The Prevalence of Undiagnosed HIV Infection in Those Who Decline HIV Screening in an Urban Emergency Department

Objective. To determine the prevalence of occult HIV infection in patients who decline routine HIV testing in an urban emergency department. Design, Setting, and Patients. Discarded blood samples were obtained from patients who had declined routine ED HIV testing. After insuring that the samples came from patients not known to be HIV positive, they were deidentified, and rapid HIV testing was preformed using 5 μL of whole blood. Main Outcome Measures. The prevalence of occult HIV infection in those who declined testing compared with prevalence in those who accepted testing. Results. 600 consecutive samples of patients who declined routine HIV screening were screened for HIV. Twelve (2%) were reactive. Over the same period of time, 4845 patients accepted routine HIV testing. Of these, 35 (0.7%) were reactive. The difference in the prevalence of HIV infection between those who declined and those who accepted testing was significant (P = .001). The relative risk of undetected HIV infection in the group that declined testing was 2.74 times higher (95% CI 1.44–5.18) compared with those accepted testing. Conclusion. The rate of occult HIV infection is nearly three-times higher in those who decline routine ED HIV testing compared with those who accept such testing. Interventions are urgently needed to decrease the opt-out rate in routine ED HIV testing settings

The effect of Cissus quadrangularis (CQR-300) and a Cissus formulation (CORE) on obesity and obesity-induced oxidative stress

AIM: Obesity is generally linked to complications in lipid metabolism and oxidative stress. The aim of this study was to compare the effect of a proprietary extract of Cissus quadrangularis (CQR-300) to that of a proprietary formulation containing CQR-300 (CORE) on weight, blood lipids, and oxidative stress in overweight and obese people. METHODS: The first part of the study investigated the in vitro antioxidant properties of CQR-300 and CORE using 3 different methods, while the second part of the study was a double-blind placebo controlled design, involving initially 168 overweight and obese persons (38.7% males; 61.3% females; ages 19–54), of whom 153 completed the study. All participants received two daily doses of CQR-300, CORE, or placebo and were encouraged to maintain their normal levels of physical activity. Anthropometric measurements and blood sampling were done at the beginning and end of the study period. RESULTS: CQR-300 as well as CORE exhibited antioxidant properties in vitro. They also acted as in vivo antioxidants, bringing about significant (p < 0.001) reductions in plasma TBARS and carbonyls. Both CQR-300 and CORE also brought about significant reductions in weight, body fat, total cholesterol, LDL-cholesterol, triglycerides, and fasting blood glucose levels over the respective study periods. These changes were accompanied by a significant increase in HDL-cholesterol levels, plasma 5-HT, and creatinine. CONCLUSION: CQR-300 (300 mg daily) and CORE (1028 mg daily) brought about significant reductions in weight and blood glucose levels, while decreasing serum lipids thus improving cardiovascular risk factors. The increase in plasma 5-HT and creatinine for both groups hypothesizes a mechanism of controlling appetite and promoting the increase of lean muscle mass by Cissus quadrangularis, thereby supporting the clinical data for weight loss and improving cardiovascular health

Oxidative stress and blood lipid profile in Cameroonian obese subjects

The relationship between obesity, blood lipids and oxidative stress was investigated in 200 participants. The Body Mass Index of the subjects were positively correlated with the percentage body fat, the systolic and diastolic blood pressure, the fasting blood glucose level, the oxidation of proteins and lipids as well as the concentrations of total and LDL cholesterol. On the other hand, the Body Mass Index was negatively correlated to sulhydryl and protein levels. Obese subjects also had significantly higher body fat (p<.001), waist circumference (p<.001), fasting blood glucose (p<.01) as well as systolic blood pressure (p<.05). Obesity, therefore, can be said to increase the oxidation of plasma proteins and lipids while reducing the antioxidant status as observed by the inverse relation between plasma sulfhydryl groups and the percentage body fat. This increase in oxidative stress can predispose obese people to illnesses such as cardiovascular diseases and diabetes mellitus

TRAIL regulatory receptors constrain human hepatic stellate cell apoptosis

This work was funded by UCLH NIHR BRC (sample collection), Wellcome Trust Investigator award (MKM) and Clinical Research Training Fellowship (USG); Medical Research Council grant (MKM) and Clinician Scientist Fellowship (DP); EASL fellowship (IO); National Health and Medical Research Council Australia (KPS)

GDF11 induces mild hepatic fibrosis independent of metabolic health

Background & aims: Growth Differentiation Factor 11 (GDF11) is an anti-aging factor, yet its role in liver diseases is not established. We evaluated the role of GDF11 in healthy conditions and in the transition from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH). Results: GDF11 mRNA levels positively correlated with NAFLD activity score and with CPT1, SREBP, PPARγ and Col1A1 mRNA levels, and associated to portal fibrosis, in morbidly obese patients with NAFLD/NASH. GDF11-treated mice showed mildly exacerbated hepatic collagen deposition, accompanied by weight loss and without changes in liver steatosis or inflammation. GDF11 triggered ALK5-dependent SMAD2/3 nuclear translocation and the pro-fibrogenic activation of HSC. Conclusions: GDF11 supplementation promotes mild liver fibrosis. Even considering its beneficial metabolic effects, caution should be taken when considering therapeutics that regulate GDF11. Methods: We analyzed liver biopsies from a cohort of 33 morbidly obese adults with NAFLD/NASH. We determined the correlations in mRNA expression levels between GDF11 and genes involved in NAFLD-to-NASH progression and with pathological features. We also exposed wild type or obese mice with NAFLD to recombinant GDF11 by daily intra-peritoneal injection and monitor the hepatic pathological changes. Finally, we analyzed GDF11-activated signaling pathways in hepatic stellate cells (HSC)

Influence of the initial chemical conditions on the rational design of silica particles

The influence of the water content in the initial composition on the size of silica particles produced using the Stöber process is well known. We have shown that there are three morphological regimes defined by compositional boundaries. At low water levels (below stoichiometric ratio of water:tetraethoxysilane), very high surface area and aggregated structures are formed; at high water content (>40 wt%) similar structures are also seen. Between these two boundary conditions, discrete particles are formed whose size are dictated by the water content. Within the compositional regime that enables the classical Stöber silica, the structural evolution shows a more rapid attainment of final particle size than the rate of formation of silica supporting the monomer addition hypothesis. The clearer understanding of the role of the initial composition on the output of this synthesis method will be of considerable use for the establishment of reliable reproducible silica production for future industrial adoption

Evidence-based assessment of antiosteoporotic activity of petroleum-ether extract of Cissus quadrangularis Linn. on ovariectomy-induced osteoporosis

The increasing incidence of postmenopausal osteoporosis and its related fractures have become global health issues in the recent days. Postmenopausal osteoporosis is the most frequent metabolic bone disease; it is characterized by a rapid loss of mineralized bone tissue. Hormone replacement therapy has proven efficacious in preventing bone loss but not desirable to many women due to its side-effects. Therefore we are in need to search the natural compounds for a treatment of postmenopausal symptoms in women with no toxic effects. In the present study, we have evaluated the effect of petroleum-ether extract of Cissus quadrangularis Linn. (CQ), a plant used in folk medicine, on an osteoporotic rat model developed by ovariectomy. In this experiment, healthy female Wistar rats were divided into four groups of six animals each. Group 1 was sham operated. All the remaining groups were ovariectomized. Group 2 was fed with an equivolume of saline and served as ovariectomized control (OVX). Groups 3 and 4 were orally treated with raloxifene (5.4 mg/kg) and petroleum-ether extract of CQ (500 mg/kg), respectively, for 3 months. The findings were assessed on the basis of animal weight, morphology of femur, and histochemical localization of alkaline phosphatase (ALP) (an osteoblastic marker) and tartrate-resistant acid phosphatase (TRAP) (an osteoclastic marker) in upper end of femur. The study revealed for the first time that the petroleum-ether extract of CQ reduced bone loss, as evidenced by the weight gain in femur, and also reduced the osteoclastic activity there by facilitating bone formation when compared to the OVX group. The osteoclastic activity was confirmed by TRAP staining, and the bone formation was assessed by ALP staining in the femur sections. The color intensity of TRAP and ALP enzymes from the images were evaluated by image analysis software developed locally. The effect of CQ was found to be effective on both enzymes, and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis. The biological activity of CQ on bone may be attributed to the phytogenic steroids present in it

Early Hypothalamic FTO Overexpression in Response to Maternal Obesity – Potential Contribution to Postweaning Hyperphagia

Intrauterine and postnatal overnutrition program hyperphagia, adiposity and glucose intolerance in offspring. Single-nucleotide polymorphisms (SNPs) of the fat mass and obesity associated (FTO) gene have been linked to increased risk of obesity. FTO is highly expressed in hypothalamic regions critical for energy balance and hyperphagic phenotypes were linked with FTO SNPs. As nutrition during fetal development can influence the expression of genes involved in metabolic function, we investigated the impact of maternal obesity on FTO.Female Sprague Dawley rats were exposed to chow or high fat diet (HFD) for 5 weeks before mating, throughout gestation and lactation. On postnatal day 1 (PND1), some litters were adjusted to 3 pups (vs. 12 control) to induce postnatal overnutrition. At PND20, rats were weaned onto chow or HFD for 15 weeks. FTO mRNA expression in the hypothalamus and liver, as well as hepatic markers of lipid metabolism were measured.At weaning, hypothalamic FTO mRNA expression was increased significantly in offspring of obese mothers and FTO was correlated with both visceral and epididymal fat mass (P<0.05); body weight approached significance (P = 0.07). Hepatic FTO and Fatty Acid Synthase mRNA expression were decreased by maternal obesity. At 18 weeks, FTO mRNA expression did not differ between groups; however body weight was significantly correlated with hypothalamic FTO. Postnatal HFD feeding significantly reduced hepatic Carnitine Palmitoyltransferase-1a but did not affect the expression of other hepatic markers investigated. FTO was not affected by chronic HFD feeding.Maternal obesity significantly impacted FTO expression in both hypothalamus and liver at weaning. Early overexpression of hypothalamic FTO correlated with increased adiposity and later food intake of siblings exposed to HFD suggesting upregulation of FTO may contribute to subsequent hyperphagia, in line with some human data. No effect of maternal obesity was observed on FTO in adulthood

Catch-up growth following intra-uterine growth-restriction programmes an insulin-resistant phenotype in adipose tissue.

BACKGROUND: It is now widely accepted that the early-life nutritional environment is important in determining susceptibility to metabolic diseases. In particular, intra-uterine growth restriction followed by accelerated postnatal growth is associated with an increased risk of obesity, type-2 diabetes and other features of the metabolic syndrome. The mechanisms underlying these observations are not fully understood. AIM: Using a well-established maternal protein-restriction rodent model, our aim was to determine if exposure to mismatched nutrition in early-life programmes adipose tissue structure and function, and expression of key components of the insulin-signalling pathway. METHODS: Offspring of dams fed a low-protein (8%) diet during pregnancy were suckled by control (20%)-fed dams to drive catch-up growth. This 'recuperated' group was compared with offspring of dams fed a 20% protein diet during pregnancy and lactation (control group). Epididymal adipose tissue from 22-day and 3-month-old control and recuperated male rats was studied using histological analysis. Expression and phosphorylation of insulin-signalling proteins and gene expression were assessed by western blotting and reverse-transcriptase PCR, respectively. RESULTS: Recuperated offspring at both ages had larger adipocytes (P<0.001). Fasting serum glucose, insulin and leptin levels were comparable between groups but increased with age. Recuperated offspring had reduced expression of IRS-1 (P<0.01) and PI3K p110β (P<0.001) in adipose tissue. In adult recuperated rats, Akt phosphorylation (P<0.01) and protein levels of Akt-2 (P<0.01) were also reduced. Messenger RNA expression levels of these proteins were not different, indicating a post-transcriptional effect. CONCLUSION: Early-life nutrition programmes alterations in adipocyte cell size and impairs the protein expression of several insulin-signalling proteins through post-transcriptional mechanisms. These indices may represent early markers of insulin resistance and metabolic disease risk