Lower Erythrocyte GST activity in Autism Spectrum Disorder (ASD) patients compared to normal controls

Glutathione S-transferases (GST) are antioxidant enzymes that play an important role in the cellular detoxification and excretion of environmental pollutants including heavy metals. GST mu (GSTM1) and G theta (GSTT1) are known to be highly polymorphic and homozygous deletions of these genes result in the lack of enzyme activity and when combined with decreased levels of antioxidants, they have been associated with the Autism Spectrum Disorder (ASD). This preliminary study was performed to investigate the role of GSTM1 and GSTT1 polymorphisms as risk factors of ASD associated with GST activity and phenotype expression. Fifty one ASD patients and 45 controls were recruited for GSTM1 and GSTT1 genotyping while 6 ASD patients and 8 controls were assessed for GST activity. The results showed no significant differences in frequencies of GSTM1 null, GSTT1 null and combination both genotype between ASD patients and controls. However the mean erythrocyte GST activity in ASD is significantly decreased compared with controls (p = 0.043). The mean erythrocyte GST activity is lower in the severely autistic group compare to the mild to moderately autistic group, although it was not statistically significant. Further investigations are needed with a bigger sample size, analyzing multiple GST genes and GST activity determination to find out the gene susceptibility of ASD and factors that contribute to the phenotype expression of ASD

Screening for HLA-B*1502 Polymorphism in Febrile Seizure Predicted Lead to Epilepsy

Mutation in neuronal sodium channel -1-subunit gene (SCN1A) and neuronal sodium channel -1-subunit gene (SCN1B) has been linked with forms of generalized epilepsy with febrile seizure plus (GEFS+) and epileptic infantile syndrome like severe myoclonic epilepsy of infancy (SMEI) (Mulley et al., 2005; Scheffer et al., 2007). Since this idiopathic epilepsy typically begins with prolonged febrile seizures (FS) in the first year of life, therefore febrile seizure patient with mutation in SCN1A has a high risk to develop epilepsy on their later life (Dube et al., 2009). Carbamazepine (CBZ) has been known as the most common anti-epileptic drug which can cause Steven-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients with HLA-B*1502 polymorphism. Since the Javanese population have 16,67% of these allele, studying the presence of these allele in patients predicted epilepsy is important. Furthermore, this study was intended to develop a PCR-based diagnostic protocol to screen HLA-B*1502 polymorphism in epileptic patients to prevent SJS/TEN by carbamazepine. Focusing on epileptic predicted patients, HLA-B*1502 genotyping by sequence specific primer (SSP)-PCR was performed on 31 repeated FS patients with mutation in SCN1A and SCN1A/SCN1B gene. The result show that the HLA-B*1502 polymorphism was detected in 14 (45,2%) individuals including 8 cases related to mutation SCN1A gene and 6 to SCN1A/SCN1B gene. It illustrates that HLA-B*1502 allele is frequent in these patients. It can thus be suggested that detection of this allele should be done before epilepsy treatment. Later, patients with this allele should avoid CBZ to prevent SJS/TEN during drug administration

Automotive leaf spring design and manufacturing process improvement using failure mode and effects analysis (FMEA)

Nowadays human safety and comfort are the most considerable parameters in designing and manufacturing of a vehicle, that is why every organization ensures the quality and reliability of components used in the vehicle. Leaf spring is also a component of vehicle which plays an important role in human safety and comfort. It acts as a structural member and an integral part of suspension system. It is important to eliminate the failures in designing and manufacturing process of leaf springs because of its importance in functionality and safety of vehicle. In this research, failure mode and effects analysis has been used to analyze and reduce the risks of 42 possible failures that can occur in automotive leaf spring. It starts from determining, classifying, and analyzing all potential failures and then rating them with the help numeric scores. The four numeric scores namely severity, occurrence, detection, and Risk Priority Number (RPN) are used to find the high potential failures of semi-elliptical leaf springs. In the end, actions are recommended for RPN greater than 250, to increase quality and reliably of product. </jats:p

A stable aberrant immunophenotype characterizes nearly all cases of cutaneous T-cell lymphoma in blood and can be used to monitor response to therapy

BACKGROUND: Abnormal variations in the expression level of some commonly expressed T-cell antigens are a feature of many T-cell malignancies. METHODS: We sought to assess the frequency of such abnormal antigen expression by flow cytometry in peripheral blood (PB) samples from patients with mycosis fungoides (MF) and Sézary syndrome (SS). We correlated presence of morphologically identifiable tumor cells on PB smear with the frequency of abnormalities in the level of expression of CD3, CD4, CD7, CD8 and CD26. We also examined the degree of stability of these abnormal findings in tumor cells over the course of disease. The flow cytometric findings in 100 PB samples from 44 patients, including 38 who had multiple sequential PB samples (2–8 samples each), were assessed. RESULTS: Abnormalities were seen in the expression level of one or more T-cell markers in 41 cases (93%) including CD3 in 34% of patients, CD4 in 54%, CD26 in 86% and CD 45 in 40% (10 cases tested). In all but 2 cases, the abnormal T-cell immunophenotype remained similar over the course of treatment and correlated with the relative numbers of tumor cells counted on PB smear. CONCLUSIONS: Using a standard T-cell panel, stable phenotypically aberrant T-cell populations representing the tumor are detected in the vast majority of involved PB samples in MF/SS and can be used to monitor response to therapy

Does delay in diagnosing colorectal cancer in symptomatic patients affect tumor stage and survival? A population-based observational study

<p>Abstract</p> <p>Background</p> <p>Diagnosing colorectal cancer (CRC) at an early stage improves survival. To what extent any delay affects outcome once patients are symptomatic is still unclear.</p> <p>Our objectives were to evaluate the association between diagnostic delay and survival in symptomatic patients with early stage CRC and late stage CRC.</p> <p>Methods</p> <p>Prospective population-based observational study evaluating daily clinical practice in Northern Holland. Diagnostic delay was determined through questionnaire-interviews. Dukes' stage was classified into two groups: early stage (Dukes A or B) and late stage (Dukes C or D) cancer. Patients were followed up for 3.5 years after diagnosis.</p> <p>Results</p> <p>In total, 272 patients were available for analysis. Early stage CRC was present in 136 patients while 136 patients had late stage CRC. The mean total diagnostic delay (SE) was 31 (1.5) weeks in all CRC patients. No significant difference was observed in the mean total diagnostic delay in early versus late stage CRC (<it>p </it>= 0.27).</p> <p>In early stage CRC, no difference in survival was observed between patients with total diagnostic delay shorter and longer than the median (Kaplan-Meier, log-rank <it>p </it>= 0.93).</p> <p>In late stage CRC, patients with a diagnostic delay shorter than the median had a shorter survival than patients with a diagnostic delay longer than the median (log-rank <it>p </it>= 0.01). In the multivariate Cox regression model with survival as dependent variable and median delay, age, open access endoscopy, number and type of symptoms as independent variables, the odd's ratio for survival in patients with long delay (>median) versus short delay (≤median) was 1.8 (95% confidence interval (CI) 1.1 to 3.0; <it>p </it>= 0.01). Tumor-site was not associated with patient survival. When separating late stage CRC in Dukes C and Dukes D tumors, a shorter delay was associated with a shorter survival in Dukes D tumors only and not in Dukes C tumors.</p> <p>Conclusion</p> <p>In symptomatic CRC patients, a longer diagnostic and therapeutic delay in routine clinical practice was not associated with an adverse effect on survival. The time to CRC diagnosis and initiation of treatment did not differ between early stage and late stage colorectal cancer.</p

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

Teachers' resilience: conceived, perceived or lived-in

[Extract] Schools in Western countries are places where work related conditions lead to teacher disaffection and attrition. To mitigate this employers and scholars advocate fostering teacher resilience. This chapter presents a critical examination of teacher resilience. Originally conceived as a personal trait, later research showed human resilience is an attribute that can be developed. Resilience is one’s ability to manage stressors and maintain adaptive functioning across all domains of life. Latterly, scholars investigated resilience in teachers, mainly through qualitative or quantitative self-report studies. This research constitutes perceived teacher resilience, because as formulated, teacher resilience is conceptually flawed, limited in scope, based on teachers’ functioning within their professional lives. We do not know what constitutes long serving teachers’ actual, lived-in resilience: what enables teachers to maintain their wellbeing and effectiveness in the classroom, reflecting human resilience as originally conceived. For an accurate profile of teacher resilience we must study those still teaching, and teachers who have exited the profession to determine why they left. Perhaps exiting the profession signals a resilient person who does accept working conditions that do not support wellbeing or teaching effectiveness. Perhaps ‘teacher resilience’ is inaccurately used in the context of teacher attrition and disaffection

Epidemiology of Clostridium difficile in infants in Oxfordshire, UK: Risk factors for colonization and carriage, and genetic overlap with regional C. difficile infection strains

Background: Approximately 30-40% of children <1 year of age are Clostridium difficile colonized, and may represent a reservoir for adult C. difficile infections (CDI). Risk factors for colonization with toxigenic versus non-toxigenic C. difficile strains and longitudinal acquisition dynamics in infants remain incompletely characterized. Methods: Predominantly healthy infants (≤2 years) were recruited in Oxfordshire, UK, and provided ≥1 fecal samples. Independent risk factors for toxigenic/non-toxigenic C. difficile colonization and acquisition were identified using multivariable regression. Infant C. difficile isolates were whole-genome sequenced to assay genetic diversity and prevalence of toxin-associated genes, and compared with sequenced strains from Oxfordshire CDI cases. Results: 338/365 enrolled infants provided 1332 fecal samples, representing 158 C. difficile colonization or carriage episodes (107[68%] toxigenic). Initial colonization was associated with age, and reduced with breastfeeding but increased with pet dogs. Acquisition was associated with older age, Caesarean delivery, and diarrhea. Breastfeeding and pre-existing C. difficile colonization reduced acquisition risk. Overall 13% of CDI C. difficile strains were genetically related to infant strains. 29(18%) infant C. difficile sequences were consistent with recent direct/indirect transmission to/from Oxfordshire CDI cases (≤2 single nucleotide variants [SNVs]); 79(50%) shared a common origin with an Oxfordshire CDI case within the last ~5 years (0-10 SNVs). The hypervirulent, epidemic ST1/ribotype 027 remained notably absent in infants in this large study, as did other lineages such as STs 10/44 (ribotype 015); the most common strain in infants was ST2 (ribotype 020/014)(22%). Conclusions: In predominantly healthy infants without significant healthcare exposure C. difficile colonization and acquisition reflect environmental exposures, with pet dogs identified as a novel risk factor. Genetic overlap between some infant strains and those isolated from CDI cases suggest common community reservoirs of these C. difficile lineages, contrasting with those lineages found only in CDI cases, and therefore more consistent with healthcare-associated spread