Vitamin D: a review on its effects on muscle strength, the risk of fall, and frailty.

Vitamin D is the main hormone of bone metabolism. However, the ubiquitary nature of vitamin D receptor (VDR) suggests potential for widespread effects, which has led to new research exploring the effects of vitamin D on a variety of tissues, especially in the skeletal muscle. In vitro studies have shown that the active form of vitamin D, calcitriol, acts in myocytes through genomic effects involving VDR activation in the cell nucleus to drive cellular differentiation and proliferation. A putative transmembrane receptor may be responsible for nongenomic effects leading to rapid influx of calcium within muscle cells. Hypovitaminosis D is consistently associated with decrease in muscle function and performance and increase in disability. On the contrary, vitamin D supplementation has been shown to improve muscle strength and gait in different settings, especially in elderly patients. Despite some controversies in the interpretation of meta-analysis, a reduced risk of falls has been attributed to vitamin D supplementation due to direct effects on muscle cells. Finally, a low vitamin D status is consistently associated with the frail phenotype. This is why many authorities recommend vitamin D supplementation in the frail patient

HHV-8-negative multicentric Castleman disease presenting as a crescentic immune complexes membranoproliferative glomerulonephritis.

Multicentric Castleman disease is a rare polyclonal lymphoproliferative disorder mainly associated with two renal manifestations: thrombotic microangiopathy and amyloidosis. Nevertheless, we report here a case of human herpes virus-8 negative multicentric Castleman disease with membranous proliferative glomerulonephritis and extracapillary proliferation. A patient was successfully treated with corticosteroids, anti-CD20 and cyclophosphamide therapy

A preclinical model for identifying rats at risk of alcohol use disorder.

Alcohol use is one of the world's leading causes of death and disease, although only a small proportion of individuals develop persistent alcohol use disorder (AUD). The identification of vulnerable individuals prior to their chronic intoxication remains of highest importance. We propose here to adapt current methodologies for identifying rats at risk of losing control over alcohol intake by modeling diagnostic criteria for AUD: inability to abstain during a signaled period of reward unavailability, increased motivation assessed in a progressive effortful task and persistent alcohol intake despite aversive foot shocks. Factor analysis showed that these three addiction criteria loaded on one underlying construct indicating that they represent a latent construct of addiction trait. Further, not only vulnerable rats displayed higher ethanol consumption, and higher preference for ethanol over sweetened solutions, but they also exhibited pre-existing higher anxiety as compared to resilient rats. In conclusion, the present preclinical model confirms that development of an addiction trait not only requires prolonged exposure to alcohol, but also depends on endophenotype like anxiety that predispose a minority of individuals to lose control over alcohol consumption

Handbook of Life Course Health Development

This handbook synthesizes and analyzes the growing knowledge base on life course health development (LCHD) from the prenatal period through emerging adulthood, with implications for clinical practice and public health. It presents LCHD as an innovative field with a sound theoretical framework for understanding wellness and disease from a lifespan perspective, replacing previous medical, biopsychosocial, and early genomic models of health. Interdisciplinary chapters discuss major health concerns (diabetes, obesity), important less-studied conditions (hearing, kidney health), and large-scale issues (nutrition, adversity) from a lifespan viewpoint. In addition, chapters address methodological approaches and challenges by analyzing existing measures, studies, and surveys. The book concludes with the editors’ research agenda that proposes priorities for future LCHD research and its application to health care practice and health policy

Complex regulation of CREB-binding protein by homeodomain-interacting protein kinase 2.

CREB-binding protein (CBP) and p300 are transcriptional coactivators involved in numerous biological processes that affect cell growth, transformation, differentiation, and development. In this study, we provide evidence of the involvement of homeodomain-interacting protein kinase 2 (HIPK2) in the regulation of CBP activity. We show that HIPK2 interacts with and phosphorylates several regions of CBP. We demonstrate that serines 2361, 2363, 2371, 2376, and 2381 are responsible for the HIPK2-induced mobility shift of CBP C-terminal activation domain. Moreover, we show that HIPK2 strongly potentiates the transcriptional activity of CBP. However, our data suggest that HIPK2 activates CBP mainly by counteracting the repressive action of cell cycle regulatory domain 1 (CRD1), located between amino acids 977 and 1076, independently of CBP phosphorylation. Our findings thus highlight a complex regulation of CBP activity by HIPK2, which might be relevant for the control of specific sets of target genes involved in cellular proliferation, differentiation and apoptosis

Syphilis and parvovirus B19 co-infection imitating a lupus nephropathy: A case report.

Syphilis can share clinical features with autoimmune diseases, such as cutaneous Lupus or rheumatoid arthritis. Moreover, secondary syphilis can have visceral involvement, thus affecting the kidney. Syphilitic nephropathy causes nephrotic syndrome with a classic membranous pattern. We present a unique presentation of a co-infection by syphilis and parvovirus B19 sharing all the biological and histological features of proliferative lupus nephritis (LN). We present a case of a 71-year-old Caucasian male returning from a trip to Asia presenting with nephrotic syndrome with antinuclear antibodies (ANA) positivity. Because of nephrotic syndrome a kidney biopsy was performed. It demonstrated a membranous nephropathy with extracapillary proliferation and a full house pattern (presence of IgA, IgG, IgM and C1Q deposits) on immunofluorescence (IF), highly suggestive of LN class III and V. However, several atypical clinical features notably the age, sex of the patient and the history of travel prompt us to search for another cause of nephropathy. A serology was positive for syphilis and a PCR in the renal biopsy was also positive for parvovirus B19. Thus, a co-infection by syphilis and parvovirus B19 was funded to be the cause of the renal lesions. The proteinuria improved; a course of antibiotic was administrated because of neurologic syphilitic involvement (presence of headache with positive syphilis serology in the CSF). A co-infection by syphilis and parvovirus B19 can share all the biological and histological features of proliferative LN and must be recognized as a cause of pseudo-lupus nephritis

Adolescent drug use escalation and de-escalation: a 3-year follow-up study [Abstract]

This study aims to assess adolescents drug use with a longitudinal perspective in order to identify factors interacting with drug use onset and course. Supported by the Swiss Federal Office of Public Health, the study was initiated in 1999 with a follow-up in 2001 and 2002. The first objective was to measure risk factors for substance use initiation. The second objective was to analyse the co-variation of substance use with environmental, social, relational, medical and psychological factors. A total of 102 adolescents, aged 14-19 years, were recruited for the study in the French-speaking part of Switzerland. Results clearly show that substance use is not a disorder per se in adolescence, but that it is part of a multidimensional complex of problems that some adolescents may encounter: increase and decrease in substance use is paralleled with an increase or decrease in the other areas. This implies that prevention of substance use should not be focused mainly on substances but should consider the adolescent's environment and significant life area

Preferred analysis methods for Affymetrix GeneChips revealed by a wholly defined control dataset

BACKGROUND: As more methods are developed to analyze RNA-profiling data, assessing their performance using control datasets becomes increasingly important. RESULTS: We present a 'spike-in' experiment for Affymetrix GeneChips that provides a defined dataset of 3,860 RNA species, which we use to evaluate analysis options for identifying differentially expressed genes. The experimental design incorporates two novel features. First, to obtain accurate estimates of false-positive and false-negative rates, 100-200 RNAs are spiked in at each fold-change level of interest, ranging from 1.2 to 4-fold. Second, instead of using an uncharacterized background RNA sample, a set of 2,551 RNA species is used as the constant (1x) set, allowing us to know whether any given probe set is truly present or absent. Application of a large number of analysis methods to this dataset reveals clear variation in their ability to identify differentially expressed genes. False-negative and false-positive rates are minimized when the following options are chosen: subtracting nonspecific signal from the PM probe intensities; performing an intensity-dependent normalization at the probe set level; and incorporating a signal intensity-dependent standard deviation in the test statistic. CONCLUSIONS: A best-route combination of analysis methods is presented that allows detection of approximately 70% of true positives before reaching a 10% false-discovery rate. We highlight areas in need of improvement, including better estimate of false-discovery rates and decreased false-negative rates