The cDNA and deduced amino acid sequence of the γ subunit of the L-type calcium channel from rabbit skeletal muscle

Complementary DNAs for the γ subunit of the calcium channel of rabbit skeletal muscle were isolated on the basis of peptide sequences derived from the purified protein. The deduced primary structure is without homology to other known protein sequences and is consistent with the γ subunit being an integral membrane protein

Helicobacter pylori Genotyping from American Indigenous Groups Shows Novel Amerindian vacA and cagA Alleles and Asian, African and European Admixture

It is valuable to extend genotyping studies of Helicobacter pylori to strains from indigenous communities across the world to better define adaption, evolution, and associated diseases. We aimed to genetically characterize both human individuals and their infecting H. pylori from indigenous communities of Mexico, and to compare them with those from other human groups. We studied individuals from three indigenous groups, Tarahumaras from the North, Huichols from the West and Nahuas from the center of Mexico. Volunteers were sampled at their community site, DNA was isolated from white blood cells and mtDNA, Y-chromosome, and STR alleles were studied. H. pylori was cultured from gastric juice, and DNA extracted for genotyping of virulence and housekeeping genes. We found Amerindian mtDNA haplogroups (A, B, C, and D), Y-chromosome DYS19T, and Amerindian STRs alleles frequent in the three groups, confirming Amerindian ancestry in these Mexican groups. Concerning H.pylori cagA phylogenetic analyses, although most isolates were of the Western type, a new Amerindian cluster neither Western nor Asian, was formed by some indigenous Mexican, Colombian, Peruvian and Venezuelan isolates. Similarly, vacA phylogenetic analyses showed the existence of a novel Amerindian type in isolates from Alaska, Mexico and Colombia. With hspA strains from Mexico and other American groups clustered within the three major groups, Asian, African or European. Genotyping of housekeeping genes confirmed that Mexican strains formed a novel Asian-related Amerindian group together with strains from remote Amazon Aborigines. This study shows that Mexican indigenous people with Amerindian markers are colonized with H. pylori showing admixture of Asian, European and African strains in genes known to interact with the gastric mucosa. We present evidence of novel Amerindian cagA and vacA alleles in indigenous groups of North and South America

Ritmos circadianos de sueño y rendimiento académico en estudiantes de medicina

Objective: to evaluate, with a preliminary study, the distribution of circadian rhythms, sleep schedule patterns and their relationship with academic performance on medical students. Methodology: in this descriptive study, a 10 item original questionnaire about sleep rhythms and academic performance was applied to medical students from different semesters. Week (class time) and weekend schedules, preferences, daytime somnolence and academic performance were asked. Three chronotypes (morningness, intermediate and eveningness) were defined among waking-sleeping preference, difficulty to sleep early, exam preparation preference hour and real sleep schedule. The sleep hour deficit per week night was also calculated. Results: Of the 318 medical students that answered the questionnaire, 62.6% corresponded to intermediate chronotypes, 8.8% to evening-type and 28.7% to morning-type. Significant difference was found among the two chronotype tails (p=0.000, Chi-square 31.13). No correlation was found between academic performance and age, sex, chronotype, week sleep deficit and sleep hours in week and weekends. A 71.1% of the students slept 6 or fewer hours during class time and 78% had a sleep deficit (more frequent in the evening chronotype). Conclusions: No relation was found between sleep chronotype and academic performance. Students tend to morningness. Few studies have been made on equatorial zones or without seasonsObjetivo: hacer un estudio preliminar de la distribución de los ritmos circadianos, los patrones horarios de sueño y su relación con el desempeño académico de estudiantes de medicina. Metodología: estudio descriptivo con aplicación de encuesta original de 10 ítems sobre ritmos de sueño y rendimiento académico a estudiantes de medicina de varios semestres. Se indagó sobre las preferencias y horarios de sueño en fines de semana y entre semana, la somnolencia diurna y el rendimiento académico. Según la preferencia para acostarse y levantarse, la dificultad para dormirse temprano, la preferencia horaria para preparar exámenes y el horario real de sueño, se definieron tres cronotipos (madrugador, intermedio y vespertino). También se calculó el déficit de horas de sueño por noche entre semana. Resultados: de los 318 estudiantes de medicina que respondieron la encuesta, el 62.6 % correspondió al cronotipo intermedio, el 8.8 % al vespertino y el 28.7 % al matutino. La diferencia entre los dos extremos fue estadísticamente significativa, ji-cuadrado 31.13, p=0.000. No se encontró correlación entre el rendimiento académico con edad, sexo, cronotipos, déficit de sueño entre semana y número de horas de sueño entre semana y en fines de semana. El 71.1 % de los estudiantes duerme 6 horas o menos entre semana y un 78 % presenta déficit de sueño que es mayor en los vespertinos. Conclusiones: No se encontró relación entre cronotipo de sueño y rendimiento académico. Los estudiantes tienden a una preferencia matutina. Son pocos los estudios realizados en zonas ecuatoriales o sin estaciones

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels

The cloning of the cDNA for the α1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these α1 subunits and the skeletal muscle α2/δ, β and γ subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the α1-, β- and γ-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The α1, β and γ mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle α2/δ subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the α1, β and γ subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner

Socio-economic status and the risk of developing hand, hip or knee osteoarthritis: a region-wide ecological study

SummaryObjectiveTo determine the association between socio-economic status (SES) and risk of hand, hip or knee osteoarthritis (OA) at a population level.DesignRetrospective ecological study using the System for the Development of Research in Primary Care (SIDIAP) database (primary care anonymized records for >5 million people in Catalonia (Spain)). Urban residents >15 years old (2009–2012) were eligible. Outcomes: Validated area-based SES deprivation index MEDEA (proportion of unemployed, temporary workers, manual workers, low educational attainment and low educational attainment among youngsters) was estimated for each area based on census data as well as incident diagnoses (ICD-10 codes) of hand, hip or knee OA (2009–2012). Zero-inflated Poisson models were fitted to study the association between MEDEA quintiles and the outcomes.ResultsCompared to the least deprived, the most deprived areas were younger (43.29 (17.59) vs 46.83 (18.49), years (Mean SD), had fewer women (49.1% vs 54.8%), a higher percentage of obese (16.2% vs 8.4%), smokers (16.9% vs 11.9%) and high-risk alcohol consumption subjects (1.5% vs 1.3%). Compared to the least deprived, the most deprived areas had an excess risk of OA: age-sex-adjusted Incidence Rate Ratio (IRR) 1.26 (1.11–1.42) for hand, 1.23 (1.17–1.29) hip, and 1.51 (1.45–1.57) knee. Adjustment for obesity attenuated this association: 1.06 (0.93–1.20), 1.04 (0.99–1.09), and 1.23 (1.19–1.28) respectively.ConclusionsDeprived areas have higher rates OA (hand, hip, knee). Their increased prevalence of obesity accounts for a 50% of the excess risk of knee OA observed. Public health interventions to reduce the prevalence of obesity in this population could reduce health inequalities

Maternal Hyperleptinemia Increases Arterial Stiffening and Alters Vasodilatoy Responses to Insulin in Adult Male Mice Offspring

Cardiovascular disease (CVD) is the number one cause of death in the U.S., and exposure to adverse maternal environments has been associated with the development of CVD including hypertension. Gestational diabetes mellitus (GDM) is an adverse maternal environment that has been associated with metabolic and CVD outcomes in the offspring. Key features of GDM and CVD are maternal hyperleptinemia and vascular disfunction/remodeling, respectively. Yet, there is limited information on the effects of maternal hyperleptinemia has on the function and structure of the offspring’s resistance vasculature. We hypothesize that alterations in offspring’s resistance artery structure and function underlie programming mechanisms for cardiovascular disease that are associated with maternal hyperleptinemia and GDM. To test this hypothesis, we used Leprdb/+ mice dams, which exhibit maternal hyperleptinemia and wildtype (WT) as controls. Vascular function was assessed in WT male offspring of control and hyperleptinemic dams at 31 weeks of age, after half the offspring had been fed a high fat diet (HFD) for 6 weeks. On a standard diet (SD), offspring of hyperleptinemic dams had mesenteric arteries with larger internal diameters than those of WT dams (258.36±14.99 vs 233.65±9.36 μm, p<0.05) indicative of outwardly remodeled, and enhanced maximal vasodilatory responses to insulin (39.97±6.71 vs 32.23±5.07 %, p<0.05). In offspring of WT, but not hyperleptinemic dams, HFD increased vessel wall cross-sectional area (18590.01±1251.16 vs 12807.20±1060.70 μm2, p<0.05), and enhanced the maximal vasodilatory response to acetylcholine (33.74±4.92 vs 21.86±2.73 %, p<0.05). HFD reduced the maximal response to insulin in offspring of hyperleptinemic dams compared to their WT and lean controls (21.88±3.80 vs 37.42±7.84 and 39.97±6.71 % respectively, p<0.05). Offspring of hyperleptinemic dams fed a HFD had increased elastic moduli normalized as a function of the percolation of the internal elastic lamina compared to their WT and lean controls (0.53±0.038 vs 0.34±0.023 and 0.38±0.032 ×106 dynes/cm2 respectively, p<0.05). Offspring of hyperleptinemic dams also had stiffer arteries at high pressure under both dietary conditions (2.36±0.35 vs 1.45±0.11 ×106 dynes/cm2, p<0.05). We conclude that when mice were fed a SD, maternal hyperleptinemia had beneficial effects to offspring’s vascular health, but did not protect offspring fed a HFD. Furthermore, maternal hyperleptinemia induced arterial stiffness in offspring regardless of diet. These results suggest that GDM programs offspring vascular function and structure through mechanisms that may be in part dependent on circulating maternal leptin levels and are differentially affected by postnatal developmental exposures

Characterization of enterotoxigenic Escherichia coli strains isolated from Nicaraguan children in hospital, primary care and community settings

Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhoea among young children in developing countries. ETEC vaccines offer promise in reducing the burden of ETEC disease, but the development of these vaccines relies on the characterization of ETEC isolates from a variety of settings. To best reflect the full spectrum of ETEC disease in León, Nicaragua, the aim of this study was to characterize ETEC strains isolated from children with diarrhoea attending different settings (hospital, primary care clinics and in the community) and children from different age groups. We characterized ETEC isolates in terms of their colonization factors (CFs) and enterotoxins, and determined whether these factors varied with setting and age group. Diarrhoeal stool samples were obtained from children under the age of 60 months from: (1) the regional public hospital, (2) four public primary care clinics, and (3) a population-based cohort. In total, 58 ETEC-positive isolates were analysed by multiplex-PCR assays for the identification of CFs (CS1, CS2, CS3, CS4, CS5, CS6, CS7, CS8, CS12, CS13, CS14, CS15, CS17, CS18, CS19, CS20, CS21, CS22 and CFA/I), and enterotoxins [heat-labile toxin (LT) and heat-stable variants STh and STp]. The frequency of CFs and enterotoxins was compared among the three settings and for different age groups, using Fisher’s exact test or a χ2 test. At least one CF was detected among one-half of samples; CS19 was detected among all strains in which a CF was identified, either alone or in combination with another CF. Among all CFs detected, 91.7 % were identified as members of the class 5 fimbrial family. CFs were detected more commonly among samples from infants captured in the health facility setting compared with the community setting. Overall, LT was detected among 67.2 % of samples, STh was detected among 20.7 % and both enterotoxins were detected among 12.1 %. The enterotoxin STh was detected more commonly among cases in the community, whilst a combination of STh and LT was detected more commonly among cases treated in health facilities. Our results suggest that, to protect against diarrhoeal cases associated with this E. coli pathotype in León, Nicaragua, an ETEC vaccine that effectively targets the archeotype CFA/I of the class 5 fimbrial family would be the most effective in this setting