Diffuse infiltrative lymphocytosis syndrome presenting as renal failure in South African HIV-positive individuals: a single-centre case series

Diffuse infiltrative lymphocytosis syndrome (DILS) in human immunodeficiency virus (HIV) infection presented most commonly with parotidomegaly and sicca symptoms in the pre-antiretroviral era. However, numerous clinical manifestations are possible due to the multi-organ nature of the CD8+ lymphocytic infiltration. Renal involvement is infrequently described, but common characteristics of a renal syndrome associated with DILS have been identified. This case series describes four South African HIV-positive patients with DILS, in whom renal failure was the sole clinical manifestation. As DILS responds well to antiretroviral and corticosteroid therapy, this series highlights the importance of considering this syndrome as a cause of renal failure in an HIV-positive patient

Grounding-zone wedges and mega-scale glacial lineations in the Mertz Trough, East Antarctica

Author Posting. © The Author(s), 2016. This is the author's version of the work. It is posted here under a nonexclusive, irrevocable, paid-up, worldwide license granted to WHOI. It is made available for personal use, not for redistribution. The definitive version was published in Geological Society, London, Memoirs 46 (2016): 241-242, doi:10.1144/M46.175.Glacial erosion and deposition have shaped the Mertz Trough, East Antarctica, where seafloor grounding-zone wedges (GZWs) are associated with mega-scale glacial lineations (MSGLs) (McMullen et al. 2006). GZWs form along grounded glacial margins constrained by ice shelves during stillstands and consist of wedge-shaped glacially transported sediment (Powell & Domack 2002). MSGLs are parallel elongate bedforms that typically form in soft sediments beneath rapidly flowing ice streams (Clark 1993; Canals et al. 2000; Clark et al. 2003). They are found in glacial troughs, usually parallel to trough margins. MSGLs are generally 6 to >100 km long, 200–1300 m wide and spaced 0.3–5 km apart, crest-to-crest (Clark et al. 2003; McMullen et al. 2006)

Exile Vol. XXX

Black and White by Seymour Buffalo 1 Demosthenes by A. T. McMullen 2 Losing Face by K. Kiefer 3 untitled by Christ Paul 4 Graduations by Jay Krieger 5-6 Anonymous #1 7 Sorry We Are Close by Scott Schuster 8-25 The Roommates by Gregor Macdonald 26 Perfectly Good Words by Gregor Macdonald 27 Trees Fall Without Me, Would You? by Kate Reynolds 28-29 Anonymous #2 30 Here at the House by Joan Dewitt 31-34 An 11 year old Mother in Stanton, Tennessee by Kate Reynolds 35 In the Livingroom by Don Wenzel 36-40 Minimata by Seymour Buffalo 41 Innocent Intentions by Funkmahn 42 Bird to Brittany by A. T. McMullen 43 Fall Parent\u27s Weekend by Jacqueline Ondy 44 Cover Drawing by Jim Kenne

A protocol for rapid and parallel isolation of myocytes and non-myocytes from multiple mouse hearts.

This protocol features parallel isolation of myocytes and non-myocytes from murine hearts. It was designed with considerations for (1) time required to extract cardiac cells, (2) cell viability, and (3) protocol scalability. Here, a peristaltic pump and 3D-printed elements are combined to perfuse the heart with enzymes to dissociate cells. Myocytes and non-myocytes extracted using this protocol are separated by centrifugation and/or fluorescence-activated cell sorting for use in downstream applications including single-cell omics or other bio-molecular analyses. For complete details on the use and execution of this protocol, please refer to McLellan et al. (2020)

PI3K(p110 alpha) Protects Against Myocardial Infarction-Induced Heart Failure Identification of PI3K-Regulated miRNA and mRNA

Objective: Myocardial infarction (MI) is a serious complication of atherosclerosis associated with increasing mortality attributable to heart failure. Activation of phosphoinositide 3-kinase [PI3K(p110α)] is considered a new strategy for the treatment o

Benthic and Hyporheic Macroinvertebrate Distribution Within the Heads and Tails of Riffles During Baseflow Conditions

The distribution of lotic fauna is widely acknowledged to be patchy reflecting the interaction between biotic and abiotic factors. In an in-situ field study, the distribution of benthic and hyporheic invertebrates in the heads (downwelling) and tails (upwelling) of riffles were examined during stable baseflow conditions. Riffle heads were found to contain a greater proportion of interstitial fine sediment than riffle tails. Significant differences in the composition of benthic communities were associated with the amount of fine sediment. Riffle tail habitats supported a greater abundance and diversity of invertebrates sensitive to fine sediment such as EPT taxa. Shredder feeding taxa were more abundant in riffle heads suggesting greater availability of organic matter. In contrast, no significant differences in the hyporheic community were recorded between riffle heads and tails. We hypothesise that clogging of hyporheic interstices with fine sediments may have resulted in the homogenization of the invertebrate community by limiting faunal movement into the hyporheic zone at both the riffle head and tail. The results suggest that vertical hydrological exchange significantly influences the distribution of fine sediment and macroinvertebrate communities at the riffle scale

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

International Society of Sports Nutrition Position Stand: Probiotics.

Position statement: The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the mechanisms and use of probiotic supplementation to optimize the health, performance, and recovery of athletes. Based on the current available literature, the conclusions of the ISSN are as follows: 1)Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit on the host (FAO/WHO).2)Probiotic administration has been linked to a multitude of health benefits, with gut and immune health being the most researched applications.3)Despite the existence of shared, core mechanisms for probiotic function, health benefits of probiotics are strain- and dose-dependent.4)Athletes have varying gut microbiota compositions that appear to reflect the activity level of the host in comparison to sedentary people, with the differences linked primarily to the volume of exercise and amount of protein consumption. Whether differences in gut microbiota composition affect probiotic efficacy is unknown.5)The main function of the gut is to digest food and absorb nutrients. In athletic populations, certain probiotics strains can increase absorption of key nutrients such as amino acids from protein, and affect the pharmacology and physiological properties of multiple food components.6)Immune depression in athletes worsens with excessive training load, psychological stress, disturbed sleep, and environmental extremes, all of which can contribute to an increased risk of respiratory tract infections. In certain situations, including exposure to crowds, foreign travel and poor hygiene at home, and training or competition venues, athletes' exposure to pathogens may be elevated leading to increased rates of infections. Approximately 70% of the immune system is located in the gut and probiotic supplementation has been shown to promote a healthy immune response. In an athletic population, specific probiotic strains can reduce the number of episodes, severity and duration of upper respiratory tract infections.7)Intense, prolonged exercise, especially in the heat, has been shown to increase gut permeability which potentially can result in systemic toxemia. Specific probiotic strains can improve the integrity of the gut-barrier function in athletes.8)Administration of selected anti-inflammatory probiotic strains have been linked to improved recovery from muscle-damaging exercise.9)The minimal effective dose and method of administration (potency per serving, single vs. split dose, delivery form) of a specific probiotic strain depends on validation studies for this particular strain. Products that contain probiotics must include the genus, species, and strain of each live microorganism on its label as well as the total estimated quantity of each probiotic strain at the end of the product's shelf life, as measured by colony forming units (CFU) or live cells.10)Preclinical and early human research has shown potential probiotic benefits relevant to an athletic population that include improved body composition and lean body mass, normalizing age-related declines in testosterone levels, reductions in cortisol levels indicating improved responses to a physical or mental stressor, reduction of exercise-induced lactate, and increased neurotransmitter synthesis, cognition and mood. However, these potential benefits require validation in more rigorous human studies and in an athletic population

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

The role of the HIV-1 Tat protein in acute stroke: more than just a transactivator of transcription?

Background: Individuals infected with the human immunodeficiency virus (HIV) are at increased risk of developing ischaemic stroke. The reasons for this are multifactorial, but HIV-associated vasculopathy is a potentially important cause. HIVinduced chronic inflammation may initiate endothelial dysfunction or accelerate vascular injury from other disease processes. Viral proteins such as the transactivator of transcription (Tat) are emerging role-players in HIV disease pathogenesis and have a putative role in HIV-associated endothelial dysfunction. Tat has paracrine proinflammatory effects, but its role in HIV-related stroke has not yet been investigated. Aims: The primary aim of this study was to determine whether specific Tat amino acid variants are associated with ischaemic stroke and biomarkers of inflammation and endothelial dysfunction in a group of HIV-1 subtype-C-infected individuals. In order to do so, I first determined the aetiology of stroke in these participants using clinical, biochemical and neuro-imaging data. A secondary aim of the study was to identify any HIV-related and/or other traditional stroke-related risk factors that might independently or cumulatively increase stroke risk. For comparison, these putative risk factors were also determined in a group of age-matched HIV-infected non-stroke controls. Finally, I aimed to identify any HIV-related factors and/or Tat amino acid variants that might distinguish strokes due to HIV-associated vasculopathy from other mechanisms of stroke. Methods: A case-control study was performed on 58 Subtype-C HIV-infected individuals with acute ischaemic stroke and 71 HIV-1 Subtype-C-infected non-stroke controls. Clinical, demographic, laboratory and imaging data were used to determined baseline differences between groups and to distinguish different stroke aetiologies. Exon 1 of the HIV-1 Tat protein was sequenced from peripheral blood samples of stroke participants and controls and amino acid variants were identified using viral epidemiology signature pattern analysis. Regression analyses were used to examine the correlation between residues at signature positions with biomarkers of inflammation and endothelial activation. Results: Stroke and control groups were mostly young (mean age 33 years) females (62.1% & 71.8%), and of Black African ancestry. The strokes showed a higher prevalence of some traditional cardiovascular risk factors. Individuals with strokes had a higher prevalence of antiretroviral treatment interruption (25.9% vs 0.0%, p= 0.003), lower CD4 nadir (112 vs 177.5 cells/μl, p=0.008) and CD4 count (208.5 vs 322.5 cells/μl, p=0.012) than controls. Median viral loads were elevated in both strokes and controls (4.58 & 4.13 log10 copies/ml, p=0.28). The most common causes of stroke were HIV-associated vasculopathy (43.1%) and opportunistic infections (22.4%). Two amino acid variants (proline at position 21 and histidine at position 29) were associated with acute ischaemic stroke. These positions were also associated with modulation of plasma interleukin 6 and monocyte chemoattractant protein 1 levels. Threonine at position 58 distinguished strokes due to alternative mechanisms from strokes due to HIV-associated vasculopathy. Conclusions: Two Tat protein amino acid variants are associated with stroke in HIV. The precise mechanisms by which these associations occur are not known. However, they are likely to be part of a multiple-hit phenomenon in HIV stroke pathogenesis. Tatmediated inflammation with endothelial dysfunction, HIV disease severity, treatment interruption and conventional cardiovascular risk factors probably all contribute to stroke aetiology. Thus, a multi-modal approach is needed to reduce ischaemic stroke risk in HIV infection