Developmental mutant mouse models for external genitalia formation

Development of external genitalia and perineum is the subject of developmental biology as well as toxicology and teratology researches. Cloaca forms in the lower (caudal) end of endoderm. Such endodermal epithelia and surrounding mesenchyme interact with various signals to form the external genitalia. External genitalia (the anlage termed as genital tubercle: GT) formation shows prominent sexually dimorphic morphogenesis in late embryonic stages, which is an unexplored developmental research field because of many reasons. External genitalia develop adjacent to the cloaca which develops urethra and corporal bodies. Developmental regulators including growth factor signals are necessary for epithelia‐mesenchyme interaction (EMI) in posterior embryos including the cloaca and urethra in the genitalia. In the case of male type urethra, formation of tubular urethra proceeds from the lower (ventral) side of external genitalia as a masculinization process in contrast to the case of female urethra. Mechanisms for its development are not elucidated yet due to the lack of suitable mutant mouse models. Because of the recent progresses of Cre (recombinase)‐mediated conditional target gene modification analyses, many developmental regulatory genes become increasingly analyzed. Conditional gene knockout mouse approaches and tissue lineage approaches are expected to offer vital information for such sexually dimorphic developmental processes. This review aims to offer recent updates on the progresses of these emerging developmental processes for the research field of congenital anomalies.     

Substance-Induced Psychosis

Intoxication and withdrawal from a variety of central nervous system depressants and stimulants may induce hallucinations or delusions, which, when unaccompanied by insight, are the hallmarks of psychosis. A substance-induced psychosis may, in many instances, present as an organic psychosis or as an independent mental disorder (eg, schizophrenia), complicating diagnostic efforts. Ramifications of a misdiagnosed psychotic illness are potentially long-lasting and harmful to a patient. It is, therefore, crucial that health care providers be aware of the complex relationship between substance abuse, psychotic symptoms, and independent psychotic disorders. This report addresses substance-induced psychosis, by describing those psychotic symptoms most commonly associated with the abuse of specific drugs and alcohol, detailing useful diagnostic techniques and outlining treatment recommendations.     

Measurement and prediction of METs during household activities in 35- to 45-year-old females

This study determined whether four self-paced household tasks, conducted in the subjects homes and a standardised laboratory environment, were performed at a moderate intensity [3–6 metabolic equivalents (METs)] in a representative sample of thirty-six 35- to 45-year-old females. Energy expenditure was also predicted via indirect methods. Self-paced energy expenditure during sweeping, window cleaning, vacuuming and mowing was measured using the Douglas bag technique. Heart rate, respiratory frequency, Computer Science Applications (CSA) movement counts (hip and wrist), Borg rating of perceived exertion and Quetelets index were also recorded as potential predictors of energy expenditure. While the four activities were performed at mean intensities 3.0 METs in both the home and laboratory, all comparisons between these two environments were statistically significant (P<0.001). The 95% confidence intervals (CIs) for the home and laboratory prediction equations were ±1.1 METs and ±1.0 MET, respectively. These data suggest that the aforementioned household chores can contribute to the 30 min·day^–1 of moderate-intensity activity required to confer health benefits. However, the substantial between-subject variability in energy expenditure resulted in some persons performing these tasks at a light intensity (<3.0 METs). The significant MET differences between the home and laboratory emphasise the effects of environment and terrain and the mental approach to a task on self-paced energy expenditure. Considering the means for the five activities ranged from 3.1 METs to 6.0 METs, the 95% CIs for the regression equations lack predictive precision.     

Effect of creatine supplementation on metabolism and performance in humans during intermittent sprint cycling

This double blind study investigated the effect of oral creatine supplementation (CrS) on 4 × 20 s of maximal sprinting on an air-braked cycle ergometer. Each sprint was separated by 20 s of recovery. A group of 16 triathletes [mean age 26.6 (SD 5.1) years. mean body mass 77.0 (SD 5.8) kg, mean body fat 12.9 (SD 4.6)%, maximal oxygen uptake 4.86 (SD 0.7) l · min⁻¹] performed an initial 4 × 20 s trial after a muscle biopsy sample had been taken at rest. The subjects were then matched on their total intramuscular creatine content (TCr) before being randomly assigned to groups to take by mouth either a creatine supplement (CRE) or a placebo (CON) before a second 4 × 20 s trial. A muscle biopsy sample was also taken immediately before this second trial. The CrS of 100 g comprised 4 × 5 g for 5 days. The initial mean TCr were 112.5 (SD 8.7) and 112.5 (SD 10.7) mmol · kg⁻¹ dry mass for CRE and CON, respectively. After creatine loading and placebo ingestion respectively, CRE [128.7 (SD 11.8) mmol · kg⁻¹ dry mass] had a greater (P=0.01) TCr than CON [112.0 (SD 10.0) mmol · kg⁻¹ dry mass]. While the increase in free creatine for CRE was statistically significant (P=0.034), this was not so for the changes in phosphocreatine content [trial 1: 75.7 (SD 6.9), trial 2: 84.7 (SD 11.0) mmol · kg⁻¹ dry mass, P=0.091]. There were no significant differences between CRE and CON for citrate synthase activity (P=0.163). There was a tendency towards improved performance in terms of 1 s peak power (in watts P=0.07; in watts per kilogram P=0.05), 5 s peak power (in watts P=0.08) and fatigue index (P=0.08) after CrS for sprint 1 of the second trial. However, there was no improvement for mean power (in watts P=0.15; in watts per kilogram P=0.1) in sprint 1 or for any performance values in subsequent sprints. Our results suggest that, while CrS elevates the intramuscular stores of free creatine, this does not have an ergogenic effect on 4 × 20 s all-out cycle sprints with intervening 20-s rest periods. Accepted: 2 October 2000     

The APRU Global Health Program: Past and Future

The Association of Pacific Rim Universities (APRU) is an international consortium of 45 universities in the Pacific Rim, representing 16 economies, 130 000 faculty members and more than two million students. The APRU Global Health Program aims to expand existing collaborative research efforts among universities to address regional and global health issues. Since its launch in 2007–08, the program has covered a significant range of topics including emerging public health threats, ageing and chronic diseases, infectious diseases and health security issues, among others. The Program’s activities in research, training, and service around the globe illustrate the diverse dimensions of global health. In this paper, the major activities to date are outlined and future planned activities are discussed.Key words: Pacific Rim, Asia-Pacific, education, training, universities, global health     

Perivascular adipose tissue from human systemic and coronary vessels: the emergence of a new pharmacotherapeutic target

Fat cells or adipocytes are distributed ubiquitously throughout the body and are often regarded purely as energy stores. However, recently it has become clear that these adipocytes are engine rooms producing large numbers of metabolically active substances with both endocrine and paracrine actions. White adipocytes surround almost every blood vessel in the human body and are collectively termed perivascular adipose tissue (PVAT). It is now well recognized that PVAT not only provides mechanical support for any blood vessels it invests, but also secretes vasoactive and metabolically essential cytokines known as adipokines, which regulate vascular function. The emergence of obesity as a major challenge to our healthcare systems has contributed to the growing interest in adipocyte dysfunction with a view to discovering new pharmacotherapeutic agents to help rescue compromised PVAT function. Very few PVAT studies have been carried out on human tissue. This review will discuss these and the hypotheses generated from such research, as well as highlight the most significant and clinically relevant animal studies showing the most pharmacological promise. LINKED ARTICLES: This article is part of a themed section on Fat and Vascular Responsiveness. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-3.     

Diversified bursal medullary B cells survive and expand independently after depletion following neonatal infectious bursal disease virus infection

The primary immunoglobulin repertoire of chickens is generated not by gene rearrangement but by a subsequent process of gene conversion in proliferating immature B cells within the follicles of a specialized gut-associated lymphoid organ, the bursa of Fabricius. Neonatal infection with infectious bursal disease virus can eliminate almost the entire bursal B-cell compartment. Thereafter, two types of follicle reappear. Larger follicles, with rapidly proliferating B cells and normal structure, are correlated with partial recovery of antibody response. Smaller follicles, lacking distinct cortex and medulla, appear unable to produce antigen-responsive B cells. To understand the genesis of the two types of follicle, we analysed their VL sequences and activation-induced deaminase mRNA levels. The results provide a model of bursal repopulation in which surviving bursal stem cells generate new follicles with normal morphology and function, while surviving medullary B cells continue to proliferate slowly, under the influence of stromal cells, giving rise to the smaller follicles. The latter remain fixed in a stage of development incapable of further gene diversification.