Investigation of Behavior and Plasma Levels of Corticosterone in Restrictive- and Ad Libitum-Fed Diet-Induced Obese Mice

Diet-induced obesity (DIO) mice models are commonly used to investigate obesity-related health problems. Until now, only sparse data exist on the influence of DIO on behavior and stress hormones in mice. The present study investigates high-fat DIO with two different feeding regimes on behavioral parameters in mice. Various behavioral tests (open field, elevated plus maze, social interaction, hotplate) were performed with female BALB/c and male C57BL/6 mice after a feeding period of twelve weeks (restrictive vs. ad libitum and normal-fat diet vs. high-fat diet) to investigate levels of anxiety and aggression. BALB/c mice were DIO-resistant and therefore the prerequisite for the behavior analyses was not attained. C57BL/6 mice fed a high-fat diet had a significantly higher body weight and fat mass compared to C57BL/6 mice fed a control diet. Interestingly, the DIO C57BL/6 mice showed no changes in their aggression- or anxiety-related behavior but showed a significant change in the anxiety index. This was probably due to a lower activity level, as other ethological parameters did not show an altered anxiety-related behavior. In the ad libitum-fed DIO group, the highest corticosterone level was detected. Changes due to the feeding regime (restrictive vs. ad libitum) were not observed. These results provide a possible hint to a bias in the investigation of DIO-related health problems in laboratory animal experiments, which may be influenced by the lower activity level.     

Which Vitamin D Oral Supplement is Best for Postmenopausal Women?

Next to a healthy calcium and protein rich diet and exercise, vitamin D supplementation is a key pillar of osteoporosis prevention among postmenopausal women. This article reviews the recent recommendations on vitamin D by the IOF (2010), the Institute of Medicine (2010), and the US Endocrine Society (2011), including the evidence to support these recommendations for fracture and fall prevention. The recent recommendations agree that supplementation should be performed with vitamin D3 or vitamin D2, and that a minimal serum 25-hydroxyvitamin D threshold of 50?nmol/l (20 ng/ml)should be achieved to overcome vitamin D deficiency. In contrast to the Institute of Medicine, the IOF and the US Endocrine Society recommend vitamin D also for the prevention of falls, and state that for fracture prevention a higher serum 25-hydroxyvitamin D threshold of 75?nmol/l (30?ng/ml) should be targeted.     

Activation of RhoA,B,C by Yersinia Cytotoxic Necrotizing Factor (CNFy) Induces Apoptosis in LNCaP Prostate Cancer Cells

Prostate cancer is the most common malignancy, accounting for about 25% of all incident cases among men in industrialized countries. The human androgen-dependent prostate cancer cell line LNCaP, which is derived from a metastatic lesion of human prostatic adenocarcinoma, is frequently used to study prostate cancer associated signaling pathways in vitro. Recently it was described that Rho GTPase activation in these cells leads to apoptotic responses. We used the bacterial toxins CNFy and CNF1, which specifically and directly activate Rho GTPases by deamidation of a single glutamine. We asked whether these Rho activators could induce apoptosis in LNCaP cells. Our results indicate that RhoA activation, induced by CNFy, does lead to intrinsic apoptosis of the cells. Analysis of the underlying signaling pathway reveals that apoptosis induction requires the activity of Rho kinase (ROCK) and myosin activation, an apoptotic pathway previously identified in cancer stem cells.     

Validating the International Classification of Functioning, Disability and Health Comprehensive Core Set for Rheumatoid Arthritis from the patient perspective: a qualitative study

OBJECTIVE: To validate the International Classification of Functioning, Disability and Health (ICF) Comprehensive Core Set for Rheumatoid Arthritis (RA) from the patient perspective. METHODS: Patients with RA were interviewed about their problems in daily functioning. Interviews were tape recorded and transcribed verbatim. Interview texts were divided into meaning units. The concepts contained in these meaning units were linked to the ICF according to 10 established linking rules. Of the transcribed data, 15% were analyzed and linked by a second health professional. The degree of agreement was calculated using the kappa statistic. RESULTS: Twenty-one patients were interviewed. Two hundred twenty different concepts contained in 367 meaning units were identified in the qualitative analysis of the interviews and linked to 109 second-level ICF categories. Of the 76 second-level categories from the ICF RA Core Set, 63 (83%) were also found in the interviews. Twenty-five second-level categories, which are not part of the current ICF RA Core Set, were identified in the interviews. The result of the kappa statistic for agreement was 0.62 (95% boot-strapped confidence interval 0.59-0.66). CONCLUSION: The validity of the ICF RA Core Set was supported by the perspective of individual patients. However, some additional issues raised in this study but not covered in the current ICF RA Core Set need to be investigated.     

Modafinil in the treatment of idiopathic hypersomnia without long sleep time—a randomized,double‐blind,placebo‐controlled study

In 2010 the European Medicines Agency withdrew the indication of modafinil for the treatment of obstructive sleep apnea, shift work sleep disorder and for idiopathic hypersomnia (IH). In uncontrolled studies, modafinil has been reported to be efficacious in the treatment of sleep disorders. We therefore performed a randomized, placebo‐controlled study with the aim of proving the efficacy of modafinil treatment in these patients. Drug‐free IH patients without long sleep according to ICSD2 criteria, age >18 years and disease duration >2 years were included. After a washout phase, patients at baseline received placebo or 100 mg modafinil in the morning and at noon over 3 weeks, followed by 1 week without medication. At each visit the Epworth Sleepiness Scale (ESS) and Clinical Global Impression (CGI) rating scale were performed. At baseline and on days 8 and 21 four Maintenance of Wakefulness Tests (MWTs)/day or per day were performed. Patients kept a sleep–wake diary throughout the study. Between 2009 and 2011 three sleep centres recruited 33 participants. Compared to placebo, modafinil decreased sleepiness significantly and improved mean sleep latency in the MWT non‐significantly. The CGI improved significantly from baseline to the last visit on treatment. The most frequent adverse events were headaches and gastrointestinal disorders; skin and psychiatric reactions were not reported. The number of reported naps and duration of daytime sleepiness decreased significantly. Total sleep time of nocturnal sleep was slightly reduced. The sleep diaries showed increases in feeling refreshed in the morning; the diurnal diaries showed significant improvement of performance and of exhaustion. Modafinil is an effective and safe medication in the treatment of IH. Adverse events are mild to moderate.