How Does a Delay Between Temperate Running Exercise and Hot-Water Immersion Alter the Acute Thermoregulatory Response and Heat-Load?

Hot-water immersion following exercise in a temperate environment can elicit heat acclimation in endurance-trained individuals. However, a delay between exercise cessation and immersion is likely a common occurrence in practice. Precisely how such a delay potentially alters hot-water immersion mediated acute physiological responses (e.g., total heat-load) remains unexplored. Such data would aid in optimizing prescription of post-exercise hot-water immersion in cool environments, relative to heat acclimation goals. Twelve male recreational runners (mean ± SD; age: 38 ± 13 years, height: 180 ± 7 cm, body mass: 81 ± 13.7 kg, body fat: 13.9 ± 3.5%) completed three separate 40-min treadmill runs (18°C), followed by either a 10 min (10M), 1 h (1H), or 8 h (8H) delay, prior to a 30-min hot-water immersion (39°C), with a randomized crossover design. Core and skin temperatures, heart rate, sweat, and perceptual responses were measured across the trials. Mean core temperature during immersion was significantly lower in 1H (37.39 ± 0.30°C) compared to 10M (37.83 ± 0.24°C; p = 0.0032) and 8H (37.74 ± 0.19°C; p = 0.0140). Mean skin temperature was significantly higher in 8H (32.70 ± 0.41°C) compared to 10M (31.93 ± 0.60°C; p = 0.0042) at the end of the hot-water immersion. Mean and maximal heart rates were also higher during immersion in 10M compared to 1H and 8H (p < 0.05), despite no significant differences in the sweat or perceptual responses. The shortest delay between exercise and immersion (10M) provoked the greatest heat-load during immersion. However, performing the hot-water immersion in the afternoon (8H), which coincided with peak circadian body temperature, provided a larger heat-load stimulus than the 1 h delay (1H)

Uncertainty Compensation in Human Attention: Evidence from Response Times and Fixation Durations

BACKGROUND: Uncertainty and predictability have remained at the center of the study of human attention. Yet, studies have only examined whether response times (RT) or fixations were longer or shorter under levels of stimulus uncertainty. To date, no study has examined patterns of stimuli and responses through a unifying framework of uncertainty. METHODOLOGY/PRINCIPAL FINDINGS: We asked 29 college students to generate repeated responses to a continuous series of visual stimuli presented on a computer monitor. Subjects produced these responses by pressing on a keypad as soon a target was detected (regardless of position) while the durations of their visual fixations were recorded. We manipulated the level of stimulus uncertainty in space and time by changing the number of potential stimulus locations and time intervals between stimulus presentations. To allow the analyses to be conducted using uncertainty as common description of stimulus and response we calculated the entropy of the RT and fixation durations. We tested the hypothesis of uncertainty compensation across space and time by fitting the RT and fixation duration entropy values to a quadratic surface. The quadratic surface accounted for 80% of the variance in the entropy values of both RT and fixation durations. RT entropy increased as a function of spatial and temporal uncertainty of the stimulus, alongside a symmetric, compensatory decrease in the entropy of fixation durations as the level of spatial and temporal uncertainty of the stimuli was increased. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that greater uncertainty in the stimulus leads to greater uncertainty in the response, and that the effects of spatial and temporal uncertainties are compensatory. We also observed compensatory relationship across the entropies of fixation duration and RT, suggesting that a more predictable visual search strategy leads to more uncertain response patterns and vice versa

A Randomized Controlled Phase IIb Trial of Antigen-Antibody Immunogenic Complex Therapeutic Vaccine in Chronic Hepatitis B Patients

BACKGROUND: The safety of the immune complexes composed of yeast-derived hepatitis B surface antigen (HBsAg) and antibodies (abbreviated as YIC) among healthy adults and chronic hepatitis B patients has been proved in phase I and phase IIa trial. A larger number of patients for study of dosage and efficacy are therefore needed. METHODS AND PRINCIPAL FINDINGS: Two hundred forty two HBeAg-positive chronic hepatitis B patients were immunized with six injections of either 30 microg YIC, 60 microg of YIC or alum adjuvant as placebo at four-week intervals under code. HBV markers and HBV DNA were monitored during immunization and 24 weeks after the completion of immunization. The primary endpoint was defined as loss of HBeAg, or presence of anti-HBe antibody or suppression of HBV DNA, while the secondary endpoint was both HBeAg seroconversion and suppression of HBV DNA. Statistical significance was not reached in primary endpoints four weeks after the end of treatment among three groups, however, at the end of follow-up, HBeAg sero-conversion rate was 21.8% (17/78) and 9% (7/78) in the 60 microg YIC and placebo groups respectively (p = 0.03), with 95% confidence intervals at 1.5% to 24.1%. Using generalized estimating equations (GEEs) model, a significant difference of group effects was found between 60 microg YIC and the placebo groups in terms of the primary endpoint. Eleven serious adverse events occurred, which were 5.1%, 3.6%, and 5.0% in the placebo, 30 microg YIC and 60 microg YIC groups respectively (p>0.05). CONCLUSIONS: Though statistical differences in the preset primary and secondary endpoints among the three groups were not reached, a late and promising HBeAg seroconversion effect was shown in the 60 microg YIC immunized regimen. By increasing the number of patients and injections, the therapeutic efficacy of YIC in chronic hepatitis B patients will be further evaluated. TRIAL REGISTRATION: ChiCTR.org ChiCTR-TRC-00000022

Classification and nomenclature of all human homeobox genes

<p>Abstract</p> <p>Background</p> <p>The homeobox genes are a large and diverse group of genes, many of which play important roles in the embryonic development of animals. Increasingly, homeobox genes are being compared between genomes in an attempt to understand the evolution of animal development. Despite their importance, the full diversity of human homeobox genes has not previously been described.</p> <p>Results</p> <p>We have identified all homeobox genes and pseudogenes in the euchromatic regions of the human genome, finding many unannotated, incorrectly annotated, unnamed, misnamed or misclassified genes and pseudogenes. We describe 300 human homeobox loci, which we divide into 235 probable functional genes and 65 probable pseudogenes. These totals include 3 genes with partial homeoboxes and 13 pseudogenes that lack homeoboxes but are clearly derived from homeobox genes. These figures exclude the repetitive <it>DUX1 </it>to <it>DUX5 </it>homeobox sequences of which we identified 35 probable pseudogenes, with many more expected in heterochromatic regions. Nomenclature is established for approximately 40 formerly unnamed loci, reflecting their evolutionary relationships to other loci in human and other species, and nomenclature revisions are proposed for around 30 other loci. We use a classification that recognizes 11 homeobox gene 'classes' subdivided into 102 homeobox gene 'families'.</p> <p>Conclusion</p> <p>We have conducted a comprehensive survey of homeobox genes and pseudogenes in the human genome, described many new loci, and revised the classification and nomenclature of homeobox genes. The classification scheme may be widely applicable to homeobox genes in other animal genomes and will facilitate comparative genomics of this important gene superclass.</p

Primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9–10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13–15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC

Body Mindsets are Associated With Pain and Threat-Related Risk Factors for Pain in Survivors of Childhood Cancer.

Pain is a common consequence of childhood cancer. While most research has examined biomedical predictors of post-cancer pain, biopsychosocial conceptualisations such as the cancer threat interpretation (CTI) model hold promise for guiding comprehensive pain management strategies. Guided by the CTI model, this cross-sectional study evaluated correlates of post-cancer pain in childhood cancer survivors including threat-related risk factors (bodily threat monitoring, fear of cancer recurrence, help-seeking) and mindsets about the body. In the preceding three months, 21.8% of the survivors reported chronic pain (>3 months), and 14.3% experienced pain most days. Greater bodily threat monitoring, more fear of cancer recurrence, and more help-seeking were associated with more pain. There was heterogeneity in the mindsets that survivors of childhood cancer hold about their bodies. Holding the mindset that the 'body is an adversary' was associated with more pain, greater bodily threat monitoring, and more fear of cancer recurrence. Holding the mindset that the 'body is responsive' was associated with less bodily threat monitoring, while the mindset that the 'body is capable' was associated with greater help-seeking. A path model demonstrated a significant combined indirect effect of the 'body is an adversary' mindset on pain through bodily threat monitoring and fear of cancer recurrence. Overall, this study supported that a sub-group of childhood cancer survivors experience persistent and interfering pain and provided cross-sectional support for threat-related correlates for pain aligning with the CTI model. Body mindsets were associated with pain and threat-related correlates and may represent a novel target to support survivors with pain. PERSPECTIVE: This article presents associations of body mindsets, threat-related risk factors, and pain in survivors of childhood cancer (aged 11-25), guided by the Cancer Threat Interpretation model. The study indicates that body mindsets may be novel targets to embed in comprehensive post-cancer pain management approaches to support young survivors with pain