1,309 research outputs found

    Analysis of resolvins in fish cultured cells challenged with docosahexaenoic acid by liquid chromatography triple quadrupole mass spectrometry.

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    Master's Thesis in Quality in the Analytical LaboratoryQAL399BJMAMN-QAL

    STAT3 Genotypic Variant rs744166 and Increased Tyrosine Phosphorylation of STAT3 in IL-23 Responsive Innate Lymphoid Cells during Pathogenesis of Crohn\u27s Disease

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    Crohn\u27s disease (CD) results from dysregulated immune responses to gut microbiota in genetically susceptible individuals, affecting multiple areas of the gastrointestinal tract. Innate lymphoid cells (ILCs) are tissue-resident innate effector lymphocytes which play crucial roles in mucosal immune defense, tissue repair, and maintenance of homeostasis. The accumulation of IFN-Îł-producing ILC1s and increased level of proinflammatory cytokines produced by ILCs has been observed in the inflamed terminal ileum of CD patients. To date, the precise mechanisms of ILC plasticity and gene regulatory pathways in ILCs remain unclear. Signal transducer and activator of transcription 3 (STAT3) regulates gene expression in a cell-specific, cytokine-dependent manner, involving multiple immune responses. This study proposes the positive correlation between the prevalence of STAT3 rs744166 risky allele A with the severity of disease in a cohort of 94 CD patients. In addition, the results suggest an increased STAT3 activity in the inflamed ileum of CD patients, compared to unaffected ileum sections. Notably, IL-23 triggers the differentiation of CD117+NKp44- ILC3s and induces the activation of STAT3 in both CD117+NKp44- and CD117-NKp44- ILC subsets, implying the involvement of STAT3 in the initiation of ILC plasticity. Moreover, carriage of STAT3 A risk allele exhibited a higher basal level of STAT3 tyrosine phosphorylation, and an increased IL-23 triggered the pSTAT3 level. We also demonstrated that there was no delayed dephosphorylation of STAT3 in ILCs of both A/A and G/G donors. Overall, the results of this study suggest that IL-23-induced activation of STAT3 in the CD117-NKp44- ILC1s involves in ILC1-to-ILC3 plasticity and a potential regulatory role of ILC1 function. Those genetically susceptible individuals carried STAT3 rs744166 risky allele appear to have higher basal and cytokine-stimulated activation of STAT3 signal, leading to prolonged inflammation and chronic relapse

    Sigmoid perforation caused by an ingested chicken bone presenting as right iliac fossa pain mimicking appendicitis: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Gastrointestinal perforation due to a foreign body is not unknown. The foreign body often mimics another cause of acute abdomen and requires emergency surgical intervention. The majority of patients do not recall ingesting the foreign body. Perforations have been reported to occur in a pathologically abnormal colon.</p> <p>Case presentation</p> <p>We report an interesting case of a 47-year-old Caucasian man who had a perforation of the sigmoid colon caused by an ingested chicken bone mimicking acute appendicitis. Our patient presented with right iliac fossa pain and local tenderness. When a laparotomy was performed, a chicken bone was found protruding through the sigmoid colon, which was found to lie in the right iliac fossa, thus mimicking acute appendicitis. Our case is different from previously reported cases in that perforation occurred in a non-pathological colon.</p> <p>Conclusion</p> <p>Our case emphasises the fact that the operating surgeon has to be aware of various differential diagnostic possibilities which mimic acute appendicitis. This has implications on the training of junior surgeons who are often involved in performing these procedures, and may do so out of hours. Care needs to be taken while obtaining consent for the necessary operation.</p

    Association of obesity with infertility among Pakistani men: A case control study

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    Background: The reported prevalence of infertility in Pakistan is 21% of which 35% is contributed by male factor. Male infertility has multifactorial etiologies ranging from modifiable to genetic risk factors. Among all the risk factors that may account for male infertility, obesity is one of the emerging public health problems. Therefore, the aim of the study was to determine the association of obesity with infertility in Pakistani men.Methods: We conducted a case control study. Cases were men with impaired semen parameters and controls did not have impaired semen parameters.Results: The final multivariable logistic regression model after adjusting for the effect of other variables revealed that with every 1 kg/m2 increase in BMI the odds of being infertile was 6% higher as compared to being fertile (aOR = 1.06; 95% CI = 1.01, 1.11). Moreover the odds of having education of higher secondary or above was 3 times greater among cases as compared with the controls (OR = 3.10; 95% CI = 1.66, 5.77). Furthermore the odds of having previous medical conditions increasing the risk of infertility was higher among cases as compared with the controls (OR = 3.07; 95% CI = 1.63, 5.79).Conclusion & recommendations: This study indicates that obesity is an important risk factor for male infertility. Moreover our findings also indicate that higher educational status and previous medical conditions are also associated with male infertility. Thus awareness can be raised through treating physicians and public health messages

    A microfibril assembly assay identifies different mechanisms of dominance underlying Marfan syndrome, stiff skin syndrome and acromelic dysplasias

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    Fibrillin-1 is the major component of the 10–12 nm diameter extracellular matrix microfibrils. The majority of mutations affecting the human fibrillin-1 gene, FBN1, result in Marfan syndrome (MFS), a common connective tissue disorder characterised by tall stature, ocular and cardiovascular defects. Recently, stiff skin syndrome (SSS) and a group of syndromes known collectively as the acromelic dysplasias, which typically result in short stature, skin thickening and joint stiffness, have been linked to FBN1 mutations that affect specific domains of the fibrillin-1 protein. Despite their apparent phenotypic differences, dysregulation of transforming growth factor β (TGFβ) is a common factor in all of these disorders. Using a newly developed assay to track the secretion and incorporation of full-length, GFP-tagged fibrillin-1 into the extracellular matrix, we investigated whether or not there were differences in the secretion and microfibril assembly profiles of fibrillin-1 variants containing substitutions associated with MFS, SSS or the acromelic dysplasias. We show that substitutions in fibrillin-1 domains TB4 and TB5 that cause SSS and the acromelic dysplasias do not prevent fibrillin-1 from being secreted or assembled into microfibrils, whereas MFS-associated substitutions in these domains result in a loss of recombinant protein in the culture medium and no association with microfibrils. These results suggest fundamental differences in the dominant pathogenic mechanisms underlying MFS, SSS and the acromelic dysplasias, which give rise to TGFβ dysregulation associated with these diseases

    Factors Affecting Clinical Performance among Pakistani Dental Students: A Cross-Sectional Study

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    Objective:&nbsp;To identify the factors affecting clinical performance among dental students and to help addressing these problems.&nbsp;Material and Methods:&nbsp;A cross-sectional study in which students of third and final year of dentistry participated. Data was collected from June 2022 till September 2022. Data was collected from the third and final year dental students of both public and private dental colleges within the Pakistan using a purposive sampling technique.&nbsp;Results:&nbsp;A total of 372 dental students participated in this study. Thirty eight (31.9%) students belonged to third year while 81 (68.1%) were final year students from government college. For the private dental college, 121 (47.8%) were third year students while 132 (52.2%) were final year students. Majority of the participants were males from both the colleges. 42.9% of government dental students and 26.5% of private dental students agreed on well-preparedness of clinical instructors. 5.5% from private and 21.0% from government dental colleges agreed that adequate personal protective equipment were present in clinical departments.&nbsp;Conclusion:&nbsp;From this study, it is concluded that there should be focus more focus on the factors to enhance clinical skills, supervision of students in clinical practice to help addressing the problems faced during learning and performance in a clinical environment, to produce self-confident, motivated, knowledgeable, skillful and a professional dental graduates

    Analysis of occludin trafficking, demonstrating continuous endocytosis, degradation, recycling and biosynthetic secretory trafficking

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    Š 2014 Fletcher et al. Tight junctions (TJs) link adjacent cells and are critical for maintenance of apicalbasolateral polarity in epithelial monolayers. The TJ protein occludin functions in disparate processes, including wound healing and Hepatitis C Virus infection. Little is known about steady-state occludin trafficking into and out of the plasma membrane. Therefore, we determined the mechanisms responsible for occludin turnover in confluent Madin-Darby canine kidney (MDCK) epithelial monolayers. Using various biotin-based trafficking assays we observed continuous and rapid endocytosis of plasma membrane localised occludin (the majority internalised within 30 minutes). By 120 minutes a significant reduction in internalised occludin was observed. Inhibition of lysosomal function attenuated the reduction in occludin signal post-endocytosis and promoted co-localisation with the late endocytic system. Using a similar method we demonstrated that ∟20% of internalised occludin was transported back to the cell surface. Consistent with these findings, significant co-localisation between internalised occludin and recycling endosomal compartments was observed. We then quantified the extent to which occludin synthesis and transport to the plasma membrane contributes to plasma membrane occludin homeostasis, identifying inhibition of protein synthesis led to decreased plasma membrane localised occludin. Significant co-localisation between occludin and the biosynthetic secretory pathway was demonstrated. Thus, under steady-state conditions occludin undergoes turnover via a continuous cycle of endocytosis, recycling and degradation, with degradation compensated for by biosynthetic exocytic trafficking. We developed a mathematical model to describe the endocytosis, recycling and degradation of occludin, utilising experimental data to provide quantitative estimates for the rates of these processes
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