Freezing of Enkephalinergic Functions by Multiple Noxious Foci: A Source of Pain Sensitization?

BACKGROUND:The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments. METHODOLOGY/PRINCIPAL FINDINGS:Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously. CONCLUSION/SIGNIFICANCE:We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis

Association of self-reported physical activity patterns and socio-demographic factors among normal-weight and overweight Japanese men

<p>Abstract</p> <p>Background</p> <p>It is still not known whether overweight men have different patterns and socio-demographic correlates of self-reported physical activity (PA) compared with normal-weight men. Thus, this study examined the perceived PA patterns and associated socio-demographic factors among normal-weight and overweight Japanese men.</p> <p>Methods</p> <p>Data were analyzed for 1,420 men (aged 44.48.3years) who responded to an Internet-based cross-sectional survey relating to socio-demographic variables, BMI status, and a short version of the International Physical Activity Questionnaire. Mann-Whitney, chi-square, and binary logistic regression analyses were employed.</p> <p>Results</p> <p>Normal-weight men were significantly more likely to attain 150 minutes per week of moderate-to-vigorous PA than overweight men (26.6% vs. 21.3%; <it>p</it>=0.035), whereas there were no significant proportional differences in total PA and walking between the two BMI subgroups. With PA, a significant interaction was observed between BMI status and household income (<it>p</it>=0.004 for total PA; <it>p</it>=0.02 for walking). In the subgroup analyses, having a lower household income (odds ratio, 0.63; 95% confidence interval, 0.41-0.96) was negatively associated with attaining 150 minutes of walking per week among normal-weight men. No significant associations between household income and attaining 150 minutes per week of total PA and walking were found among overweight men.</p> <p>Conclusions</p> <p>The results revealed that patterns and socio-demographic correlates of self-reported PA in overweight men are different from those in normal-weight men. This finding suggests the necessity of developing specific strategies for PA intervention among overweight men. Socio-demographic correlates of PA may be more important for normal-weight than overweight men.</p

Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC). A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes

Lessons learned from the AFLY5 RCT process evaluation: Implications for the design of physical activity and nutrition interventions in schools Health behavior, health promotion and society

© 2015 Jago et al. Background: Systematic reviews have highlighted that school-based diet and physical activity (PA) interventions have had limited effects. This study used qualitative methods to examine how the effectiveness of future primary (elementary) school diet and PA interventions could be improved. Methods: Data are from the Active For Life Year 5 (AFLY5) study, which was a cluster randomised trial conducted in 60 UK primary schools. Year 5 (8-9 years of age) pupils in the 30 intervention schools received a 12-month intervention. At the end of the intervention period, interviews were conducted with: 28 Year 5 teachers (including 8 teachers from control schools); 10 Headteachers (6 control); 31 parents (15 control). Focus groups were conducted with 70 year 5 pupils (34 control). Topics included how the AFLY5 intervention could have been improved and how school-based diet and PA interventions should optimally be delivered. All interviews and focus groups were transcribed and thematically analysed across participant groups. Results: Analysis yielded four themes. Child engagement: Data suggested that programme success is likely to be enhanced if children feel that they have a sense of autonomy over their own behaviour and if the activities are practical. School: Finding a project champion within the school would enhance intervention effectiveness. Embedding diet and physical activity content across the curriculum and encouraging teachers to role model good diet and physical activity behaviours were seen as important. Parents and community: Encouraging parents and community members into the school was deemed likely to enhance the connection between schools, families and communities, and "create a buzz" that was likely to enhance behaviour change. Government/Policy: Data suggested that there was a need to adequately resource health promotion activity in schools and to increase the infrastructure to facilitate diet and physical activity knowledge and practice. Discussion and Conclusions: Future primary school diet and PA programmes should find ways to increase child engagement in the programme content, identify programme champions, encourage teachers to work as role models, engage parents and embed diet and PA behaviour change across the curriculum. However, this will require adequate funding and cost-effectiveness will need to be established. Trial registration: ISRCTN5013374

Reproductive tract infections in women seeking abortion in Vietnam

<p>Abstract</p> <p>Background</p> <p>Women requesting abortion are at increased risk of developing RTI complications. However, RTI control in many resource-poor countries including Vietnam have been faced with logistical and methodological problems due to lack of standardized definitions of RTIs, lack of well-validated diagnostic criteria, lack of accurate laboratory tests, and lack of diagnostic equipment and skills. This article investigates the prevalence of RTIs among Vietnamese abortion-seeking women, to evaluate the available diagnostic techniques, and to assess antibiotic resistance among aetiological agents of RTI.</p> <p>Method</p> <p>The study was conducted in Phu-San hospital (PSH) from December 2003 through April 2004 among 748 abortion clients. A structured questionnaire was used to collect data on socio-economic and reproductive characteristics. Specimens were collected for laboratory analyses of chlamydia, gonorrhoea, trichomoniasis, vaginal candidiasis (VC), bacterial vaginosis (BV) and syphilis. To assess the validity of the obtained results, the study was repeated among 100 women and the duplicate samples were analysed at PSH and Copenhagen University Hospital (CUH).</p> <p>Results</p> <p>In all 54% of the women were diagnosed as having an RTI, including 3.3% with sexually transmitted infections. Endogenous infections were most prevalent (VC 34% and BV 12%) followed by chlamydia (1.3%) and trichomoniasis (0.7%). The sensitivity of culture for VC and BV was 30% and 88%, respectively, when tests in PSH were measured against tests in CUH. Antibiotic resistance was common among bacterial isolates.</p> <p>Conclusion</p> <p>RTIs are common among women seeking abortion. The presence of RTIs is associated with an increased risk of developing iatrogenic infections, routine administration of prophylactic antibiotic to all women undergoing abortion should be considered. However, the choice of routine prophylactic antibiotics should be based on relevant surveillance data of antibiotic resistance. Moreover, since the accuracy of diagnosis is doubtful and to address the problem of under-diagnosed and treated RTIs new investment in diagnostic facilities with simple performed microscopy or improved rapid tests should also be taken into consideration.</p

Sugar-added beverages consumption among kindergarten children of Crete: effects on nutritional status and risk of obesity

<p>Abstract</p> <p>Objective</p> <p>To assess the intake of sugar-added beverages such as soft drinks and commercially available fruit juices in kindergarten children, and to examine its association with obesity indices, physical activity levels and dietary habits.</p> <p>Methods</p> <p>A total of 856 children aged 4–7 years living in Crete, Greece in 2004–5 were included in this cross-sectional study. Nutrient and food intake was assessed with the use of 3-day weighed food records. Body measurements were used in order to assess BMI and waist circumference, and moderate-to-vigorous physical activity was calculated with the use of a questionnaire.</p> <p>Results</p> <p>Approximately 59.8% of all children consumed sugar-added beverages on a daily basis. High intake of sugar-added beverages (> 250 g/day) was associated with low intakes of calcium (p < 0.001), vitamin A and E (p < 0.010), fruits and vegetables (p = 0.007), and milk and yogurt (p = 0.048). Compared to non or low consumers, high consumers of sugar-added beverages (> 250 g/day) had higher BMI levels and two times greater risk of being overweight and/or obese (OR:2.35, p = 0.023).</p> <p>Conclusion</p> <p>High intake of sugar-added beverages in kindergarten children is associated with poor eating habits and inadequate nutrient intake, as well as increased risk for developing childhood obesity.</p

Ethanolamine phosphoglycerol attachment to eEF1A is not essential for normal growth of Trypanosoma brucei

Eukaryotic elongation factor 1A (eEF1A) is the only protein modified by ethanolamine phosphoglycerol (EPG). In mammals and plants, EPG is attached to conserved glutamate residues located in eEF1A domains II and III, whereas in the unicellular eukaryote, Trypanosoma brucei, a single EPG moiety is attached to domain III. A biosynthetic precursor of EPG and structural requirements for EPG attachment to T. brucei eEF1A have been reported, but the role of this unique protein modification in cellular growth and eEF1A function has remained elusive. Here we report, for the first time in a eukaryotic cell, a model system to study potential roles of EPG. By down-regulation of EF1A expression and subsequent complementation of eEF1A function using conditionally expressed exogenous eEF1A (mutant) proteins, we show that eEF1A lacking EPG complements trypanosomes deficient in endogenous eEF1A, demonstrating that EPG attachment is not essential for normal growth of T. brucei in culture

Sociodemographic correlates of food habits among school adolescents (12–15 year) in north Gaza Strip

Background: There is little information about meal patterns and food consumption of adolescents in Palestine. The objective of this study was to describe the association between sociodemographic factors and food intake, and meal patterns among Palestinian school adolescents (12–15 year) in North Gaza Strip. Methods: A cross-sectional study was conducted in 2002 comprising 944 subjects in 10 schools in Gaza city, Jabalia village and Jabalia refugee camp. Self-administered questionnaires were filled in by students and parents to obtain data on frequency of meals, food intake and sociodemographic characteristics. Results: High household socioeconomic status (SES) was associated with the increased number of meals and the increased intakes of many nutritious foods such as; animal food items, fruits and vegetables and dairy foods. The percentage of adolescents having breakfast daily of high and low SES was 74.5% vs 55% in boys and 65.6% vs 45% in girls. The percentage of girls with refugee status who had lunch was higher (90.2%) compared to the local citizen girls (83.9%), (p = 0.03). Girls were less likely to skip daily lunch (OR = 0.55, 95% CI = 0.36–0.87, p = 0.01) compared to boys. Risk of skipping lunch was three times higher among adolescents living in the village compared to Gaza well-off area (OR = 3.3, 95% CI = 1.72–6.31, p < 0.001). Adolescents who were having lunch daily were less likely to skip breakfast or dinner. Only 11.6% of boys and 16.2% of girls consumed fruits daily. In multivariate analysis, SES was positively associated with food frequency intake scores in both genders. Boys from the refugee camp and the village had a significant higher consumption of fruits and vegetables than boys from high and low income area in Gaza City, while it was the opposite in girls. Conclusion: Meal skipping is common, particularly among those of low SES and the intakes of many nutritious foods such as animal food items, fruits and vegetables and dairy foods seem to be low among adolescents of low SES. The results of this study could be used as an important baseline for future monitoring of the nutritional situation of adolescents.Abdallah H Abudayya, Hein Stigum, Zumin Shi, Yehia Abed and Gerd Holmboe-Ottese

Presenilin Is the Molecular Target of Acidic γ-Secretase Modulators in Living Cells

The intramembrane-cleaving protease γ-secretase catalyzes the last step in the generation of toxic amyloid-β (Aβ) peptides and is a principal therapeutic target in Alzheimer's disease. Both preclinical and clinical studies have demonstrated that inhibition of γ-secretase is associated with prohibitive side effects due to suppression of Notch processing and signaling. Potentially safer are γ-secretase modulators (GSMs), which are small molecules that selectively lower generation of the highly amyloidogenic Aβ42 peptides but spare Notch processing. GSMs with nanomolar potency and favorable pharmacological properties have been described, but the molecular mechanism of GSMs remains uncertain and both the substrate amyloid precursor protein (APP) and subunits of the γ-secretase complex have been proposed as the molecular target of GSMs. We have generated a potent photo-probe based on an acidic GSM that lowers Aβ42 generation with an IC50 of 290 nM in cellular assays. By combining in vivo photo-crosslinking with affinity purification, we demonstrated that this probe binds the N-terminal fragment of presenilin (PSEN), the catalytic subunit of the γ-secretase complex, in living cells. Labeling was not observed for APP or any of the other γ-secretase subunits. Binding was readily competed by structurally divergent acidic and non-acidic GSMs suggesting a shared mode of action. These findings indicate that potent acidic GSMs target presenilin to modulate the enzymatic activity of the γ-secretase complex