Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

The Hidden Curriculum of Veterinary Education: Mediators and Moderators of Its Effects

The “hidden curriculum” has long been supposed to have an effect on students' learning during their clinical education, and in particular in shaping their ideas of what it means to be a professional. Despite this, there has been little evidence linking specific changes in professional attitudes to the individual components of the hidden curriculum. This study aimed to recognize those components that led to a change in students' professional attitudes at a UK veterinary school, as well as to identify the attitudes most affected. Observations were made of 11 student groups across five clinical rotations, followed by semi-structured interviews with 23 students at the end of their rotation experience. Data were combined and analyzed thematically, taking both an inductive and deductive approach. Views about the importance of technical competence and communication skills were promoted as a result of students' interaction with the hidden curriculum, and tensions were revealed in relation to their attitudes toward compassion and empathy, autonomy and responsibility, and lifestyle ethic. The assessment processes of rotations and the clinical service organization served to communicate the messages of the hidden curriculum, bringing about changes in student professional attitudes, while student-selected role models and the student rotation groups moderated the effects of these influences

Charming CP Violation and Dipole Operators from RS Flavor Anarchy

Recently the LHCb collaboration reported evidence for direct CP violation in charm decays. The value is sufficiently large that either substantially enhanced Standard Model contributions or non-Standard Model physics is required to explain it. In the latter case only a limited number of possibilities would be consistent with other existing flavor-changing constraints. We show that warped extra dimensional models that explain the quark spectrum through flavor anarchy can naturally give rise to contributions of the size required to explain the the LHCb result. The D meson asymmetry arises through a sizable CP-violating contribution to a chromomagnetic dipole operator. This happens naturally without introducing inconsistencies with existing constraints in the up quark sector. We discuss some subtleties in the loop calculation that are similar to those in Higgs to \gamma\gamma. Loop-induced dipole operators in warped scenarios and their composite analogs exhibit non-trivial dependence on the Higgs profile, with the contributions monotonically decreasing when the Higgs is pushed away from the IR brane. We show that the size of the dipole operator quickly saturates as the Higgs profile approaches the IR brane, implying small dependence on the precise details of the Higgs profile when it is quasi IR localized. We also explain why the calculation of the coefficient of the lowest dimension 5D operator is guaranteed to be finite. This is true not only in the charm sector but also with other radiative processes such as electric dipole moments, b to s\gamma, \epsilon'/\epsilon_K and \mu\ to e\gamma. We furthermore discuss the interpretation of this contribution within the framework of partial compositeness in four dimensions and highlight some qualitative differences between the generic result of composite models and that obtained for dynamics that reproduces the warped scenario.Comment: 14 page

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

&lt;p&gt;Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.&lt;/p&gt; &lt;p&gt;Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.&lt;/p&gt; &lt;p&gt;Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.&lt;/p&gt

A Novel Behavioral Assay for Measuring Cold Sensation in Mice

Behavioral models of cold responses are important tools for exploring the molecular mechanisms of cold sensation. To complement the currently cold behavioral assays and allow further studies of these mechanisms, we have developed a new technique to measure the cold response threshold, the cold plantar assay. In this assay, animals are acclimated on a glass plate and a cold stimulus is applied to the hindpaw through the glass using a pellet of compressed dry ice. The latency to withdrawal from the cooled glass is used as a measure of the cold response threshold of the rodents, and the dry ice pellet provides a ramping cold stimulus on the glass that allows the correlation of withdrawal latency values to rough estimates of the cold response threshold temperature. The assay is highly sensitive to manipulations including morphine-induced analgesia, Complete Freund's Adjuvant-induced inflammatory allodynia, and Spinal Nerve Ligation-induced neuropathic allodynia

Outcomes of an inpatient refeeding protocol in youth with anorexia nervosa: Rady Children’s Hospital San Diego/University of California, San Diego

BACKGROUND: Current guidelines for nutritional rehabilitation in hospitalized restrictive eating disorder patients recommend a cautious approach to refeeding. Several studies suggest that higher calorie diets may be safe and effective, but have traditionally excluded severely malnourished patients. The goal of this study was to evaluate the safety of a higher calorie nutritional rehabilitation protocol (NRP) in a broad sample of inpatients with restrictive eating disorders, including those who were severely malnourished. METHODS: A retrospective chart review was conducted among eating disorder inpatients between January 2015 and March 2016. Patients were started on a lower calorie diet (≤1500 kcals/day) or higher calorie diet (≥1500 kcals/day). Calorie prescription on admission was based on physician clinical judgement. The sample included patients aged 8–20 years with any DSM-5 restrictive eating disorder. Those who were severely malnourished (<75% expected body weight [EBW]) or required tube feeding during admission were included. Multivariable regression models were used to determine whether level of nutritional rehabilitation was associated with hypophosphatemia, hypomagnesemia, or hypokalemia. RESULTS: The sample included 87 patients; mean age was 14.4 years (S.D. 32.7); 29% were <75% EBW. The majority (75.8%) was started on higher calorie diets (mean 1781 kcal/day). Controlling for rate of calorie change, initial %EBW, age, race/ethnicity, insurance, diagnosis, and NG/NJ tube placement, higher calorie diets were not associated with hypophosphatemia, hypomagnesemia, or hypokalemia on admission or within the first 72 h. Increased risk of hypophosphatemia on admission was associated with lower baseline %EBW. CONCLUSION: A higher calorie NRP was tolerated in this broad population of inpatients with restrictive eating disorders. Lower %EBW on admission was a more important predictor of hypophosphatemia than initial calorie level. Larger studies are required to demonstrate the safety of higher calorie diets in severely malnourished patients

Oral tolerance inhibits pulmonary eosinophilia in a cockroach allergen induced model of asthma: a randomized laboratory study

<p>Abstract</p> <p>Background</p> <p>Antigen desensitization through oral tolerance is becoming an increasingly attractive treatment option for allergic diseases. However, the mechanism(s) by which tolerization is achieved remain poorly defined. In this study we endeavored to induce oral tolerance to cockroach allergen (CRA: a complex mixture of insect components) in order to ameliorate asthma-like, allergic pulmonary inflammation.</p> <p>Methods</p> <p>We compared the pulmonary inflammation of mice which had received four CRA feedings prior to intratracheal allergen sensitization and challenge to mice fed PBS on the same time course. Respiratory parameters were assessed by whole body unrestrained plethysmography and mechanical ventilation with forced oscillation. Bronchoalveolar lavage fluid (BAL) and lung homogenate (LH) were assessed for cytokines and chemokines by ELISA. BAL inflammatory cells were also collected and examined by light microscopy.</p> <p>Results</p> <p>CRA feeding prior to allergen sensitization and challenge led to a significant improvement in respiratory health. Airways hyperreactivity measured indirectly via enhanced pause (Penh) was meaningfully reduced in the CRA-fed mice compared to the PBS fed mice (2.3 ± 0.4 vs 3.9 ± 0.6; p = 0.03). Directly measured airways resistance confirmed this trend when comparing the CRA-fed to the PBS-fed animals (2.97 ± 0.98 vs 4.95 ± 1.41). This effect was not due to reduced traditional inflammatory cell chemotactic factors, Th2 or other cytokines and chemokines. The mechanism of improved respiratory health in the tolerized mice was due to significantly reduced eosinophil numbers in the bronchoalveolar lavage fluid (43300 ± 11445 vs 158786 ± 38908; p = 0.007) and eosinophil specific peroxidase activity in the lung homogenate (0.59 ± 0.13 vs 1.19 ± 0.19; p = 0.017). The decreased eosinophilia was likely the result of increased IL-10 in the lung homogenate of the tolerized mice (6320 ± 354 ng/mL vs 5190 ± 404 ng/mL, p = 0.02).</p> <p>Conclusion</p> <p>Our results show that oral tolerization to CRA can improve the respiratory health of experimental mice in a CRA-induced model of asthma-like pulmonary inflammation by reducing pulmonary eosinophilia.</p

A fresh look at the evolution and diversification of photochemical reaction centers

In this review, I reexamine the origin and diversification of photochemical reaction centers based on the known phylogenetic relations of the core subunits, and with the aid of sequence and structural alignments. I show, for example, that the protein folds at the C-terminus of the D1 and D2 subunits of Photosystem II, which are essential for the coordination of the water-oxidizing complex, were already in place in the most ancestral Type II reaction center subunit. I then evaluate the evolution of reaction centers in the context of the rise and expansion of the different groups of bacteria based on recent large-scale phylogenetic analyses. I find that the Heliobacteriaceae family of Firmicutes appears to be the earliest branching of the known groups of phototrophic bacteria; however, the origin of photochemical reaction centers and chlorophyll synthesis cannot be placed in this group. Moreover, it becomes evident that the Acidobacteria and the Proteobacteria shared a more recent common phototrophic ancestor, and this is also likely for the Chloroflexi and the Cyanobacteria. Finally, I argue that the discrepancies among the phylogenies of the reaction center proteins, chlorophyll synthesis enzymes, and the species tree of bacteria are best explained if both types of photochemical reaction centers evolved before the diversification of the known phyla of phototrophic bacteria. The primordial phototrophic ancestor must have had both Type I and Type II reaction centers

Study protocol to investigate the effect of a lifestyle intervention on body weight, psychological health status and risk factors associated with disease recurrence in women recovering from breast cancer treatment

Background Breast cancer survivors often encounter physiological and psychological problems related to their diagnosis and treatment that can influence long-term prognosis. The aim of this research is to investigate the effects of a lifestyle intervention on body weight and psychological well-being in women recovering from breast cancer treatment, and to determine the relationship between changes in these variables and biomarkers associated with disease recurrence and survival. Methods/design Following ethical approval, a total of 100 patients will be randomly assigned to a lifestyle intervention (incorporating dietary energy restriction in conjunction with aerobic exercise training) or normal care control group. Patients randomised to the dietary and exercise intervention will be given individualised healthy eating dietary advice and written information and attend moderate intensity aerobic exercise sessions on three to five days per week for a period of 24 weeks. The aim of this strategy is to induce a steady weight loss of up to 0.5 Kg each week. In addition, the overall quality of the diet will be examined with a view to (i) reducing the dietary intake of fat to ~25% of the total calories, (ii) eating at least 5 portions of fruit and vegetables a day, (iii) increasing the intake of fibre and reducing refined carbohydrates, and (iv) taking moderate amounts of alcohol. Outcome measures will include body weight and body composition, psychological health status (stress and depression), cardiorespiratory fitness and quality of life. In addition, biomarkers associated with disease recurrence, including stress hormones, estrogen status, inflammatory markers and indices of innate and adaptive immune function will be monitored. Discussion This research will provide valuable information on the effectiveness of a practical, easily implemented lifestyle intervention for evoking positive effects on body weight and psychological well-being, two important factors that can influence long-term prognosis in breast cancer survivors. However, the added value of the study is that it will also evaluate the effects of the lifestyle intervention on a range of biomarkers associated with disease recurrence and survival. Considered together, the results should improve our understanding of the potential role that lifestyle-modifiable factors could play in saving or prolonging lives