N,N′-Bis[1-(thiophen-2-yl)ethylidene]ethane-1,2-diamine

Mol­ecules of the title compound, C14H16N2S2, have a centre of inversion in the middle of the –CH2–CH2– bond; the (C4H3S)(CH3)C=N–CH2– moiety is almost planar (r.m.s. deviation for non-H atoms 0.027 Å)

Absence of Self-Averaging and Universal Fluctuations in Random Systems Near Critical Points

The distributions P(X) of singular thermodynamic quantities, on an ensemble of d-dimensional quenched random samples of linear size L near a critical point, are analyzed using the renormalization group. For L much larger than the correlation length ξ, we recover strong self-averaging (SA): P(X) approaches a Gaussian with relative squared width RX~(L/ξ)−d. For L≪ξ we show weak SA (RX decays with a small power of L) or no SA [P(X) approaches a non-Gaussian, with universal L-independent relative cumulants], when the randomness is irrelevant or relevant, respectively

Circulating levels of dickkopf-1, osteoprotegerin and sclerostin are higher in old compared with young men and women and positively associated with whole-body bone mineral density in older adults

Summary: Bone mineral density declines with increasing older age. We examined the levels of circulating factors known to regulate bone metabolism in healthy young and older adults. The circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin were positively associated with WBMD in older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young. Purpose: To investigate the relationship between whole-body bone mineral density (WBMD) and levels of circulating factors with known roles in bone remodelling during 'healthy' ageing. Methods: WBMD and fasting plasma concentrations of dickkopf-1, fibroblast growth factor-23, osteocalcin, osteoprotegerin, osteopontin and sclerostin were measured in 272 older subjects (69 to 81 years; 52% female) and 171 younger subjects (18-30 years; 53% female). Results: WBMD was lower in old than young. Circulating osteocalcin was lower in old compared with young, while dickkopf-1, osteoprotegerin and sclerostin were higher in old compared with young. These circulating factors were each positively associated with WBMD in the older adults and the relationships remained after adjustment for covariates (r-values ranging from 0.174 to 0.254, all p<0.01). In multivariate regression, the body mass index, circulating sclerostin and whole-body lean mass together accounted for 13.8% of the variation with WBMD in the older adults. In young adults, dickkopf-1 and body mass index together accounted for 7.7% of variation in WBMD. Conclusion: Circulating levels of dickkopf-1, osteocalcin, osteoprotegerin and sclerostin are positively associated with WBMD in community-dwelling older adults, despite the average WBMD being lower and circulating dickkopf-1, osteoprotegerin and sclerostin being higher in old than young

The interaction of Wnt-11 and signalling cascades in prostate cancer

Prostate cancer (PCa) is the second most common cancer among the male population. Conventional therapies target androgen signalling, which drives tumour growth; however, they provide limited survival benefits for patients. It is essential, therefore, to develop a more specific biomarker than the current gold standard, PSA testing. The Wnt signalling pathway induces expression of target genes through cell surface receptors. A non-canonical member of this family, Wnt-11, is evolutionarily highly conserved and is normally expressed by various cells in the developing embryo, as well as in the heart, liver and skeletal muscle of adult humans. We comprehensively review several cell signalling pathways to explain how they interact with Wnt-11, demonstrating its use as a potential biomarker for PCa. Several studies have shown that the expression of Wnt-11 is associated with gastric, renal and colorectal adenocarcinomas and PCa. Moreover, Wnt-11 affects extracellular matrix composition and cytoskeletal rearrangement, and it is required for proliferation and/or survival during cell differentiation. It was found that PCa cell lines express high levels of Wnt-11, which allows differentiation of the epithelial prostate tumour cells to neuron-like (NE) cells. The NE cells produce additional factors that can cause regression after treatment. Accumulating evidence shows that Wnt-11 could be a potential biomarker in diagnosing PCa. Many studies have shown both non-canonical and canonical Wnts interact with several signalling cascades such as PKC, JNK, NF-κB, Rho, PKA and PI3K. In particular, evidence demonstrates Wnt-11 is involved in the progression of PCa, thus it could have the potential to become both a specific disease marker and an important therapeutic target

Bone Loss in Diabetes: Use of Antidiabetic Thiazolidinediones and Secondary Osteoporosis

Clinical evidence indicates that bone status is affected in patients with type 2 diabetes mellitus (T2DM). Regardless of normal or even high bone mineral density, T2DM patients have increased risk of fractures. One class of antidiabetic drugs, thiazolidinediones (TZDs), causes bone loss and further increases facture risk, placing TZDs in the category of drugs causing secondary osteoporosis. Risk factors for development of TZD-induced secondary osteoporosis are gender (women), age (elderly), and duration of treatment. TZDs exert their antidiabetic effects by activating peroxisome proliferator-activated receptor-γ (PPAR-γ) nuclear receptor, which controls glucose and fatty acid metabolism. In bone, PPAR-γ controls differentiation of cells of mesenchymal and hematopoietic lineages. PPAR-γ activation with TZDs leads to unbalanced bone remodeling: bone resorption increases and bone formation decreases. Laboratory research evidence points toward a possible separation of unwanted effects of PPAR-γ on bone from its beneficial antidiabetic effects by using selective PPAR-γ modulators. This review also discusses potential pharmacologic means to protect bone from detrimental effects of clinically used TZDs (pioglitazone and rosiglitazone) by using combinational therapy with approved antiosteoporotic drugs, or by using lower doses of TZDs in combination with other antidiabetic therapy. We also suggest a possible orthopedic complication, not yet supported by clinical studies, of delayed fracture healing in T2DM patients on TZD therapy

Time-restricted feeding attenuates hypercholesterolaemia and atherosclerosis development during circadian disturbance in APOE∗3-Leiden.CETP mice

Circadian disturbance (CD) is the consequence of a mismatch between endogenous circadian rhythms, behaviour, and/or environmental cycles, and frequently occurs during shift work. Shift work has been associated with elevated risk for atherosclerotic cardiovascular disease (asCVD) in humans, but evidence for the effectiveness of prevention strategies is lacking.\nHere, we applied time-restricted feeding (TRF) as a strategy to counteract atherosclerosis development during CD in female APOE∗3-Leiden.CETP mice, a well-established model for humanized lipoprotein metabolism. Control groups were subjected to a fixed 12:12 h light-dark cycle, while CD groups were subjected to 6-h phase advancement every 3 days. Groups had either ad libitum (AL) access to food or were subjected to TRF with restricted food access to the dark phase.\nTRF did not prevent the increase in the relative abundance of circulating inflammatory monocytes and elevation of (postprandial) plasma triglycerides during CD. Nonetheless, TRF reduced atherosclerotic lesion size and prevented an elevation in macrophage content of atherosclerotic lesions during CD, while it increased the relative abundance of anti-inflammatory monocytes, prevented activation of T cells, and lowered plasma total cholesterol levels and markers of hepatic cholesterol synthesis. These effects were independent of total food intake.\nWe propose that time restricted eating could be a promising strategy for the primary prevention of asCVD risk in shift workers, which warrants future study in humans.\nThis work was funded by the Novo Nordisk Foundation, the Netherlands Ministry of Social Affairs and Employment, Amsterdam Cardiovascular Sciences, and the Dutch Heart Foundation.Biopharmaceutic

Eating for 1, Healthy and Active for 2; feasibility of delivering novel, compact training for midwives to build knowledge and confidence in giving nutrition, physical activity and weight management advice during pregnancy

Gold OABackground: Women in Wales are more likely to be obese in pregnancy than in any other United Kingdom (UK) country. Midwives are ideally placed to explore nutrition, physical activity and weight management concerns however qualitative studies indicate they lack confidence in raising the sensitive issue of weight. Acknowledging this and the reality of finite time and resources, this study aimed to deliver compact training on nutrition, physical activity and weight management during pregnancy to increase the knowledge and confidence of midwives in this subject. Methods A compact training package for midwives was developed comprising of evidence based nutrition, physical activity and weight management guidance for pregnancy. Training was promoted via midwifery leads and delivered within the Health Board. Questionnaires based on statements from national public health guidance were used to assess changes in self-reported knowledge and confidence pre and post training. Descriptive statistics were applied and 95% confidence intervals were calculated. Results 43 midwives registered for training, 32 (74%) attended and completed the questionnaires. Although, pre training knowledge and confidence varied between participants, statistically significant improvements in self-reported knowledge and confidence were observed post training. 97% indicated knowledge of pregnancy specific food and nutrition messages as ‘better’ (95% CI 85 to 100), as opposed to 3% stating ‘stayed the same’ – 60% stated ‘much better’. 83% indicated confidence to explain the risks of raised BMI in pregnancy was either ‘much’ or ‘somewhat better’ (95% CI 66 to 93), as opposed to 17% stating ‘stayed the same’. 89% indicated confidence to discuss eating habits and physical activity was ‘much’ or ‘somewhat better’ (95% CI 73 to 97) as opposed to 11% stating ‘stayed the same’. Emergent themes highlighted that training was positively received and relevant to midwifery practice. Conclusions This study provides early indications that a compact nutrition, physical activity and weight management training package improves midwives self-reported knowledge and confidence. Cascading training across the midwifery service in the Health Board and conducting further studies to elicit longer term impact on midwifery practice and patient outcomes are recommended