C-type natriuretic peptide is a pivotal regulator of metabolic homeostasis

Thermogenesis and adipogenesis are tightly regulated mechanisms that maintain lipid homeostasis and energy balance; dysfunction of these critical processes underpins obesity and contributes to cardiometabolic disease. C-type natriuretic peptide (CNP) fulfills a multimodal protective role in the cardiovascular system governing local blood flow, angiogenesis, cardiac function, and immune cell reactivity. Herein, we investigated a parallel, preservative function for CNP in coordinating metabolic homeostasis. Global inducible CNP knockout mice exhibited reduced body weight, higher temperature, lower adiposity, and greater energy expenditure in vivo. This thermogenic phenotype was associated with increased expression of uncoupling protein-1 and preferential lipid utilization by mitochondria, a switch corroborated by a corresponding diminution of insulin secretion and glucose clearance. Complementary studies in isolated murine and human adipocytes revealed that CNP exerts these metabolic regulatory actions by inhibiting sympathetic thermogenic programming via G(i)-coupled natriuretic peptide receptor (NPR)-C and reducing peroxisome proliferator-activated receptor-γ coactivator-1α expression, while concomitantly driving adipogenesis via NPR-B/protein kinase-G. Finally, we identified an association between CNP/NPR-C expression and obesity in patient samples. These findings establish a pivotal physiological role for CNP as a metabolic switch to balance energy homeostasis. Pharmacological targeting of these receptors may offer therapeutic utility in the metabolic syndrome and related cardiovascular disorders

The incidence of healthcare use, ill health and mortality in adults with intellectual disabilities and mealtime support needs

This is the final published version. It first appeared at http://onlinelibrary.wiley.com/doi/10.1111/jir.12167/full.Background\ud Adults with intellectual disabilities (ID) experience a wide range of eating, drinking and/or swallowing (EDS) problems, for which they receive diverse mealtime support interventions. Previous research has estimated that dysphagia (difficulty swallowing) affects 8% of all adults with ID and that 15% require some form of mealtime support. People with ID (whether they require mealtime support or not) also experience a greater burden of ill-health and die younger than their peers in the general population with no ID.\ud \ud Methods\ud Using an exploratory, population-based cohort study design, we set out to explore health-related outcomes in adults with ID who receive mealtime support for any eating, drinking or swallowing problem, by establishing the annual incidence of healthcare use, EDS-related ill-health, and all-cause mortality. This study was conducted in two counties in the East of England.\ud \ud Results\ud In 2009, 142 adults with mild to profound ID and a need for any type of mealtime support were recruited for a baseline survey. At follow-up one year later, 127 individuals were alive; eight had died; and seven could not be contacted. Almost all participants had one or more GP consultations each year (85-95%) and, in the first year, 20% reportedly had one or more emergency hospitalisations. Although their annual number of GP visits was broadly comparable to that of the general population, one-fifth of this population?s primary healthcare use was directly attributable to EDS-related ill-health. Respiratory infections were the most common cause of morbidity, and the immediate cause of all eight deaths, while concerns about nutrition and dehydration were surprisingly minor. Our participants had a high annual incidence of death (5%) and, with a standardised mortality ratio of 267, their observed mortality was more than twice that expected in the general population of adults with ID (not selected because of mealtime support for EDS problems).\ud \ud Conclusions\ud All Annual Health Checks now offered to adults with ID should include questions about respiratory infections and EDS functioning, in order to focus attention on EDS problems in this population. This has the potential to reduce life-threatening illness

Liberalism, lack and living the dream : re-considering youth, consumer sovereignty and the attractions of night-time leisure in Magaluf

Much of the academic literature on alcohol-based leisure focuses on the pleasures of hedonism and youthful cultural exploration in environments free from the prescriptions, pressures and routines of everyday life. In this article – in which we present data from our ongoing ethnographic research exploring the experiences and attitudes of young British tourists in the Spanish resort of Magaluf on the island of Majorca – we argue that the standard liberal social-scientific image of youth leisure is naive and misrepresents its variegated reality. Our research indicates that many young British tourists gain little contentment from their holiday in the sun. Rather than embarking on a leisure experience composed of boundless freedom, choice, indulgence, excess and that is indicative of personal consumer sovereignty, many of our interviewees could identify the regimented and commodified nature of alcohol-based tourism. Rather than satisfaction, they felt an imprecise dissatisfaction. Drawing upon elements of psychoanalytic theory, we argue that underneath our interviewees’ accounts of drunkenness and promiscuity lies an obdurate but imprecise sense of lack. Yet, it is precisely this absence which only recharges their motivation to do more of the same the year after in similar destinations, thus confirming the presence, power and domination of consumer sovereignty

Starch Digestion Enhances Bioaccessibility of Anti-Inflammatory Polyphenols from Borlotti Beans (Phaseolus vulgaris)

The consumption of beans has been associated with chronic disease prevention which may be attributed to the polyphenols present in the seed coat and endosperm. However, their bioaccessibility is likely to be limited by interactions with bean matrix components, including starch, protein and fibre. The aim of this project was to evaluate the effect of domestic processing and enzymatic digestion on the bioaccessibility of polyphenols from Borlotti beans (Phaseolus vulgaris) and to test their anti-inflammatory properties in a macrophage cell model. In vitro digestion of cooked beans released twenty times more polyphenols (40.4 ± 2.5 mg gallic acid equivalents (GAE)/g) than domestic processing (2.22 ± 0.1 mg GAE/g), with starch digestion contributing to the highest release (30.9 ± 0.75 mg GAE/g). Fluorescence microscopy visualization of isolated bean starch suggests that polyphenols are embedded within the granule structure. LC-MS analysis showed that cooked Borlotti bean contain flavonoids, flavones and hydroxycinnamic acids, and cooked bean extracts exerted moderate anti-inflammatory effects by decreasing mRNA levels of IL1β and iNOS by 25% and 40%, respectively. In conclusion, the bioaccessibility of bean polyphenols is strongly enhanced by starch digestion. These polyphenols may contribute to the health benefits associated with bean consumption

Intergenerational change and familial aggregation of body mass index

The relationship between parental BMI and that of their adult offspring, when increased adiposity can become a clinical issue, is unknown. We investigated the intergenerational change in body mass index (BMI) distribution, and examined the sex-specific relationship between parental and adult offspring BMI. Intergenerational change in the distribution of adjusted BMI in 1,443 complete families (both parents and at least one offspring) with 2,286 offspring (1,263 daughters and 1,023 sons) from the west of Scotland, UK, was investigated using quantile regression. Familial correlations were estimated from linear mixed effects regression models. The distribution of BMI showed little intergenerational change in the normal range (\25 kg/m2), decreasing overweightness (25– \30 kg/m2) and increasing obesity (C30 kg/m2). Median BMI was static across generations in males and decreased in females by 0.4 (95% CI: 0.0, 0.7) kg/m2; the 95th percentileincreased by 2.2 (1.1, 3.2) kg/m2 in males and 2.7 (1.4, 3.9) kg/m2 in females. Mothers’ BMI was more strongly associated with daughters’ BMI than was fathers’ (correlation coefficient (95% CI): mothers 0.31 (0.27, 0.36), fathers 0.19 (0.14, 0.25); P = 0.001). Mothers’ and fathers’ BMI were equally correlated with sons’ BMI (correlation coefficient: mothers 0.28 (0.22, 0.33), fathers 0.27 (0.22, 0.33). The increase in BMI between generations was concentrated at the upper end of the distribution. This, alongside the strong parent-offspring correlation, suggests that the increase in BMI is disproportionally greater among offspring of heavier parents. Familial influences on BMI among middle-aged women appear significantly stronger from mothers than father

New Symmetries in Crystals and Handed Structures

For over a century, the structure of materials has been described by a combination of rotations, rotation-inversions and translational symmetries. By recognizing the reversal of static structural rotations between clockwise and counterclockwise directions as a distinct symmetry operation, here we show that there are many more structural symmetries than are currently recognized in right- or left-handed handed helices, spirals, and in antidistorted structures composed equally of rotations of both handedness. For example, though a helix or spiral cannot possess conventional mirror or inversion symmetries, they can possess them in combination with the rotation reversal symmetry. Similarly, we show that many antidistorted perovskites possess twice the number of symmetry elements as conventionally identified. These new symmetries predict new forms for "roto" properties that relate to static rotations, such as rotoelectricity, piezorotation, and rotomagnetism. They also enable symmetry-based search for new phenomena, such as multiferroicity involving a coupling of spins, electric polarization and static rotations. This work is relevant to structure-property relationships in all material structures with static rotations such as minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error

A rare case of renal oncocytoma associated with erythrocytosis: case report

BACKGROUND: Oncocytomas are benign tumors of the kidney that are usually diagnosed postoperatively due to differential diagnostic problems from renal cell carcinoma. Although the latter are neoplasms that have been associated with erythrocytosis in 3.5% of cases, there are no reports in the literature about a similar occurrence in oncocytomas. CASE PRESENTATION: In this case report we present a unique case of a right lower pole oncocytoma associated with erythrocytosis. Erythrocytosis subsided after partial nephrectomy. CONCLUSION: Erythrocytosis can sometimes occur in association with renal oncocytomas