Prevalence of detectable HIV-DNA and HIV-RNA in cerebrospinal fluid of youth with perinatal HIV and impaired cognition on antiretroviral therapy.

OBJECTIVE: Central nervous system (CNS) HIV infection can impact cognition and may be an obstacle to cure in adolescents and young adults with perinatal HIV (AYAPHIV). IMPAACT2015 enrolled AYAPHIV on suppressive antiretroviral therapy (ART) with cognitive impairment to detect and quantify HIV in blood and cerebrospinal fluid (CSF). DESIGN: IMPAACT2015 was a U.S.-based multi-site, exploratory, observational study. METHODS: Cognitive impairment was defined as NIH Toolbox Fluid Cognition Composite score (FCCS) more than 1 standard deviation below age-adjusted normative group mean. Cell-free HIV-RNA and cell-associated HIV pol/gag -DNA and 10 biomarkers of inflammation/neuronal injury were measured in paired CSF and blood. ART exposure concentrations were quantified in hair. RESULTS: Among 24 participants, 20 had successful CSF collection and 18 also met viral suppression criteria. Nine of 18 (50%) were female sex-at-birth, and 14 of 18 (78%) were black. Median (range) age was 20 years (13-27), time on ART was 18.3 years (8.0-25.5), and FCCS was 68 (53-80). HIV-DNA was detected in PBMCs from all participants. In CSF, two of 18 (11%, 95% CI: 1.4-34.7%) participants had detectable cell-free HIV-RNA, while HIV gag or pol -DNA was detectable in 13 of 18 (72%, 95% confidence interval: 47-90). Detectable HIV-DNA in CSF was associated with male sex-at-birth ( P  = 0.051), lower CD4 + cell count at enrollment ( P  = 0.016), and higher PBMC HIV pol -DNA copies ( P  = 0.058). Hair antiretroviral concentrations and biomarkers were not associated with CSF HIV-DNA detection. CONCLUSION: We found that a high proportion of AYAPHIV with neurocognitive impairment had CSF cells harboring HIV-DNA during long-term virologic suppression. This evidence of persistent HIV-DNA in CSF suggests that the CNS should be considered in treatment and cure studies

The clinical utility of pain classification in non-specific arm pain

Mechanisms-based pain classification has received considerable attention recently for its potential use in clinical decision making. A number of algorithms for pain classification have been proposed. Non-specific arm pain (NSAP) is a poorly defined condition, which could benefit from classification according to pain mechanisms to improve treatment selection. This study used three published classification algorithms (hereafter called NeuPSIG, Smart, Schafer) to investigate the frequency of different pain classifications in NSAP and the clinical utility of these systems in assessing NSAP. Forty people with NSAP underwent a clinical examination and quantitative sensory testing. Findings were used to classify participants according to three classification algorithms. Frequency of pain classification including number unclassified was analysed using descriptive statistics. Inter-rater agreement was analysed using kappa coefficients. NSAP was primarily classified as ‘unlikely neuropathic pain’ using NeuPSIG criteria, ‘peripheral neuropathic pain’ using the Smart classification and ‘peripheral nerve sensitisation’ using the Schafer algorithm. Two of the three algorithms allowed classification of all but one participant; up to 45% of participants (n = 18) were categorised as mixed by the Smart classification. Inter-rater agreement was good for the Schafer algorithm (к = 0.78) and moderate for the Smart classification (к = 0.40). A kappa value was unattainable for the NeuPSIG algorithm but agreement was high. Pain classification was achievable with high inter-rater agreement for two of the three algorithms assessed. The Smart classification may be useful but requires further direction regarding the use of clinical criteria included. The impact of adding a pain classification to clinical assessment on patient outcomes needs to be evaluated

Fish sperm motility assessment as a tool for aquaculture research, a historical approach

[EN] Fish sperm motility is nowadays considered the best biomarker for the quality of fish spermatozoa, and sperm motion parameters from more than 300 fish species have been reported in more than 1500 scientific articles covering a wide range of topics, from molecular biology to ecology. The most studied topics have been (i) the sperm storage (involving both the use of chilled¿storage protocols for short¿term periods and sperm cryopreservation techniques for long¿term storage), (ii) the sperm physiology (fathom in the spermatozoa activation process and the whole propulsion machinery of the sperm cells) and (iii) the broodstock management (covering aspects such as rearing conditions, dietary requirements or hormonal induction treatments). In addition, other aquaculture and ecological topics, such as (iv) the knowledge of the breeding cycle of the species, (v) the phenomenon of the sperm competition and (vi) ecotoxicological studies for the evaluation of aquatic environments, have also been approached from the evaluation of sperm motion performance. Therefore, fish sperm motility assessment can serve as a potential tool for aquaculture and ecological purposes, covering key topics of fundamental and applied research. This review gives an overview of the major research areas in which fish sperm motility has been applied successfully.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 642893 (IMPRESS). VG has a postdoc grant from the UPV (PAID-10-16).Gallego Albiach, V.; Asturiano Nemesio, JF. (2018). Fish sperm motility assessment as a tool for aquaculture research, a historical approach. Reviews in Aquaculture (Online). 1-28. https://doi.org/10.1111/raq.12253S12

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Omission and Commission as Marketplace Trauma

2280-2913

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication