MORPHOLOGIC SPECTRUM AND CLINICO-PATHOLOGICAL CORRELATION OF GASTROINTESTINAL STROMAL TUMOURS: AN EXPERIENCE OF SIX YEARS AT A TERTIARY CARE HOSPITAL.

Objective: The objective of this study was to determine the morphologic spectrum and risk category of gastrointestinal stromal tumour (GIST) and compare with overall patient survival.Materials and Methods: It is a descriptive observational study. The study was carried at Shifa International Hospital, Islamabad. Duration of the study was from January 2009 to January 2015. A total of 31 patients with the diagnosis of GIST were included, irrespective of age and gender. Data were retrieved from laboratory information system. Results were analysed by statistical software, Statistical Package of the Social Sciences. Morphologic type, site of tumour, risk category and overall survival were determined and mean, standard deviation, frequencies and percentages were calculated for age site and risk category. Results: Of 31 patients, 21 (67.7%) were male and 10 (32.3%) were female. Site of tumour was as follows: Gastric 13 (41.9%), extra visceral 6 (19.4%), small intestine 9 (29.0%), rectum 2 (6.5%) and pancreas 1 (3.2%). According to risk categorisation, one was categorised as (3.2%) very low risk, 3 (9.7%) low risk, 5 (16.1%) intermediate risk and 22 (71%) high risk. Follow-up was available in 21 patients. 7 patients (22.5%) lost to follow-up. 8 (25%) had recurrence and 4 (12.9%) died. Conclusion: Majority of cases diagnosed at our centre were gastric in origin followed by small intestine, and as per risk categorisation, most were high risk. Patient survival with high-risk tumours was dismal. Key words: Gastrointestinal stromal tumour, immunohistochemistry, risk categorisation

A study of ghrelin and leptin levels and their relationship to metabolic profiles in obese and lean Saudi women with polycystic ovary syndrome (PCOS)

BACKGROUND: Polycystic ovary syndrome (PCOS) is considered as one of the most frequently encountered hormonal pathologies in women during their reproductive years. Leptin and ghrelin, peptide hormones with adipostatic and orexigenic effect, respectively, seem to be involved in the metabolic changes that occur in PCOS. The aim of this study was to determine serum ghrelin and leptin levels in obese and lean Saudi women with PCOS and to investigate their relationship to the metabolic profiles in these women. METHODS: This study was conducted as a prospective, observational, cross-sectional, case-control study, at the Department of Obstetrics and Gynecology, Al-Noor Hospital, Makkah, Kingdom of Saudi Arabia. The study population included 252 women [130 women with PCOS (diagnosed according to the Rotterdam ESHRE/ASRM-Sponsored PCOS Consensus, 2003) and 122 normo-ovulatory women as matched controls] attending the outpatient Gynecology Clinic. Demographic details were recorded, blood was extracted following overnight fast and serum was used for the determination of serum ghrelin and leptin levels and other hormonal and biochemical parameters including total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, glucose, and insulin. Insulin resistance and sensitivity were calculated as HOMA-IR and HOMA-S. RESULTS: No significant differences in ghrelin (P\u2009=\u20090.1830) and leptin (P\u2009=\u20090.8329) levels were detected between the PCOS and control groups. However, ghrelin levels were significantly lower; and leptin levels were significantly higher in obese PCOS patients in comparison with lean patients (P\u2009=\u20090.0001 for both). In the PCOS group, there were significant correlations between ghrelin and leptin levels with Body Mass Index (BMI), waist-hip ratio, total cholesterol, triglycerides, HDL, LDL and insulin levels. Multiple regression analysis demonstrated that insulin was the main determinant for ghrelin (R2\u2009=\u20090.316) and leptin (R2\u2009=\u20090.352) levels (P\u2009=\u20090.0001 for both). CONCLUSIONS: Although serum ghrelin and leptin levels were found to be normal in women with PCOS; yet, there is a relationship, possibly linked to obesity, hyperinsulinemia and insulin resistance between these levels and metabolic profile of Saudi PCOS

Psychological impact of COVID-19 restrictions among individuals at risk of exercise addiction and their socio-demographic correlates: a Saudi Arabian survey study

Exercise addiction (EA) has been described as a condition of psychological dysfunction characterized by excessive and obsessive exercise patterns, show withdrawal symptoms when unable to exercise, and experience numerous conflicts and other negative consequences in their social and professional lives, due to the extremely high volumes of exercise. The main objective of the present study was to assess the risk of exercise addiction among a Saudi Arabian sample of regular exercisers and to investigate possible associations between their inability to exercise during the COVID-19 pandemic lockdown (due to the closure of public gyms, swimming pools, and health clubs) and depression, anxiety, and loneliness. A total of 388 regular-exercising Saudis participated in an online cross-sectional survey over three months (December to February 2021). The study sample comprised 89.9% (males) and 10.1% (females), with a mean age of 28.59 years (SD ± 6.69). A 36-item online self-report survey was used for data collection. The prevalence of being at risk of exercise addiction among participants of the present study was 13.1%. Positive significant associations were noted between risk of exercise addiction and depression (r = .41; p < .01), risk of exercise addiction and anxiety (r = .20; p < .01), and risk of exercise addiction and loneliness (r = .17; p < .01). The findings of the present study suggest that those individuals at risk of exercise addiction might also be at an elevated risk of developing negative psychological impact owing to the disruption of the amount of exercise engaged in due to COVID-19 pandemic-related restrictions and therefore these high-risk individuals should receive appropriate psychological support to help them overcome the negative impact of the ongoing pandemic

Malignancy risk analysis in patients with inadequate fine needle aspiration cytology (FNAC) of the thyroid

Background Thyroid fine needle aspiration cytology (FNAC) is the standard diagnostic modality for thyroid nodules. However, it has limitations among which is the incidence of non-diagnostic results (Thy1). Management of cases with repeatedly non-diagnostic FNAC ranges from simple observation to surgical intervention. We aim to evaluate the incidence of malignancy in non-diagnostic FNAC, and the success rate of repeated FNAC. We also aim to evaluate risk factors for malignancy in patients with non-diagnostic FNAC. Materials and Methods Retrospective analyses of consecutive cases with thyroid non diagnostic FNAC results were included. Results Out of total 1657 thyroid FNAC done during the study period, there were 264 (15.9%) non-diagnostic FNAC on the first attempt. On repeating those, the rate of a non-diagnostic result on second FNAC was 61.8% and on third FNAC was 47.2%. The overall malignancy rate in Thy1 FNAC was 4.5% (42% papillary, 42% follicular and 8% anaplastic), and the yield of malignancy decreased considerably with successive non-diagnostic FNAC. Ultrasound guidance by an experienced head neck radiologist produced the lowest non-diagnostic rate (38%) on repetition compared to US guidance by a generalist radiologist (65%) and by non US guidance (90%). Conclusions There is a low risk of malignancy in patients with a non-diagnostic FNAC result, commensurate to the risk of any nodule. The yield of malignancy decreased considerably with successive non-diagnostic FNAC

Knowledge retention in ERP implementations: the context of UK SMEs

Knowledge retention (k-retention) is vital for various enterprise resource planning (ERP) implementations in small and medium-sized enterprises (SMEs), though it is a highly demanding and challenging task. The aim of this paper is to investigate different types of approaches to k-retention and factors influencing k-retention in SMEs. Our study adopts a grounded theory approach with cases based on 12 ERP implementations in UK SMEs. We analyze our data using thematic analysis. The findings reveal specific elements that support the k-retention of ERP package knowledge and business process knowledge. These elements are: k-retention tools, documentation, human capital and the understanding of k-retention challenges. In addition to insights from these aspects, our study reveals two additional factors (project management and organizational culture) that influence ERP package k-retention and business process k-retention. Based on these findings, we develop an ERP k-retention (EKR) framework that can be utilized by SMEs which are considering implementing ERP systems, to facilitate knowledge retention during implementation

High grade angiosarcoma arising in fibroadenoma

Primary angiosarcoma of the breast is a rare tumour that account for fewer than 0.05% of all malignant mammary tumours. Angiosarcoma may have an perfidious clinical onset. Radiologic findings are often nonspecific and may appear completely normal in one-third of cases with primary angiosarcoma. The prognosis is usually poor because of the high rates of local recurrence and early development of metastases. Aggressive surgical resection is the mainstay of treatment. The role of adjuvant therapy has not yet been well established

Purification of Reversibly Oxidized Proteins (PROP) Reveals a Redox Switch Controlling p38 MAP Kinase Activity

Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity

Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and β-adrenoceptors

The normal physiological contraction of the urinary bladder, which is required for voiding, is predominantly mediated by muscarinic receptors, primarily the M3 subtype, with the M2 subtype providing a secondary backup role. Bladder relaxation, which is required for urine storage, is mediated by β-adrenoceptors, in most species involving a strong β3-component. An excessive stimulation of contraction or a reduced relaxation of the detrusor smooth muscle during the storage phase of the micturition cycle may contribute to bladder dysfunction known as the overactive bladder. Therefore, interference with the signal transduction of these receptors may be a viable approach to develop drugs for the treatment of overactive bladder. The prototypical signaling pathway of M3 receptors is activation of phospholipase C (PLC), and this pathway is also activated in the bladder. Nevertheless, PLC apparently contributes only in a very minor way to bladder contraction. Rather, muscarinic-receptor-mediated bladder contraction involves voltage-operated Ca2+ channels and Rho kinase. The prototypical signaling pathway of β-adrenoceptors is an activation of adenylyl cyclase with the subsequent formation of cAMP. Nevertheless, cAMP apparently contributes in a minor way only to β-adrenoceptor-mediated bladder relaxation. BKCa channels may play a greater role in β-adrenoceptor-mediated bladder relaxation. We conclude that apart from muscarinic receptor antagonists and β-adrenoceptor agonists, inhibitors of Rho kinase and activators of BKCa channels may have potential to treat an overactive bladder