Cardio-protective effects of carnitine in streptozotocin-induced diabetic rats

BACKGROUND: Streptozotocin-induced diabetes (STZ-D) in rats has been associated with carnitine deficiency, bradycardia and left ventricular enlargement. AIM: The purpose of this study was to determine whether oral carnitine supplementation would normalize carnitine levels and cardiac function in STZ-D rats. METHODS: Wistar rats (48) were made hyperglycemic by STZ at 26 weeks of age. Same age normal Wistar rats (24) were used for comparison. Echocardiograms were performed at baseline 2, 6, 10, and 18 weeks after STZ administration in all animals. HbA1c, serum carnitine and free fatty acids (FFA) were measured at the same times. Since STZ-D rats become carnitine deficient, 15 STZ-D rats received supplemental oral carnitine for 16 weeks. RESULTS: The heart rates for the STZ-D rats (290 ± 19 bpm) were less than control rats (324 ± 20 bpm) (p < 0.05). After 4 weeks of oral carnitine supplementation, the serum carnitine and heart rates of the STZ-D rats returned to normal. Dobutamine stress increased the heart rates of all study animals, but the increase in STZ-D rats (141 ± 8 bpm) was greater than controls (79 ± 8 bpm) (p < 0.05). The heart rates of STZ-D rats given oral carnitine, however, were no different than controls (94 ± 9 bpm). The left ventricular mass/body weight ratio (LVM/BW) in the diabetic animals (2.7 ± 0.5) was greater than control animals (2.2 ± 0.3) (p < 0.05) after 18 weeks of diabetes. In contrast, the LVM/BW (2.3 ± .2) of the STZ-D animals receiving supplemental carnitine was the same as the control animals at 18 weeks. CONCLUSION: Thus, supplemental oral carnitine in STZ-D rats normalized serum carnitine, heart rate regulation and left ventricular size. These findings suggest a metabolic mechanism for the cardiac dysfunction noted in this diabetic animal model

Germline-dependent gene expression in distant non-gonadal somatic tissues of Drosophila

<p>Abstract</p> <p>Background</p> <p><it>Drosophila </it>females commit tremendous resources to egg production and males produce some of the longest sperm in the animal kingdom. We know little about the coordinated regulation of gene expression patterns in distant somatic tissues that support the developmental cost of gamete production.</p> <p>Results</p> <p>We determined the non-gonadal gene expression patterns of <it>Drosophila </it>females and males with or without a germline. Our results show that germline-dependent expression in the non-gonadal soma is extensive. Interestingly, gene expression patterns and hormone titers are consistent with a hormone axis between the gonads and non-gonadal soma.</p> <p>Conclusions</p> <p>The germline has a long-range influence on gene expression in the <it>Drosophila </it>sexes. We suggest that this is the result of a germline/soma hormonal axis.</p

Cortical tau is associated with microstructural imaging biomarkers of neurite density and dendritic complexity in Alzheimer's disease

INTRODUCTION: In Alzheimer's disease (AD), hyperphosphorylated tau is closely associated with focal neurodegeneration, but the mechanism remains uncertain. METHODS: We quantified cortical microstructure using neurite orientation dispersion and density imaging in 14 individuals with young onset AD. Diffusion tensor imaging measured mean diffusivity (MD). Amyloid beta and tau positron emission tomography were acquired and associations with microstructural measures were assessed. RESULTS: When regional volume was adjusted for, in the medial temporal lobe there was a significant negative association between neurite density and tau (partial R2  = 0.56, p = 0.008) and between orientation dispersion and tau (partial R2  = 0.66, p = 0.002), but not between MD and tau. In a wider cortical composite, there was an association between orientation dispersion and tau (partial R2  = 0.43, p = 0.030), but not between other measures and tau. DISCUSSION: Our findings are consistent with tau causing first dendritic pruning (reducing dispersion/complexity) followed by neuronal loss. Advanced magnetic resonance imaging (MRI) microstructural measures have the potential to provide information relating to underlying tau deposition

The tobacco industry’s past role in weight control related to smoking

Background: Smoking is thought to produce an appetite-suppressing effect by many smokers. Thus, the fear of body weight gain often outweighs the perception of health benefits associated with smoking cessation, particularly in adolescents. We examined whether the tobacco industry played a role in appetite and body weight control related to smoking and smoking cessation. Methods: We performed a systematic search within the archives of six major US and UK tobacco companies (American Tobacco, Philip Morris, RJ Reynolds, Lorillard, Brown & Williamson and British American Tobacco) that were Defendants in tobacco litigation settled in 1998. Findings are dated from 1949 to 1999. Results: The documents revealed the strategies planned and used by the industry to enhance effects of smoking on weight and appetite, mostly by chemical modifications of cigarettes contents. Appetite-suppressant molecules, such as tartaric acid and 2-acetylpyridine were added to some cigarettes. Conclusion: These tobacco companies played an active and not disclaimed role in the anti-appetite effects of smoking, at least in the past, by adding appetite-suppressant molecules into their cigarettes

Patterns of Reproductive Isolation in Toads

Understanding the general features of speciation is an important goal in evolutionary biology, and despite significant progress, several unresolved questions remain. We analyzed an extensive comparative dataset consisting of more than 1900 crosses between 92 species of toads to infer patterns of reproductive isolation. This unique dataset provides an opportunity to examine the strength of reproductive isolation, the development and sex ratios of hybrid offspring, patterns of fertility and infertility, and polyploidization in hybrids all in the context of genetic divergence between parental species. We found that the strength of intrinsic postzygotic isolation increases with genetic divergence, but relatively high levels of divergence are necessary before reproductive isolation is complete in toads. Fertilization rates were not correlated to genetic divergence, but hatching success, the number of larvae produced, and the percentage of tadpoles reaching metamorphosis were all inversely related with genetic divergence. Hybrids between species with lower levels of divergence developed to metamorphosis, while hybrids with higher levels of divergence stopped developing in gastrula and larval stages. Sex ratios of hybrid offspring were biased towards males in 70% of crosses and biased towards females in 30% of crosses. Hybrid females from crosses between closely related species were completely fertile, while approximately half (53%) of hybrid males were sterile, with sterility predicted by genetic divergence. The degree of abnormal ploidy in hybrids was positively related to genetic divergence between parental species, but surprisingly, polyploidization had no effect on patterns of asymmetrical inviability. We discuss explanations for these patterns, including the role of Haldane's rule in toads and anurans in general, and suggest mechanisms generating patterns of reproductive isolation in anurans

Using an online survey of healthcare-seeking behaviour to estimate the magnitude and severity of the 2009 H1N1v influenza epidemic in England

Background : During the 2009 H1N1v influenza epidemic, the total number of symptomatic cases was estimated by combining influenza-like illness (ILI) consultations, virological surveillance and assumptions about healthcare-seeking behaviour. Changes in healthcare-seeking behaviour due to changing scientific information, media coverage and public anxiety, were not included in case estimates. The purpose of the study was to improve estimates of the number of symptomatic H1N1v cases and the case fatality rate (CFR) in England by quantifying healthcare-seeking behaviour using an internet-based survey carried out during the course of the 2009 H1N1v influenza epidemic. Methods : We used an online survey that ran continuously from July 2009 to March 2010 to estimate the proportion of ILI cases that sought healthcare during the 2009 H1N1v influenza epidemic. We used dynamic age- and gender-dependent measures of healthcare-seeking behaviour to re-interpret consultation numbers and estimate the true number of cases of symptomatic ILI in 2009 and the case fatality rate (CFR). Results : There were significant differences between age groups in healthcare usage. From the start to the end of the epidemic, the percentage of individuals with influenza-like symptoms who sought medical attention decreased from 43% to 32% (p < 0.0001). Adjusting official numbers accordingly, we estimate that there were 1.1 million symptomatic cases in England, over 320,000 (40%) more cases than previously estimated and that the autumn epidemic wave was 45% bigger than previously thought. Combining symptomatic case numbers with reported deaths leads to a reduced overall CFR estimate of 17 deaths per 100,000 cases, with the largest reduction in adults. Conclusions : Active surveillance of healthcare-seeking behaviour, which can be achieved using novel data collection methods, is vital for providing accurate real-time estimates of epidemic size and disease severity. The differences in healthcare-seeking between different population groups and changes over time have significant implications for estimates of total case numbers and the case fatality rate

Development and validation of the Diabetes Numeracy Test (DNT)

<p>Abstract</p> <p>Background</p> <p>Low literacy and numeracy skills are common. Adequate numeracy skills are crucial in the management of diabetes. Diabetes patients use numeracy skills to interpret glucose meters, administer medications, follow dietary guidelines and other tasks. Existing literacy scales may not be adequate to assess numeracy skills. This paper describes the development and psychometric properties of the Diabetes Numeracy Test (DNT), the first scale to specifically measure numeracy skills used in diabetes.</p> <p>Methods</p> <p>The items of the DNT were developed by an expert panel and refined using cognitive response interviews with potential respondents. The final version of the DNT (43 items) and other relevant measures were administered to a convenience sample of 398 patients with diabetes. Internal reliability was determined by the Kuder-Richardson coefficient (KR-20). An <it>a priori </it>hypothetical model was developed to determine construct validity. A shortened 15-item version, the DNT15, was created through split sample analysis.</p> <p>Results</p> <p>The DNT had excellent internal reliability (KR-20 = 0.95). The DNT was significantly correlated (p < 0.05) with education, income, literacy and math skills, and diabetes knowledge, supporting excellent construct validity. The mean score on the DNT was 61% and took an average of 33 minutes to complete. The DNT15 also had good internal reliability (KR-20 = 0.90 and 0.89). In split sample analysis, correlations of the DNT-15 with the full DNT in both sub-samples was high (rho = 0.96 and 0.97, respectively).</p> <p>Conclusion</p> <p>The DNT is a reliable and valid measure of diabetes related numeracy skills. An equally adequate but more time-efficient version of the DNT, the DNT15, can be used for research and clinical purposes to evaluate diabetes related numeracy.</p

Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer