Major CD4 T-Cell Depletion and Immune Senescence in a Patient with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) results from primary defects in phagocytic reactive oxygen species (ROS) production. T-cell evaluation is usually neglected during patients’ follow-up, although T-cell depletion has been reported in CGD through unknown mechanisms. We describe here a 36-year-old patient with X-linked CGD with severe CD4 T-cell depletion <200 CD4 T-cells/μl, providing insights into the mechanisms that underlie T-cell loss in the context of oxidative burst defects. In addition to the typical infections, the patient featured a progressive T-cell loss associated with persistent lymphocyte activation, expansion of interleukin (IL)-17-producing CD4 T-cells, and impaired thymic activity, leading to a reduced replenishment of the T-cell pool. A relative CD4 depletion was also found at the gut mucosal level, although no bias to IL-17-production was documented. This immunological pattern of exhaustion of immune resources favors prompt, potentially curative, therapeutic interventions in CGD patients, namely, stem-cell transplantation or gene therapy. Moreover, this clinical case raises new research questions on the interplay of ROS production and T-cell homeostasis and immune senescence

Urinary incontinence related to perineal muscle strength in the first trimester of pregnancy: cross-sectional study

Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.
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Toxic metal enrichment and boating intensity: sediment records of antifoulant copper in shallow lakes of eastern England

Tributyltin (TBT), an aqueous biocide derived from antifouling paint pollution, is known to have impacted coastal marine ecosystems, and has been reported in the sediment of the Norfolk and Suffolk Broads, a network of rivers and shallow lakes in eastern England. In the marine environment, the 1987 TBT ban has resulted in expanded use of alternative biocides, raising the question of whether these products too have impacted the Broads ecosystem and freshwaters in general. Here we examine the lake sediment record in the Norfolk and Suffolk Broads for contamination by copper (Cu) (as an active biocide agent) and zinc (Zn) (as a component of booster biocides), to assess their occurrence and potential for causing environmental harm in freshwater ecosystems. We find that, after the introduction of leisure boating, there is a statistically significant difference in Cu enrichment between heavily and lightly boated sites, while no such difference exists prior to this time. At the heavily boated sites the onset of Cu enrichment coincides with a period of rapid increase in leisure boating. Such enrichment is maintained to the present day, with some evidence of continued increase. We conclude that Cu-based antifouling has measurably contaminated lakes exposed to boating, at concentrations high enough to cause ecological harm. Similar findings can be expected at other boated freshwater ecosystems elsewhere in the world

Risk prediction model for knee pain in the Nottingham Community: a Bayesian modeling approach

Background: 25% of the British population over the age of 50 experience knee pain. It can limit physical ability, cause distress and bears significant socioeconomic costs. Knee pain, not knee osteoarthritis (KOA) is the all to common malady. The objectives of this study were to develop and validate the first risk prediction model for incident knee pain in the Nottingham community and validate this internally within the Nottingham cohort and externally within the Osteoarthritis Initiaitve (OAI) Cohort. Methods: 1822 participants at risk for knee pain from the Nottingham community were followed up for 12 years. Of this cohort, 2/3 (n=1203) were used to develop the risk prediction model and 1/3 (n=619) were used to validate the model. Incident knee pain was defined as pain on most days for at least one month in the past 12 months. Predictors were age, gender, body mass index (BMI), pain elsewhere, prior knee injury and knee alignment. Bayesian logistic regression model was used to determine the probability of an odds ratio >1. The Hosmer-Lemeshow x2 statistic (HLS) was used for calibration and receiver operator characteristics (ROC) was used for discrimination. The OAI cohort was used to examine the performance of the model in a secondary care population. Results: A risk prediction model for knee pain incidence was developed using a Bayesian approach. The model had good calibration with HLS of 7.17 (p=0.52) and moderate discriminative abilities (ROC 0.70) in the community. Individual scenarios are given using the model. However, the model had poor calibration (HLS 5866.28, p<0.01) and poor discriminative ability (ROC 0.54) in the OAI secondary care dataset. Conclusion: This is the first risk prediction model for knee pain, irrespective of underlying structural changes of KOA, in the community using a Bayesian modelling approach. The model appears to work well in a community-based population but not in a hospital derived cohort and may provide a convenient tool for primary care to predict the risk of knee pain in the general population

Gene expression and matrix turnover in overused and damaged tendons

Chronic, painful conditions affecting tendons, frequently known as tendinopathy, are very common types of sporting injury. The tendon extracellular matrix is substantially altered in tendinopathy, and these changes are thought to precede and underlie the clinical condition. The tendon cell response to repeated minor injuries or “overuse” is thought to be a major factor in the development of tendinopathy. Changes in matrix turnover may also be effected by the cellular response to physical load, altering the balance of matrix turnover and changing the structure and composition of the tendon. Matrix turnover is relatively high in tendons exposed to high mechanical demands, such as the supraspinatus and Achilles, and this is thought to represent either a repair or tissue maintenance function. Metalloproteinases are a large family of enzymes capable of degrading all of the tendon matrix components, and these are thought to play a major role in the degradation of matrix during development, adaptation and repair. It is proposed that some metalloproteinase enzymes are required for the health of the tendon, and others may be damaging, leading to degeneration of the tissue. Further research is required to investigate how these enzyme activities are regulated in tendon and altered in tendinopathy. A profile of all the metalloproteinases expressed and active in healthy and degenerate tendon is required and may lead to the development of new drug therapies for these common and debilitating sports injuries

Molecular characterisation of protist parasites in human-habituated mountain gorillas (Gorilla beringei beringei), humans and livestock, from Bwindi impenetrable National Park, Uganda

Over 60 % of human emerging infectious diseases are zoonotic, and there is growing evidence of the zooanthroponotic transmission of diseases from humans to livestock and wildlife species, with major implications for public health, economics, and conservation. Zooanthroponoses are of relevance to critically endangered species; amongst these is the mountain gorilla (Gorilla beringei beringei) of Uganda. Here, we assess the occurrence of Cryptosporidium, Cyclospora, Giardia, and Entamoeba infecting mountain gorillas in the Bwindi Impenetrable National Park (BINP), Uganda, using molecular methods. We also assess the occurrence of these parasites in humans and livestock species living in overlapping/adjacent geographical regions

A Review of Pharmacologic Treatment for Compulsive Buying Disorder

At present, no treatment recommendations can be made for compulsive buying disorder. Recent studies have found evidence for the efficacy of psychotherapeutic options, but less is known regarding the best pharmacologic treatment. The purpose of this review is to present and analyze the available published evidence on the pharmacological treatment of compulsive buying disorder. To achieve this, we conducted a review of studies focusing on the pharmacological treatment of compulsive buying by searching the PubMed/MEDLINE database. Selection criteria were applied, and 21 studies were identified. Pharmacological classes reported included antidepressants, mood stabilizers, opioid antagonists, second-generation antipsychotics, and N-methyl-D-aspartate receptor antagonists. We found only placebo-controlled trials for fluvoxamine; none showed effectiveness against placebo. Three open-label trials reported clinical improvement with citalopram; one was followed by a double-blind discontinuation. Escitalopram was effective in an open-label trial but did not show efficacy in the double-blind phase. Memantine was identified as effective in a pilot open-label study. Fluoxetine, bupropion, nortriptyline, clomipramine, topiramate and naltrexone were only reported to be effective in clinical cases. According to the available literature, there is no evidence to propose a specific pharmacologic agent for compulsive buying disorder. Future research is required for a better understanding of both pathogenesis and treatment of this disorder.info:eu-repo/semantics/publishedVersio