Biomedia

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: The AUC0-10hr and Cmax values increased nonlinearly between100 mg and 1500 mg. The slope of the AUC0-10hr vs dose, as well as the Cmax vs dose, plots are steepest at the lowest thiamine doses. Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process.

Background: Studies have shown the existence of p21 induction in a p53-dependent and -independent pathway. Our previous study indicates that DOX-induced p65 is able to bind the p21 promoter to activate its transactivation in the cells. Methods: Over-expression and knock-down experiments were performed in Human Pancreatic Carcinoma (PANC1) cells. Cell cycle and cell death related proteins were assessed by Western Blotting. Cytotoxicity assay was checked by CCK-8 kit. Cell growth was analyzed by flow cytometers. Results: Here we showed that over-expression of p65 decreased the cytotoxic effect of DOX on PANC1 cells, correlating with increased induction of cytoplasmic p21. We observed that pro-caspase-3 physically associated with cytoplasmic p21, which may be contribution to prevent p21 translocation into the nucleus. Our data also suggested that no clear elevation of nuclear p21 by p65 provides a survival advantage by progression cell cycle after treatment of DOX. Likewise, down-regulation of p65 expression enhanced the cytotoxic effect of DOX, due to a significant decrease of mRNA levels of anti-apoptotic genes, such as the cellular inhibitor of apoptosis-1 (c-IAP1), and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2), leading to efficient induction of caspase-3 cleavage in the cells. More, we present evidence that over-expression of p53 or p53/p65 in the PANC1 cells were more sensitive to DOX treatment, correlated with activation of caspase-3 and clear elevation of nuclear p21 level. Our previous data suggested that expression of p21 increases Gefitinib-induced cell death by blocking the cell cycle at the G1 and G2 phases. The present findings here reinforced this idea by showing p21's ability of potentiality of DOX-induced cell death correlated with its inhibition of cell cycle progression after over-expression of p53 or p53/p65. Conclusion: Our data suggested p65 could increase p53-mediated cell death in response to DOX in PANC1 cells. Thus, it is worth noting that in p53 null or defective tumors, targeting in down-regulation of p65 may well be useful, leading to the potentiality of chemotherapeutic drugs.

IntroductionIn intensive care units (ICU), peripherally inserted central catheters (PICC) may be an alternative option to standard central venous catheters, particularly in patients with coagulation disorders or at high risk for infection. Some limits of PICCs (such as low flow rates) may be overcome by the use of power-injectable catheters.MethodWe have retrospectively reviewed all the power injectable PICCs inserted in adult and pediatric patients in the ICU during a 12-month period, focusing on the rate of complications at insertion and during maintenance. Results: We have collected 89 power injectable PICCs (in adults and in children), both multiple and single lumen. All insertions were successful. There were no major complications at insertion and no episodes of catheter-related blood stream infection. Non-infective complications during management were not clinically significant. There was one episode of symptomatic thrombosis during the stay in ICU and one episode after transfer of the patient in a non-intensive ward. Conclusions: Power injectable PICCs have many advantages in the ICU: they can be used as multi-purpose central lines for any type of infusion including high flow infusion, for hemodynamic monitoring, and for high-pressure injection of contrast media during radiological procedures. Their insertion is successful in 100% of cases and is not associated with significant risks, even in patients with coagulation disorders. Their maintenance is associated with an extremely low rate of infective and non-infective complications.

Background: Bird species show a high degree of variation in the composition of their preen gland waxes. For instance, galliform birds like chicken contain fatty acid esters of 2,3-alkanediols, while Anseriformes like goose or Strigiformes like barn owl contain wax monoesters in their preen gland secretions. The final biosynthetic step is catalyzed by wax synthases (WS) which have been identified in pro- and eukaryotic organisms. Results: Sequence similarities enabled us to identify six cDNAs encoding putative wax synthesizing proteins in chicken and two from barn owl and goose. Expression studies in yeast under in vivo and in vitro conditions showed that three proteins from chicken performed WS activity while a sequence from chicken, goose and barn owl encoded a bifunctional enzyme catalyzing both wax ester and triacylglycerol synthesis. Mono- and bifunctional WS were found to differ in their substrate specificities especially with regard to branched-chain alcohols and acyl-CoA thioesters. According to the expression patterns of their transcripts and the properties of the enzymes, avian WS proteins might not be confined to preen glands. Conclusions: We provide direct evidence that avian preen glands possess both monofunctional and bifunctional WS proteins which have different expression patterns and WS activities with different substrate specificities.

Background: The purpose of this study was to describe the food and nutrient intake of a population of rural Australian children particularly Indigenous children. Participants were aged 10 to 12 years, and living in areas of relative socio-economic disadvantage on the north coast of New South Wales. Methods: In this descriptive cross-sectional study 215 children with a mean age of 11.30 (SD 0.04) years (including 82 Indigenous children and 93 boys) completed three 24-hour food recalls (including 1 weekend day) during school time, over an average of two weeks in the Australian summer of late 2005. Results: A high proportion of children consumed less than the Australian Nutrient Reference Values for fibre (74-84% less than Adequate Intake (AI)), calcium (54-86% less than Estimated Average Requirement (EAR)), folate and magnesium (36% and 28% respectively less than EAR among girls), and the majority of children exceeded the upper limit for sodium (68-76% greater than Upper Limit (UL)). Energy-dense nutrient-poor (EDNP) food consumption contributed between 45% and 49% to energy. Hot chips, sugary drinks, high-fat processed meats, salty snacks and white bread were the highest contributors to key nutrients and sugary drinks were the greatest per capita contributor to daily food intake for all. Per capita intake differences were apparent by Indigenous status. Consumption of fruit and vegetables was low for all children. Indigenous boys had a higher intake of energy, macronutrients and sodium than non-Indigenous boys. Conclusions: The nutrient intake and excessive EDNP food consumption levels of Australian rural children from disadvantaged areas are cause for concern regarding their future health and wellbeing, particularly for Indigenous boys. Targeted intervention strategies should address the high consumption of these foods.

Background: Mycoplasma bovis is associated with pneumonia in calves characterized by the development of chronic caseonecrotic lesions with the agent persisting within the lesion. The purposes of this study were to characterize the morphology of lung lesions, examine the presence of M. bovis variable surface protein (Vsp) antigens and study the local immune responses in calves after infection with M. bovis strain 1067. Methods: Lung tissue samples from eight calves euthanased three weeks after experimental infection with M. bovis were examined by bacteriology and pathology. Lung lesions were evaluated by immunohistochemical (IHC) staining for wide spectrum cytokeratin and for M. bovis Vsp antigens and pMB67 antigen. IHC identification and quantitative evaluation of CD4+ and CD8+ T lymphocytes and immunoglobulin (IgG1, IgG2, IgM, IgA)-containing plasma cells was performed. Additionally, expression of major histocompatibility complex class II (MHC class II) was studied by IHC. Results: Suppurative pneumonic lesions were found in all calves. In two calves with caseonecrotic pneumonia, necrotic foci were surrounded by epithelial cells resembling bronchial or bronchiolar epithelium. In all calves, M. bovis Vsp antigens were constantly present in the cytoplasm of macrophages and were also present extracellularly at the periphery of necrotic foci. There was a considerable increase in numbers of IgG1- and IgG2-positive plasma cells among which IgG1-containing plasma cells clearly predominated. Statistical evaluation of the numbers of CD4+ and CD8+ T cells, however, did not reveal statistically significant differences between inoculated and control calves. In M. bovis infected calves, hyperplasia of bronchus-associated lymphoid tissue (BALT) was characterized by strong MHC class II expression of lymphoid cells, but only few of the macrophages demarcating the caseonecrotic foci were positive for MHC class II. Conclusions: The results from this study show that infection of calves with M. bovis results in various lung lesions including caseonecrotic pneumonia originating from bronchioli and bronchi. There is long-term persistence of M. bovis as demonstrated by bacteriology and immunohistochemistry for M. bovis antigens, i.e. Vsp antigens and pMB67. The persistence of the pathogen and its ability to evade the specific immune response may in part result from local downregulation of antigen presenting mechanisms and an ineffective humoral immune response with prevalence of IgG1 antibodies that, compared to IgG2 antibodies, are poor opsonins.

Naturally occurring native peptides provide important information about physiological states of an organism and its changes in disease conditions but protocols and methods for assessing their abundance are not well-developed. In this paper, we describe a simple procedure for the quantification of non-tryptic peptides in body fluids. The workflow includes an enrichment step followed by two-dimensional fractionation of native peptides and MS/MS data management facilitating the design and validation of LC- MRM MS assays. The added value of the workflow is demonstrated in the development of a triplex LC-MRM MS assay used for quantification of peptides potentially associated with the progression of liver disease to hepatocellular carcinoma.

Background: Variations in gene expression, mediated by epigenetic mechanisms, may cause broad phenotypic effects in animals. However, it has been debated to what extent expression variation and epigenetic modifications, such as patterns of DNA methylation, are transferred across generations, and therefore it is uncertain what role epigenetic variation may play in adaptation. Results: In Red Junglefowl, ancestor of domestic chickens, gene expression and methylation profiles in thalamus/hypothalamus differed substantially from that of a domesticated egg laying breed. Expression as well as methylation differences were largely maintained in the offspring, demonstrating reliable inheritance of epigenetic variation. Some of the inherited methylation differences were tissue-specific, and the differential methylation at specific loci were little changed after eight generations of intercrossing between Red Junglefowl and domesticated laying hens. There was an over-representation of differentially expressed and methylated genes in selective sweep regions associated with chicken domestication. Conclusions: Our results show that epigenetic variation is inherited in chickens, and we suggest that selection of favourable epigenomes, either by selection of genotypes affecting epigenetic states, or by selection of methylation states which are inherited independently of sequence differences, may have been an important aspect of chicken domestication.

Background: China is in the midst of history's largest flow of rural-urban migration in the world; a flow that includes growing numbers of children and adolescents. Their health status is an important public health issue. This study compares self-rated physical and mental health of migrant and local adolescents in China, and examines to what extent layered social connections account for health outcomes. Methods: In 2010, we conducted a cross-sectional study among middle school students in Pudong New Area, Shanghai. Information about health status, social connections, and demographic factors were collected using a questionnaire survey. After controlling for sociodemographic factors, we used the t-test, Chi-square analysis, and a series of regression models to compare differences in health outcomes and explore the effects of social connections. Results: Migrant adolescents reported significantly higher rates of good physical health. However, they also had significantly fewer social connections, lower self-esteem, and higher levels of depression than their native peers. Family cohesion was associated with depressive symptoms and low self-esteem among all adolescents; peer association and social cohesion played major roles in migrants' well-being. Gender, age, and socioeconomic (SES) factors also affected adolescents' self-rated physical and mental health. Conclusions: Self-rated data suggest that migrant adolescents enjoy a physical health advantage and a mental health disadvantage. Layered social connections, such as peer association and social cohesion, may be particularly important for migrants. A public health effort is required to improve the health status of migrant youth.

Background: Differentiated thyroid cancer is usually associated with an excellent prognosis and indolent course. Distant metastases are rare events at the onset of thyroid cancer. Among these presentations, metastasis to the axillary lymph nodes is even more unusual: only few cases were previously reported in the literature; there has been no report of axillary lymph node metastasis from follicular thyroid carcinoma. Axillary lymph node metastasis generally arises in the context of disseminated disease and carries an ominous prognosis.Case presentationHere we present a case of axillary lymph node metastasis in the context of disseminated differentiated thyroid cancer. The patient underwent near total thyroidectomy and neck and axillary lymph node dissection. A histopathological diagnosis of poorly differentiated follicular carcinoma with "signet ring cells" and Hurthle cell features was established. The patient received radioactive iodine therapy and TSH suppression therapy. Subsequently his serum thyroglobulin level decreased to 44.000 ng/ml from over 100.000 ng/ml.Discussion and ConclusionCurrently there are only few reported cases of axillary node metastases from thyroid cancer, and to our knowledge, this is the first report on axillary lymph node metastasis from follicular thyroid carcinoma. "Signet ring cell" is a morphologic feature shared by both benign and, more rarely, malignant follicular thyroid neoplasm, and it generally correlates with an arrest in folliculogenesis. Our case is one of the rare "signet ring cells" carcinomas so far described.

Objectives: Health utility combines health related quality of life and mortality to produce a generic outcome measure reflecting both morbidity and mortality. It has not been widely used as an outcome measure in evaluations of emergency care and little is known about the feasibility of measurement, typical values obtained or baseline factors that predict health utility. We aimed to measure health utility after emergency medical admission, to compare health utility to age, gender and regional population norms, and identify independent predictors of health utility. Methods: We selected 5760 patients across three hospitals who were admitted to hospital by ambulance as a medical emergency. The EQ-5D questionnaire was mailed to all who were still alive 30 days after admission. Health utility was estimated by applying tariff values to the EQ-5D responses or imputing a value of zero for those who had died. Multivariable analysis was used to identify independent predictors of health utility at 30 days. Results: Responses were received from 2488 (47.7%) patients, while 541 (9.4%) had died. Most respondents reported some or severe problems with each aspect of health. Mean health utility was 0.49 (standard deviation 0.35) in survivors and 0.45 (0.36) including non-survivors. Some 75% had health utility below their expected value (mean loss 0.32, 95% confidence interval 0.31 to 0.33) and 11% had health utility below zero (worse than death). On multivariable modelling, reduced health utility was associated with increased age and lower GCS, varied according to ICD10 code and was lower among females, patients with recent hospital admission, steroid therapy, or history of chronic respiratory disease, malignancy, diabetes or epilepsy. Conclusions: Health utility can be measured after emergency medical admission, although responder bias may be significant. Health utility after emergency medical admission is poor compared to population norms. We have identified independent predictors or health utility that need to be measured and taken into account in non-randomized evaluations of emergency care.

Background: Despite warfarin's marked efficacy, not all eligible patients receive it for stroke prevention in AF. The aim of this meta-analysis was to evaluate the association between prescriber and/or patient characteristics and subsequent prescription of warfarin for stroke prevention in patients with atrial fibrillation (AF). Methods: Observational studies conducted in the US using multivariate analysis to determine the relationship between characteristics and the odds of receiving warfarin for stroke prevention were identified in MEDLINE, EMBASE and a manual review of references. Effect estimates of prescriber and/or patient characteristics from individual studies were pooled to calculate odds ratios (ORs) with 95% confidence intervals. Results: Twenty-eight studies reporting results of 33 unique multivariate analyses were identified. Warfarin use across studies ranged from 9.1%-79.8% (median=49.1%). There was a moderately-strong correlation between warfarin use and year of study (r=0.60, p=0.002). Upon meta-analysis, characteristics associated with a statistically significant increase in the odds of warfarin use included history of cerebrovascular accident (OR=1.59), heart failure (OR=1.36), and male gender (OR=1.12). Those associated with a significant reduction in the odds of warfarin use included alcohol/drug abuse (OR=0.62), perceived barriers to compliance (OR=0.87), contraindication(s) to warfarin (OR=0.81), dementia (OR=0.32), falls (OR=0.60), gastrointestinal hemorrhage (OR=0.47), intracranial hemorrhage (OR=0.39), hepatic (OR=0.59), and renal impairment (OR=0.69). While age per 10-year increase (OR=0.78) and advancing age as a dichotomized variable (cut-off varied by study) (OR=0.57) were associated with significant reductions in warfarin use; qualitative review of results of studies evaluating age as a categorical variable did not confirm this relationship. Conclusions: Warfarin use has increased somewhat over time. The decision to prescribe warfarin for stroke prevention in atrial fibrillation is based upon multiple prescriber and patient characteristics. These findings can be used by family practice prescribers and other healthcare decision-makers to target interventions or methods to improve utilization of warfarin when it is indicated for stroke prevention.

Background: Differentiating amnestic mild cognitive impairment (aMCI) from normal cognition is difficult in clinical settings. Self-reported and informant-reported memory complaints occur often in both clinical groups, which then necessitates the use of a comprehensive neuropsychological examination to make a differential diagnosis. However, the ability to identify cognitive symptoms that are predictive of aMCI through informant-based information may provide some clinical utility in accurately identifying individuals who are at risk for developing Alzheimer's disease (AD). Methods: The current study utilized a case-control design using data from an ongoing validation study of the Alzheimer's Questionnaire (AQ), an informant-based dementia assessment. Data from 51 cognitively normal (CN) individuals participating in a brain donation program and 47 aMCI individuals seen in a neurology practice at the same institute were analyzed to determine which AQ items differentiated aMCI from CN individuals. Results: Forward stepwise multiple logistic regression analysis which controlled for age and education showed that 4 AQ items were strong indicators of aMCI which included: repetition of statements and/or questions [OR 13.20 (3.02, 57.66)]; trouble knowing the day, date, month, year, and time [OR 17.97 (2.63, 122.77)]; difficulty managing finances [OR 11.60 (2.10, 63.99)]; and decreased sense of direction [OR 5.84 (1.09, 31.30)]. Conclusions: Overall, these data indicate that certain informant-reported cognitive symptoms may help clinicians differentiate individuals with aMCI from those with normal cognition. Items pertaining to repetition of statements, orientation, ability to manage finances, and visuospatial disorientation had high discriminatory power.

Background: Establishing correct neuronal circuitry is crucial to proper function of the vertebrate nervous system. The abundance of chondroitin sulfate (CS) proteoglycans in embryonic neural environments suggests that matrix proteoglycans regulate axonal projections when fibre tracts have not yet formed. Among the early-born neurons, the vestibular nucleus (VN) neurons initiate commissural projections soon after generation at E12.5 and reach the contralateral target by E15.5 in the rat hindbrain. We therefore exploited 24-hour cultures (1 day in vitro, 1 DIV) of the rat embryos and chondroitinase ABC treatment of the hindbrain matrix to reveal the role of CS moieties in axonal initiation and projection in the early hindbrain. Results: DiI tracing from the VN at E12.5(+1 DIV) showed contralaterally projecting fibres assuming fascicles that hardly reached the midline in the controls. In the enzyme-treated embryos, the majority of fibres were unfasciculated as they crossed the midline at 90o. At E13.5(+1 DIV), the commissural projections formed fascicles and crossed the midline in the controls. Enzyme treatment apparently did not affect the pioneer axons that had advanced as thick fascicles normal to the midline and beyond, towards the contralateral VN. Later projections however traversed the enzyme-treated matrix as unfasciculated fibres, deviated from the normal course crossing the midline at various angles and extending beyond the contralateral VN. This suggests that CSs also limit the course of the later projections which otherwise would be attracted to alternative targets. Conclusions: CS moieties in the early hindbrain therefore control the course and fasciculation of axonal projections and the timing of axonal arrival at the target.

Background: The motivation of patients during robot-assisted rehabilitation after neurological disorders that lead to impairments of motor functions is of great importance. Due to the increasing number of patients, increasing medical costs and limited therapeutic resources, clinicians in the future may want patients to practice their movements at home or with reduced supervision during their stay in the clinic. Since people only engage in an activity and are motivated to practice if the outcome matches the effort at which they perform, an augmented feedback application for rehabilitation should take the cognitive and physical deficits of patients into account and incorporate a mechanism that is capable of balancing i.e. adjusting the difficulty of an exercise in an augmented feedback application to the patient's capabilities. Methods: We propose a computational mechanism based on Fitts' Law that balances i.e. adjusts the difficulty of an exercise for upper-extremity rehabilitation. The proposed mechanism was implemented into an augmented feedback application consisting of three difficulty conditions (easy, balanced, hard). The task of the exercise was to reach random targets on the screen from a starting point within a specified time window. The available time was decreased with increasing condition difficulty. Ten subacute stroke patients were recruited to validate the mechanism through a study. Cognitive and motor functions of patients were assessed using the upper extremity section of the Fugl-Meyer Assessment, the modified Ashworth scale as well as the Addenbrookes cognitive examination-revised. Handedness of patients was obtained using the Edinburgh handedness inventory. Patients' performance during the execution of the exercises was measured twice, once for the paretic and once for the non-paretic arm. Results were compared using a two-way ANOVA. Post hoc analysis was performed using a Tukey HSD with a significance level of p < 0.05. Results: Results show that the mechanism was capable of balancing the difficulty of an exercise to the capabilities of the patients. Medians for both arms show a gradual decrease and significant difference of the number of successful trials with increasing condition difficulty (F2;60 = 44.623; p < 0.01; eta2 = 0.623) but no significant difference between paretic and non-paretic arm (F1;60 = 3.768; p = 0.057; eta2 = 0.065). Post hoc analysis revealed that, for both arms, the hard condition significantly differed from the easy condition (p < 0.01). In the non-paretic arm there was an additional significant difference between the balanced and the hard condition (p < 0.01). Reducing the time to reach the target, i.e., increasing the difficulty level, additionally revealed significant differences between conditions for movement speeds (F2;59 = 6.013; p < 0.01; eta2 = 0.185), without significant differences for hand-closing time (F2;59 = 2.620; p = 0.082; eta2 = 0.09), reaction time (F2;59 = 0.978; p = 0.383; eta2 = 0.036) and hand-path ratio (F2;59 = 0.054; p = 0.947; eta2 = 0.002). The evaluation of a questionnaire further supported the assumption that perceived performance declined with increased effort and increased exercise difficulty leads to frustration. Conclusions: Our results support that Fitts' Law indeed constitutes a powerful mechanism for task difficulty adaptation and can be incorporated into exercises for upper-extremity rehabilitation.

Background: Hyperuricemia is associated with obesity. The visceral adiposity and subcutaneous adiposity may be associated with the differential metabolic risk, and the distribution of abdominal adipose tissue was significantly altered in people with type 2 diabetes mellitus (DM) compared to healthy people. Our study was performed to determine to the association between the regional abdominal adipose tissue distribution and serum uric acid levels in people with type 2 DM. Methods: A total of 699 people with type 2 DM and who had undergone abdominal computed tomography assessment of the visceral fat area and subcutaneous fat area were included. The serum uric acid levels were measured by the uricase method. Hyperuricemia was defined by cut-off value of > 7 mg/dl for men and > 6 mg/dl for women. Results: The visceral fat area was positively associated with the serum uric acid levels after adjustment for age, sex, systolic blood pressure, diastolic blood pressure, serum creatinine, hemoglobin, serum albumin, serum high-density lipoprotein, serum triglyceride and hemoglobin A1c (beta-coefficient = 0.117, p < 0.001). The logistic regression analysis showed that the visceral fat area was the significant independent predictor of hyperuricemia (OR 2.33, 95% CI, 1.21-4.50, p = 0.012). But there was no significant association between the subcutaneous fat area and the serum uric acid levels (beta-coefficient = 0.061, p = 0.255). Conclusions: our data shows that the visceral fat area was positively associated with the serum uric acid levels, but the subcutaneous fat area was not in people with type 2 DM.

Despite the appearance of new treatment, dietary approach remains the mainstay of PKU therapy. The nutritional management has become complex to optimize PKU patients' growth, development and diet compliance. This paper review critically new advances and challenges that have recently focused attention on potential relevant of LCPUFA supplementation, progress in protein substitutes and new protein sources, large neutral amino acids and sapropterin. Given the functional effects, DHA is conditionally essential substrates that should be supplied with PKU diet in infancy but even beyond. An European Commission Programme is going on to establish quantitative DHA requirements in this population. Improvements in the palatability, presentation, convenience and nutritional composition of protein substitutes have helped to improve long-term compliance with PKU diet, although it can be expected for further improvement in this area. Glycomacropeptide, a new protein source, may help to support dietary compliance of PKU subject but further studies are needed to evaluate this metabolic and nutritional issues. The PKU diet is difficult to maintain in adolescence and adult life. Treatment with large neutral amino acids or sapropterin in selected cases can be helpful. However, more studies are necessary to investigate the potential role, dose, and composition of large neutral amino acids in PKU treatment and to show long-term efficacy and tolerance. Ideally treatment with sapropterin would lead to acceptable blood Phe control without dietary treatment but this is uncommon and sapropterin will usually be given in combination with dietary treatment, but clinical protocol evaluating adjustment of PKU diet and sapropterin dosage are needed.In conclusion PKU diet and the new existing treatments, that need to be optimized, may be a complete and combined strategy possibly positive impacting on the psychological, social, and neurocognitive life of PKU patients.

Background: Blunt implementation of Western trauma system models is not feasible in low-resource communities with long prehospital transit times. The aims of the study were to evaluate to which extent a low-cost prehospital trauma system reduces trauma deaths where prehospital transit times are long, and to identify specific life support interventions that contributed to survival. Methods: In the study period from 1997 to 2006, 2,788 patients injured by land mines, war, and traffic accidents were managed by a chain-of-survival trauma system where non-graduate paramedics were the key care providers. The study was conducted with a time-period cohort design. Results: 37% of the study patients had serious injuries with Injury Severity Score [greater than or equal to] 9. The mean prehospital transport time was 2.5 hours (95% CI 1.9 - 3.2). During the ten-year study period trauma mortality was reduced from 17% (95% CI 15 -19) to 4% (95% CI 3.5 - 5), survival especially improving in major trauma victims. In most patients with airway problems, in chest injured, and in patients with external hemorrhage, simple life support measures were sufficient to improve physiological severity indicators. Conclusion: In case of long prehospital transit times simple life support measures by paramedics and lay first responders reduce trauma mortality in major injuries. Delegating life-saving skills to paramedics and lay people is a key factor for efficient prehospital trauma systems in low-resource communities..

IntroductionGlucocorticoids are widely prescribed drugs. In the human body, glucocorticoid is the main stress hormone, and controls a variety of physiological and cellular processes, including metabolism and immune response. It belongs to the same steroid superfamily as estrogens, which are known to play a role in breast cancer. However, the effect of glucocorticoid use on the risk of breast cancer is not clear. Methods: We conducted a case-control study using population-based medical databases from Northern Denmark (1.8 million inhabitants) to investigate the association between glucocorticoid prescriptions and breast cancer risk. The study included 9,488 incident breast cancer cases diagnosed between 1994 and 2008 and 94,876 population controls. We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) associating glucocorticoid use with breast cancer occurrence, controlling for prescriptions of postmenopausal hormone replacement therapy, anti-diabetics, immunosuppressive drugs, and hospital diagnosis of obesity, diabetes, chronic pulmonary diseases and autoimmune diseases. Results: We found no effect on breast cancer risk in ever users (>2 prescriptions) of any glucocorticoids (adjusted OR (aOR)=1.0; 95% CI: 0.96, 1.1), systemic glucocorticoids (aOR=1.0; 95% CI: 0.96, 1.1), or inhaled glucocorticoids (aOR=1.0; 95% CI: 0.95, 1.1), each compared to never users of any glucocorticoids. Associations for recent use (preceding 2 years) and former use (more than 2 years earlier) were near null in all dose categories (low, medium and high number of prescriptions). Intensity of systemic glucocorticoid use (cumulative prednisolone equivalent doses), regardless of duration (<1, 1-5, 5+ years), was also not associated with breast cancer risk. Conclusions: Overall, our study provides no evidence that glucocorticoid use affects the risk of breast cancer.

Background: Since the rapid scale-up of antiretroviral therapy (ART) programs in sub-Saharan Africa, electronic patient tracking systems (EPTS) have been deployed to respond to the growing demand for program monitoring, evaluation and reporting to governments and donors. These routinely collected data are often used in epidemiologic and operations research studies intended to improve programs. To ensure accurate reporting and good quality for research, the reliability and completeness of data systems need to be assessed and reported. We assessed the completeness and reliability of EPTS used in 16 HIV care and treatment clinics in Manica and Sofala provinces of Mozambique. Methods: We conducted a cross-sectional study to assess the completeness and reliability of key variables in the electronic data system for patients enrolling in 16 public sector HIV treatment clinics between 1 July 2004 and 30 June 2008. Data from the electronic database was compared with data abstracted from a stratified random sample of 520 patient charts. Percent agreement, kappa scores and concordance correlation coefficients were calculated for specified variables. Percentile bootstrap confidence intervals were calculated to account for the stratified nature of our sampling. Results: A total of 16,149 patients with a median age of 33 years and a median CD4 count of 151 enrolled in these 16 clinics between 1 July 2004 and 30 June 2008. The level of completeness was high for most variables with height (18.6%) and weight (11.5%) having the highest amount of missing data. The level of agreement for available data was also high with reliability statistics of 0.95 (95% CI: 0.92-0.98) for gender, 0.91 (95% CI: 0.80-1.00) for pre-ART CD4 value and 0.97 (95% CI: 0.95-0.99) for patient retention. Conclusions: Electronic patient tracking systems have been deployed to respond to the growing monitoring, evaluation and reporting requirements. In our cross-sectional study of clinics in Manica and Sofala provinces of Mozambique, we found high levels of completeness and reliability for key variables indicating that these electronic databases provided adequate data not only for monitoring and evaluation but also for research. Routine evaluations of the completeness and reliability of these databases need to occur to ensure high quality data are being used for reporting and research.