Reproducibility of the bronchoconstrictive response to eucapnic voluntary hyperpnoea

Background: Eucapnic voluntary hyperpnoea (EVH) is considered an effective bronchoprovocation challenge for identifying exercise-induced bronchoconstriction (EIB). However, the reproducibility of the hyperpnoea-induced bronchoconstriction (HIB) response elicited by EVH remains unknown and was therefore the focus of this study. Methods: Two cohorts of 16 physically active males (each cohort comprised 8 controls and 8 with physician diagnosis of asthma) participated in two studies of the short- and long-term reproducibility of the bronchoconstrictive response to an EVH test with dry air. EVH was performed on days 0, 7, 14, and 21 (short-term study), and 0, 35, and 70 (long-term study). HIB was diagnosed by a ≥10% fall in forced expiratory volume in 1 s (FEV1) after EVH. Results: On day 0 of the short-term study, FEV1 fell by 2 ± 1% (P < 0.05) and 27 ± 18% (P < 0.01) from pre-to post-EVH in control and HIB-positive groups respectively. The post-EVH fall in FEV1 did not differ across the short-term study test days. In the HIB-positive group, the day-to-day coefficient of variation, reproducibility, and smallest meaningful change for the fall in FEV1 were 12%, 328 mL, and 164 mL, respectively. On day 0 of the long-term study, FEV1 fell by 2 ± 2% and 25 ± 18% (P < 0.01) after EVH in control and HIB-positive groups respectively. The post-EVH fall in FEV1 did not differ across the long-term study test days. In the HIB-positive group, the day-to-day coefficient of variation, reproducibility, and smallest meaningful change for the fall in FEV1 were 10%, 196 mL, and 98 mL respectively. Conclusion: The EVH test elicits a reproducible bronchoconstrictive response in physically active males with physician diagnosed asthma. These data thus support the clinical utility of the EVH test for EIB screening and monitoring

Does Socio-Economic Background Affect First Year Economics Performance? A Preliminary Study

The paper examines the determination of academic performance in tertiary economics by adding a slightly broader range of factors that include socio-economic background to the main factors already identified in the literature

Wide variation in susceptibility of transmitted/founder HIV-1 subtype C Isolates to protease inhibitors and association with in vitro replication efficiency

© 2016 The Author(s).The gag gene is highly polymorphic across HIV-1 subtypes and contributes to susceptibility to protease inhibitors (PI), a critical class of antiretrovirals that will be used in up to 2 million individuals as second-line therapy in sub Saharan Africa by 2020. Given subtype C represents around half of all HIV-1 infections globally, we examined PI susceptibility in subtype C viruses from treatment-naïve individuals. PI susceptibility was measured in a single round infection assay of full-length, replication competent MJ4/gag chimeric viruses, encoding the gag gene and 142 nucleotides of pro derived from viruses in 20 patients in the Zambia-Emory HIV Research Project acute infection cohort. Ten-fold variation in susceptibility to PIs atazanavir and lopinavir was observed across 20 viruses, with EC50 s ranging 0.71-6.95 nM for atazanvir and 0.64-8.54 nM for lopinavir. Ten amino acid residues in Gag correlated with lopinavir EC50 (p < 0.01), of which 380 K and 389I showed modest impacts on in vitro drug susceptibility. Finally a significant relationship between drug susceptibility and replication capacity was observed for atazanavir and lopinavir but not darunavir. Our findings demonstrate large variation in susceptibility of PI-naïve subtype C viruses that appears to correlate with replication efficiency and could impact clinical outcomes

Bone mineral as a drug-seeking moiety and a waste dump

Bone is a dynamic tissue with a quarter of the trabecular and a fifth of the cortical bone being replaced continuously each year in a complex process that continues throughout an individual’s lifetime. Bone has an important role in homeostasis of minerals with non-stoichiometric hydroxyapatite bone mineral forming the inorganic phase of bone. Due to its crystal structure and chemistry, hydroxyapatite (HA) and related apatites have a remarkable ability to bind molecules. This review article describes the accretion of trace elements in bone mineral giving a historical perspective. Implanted HA particles of synthetic origin have proved to be an efficient recruiting moiety for systemically circulating drugs which can locally biomodulate the material and lead to a therapeutic effect. Bone mineral and apatite however also act as a waste dump for trace elements and drugs, which significantly affects the environment and human health

Appetite, gut hormone and energy intake responses to low volume sprint interval and traditional endurance exercise.

Sprint interval exercise improves several health markers but the appetite and energy balance response is unknown. This study compared the effects of sprint interval and endurance exercise on appetite, energy intake and gut hormone responses. Twelve healthy males [mean (SD): age 23 (3) years, body mass index 24.2 (2.9) kg m(-2), maximum oxygen uptake 46.3 (10.2) mL kg(-1) min(-1)] completed three 8 h trials [control (CON), endurance exercise (END), sprint interval exercise (SIE)] separated by 1 week. Trials commenced upon completion of a standardised breakfast. Sixty minutes of cycling at 68.1 (4.3) % of maximum oxygen uptake was performed from 1.75-2.75 h in END. Six 30-s Wingate tests were performed from 2.25-2.75 h in SIE. Appetite ratings, acylated ghrelin and peptide YY (PYY) concentrations were measured throughout each trial. Food intake was monitored from buffet meals at 3.5 and 7 h and an overnight food bag. Appetite (P 0.05). Therefore, relative energy intake (energy intake minus the net energy expenditure of exercise) was lower in END than that in CON (15.7 %; P = 0.006) and SIE (11.5 %; P = 0.082). An acute bout of endurance exercise resulted in lower appetite perceptions in the hours after exercise than sprint interval exercise and induced a greater 24 h energy deficit due to higher energy expenditure during exercise

Effective connectivity reveals strategy differences in an expert calculator

Mathematical reasoning is a core component of cognition and the study of experts defines the upper limits of human cognitive abilities, which is why we are fascinated by peak performers, such as chess masters and mental calculators. Here, we investigated the neural bases of calendrical skills, i.e. the ability to rapidly identify the weekday of a particular date, in a gifted mental calculator who does not fall in the autistic spectrum, using functional MRI. Graph-based mapping of effective connectivity, but not univariate analysis, revealed distinct anatomical location of “cortical hubs” supporting the processing of well-practiced close dates and less-practiced remote dates: the former engaged predominantly occipital and medial temporal areas, whereas the latter were associated mainly with prefrontal, orbitofrontal and anterior cingulate connectivity. These results point to the effect of extensive practice on the development of expertise and long term working memory, and demonstrate the role of frontal networks in supporting performance on less practiced calculations, which incur additional processing demands. Through the example of calendrical skills, our results demonstrate that the ability to perform complex calculations is initially supported by extensive attentional and strategic resources, which, as expertise develops, are gradually replaced by access to long term working memory for familiar material

Association between Plasma Antibody Response and Protection in Rainbow Trout Oncorhynchus mykiss Immersion Vaccinated against Yersinia ruckeri

A key hallmark of the vertebrate adaptive immune system is the generation of antigen-specific antibodies from B cells. Fish are the most primitive gnathostomes (jawed vertebrates) possessing an adaptive immune system. Vaccination of rainbow trout against enteric redmouth disease (ERM) by immersion in Yersinia ruckeri bacterin confers a high degree of protection to the fish. The immune mechanisms responsible for protection may comprise both cellular and humoral elements but the role of specific immunoglobulins in this system has been questioned and not previously described. The present study demonstrates significant increase in plasma antibody titers following immersion vaccination and significantly reduced mortality during Y. ruckeri challenge

Protein trafficking through the endosomal system prepares intracellular parasites for a home invasion

Toxoplasma (toxoplasmosis) and Plasmodium (malaria) use unique secretory organelles for migration, cell invasion, manipulation of host cell functions, and cell egress. In particular, the apical secretory micronemes and rhoptries of apicomplexan parasites are essential for successful host infection. New findings reveal that the contents of these organelles, which are transported through the endoplasmic reticulum (ER) and Golgi, also require the parasite endosome-like system to access their respective organelles. In this review, we discuss recent findings that demonstrate that these parasites reduced their endosomal system and modified classical regulators of this pathway for the biogenesis of apical organelles