Injuries and accidents are acknowledged as leading causes of mortality among children and adolescents in the developing countries of the world. However, little is known of the extent of non-fatal injuries and of their potential risk factors. The Pan American Health Organization sponsored the first collaborative study to examine morbidity incidence in specified areas of four selected countries in Latin America, and to test the feasibility and practicality of the developed methodology for application in other regions of the world. The study subjects were injured children and adolescents (0-19 years of age) presenting at the study hospitals in the chosen urban centres, as well as injured that were surveyed in households in the catchment area of the hospitals. Falls constituted the most common (40-52%) cause of injury in all areas, and tended to occur in the younger age groups. Motor vehicle injuries were not as frequent (5-24%) as expected from mortality studies. Males outnumbered females 2:1. The home was the most frequent (37-57%) site of injuries, especially for younger ages. Few received medical care at the site of the injury or en route to a hospital, if they went at all. The results found are consistent with those found in other studies in the developed world. The study methodology provides initial valid information for investigating the injury situation in countries with limited resources.

A hepatitis E virus (HEV) infection alters cholesterol homeostasis in vitro and in vivo. Reduced cholesterol levels enhance viral release, yet an increase induces lysosomal HEV degradation. Concordantly, cholesterol-modulating drugs such as fenofibrate and PSC833 were identified as novel antivirals against HEV making use of this mechanism. BACKGROUND AND AIMS:The Hepatitis E virus hijacks the endosomal system for its release. These structures are highly dependent on cholesterol. Hence, this study investigates the impact of HEV on cholesterol-metabolism, the effect of intracellular cholesterol content on HEV-release and the potential of cholesterol-modulators to serve as antivirals.METHODS: Intracellular cholesterol-content of cells was modulated and impacts on HEV were monitored using qPCR, Western blot, microscopy, virus-titration and density-gradient centrifugation. Blood-lipids and HEV-RNA were routinely quantified in chronically infected patients during follow-up visits. RESULTS:In HEV-infected cells, decreased levels of cholesterol are found. In patients, HEV infection decreases serum-lipid concentrations. Importantly, statin treatment herein increases viral titers. Similarly, reduction of intracellular cholesterol via simvastatin treatment increases viral release in vitro. On the contrary, elevating intracellular cholesterol via LDL or 25hydroxycholesterol strongly reduces viral release due to enhanced lysosomal degradation of HEV. Drug-induced elevation of intracellular cholesterol via fenofibrate or PSC833 impairs HEV release via the same mechanism. CONCLUSIONS:This study analyses the crosstalk between HEV and intracellular cholesterol. The results highlight the importance of an intact cholesterol homeostasis for HEV-release and thereby identify a potential target for antiviral strategies. Especially fenofibrate is considered a promising novel antiviral against HEV. Beyond this, the study may help clinicians evaluating co-treatments of HEV-infected patients with statins, as this may be counter indicated.

Context Hyperphosphatemia and high levels of fibroblast growth factor 23 (FGF23) are risk factors for cardiovascular events in patients with chronic kidney diseases. However, the impact of an inorganic phosphorus additive in healthy people is largely unknown. Objective To investigate the acute effect of excessive dietary phosphorus administered as sodium-dihydrogen phosphate on the postprandial levels of Pi and FGF23 and the response to food. Design Double-blind placebo-controlled crossover study. Setting General community. Participants Twenty-nine healthy males and females. Intervention Administration of a single dose of either 700 mg phosphorus (NaH2PO4) or a sodium-adjusted placebo in combination with a test meal. Main Outcome Measure Postprandial plasma levels of Pi and FGF23. Results Compared to placebo, oral phosphorus increased the plasma Pi level, which remained elevated during the ensuing 8 h (at 480 min: 1.31 vs. 1.16 mmol/l, P < 0.001), increased urinary Pi (iAUC0-480 789 vs. 95 mmol/mmol, P < 0.001), reduced tubular Pi reabsorption (iAUC0-480 -31.5 vs. -6.2, P < 0.001), decreased urinary calcium (iAUC0-240 30.6 vs. 53.0 mmol/mmol, P = 0.009), and stimulated the release of parathyroid hormone (iAUC0-480 2212 vs. 768 ng/l, P < 0.001). However, the FGF23 levels did not change. Postprandial levels of glucose, insulin, and lipids were not substantially affected by phosphorus vs. placebo. Conclusion An oral phosphorus load can induce elevated postprandial levels of circulating Pi for hours in healthy subjects, despite rapid homeostatic counterreactions. FGF23 levels and the postprandial response to food were not affected.

Glycogen is the main store of readily energy in skeletal muscle and plays a key role in muscle function, demonstrated by the inability to sustain prolonged high-intensity exercise upon depletion of these glycogen stores. With prolonged exercise, glycogen depletion occurs and 5'-AMP-activated protein kinase (AMPK), a potent regulator of muscle metabolism and gene expression, is activated promoting molecular signalling that increases glucose uptake by muscular skeletal cells. The aim of this study was primarily to determine the effect of ultra-endurance exercise on muscle glycogen reserves and secondly to verify the influence of this type of exercise on AMPK protein expression. Twenty-four male Wistar rats, 60 days old, were divided into four experimental groups: sedentary, sedentary exhausted (SE), endurance trained (T) and endurance trained exhausted (TE). The animals ran for 10 to 90 min/day, 5 days/week, for 12 weeks to attain trained status. Rats were killed immediately after the exhaustion protocol, which consisted of running on a treadmill (at approximately 60% Vmax until exhaustion). Optical density of periodic acid-Schiff was detected and glycogen depletion observed predominantly in type I muscle fibres of the TE group and in both type I and II muscle fibres in the SE group. Plasma glucose decreased only in the TE group. Hepatic glycogen was increased in T group and significantly depleted in TE group. AMPK protein expression was significantly elevated in TE and T groups. In conclusion, acute exhaustive ultra-endurance exercise promoted muscle glycogen depletion. It seems that total AMPK protein and gene expression is more influenced by status training.

A 17-year-old boy had exercise-induced cramps and myoglobinuria. The mother had myalgia and weakness after exercise but the father was asymptomatic. Muscle biopsy was normal in the father but showed glycogen storage and absent or markedly decreased histochemical stain for phosphorylase in mother and son. Autosomal dominant McArdle's disease was considered likely, but biochemical studies showed that muscle phosphorylase activity was 0.6% of normal in the son, 20% in the mother, and 45% in the father, with corresponding decreases of cross-reacting material by immunotitration. These data suggest autosomal recessive transmission. One of the parents was clinically silent and the other was a manifesting heterozygote.