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Anthropogenic changes to the temperature regimes of rivers, whether through thermal pollution, removal of shade, or climate change, could affect community stability and cause phenological changes in aquatic species. This study examines the impact of a thermal discharge from a power station on the diversity and composition of the aquatic macroinvertebrate community in the River Severn, UK. Daily temperatures up to 2 km downstream of the thermal discharge averaged 4.5°C above ambient. Abundance and taxon richness metrics were reduced at a site approximately 0.5 km downstream of the power station outfall, but were largely unaffected at a second site about 2 km downstream. The majority of the macroinvertebrate taxa observed were recorded at both control and heated sites, suggesting species were below their thermal tolerance threshold or had developed adaptations to survive increased temperatures. However, indicator species analysis suggests certain taxa were associated with particular sites; abundances of Musculium lacustre , Simulium reptans , and Orthocladiinae were greater at the unheated control site, whereas more pollution-tolerant species such Asellus aquaticus and Erpobdella octoculata were more common in the thermally impacted reaches. Overall, the results provide an indication of potential species and community response to future warming under climate change scenarios.

Randomized controlled trials (RCTs) remain the gold standard to evaluate clinical interventions, producing the highest level of evidence while minimizing potential bias. Inadequate recruitment is a commonly encountered problem that undermines the completion and generalizability of RCTs—and is even more challenging when enrolling amidst a pandemic. Here, we reflect on our experiences with virtual recruitment of non‐hospitalized patients in the United States for ColCorona, an international, multicenter, randomized, placebo‐controlled coronavirus disease 2019 (COVID‐19) drug trial. Recruitment challenges during a pandemic include constraints created by shelter‐in‐place policies and targeting enrollment according to national and local fluctuations in infection rate. Presenting a study to potential participants who are sick with COVID‐19 and may be frightened, overwhelmed, or mistrusting of clinical research remains a challenge. Strategies previously reported to improve recruitment include transparency, patient and site education, financial incentives, and person‐to‐person outreach. Active measures taken during ColCorona to optimize United States recruitment involved rapid expansion of sites, adjustment of recruitment scripts, assessing telephone calls versus text messages for initial contact with participants, institutional review board‐approved financial compensation, creating an infrastructure to systematically identify potentially eligible patients, partnering with testing sites, appealing to both self‐interest and altruism, and large‐scale media efforts with varying degrees of success.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), the etiology of which is poorly understood. The most common laboratory abnormality associated with MS is increased intrathecal immunoglobulin G (IgG) synthesis and the presence of oligoclonal bands (OCBs) in the brain and cerebrospinal fluid (CSF). However, the major antigenic targets of these antibody responses are unknown. The risk of MS is increased after infectious mononucleosis (IM) due to EBV infection, and MS patients have higher serum titers of anti-EBV antibodies than control populations. Our goal was to identify disease-relevant epitopes of IgG antibodies in MS; to do so, we screened phage-displayed random peptide libraries (12-mer) with total IgG antibodies purified from the brain of a patient with acute MS. We identified and characterized the phage peptides for binding specificity to intrathecal IgG from patients with MS and from controls by ELISA, phage-mediated Immuno-PCR, and isoelectric focusing. We identified two phage peptides that share sequence homologies with EBV nuclear antigens 1 and 2 (EBNA1 and EBNA2), respectively. The specificity of the EBV epitopes found by panning with MS brain IgG was confirmed by ELISA and competitive inhibition assays. Using a highly sensitive phage-mediated immuno-PCR assay, we determined specific bindings of the two EBV epitopes to IgG from CSF from 46 MS and 5 inflammatory control (IC) patients. MS CSF IgG have significantly higher bindings to EBNA1 epitope than to EBNA2 epitope, whereas EBNA1 and EBNA2 did not significantly differ in binding to IC CSF IgG. Further, the EBNA1 epitope was recognized by OCBs from multiple MS CSF as shown in blotting assays with samples separated by isoelectric focusing. The EBNA1 epitope is reactive to MS intrathecal antibodies corresponding to oligoclonal bands. This reinforces the potential role of EBV in the etiology of MS. Graphical abstract Antibodies purified from an MS brain plaque were panned by phage display peptide libraries to discern potential antigens. Phage displaying peptide sequences resembling Epstein-Barr Virus Nuclear Antigens 1 & 2 (EBNA1 & 2) epitopes were identified. Antibodies from sera and CSF from other MS patients also reacted to those epitopes.

Objectives The purpose of this study was to determine sex differences in recovery trajectories of assessments for sport-related concussion using Concussion Assessment, Research and Education (CARE) Consortium data. Methods National Collegiate Athletic Association athletes ( N  = 906; 61% female) from sex-comparable sports completed a pre-season baseline assessment and post-sport-related concussion assessments within 6 h of injury, 24–48 h, when they initiated their return to play progression, when they were cleared for unrestricted return to play, and 6 months post-injury. Assessments included the Standardized Assessment of Concussion, Balance Error Scoring System, Brief Symptom Inventory-18, Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), Sport Concussion Assessment Tool-3 symptom evaluation, Clinical Reaction Time, King–Devick test, Vestibular Ocular Motor Screen, 12-item Short-Form Health Survey, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale. Results Only the Vestibular Ocular Motor Screen Total Symptom Score at the 24–48 h timepoint ( p  = 0.005) was statistically significantly different between sexes. Specifically, female athletes (mean = 60.2, 95% confidence interval [CI] 51.5–70.4) had higher Vestibular Ocular Motor Screen Total Symptom Scores than male athletes (mean = 36.9, 95% CI 27.6–49.3), but this difference resolved by the time of return-to-play initiation (female athletes, mean = 1.8, 95% CI 1.1–2.9; male athletes, mean = 4.1, 95% CI 1.5–10.9). Conclusions Sport-related concussion recovery trajectories for most assessments were similar for female and male National Collegiate Athletic Association athletes except for Vestibular Ocular Motor Screen symptoms within 48 h of sport-related concussion, which was greater in female athletes. Female athletes had a greater symptom burden across all timepoints, suggesting that cross-sectional observations may indicate sex differences despite similar recovery trajectories.

HIV-1 Tat is a potent neurotoxic protein that is released by HIV-1 infected cells in the brain and perturbs neuronal homeostasis, causing a broad range of neurological disorders in people living with HIV-1. Furthermore, the effects of Tat have been addressed in numerous studies to investigate the molecular events associated with neuronal cells survival and death. Here, we discovered that exposure of rat primary neurons to Tat resulted in the up-regulation of an uncharacterized long non-coding RNA (lncRNA), LOC102549805 (lncRNA-U1). Our observations showed that increased expression of lncRNA-U1 in neurons disrupts bioenergetic pathways by dysregulating homeostasis of Ca 2+ , mitigating mitochondrial oxygen reduction, and decreasing ATP production, all of which point mitochondrial impairment in neurons via the Tat-mediated lncRNA-U1 induction. These changes were associated with imbalances in autophagy and apoptosis pathways. Additionally, this study showed the ability of Tat to modulate expression of the neuropeptide B/W receptor 1 ( NPBWR1 ) gene via up-regulation of lncRNA-U1. Collectively, our results identified Tat-mediated lncRNA-U1 upregulation resulting in disruption of neuronal homeostasis.

PurposeSymptom management among patients diagnosed with advanced cancer is a high priority in clinical care that often involves the support of a family caregiver. However, limited studies have examined parallel patient and caregiver symptom burden and associations with their own and each other’s quality of life (QOL). This study seeks to identify patient and caregiver symptom clusters and investigate associations between identified clusters and demographic, clinical, and psychosocial factors (cognitive appraisals and QOL).MethodsThis study was a secondary analysis of self-reported baseline survey data collected from a randomized clinical trial of 484 adult advanced cancer patients and their caregivers. Latent class analysis and factor analysis were used to identify symptom clusters. Bivariate statistics tested associations between symptom clusters and demographic, clinical, and psychosocial variables.ResultsThe most prevalent symptom for patients was energy loss/fatigue and for caregivers, mental distress. Low, moderate, and high symptom burden subgroups were identified at the patient, caregiver, and dyad level. Age, gender, race, income, chronic conditions, cancer type, and treatment type were associated with symptom burden subgroups. Higher symptom burden was associated with more negative appraisals of the cancer and caregiving experience, and poorer QOL (physical, social, emotional, functional, and overall QOL). Dyads whose caregivers had more chronic conditions were more likely to be in the high symptom burden subgroup.ConclusionPatient and caregiver symptom burden influence their own and each other’s QOL. These findings reinforce the need to approach symptom management from a dyadic perspective.

CUPID will be a next generation experiment searching for the neutrinoless double β decay, whose discovery would establish the Majorana nature of the neutrino. Based on the experience achieved with the CUORE experiment, presently taking data at LNGS, CUPID aims to reach a background free environment by means of scintillating Li2100MoO4 crystals coupled to light detectors. Indeed, the simultaneous heat and light detection allows us to reject the dominant background of α particles, as proven by the CUPID-0 and CUPID-Mo demonstrators. In this work we present the results of the first test of the CUPID baseline module. In particular, we propose a new optimized detector structure and light sensors design to enhance the engineering and the light collection, respectively. We characterized the heat detectors, achieving an energy resolution of (5.9 ± 0.2) keV FWHM at the Q-value of 100Mo (about 3034 keV). We studied the light collection of the baseline CUPID design with respect to an alternative configuration which features gravity-assisted light detectors’ mounting. In both cases we obtained an improvement in the light collection with respect to past measures and we validated the particle identification capability of the detector, which ensures an α particle rejection higher than 99.9%, fully satisfying the requirements for CUPID.

HIV-1 Tat protein is released from HIV-1-infected cells and can enter non-permissive cells including neurons. Tat disrupts neuronal homeostasis and may contribute to the neuropathogenesis in people living with HIV (PLWH). The use of cocaine by PLWH exacerbates neuronal dysfunction. Here, we examined the mechanisms by which Tat and cocaine facilitate alterations in neuronal homeostatic processes. Bioinformatic interrogation of the results from RNA deep sequencing of rat hippocampal neurons exposed to Tat alone indicated the dysregulation of several genes involved in lipid and cholesterol metabolism. Following exposure to Tat and cocaine, the activation of cholesterol biosynthesis genes led to increased levels of free cholesterol and cholesteryl esters in rat neurons. Results from lipid metabolism arrays validated upregulation of several processes implicated in the biogenesis of β-amyloid and Alzheimer’s disease (AD), including sterol o-acyltransferase 1/acetyl-coenzyme A acyltransferase 1 (SOAT1/ACAT1), sortilin-related receptor L1 (SORL1) and low-density lipoprotein receptor-related protein 12 (LRP12). Further studies in Tat-treated primary neuronal cultures and brain tissues from HIV-1 transgenic mice as well as SIV-infected macaques confirmed elevated levels of SOAT1/ACAT 1 proteins. Our results offer novel insights into the molecular events involved in HIV and cocaine-mediated neuronal dysfunction that may also contribute to neuropathogenic events associated with the development of AD.

Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS –a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.