Mass spectrometry imaging identifies palmitoylcarnitine as an immunological mediator during Salmonella Typhimurium infection

Salmonella Typhimurium causes a self-limiting gastroenteritis that may lead to systemic disease. Bacteria invade the small intestine, crossing the intestinal epithelium from where they are transported to the mesenteric lymph nodes (MLNs) within migrating immune cells. MLNs are an important site at which the innate and adaptive immune responses converge but their architecture and function is severely disrupted during S. Typhimurium infection. To further understand host-pathogen interactions at this site, we used mass spectrometry imaging (MSI) to analyse MLN tissue from a murine model of S. Typhimurium infection. A molecule, identified as palmitoylcarnitine (PalC), was of particular interest due to its high abundance at loci of S. Typhimurium infection and MLN disruption. High levels of PalC localised to sites within the MLNs where B and T cells were absent and where the perimeter of CD169+ sub capsular sinus macrophages was disrupted. MLN cells cultured ex vivo and treated with PalC had reduced CD4+CD25+ T cells and an increased number of B220+CD19+ B cells. The reduction in CD4+CD25+ T cells was likely due to apoptosis driven by increased caspase-3/7 activity. These data indicate that PalC significantly alters the host response in the MLNs, acting as a decisive factor in infection outcome

The disabilities of the arm, shoulder and hand (DASH) outcome questionnaire: longitudinal construct validity and measuring self-rated health change after surgery

BACKGROUND: The disabilities of the arm, shoulder and hand (DASH) questionnaire is a self-administered region-specific outcome instrument developed as a measure of self-rated upper-extremity disability and symptoms. The DASH consists mainly of a 30-item disability/symptom scale, scored 0 (no disability) to 100. The main purpose of this study was to assess the longitudinal construct validity of the DASH among patients undergoing surgery. The second purpose was to quantify self-rated treatment effectiveness after surgery. METHODS: The longitudinal construct validity of the DASH was evaluated in 109 patients having surgical treatment for a variety of upper-extremity conditions, by assessing preoperative-to-postoperative (6–21 months) change in DASH score and calculating the effect size and standardized response mean. The magnitude of score change was also analyzed in relation to patients' responses to an item regarding self-perceived change in the status of the arm after surgery. Performance of the DASH as a measure of treatment effectiveness was assessed after surgery for subacromial impingement and carpal tunnel syndrome by calculating the effect size and standardized response mean. RESULTS: Among the 109 patients, the mean (SD) DASH score preoperatively was 35 (22) and postoperatively 24 (23) and the mean score change was 15 (13). The effect size was 0.7 and the standardized response mean 1.2. The mean change (95% confidence interval) in DASH score for the patients reporting the status of the arm as "much better" or "much worse" after surgery was 19 (15–23) and for those reporting it as "somewhat better" or "somewhat worse" was 10 (7–14) (p = 0.01). In measuring effectiveness of arthroscopic acromioplasty the effect size was 0.9 and standardized response mean 0.5; for carpal tunnel surgery the effect size was 0.7 and standardized response mean 1.0. CONCLUSION: The DASH can detect and differentiate small and large changes of disability over time after surgery in patients with upper-extremity musculoskeletal disorders. A 10-point difference in mean DASH score may be considered as a minimal important change. The DASH can show treatment effectiveness after surgery for subacromial impingement and carpal tunnel syndrome. The effect size and standardized response mean may yield substantially differing results

Microdevices for extensional rheometry of low viscosity elastic liquids : a review

Extensional flows and the underlying stability/instability mechanisms are of extreme relevance to the efficient operation of inkjet printing, coating processes and drug delivery systems, as well as for the generation of micro droplets. The development of an extensional rheometer to characterize the extensional properties of low viscosity fluids has therefore stimulated great interest of researchers, particularly in the last decade. Microfluidics has proven to be an extraordinary working platform and different configurations of potential extensional microrheometers have been proposed. In this review, we present an overview of several successful designs, together with a critical assessment of their capabilities and limitations

Bullous lesions as a manifestation of systemic lupus erythematosus in two Mexican teenagers

Rarely, systemic lupus erythematosus (SLE) presents with bullous lesions due to severe edema and hydropic degeneration of the basal layer, or as a subepidermal blistering disease. Here, we describe two Mexican teenagers, one with SLE with blisters and another with bullous SLE. We also discuss the mechanisms and clinical implications of lesion formation in patients with SLE and bullae

The Effect of Bacterial Infection on the Biomechanical Properties of Biological Mesh in a Rat Model

BACKGROUND: The use of biologic mesh to repair abdominal wall defects in contaminated surgical fields is becoming the standard of practice. However, failure rates and infections of these materials persist clinically. The purpose of this study was to determine the mechanical properties of biologic mesh in response to a bacterial encounter. METHODS: A rat model of Staphylococcus aureus colonization and infection of subcutaneously implanted biologic mesh was used. Samples of biologic meshes (acellular human dermis (ADM) and porcine small intestine submucosa (SIS)) were inoculated with various concentrations of methicillin-resistant Staphylococcus aureus [10(5), 10(9) colony-forming units] or saline (control) prior to wound closure (n = 6 per group). After 10 or 20 days, meshes were explanted, and cultured for bacteria. Histological changes and bacterial recovery together with biomechanical properties were assessed. Data were compared using a 1-way ANOVA or a Mann-Whitney test, with p<0.05. RESULTS: The overall rate of staphylococcal mesh colonization was 81% and was comparable in the ADM and SIS groups. Initially (day 0) both biologic meshes had similar biomechanical properties. However after implantation, the SIS control material was significantly weaker than ADM at 20 days (p = 0.03), but their corresponding modulus of elasticity were similar at this time point (p>0.05). After inoculation with MRSA, a time, dose and material dependent decrease in the ultimate tensile strength and modulus of elasticity of SIS and ADM were noted compared to control values. CONCLUSION: The biomechanical properties of biologic mesh significantly decline after colonization with MRSA. Surgeons selecting a repair material should be aware of its biomechanical fate relative to other biologic materials when placed in a contaminated environment

Triatoma dimidiata Infestation in Chagas Disease Endemic Regions of Guatemala: Comparison of Random and Targeted Cross-Sectional Surveys

Chagas disease is a vector-borne parasitic zoonosis endemic throughout South and Central America and Mexico. Guatemala is engaged in the Central America Initiative to interrupt Chagas disease transmission. A major strategy is the reduction of Triatoma dimidiata domiciliary infestations through indoor application of residual insecticides. Successful control of T. dimidiata will depend on accurate identification of areas at greatest risk for infestation. Initial efforts focused primarily on targeted surveys of presumed risk factors and suspected infestation to define intervention areas. This policy has not been evaluated and might not maximize the effectiveness of limited resources if high prevalence villages are missed or low prevalence villages are visited unnecessarily. We compare findings from the targeted surveys to concurrent random surveys in two primary foci of Chagas disease transmission in Guatemala to evaluate the performance of the targeted surveys. Our results indicate that random surveys performed better than targeted surveys and should be considered over targeted surveys when reliability of risk factors has not been evaluated, identify useful environmental factors to predict infestation, and indicate that infestation risk varies locally. These findings are useful for decision-makers at national Chagas Disease control programs in Central America, institutions supporting development efforts, and funding agencies

Influence of mycotoxin zearalenone and its derivatives (alpha and beta zearalenol) on apoptosis and proliferation of cultured granulosa cells from equine ovaries

BACKGROUND: The mycotoxin zearalenone (ZEA) and its derivatives, alpha and beta-zearalenol (alpha and beta-ZOL), synthesized by genera Fusarium, often occur as contaminants in cereal grains and animal feeds. The importance of ZEA on reproductive disorders is well known in domestic animals species, particularly in swine and cattle. In the horse, limited data are available to date on the influence of dietary exposure to ZEA on reproductive health and on its in vitro effects on reproductive cells. The aim of this study was to evaluate the effects of ZEA and its derivatives, alpha and beta-ZOL, on granulosa cells (GCs) from the ovaries of cycling mares. METHODS: The cell proliferation was evaluated by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test after 3 days exposure at different concentrations of ZEA and its derivatives (from 1 × 10-7 to 0.1 microM). The apoptosis induction was evaluated after 1 day exposure, by DNA analysis using flow cytometry. RESULTS: An increase in cell proliferation with respect to the control was observed in the presence of ZEA at 1 × 10-3 and 1 × 10-4 microM and apoptosis was induced by all mycotoxins at different concentrations. CONCLUSION: The simultaneous presence of apoptosis and proliferation in GC cultures treated with zearalenones could indicate that these mycotoxins could be effective in inducing follicular atresia. These effects of zearalenones may result from both direct interaction with oestrogen-receptors as well as interaction with the enzymes 3alpha (beta)-hydroxysteroid dehydrogenase (HSD), involved in the synthesis and metabolism of endogenous steroid hormones. These cellular disturbances, described for the first time in equine GCs cultured in vitro, could be hypothesized as referred to reproductive failures of unknown ethiology in the mare

Occupation and skin cancer: the results of the HELIOS-I multicenter case-control study

<p>Abstract</p> <p>Background</p> <p>Non-melanoma skin cancer (NMSC) is the most frequent tumour among Caucasian populations worldwide. Among the risk factors associated with this tumour, there are host-related factors and several environmental agents. A greater likelihood of high exposure to physical agents (with the exception of solar radiation) and chemical agents depends on the work setting. Our objective is to evaluate the role of occupational exposures in NMSC, with special emphasis on risk factors other than solar radiation and skin type.</p> <p>Methods</p> <p>We analysed 1585 cases (1333 basal cell carcinoma (BCC) and 183 squamous cell carcinoma (SCC)) and 1507 controls drawn from the Helios-I multicenter study. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression mixed models.</p> <p>Results</p> <p>For NMSC as a whole (both <it>histological types</it>), miners and quarrymen, secondary education teachers, and masons registered excess risk, regardless of exposure to solar radiation and skin type (OR 7.04, 95% CI 2.44–20.31; OR 1.75, 95% CI 1.05–2.89 and OR 1.54, 95% CI 1.04–2.27, respectively). Frequency of BCC proved higher among railway engine drivers and firemen (OR 4.55; 95% CI 0.96–21.57), specialised farmers (OR 1.65; 95% CI 1.05–2.59) and salesmen (OR 3.02; 95% CI 1.05–2.86), in addition to miners and quarrymen and secondary education teachers (OR 7.96; 95% CI 2.72–23.23 and OR 1.76; 95% CI 1.05–2.94 respectively). The occupations that registered a higher risk of <it>SCC (though not of BCC</it>) were those involving direct contact with livestock, construction workers not elsewhere classified (OR 2.95, 95% CI 1.12–7.74), stationary engine and related equipment operators not elsewhere classified (OR 5.31, 95% CI 1.13–21.04) and masons (OR 2.55, 95% CI 1.36–4.78).</p> <p>Conclusion</p> <p>Exposure to hazardous air pollutants, arsenic, ionizing radiations and burns may explain a good part of the associations observed in this study. The Helios study affords an excellent opportunity for further in-depth study of physical and chemical agents and NMSC based on matrices of occupational exposure.</p

Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation

Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue containing the antigen, supplemented with an adjuvant, and coming from plants conferring resistance to kanamycin. The objective of this study was to develop a prototype oral vaccine formula suitable for human immunization. Herbicide-resistant lettuce was engineered, stably expressing through progeny generation micrograms of S-HBsAg per g of fresh weight and formed into virus-like particles (VLPs). Lyophilized tissue containing a relatively low, 100-ng VLP-assembled antigen dose, administered only orally to mice with a long, 60-day interval between prime and boost immunizations and without exogenous adjuvant, elicited mucosal and systemic humoral anti-HBs responses at the nominally protective level. Lyophilized tissue was converted into tablets, which preserved S-HBsAg content for at least one year of room temperature storage. The results of the study provide indications on immunization methodology using a durable, efficacious, and convenient plant-derived prototype oral vaccine against hepatitis B