Examining Mediators of the Relationship Between Community Mobilization and HIV Incidence Among Young South African Women Participating in the HPTN 068 Study Cohort

AIDS and Behavior - We previously demonstrated that village community mobilization (CM) was associated with reduced HIV incidence among adolescent girls and young women (AGYW) in South Africa....     

Unexpected results found in larvae samples from two postmortem forensic cases

Forensic Toxicology - In forensics, entomological specimens can be used as additional/alternative matrices to detect xenobiotics when human specimens are limited in their application. Despite some...     

The effect of hepatectomy on glucose homeostasis in pig and in man.

BACKGROUND/AIMS: The liver is regarded the most important source of glucose production and it is common practice to administer glucose during human liver transplantations to avoid hypoglycaemia. The purpose of this study was to evaluate the importance of extra-hepatic contribution (kidney, gut and muscle) to the glucose homeostasis in the anhepatic pig and in man during the anhepatic phase of human liver transplantations. METHODS: Blood glucose and lactate were monitored in the anhepatic phase in 46 patients undergoing liver transplantation. Arterial-venous differences of lactate, glucose, glycerol, alanine and free fatty acids were measured over kidney, gut and hind leg in 18 pigs made anhepatic. RESULTS: Blood glucose did not change significantly and blood lactate increased only marginally during the anhepatic phase of human orthotopic liver transplantation. In the anhepatic pig, however, blood glucose decreased with a halflife of about 26 min and blood lactate increased. Kidney gluconeogenesis was 0.116+/-0.016 mmol min(-1). Fifty percent of kidney glucose output could be accounted for by lactate- and glycerol uptake. CONCLUSIONS: The results show that in humans extra hepatic gluconeogenesis is sufficient to maintain normal blood glucose in the anhepatic phase of orthotopic liver transplantation, while in the pig this was not the case.     

The -250G>A promoter variant in hepatic lipase associates with elevated fasting serum high-density lipoprotein cholesterol modulated by interaction with physical activity in a study of 16,156 Danish subjects

CONTEXT: Hepatic lipase plays a pivotal role in the metabolism of high-density lipoprotein (HDL) and low-density lipoprotein by involvement in reverse cholesterol transport and the formation of atherogenic small dense low-density lipoprotein. OBJECTIVES: The objective was to investigate the impact of variants in LIPC on metabolic traits and type 2 diabetes in a large sample of Danes. Because behavioral factors influence hepatic lipase activity, we furthermore examined possible gene-environment interactions in the population-based Inter99 study. DESIGN: The LIPC -250G>A (rs2070895) variant was genotyped in the Inter99 study (n = 6070), the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care Denmark screening cohort of individuals with risk factors for undiagnosed type 2 diabetes (n = 8662), and in additional type 2 diabetic patients (n = 1,064) and glucose-tolerant control subjects (n = 360). RESULTS: In the Inter99 study, the A allele of rs2070895 associated with a 0.057 mmol/liter [95% confidence interval (CI) 0.039-0.075] increase in fasting serum HDL-cholesterol (HDL-c) (P = 8 x 10(-10)) supported by association in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care study [0.038 mmol/liter per allele (95% CI 0.024-0.053); P = 2 x 10(-7)). The allelic effect on HDL-c was modulated by interaction with self-reported physical activity (P(interaction) = 0.002) because vigorous physically active homozygous A-allele carriers had a 0.30 mmol/liter (95% CI 0.22-0.37) increase in HDL-c compared with homozygous G-allele carriers. CONCLUSIONS: We validate the association of LIPC promoter variation with fasting serum HDL-c and present data supporting an interaction with physical activity implying an increased effect on HDL-c in vigorous physically active subjects carrying the -250 A allele. This interaction may have potential implications for public health and disease prevention.     

Mutated Desmoglein‐2 Proteins are Incorporated into Desmosomes and Exhibit Dominant‐Negative Effects in Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a hereditary cardiac condition associated with ventricular arrhythmias, heart failure, and sudden death. The most frequent ARVC genes encode desmosomal proteins of which mutations in desmoglein‐2 (DSG2), account for 10%–20% of cases. This study aimed to investigate how DSG2 mutations contribute to the pathogenesis of ARVC. Initial mutation analysis of DSG2 in 71 probands identified the first family reported with recessively inherited ARVC due to a missense mutation. In addition, three recognized DSG2 mutations were identified in 12 families. These results and further mutation analyses of four additional desmosomal genes indicated that ARVC caused by DSG2 mutations is often transmitted by recessive or digenic inheritance. Because desmosomal proteins are also expressed in skin tissue, keratinocytes served as a cell model to investigate DSG2 protein expression by Western blotting, 2D‐PAGE, and liquid chromatography–mass spectrometry. The results showed that heterozygous mutation carriers expressed both mutated and wild‐type DSG2 proteins. These findings were consistent with the results obtained by immunohistochemistry of endomyocardial biopsies and epidermal tissue of mutation carriers, which indicated a normal cellular distribution of DSG2. The results suggested a dominant‐negative effect of the mutated DSG2 proteins because they were incorporated into the desmosomes.     

Unique method of tooth replacement in durophagous placodont marine reptiles,with new data on the dentition of Chinese taxa

The placodonts of the Triassic period (~252–201 mya) represent one of the earliest and most extreme specialisations to a durophagous diet of any known reptile group. Exceptionally enlarged crushing tooth plates on the maxilla, dentary and palatine cooperated to form functional crushing areas in the buccal cavity. However, the extreme size of these teeth, combined with the unusual way they occluded, constrained how replacement occurred. Using an extensive micro‐computed tomographic dataset of 11 specimens that span all geographic regions and placodont morphotypes, tooth replacement patterns were investigated. In addition, the previously undescribed dental morphologies and formulae of Chinese taxa are described for the first time and incorporated into the analysis. Placodonts have a unique tooth replacement pattern and results follow a phylogenetic trend. The plesiomorphic Placodus species show many replacement teeth at various stages of growth, with little or no discernible pattern. On the other hand, the more derived cyamodontoids tend to have fewer replacement teeth growing at any one time, replacing teeth unilaterally and/or in functional units, thus maintaining at least one functional crushing area at all times. The highly derived placochelyids have fewer teeth and, as a result, only have one or two replacement teeth in the upper jaw. This supports previous suggestions that these taxa had an alternative diet to other placodonts. Importantly, all specimens show at least one replacement tooth growing at the most posterior palatine tooth plates, indicating increased wear at this point and thus the most efficient functional crushing area.