Quantitative expression of genes involved in the leptin receptor-mediated STAT signalling pathway in rodent models of obesity

In most cases of human obesity serum leptin levels are elevated, suggesting that reduced sensitivity to endogenous leptin may contribute towards the increase in body weight. There are several potential areas that may be involved in reduced leptin sensitivity, including the blood-brain-barrier (BBB) transport system, changes in expression of the functional leptin receptor, OB- Rb, and components of the leptin receptor-mediated STAT signalling pathway in which members of the SOCS family, SOCS-3 and CIS, act as negative regulators. The aim of this thesis was to examine how the mRNA expression of the leptin receptor and components of the leptin receptor-mediated signalling pathway alters in obesity models and thereby establish to what extent such genes are involved in leptin sensitivity. A novel fluorogenic method of quantitative RT-PCR, TaqMan, was utilised to examine the changes in mRNA expression. Gene expression was examined in central and peripheral tissues of obesity-prone AKR/J mice fed either a chow or a palatable diet for 14 weeks and compared to C57BL/6 lean and ob/ob mice fed a chow diet. The expression of OB-Ra mRNA was reduced in the hypothalamus and pituitary of AKR/J mice fed a palatable diet compared to those fed chow, which may implicate reduced OB-Ra-mediated signalling. In WAT of palatable diet-fed mice compared to those fed on chow, the expression of STATS and CIS mRNA was increased but SOCS-3 mRNA was reduced, which suggests this tissue may have increased sensitivity to leptin, but the increased CIS mRNA may compensate for the increased STATS mRNA. In contrast, in the small intestine, all of the components of leptin receptor-mediated signalling were reduced, except for CIS, which suggests this tissue has low leptin sensitivity and may have reduced leptin signalling. In the hypothalamus of ob/ob mice compared to leans, the expression of STATS and SOCS-3 mRNA were reduced. In the pituitary of ob/ob mice compared to leans, the expression of OB-Rb, STATS, STATS and SOCS-S mRNA was reduced, which may be due a consequence of the leptin deficiency. In the pancreas, the expression of STATS, STATS and SOCS-3 mRNA was increased perhaps reflecting an increase in leptin sensitivity or increased insulin signalling. In BAT, the increased expression of OB-Ra, OB-Rb and STATS mRNA and reduced CIS mRNA appears consistent with elevated leptin sensitivity in this tissue although SOCS-S mRNA was considerably elevated which may be due to obesity-related factors other than leptin. In order to further expand our understanding of the regulation of leptin sensitivity, the expression of components of the leptin receptor-mediated signalling pathway were analysed in the hypothalamus of ob/ob mice intraperitoneally treated with leptin for 24 hours compared to 2 weeks. In comparing ob/ob mice to leans in this study, the expression of OB-Rb, STATS, STATS was increased in contrast to the changes reported in the previous study. The treatment of ob/ob mice with leptin for 24 hours showed a significant reduction in the hypothalamus of SOCS-3 mRNA, but after 2 weeks of leptin treatment the expression of SOCS-S mRNA was increased not only in ob/ob mice but also in pair-fed controls. The involvement of SOCS-3 in hypothalamic leptin sensitivity has previously been reported but in this study the increase after 2 weeks of leptin treatment may be due to feeding rather than leptin. The expression of OB-Ra and OB-Rb mRNA was also examined in ZDF fa/fa rats to examine if the mutated leptin receptor has an effect on its expression. An increase of both OB-Ra and OB-Rb mRNA was observed in ZDF fa/fa rats compared to ZDF +/-- rats, which may be a compensatory change to the reduced leptin receptor-mediated signalling and leptin receptor cell surface expression in these animals. The gene expression changes in tissues of dietary obese and genetically obese mice followed no consistent pattern in relation to leptin sensitivity and can be interpreted in a number of different ways. The changes suggest, however, that some tissues may be more sensitive to the effects of leptin and changes in sensitivity compared to others but there appears to be no clear gene or set of gene changes predictive amongst the genes examined of leptin sensitivity. Since the expression of STATs and SOCs can be regulated by a number of signals it is difficult to definitively distinguish the effects of leptin, tissue-specific effects and other obesity-related factors in these tissues

Mediastinal seminoma presenting as superior vena cava syndrome and tracheal obstruction

Malignant germ cell tumours of the mediastinum are rare, presenting mostly in young males. These are bulky tumours, mostly intrathoracic, infiltrating into adjacent structures early in the growth process. Patients may present with symptoms of compression. Occasionally, mediastinal adenopathy and superior vena cava (SVC) syndrome may occur. We discuss a case of a 19 year old boy with six weeks history of progressively worsening shortness of breath and mid-sternal chest heaviness and one month history of swelling of the face and upper limbs. The entire face and upper extremities were grossly oedematous with engorged veins suggesting SVC syndrome. CT scan chest showed a large mediastinal mass 18 x 24 cm extending from the superior mediastinum to the mid pericardial area. The trachea was extrinsically compressed to almost 80% at its distal portion. Mass was resected completely. Post operative course was unremarkable. The final histopathology showed a fibrotic mass with no viable tumour. Surgery followed by radiation therapy has been the usual initial treatment with multimodal chemotherapy showing remarkable results

The sedimentology of the Lower Permian Dandot Formation: a component of the Gondwana deglaciation sequence of the Salt Range, Pakistan

The Dandot Formation is a part of the Lower Permian, dominantly continental, Gondwanan Nilawahan Group in the Salt Range, Pakistan. The formation conformably overlies the glacio-fluvial Tobra Formation and has a sharp conformable contact with the overlying fluvio-continental Warchha Sandstone. Sedimentary analyses show that the Dandot Formation consists of 1: bioturbated sandstone lithofacies (L1), 2: dark green mudstone/shale lithofacies (L2), 3: flaser bedded sandstone lithofacies (L3), 4: rippled sandstone lithofacies (L4), 5: cross-bedded sandstone lithofacies (L5), and 6: planar sandstone lithofacies (L6). These can be grouped into shoreface, inner shelf, and tidal flat and estuarine facies associations, deposited in shallow marine to intertidal environments. The upper part of the Tobra Formation at the Choa-Khewra road section, where it conformably underlies the Dandot Formation, contains palynomorphs assignable to the earliest Permian 2141B Biozone. In south Oman, the 2141B Biozone is closely associated with the Rahab Shale Member, a widespread shale unit which is considered to represent part of a Permian deglaciation sequence which culminates in the marine beds of the Lower Gharif Member, interpreted as due to post glacial marine transgression. Thus, the Tobra Formation and the overlying marine Dandot Formation may form part of a similar deglaciation sequence

Role of Person-Organizational Fit between Job Stress, Organizational Justice, and Turnover Intentions: A Developing Country Perspective

The purpose of this research is to investigate the interrelationship between job stress, organizational justice, and turnover intention in the hospitality industry of Bahawalpur, with the moderating effect of person-organization-fit. The study used self-administered questionnaires to collect data, which was then analyzed using advanced statistical techniques such as SPSS and SEM-PLS. The findings indicate a positive correlation between job stress and turnover intention, as well as between organizational justice and turnover intention. The results also suggest that person-organization-fit plays a moderating role in the relationship between job stress and turnover intention, but not in the relationship between organizational justice and turnover intention. The study contributes to both practical and theoretical aspects of the literature and provides recommendations for future research while acknowledging its limitations. &nbsp

SHORT TERM OUTCOME OF PATIENTS WITH HEPATOPANCREATOBILIARY MALIGNANCIES TREATED IN A MULTIDISCIPLINARY HEPATOBILIARY UNIT IN A TERTIARY REFERRAL CENTER

Purpose: Specialisation in hepatopancreatobiliary (HPB) surgery has evolved over the past few decades based on better understanding of the biology and the behaviour of the diseases. In this review from a specialised HPB service, we aim to provide an overview of the HPB oncological cases managed in a tertiary care cancer hospital. Methods: All cases of HPB malignancies treated in our hospital between October 2014 and September 2015 were included in the study. Clinical findings, operative details and short-term post-operative outcomes were assessed from a prospectively managed database. Results: A total of 65 oncological procedures were performed over 1 year. These included 23 hepatic resections, 27 pancreaticoduodenectomies, 5 radical surgeries for gallbladder cancer, 2 distal pancreatectomy and 8 nephrectomies with exploration of the inferior vena cava. One patient successfully underwent Associated Liver Partition with Portal vein ligation and staged hepatectomy (ALPPS Procedure), which to our knowledge was the rst ALPPS procedure carried out in Pakistan. Conclusion: The short-term experience of patients managed in specialised HPB unit has shown good outcomes.There is a need for establishing HPB units in most tertiary care hospitals in the country. Key words: Associated liver partition with portal vein ligation and staged hepatectomy procedure, hepatic resections, hepatopancreatobiliary surgery, pancreaticoduodenectomy

Taxation policy and regulation efficiency on increasing zakat collection: countries comparison analysis

Purpose - This study investigated the policies over countries, specifically concerning the taxation in its regard with the zakat collection. The aim is to see whether making zakat compulsory helps solving zakat collection problem or not.Method - The study used a descriptive analysis model with a qualitative approach.  The range of data collected in 2006-2017 came from nine countries, namely Saudi Arabia, Kuwait, Sudan, Jordan, Brunei Darussalam, Malaysia, Indonesia, Singapore, Pakistan.Result - The results of this study indicate that Sudan, Brunei Darussalam, Singapore and Pakistan follow a mandatory approach while Malaysia, Kuwait, Indonesia, Jordan and Saudi Arabia follow a voluntary approach.  It was also found that a mandatory approach attracted more zakat collection as indicated by the zakat collection ratio.Implication - Pointing out that mandating zakat by imposing it through regulations helps collect more zakat payments.Originality - This research specifically contributes to studying the tax system in various countries to stimulate the collection of zakat by using a comparative study

COMPARISON OF OUTCOMES OF ENDOSCOPIC MICRODISCECTOMY VERSUS CONVENTIONAL DISCECTOMY FOR LUMBER DISC DISEASES

Introduction: Chronic lumbosacral pain is a communal and difficult clinical condition at the center of pain management. The most common surgical indication is back pain or intractable and severe functional impairment that does not respond to conservative measures. In this study we have compared the results of endoscopic d microdiscectomy and conventional discectomy procedure. Material and Methods: We included 54 patients with severe lower back pain who did not improve after long-term conservative treatment and who had level 3 disc prolapse, radiating to one or both lower limbs. Oswestry Disability Index (For Low Back Pain) was documented with questionnaire comeback and applied as a clinical tool for valuation. Results: The average age of the 54 patients was 46 years and 75% of patients have paracentral disc protrusion. The mean endoscopic microdiscectomy surgery time was 110 minutes; was longer than conventional discectomy (82 minutes). However, blood loss was very small compared to conventional discectomy. According to the ODI result, both conventional and endoscopic discectomy gave same outcomes in all classes. Conclusion: Endoscopic microdiscectomy is a new, effective and safe procedure that reduces the invasiveness of the surgical approach. The results obtained by this approach are comparable with those obtained with open discectomy to alleviate symptoms during prolonged observation, and because the tissue has minimal trauma, it is much better in early mobilization and morbidity

Advancing the use of real world evidence in health technology assessment:insights from a multi-stakeholder workshop

Introduction: Real-world evidence (RWE) in health technology assessment (HTA) holds significant potential for informing healthcare decision-making. A multistakeholder workshop was organised by the European Health Data and Evidence Network (EHDEN) and the GetReal Institute to explore the status, challenges, and opportunities in incorporating RWE into HTA, with a focus on learning from regulatory initiatives such as the European Medicines Agency (EMA) Data Analysis and Real World Interrogation Network (DARWIN EU ®). Methods: The workshop gathered key stakeholders from regulatory agencies, HTA organizations, academia, and industry for three panel discussions on RWE and HTA integration. Insights and recommendations were collected through panel discussions and audience polls. The workshop outcomes were reviewed by authors to identify key themes, challenges, and recommendations. Results: The workshop discussions revealed several important findings relating to the use of RWE in HTA. Compared with regulatory processes, its adoption in HTA to date has been slow. Barriers include limited trust in RWE, data quality concerns, and uncertainty about best practices. Facilitators include multidisciplinary training, educational initiatives, and stakeholder collaboration, which could be facilitated by initiatives like EHDEN and the GetReal Institute. Demonstrating the impact of “driver projects” could promote RWE adoption in HTA. Conclusion: To enhance the integration of RWE in HTA, it is crucial to address known barriers through comprehensive training, stakeholder collaboration, and impactful exemplar research projects. By upskilling users and beneficiaries of RWE and those that generate it, promoting collaboration, and conducting “driver projects,” can strengthen the HTA evidence base for more informed healthcare decisions.</p

Evaluation of Safety of Stewart’s Wood Fern (Dryopteris stewartii) and Its Anti-Hyperglycemic Potential in Alloxan-Induced Diabetic Mice

Diabetes has become a critical challenge to the global health concerns. Cytotoxicity and development of resistance against available drugs for management of diabetes have shifted the focus of global scientific researchers from synthetic to herbal medications. Therefore, the current study was conducted to investigate the possible anti-hyperglycemic potential of Dryopteris stewartii using Swiss albino mice. To evaluate any possible toxic effect of the plant, acute oral toxicity test was performed while the anti-diabetic effects of aqueous and ethanol extracts at 500 mg/kg, positive, negative and normal control were assessed simultaneously. The anti-diabetic study revealed that aqueous extract has higher anti-diabetic potential than ethanol extract while lowered blood glucose level at second week reaching 150 mg/dL, exerting stronger anti-diabetic effects, compared to ethanol extract (190 mg/dL). Oral glucose tolerance findings revealed that aqueous extract decreased blood glucose level by −0.41-fold, compared to ethanol extract showing a decrease by only −0.29-folds. The histopathological evaluation of liver and pancreas of all groups revealed normal cell architecture with no morphological abnormalities. These results suggested the possible use of D. stewartii as anti-diabetic herbal drug in near future. However, these recommendations are conditioned by deep mechanistic studies

Academic Integrity: Effects of Demographic Variables on Students’ Conduct

This study aimed to find out the effects of demographic variable i.e. gender, age, group of studies, GPA etc. on level of academic integrity among Pakistani students. The design of the study is quantitative in nature, in which the survey research method was employed to gather data from the respondents. A self-reported questionnaire was adapted on the basis of previously developed and validated questionnaire, with the consent of the authors. The developed scale was validated with the help of experts and pilot tested. Multilevel stratified convenience sampling technique was used to collect data from 4 provinces and federal area of Pakistan. The collected data was analyzed by using SPSS 16.0 versio