Elite male Flat jockeys display lower bone density and lower resting metabolic rate than their female counterparts: implications for athlete welfare

To test the hypothesis that daily weight-making is more problematic to health in male compared with female jockeys, we compared the bone-density and resting metabolic rate (RMR) in weight-matched male and female Flat-jockeys. RMR (kcal.kg-1 lean mass) was lower in males compared with females as well as lower bone-density Z-scores at the hip and lumbar spine. Data suggest the lifestyle of male jockeys’ compromise health more severely than females, possibly due to making-weight more frequently

Using a Mathematical Model to Analyze the Role of Probiotics and Inflammation in Necrotizing Enterocolitis

Background: Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract of pre-term babies and is thought to be related to the physiological immaturity of the intestine and altered levels of normal flora in the gut. Understanding the factors that contribute to the pathology of NEC may lead to the development of treatment strategies aimed at re-establishing the integrity of the epithelial wall and preventing the propagation of inflammation in NEC. Several studies have shown a reduced incidence and severity of NEC in neonates treated with probiotics (beneficial bacteria species). Methodology/Principal Findings: The objective of this study is to use a mathematical model to predict the conditions under which probiotics may be successful in promoting the health of infants suffering from NEC. An ordinary differential equation model is developed that tracks the populations of pathogenic and probiotic bacteria in the intestinal lumen and in the blood/tissue region. The permeability of the intestinal epithelial layer is treated as a variable, and the role of the inflammatory response is included. The model predicts that in the presence of probiotics health is restored in many cases that would have been otherwise pathogenic. The timing of probiotic administration is also shown to determine whether or not health is restored. Finally, the model predicts that probiotics may be harmful to the NEC patient under very specific conditions, perhaps explaining the detrimental effects of probiotics observed in some clinical studies. Conclusions/Significance: The reduced, experimentally motivated mathematical model that we have developed suggests how a certain general set of characteristics of probiotics can lead to beneficial or detrimental outcomes for infants suffering from NEC, depending on the influences of probiotics on defined features of the inflammatory response. © 2010 Arciero et al

Modeling the interactions of bacteria and Toll-like receptor-mediated inflammation in necrotizing enterocolitis

Necrotizing enterocolitis (NEC) is a severe disease of the gastrointestinal tract in premature infants, characterized by a disrupted intestinal epithelium and an exaggerated pro-inflammatory response. Since the activation of Toll-like receptor-4 (TLR4) blocks cell migration and proliferation and contributes to an uncontrolled inflammatory response within the intestine, this receptor has been identified as a key contributor to the development of NEC. Toll-like receptor-9 (TLR9) has been shown to sense bacterial genome components (CpG DNA) and to play an anti-inflammatory role in NEC. We present in vitro results demonstrating direct inhibition of TLR4 activation by CpG DNA, and we develop a mathematical model of bacteria-immune interactions within the intestine to investigate how such inhibition of TLR4 signaling might alter inflammation, associated bacterial invasion of tissue, and resulting outcomes. The model predicts that TLR9 can inhibit both the beneficial and detrimental effects of TLR4, and thus a proper balance of action by these two receptors is needed to promote intestinal health. The model results are also used to explore three interventions that could potentially prevent the development of NEC: reducing bacteria in the mucus layer, administering probiotic treatment, and blocking TLR4 activation. While the model shows that these interventions would be successful in most cases, the model is also used to identify situations in which the proposed treatments might be harmful

Time-delayed model of RNA interference

RNA interference (RNAi) is a fundamental cellular process that inhibits gene expression through cleavage and destruction of target mRNA. It is responsible for a number of important intracellular functions, from being the first line of immune defence against pathogens to regulating development and morphogenesis. In this paper we consider a mathematical model of RNAi with particular emphasis on time delays associated with two aspects of primed amplification: binding of siRNA to aberrant RNA, and binding of siRNA to mRNA, both of which result in the expanded production of dsRNA responsible for RNA silencing. Analytical and numerical stability analyses are performed to identify regions of stability of different steady states and to determine conditions on parameters that lead to instability. Our results suggest that while the original model without time delays exhibits a bi-stability due to the presence of a hysteresis loop, under the influence of time delays, one of the two steady states with the high (default) or small (silenced) concentration of mRNA can actually lose its stability via a Hopf bifurcation. This leads to the co-existence of a stable steady state and a stable periodic orbit, which has a profound effect on the dynamics of the system

Inhibitory effect of green coffee bean extract on fat accumulation and body weight gain in mice

BACKGROUND: An epidemiological study conducted in Italy indicated that coffee has the greatest antioxidant capacity among the commonly consumed beverages. Green coffee bean is rich in chlorogenic acid and its related compounds. The effect of green coffee bean extract (GCBE) on fat accumulation and body weight in mice was assessed with the objective of investigating the effect of GCBE on mild obesity. METHODS: Male ddy mice were fed a standard diet containing GCBE and its principal constituents, namely, caffeine and chlorogenic acid, for 14 days. Further, hepatic triglyceride (TG) level was also investigated after consecutive administration (13 days) of GCBE and its constituents. To examine the effect of GCBE and its constituents on fat absorption, serum TG changes were evaluated in olive oil-loaded mice. In addition, to investigate the effect on hepatic TG metabolism, carnitine palmitoyltransferase (CPT) activity in mice was evaluated after consecutive ingestion (6 days) of GCBE and its constituents (caffeine, chlorogenic acid, neochlorogenic acid and feruloylquinic acid mixture). RESULTS: It was found that 0.5% and 1% GCBE reduced visceral fat content and body weight. Caffeine and chlorogenic acid showed a tendency to reduce visceral fat and body weight. Oral administration of GCBE (100 and 200 mg/kg· day) for 13 days showed a tendency to reduce hepatic TG in mice. In the same model, chlorogenic acid (60 mg/kg· day) reduced hepatic TG level. In mice loaded with olive oil (5 mL/kg), GCBE (200 and 400 mg/kg) and caffeine (20 and 40 mg/kg) reduced serum TG level. GCBE (1%), neochlorogenic acid (0.028% and 0.055%) and feruloylquinic acid mixture (0.081%) significantly enhanced hepatic CPT activity in mice. However, neither caffeine nor chlorogenic acid alone was found to enhance CPT activity. CONCLUSION: These results suggest that GCBE is possibly effective against weight gain and fat accumulation by inhibition of fat absorption and activation of fat metabolism in the liver. Caffeine was found to be a suppressor of fat absorption, while chlorogenic acid was found to be partially involved in the suppressive effect of GCBE that resulted in the reduction of hepatic TG level. Phenolic compounds such as neochlorogenic acid and feruloylquinic acid mixture, except chlorogenic acid, can enhance hepatic CPT activity

Treatment of glenohumeral instability in rugby players

Rugby is a high-impact collision sport, with impact forces. Shoulder injuries are common and result in the longest time off sport for any joint injury in rugby. The most common injuries are to the glenohumeral joint with varying degrees of instability. The degree of instability can guide management. The three main types of instability presentations are: (1) frank dislocation, (2) subluxations and (3) subclinical instability with pain and clicking. Understanding the exact mechanism of injury can guide diagnosis with classical patterns of structural injuries. The standard clinical examination in a large, muscular athlete may be normal, so specific tests and techniques are needed to unearth signs of pathology. Taking these factors into consideration, along with the imaging, allows a treatment strategy. However, patient and sport factors need to be also considered, particularly the time of the season and stage of sporting career. Surgery to repair the structural damage should include all lesions found. In chronic, recurrent dislocations with major structural lesions, reconstruction procedures such as the Latarjet procedure yields better outcomes. Rehabilitation should be safe, goal-driven and athlete- specific. Return to sport is dependent on a number of factors, driven by the healing process, sport requirements and extrinsic pressures

Comparative Genomic Analyses of Copper Transporters and Cuproproteomes Reveal Evolutionary Dynamics of Copper Utilization and Its Link to Oxygen

Copper is an essential trace element in many organisms and is utilized in all domains of life. It is often used as a cofactor of redox proteins, but is also a toxic metal ion. Intracellular copper must be carefully handled to prevent the formation of reactive oxygen species which pose a threat to DNA, lipids, and proteins. In this work, we examined patterns of copper utilization in prokaryotes by analyzing the occurrence of copper transporters and copper-containing proteins. Many organisms, including those that lack copper-dependent proteins, had copper exporters, likely to protect against copper ions that inadvertently enter the cell. We found that copper use is widespread among prokaryotes, but also identified several phyla that lack cuproproteins. This is in contrast to the use of other trace elements, such as selenium, which shows more scattered and reduced usage, yet larger selenoproteomes. Copper transporters had different patterns of occurrence than cuproproteins, suggesting that the pathways of copper utilization and copper detoxification are independent of each other. We present evidence that organisms living in oxygen-rich environments utilize copper, whereas the majority of anaerobic organisms do not. In addition, among copper users, cuproproteomes of aerobic organisms were larger than those of anaerobic organisms. Prokaryotic cuproproteomes were small and dominated by a single protein, cytochrome c oxidase. The data are consistent with the idea that proteins evolved to utilize copper following the oxygenation of the Earth