Diet modification and its influence on metabolic and related pathological alterations in the SHR/NDmcr-cp rat,an animal model of the metabolic syndrome

SHR/NDmcr-cp (SHR/NDcp) rats, which carry a nonsense mutation of the leptin receptor gene, are known to spontaneously develop hypertension, obesity and hyperlipidemia, and have therefore found use as an animal model of the metabolic syndrome and type 2 diabetes. However, some recent studies on SHR/NDcp rats revealed only mild elevation of blood glucose levels. To investigate whether metabolic factors including blood glucose and histopathological alterations of SHR/NDcp rats deteriorate with a diabetogenic diet, biochemical and histopathological examinations were conducted with animals fed normal or diabetogenic diets for 20 weeks. SHR/NDcp rats receiving the normal diet displayed obesity, hypertension, hyperlipidemia, and mild elevation of blood glucose and HbA1c levels. Urinary glucose excretion was noted in only 1 out of 6 animals. Histologically, macro- and micro-vesicular steatosis in the liver, glomerular and tubular damages in the kidney and islet hyperplasia mainly of beta cells in the pancreas were characteristically noted. In SHR/NDcp rats fed the diabetogenic diet, obesity was more severe, with higher blood glucose and HbA1c levels, increased numbers of animals with urinary glucose excretion, and more pronounced hepatic steatosis and renal tubular changes. However, elevation of blood glucose levels and urinary glucose excretion proved transient. These observations indicate that the diabetic state and associated histopathological alterations in SHR/NDcp rats are exacerbated by feeding a diabetogenic diet, but the effects are limited. Elevated islet function with compensative insulin secretion might be related to amelioration of the hyperglycemic state. Further diet modification could be needed to induce a more prominent and persistent diabetic state in SHR/NDcp rats.     

Age determination of adult individuals by three-dimensional modelling of canines

Accurate age determination is fundamental in both forensic medicine and anthropology. Many methods that relate dental characteristics to adult age have been proposed, but there is still no simple and reliable method that does not damage the study material. The aim of this work was to propose a relevant and practical technique for determining age in adults that could be used in both living and deceased individuals. The sample was composed of 210 CT scans from individuals aged from 15 to 85 years old, with four healthy canines present in the mouth. The 840 canines were modelled using Mimics® 10.01 software. The pulp volume/total volume ratio ×100 was determined for each tooth. Seven mathematical models, corresponding to all possible real situations, were determined by the weighted least squares method and ranked in order of relative performance. The adequacy of the seven models to the data was very high with the regressions proposed (0.915?<?R ² _adjusted?<?0.964). Ranked in order of performance, the maxillary model was the most powerful of the seven models for age determination, followed by the 4 canines model, the 13 model and the 23 model.     

Novel Linker Variants of Antileishmanial/Antitubercular 7-Substituted 2-Nitroimidazooxazines Offer Enhanced Solubility

Antitubercular 7-substituted 2-nitroimidazo[2,1-b][1,3]oxazines were previously shown to exhibit potent antileishmanial and antitrypanosomal activities, culminating in a new clinical investigational drug for visceral leishmaniasis (DNDI-0690). To offset development risks, we continued to seek further leads with divergent candidate profiles, especially analogues possessing greater aqueous solubility. Starting from an efficacious monoaryl derivative, replacement of the side chain ether linkage by novel amine, amide, and urea functionality was first explored; the former substitution was well-tolerated in vitro and in vivo but elicited marginal alterations to solubility (except through a less stable benzylamine), whereas the latter groups resulted in significant solubility improvements (up to 53-fold) but an antileishmanial potency reduction of at least 10-fold. Ultimately, we discovered that O-carbamate 66 offered a more optimal balance of increased solubility, suitable metabolic stability, excellent oral bioavailability (100%), and strong in vivo efficacy in a visceral leishmaniasis mouse model (97% parasite load reduction at 25 mg/kg).     

Associations between Nighttime Traffic Noise and Sleep: The Finnish Public Sector Study

Background: Associations between traffic noise and sleep problems have been detected in experimental studies, but population-level evidence is scarce.Objectives: We studied the relationship between the levels of nighttime traffic noise and sleep disturbances and identified vulnerable population groups.Methods: Noise levels of nighttime–outdoor traffic were modeled based on the traffic intensities in the cities of Helsinki and Vantaa, Finland. In these cities, 7,019 public sector employees (81% women) responded to postal surveys on sleep and health. We linked modeled outdoor noise levels to the residences of the employees who responded to the postal survey. We used logistic regression models to estimate associations of noise levels with subjectively assessed duration of sleep and symptoms of insomnia (i.e., difficulties falling asleep, waking up frequently during the night, waking up too early in the morning, nonrestorative sleep). We also used stratified models to investigate the possibility of vulnerable subgroups.Results: For the total study population, exposure to levels of nighttime–outside (L_{night, outside}) traffic noise > 55 dB was associated with any insomnia symptom ≥ 2 nights per week [odds ratio (OR) = 1.32; 95% confidence interval (CI): 1.05, 1.65]. Among participants with higher trait anxiety scores, which we hypothesized were a proxy for noise sensitivity, the ORs for any insomnia symptom at exposures to L_{night, outside} traffic noises 50.1–55 dB and > 55 dB versus ≤ 45 dB were 1.34 (95% CI: 1.00, 1.80) and 1.61 (95% CI: 1.07, 2.42), respectively.Conclusions: Nighttime traffic noise levels > 50 dB L_{night, outside} was associated with insomnia symptoms among persons with higher scores for trait anxiety. For the total study population, L_{night, outside} > 55 dB was positively associated with any symptoms.     

Two Japanese cases of dermatitis herpetiformis associated each with lung cancer and autoimmune pancreatitis but showing no intestinal symptom or circulating immunoglobulin A antibodies to any known antigens

Dermatitis herpetiformis (DH) is common in some Caucasian populations but extremely rare in Japanese, probably because of different immunogenetic backgrounds. We report two Japanese DH cases with typical clinical, histological and direct immunofluorescence features. However, no symptom of gluten‐sensitive enteropathy was shown. The diagnosis was confirmed by eliminating other autoimmune blistering diseases by indirect immunofluorescence, enzyme‐linked immunosorbent assays and immunoblotting. However, circulating immunoglobulin (Ig)A anti‐endomysium, reticulin and gliadin antibodies were not detected. IgA antibodies to tissue and epidermal transglutaminases were also negative. One case was associated with lung cancer and the other one with autoimmune pancreatitis. On review of 17 cases of DH reported in Japan over the previous 10 years, including our cases, one case was associated with gluten‐sensitive enteropathy, four with malignant neoplasms, two with autoimmune systemic disorders and one with psoriasis. Although our cases were typical of DH in clinical, histopathological and IgA deposit features, they showed different human leukocyte antigen haplotypes, no gluten‐sensitive enteropathy and no DH‐specific IgA antibodies, including those to epidermal and tissue transglutaminases. These results suggest that studies of unique characteristics in Japanese DH patients should facilitate further understanding of pathogenesis in DH.