Protein biomarkers of susceptibility and resilience to stress in a rat model of depression.

The molecular etiologies of psychological stress and major depressive disorder (MDD) are highly complex and many brain regions are involved. The prefrontal cortex (PFC) has gained attention in depression research due to its role in cognition including working memory and decision-making, which are impaired in MDD. The aim of the present study was to identify differentially regulated synaptosomal proteins from PFC in stress-exposed animals. The well-established chronic mild stress (CMS) rodent model was applied and three groups of rats were studied: unstressed controls, stress-susceptible and stress resilient. Large-scale proteomics based on relative iTRAQ quantification was applied on three synaptosomal Percoll gradient fractions and 27 proteins were found to undergo significant differential regulation. Gradient fraction two (F2) contained the highest amounts of synaptosomal proteins and is therefore recommended to be included in proteomic studies onwards, in addition to the traditionally used fractions F3 and F4. The regulated proteins corroborate previous studies on depression regulated proteins; including GFAP, HOMER1 and glutamatergic transmission (vesicular transporter 1, VGLUT1). However, additional functionalities were represented - especially in stress-resilient rats - such as oxidative stress protection (peroxiredoxins PRDX1 and PRDX2), Na/K-transporter ATP1A2 and respiratory chain subunits (UQCRC1 and UQCRFS1), which illustrate the biochemical complexity behind the stress phenotypes, but may also aid in the development of novel treatment strategies.

Bone and vitamin D status in patients with anorexia nervosa.

INTRODUCTION: The aim of the present study was to investigate bone status and biological mechanisms involved in the negative impact of anorexia nervosa (AN) on osteogenesis. METHODS: A total of 30 AN patients from Aalborg University Hospital who underwent bone scans were included in a cross-sectional study. Biochemical data, bone scans (dual-energy X-ray absorptiometry (DXA)) as well as general health and medical information had been collected during the 2009-2011 period and stored via local and national clinical databases in Denmark, and from these databases we identified all patients with an AN diagnosis who underwent bone scans. RESULTS: AN patients had a mean Z-score of -1.5 to -1.6 in lumbar spine and total hip, respectively. The hip Z-score decreased with duration of disease, and a positive correlation was seen between serum 25-hydroxy-vitamin D level and spine Z-score but not hip Z-score. Bone mineral density did not seem to change with time since diagnosis. Additionally, a negative correlation between serum 25-hydroxy-vitamin D levels and serum total alkaline phosphatase levels was found. A serum 25-hydroxy-vitamin D level below 50 nmol/l was associated with increased alkaline phosphatase levels. CONCLUSION: Rather than clinical measures including BMI and biochemical measures disease duration was the main predictor of bone status. This implies that long-term disease should be a main factor in selecting patients for referral to DXA. Moreover, results from this study indicate normal osteoblastic response to malnutrition. FUNDING: not relevant. TRIAL REGISTRATION: The present study was not registered due to its register-based design. However, the study was approved by the Danish Data Protection Agency.

CARING (CAncer Risk and INsulin analoGues): the association of diabetes mellitus and cancer risk with focus on possible determinants - a systematic review and a meta-analysis.

BACKGROUND: Patients suffering from diabetes mellitus (DM) may experience an increased risk of cancer; however, it is not certain whether this effect is due to diabetes per se. OBJECTIVE: To examine the association between DM and cancers by a systematic review and meta-analysis according to the PRISMA guidelines. DATA SOURCES: The systematic literature search includes Medline at PubMed, Embase, Cinahl, Bibliotek.dk, Cochrane library, Web of Science and SveMed+ with the search terms: "Diabetes mellitus", "Neoplasms", and "Risk of cancer". STUDY ELIGIBILITY CRITERIA: The included studies compared the risk of cancer in diabetic patients versus non-diabetic patients. All types of observational study designs were included. RESULTS: Diabetes patients were at a substantially increased risk of liver (RR=2.1), and pancreas (RR=2.2) cancer. Modestly elevated significant risks were also found for ovary (RR=1.2), breast (RR=1.1), cervix (RR=1.3), endometrial (RR=1.4), several digestive tract (RR=1.1-1.5), kidney (RR=1.4), and bladder cancer (RR=1.1). The findings were similar for men and women, and unrelated to study design. Meta-regression analyses showed limited effect modification of body mass index, and possible effect modification of age, gender, with some influence of study characteristics (population source, cancer- and diabetes ascertainment). LIMITATIONS: Publication bias seemed to be present. Only published data were used in the analyses. CONCLUSIONS: The systematic review and meta-analysis confirm the previous results of increased cancer risk in diabetes and extend this to additional cancer sites. Physicians in contact with patients with diabetes should be aware that diabetes patients are at an increased risk of cancer.