Sharp Global Bounds for the Hessian on Pseudo-Hermitian Manifolds

We find sharp bounds for the norm inequality on a Pseudo-hermitian manifold, where the L^2 norm of all second derivatives of the function involving horizontal derivatives is controlled by the L^2 norm of the sub-Laplacian. Perturbation allows us to get a-priori bounds for solutions to sub-elliptic PDE in non-divergence form with bounded measurable coefficients. The method of proof is through a Bochner technique. The Heisenberg group is seen to be en extremal manifold for our inequality in the class of manifolds whose Ricci curvature is non-negative.Comment: 13 page

Dealing with substance use disorders in general practice

Substance use disorders are highly prevalent in South Africa. General practitioners are often the first point of contact and play an essential role in correctly identifying the substance use problem. This article provides an overview of the importance of screening for and assessing substance use disorders and identifying the severity of the substance use disorder, so that the right level of management can be ensured. It also examines associated co-morbidities and provides a general overview of the management of substance use disorders.S Afr Fam Pract 2012;54(5):404-40

A Systematic Review of Online Sex Addiction and Clinical Treatments Using CONSORT Evaluation

Researchers have suggested that the advances of the Internet over the past two decades have gradually eliminated traditional offline methods of obtaining sexual material. Additionally, research on cybersex and/or online sex addictions has increased alongside the development of online technology. The present study extended the findings from Griffiths’ (2012) systematic empirical review of online sex addiction by additionally investigating empirical studies that implemented and/or documented clinical treatments for online sex addiction in adults. A total of nine studies were identified and then each underwent a CONSORT evaluation. The main findings of the present review provide some evidence to suggest that some treatments (both psychological and/or pharmacological) provide positive outcomes among those experiencing difficulties with online sex addiction. Similar to Griffiths’ original review, this study recommends that further research is warranted to establish the efficacy of empirically driven treatments for online sex addiction

Neonatal-onset multisystem inflammatory disease responsive to interleukin-1 beta inhibition

BACKGROUND:Neonatal-onset multisystem inflammatory disease is characterized by fever, urticarial rash, aseptic meningitis, deforming arthropathy, hearing loss, and mental retardation. Many patients have mutations in the cold-induced autoinflammatory syndrome 1 (CIAS1) gene, encoding cryopyrin, a protein that regulates inflammation.METHODS:We selected 18 patients with neonatal-onset multisystem inflammatory disease (12 with identifiable CIAS1 mutations) to receive anakinra, an interleukin-1-receptor antagonist (1 to 2 mg per kilogram of body weight per day subcutaneously). In 11 patients, anakinra was withdrawn at three months until a flare occurred. The primary end points included changes in scores in a daily diary of symptoms, serum levels of amyloid A and C-reactive protein, and the erythrocyte sedimentation rate from baseline to month 3 and from month 3 until a disease flare.RESULTS:All 18 patients had a rapid response to anakinra, with disappearance of rash. Diary scores improved (P<0.001) and serum amyloid A (from a median of 174 mg to 8 mg per liter), C-reactive protein (from a median of 5.29 mg to 0.34 mg per deciliter), and the erythrocyte sedimentation rate decreased at month 3 (all P<0.001), and remained low at month 6. Magnetic resonance imaging showed improvement in cochlear and leptomeningeal lesions as compared with baseline. Withdrawal of anakinra uniformly resulted in relapse within days; retreatment led to rapid improvement. There were no drug-related serious adverse events.CONCLUSIONS:Daily injections of anakinra markedly improved clinical and laboratory manifestations in patients with neonatal-onset multisystem inflammatory disease, with or without CIAS1 mutations

Contribution of Heptose Metabolites and the cag Pathogenicity Island to the Activation of Monocytes/Macrophages by Helicobacter pylori.

The human gastric pathogen Helicobacter pylori activates human epithelial cells by a particular combination of mechanisms, including NOD1 and ALPK1-TIFA activation. These mechanisms are characterized by a strong participation of the bacterial cag pathogenicity island, which forms a type IV secretion system (CagT4SS) that enables the bacteria to transport proteins and diverse bacterial metabolites, including DNA, glycans, and cell wall components, into human host cells. Building on previous findings, we sought to determine the contribution of lipopolysaccharide inner core heptose metabolites (ADP-heptose) in the activation of human phagocytic cells by H. pylori. Using human monocyte/macrophage-like Thp-1 cells and human primary monocytes and macrophages, we were able to determine that a substantial part of early phagocytic cell activation, including NF-kappa B activation and IL-8 production, by live H. pylori is triggered by bacterial heptose metabolites. This effect was very pronounced in Thp-1 cells exposed to bacterial purified lysates or pure ADP-heptose, in the absence of other bacterial MAMPs, and was significantly reduced upon TIFA knock-down. Pure ADP-heptose on its own was able to strongly activate Thp-1 cells and human primary monocytes/macrophages. Comprehensive transcriptome analysis of Thp-1 cells co-incubated with live H. pylori or pure ADP-heptose confirmed a signature of ADP-heptose-dependent transcript activation in monocyte/macrophages. Bacterial enzyme-treated lysates (ETL) and pure ADP-heptose-dependent activation differentiated monocytes into macrophages of predominantly M1 type. In Thp-1 cells, the active CagT4SS was less required for the heptose-induced proinflammatory response than in epithelial cells, while active heptose biosynthesis or pure ADP-heptose was required and sufficient for their early innate response and NF-kappa B activation. The present data suggest that early activation and maturation of incoming and resident phagocytic cells (monocytes, macrophages) in the H. pylori-colonized stomach strongly depend on bacterial LPS inner core heptose metabolites, also with a significant contribution of an active CagT4SS

Challenges in Using Cultured Primary Rodent Hepatocytes or Cell Lines to Study Hepatic HDL Receptor SR-BI Regulation by Its Cytoplasmic Adaptor PDZK1

Background: PDZK1 is a four PDZ-domain containing cytoplasmic protein that binds to a variety of membrane proteins via their C-termini and can influence the abundance, localization and/or function of its target proteins. One of these targets in hepatocytes in vivo is the HDL receptor SR-BI. Normal hepatic expression of SR-BI protein requires PDZK1 - <5% of normal hepatic SR-BI is seen in the livers of PDZK1 knockout mice. Progress has been made in identifying features of PDZK1 required to control hepatic SR-BI in vivo using hepatic expression of wild-type and mutant forms of PDZK1 in wild-type and PDZK1 KO transgenic mice. Such in vivo studies are time consuming and expensive, and cannot readily be used to explore many features of the underlying molecular and cellular mechanisms. Methodology/Principal Findings: Here we have explored the potential to use either primary rodent hepatocytes in culture using 2D collagen gels with newly developed optimized conditions or PDZK1/SR-BI co-transfected cultured cell lines (COS, HEK293) for such studies. SR-BI and PDZK1 protein and mRNA expression levels fell rapidly in primary hepatocyte cultures, indicating this system does not adequately mimic hepatocytes in vivo for analysis of the PDZK1 dependence of SR-BI. Although PDZK1 did alter SR-BI protein expression in the cell lines, its influence was independent of SR-BI’s C-terminus, and thus is not likely to occur via the same mechanism as that which occurs in hepatocytes in vivo. Conclusions/Significance: Caution must be exercised in using primary hepatocytes or cultured cell lines when studying the mechanism underlying the regulation of hepatic SR-BI by PDZK1. It may be possible to use SR-BI and PDZK1 expression as sensitive markers for the in vivo-like state of hepatocytes to further improve primary hepatocyte cell culture conditions.National Institutes of Health (U.S.) (Grant HL052212)National Institutes of Health (U.S.) (Grant HL066105)National Institutes of Health (U.S.) (Grant ES015241)National Institutes of Health (U.S.) (Grant GM068762

Patterns of adiposity, vascular phenotypes and cognitive function in the 1946 British Birth Cohort.

BACKGROUND: The relationship between long-term exposure to whole body or central obesity and cognitive function, as well as its potential determinants, remain controversial. In this study, we assessed (1) the potential impact of 30 years exposure to different patterns of whole body and central adiposity on cognitive function at 60-64 years, (2) whether trajectories of central adiposity can provide additional information on later cognitive function compared to trajectories of whole body adiposity, and (3) the influence of vascular phenotypes on these associations. METHODS: The study included 1249 participants from the prospective cohort MRC National Survey of Health and Development. Body mass index (BMI), waist circumference (WC), and vascular (carotid intima-media thickness, carotid-femoral pulse wave velocity) and cognitive function (memory, processing speed, reaction time) data, at 60-64 years, were used to assess the associations between different patterns of adult WC or BMI (from 36 years of age) and late midlife cognitive performance, as well as the proportion of this association explained by cardiovascular phenotypes. RESULTS: Longer exposure to elevated WC was related to lower memory performance (p < 0.001 for both) and longer choice reaction time (p = 0.003). A faster gain of WC between 36 and 43 years of age was associated with the largest change in reaction time and memory test (P < 0.05 for all). Similar associations were observed when patterns of WC were substituted with patterns of BMI, but when WC and BMI were included in the same model, only patterns of WC remained significantly associated with cognitive function. Participants who dropped one BMI category and maintained a lower BMI had similar memory performance to those of normal weight during the whole follow-up. Conversely, those who dropped and subsequently regained one BMI category had a memory function similar to those with 30 years exposure to elevated BMI. Adjustment for vascular phenotypes, levels of cardiovascular risk factors, physical activity, education, childhood cognition and socioeconomic position did not affect these associations. CONCLUSIONS: Longer exposure to elevated WC or BMI and faster WC or BMI gains between 36 and 43 years are related to lower cognitive function at 60-64 years. Patterns of WC in adulthood could provide additional information in predicting late midlife cognitive function than patterns of BMI. The acquisition of an adverse cardiovascular phenotype associated with adiposity is unlikely to account for these relationships

Interaction Between Convection and Pulsation

This article reviews our current understanding of modelling convection dynamics in stars. Several semi-analytical time-dependent convection models have been proposed for pulsating one-dimensional stellar structures with different formulations for how the convective turbulent velocity field couples with the global stellar oscillations. In this review we put emphasis on two, widely used, time-dependent convection formulations for estimating pulsation properties in one-dimensional stellar models. Applications to pulsating stars are presented with results for oscillation properties, such as the effects of convection dynamics on the oscillation frequencies, or the stability of pulsation modes, in classical pulsators and in stars supporting solar-type oscillations.Comment: Invited review article for Living Reviews in Solar Physics. 88 pages, 14 figure

Co-occurrence of diabetes and hopelessness predicts adverse prognosis following percutaneous coronary intervention

We examined the impact of co-occurring diabetes and hopelessness on 3-year prognosis in percutaneous coronary intervention patients. Consecutive patients (n = 534) treated with the paclitaxel-eluting stent completed a set of questionnaires at baseline and were followed up for 3-year adverse clinical events. The incidence of 3-year death/non-fatal myocardial infarction was 3.5% in patients with no risk factors (neither hopelessness nor diabetes), 8.2% in patients with diabetes, 11.2% in patients with high hopelessness, and 15.9% in patients with both factors (p = 0.001). Patients with hopelessness (HR: 3.28; 95% CI: 1.49-7.23) and co-occurring diabetes and hopelessness (HR: 4.89; 95% CI: 1.86-12.85) were at increased risk of 3-year adverse clinical events compared to patients with no risk factors, whereas patients with diabetes were at a clinically relevant but not statistically significant risk (HR: 2.40; 95% CI: 0.82-7.01). These results remained, adjusting for baseline characteristics an

Menu labelling and food choice in obese adults: a feasibility study.

BACKGROUND: To date research examining the benefits of menu labelling in the UK is sparse. The aim of the present study was to examine the impact of menu labelling in a UK obese population. METHODS: Using a repeated measures design, 61 patients at a tier 3 weight management service completed four questionnaires to assess their food choice (control) and behaviour change when presented with 3 menu labelling formats (calorie content; nutrient content; and energy expenditure). RESULTS: All three forms of labelling increased participants weight control concerns compared to the control condition. There was a significant difference in content of food ordered in the three menu labelling formats compared to the control condition. The calorie condition had the largest percentage decrease in calories selected followed by energy expenditure and nutrient content. However, no difference was observed between the three conditions in the desire for menu labelling in restaurants to be introduced in the UK. CONCLUSIONS: The findings suggest that menu labelling should be enforced in the UK as it is both beneficial to promoting healthy eating and in demand. This study is the first to examine menu labelling in a UK obese population using energy expenditure equivalents to provide nutritional information