Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis

The osteoblast-derived hormone osteocalcin promotes testosterone biosynthesis in the mouse testis by binding to GPRC6A in Leydig cells. Interestingly, Osteocalcin-deficient mice exhibit increased levels of luteinizing hormone (LH), a pituitary hormone that regulates sex steroid synthesis in the testes. These observations raise the question of whether LH regulates osteocalcin’s reproductive effects. Additionally, there is growing evidence that osteocalcin levels are a reliable marker of insulin secretion and sensitivity and circulating levels of testosterone in humans, but the endocrine function of osteocalcin is unclear. Using mouse models, we found that osteocalcin and LH act in 2 parallel pathways and that osteocalcin-stimulated testosterone synthesis is positively regulated by bone resorption and insulin signaling in osteoblasts. To determine the importance of osteocalcin in humans, we analyzed a cohort of patients with primary testicular failure and identified 2 individuals harboring the same heterozygous missense variant in one of the transmembrane domains of GPRC6A, which prevented the receptor from localizing to the cell membrane. This study uncovers the existence of a second endocrine axis that is necessary for optimal male fertility in the mouse and suggests that osteocalcin modulates reproductive function in humans.     

Williams syndrome in a preterm infant with phenotype of Alagille syndrome

We report on a preterm infant born at 31 weeks of gestation with a phenotype suggestive of Alagille syndrome, yet microarray analysis identified a deletion on 7q11.23 at the Williams syndrome locus. The infant died on day 18 of life with overwhelming sepsis. This case illustrates the importance of microarray analysis in diagnosing genetic conditions, especially in preterm babies whose facial and other clinical manifestations have not fully developed.     

Correlation between biofilm production and multiple drug resistance in imipenem resistant clinical isolates of Acinetobacter baumannii

Purpose: To study the qualitative and quantitative methods for the investigation of biofilm formation and to examine the correlation between biofilm and antibiotic resistance among the clinical isolates of Acinetobacter baumannii. We also verified the association between biofilm and presence of extended spectrum β-lactamases, particularly, bla_PER-1. Methods: A total of 55 isolates were subjected to susceptibility testing by disc diffusion method for 13 clinically relevant antibiotics. Screening for biofilm production was done by both qualitative and quantitative methods through tube and microtitre plate assay respectively. The presence of bla_PER-1was checked by PCR. Results: A. baumannii isolates showed very high resistance (>75%) to imipenem, cephotaxime, amikacin and ciprofloxacin. Only cefoperazone, netillin and norfloxacin were found to be effective agents. Results of microtitre and tube methods were concordant with 34 isolates (62%) showing biofilm formation. Resistance to four antibiotics such as amikacin (82% vs. 17.6%, P<0.001), cephotaxime (88% vs. 11%, P P<0.001), ciprofloxacin (70% vs. 29%, P=0.005) and aztreonam (38% vs. 11%, P=0.039) was comparatively higher among biofilm producers than non-biofilm producers. Microtitre assay additionally detected 14 weakly adherent isolates. Only 11 isolates had bla_PER-1gene and among these two were strong biofilm producers, while remaining were weakly adherent isolates. Conclusion: Microtitre plate method was found to be a more sensitive method for biofilm detection. This study demonstrates a high propensity among the clinical isolates of A. baumannii to form biofilm and a significant association of biofilms with multiple drug resistance. Presence of bla_PER-1appears to be more critical for cell adherence than for biofilm formation.     

The possible influence of noise frequency components on the health of exposed industrial workers--a review

Noise is a common occupational health hazard in most industrial settings. An assessment of noise and its adverse health effects based on noise intensity is inadequate. For an efficient evaluation of noise effects, frequency spectrum analysis should also be included. This paper aims to substantiate the importance of studying the contribution of noise frequencies in evaluating health effects and their association with physiological behavior within human body. Additionally, a review of studies published between 1988 and 2009 that investigate the impact of industrial/occupational noise on auditory and non-auditory effects and the probable association and contribution of noise frequency components to these effects is presented. The relevant studies in English were identified in Medknow, Medline, Wiley, Elsevier, and Springer publications. Data were extracted from the studies that fulfilled the following criteria: title and/or abstract of the given study that involved industrial/occupational noise exposure in relation to auditory and non-auditory effects or health effects. Significant data on the study characteristics, including noise frequency characteristics, for assessment were considered in the study. It is demonstrated that only a few studies have considered the frequency contributions in their investigations to study auditory effects and not non-auditory effects. The data suggest that significant adverse health effects due to industrial noise include auditory and heart-related problems. The study provides a strong evidence for the claims that noise with a major frequency characteristic of around 4 kHz has auditory effects and being deficient in data fails to show any influence of noise frequency components on non-auditory effects. Furthermore, specific noise levels and frequencies predicting the corresponding health impacts have not yet been validated. There is a need for advance research to clarify the importance of the dominant noise frequency contribution in evaluating health effects.