Low Density Lipoproteins as Circulating Fast Temperature Sensors

Background: The potential physiological significance of the nanophase transition of neutral lipids in the core of low density lipoprotein (LDL) particles is dependent on whether the rate is fast enough to integrate small (62uC) temperature changes in the blood circulation. Methodology/Principal Findings: Using sub-second, time-resolved small-angle X-ray scattering technology with synchrotron radiation, we have monitored the dynamics of structural changes within LDL, which were triggered by temperature-jumps and-drops, respectively. Our findings reveal that the melting transition is complete within less than 10 milliseconds. The freezing transition proceeds slowly with a half-time of approximately two seconds. Thus, the time period over which LDL particles reside in cooler regions of the body readily facilitates structural reorientation of the apolar core lipids. Conclusions/Significance: Low density lipoproteins, the biological nanoparticles responsible for the transport of cholesterol in blood, are shown to act as intrinsic nano-thermometers, which can follow the periodic temperature changes during blood circulation. Our results demonstrate that the lipid core in LDL changes from a liquid crystalline to an oily state within fractions of seconds. This may, through the coupling to the protein structure of LDL, have important repercussions o

Educating and training a workforce for nutrition in a post-2015 world.

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals

Serum Metabolomics Reveals Higher Levels of Polyunsaturated Fatty Acids in Lepromatous Leprosy: Potential Markers for Susceptibility and Pathogenesis

Leprosy is an infectious disease caused by the obligate intracellular bacterium Mycobacterium leprae. M. leprae infects the skin and nerves, leading to disfigurement and nerve damage, with the severity of the disease varying widely. We believe there are multiple factors (genetic, bacterial, nutritional and environmental), which may explain the differences in clinical manifestations of the disease. We studied the metabolites in the serum of infected patients to search for specific molecules that may contribute to variations in the severity of disease seen in leprosy. We found that there were variations in levels of certain lipids in the patients with different bacterial loads. In particular, we found that three polyunsaturated fatty acids (PUFAs) involved in the inhibition of inflammation were more abundant in the serum of patients with higher bacterial loads. However, we do not know whether these PUFAs originated from the host or the bacteria. The variations in the metabolite profile that we observed provide a foundation for future research into the explanations of how leprosy causes disease

Educating and Training a Workforce for Nutrition in a Post-2015 World

Nearly all countries in the world today are burdened with malnutrition, manifesting as undernutrition, micronutrient deficiencies, and/or overweight and obesity. Despite some progress, efforts to alleviate malnutrition are hampered by a shortage in number, skills, and geographic coverage, of a workforce for nutrition. Here, we report the findings of the Castel Gandolfo workshop, a convening of experts from diverse fields in March 2014 to consider how to develop the capacity of a global cadre of nutrition professionals for the post-2015 development era. Workshop participants identified several requirements for developing a workforce for nutrition, including an ability to work as part of a multisectoral team; communication, advocacy, and leadership skills to engage decision makers; and a set of technical skills to address future challenges for nutrition. Other opportunities were highlighted that could immediately contribute to capacity development, including the creation of a consortium to link global North and South universities, online training modules for middle managers, and practical, hands-on experiences for frontline nutrition workers. Institutional and organizational support is needed to enable workshop recommendations on education and training to be effectively implemented and sustained. The findings from the Castel Gandolfo workshop can contribute to the delivery of successful nutrition-relevant actions in the face of mounting external pressures and informing and attaining the forthcoming Sustainable Development Goals. Adv Nutr 2015;6:639–47

Lifestyle modification and metformin as long-term treatment options for obese adolescents: study protocol

<p>Abstract</p> <p>Background</p> <p>Childhood obesity is a serious health concern affecting over 155 million children in developed countries worldwide. Childhood obesity is associated with significantly increased risk for development of type 2 diabetes, cardiovascular disease and psychosocial functioning problems (i.e., depression and decreased quality of life). The two major strategies for management of obesity and associated metabolic abnormalities are lifestyle modification and pharmacologic therapy. This paper will provide the background rationale and methods of the REACH childhood obesity treatment program.</p> <p>Methods/design</p> <p>The REACH study is a 2-year multidisciplinary, family-based, childhood obesity treatment program. Seventy-two obese adolescents (aged 10-16 years) and their parents are being recruited to participate in this randomized placebo controlled trial. Participants are randomized to receive either metformin or placebo, and are then randomized to a moderate or a vigorous intensity supervised exercise program for the first 12-weeks. After the 12-week exercise program, participants engage in weekly exercise sessions with an exercise facilitator at a local community center. Participants engage in treatment sessions with a dietitian and social worker monthly for the first year, and then every three months for the second year. The primary outcome measure is change in body mass index and the secondary outcome measures are changes in body composition, risk factors for type 2 diabetes and cardiovascular disease, changes in diet, physical activity, and psychosocial well-being (e.g., quality of life). It is hypothesized that participants who take metformin and engage in vigorous intensity exercise will show the greatest improvements in body mass index. In addition, it is hypothesized that participants who adhere to the REACH program will show improvements in body composition, physical activity, diet, psychosocial functioning and risk factor profiles for type 2 diabetes and cardiovascular disease. These improvements are expected to be maintained over the 2-year program.</p> <p>Discussion</p> <p>The findings from this study will advance the knowledge regarding the long-term efficacy and sustainability of interventions for childhood obesity.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov number NCT00934570</p

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Laparoscopy in management of appendicitis in high-, middle-, and low-income countries: a multicenter, prospective, cohort study.

BACKGROUND: Appendicitis is the most common abdominal surgical emergency worldwide. Differences between high- and low-income settings in the availability of laparoscopic appendectomy, alternative management choices, and outcomes are poorly described. The aim was to identify variation in surgical management and outcomes of appendicitis within low-, middle-, and high-Human Development Index (HDI) countries worldwide. METHODS: This is a multicenter, international prospective cohort study. Consecutive sampling of patients undergoing emergency appendectomy over 6 months was conducted. Follow-up lasted 30 days. RESULTS: 4546 patients from 52 countries underwent appendectomy (2499 high-, 1540 middle-, and 507 low-HDI groups). Surgical site infection (SSI) rates were higher in low-HDI (OR 2.57, 95% CI 1.33-4.99, p = 0.005) but not middle-HDI countries (OR 1.38, 95% CI 0.76-2.52, p = 0.291), compared with high-HDI countries after adjustment. A laparoscopic approach was common in high-HDI countries (1693/2499, 67.7%), but infrequent in low-HDI (41/507, 8.1%) and middle-HDI (132/1540, 8.6%) groups. After accounting for case-mix, laparoscopy was still associated with fewer overall complications (OR 0.55, 95% CI 0.42-0.71, p < 0.001) and SSIs (OR 0.22, 95% CI 0.14-0.33, p < 0.001). In propensity-score matched groups within low-/middle-HDI countries, laparoscopy was still associated with fewer overall complications (OR 0.23 95% CI 0.11-0.44) and SSI (OR 0.21 95% CI 0.09-0.45). CONCLUSION: A laparoscopic approach is associated with better outcomes and availability appears to differ by country HDI. Despite the profound clinical, operational, and financial barriers to its widespread introduction, laparoscopy could significantly improve outcomes for patients in low-resource environments. TRIAL REGISTRATION: NCT02179112