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BACKGROUND AIMS: Nitric oxide, a major inhibitory nonadrenergic, noncholinergic neurotransmitter that relaxes smooth muscle, may be implicated in the pathophysiology of visceral hypersensitivity in irritable bowel syndrome (IBS). Impaired bioavailability of the nitric oxide precursor molecule L-arginine and higher concentrations of methylarginines (endogenous inhibitors of nitric oxide synthesis) are known to impair nitric oxide synthesis in numerous gastrointestinal cell types. We therefore examined serum concentrations of L-arginine and the methylarginines in a nested case-control study, to assess whether these factors are associated with adult IBS.Data on clinical characteristics, methylarginines, and L-arginine (measured using LC-MS/MS) were collected from a random population-based cohort of Australian adults (median age = 64 years; IQR = 60-70). Cases of IBS, defined according to Rome III criteria (N = 156), and controls (N = 332) were identified from within the cohort at the 5-year follow-up.In adjusted logistic regression analyses, L-arginine, asymmetric dimethylarginine, symmetric dimethylarginine, L-arginine/asymmetric dimethylarginine ratio, and Kessler-10 psychological distress scores were significantly associated with IBS (p 0.05). [Correction added on 18 September 2021, after first online publication: In the preceding sentence, the value (p 0.05) has been changed to (p 0.05)]. Similar results were found for IBS subtypes. Higher serum L-arginine concentration had the strongest association with IBS diagnosis, with an odds ratio of 9.03 for those with serum L-arginine at the 75th (84 μmol/L) versus 25th (46 μmol/L) percentile (95% CI: 5.99-13.62). L-arginine had the best discriminative ability with a bias-adjusted area under the receiver operator characteristic curve of 0.859.Higher serum concentrations of L-arginine and endogenous methylarginines are strongly associated with IBS in adults.

Aim: Estimate the 3-year budget impact in England from 2016/17 of improving nonvalvular atrial fibrillation management in high-risk stroke patients. Materials & methods: The Academic Health Science Network’s AF Business Case Model was used to identify detection, protection (risk assessment and treatment initiation) and perfection (optimized treatment) gaps and to project the budget impact of closing these. Results: Closing all gaps over 3 years could prevent 27,550 strokes. Overall, perfection gap savings were £136,650,962 and protection gap savings were £58,146,171. Detection by screening in year one could cost £149,048,676, but with stroke-prevention savings would be £47,081,047 at 3 years. Thus, total potential savings were £194,797,133 and the cost-adjusted budget impact was £147,716,086. Conclusion: The detection and perfection gaps are key areas for investment.

BACKGROUND Obesity and hypertension prevalence among children are a concern, with limited evidence available on sex and ethnic differences in childhood blood pressure. We aimed to determine the number of children with hypertension and obesity to identify unique adiposity and blood pressure characteristics by sex and ethnicity, and to estimate the odds of having elevated blood pressure with increasing adiposity. METHODS We included 1062 healthy children (5-9 years of age) in an observational school-based study in South Africa. Pediatric validated automated devices were used to measure brachial blood pressure and performed pulse wave analysis to assess central hemodynamics. Standard anthropometry was carried out to determine body composition and demographic questionnaires were completed. RESULTS Almost 20% of children were overweight/obese and 14.1% had elevated blood pressure or hypertension (22.8%). Ethnic differences included greater adiposity in white compared with black children (all P

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne virus endemic to a vast geographical area spanning from Africa to the shores of the Mediterranean Sea and north to the Balkans. The infection carries a high case fatality rate, which prompts the development of new treatment and prophylactic measures. This review explores the different treatment and prophylactic measures found in recent literature. For this purpose, we used Medical Subject Headings (MeSH) as well as PubMed advanced search. The inclusion criteria included full-text studies conducted on humans and in the English language. We found that plasma exchange was associated with a decrease in mortality rates. Similarly, the use of immunoglobulins proved effective in decreasing the severity and mortality risk. Ribavirin use was determined as a post-exposure prophylaxis drug with no statistically significant difference in oral or intravenous routes of administration. More studies should be conducted on CCHF as the number of outbreaks and endemic areas seem to be on the rise. For the time being, supportive therapy along with adjuvant antivirals appear to be the main course of management of CCHF. However, the need for definitive therapeutic agents and guidelines is warranted.

OBJECTIVES The cardiotonic steroid, marinobufagenin (MBG), has been shown to play a physiological natriuretic role in response to salt intake. However, recent studies in clinical and animal models demonstrated possible links between elevated levels of endogenous MBG and increased arterial stiffness. Large artery stiffness is a known predictor of future cardiovascular disease. We, therefore, investigated whether large artery stiffness relates to 24-h urinary MBG excretion in young apparently healthy black and white adults. METHODS This study included data of 711 participants (black 51%, men 42%, mean age 24.8 ± 3.02 years). We measured the carotid-femoral pulse wave velocity (cfPWV), 24-h urinary MBG and sodium excretion. RESULTS In single, partial and multivariable adjusted (Adj.) regression analyses, we found a persistent positive association between cfPWV and MBG excretion in women [Adj. R = 0.23; standardized (std.) β = 0.15; P = 0.002], but not men (Adj. R = 0.17; std. β = 0.06; P = 0.31). Multiple regression models were adjusted for ethnicity, age, waist-to-height ratio, mean arterial pressure, high-density lipoprotein cholesterol, C-reactive protein, γ-glutamyl transferase and glucose. CONCLUSION In conclusion, already at a young age heightened endogenous MBG levels may contribute to large artery stiffness in women via pressure-independent mechanisms, increasing their risk for future cardiovascular disease.

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that affects multiple systems. TSC encompasses neurobehavioral abnormalities that are considered less sensitive and specific to the disease. Autism spectrum disorder, attention deficit disorder, anxiety, mood disorders, and self-injurious behavior (SIB) are neurobehavioral manifestations associated with tuberous sclerosis. Among them, SIB is poorly described and studied. We present a case report and a brief review of the literature, which offers us insight into the pathological mechanism that explains associated SIB in TSC patients and provides a possible multidisciplinary approach to handle this complicated association. The case details a 21-year-old female with tuberous sclerosis who went to the emergency department and then transfer to the psychiatric floor due to aggressive behavior and SIB. The patient had a history of infantile spasm in childhood and generalized tonic-clonic seizures (GTCS); the last episode was four years ago at the age of 17. During the hospital admission, the patient developed an apparent tonic-clonic seizure. Nevertheless, the electroencephalogram (EEG) shows no epileptiform pattern and because of the clinical presentation, it was concluded she had psychogenic nonepileptic seizures (PNES). The patient's CT scan showed a stable appearance of multiple calcified subependymal nodules and left frontal hypodensity. Mini-mental examination (MMSE) revealed mild cognitive impairment. Patients with TSC/SIB have higher frequencies of mental retardation, TSC2 mutations, history of infantile spasms, spike focus in the left frontal lobe. Also, TSC/SIB patients have a higher frequency of tubers in quadrants other than the left posterior neuroanatomical region in left occipital, parietal, and posterior temporal lobes. Our patient had four out of five of the risks factor for developing TSC/SIB. Almost all patients with tuberous sclerosis are expected to develop seizures. Nevertheless, our patient was seizure-free for two years and managed prophylactically with antiepileptic medication. PNES can also occur in patients with tuberous sclerosis. It is essential to be attentive to differentiate PNES from actual seizures due to their history of the high frequency of seizures in TSC. Given the multiple systems involved in the symptomatology of TSC, including the SIB and neurological concerns, multidisciplinary treatment strategies must be implemented. Treatment of TSC with SIB should include antiepileptic drugs covering seizures and managing the SIB's mood component. A neuroleptic could be added for patients who are difficult to manage.

ObjectiveTo assess temporal clinical and budget impacts of changes in atrial fibrillation (AF)-related prescribing in England.MethodsData on AF prevalence, AF-related stroke incidence and prescribing for all National Health Service general practices, hospitals and registered patients with hospitalised AF-related stroke in England were obtained from national databases. Stroke care costs were based on published data. We compared changes in oral anticoagulation prescribing (warfarin or direct oral anticoagulants (DOACs)), incidence of hospitalised AF-related stroke, and associated overall and per-patient costs in the periods January 2011–June 2014 and July 2014–December 2017.ResultsBetween 2011–2014 and 2014–2017, recipients of oral anticoagulation for AF increased by 86.5% from 1 381 170 to 2 575 669. The number of patients prescribed warfarin grew by 16.1% from 1 313 544 to 1 525 674 and those taking DOACs by 1452.7% from 67 626 to 1 049 995. Prescribed items increased by 5.9% for warfarin (95% CI 2.9% to 8.9%) but by 2004.8% for DOACs (95% CI 1848.8% to 2160.7%). Oral anticoagulation prescription cost rose overall by 781.2%, from £87 313 310 to £769 444 028, (£733,466,204 with warfarin monitoring) and per patient by 50.7%, from £293 to £442, giving an incremental cost of £149. Nevertheless, as AF-related stroke incidence fell by 11.3% (95% CI −11.5% to −11.1%) from 86 467 in 2011–2014 to 76 730 in 2014–2017 with adjustment for AF prevalence, the overall per-patient cost reduced from £1129 to £840, giving an incremental per-patient saving of £289.ConclusionsDespite nearly one million additional DOAC prescriptions and substantial associated spending in the latter part of this study, the decline in AF-related stroke led to incremental savings at the national level.

PurposeThe purpose of this study was to use a mouse model of diet-induced obesity to determine if corneal dysfunction begins prior to the onset of sustained hyperglycemia and if the dysfunction is ameliorated by diet reversal.MethodsSix-week-old male C57BL/6 mice were fed a high fat diet (HFD) or a normal diet (ND) for 5-15 weeks. Diet reversal (DiR) mice were fed a HFD for 5 weeks, followed by a ND for 5 or 10 weeks. Corneal sensitivity was determined using aesthesiometry. Corneal cytokine expression was analyzed using a 32-plex Luminex assay. Excised corneas were prepared for immunofluorescence microscopy to evaluate diet-induced changes and wound healing. For wounding studies, mice were fed a HFD or a ND for 10 days prior to receiving a central 2mm corneal abrasion.ResultsAfter 10 days of HFD consumption, corneal sensitivity declined. By 10 weeks, expression of corneal inflammatory mediators increased and nerve density declined. While diet reversal restored nerve density and sensitivity, the corneas remained in a heightened inflammatory state. After 10 days on the HFD, corneal circadian rhythms (limbal neutrophil accumulation, epithelial cell division and Rev-erbα expression) were blunted. Similarly, leukocyte recruitment after wounding was dysregulated and accompanied by delays in wound closure and nerve recovery.ConclusionIn the mouse, obesogenic diet consumption results in corneal dysfunction that precedes the onset of sustained hyperglycemia. Diet reversal only partially ameliorated this dysfunction, suggesting a HFD diet may have a lasting negative impact on corneal health that is resistant to dietary therapeutic intervention.

Background People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. Methods In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. Results At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m(2)) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (allp < 0.047) in PLHIV. Conclusion Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV. The EndoAfrica-NWU study formed part of a broader consortium under the ERAfrica program of the European Union 7th Framework Program. Funding is disbursed via the Department of Science and Innovation in South Africa (contract number DST/CON 0077/2014). AES is funded by the South African National Research Foundation (SARChI GUN 86895) and South African Medical Research Council. PDB and NG received funding from the Belgian Science Policy in Belgium (Grant number BL/67/eranet03), and the Osterreichische Agentur fur internationale Mobilitat und Kooperation in Bildung, Wissenschaft und Forschung, OeAD GmbH (OAD) in Austria (Grant number: KEF-Projekt P202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fourie, CMT (corresponding author), North West Univ, Hypertens Africa Res Team HART, Private Bag X1290, Potchefstroom, South Africa; North West Univ, Fac Hlth Sci, South African Med Res Council, Unit Hypertens & Cardiovasc Dis, Potchefstroom, South Africa. carla.fourie@nwu.ac.za

Background: The impact of a sedentary and unhealthy lifestyle on cardiovascular health is well documented, however the current obesity and hypertension trends among children is concerning. The ExAMIN Youth SA study aims to investigate the impact of lifestyle behaviors (physical fitness/activity, dietary intake and psychosocial factors) involved in early vascular aging among South African children. Methods: This study is an analytical, multidisciplinary, observational cohort study in a school-based setting. We aim to phenotype a cohort of approximately 1000 primary school children (black and white boys and girls between ages 5–9 years) based on current clinical childhood conditions including hypertension and obesity. The primary phenotype is large artery stiffness and retinal microvascular diameters, both biomarkers of early vascular aging. The risk factors and mediators of early vascular ageing and also responsible for the clinical conditions include physical inactivity, unhealthy diet, and life stress. Additionally, urinalysis and salivary analyses will be performed to identify biomarkers related to the pathophysiology of early vascular aging. Discussion: In line with the growing prevalence of obesity and hypertension responsible for the development of early vascular ageing from childhood to adulthood, this study will address the critical areas in which we observe unfavorable arterial modulation related to dietary behaviors, physical inactivity and early life stress. Implementation of novel biological markers may further contribute to our understanding of early cardiovascular adaptations in childhood, and aid in the development of primary prevention programs. Trial registration: The study was retrospectively registered on ClinicalTrials.gov on 15 August 2019 (NCT04056377).

Introduction Low circulating levels of insulin-like growth factor-1 (IGF-1) are associated with endothelial dysfunction, subsequently leading to the development of cardiovascular disease. Objective To better understand the early phases of vascular deterioration in a young, healthy population, we investigated, cross-sectionally, whether biomarkers of endothelial function (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and von Willebrand factor antigen (vWFag)) are associated with IGF-1 in a healthy study population forming part of the larger African Prospective study on the Early Detection and Identification of Cardiovascular diseases and Hypertension (African-PREDICT). Method We included 825 black and white men and women (aged 20–30 years) and determined IGF-1, IGF binding protein-3 (IGFBP-3), ICAM-1, VCAM-1 and vWFag from blood samples. We also measured 24-h blood pressure and health behaviours namely waist circumference, accelerometery, cotinine and gamma glutamyl transferase. We used the IGF-1/IGFBP-3 M ratio as an estimate of bioavailable IGF-1. Results In multivariable-adjusted regression analyses performed in the total group, VCAM-1 associated positively with IGFBP-3 (β = 0.21; p Conclusion VCAM-1 is beneficially associated with IGF-1 in a young healthy cohort, independent of sex, ethnicity, blood pressure and health behaviours – thereby confirming the potential importance of bioavailable IGF-1 in early vascular endothelial protection.

The trachea and esophagus share a common blood supply from a longitudinal artery along the tracheoesophageal groove on each side. Esophagectomy, especially with lymph node dissection, compromises the blood supply to the trachea and carina resulting in ischemia at the anastomosis and predisposing to failure. As a result, combined esophagectomy with circumferential tracheal or carinal resection and reconstruction has been reported only sporadically (1-4).

Consistent reports indicate that hypertension is a particularly common finding in black populations. Hypertension occurs at younger ages and is often more severe in terms of blood pressure levels and organ damage than in whites, resulting in a higher incidence of cardiovascular disease and mortality. This review provides an outline of recent advances in the pathophysiological understanding of blood pressure elevation and the consequences thereof in black populations in Africa. This is set against the backdrop of populations undergoing demanding and rapid demographic transition, where infection with the human immunodeficiency virus predominates, and where under and over-nutrition coexist. Collectively, recent findings from Africa illustrate an increased lifetime risk to hypertension from foetal life onwards. From young ages black populations display early endothelial dysfunction, increased vascular tone and reactivity, microvascular structural adaptions as well as increased aortic stiffness resulting in elevated central and brachial blood pressures during the day and night, when compared to whites. Together with knowledge on the contributions of sympathetic activation and abnormal renal sodium handling, these pathophysiological adaptations result in subclinical and clinical organ damage at younger ages. This overall enhanced understanding on the determinants of blood pressure elevation in blacks encourages (a) novel approaches to assess and manage hypertension in Africa better, (b) further scientific discovery to develop more effective prevention and treatment strategies and (c) policymakers and health advocates to collectively contribute in creating health-promoting environments in Africa.

Meibomian gland dysfunction (MGD) is the leading cause of dry eye disease and loss of ocular surface homeostasis. Increasingly, several observational clinical studies suggest that dyslipidemia (elevated blood cholesterol, triglyceride or lipoprotein levels) can initiate the development of MGD. However, conclusive evidence is lacking, and an experimental approach using a suitable model is necessary to interrogate the relationship between dyslipidemia and MGD. This systematic review discusses current knowledge on the associations between dyslipidemia and MGD. We briefly introduce a diet-induced obesity model where mice develop dyslipidemia, which can serve as a potential tool for investigating the effects of dyslipidemia on the meibomian gland. Finally, the utility of lipidomics to examine the link between dyslipidemia and MGD is considered.

CONTEXT: Obesity is associated with increased incidence of chronic diseases such as type 2 diabetes mellitus, systemic hypertension, and other risk factors for cardiovascular disease. Obesity is also associated with increased use of outpatient clinical services, a metric of health care utilization. However, little is known of temporal changes in health care utilization among obese participants of a medical weight management program. OBJECTIVE: To assess changes in 3 health care utilization metrics (primary care physician office visits, ambulatory clinic office visits, and health care touches [encounters]) in weight management program participants across 21 Kaiser Permanente Northern California Medical Centers during a 5-year period. DESIGN: Retrospective observational study of 10,693 participants, with a linear-mixed effects model to account for repeated-measures analysis. MAIN OUTCOME MEASURES: Five-year temporal changes in the 3 health care metrics. RESULTS: At baseline, the participants’ average age (standard deviation) was 51.1 (12.4) years, and their mean body mass index (standard deviation) was 39.7 (7.2) kg/m(2). At the end of 4 months, there was a decrease in primary care visits (p < 0.001), with an increase in ambulatory clinic visits and health care touches (p < 0.001), because of increased weight management visits. At the end of 5 years, there was a 25% to 35% decrease from baseline in all 3 health care utilization metrics (p < 0.0001). Although slightly attenuated, these findings were similar in a risk-adjusted model. CONCLUSION: Our findings may be useful to other integrated health care delivery systems considering initiating a similar weight management program.

BACKGROUND AND AIM Information regarding the effect of leptin on the vasculature in young healthy adults at risk for cardiovascular disease development is limited. We therefore examined the associations between measures of subclinical atherosclerosis (carotid intima-media thickness, carotid cross-sectional wall area), large artery stiffness (pulse wave velocity) and a measure of endothelial dysfunction (von Willebrand factor [vWF]) with leptin in young healthy men and women. METHODS In a cross-sectional study in South Africa involving 820 normotensive individuals (337 men and 483 women) aged 20-30 years, we measured carotid intima-media thickness, carotid cross-sectional wall area, pulse wave velocity, vWF from citrated plasma and leptin from serum. RESULTS Despite sevenfold higher leptin in women than men (P

Aims Plasminogen activator inhibitor-1 (PAI-1), traditionally associated with fibrinolysis, is increasingly implicated in impaired vascular function. However, studies on its association with microvascular function are limited to the cutaneous and coronary microvascular beds in older and diseased individuals. To better understand its potential involvement in the early stages of disease development, we investigated the associations of retinal vasodilatory responses to flicker light with PAI-1 activity (PAI-1act) in young and healthy individuals. Methods We included healthy Black and White women and men (n = 518; aged 20–30 years), and measured plasma PAI-1act and retinal vasodilatory responses to flicker light provocation. We also collected demographic and lifestyle data, measured blood pressure, anthropometry, blood lipids, inflammatory and other biomarkers. Results In multivariate regression analyses, maximal retinal venular dilation associated independently and inversely with PAI-1act (adj. R2 = 0.11; β = −0.15; p = 0.001) in the total group. In exploratory subgroup analyses, this association remained in White women (adj. R2 = 0.07; β = −0.23; p = 0.005), and was more robust with younger age and lower blood pressure and in non-smokers, but also with greater central adiposity, higher low-density lipoprotein cholesterol and inflammation (all p Conclusions Our data suggest that in young individuals, PAI-1 may already be associated with subclinical microvascular dysfunction.

Purpose : To report peri-operative fractionated high-dose-rate (HDR) brachytherapy with a 3D customized Freiburg flap applicator to treat locally recurrent Wilms’ tumor, followed by immediate hyperthermic intraperitoneal chemotherapy for a 16-year-old with a second recurrence of nephroblastoma (Wilms’ tumor). Material and methods: The tumor was excised and surgical bed was treated with fractionated HDR brachytherapy using a Freiburg flap applicator. Hyperthermic intraperitoneal chemotherapy was performed immediately after the removal of brachytherapy applicator. Results: The Freiburg flap was successfully reconstructed to enable delivery of conformable peri-operative HDR brachytherapy. The clinical target volume (CTV) D90 was 26 Gy in 5 fractions. Conclusions : Peri-operative fractionated HDR brachytherapy with a customized Freiburg flap applicator was delivered successfully across a large multi-disciplinary team.

Background Black populations exhibit lower concentrations of the cardioprotective peptide, insulin-like growth factor-1 (IGF-1), and are more prone to develop hypertensive heart disease than whites. We therefore determined whether lower IGF-1 in black individuals relates to a marker of cardiac overload and systolic dysfunction, namely N-terminal prohormone B-type natriuretic peptide (NT-proBNP). Materials and methods We included 160 black and 195 white non-diabetic South African men and women (aged 44.4 ± 9.81 years), and measured ambulatory blood pressure, NT-proBNP, IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3). Results Although the black group presented elevated ambulatory blood pressure accompanied by lower IGF-1 compared to the white group (all p

Clinical data advocating an adverse effect of obesity on left ventricular (LV) systolic function independent of comorbidities is controversial. We hypothesized that in obesity with prediabetic insulin resistance, circulating fatty acids (FAs) become a valuable fuel source in the maintenance of normal systolic function.Male Wistar rats were fed a high caloric diet for 32 weeks to induce obesity. Myocardial LV systolic function was assessed using echocardiography and isolated heart preparations.Aortic output was reduced in obese rat hearts over a range of filling pressures (for example: 15 cmH2O, obese: 32.6 ± 1.2 ml/min vs control: 46.2 ± 0.9 ml/min, P .05) when perfused with glucose alone. Similarly, the slope of the LV end-systolic pressure-volume relationship decreased, and there was a right shift in the LV end-systolic stress-strain relationship as determined in Langendorff perfused, isovolumic rat heart preparations in the presence of isoproterenol (10(-8)M) (LV systolic stress-strain relationship and a reduced load-independent intrinsic systolic myocardial function, obese: 791 ± 62 g/cm(2) vs control: 1186 ± 74 g/cm(2), P .01). The addition of insulin to the perfusion buffer improved aortic output, whereas the addition of FAs completely normalized aortic output. LV function was maintained in obese animals in vivo during an inotropic challenge.Elevated circulating FA levels may be important to maintain myocardial systolic function in the initial stages of obesity and insulin resistance.

Background: Dyslipidemia may be linked to meibomian gland dysfunction (MGD) and altered meibum lipid composition. The purpose was to determine if plasma and meibum cholesteryl esters (CE), triglycerides (TG), ceramides (Cer) and sphingomyelins (SM) change in a mouse model of diet-induced obesity where mice develop dyslipidemia. Methods: Male C57/BL6 mice (8/group, age = 6 wks) were fed a normal (ND, 15% kcal fat) or an obesogenic high-fat diet (HFD, 42% kcal fat) for 10 wks. Tear production was measured and meibography was performed. Body and epididymal adipose tissue (eAT) weights were determined. Nano-ESI-MS/MS and LC-ESI-MS/MS were used to detect CE, TG, Cer and SM species. Data were analyzed by principal component analysis, Pearson&rsquo, s correlation and unpaired t-tests adjusted for multiple comparisons, significance set at p &le, 0.05. Results: Compared to ND mice, HFD mice gained more weight and showed heavier eAT and dyslipidemia with higher levels of plasma CE, TG, Cer and SM. HFD mice had hypertrophic meibomian glands, increased levels of lipid species acylated by saturated fatty acids in plasma and meibum and excessive tear production. Conclusions: The majority of meibum lipid species with saturated fatty acids increased with HFD feeding with evidence of meibomian gland hypertrophy and excessive tearing. The dyslipidemia is associated with altered meibum composition, a key feature of MGD.

The endogenous Na+/K+-ATPase inhibitor, marinobufagenin (MBG), strongly associates with salt intake and a greater left ventricular mass index (LVMi) in humans and was shown to promote cardiac fibrosis and hypertrophy in animals. The adverse effects of MBG on cardiac remodeling may be exacerbated with obesity, due to an increased sensitivity of Na+/K+-ATPase to MBG. This study determined whether MBG is related to the change in LVMi over time in adults with a body mass index (BMI) &ge, 30 kg/m2 (obese) and &lt, 30 kg/m2 (non-obese). The study followed 275 healthy participants (aged 20&ndash, 30 years) from the African-Prospective study on the Early Detection and Identification of Cardiovascular disease and Hypertension (African-PREDICT) study over 4.5 years. At baseline, we measured 24 h urine MBG excretion. MBG levels were positively associated with salt intake. LVMi was determined by two-dimensional echocardiography at baseline and after &gt, 4.5 years. With multivariate adjusted analyses in obese adults (N = 56), we found a positive association of follow-up LVMi (Adjusted (Adj.) R2 = 0.35, Std. &beta, = 0.311, p = 0.007) and percentage change in LVMi (Adj. R2 = 0.40, = 0.336, p = 0.003) with baseline MBG excretion. No association of LVMi (Adj. R2 = 0.37, p = 0.85) or percentage change in LVMi (Adj. R2 = 0.19, p = 0.68) with MBG excretion was evident in normal weight adults (N = 123). These findings suggest that obese adults may be more sensitive to the adverse cardiac effects of MBG and provide new insight into the potential role of dietary salt, by way of MBG, in the pathogenesis of cardiac remodeling in obese individuals.

Objective: Pulse pressure amplification (PPA) is described as the amplification of pulse pressure from central arteries to the periphery [1] and individuals with a decreased PPA have an increased risk of cardiovascular disease [2]. Adverse changes in PPA are evident in diabetic populations [3]; however, it is unclear whether PPA differs along varying degrees of glycaemia in young healthy populations. We therefore investigated whether PPA is attenuated with higher levels of glycemic markers and whether PPA is associated with glycemic markers independent of other known risk factors. Methods: We included 1195 men and women from the African-PREDICT study, aged 20–30 years, with no prior diagnosis of chronic disease. We determined supine central PP (cPP) using the SphygmoCor XCEL device and PPA was defined as the ratio of the amplitude of the PP between the distal and proximal locations (bPP/cPP). Fasting glucose and glycated haemoglobin were determined and the study population was stratified by tertiles of each glycemic marker. Results: The mean PPA was lower in the highest tertile of fasting glucose when compared to the lowest tertile (1.11 vs. 1.23; p ≤ 0.001). PPA declined with increasing levels of fasting glucose (p–trend ≤ 0.001) after adjustment for age, sex, ethnicity, height, heart rate and mean arterial pressure. In multivariable adjusted regression, we found an independent inverse association between PPA and fasting glucose (β = −0.15, p ≤ 0.001). Conclusion: PPA decreases with an increase in fasting glucose in adults younger than 30 years, exemplifying early vascular changes which may increase future cardiovascular risk. FigurePulse pressure amplification plotted against tertiles of fasting glucose. Values are adjusted for age, sex, heart rate, height and mean arterial pressure. *indicates p-value < 0.05 between the lowest and highest glucose group. Adjusted R2 Pulse pressure amplification 0.15 β (SE) p Age (years) –0.17 (0.03)

Background The endogenous steroidal inhibitor of sodium–potassium-dependent adenosine triphosphate and natriuretic hormone, marinobufagenin, plays a physiological role in ionic homeostasis. Animal models suggest that elevated marinobufagenin adversely associates with cardiac and renal, structural and functional alterations. It remains uncertain whether marinobufagenin relates to the early stages of target organ damage development, especially in young adults without cardiovascular disease. We therefore explored whether elevated 24-hour urinary marinobufagenin excretion was related to indices of subclinical target organ damage in young healthy adults. Design This cross-sectional study included 711 participants from the African-PREDICT study (black 51%, men 42%, 24.8 ± 3.02 years). Methods We assessed cardiac geometry and function by two-dimensional echocardiography and pulse wave Doppler imaging. 24-Hour urinary marinobufagenin and sodium excretion were measured, and the estimated glomerular filtration rate determined. Results Across marinobufagenin excretion quartiles, left ventricular mass ( P 2 = 0.20; β = 0.15; P = 0.043). This relationship between left ventricular mass and marinobufagenin excretion was evident in women (adjusted R2 = 0.06; β = 0.127; P = 0.015) but not in men (adjusted R2 = 0.06; β = 0.007; P = 0.92). Conclusions Left ventricular mass positively and independently associates with marinobufagenin excretion in young healthy adults with excessively high marinobufagenin excretion. Women may be more sensitive to the effects of marinobufagenin on early structural cardiac changes.

There is global consensus on the benefits of reducing excessive salt intake. Indeed, lower salt intake associates with reduced arterial stiffness, a well-established predictor of cardiovascular risk, in older populations. Whether high habitual salt intake in healthy normotensive youth may already contribute to increased arterial stiffness is unknown. We, therefore, determined whether estimated salt intake is associated with large artery stiffness in young healthy black and white adults.We included 693 black and white adults (51% black; 42% men), aged 20-30 years. Participants were normotensive based on clinic blood pressure, and no previous diagnosed chronic illnesses. We measured carotid femoral pulse wave velocity (cfPWV) and determined estimated salt intake based on 24 h urinary sodium excretion.We found estimated salt consumption of 5 g/day in 47% of our population, whereas 21% consumed 10 g/day. In multivariable-adjusted regression analyses a positive association existed between estimated salt intake and cfPWV in the total group (Adj. RExcessive salt intake is positively associated with large artery stiffness-independent of blood pressure-in young adults, especially in black individuals. Our results suggest a potential contributory role of salt consumption towards early vascular aging.

Insulin-like growth factor 1 (IGF-1), an insulin sensitivity and vasculoprotective factor, associates negatively with the metabolic syndrome. However, IGF-1 is reduced by factors such as inflammation, oxidative stress and liver dysfunction. We investigated the relationship between bioavailable IGF-1 and the number of metabolic syndrome components and determined whether this relationship is independent of inflammation, oxidative stress and gamma glutamyl transferase (γ-GT; a marker of liver dysfunction). This study included 907 black and white participants stratified by sex (aged 43.0±11.8 years). Among them 63 participants had fasting glucose levels of ≥+7.0+mmol/l and/or used diabetes medication. Via standard methods we determined waist circumference, fasting glucose, triglycerides, high-density lipoprotein cholesterol and blood pressure. We also determined high-sensitivity C-reactive protein (CRP), reactive oxygen species (ROS), γ-GT, IGF-1 and insulin-like growth factor binding protein 3 (IGFBP-3). IGF-1/IGFBP-3 was used as an estimate of bioavailable IGF-1. Total IGF-1 was similar between men and women (p=0.10), however, bioavailable IGF-1 was lower in women (p

Adipose tissue macrophages (ATMs) play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet (HFD)-induced obesity has been shown to lead to ATM accumulation in rodents; however, the impact of hyperglycemia on ATM dynamics in HFD-fed type 2 diabetic models has not been studied. We previously showed that hyperglycemia induces the appearance of proinsulin (PI)-producing proinflammatory bone marrow (BM)-derived cells (PI-BMDCs) in rodents. We fed a 60% HFD to C57BL6/J mice to produce an obese type 2 diabetes model. Absent in chow-fed animals, PI-BMDCs account for 60% of the ATMs in the type 2 diabetic mice. The PI-ATM subset expresses TNF-α and other inflammatory markers, and is highly enriched within crownlike structures (CLSs). We found that amelioration of hyperglycemia by different hypoglycemic agents forestalled PI-producing ATM accumulation and adipose inflammation in these animals. We developed a diphtheria toxin receptor-based strategy to selectively ablate PI-BMDCs among ATMs. Application of the maneuver in HFD-fed type 2 diabetic mice was found to lead to near total disappearance of complex CLSs and reversal of insulin resistance and hepatosteatosis in these animals. In sum, we have identified a novel ATM subset in type 2 diabetic rodents that underlies systemic insulin resistance.—Buras, E. D., Yang, L., Saha, P., Kim, J., Mehta, P., Yang, Y., Hilsenbeck, S., Kojima, H., Chen, W., Smith, C. W., Chan, L. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice.

The role the human immunodeficiency virus (HIV) and antiretroviral treatment on endothelial activation, and the subsequent relationship with cardiovascular disease, is not well understood. We investigated endothelial activation, inflammatory and cardiometabolic profiles, and measures of vascular structure and function of 66 antiretroviral treated (ART), 78 never-treated (no-ART) HIV infected and 165 HIV free Africans. Methods Blood samples were obtained for biochemical analysis and blood pressure, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) measurements were performed. Results The HIV infection duration was at least five years and the treatment 2.86 ± 0.13 years. The intracellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) levels were elevated in the HIV infected groups compared to the controls. The odds of higher adhesion molecule levels were increased when HIV infected (especially in the no-ART group); OR no-ART vs. no-HIV: ICAM 3.92 (2.2–7.0); VCAM 16.2 (7.5–35). ICAM and VCAM associated with HIV status and interleukin-6 (IL-6) in the total group (all p < 0.01). In both HIV infected groups VCAM associated inversely with CD4 counts (no-ART: β = −0.28, p = 0.01; ART: β = −0.22, p = 0.07) and TC (no-ART: β = −0.36, p < 0.01; ART: β = −0.27, p = 0.03). The ART group had an unfavourable lipid profile compared to the no-ART group. The inflammatory markers (C-reactive protein (CRP) and IL-6), PWV and IMT did not differ between the three groups. Conclusion HIV infected Africans showed endothelial activation when compared to HIV free controls. The endothelial activation was not accompanied by increased inflammation (as measured with CRP and IL-6), arterial stiffness or sub-clinical atherosclerosis.

Evidence of the relationship between left ventricular hypertrophy and urinary albumin excretion is contradictory and limited in black adults in whom hypertensive heart disease is common. We aimed to investigate the relationship between subclinical left ventricular hypertrophy and albuminuria in non-diabetic hypertensive blacks. Urinary albumin-to-creatinine ratio (UACR) was determined from 8-hour overnight urine collection. We recorded ambulatory blood pressure and 12-lead electrocardiogram during a typical working day. Cornell product (P = .002), UACR (P = .042), 24-hour systolic pressure (P .0001), and 24-hour pulse pressure (P .0001) were higher in the hypertensive group. Cornell product was associated with UACR in single (r = 0.25; P = .012), partial (P trend = .002), and multiple regression (β = 0.326; P = .0005) analyses in the hypertensive group only, even below the threshold for microalbuminuria and independent of 24-hour systolic pressure. Urinary albumin excretion is associated with subclinical left ventricular hypertrophy in non-diabetic hypertensive blacks and may be a useful marker of early cardiovascular disease in blacks.

This case study focused on pressure, stereotype threat, choking, and the coping experiences of the New Zealand All Blacks rugby team during the period from 2004-2011 leading into their success at the 2011 Rugby World Cup (RWC). Employing a narrative approach this case study examined public expectation, pressure, and coach-led coping strategies designed to “avoid the choke” by the All Blacks team. An in-depth interview was completed with one of the All Blacks’ coaches and analyzed via collaborative thematic analysis (Riessman, 2008). In addition multiple secondary data sources (e.g., coach & player autobiographies; media interviews) were analyzed via holistic-content analysis (Lieblich et al., 1998). Collectively these analyses revealed five key themes: public expectation and pressure, learning from 2007 RWC, coping with RWC pressure, decision-making under pressure, and avoiding the choke. Practical recommendations are offered for team sport coaches with respect to coping with pressure and avoiding choking.

γδ T cells are resident in AT and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5 to 10 week milk HFD. The HFD resulted in significant increases in CD44hi, CD62Llo, and TNF-α+ γδ T cells in eAT of WT mice. Mice deficient in all γδ T cells (TCRδ−/−) or only Vγ4 and Vγ6 subsets (Vγ4/6−/−) were compared with WT mice with regard to proinflammatory cytokine production and macrophage accumulation in eAT. Obesity among these mouse strains did not differ, but obese TCRδ−/− and Vγ4/6−/− mice had significantly reduced eAT expression of F4/80, a macrophage marker, and inflammatory mediators CCL2 and IL-6 compared with WT mice. Obese TCRδ−/− mice had significantly reduced CD11c+ and TNF-α+ macrophage accumulation in eAT after 5 and 10 weeks on the HFD, and obese Vγ4/6−/− mice had significantly increased CD206+ macrophages in eAT after 5 weeks on the diet and significantly reduced macrophages after 10 weeks. Obese TCRδ−/− mice had significant reductions in systemic insulin resistance and inflammation in liver and skeletal muscle after longer-term HFD feeding (10 and 24 weeks). In vitro studies revealed that isolated γδ T cells directly stimulated RAW264.7 macrophage TNF-α expression but did not stimulate inflammatory mediator expression in 3T3-L1 adipocytes. These findings are consistent with a role for γδ T cells in the proinflammatory response that accompanies diet-induced obesity.

High-fat diet (HFD) feeding in mice is characterized by accumulation of αβ T cells in adipose tissue. However, the contribution of αβ T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of αβ T cells on insulin sensitivity and inflammatory state of skeletal muscle and adipose tissue in obesity. Furthermore, we investigated whether CD4+IFNγ+ (TH1) cells are involved in skeletal muscle and adipose tissue metabolic dysfunction that accompanies obesity.Mice lacking αβ T cells (T cell receptor beta chain-deficient [TCRb-/-] mice) were fed HFD for 12 weeks. Obesity-induced skeletal muscle and adipose tissue inflammation was assessed by flow cytometry and quantitative RT-PCR. To investigate the effect of TH1 cells on skeletal muscle and adipose tissue inflammation and metabolic functions, we injected 5×10(5) TH1 cells or PBS weekly over 12 weeks into HFD-fed TCRb-/- mice. We also cultured C2C12 myofibers and 3T3-L1 adipocytes with TH1-conditioned medium.We showed that similar to adipose tissue, skeletal muscle of obese mice have higher αβ T cell content, including TH1 cells. TCRb-/- mice were protected against obesity-induced hyperglycemia and insulin resistance. We also demonstrated suppressed macrophage infiltration and reduced inflammatory cytokine expression in skeletal muscle and adipose tissue of TCRb-/- mice on HFD compared to wild-type obese controls. Adoptive transfer of TH1 cells into HFD-fed TCRb-/- mice resulted in increased skeletal muscle and adipose tissue inflammation and impaired glucose metabolism. TH1 cells directly impaired functions of C2C12 myotubes and 3T3-L1 adipocytes in vitro.We conclude that reduced adipose tissue and skeletal muscle inflammation in obese TCRb-/- mice is partially attributable to the absence of TH1 cells. Our results suggest an important role of TH1 cells in regulating inflammation and insulin resistance in obesity.

Background Increased urinary albumin excretion reflects general vascular damage and predicts adverse cardiovascular and renal outcomes. Albuminuria can be determined from easily collected spot urine samples, especially in low-resource settings. However, no prognostic evidence exists for Africans. Methods We followed clinical outcomes in 1,061 randomly selected non diabetic, human immunodeficiency virus (HIV)-negative Africans (mean age: 51.5 years; 62.0% women). Baseline urinary albumin-to-creatinine ratio was assessed from spot urine samples. Results Over a median follow-up of 4.52 years, 132 deaths occurred, of which 47 were cardiovascular related. The urinary albumin-to-creatinine ratio averaged 6.1 μg/mg (5th to 95th percentile interval; 1.2-70.0). In multivariable-adjusted analyses, urinary albumin excretion predicted all-cause mortality (hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.07-1.48; P = 0.006), and a tendency existed for cardiovascular mortality (HR, 1.26; 95% CI, 0.97-1.63; P = 0.087), which seemed to be driven by fatal stroke (HR, 1.72; 95% CI, 1.17-2.54; P = 0.006) rather than cardiac mortality (HR, 0.67; 95% CI, 0.41-1.07; P = 0.094). The predictive value remained in 528 hypertensives for both all-cause (HR, 1.38; 95% CI, 1.13-1.69; P = 0.001) and cardiovascular (HR, 1.45; 95% CI, 1.07-1.96; P = 0.017) mortality, again driven by stroke. Our findings also remained significant after we excluded participants with macroalbuminuria, those on antihypertensive treatment, as well as participants who died within 1 year after enrollment. Conclusion In nondiabetic HIV-negative Africans, albuminuria predicts all-cause and stroke mortality.

It is known that low testosterone (T) and high cortisol levels are associated with hypertension as well as with chronic stress, linking stress with elevated blood pressure (BP). However, the association between acute stress-, chronic stress responses and BP is not clear in Africans. Therefore, we examined the association between cortisol, psychological distress and BP responses in low- and high-T male subgroups. Beat-to-beat and ambulatory blood pressure (ABPM) and electrocardiogram measures were obtained. Serum samples were collected and analyzed for sex hormones and cortisol. Chronic psychological distress was verified with the General Health Questionnaire and acute stress with the cold pressor test. More chronic psychological distress was observed in both low- and high-T Africans compared with the Caucasians. The low-T Africans tended to have more ischemic events (P=0.06) and ABPM values (Pless than or equal to0.01) than any of the other groups. Both chronic distress (cortisol) and acute stress (total peripheral resistance cold pressor responses) were associated with ABPM in the low-T African group. Acute and chronic stress may contribute to increased BP in low-T African men. Their cortisol and vascular responses supported a tendency for ischemia, increasing their risk for coronary artery disease. http://www.nature.com/jhh/journal/v28/n6/abs/jhh2013124a.html

Globally the prevalence of non-communicable diseases, such as hypertension and type 2 diabetes, are escalating. Metabolomic studies indicated that circulating branched chain amino acids (BCAAs) are associated with insulin resistance, coronary artery disease and increased risk for cardiovascular events. We aimed to extend the current understanding of the cardiovascular risk associated with BCAAs. We explored whether BCAAs are related to markers of cardiovascular disease in a bi-ethnic population and whether this relationship was influenced by chronic hyperglycaemia. We included 200 African and 209 Caucasian participants, and determined their ambulatory blood pressure and carotid intima-media thickness (cIMT). We analysed blood samples for glycated haemoglobin (HbA1c) and BCAAs. Participants were stratified into two groups according to their HbA1c value using the median cut-off value of 5.6 %. Ambulatory BP, cIMT and BCAAs were significantly higher (all p < 0.001) in the high HbA1c group. Single regression analyses indicated significant positive associations of ambulatory blood pressure and cIMT with BCAAs (all p < 0.05) in both the groups. These associations between ambulatory systolic blood pressure (SBP) (r = 0.16, p = 0.035) and cIMT (r = 0.22, p = 0.004) with BCAAs remained in the high HbA1c group after adjusting for age, gender, ethnicity and body mass index (BMI) and were confirmed in multiple regression analyses (ambulatory SBP: R2 = 0.17, β = 0.21, p = 0.005 and cIMT: R2 = 0.30, β = 0.19, p = 0.003). Our results demonstrate that BCAAs are independently related to ambulatory BP and cIMT in individuals with high HbA1c levels and suggest that potential cardiovascular deterioration accompany the rise in BCAAs in conditions of hyperglycaemia.

Background Methylarginines are endogenous nitric oxide synthase inhibitors that have been implicated in depression. This study measured serum concentrations of l -arginine, asymmetric (ADMA) and symmetric (SDMA) dimethylarginine in a representative sample of older community-dwelling adults and determined their association with incident depression over 6-years of follow-up. Methods Data on clinical, lifestyle, and demographic characteristics, methylated arginines, and l -arginine (measured using LC–MS/MS) were collected from a population-based sample of older Australian adults (Median age=64 years; IQR=60–70) from the Hunter Community Study. Clinical depression was defined as a Centre for Epidemiological Studies Depression Scale (CES-D) score ≥16 or use of antidepressant medications. Results In adjusted analyses ADMA (Q3), SDMA (Q2), l -arginine (Q2), gender, and asthma remained statistically significant predictors of incident depression at follow-up. Quartile 3 of ADMA concentration was associated with 3.5 times the odds of developing depression compared with Q1 (OR=3.54; 95% CI: 1.25–9.99). Limitations Limitations of our study include the use of a subjective self-reported questionnaire tool using a dichotomous cut-off, together with use of antidepressant medications, as proxies for clinical depression. Moreover, similarly to most population studies on methylated arginines, the measurement of ADMA and SDMA from blood does not necessarily reflect intracellular concentrations of these compounds. Finally, there were no measures of nitric oxide metabolites to determine if these levels were altered in the presence of elevated methylarginines and depression. Conclusions After adjusting for clinical, demographic, biochemical, and pharmacological confounders, higher serum ADMA was independently associated with incident depression at 6-years follow-up.

BACKGROUND Heart failure in the African population is reaching alarming levels. Increased afterload as a result of increased vasoconstriction during stress may lead to impaired ventricular function and stroke volume (SV) as well as vascular hypertrophy. In this study, we challenged the cardiovascular system in order to evaluate the possible contribution of indicators of α-adrenergic vasoconstriction (i.e., vascular resistance and SV reactivity) on left ventricular mass and carotid intima-media thickness (CIMT) in African and Caucasian men. METHODS We evaluated 101 African and 101 Caucasian male schoolteachers. Ambulatory blood pressure measurements were taken. Total peripheral resistance, Windkessel compliance and SV, and resting and reactivity values were obtained using a Finometer device while the Stroop color word conflict test was being applied. The electrocardiogram was recorded to obtain the Cornell product as indication of left ventricular mass. The CIMT was measured and the cross-sectional wall area (CSWA) calculated. RESULTS African men showed higher total vascular resistance resting values as well as higher positive reactivity values compared with Caucasian men. The SV decreased significantly during stress in African men while resting blood pressure and the Cornell product value increased. SV showed a consistent association with left ventricular mass (β = -0.21; P = 0.04) and CSWA (β = -0.24; P = 0.01) in single and multiple regression analyses. No such associations were evident in the Caucasian men. CONCLUSIONS African men showed a suppressed SV, possibly as a result of an increased ventricular afterload leading to end-organ damage.

Correction to: Hypertension Research (2016) 39, 730–736; doi:10.1038/hr.2016.48; published online 19 May 2016 After online publication of this article, the authors noticed an error in the affiliation of the list of authors. The affiliation of Rudolph Schutte and Walthard Vilser was wrong. The error has now been rectified, and the article with correct authors’ affiliations now appears in this issue.

Background Hypertensive heart disease is a rising concern, especially among black South African women. As high sensitivity cardiac troponin T (cTnT) is a marker of cardiomyocyte damage, we determined the potential link of (i) systemic endothelial dysfunction (reflected by urinary albumin-to-creatinine ratio), (ii) large artery stiffness, (iii) cardiac volume load (estimated by the N-terminal prohormone B-type natriuretic peptide (Nt-proBNP)), and (iv) ECG left ventricular hypertrophy in post-menopausal black women. Methods In 121 (50 normotensive and 71 hypertensive) black women (mean age: 60.6 years), basic cardiovascular assessments including blood pressure and ECG were performed, along with plasma and urinary biomarkers including cTnT. Results The cTnT levels (p=0.049) along with Nt-proBNP (p=0.003), pulse pressure (p

Objective To clarify possible associations between cataract surgery and progression of age-related macular degeneration (AMD). Design Clinic-based cohort. Participants We followed cataract surgical patients aged 65+ years in the Australian Cataract Surgery and Age-related Macular Degeneration (CSAMD) study. Patients who remained unilaterally phakic for at least 24 months after recruitment were included. Methods We performed annual examinations with retinal photography. We assessed AMD using side-by-side grading of images from all visits. Paired comparisons between operated and nonoperated fellow eyes (defined as nonoperated or operated Main Outcome Measures Incident early AMD was defined as the new appearance of soft indistinct/reticular drusen or coexisting retinal pigmentary abnormality and soft distinct drusen in eyes at risk of early AMD. Incident late AMD was defined as the new appearance of neovascular AMD or geographic atrophy (GA) in eyes at risk of late AMD. Results Among 2029 recruited, eligible participants, 1851 had cataract surgery performed at Westmead Hospital, Sydney, and 1244 (70.7%) had 36-month postoperative visits. Of these participants, 1178 had gradable photographs at baseline and at least 1 follow-up visit. Of 308 unilaterally operated participants at risk of late AMD, this developed in 4 (1.3%) operated and 7 (2.3%) nonoperated fellow eyes (odds ratio [OR], 0.74; 95% confidence interval [CI], 0.23–2.36) after adjusting for the presence of early AMD at baseline. Of 217 unilaterally operated participants at risk of early AMD, this developed in 23 (10.6%) operated and 21 (9.7%) nonoperated fellow eyes (OR, 1.07; 95% CI, 0.74–1.65). Incident retinal pigment abnormalities were more frequent in operated than nonoperated fellow eyes (15.3% vs. 9.9%; OR, 1.64; 95% CI, 1.07–2.52). There was no difference in the 3-year incidence of large soft indistinct or reticular drusen between the 2 eyes (8.8% vs. 7.9%; OR, 1.12; 95% CI, 0.79–1.60). Conclusions Prospective follow-up data and paired eye comparisons of this older surgical cohort showed no increased risk of developing late AMD, early AMD, or soft/reticular drusen over 3 years. There was a 60% increased detection of retinal pigmentary changes in surgical eyes. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Hypertension and obesity are serious health burdens in sub-Saharan Africa. Urbanized Africans seem to be more susceptible to the development of these diseases than Caucasians. Current research suggests that leptin may be an important contributor to the development of hypertension and atherosclerosis. The aim of this study was to investigate leptin levels and their associations with cardiovascular function in urbanized Africans and Caucasians. Serum leptin, ambulatory blood pressure and carotid intima-media thickness were measured, and the cross-sectional wall area (CSWA) was calculated. The results showed that Africans had higher leptin levels (P

Background Previous studies have shown variable correlation of patients’ self-assessed skin severity measures and clinician-assessed objective measures of severity. But, generally, correlation has not been as good as might be expected for conditions in which the objective physical extent of skin disease is apparent to the sufferer to an extent that is not applicable in many other diseases. Methods This paper reports agreement and correlation of self-assessed and objective severity measures in a study of 108 subjects with acne, psoriasis, or atopic eczema. The study was a cross-sectional study examining psychological associations of these skin diseases. Objective severity was assessed with the Leeds technique (acne), the Psoriasis Area and Severity Index, and Six Area Six Sign Atopic Dermatitis instruments. Agreement is a more appropriate measure than correlation in this situation and was measured with weighted kappa, while correlation was measured with Spearman’s rank correlation. Results There was a modest correlation of ρ = 0.46 and similarly very modest agreement of 0.35 (weighted kappa) of self-assessed and clinician-assessed disease severity. Furthermore, self-assessed (but not clinician-assessed) severity was statistically associated with psychological morbidity in this study; i.e. – depression, anxiety, and overall psychological morbidity. Conclusions Clinicians should consider psychological sequelae of skin disease, not only in those with objectively more severe disease but in patients across the severity spectrum. Both observational and interventional studies of skin disease should include both clinician-assessed and self-assessed measures of severity among assessed variables.

We studied the effects of weight loss induced by either a low-fat normal diet (ND) or restriction of high-fat diet (HFD) on hepatic steatosis, inflammation in the liver and adipose tissue (AT), and blood monocytes of obese mice.In mice with HFD-induced obesity, weight loss was achieved by switching from HFD to ND and maintaining on ND ad libitum or by restricting HFD intake to match body weight of mice with ND-induced weight loss. After diet interventions for 4 weeks, hepatic steatosis, hepatic and AT inflammation, and blood CD11c(+) monocytes were examined.At 4 weeks after switching diets, body weight was reduced by 23% from baseline. To achieve the same reduced body weight required restricting calorie intake from HFD. Weight loss with either ND or HFD restriction decreased body fat mass and ameliorated liver steatosis; both effects were greater with ND-induced weight loss than HFD restriction-induced weight loss. Weight loss with ND but not HFD restriction normalized blood CD11c(+) monocytes and attenuated hepatic inflammation assessed by chemokine and CD11c expression. In contrast, weight loss with HFD restriction significantly reduced chemokine levels and CD11c(+) cells in AT compared to obese controls, and tended to reduce AT chemokines and CD11c(+) cells more than ND-induced weight loss.In mice with diet-induced obesity, weight loss with ND was superior in alleviating hepatic inflammation and steatosis, whereas weight loss with HFD calorie restriction provided greater amelioration of AT inflammation.

A woman in her late 20s presented one week after an abdominoplasty surgical procedure to the emergency room complaining of shortness of breath and chest pain. A chest computed tomography angiogram (CTA) pulmonary embolism protocol (PE) was ordered to rule out acute PE. The CTA study was negative for PE, but an incidental finding of complete obstruction of the right subclavian vein was noted.

Pro-inflammatory and stress-activated signalling pathways are important role players in the pathogenesis of obesity and insulin resistance. Obesity and type II diabetes are associated with chronic, low-grade inflammation and elevated tumour necrosis factor-α (TNF-α) levels. There is increasing evidence that TNF-α may play a critical role in skeletal muscle atrophy. However, the effects of obesity-induced insulin resistance on these signalling pathways are poorly understood in skeletal muscle. Therefore, the present study addressed the effects of obesity-induced insulin resistance on the activity of the ubiquitin ligases, nuclear factor-κB, p38 MAPK and phosphoinositide 3-kinase signalling pathways in the gastrocnemius muscle and compared these with muscle of standard chow-fed control rats. Male Wistar rats were randomly allocated to a control diet group (standard commercial chow; 60% carbohydrates, 30% protein and 10% fat) or a cafeteria diet group (65% carbohydrates, 19% protein and 16% fat) for 16 weeks. Blood analysis was conducted to determine the impact of the model of obesity on circulating insulin, glucose, free fatty acids, TNF-α and angiotensin II concentrations. The experimental animals were 18% heavier and had 68% greater visceral fat mass than their control counterparts and were dyslipidaemic. Significant increases in the ubiquitin ligase and MuRF-1, as well as in caspase-3 and poly-ADP-ribose polymerase cleavage were observed in the muscle of obese animals compared with the control rats. We propose that dyslipidaemia may be a mechanism for the activation of inflammatory/stress-activated signalling pathways in obesity and type II diabetes, which will lead to apoptosis and atrophy in skeletal muscle.

Tumor infiltration of immune cells (polymorphonuclear cells [PMNs] and macrophages) was initially thought to be an attempt by the host organism to combat malignancy. It appears, however, that certain subsets of chronically activated immune cells likely promote tumor growth, facilitate tumor cell survival and aid in metastasis. The association between tumor cells and tumor-associated PMNs has been demonstrated in several types of cancer, but the presence of tumor-associated PMNs in pancreatic cancer has not been well studied in vivo. Intercellular adhesion molecule-1 (ICAM-1) functions in cell–cell and cell–extracellular matrix adhesion and has a physiological role in PMN tight adhesion of leukocytes via interaction with the ligands LFA-1 and Mac-1. Increased ICAM-1 expression correlates with poor prognosis in pancreatic cancer. Therefore, the aim of this study was to investigate the function of ICAM-1 and tumor-associated PMNs in pancreatic cancer progression using ICAM-1-null (ICAM-1−/−) mice. We hypothesize that ICAM-1 null mice have decreased pancreatic cancer progression. Surprisingly, there is no significant difference in pancreatic cancer progression in wild-type versus ICAM-1 null mice. Interestingly, we found that tumor-derived ICAM-1 co-localizes with host PMNs at the leading edge of the tumor in ICAM-1 null mice. These results suggest that tumor-derived ICAM-1 is a sufficient ligand for tumor-associated PMNs and may play a role in subsequent tumor growth and metastasis.

Background There is a considerable number of studies linking acne with psychological and psychiatric morbidities, although this literature is not entirely consistent and is largely cross-sectional in methodology. Objective This study aims to establish the relationship of acne and psychological and psychiatric morbidity in adolescents in a community setting and, via a longitudinal methodology, provide evidence for causality in the relationship. Methods The study was a 12-month cohort study. Two hundred and forty-four students in Years 8, 9 and 11 (ages 14–17) at four Australian high schools were assessed at baseline 6 months and 12 months. Presence and severity of acne were assessed, along with a number of psychological and psychiatric morbidities and personality traits (depression, anxiety, overall psychiatric morbidity, self-consciousness, neuroticism and introversion/extraversion) and other demographic variables. Results Of the 244 participating students, 209 (86%) completed all three rounds of data collection. A further 26 (11%) completed two rounds. The study failed to demonstrate an association of the presence of acne or of acne severity with the examined measures of psychological and psychiatric morbidity, and no evidence for an effect of acne in their causation. Conclusion The relationship of acne and psychological morbidities found in previous health care settings was not found in this community sample. This may be due to differences between community and clinical acne populations. Other possible reasons for this finding are attenuation of psychological morbidity in subjects in this study by successful acne treatment, and the role of personality traits in the complex relationship between acne and psychological morbidities. It is suggested that this relationship would be best investigated by means of longer-term cohort studies enlisting subjects at an zearly age, prior to the onset of acne.

Malnutrition among the rural Bangladeshi women of reproductive age is still very high. This high prevalence attributes to a range of adverse health consequences on the women and their offspring. A total of 2341 women aged between 20 and 45 years residing in the study area were interviewed in this cross-sectional study. Information on socioeconomic variables, nutritional status, and pregnancy-related history was obtained using interviewer administered questionnaire. A total of 34% of the reproductive aged rural women suffer from malnutrition. A multivariate analysis shows association between malnutrition and monthly household income, history of taking oral contraceptive, current pregnancy status, and history of breastfeeding. The final regression model shows a statistically significant decreasing trend in malnutrition status with increasing income ( P for trend