

Background: Globally there are few reports of the impairments, disabilities and medications used in people living with idiopathic Parkinson’s disease. Caregiver characteristics and caregiver burden have seldom been reported. We examined the health status in a large cohort of people living with Parkinson’s disease and their caregivers managed in a comprehensive health care setting. Methods/Design: A prospective, cross sectional analysis of impairments, disabilities and Parkinson’s disease medication use was conducted in a sample of 100 people with Parkinson’s disease rated I-IV on the modified Hoehn & Yahr scale. Participants were recruited from the Victorian Comprehensive Parkinson Program in Melbourne, Australia. Their caregivers were invited to provide their views on the burden of care, services provided and support received. Results: The severity of impairments and disabilities was strongly associated with disease duration (mean of 5.5 years). Those with long standing disease or more severe disease also used more Parkinson’s disease medications and participated in fewer social roles than people who were newly diagnosed or mildly affected. The severity of impairments was strongly correlated with limitations in performing activities of daily living. Limitations in performing daily activities were also found to be a significant contributing factor for health-related quality of life (PDQ-39 SI β=0.55, p=0.000; EQ-5D SI β=0.43, p=0.001). People with Parkinson’s disease lived at home with relatives. The average caregiver was a spouse or child providing approximately 3.5 hours of care per day, with the capacity to provide 9.4 hours per day and had provided care for four years. Additional support was high (63%) for 2.5 hours per day. Conclusion: The comprehensive care setting of this cohort describes a relatively benign condition despite a wide range of disease duration and severity. This report provides a baseline with which to compare other delivery models

Parents’ experiences of health visiting for children with Down syndrome

© MA Healthcare Limited.Children with Down syndrome have an increased likelihoodof experiencing serious health conditions. Health visitors canhave an important role in monitoring and promoting healthand development for young children with Down syndrome.This study aimed to explore parents’ experiences of healthvisiting services for children with Down syndrome. Twentyfour parents of children with Down syndrome aged 0–5 yearscompleted a brief questionnaire about the number and natureof visits from health visitors in the previous 12 months andtheir support needs. Some parents commented that otherprofessionals met the needs of their child, whereas others saidthat they would like more advice and support from healthvisitors. A further exploration of broader health serviceprovision, including health visiting, for young children withDown syndrome is needed.Peer reviewedFinal Accepted Versio

High Resolution Spectroscopy of Two-Dimensional Electron Systems

Spectroscopic methods involving the sudden injection or ejection of electrons in materials are a powerful probe of electronic structure and interactions. These techniques, such as photoemission and tunneling, yield measurements of the "single particle" density of states (SPDOS) spectrum of a system. The SPDOS is proportional to the probability of successfully injecting or ejecting an electron in these experiments. It is equal to the number of electronic states in the system able to accept an injected electron as a function of its energy and is among the most fundamental and directly calculable quantities in theories of highly interacting systems. However, the two-dimensional electron system (2DES), host to remarkable correlated electron states such as the fractional quantum Hall effect, has proven difficult to probe spectroscopically. Here we present an improved version of time domain capacitance spectroscopy (TDCS) that now allows us to measure the SPDOS of a 2DES with unprecedented fidelity and resolution. Using TDCS, we perform measurements of a cold 2DES, providing the first direct measurements of the single-particle exchange-enhanced spin gap and single particle lifetimes in the quantum Hall system, as well as the first observations of exchange splitting of Landau levels not at the Fermi surface. The measurements reveal the difficult to reach and beautiful structure present in this highly correlated system far from the Fermi surface.Comment: There are formatting and minor textual differences between this version and the published version in Nature (follow the DOI link below

L-theanine in the adjunctive treatment of generalized anxiety disorder: a double-blind, randomised, placebo-controlled trial

Partial or non-response to antidepressants in Generalized Anxiety Disorder (GAD) is common in clinical settings, and adjunctive biological interventions may be required. Adjunctive herbal and nutraceutical treatments are a novel and promising treatment option. L-theanine is a non-protein amino acid derived most-commonly from tea (Camellia sinensis) leaves, which may be beneficial in the treatment of anxiety and sleep disturbance as suggested by preliminary evidence. We conducted a 10-week study (consisting of an 8-week double-blind placebo-controlled period, and 1-week pre-study and 2-week post-study single-blinded observational periods) involving 46 participants with a DSM-5 diagnosis of GAD. Participants received adjunctive L-theanine (450–900 mg) or matching placebo with their current stable antidepressant treatment, and were assessed on anxiety, sleep quality, and cognition outcomes. Results revealed that adjunctive L-theanine did not outperform placebo for anxiety reduction on the HAMA (p = 0.73) nor insomnia severity on the Insomnia Severity Index (ISI; p = 0.35). However, LT treated participants reported greater self-reported sleep satisfaction than placebo (ISI item 4; p = 0.015). Further, a separation in favour of L-theanine was noted on the ISI in those with non-clinical levels of insomnia symptoms (ISI ≤ 14; p = 0.007). No significant cognitive effects (trail making time and the modified emotional Stroop) were revealed. While this preliminary study did not support the efficacy of L-theanine in the treatment of anxiety symptoms in GAD, further studies to explore the application of L-theanine in sleep disturbance are warranted

Complete analysis of the B-cell response to a protein antigen, from in vivo germinal centre formation to 3-D modelling of affinity maturation

Somatic hypermutation of immunoglobulin variable region genes occurs within germinal centres (GCs) and is the process responsible for affinity maturation of antibodies during an immune response. Previous studies have focused almost exclusively on the immune response to haptens, which may be unrepresentative of epitopes on protein antigens. In this study, we have exploited a model system that uses transgenic B and CD4<sup>+</sup> T cells specific for hen egg lysozyme (HEL) and a chicken ovalbumin peptide, respectively, to investigate a tightly synchronized immune response to protein antigens of widely differing affinities, thus allowing us to track many facets of the development of an antibody response at the antigen-specific B cell level in an integrated system <i>in</i> <i>vivo</i>. Somatic hypermutation of immunoglobulin variable genes was analysed in clones of transgenic B cells proliferating in individual GCs in response to HEL or the cross-reactive low-affinity antigen, duck egg lysozyme (DEL). Molecular modelling of the antibody–antigen interface demonstrates that recurring mutations in the antigen-binding site, selected in GCs, enhance interactions of the antibody with DEL. The effects of these mutations on affinity maturation are demonstrated by a shift of transgenic serum antibodies towards higher affinity for DEL in DEL-cOVA immunized mice. The results show that B cells with high affinity antigen receptors can revise their specificity by somatic hypermutation and antigen selection in response to a low-affinity, cross-reactive antigen. These observations shed further light on the nature of the immune response to pathogens and autoimmunity and demonstrate the utility of this novel model for studies of the mechanisms of somatic hypermutation

The antimicrobial polymer PHMB enters cells and selectively condenses bacterial chromosomes

To combat infection and antimicrobial resistance, it is helpful to elucidate drug mechanism(s) of action. Here we examined how the widely used antimicrobial polyhexamethylene biguanide (PHMB) kills bacteria selectively over host cells. Contrary to the accepted model of microbial membrane disruption by PHMB, we observed cell entry into a range of bacterial species, and treated bacteria displayed cell division arrest and chromosome condensation, suggesting DNA binding as an alternative antimicrobial mechanism. A DNA-level mechanism was confirmed by observations that PHMB formed nanoparticles when mixed with isolated bacterial chromosomal DNA and its effects on growth were suppressed by pairwise combination with the DNA binding ligand Hoechst 33258. PHMB also entered mammalian cells, but was trapped within endosomes and excluded from nuclei. Therefore, PHMB displays differential access to bacterial and mammalian cellular DNA and selectively binds and condenses bacterial chromosomes. Because acquired resistance to PHMB has not been reported, selective chromosome condensation provides an unanticipated paradigm for antimicrobial action that may not succumb to resistance