IVIG for refractory dysphagia in Antisynthetase syndrome: A truth hard to swallow

Refractory dysphasia could be the main symptom of Antisynthetase syndrome (ASS). IVIG may have a major impact in the successful treatment of dysphasia in patients with ASS. In our patient with ASS, IVIG treatment was an unreplaceable treatment option, and the patient regains her ability to swallow within 2 days

Rethinking Pedagogy: Exploring the Potential of Digital Technology in Achieving Quality Education

(First Paragraph) The Mahatma Gandhi Institute of Education for Peace and Sustainable Development (MGIEP) is UNESCO’s Category 1 education Institute in the Asia-Pacific region devoted to education for peace and sustainable development, as enshrined in SDG Target 4.7. UNESCO MGIEP promotes the use of digital learning platforms where teachers and students can co-create and share a highly interactive learning experience. With the rise of the internet, there has been a proliferation of online content and digital resources intended to support teaching and learning, albeit widely varying in quality. Digital education media and resources, if carefully designed and implemented, have a significant potential to be mobilized on a massive scale to support transformative learning for building sustainable, flourishing societies

Association of IL1B -511C/-31T haplotype and Helicobacter pylori vacA genotypes with gastric ulcer and chronic gastritis

<p>Abstract</p> <p>Background</p> <p>The association between proinflammatory cytokine gene polymorphisms and gastric diseases related to <it>Helicobacter pylori </it>varies by population and geographic area.</p> <p>Our objective was to determine if the <it>IL-1B </it>-<it>511 T>C </it>and -<it>31 C>T </it>polymorphisms and <it>H. pylori vacA </it>genotypes are associated with risk of chronic gastritis and gastric ulcer in a Mexican population.</p> <p>Methods</p> <p>We conducted endoscopic studies in 128 patients with symptoms of dyspepsia. We took two biopsies from the body, antrum, or ulcer edge from each patient, and classified our histopathological findings according to the Sydney System. <it>H. pylori </it>infection and <it>vacA </it>genotyping were accomplished via PCR from total DNA of the gastric biopsies. We confirmed the presence of anti-<it>H. pylori </it>serum IgG and IgM in 102 control subjects. In both case subjects and control subjects, the <it>IL-1B </it>-<it>511 T>C </it>polymorphism was genotyped by PCR-RFLPs and the <it>IL-1B -31 C>T </it>polymorphism was genotyped by pyrosequencing.</p> <p>Results</p> <p>Sixty-two point seven (62.7%) of the 102 control subjects were <it>H. pylori-</it>seropositive. Among the case subjects, 100 were diagnosed with chronic gastritis and 28 with gastric ulcer. We found that 77% of the patients with chronic gastritis and 85.7% of the patients with gastric ulcer were <it>H. pylori-</it>positive. The predominant <it>H. pylori </it>genotype was <it>vacA s1m1 </it>(58.4%) and the most frequent subtype was <it>vacA s1</it>. The -<it>511 TC</it>, (rs16944 -511 T>C) genotype and the -<it>511C </it>allele were associated with chronic gastritis (OR = 3.1, 95% CI = 1.4-6.8 and OR = 3.0, 95% CI = 1.4-6.0, respectively). The subjects carrying -<it>31T </it>(rs1143627 -31 C>T) were found to be at a higher risk of having chronic gastritis (OR = 2.8, 95% CI = 1.3-5.8). The <it>IL-1B </it>-<it>511C/-31T </it>haplotype was associated with chronic gastritis (OR = 2.1, 95% CI = 1.2-3.8) but not with gastric ulcer.</p> <p>Conclusions</p> <p>The <it>H. pylori vacA </it>genotypes identified herein were similar to those reported for other regions of Mexico. The <it>vacA s1m1 </it>genotype was not associated with gastric ulcer. In the southern Mexican population, the <it>IL-1B -511C </it>and -<it>31T </it>alleles and the -<it>511C/-31T </it>and -<it>511T/-31T </it>haplotypes are associated with increased risk of chronic gastritis and gastric ulcer.</p

Structural studies of T4S systems by electron microscopy

Abstract: Type IV secretion (T4S) systems are large dynamic nanomachines that transport DNA and/or proteins through the membranes of bacteria. Analysis of T4S system architecture is an extremely challenging task taking into account their multi protein organisation and lack of overall global symmetry. Nonetheless the last decade demonstrated an amazing progress achieved by X-ray crystallography and cryo-electron microscopy. In this review we present a structural analysis of this dynamic complex based on recent advances in biochemical, biophysical and structural studies

Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis

<p>Abstract</p> <p>Background</p> <p>Central nervous system is a common site of metastasis in NSCLC and confers worse prognosis and quality of life. The aim of this prospective study was to evaluate the prognostic significance of clinical-pathological factors (CPF), serum CEA levels, and EGFR and HER2 tissue-expression in brain metastasis (BM) and overall survival (OS) in patients with advanced NSCLC.</p> <p>Methods</p> <p>In a prospective manner, we studied 293 patients with NSCLC in IIIB-IV clinical stage. They received standard chemotherapy. CEA was measured prior to treatment; EGFR and HER2 were evaluated by immunohistochemistry. BM development was confirmed by MRI in symptomatic patients.</p> <p>Results</p> <p>BM developed in 27, and 32% of patients at 1 and 2 years of diagnosis with adenocarcinoma (RR 5.2; 95% CI, 1.002–29; p = 0.05) and CEA ≥ 40 ng/mL (RR 11.4; 95% CI, 1.7–74; <it>p </it>< 0.01) as independent associated factors. EGFR and HER2 were not statistically significant. Masculine gender (RR 1.4; 95% CI, 1.002–1.9; <it>p </it>= 0.048), poor performance status (RR 1.8; 95% CI, 1.5–2.3; <it>p </it>= 0.002), advanced clinical stage (RR 1.44; 95% CI, 1.02–2; <it>p </it>= 0.04), CEA ≥ 40 ng/mL (RR 1.5; 95% CI, 1.09–2.2; <it>p </it>= 0.014) and EGFR expression (RR 1.6; 95% CI, 1.4–1.9; <it>p </it>= 0.012) were independent associated factors to worse OS.</p> <p>Conclusion</p> <p>High CEA serum level is a risk factor for BM development and is associated with poor prognosis in patients with advanced NSCLC. Surface expression of CEA in tumor cells could be the physiopathological mechanism for invasion to CNS.</p

Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

BACKGROUND: Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption

Human IgG1 Responses to Surface Localised Schistosoma mansoni Ly6 Family Members Drop following Praziquantel Treatment

The heptalaminate-covered, syncytial tegument is an important anatomical adaptation that enables schistosome parasites to maintain long-term, intravascular residence in definitive hosts. Investigation of the proteins present in this surface layer and the immune responses elicited by them during infection is crucial to our understanding of host/parasite interactions. Recent studies have revealed a number of novel tegumental surface proteins including three (SmCD59a, SmCD59b and Sm29) containing uPAR/Ly6 domains (renamed SmLy6A SmLy6B and SmLy6D in this study). While vaccination with SmLy6A (SmCD59a) and SmLy6D (Sm29) induces protective immunity in experimental models, human immunoglobulin responses to representative SmLy6 family members have yet to be thoroughly explored.Using a PSI-BLAST-based search, we present a comprehensive reanalysis of the Schistosoma mansoni Ly6 family (SmLy6A-K). Our examination extends the number of members to eleven (including three novel proteins) and provides strong evidence that the previously identified vaccine candidate Sm29 (renamed SmLy6D) is a unique double uPAR/Ly6 domain-containing representative. Presence of canonical cysteine residues, signal peptides and GPI-anchor sites strongly suggest that all SmLy6 proteins are cell surface-bound. To provide evidence that SmLy6 members are immunogenic in human populations, we report IgG1 (as well as IgG4 and IgE) responses against two surface-bound representatives (SmLy6A and SmLy6B) within a cohort of S. mansoni-infected Ugandan males before and after praziquantel treatment. While pre-treatment IgG1 prevalence for SmLy6A and SmLy6B differs amongst the studied population (7.4% and 25.3% of the cohort, respectively), these values are both higher than IgG1 prevalence (2.7%) for a sub-surface tegumental antigen, SmTAL1. Further, post-treatment IgG1 levels against surface-associated SmLy6A and SmLy6B significantly drop (p = 0.020 and p < 0.001, respectively) when compared to rising IgG1 levels against sub-surface SmTAL1.Collectively, these results expand the number of SmLy6 proteins found within S. mansoni and specifically demonstrate that surface-associated SmLy6A and SmLy6B elicit immunological responses during infection in endemic communities

A population-specific material model for sagittal craniosynostosis to predict surgical shape outcomes

Sagittal craniosynostosis consists of premature fusion (ossification) of the sagittal suture during infancy, resulting in head deformity and brain growth restriction. Spring-assisted cranioplasty (SAC) entails skull incisions to free the fused suture and insertion of two springs (metallic distractors) to promote cranial reshaping. Although safe and effective, SAC outcomes remain uncertain. We aimed hereby to obtain and validate a skull material model for SAC outcome prediction. Computed tomography data relative to 18 patients were processed to simulate surgical cuts and spring location. A rescaling model for age matching was created using retrospective data and validated. Design of experiments was used to assess the effect of different material property parameters on the model output. Subsequent material optimization—using retrospective clinical spring measurements—was performed for nine patients. A population-derived material model was obtained and applied to the whole population. Results showed that bone Young’s modulus and relaxation modulus had the largest effect on the model predictions: the use of the population-derived material model had a negligible effect on improving the prediction of on-table opening while significantly improved the prediction of spring kinematics at follow-up. The model was validated using on-table 3D scans for nine patients: the predicted head shape approximated within 2 mm the 3D scan model in 80% of the surface points, in 8 out of 9 patients. The accuracy and reliability of the developed computational model of SAC were increased using population data: this tool is now ready for prospective clinical application

Moderate exercise and chronic stress produce counteractive effects on different areas of the brain by acting through various neurotransmitter receptor subtypes: A hypothesis

BACKGROUND: Regular, "moderate", physical exercise is an established non-pharmacological form of treatment for depressive disorders. Brain lateralization has a significant role in the progress of depression. External stimuli such as various stressors or exercise influence the higher functions of the brain (cognition and affect). These effects often do not follow a linear course. Therefore, nonlinear dynamics seem best suited for modeling many of the phenomena, and putative global pathways in the brain, attributable to such external influences. HYPOTHESIS: The general hypothesis presented here considers only the nonlinear aspects of the effects produced by "moderate" exercise and "chronic" stressors, but does not preclude the possibility of linear responses. In reality, both linear and nonlinear mechanisms may be involved in the final outcomes. The well-known neurotransmitters serotonin (5-HT), dopamine (D) and norepinephrine (NE) all have various receptor subtypes. The article hypothesizes that 'Stress' increases the activity/concentration of some particular subtypes of receptors (designated nt(s)) for each of the known (and unknown) neurotransmitters in the right anterior (RA) and left posterior (LP) regions (cortical and subcortical) of the brain, and has the converse effects on a different set of receptor subtypes (designated nt(h)). In contrast, 'Exercise' increases nt(h )activity/concentration and/or reduces nt(s )activity/concentration in the LA and RP areas of the brain. These effects may be initiated by the activation of Brain Derived Neurotrophic Factor (BDNF) (among others) in exercise and its suppression in stress. CONCLUSION: On the basis of this hypothesis, a better understanding of brain neurodynamics might be achieved by considering the oscillations caused by single neurotransmitters acting on their different receptor subtypes, and the temporal pattern of recruitment of these subtypes. Further, appropriately designed and planned experiments will not only corroborate such theoretical models, but also shed more light on the underlying brain dynamics