Effect of high-intensity resistance circuit-based training in hypoxia on aerobic performance and repeat sprint ability.

Recent acute studies have shown that high-intensity resistance circuit-based (HRC) training in hypoxia increases metabolic stress. However, no intervention studies have yet proven their effectiveness. This study aimed to analyze the effect of 8 weeks of HRC in hypoxia on aerobic performance, resting energy expenditure (REE), repeat sprint ability (RSA) and hematological variables. Twenty-eight subjects were assigned to hypoxia (FiO2  = 15%; HRChyp : n = 15; age: 24.6 ± 6.8 years; height: 177.4 ± 5.9 cm; weight: 74.9 ± 11.5 kg) and normoxia (FiO2  = 20.9%; HRCnorm : n = 13; age: 23.2 ± 5.2 years; height: 173.4 ± 6.2 cm; weight: 69.4 ± 7.4 kg) groups. Each training session consisted of two blocks of three exercises (Block 1: bench press, leg extension, front pull down; 2: deadlift, elbow flexion, ankle extension). Each exercise was performed at 6 repetitions maximum. Participants exercised twice weekly for 8 weeks and before and after the training program blood test, REE, RSA and treadmill running test were performed. Fatigue index in the RSA test was significantly decreased in the HRChyp (-0.9%; P < .01; ES = 2.75) but not in the HRCnorm . No changes were observed in REE and hematological variables. Absolute (4.5%; P = .014; ES = 0.42) and relative (5.2%; P = .008; ES = 0.43) maximal oxygen uptake (VO2 max), speed at VO2 max (4%; P = .010; ES = 0.25) and time to exhaustion (4.1%; P = .012; ES = 0.26) were significantly increased in HRChyp but not in the HRCnorm . No significant differences between groups were found. Compared with normoxic conditions, 8 weeks of HRC training under hypoxic conditions efficiently improves aerobic performance and RSA without changes in REE and red blood O2 -carrying capacity.

The serotonin-N-acetylserotonin-melatonin pathway as a biomarker for autism spectrum disorders.

Elevated whole-blood serotonin and decreased plasma melatonin (a circadian synchronizer hormone that derives from serotonin) have been reported independently in patients with autism spectrum disorders (ASDs). Here, we explored, in parallel, serotonin, melatonin and the intermediate N-acetylserotonin (NAS) in a large cohort of patients with ASD and their relatives. We then investigated the clinical correlates of these biochemical parameters. Whole-blood serotonin, platelet NAS and plasma melatonin were assessed in 278 patients with ASD, their 506 first-degree relatives (129 unaffected siblings, 199 mothers and 178 fathers) and 416 sex- and age-matched controls. We confirmed the previously reported hyperserotonemia in ASD (40% (35-46%) of patients), as well as the deficit in melatonin (51% (45-57%)), taking as a threshold the 95th or 5th percentile of the control group, respectively. In addition, this study reveals an increase of NAS (47% (41-54%) of patients) in platelets, pointing to a disruption of the serotonin-NAS-melatonin pathway in ASD. Biochemical impairments were also observed in the first-degree relatives of patients. A score combining impairments of serotonin, NAS and melatonin distinguished between patients and controls with a sensitivity of 80% and a specificity of 85%. In patients the melatonin deficit was only significantly associated with insomnia. Impairments of melatonin synthesis in ASD may be linked with decreased 14-3-3 proteins. Although ASDs are highly heterogeneous, disruption of the serotonin-NAS-melatonin pathway is a very frequent trait in patients and may represent a useful biomarker for a large subgroup of individuals with ASD.

Transgenic mouse model reveals an unsuspected role of the acetylcholine receptor in statin-induced neuromuscular adverse drug reactions.

High cholesterol levels are an established risk factor for cardiovascular disease (CVD), the world's leading cause of death. Inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (statins) are prescribed to lower serum cholesterol levels and reduce the risk of CVD. Despite the success of statins, many patients abandon treatment owing to neuromuscular adverse drug reactions (ADRs). Genome-wide association studies have identified the single-nucleotide polymorphism (SNP) rs4149056 in the SLCO1B1 gene as being associated with an increased risk for statin-induced ADRs. By studying slow-channel syndrome transgenic mouse models, we determined that statins trigger ADRs in mice expressing the mutant allele of the rs137852808 SNP in the nicotinic acetylcholine receptor (nAChR) α-subunit gene CHRNA1. Mice expressing this allele show a remarkable contamination of end-plates with caveolin-1 and develop early signs of neuromuscular degeneration upon statin treatment. This study demonstrates that genes coding for nAChR subunits may contain variants associated with statin-induced ADRs.

Investigations of peritoneal and intestinal infections of adult hookworms (Uncinaria spp.) in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, California (2003).

The peritoneal cavity (PNC) and intestine of northern fur seal (Callorhinus ursinus) pups and California sea lion (Zalophus californianus) pups that died in late July and early August, 2003, on San Miguel Island, California, were examined for hookworms. Prevalence and morphometric studies were done with the hookworms in addition to molecular characterization. Based on this and previous molecular studies, hookworms from fur seals are designated as Uncinaria lucasi and the species from sea lions as Uncinaria species A. Adult hookworms were found in the PNC of 35 of 57 (61.4%) fur seal pups and of 13 of 104 (12.5%) sea lion pups. The number of hookworms located in the PNC ranged from 1 to 33 (median = 3) for the infected fur seal pups and 1 to 16 (median = 2) for the infected sea lion pups. In addition to the PNC, intestines of 43 fur seal and 32 sea lion pups were examined. All of these pups were positive for adult hookworms. The worms were counted from all but one of the sea lion pups. Numbers of these parasites in the intestine varied from 3 to 2,344 (median = 931) for the fur seal pups and 39 to 2,766 (median = 643) for the sea lion pups. Sea lion pups with peritoneal infections had higher intensity infections in the intestines than did pups without peritoneal infections, lending some support for the hypothesis that peritoneal infections result from high-intensity infections of adult worms. There was no difference in intestinal infection intensities between fur seal pups with and without peritoneal infections. Female adult hookworms in the intestines of both host species were significantly larger than males, and sea lion hookworms were larger than those in fur seals. Worms in the intestine also were larger than worms found in the PNC. Gene sequencing and (RFLP) analysis of (PCR) amplified (ITS) ribosomal DNA were used to diagnose the species of 172 hookworms recovered from the PNC and intestine of 18 C. ursinus and seven Z. californianus hosts. These molecular data revealed that U. lucasi (hookworm of C. ursinus) and Uncinaria species A (of Z. californianus) infrequently mature in the intestine of the opposite host species in California rookeries. However, there is no support from molecular data for the hypothesis that cross-infection with "the wrong" Uncinaria species is a contributing factor in these cases of host peritonitis. The major significance of this research is the unusual finding of adult hookworms in the PNC of so many dead pups. No obvious explanation for this occurrence could be determined. Further research, like in the present study, should help understand and monitor the apparent ever changing role of hookworm disease in the health of northern fur seal and California sea lion pups on SMI.

Molecular phylogeny of clade III nematodes reveals multiple origins of tissue parasitism.

Molecular phylogenetic analyses of 113 taxa representing Ascaridida, Rhigonematida, Spirurida and Oxyurida were used to infer a more comprehensive phylogenetic hypothesis for representatives of 'clade III'. The posterior probability of multiple alignment sites was used to exclude or weight characters, yielding datasets that were analysed using maximum parsimony, likelihood, and Bayesian inference methods. Phylogenetic results were robust to differences among inference methods for most high-level taxonomic groups, but some clades were sensitive to treatments of characters reflecting differences in alignment ambiguity. Taxa representing Camallanoidea, Oxyurida, Physalopteroidea, Raphidascarididae, and Skrjabillanidae were monophyletic in all 9 analyses whereas Ascaridida, Ascarididae, Anisakidae, Cosmocercoidea, Habronematoidea, Heterocheilidae, Philometridae, Rhigonematida and Thelazioidea were never monophyletic. Some clades recovered in all trees such as Dracunculoidea and Spirurina included the vast majority of their sampled species, but were non-monophyletic due to the consistent behaviour of one or few 'rogue' taxa. Similarly, 102 of 103 clade III taxa were strongly supported as monophyletic, yet clade III was paraphyletic due to the grouping of Truttaedacnitis truttae with the outgroups. Mapping of host 'habitat' revealed that tissue-dwelling localization of nematode adults has evolved independently at least 3 times, and relationships among Spirurina and Camallanina often reflected tissue predilection rather than taxonomy.

Biochemical and hormonal variables in black and white women matched for age and weight.

Weight and age may influence the levels of indexes of bone remodeling and the calciotropic hormones. In a study of interracial differences in these women, our black population was heavier than our white population. We therefore matched a subset of 96 black and 96 white women from our larger population for age and weight to determine whether a racial difference exists independent of the effects of weight and age. In addition, we were able to measure other indexes of bone remodeling (N-telopeptide of cross-linked collagen and pyridinoline cross-links), as well as hormones that may influence calcium metabolism (insulin-like growth factor-1 (IGF-1), insulin, calcitonin, and gastrin) in this subset. All indexes of bone remodeling were lower in black women. Black postmenopausal women had lower serum levels of calcidiol and higher parathyroid hormone (PTH) levels. The higher bone mass of black women is associated with lower bone remodeling in the presence of skeletal resistance to PTH. Serum IGF- 1, insulin, and calcitonin levels did not differ significantly between races. Serum gastrin levels were higher in black women. The higher levels of gastrin in black women should be investigated further for its possible effect on the absorption of calcium salts.

Discordance between ultrasound of the calcaneus and bone mineral density in black and white women.

Black women have 40% of the incidence rate for hip fracture and have a higher bone mineral density (BMD) than white women. The possibility was raised that bone quality may be disproportionately greater than the advantage in bone density in protection against osteoporotic fractures in black versus white women. Ultrasound (US) of the calcaneus is believed to measure properties of bone in addition to its density. We performed bone density measurements and US of the calcaneus in 108 black and 177 healthy white women, aged 20-70 years. The highest correlation was seen between total body bone density and speed of sound (r = 0.75). The interracial differences in BMD were all statistically significant and varied from 3.4 to 7.6%. The US measurements had lesser interracial differences than the bone density measurements, with velocity barely different between races. These findings suggest that US of the calcaneus measures properties of bone different from density. Fracture prediction data using US from prospective data in white women should not be extrapolated to black women because of the discordance between bone density and US measurements. Prospective studies are needed comparing US measurements in black women to the occurrence of osteoporotic fractures.