BMI and All-Cause Mortality in a Population-Based Cohort in Rural South Africa

OBJECTIVE: This study evaluates the association between BMI and all-cause and cause-specific mortality in South Africa. METHODS: Prospective, population-based observational cohort data from rural South Africa were analyzed. BMI was measured in 2010. Demographic characteristics were recorded and deaths were verified with verbal autopsy interview. The InterVA-5 tool was used to assign causes of death. HIV testing was conducted annually. Cox proportional hazards models were fit to estimate the effect of BMI on all-cause and cause-specific mortality, accounting for the competing risk of death from other causes. Models were adjusted for sociodemographic characteristics and HIV status, and inverse probability weighting for survey nonparticipation was used. RESULTS: The cohort consisted of 9,728 individuals. In adjusted models, those with BMI of 25.0 to 29.9 kg/m2 or 30.0 to 34.9 kg/m2 had a lower hazard of death (adjusted hazard ratio: 0.80; 95% CI: 0.69-0.92 and adjusted hazard ratio: 0.75; 95% CI: 0.60-0.93, respectively) compared with those with BMI of 18.5 to 24.9 kg/m^{2}. CONCLUSIONS: Individuals in South Africa who meet clinically defined criteria for overweight or obesity had a lower risk of all-cause mortality than those with a normal BMI. These findings were stronger for women and communicable conditions

X-ray-Absorption Spectral Study of the R₂Fe₁₇₋ₓMₓ Solid Solutions (R=Ce, Nd and M=Al, Si)

The x-ray-absorption near-edge structure (XANES) spectra obtained at the cerium LIII edge of the Ce2Fe17-xAlx solid solutions and Ce2Fe14Si3, show two absorption peaks characteristic of the 4f1 and 4f0 configurations of cerium, peaks which indicate that cerium is in a mixed valent state in these compounds. All the XANES spectra have been consistently and excellently fit with one sigmoidal function and two Gaussianbroadened Lorentzian functions. The cerium spectroscopic valence obtained from the relative areas of the two peaks decreases from 3.64 to 3.43 between x=0 and 9 in Ce2Fe17-x,Alx, and correlates linearly with the cerium site volume This correlation confirms that the cerium valence is strongly dependent upon steric effects. In contrast the cerium valence obtained from the XANES spectrum of Ce2Fe14Si3 is not determined by stenc effects and indicates, in agreement with other measurements and calculations, that silicon is more covalently bonded with its near-neighbor cerium atoms than is aluminum. The neodymium LIII,-edge XANES spectra of the Nd2Fe17-x Alx solid solutions, where x is 0, 3, and 8, reveal the presence of only trivalent neodymium and an increase of the empty 5d state density when aluminum is substituted in place of iron. XANES measurements at the iron K edee of the Ce2Fe17-xAlx, and Nd2Fe17-1Alx, solid solutions show changes m the relative intensity of the multiple scattering peaks, changes which are related to the changing composition of the first three neighbor shells with increasing aluminum content

Green environment and incident depression in South Africa : a geospatial analysis and mental health implications in a resource-limited setting

Our results imply the importance of green environments for mental wellbeing in sub-Saharan African settings experiencing rapid urbanisation, economic and epidemiological transition, reaffirming the need to incorporate environmental services and benefits for sustainable socioeconomic development.Peer reviewe

Skuteczność połączenia ezetymibu/simwastatyny w dawkach 10/40 mg w porównaniu z podwójną dawką statyny u pacjentów hospitalizowanych z powodu ostrego incydentu wieńcowego: badanie INFORCE

Wstęp: Celem pracy było zbadanie skuteczności i bezpiecze&#241;stwa stosowania skojarzonego preparatu ezetymibu/simwastatyny (Eze/Simva) w dawce 10/40 mg w porównaniu z podwójną dawką statyny, które włączano przy wypisie ze szpitala u pacjentów przyjmujących dotychczas statyny, a u których powodem hospitalizacji była diagnostyka epizodu wieńcowego. Metody: Było to otwarte wieloośrodkowe badanie IV fazy, z randomizacją, prowadzone w układzie równoległym z grupą kontrolną, do którego zakwalifikowano 424 pacjentów (w wieku &#8805; 18 lat) hospitalizowanych z powodu ostrego epizodu wieńcowego. Pacjenci przyjmowali wcześniej statyny (przez &#8805; 6 tygodni) w stałej dawce, której wartość można było podwoić zgodnie z zaleceniami producenta preparatu. W momencie wypisu ze szpitala pacjent ów dzielono na grupy pod wzgl&#234;dem dawki/siły działania statyny (duża, średnia, mała) i przydzielano losowo w stosunku 1:1 do grupy, która przyjmowała następnie podwojoną dawkę tego preparatu (n = 211) lub preparat Eze/Simva w dawce 10/40 mg (n = 213) przez 12 tygodni. Pierwszorzędową zmienną określającą skuteczność zastosowanego leczenia było stężenie frakcji cholesterolu o małej gęstości (LDL-C) wyrażone w wartościach bezwzględnych [mmol/l] w momencie zakończenia badania. Wyniki: Średnie wartości stężenia cholesterolu frakcji LDL w punkcie wyjściowym wynosiły 2,48 mmol/l w grupie Eze/Simva i 2,31 mmol/l w grupie leczonej tylko statyną. W momencie zako&#241;czenia badania wartości najmniejszych kwadratów stężenie LDL-C wyniosły odpowiednio 1,74 mmol/l w grupie Eze/Simva i 2,22 mmol/l w grupie leczonej statyną; różnica pomiędzy grupami osiągnęła wartość znamienną statystycznie, rzędu -0,49 mmol/l (p &#8804; 0,001). Przyjmowanie skojarzonego preparatu Eze/Simva powodowało także znamienne zmniejszenie stężenia cholesterolu całkowitego (&#8211;0,49 mmol/l), cholesterolu frakcji lipoprotein innych ni&#191; te o dużej gęstości [(nie-HDL); &#8211;0,53 mmol/l] oraz apolipoproteiny B (&#8211;0,14 mmol/l) w porównaniu z przyjmowaniem podwójnej dawki statyny (p &#163; 0,001 dla wszystkich porównywanych warto&#339;ci). Oba protokoły leczenia miały zbliżony wpływ na stężenia triglicerydów, białka C-reaktywnego i cholesterolu frakcji lipoprotein o dużej gęstości (HDL, high-density protein); porównania pomiędzy grupami przyniosły wartości nieznamienne (p &#8805; 0,160). U istotnie większej liczby pacjentów przyjmujących Eze/Simva stężenie cholesterolu frakcji LDL spadło do poniżej 2,5 mmol/l (< 100 mg/dl; 86% pacjentów leczonych Eze/Simva vs. 72% osób leczonych podwójną dawką statyny), do poniżej 2,0 mmol/l (< 77 mg/dl; 70% vs. 42%) oraz do poniżej 1,8 mmol/l mmol/l (< 70 mg/dl; 60% vs. 13%) w porównaniu z grupą otrzymującą samą statynę (p &#8804; 0,001 dla wszystkich porównywanych wartości). Połączenie preparatów Eze/Simva było ogólnie dobrze tolerowane, a jego profil bezpieczeństwa był zbliżony do profilu samej statyny. Nie stwierdzono różnic pomiędzy grupami pod względem częstości występowania zwyżki aktywności aminotransferaz wątrobowych do wartości równej przynajmniej 3-krotności górnej granicy przedziału warto&#339;ci prawidłowych (ULN) ani zwyżki aktywności kinazy kreatynowej do wartości równej przynajmniej 10-krotności ULN. Wnioski: W populacji pacjentów leczonych wcześniej statyną, których hospitalizowano w celu diagnostyki incydentu wie&#241;cowego, leczenie skojarzonym preparatem Eze/Simva w dawce 10/40 mg przez 12 tygodni powoduje większą normalizację lipemii niż podwojenie dawki przyjmowanej wcze&#339;niej statyny, z zachowaniem zbliżonego profilu bezpieczeństwa

Robust averaging protects decisions from noise in neural computations

An ideal observer will give equivalent weight to sources of information that are equally reliable. However, when averaging visual information, human observers tend to downweight or discount features that are relatively outlying or deviant (‘robust averaging’). Why humans adopt an integration policy that discards important decision information remains unknown. Here, observers were asked to judge the average tilt in a circular array of high-contrast gratings, relative to an orientation boundary defined by a central reference grating. Observers showed robust averaging of orientation, but the extent to which they did so was a positive predictor of their overall performance. Using computational simulations, we show that although robust averaging is suboptimal for a perfect integrator, it paradoxically enhances performance in the presence of “late” noise, i.e. which corrupts decisions during integration. In other words, robust decision strategies increase the brain’s resilience to noise arising in neural computations during decision-making

LH prevents cisplatin-induced apoptosis in oocytes and preserves female fertility in mouse

Premature ovarian failure and female infertility are frequent side effects of anticancer therapies, owing to the extreme sensitivity of the ovarian reserve oocytes to the damaging effects of irradiation and chemotherapy on DNA. We report here a robust protective effect of luteinizing hormone (LH) on the primordial follicle pool of prepubertal ovaries against the cisplatin (Cs)-induced apoptosis. In vitro LH treatment of prepubertal ovarian fragments generated anti-apoptotic signals by a subset of ovarian somatic cells expressing LH receptor (LHR) through cAMP/PKA and Akt pathways. Such signals, reducing the oocyte level of pro-apoptotic TAp63 protein and favoring the repair of the Cs-damaged DNA in the oocytes, prevented their apoptosis. Noteworthy, in vivo administration to prepubertal female mice of a single dose of LH together with Cs inhibited the depletion of the primordial follicle reserve caused by the drug and preserved their fertility in reproductive age, preventing significant alteration in the number of pregnancy and of delivered pups. In conclusion, these findings establish a novel ovoprotective role for LH and further support the very attracting prospective to use physiological 'fertoprotective' approaches for preventing premature infertility and risks linked to precocious menopause in young patients who survived cancer after chemotherapy

Possible involvement of caveolin in attenuation of cardioprotective effect of ischemic preconditioning in diabetic rat heart

<p>Abstract</p> <p>Background</p> <p>Nitric oxide (NO) has been noted to produce ischemic preconditioning (IPC)-mediated cardioprotection. Caveolin is a negative regulator of NO, which inhibits endothelial nitric oxide synthase (eNOS) by making caveolin-eNOS complex. The expression of caveolin is increased during diabetes mellitus (DM). The present study was designed to investigate the involvement of caveolin in attenuation of the cardioprotective effect of IPC during DM in rat.</p> <p>Methods</p> <p>Experimental DM was induced by single dose of streptozotocin (50 mg/Kg, <it>i.p</it>,) and animals were used for experiments four weeks later. Isolated heart was mounted on Langendorff's apparatus, and was subjected to 30 min of global ischemia and 120 min of reperfusion. IPC was given by four cycles of 5 min of ischemia and 5 min of reperfusion with Kreb's-Henseleit solution (K-H). Extent of injury was measured in terms of infarct size by triphenyltetrazolium chloride (TTC) staining, and release of lactate dehydrogenase (LDH) and creatin kinase-MB (CK-MB) in coronary effluent. The cardiac release of NO was noted by measuring the level of nitrite in coronary effluent.</p> <p>Results</p> <p>IPC- induced cardioprotection and release of NO was significantly decreased in diabetic rat heart. Pre-treatment of diabetic rat with daidzein (DDZ) a caveolin inhibitor (0.2 mg/Kg/s.c), for one week, significantly increased the release of NO and restored the attenuated cardioprotective effect of IPC. Also perfusion of sodium nitrite (10 μM/L), a precursor of NO, significantly restored the lost effect of IPC, similar to daidzein in diabetic rat. Administration of 5-hydroxy deaconate (5-HD), a mito K_ATPchannel blocker, significantly abolished the observed IPC-induced cardioprotection in normal rat or daidzein and sodium nitrite perfused diabetic rat heart alone or in combination.</p> <p>Conclusions</p> <p>Thus, it is suggested that attenuation of the cardioprotection in diabetic heart may be due to decrease the IPC mediated release of NO in the diabetic myocardium, which may be due to up -regulation of caveolin and subsequently decreased activity of eNOS.</p

Trends in Pretreatment HIV-1 Drug Resistance in Antiretroviral Therapy-naive Adults in South Africa, 2000–2016: A Pooled Sequence Analysis

Background: South Africa has the largest public antiretroviral therapy (ART) programme in the world. We assessed temporal trends in pretreatment HIV-1 drug resistance (PDR) in ART-naïve adults from South Africa. Methods: We included datasets from studies conducted between 2000 and 2016, with HIV-1 pol sequences from more than ten ART-naïve adults. We analysed sequences for the presence of 101 drug resistance mutations. We pooled sequences by sampling year and performed a sequence-level analysis using a generalized linear mixed model, including the dataset as a random effect. Findings: We identified 38 datasets, and retrieved 6880 HIV-1 pol sequences for analysis. The pooled annual prevalence of PDR remained below 5% until 2009, then increased to a peak of 11·9% (95% confidence interval (CI) 9·2-15·0) in 2015. The pooled annual prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) PDR remained below 5% until 2011, then increased to 10.0% (95% CI 8.4–11.8) by 2014. Between 2000 and 2016, there was a 1.18-fold (95% CI 1.13–1.23) annual increase in NNRTI PDR (p < 0.001), and a 1.10-fold (95% CI 1.05–1.16) annual increase in nucleoside reverse-transcriptase inhibitor PDR (p = 0.001). Interpretation: Increasing PDR in South Africa presents a threat to the efforts to end the HIV/AIDS epidemic. These findings support the recent decision to modify the standard first-line ART regimen, but also highlights the need for broader public health action to prevent the further emergence and transmission of drug-resistant HIV. Source of Funding: This research project was funded by the South African Medical Research Council (MRC) with funds from National Treasury under its Economic Competitiveness and Support Package. Disclaimer: The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official views of CDC

Revascularization for coronary artery disease in diabetes mellitus: Angioplasty, stents and coronary artery bypass grafting

Author Manuscript: 2011 April 14Patients with diabetes mellitus (DM) are prone to a diffuse and rapidly progressive form of atherosclerosis, which increases their likelihood of requiring revascularization. However, the unique pathophysiology of atherosclerosis in patients with DM modifies the response to arterial injury, with profound clinical consequences for patients undergoing percutaneous coronary intervention (PCI). Multiple studies have shown that DM is a strong risk factor for restenosis following successful balloon angioplasty or coronary stenting, with greater need for repeat revascularization and inferior clinical outcomes. Early data suggest that drug eluting stents reduce restenosis rates and the need for repeat revascularization irrespective of the diabetic state and with no significant reduction in hard clinical endpoints such as myocardial infarction and mortality. For many patients with 1- or 2-vessel coronary artery disease, there is little prognostic benefit from any intervention over optimal medical therapy. PCI with drug-eluting or bare metal stents is appropriate for patients who remain symptomatic with medical therapy. However, selection of the optimal myocardial revascularization strategy for patients with DM and multivessel coronary artery disease is crucial. Randomized trials comparing multivessel PCI with balloon angioplasty or bare metal stents to coronary artery bypass grafting (CABG) consistently demonstrated the superiority of CABG in patients with treated DM. In the setting of diabetes CABG had greater survival, fewer recurrent infarctions or need for re-intervention. Limited data suggests that CABG is superior to multivessel PCI even when drug-eluting stents are used. Several ongoing randomized trials are evaluating the long-term comparative efficacy of PCI with drug-eluting stents and CABG in patients with DM. Only further study will continue to unravel the mechanisms at play and optimal therapy in the face of the profoundly virulent atherosclerotic potential that accompanies diabetes mellitus.National Institutes of Health (U.S.) (GM 49039