Borderline Tumors of the Ovary: A Clinicopathological Study

Objective: To report experience with borderline ovarian tumors (BOTs) in a developing country like Pakistan with limited resources and weak database of health system. Methods: Patients with BOTs managed at Shaukat Khanum Cancer hospital, Lahore, Pakistan from 2004 to 2014 were included and reviewed retrospectively. Data was recorded on histopathological types, age, CA-125, stage of disease, treatment modalities and outcomes. Results: Eighty-six patients with BOT were included with a median age of 35 years. Forty-two (49%) patients had serous BOTs and 43 (50%) had mucinous BOTs, while one (1%) had mixed type. Using FIGO staging, 80 patients had stage I; two patients had IIA, IIB and stage III each. Median follow-up time was 31.5 months. All patients had primary surgery. Seventy (81%) patients underwent complete surgical resection of tumor. Forty-three (50%) patients had fertility preserving surgery. Seventy-three (85%) patients remained in remission. Recurrent disease was observed in 13 (15%) patients. Median time to recurrence was 22 months. On further analysis, age above forty years, late stage at diagnosis and incomplete surgery were significantly associated with invasive recurrence. Conclusion: Despite a low malignant potential, relapses may occur in patients above forty years of age, incomplete surgery and staging information and advanced stage at presentation. Fertility sparing surgery should be considered in young patients. Complete excision of tumor and prolonged follow-up are advised because recurrence and transformation to invasive carcinoma may occur

Vitamin d3 levels in patients of left ventricular hypertrophy in essential hypertension; a case control study

Objective: Analysis of serum cholecalciferol in essential hypertension and its correlation with left ventricular hypertrophy (LVH).Methodology: This cross sectional study was conducted at Department of Medicine, Isra University, Hyderabad from September 2017 to March 2018. Hundred controls and Hundred diagnosed cases of essential hypertension with left ventricular hypertrophy were selected. LVH was estimated by echocardiography. Blood samples were centrifuged at 4000 rpm (10 minutes) to separate sera for biochemical estimation of serum cholecalciferol, serum calcium, serum phosphate and alkaline phosphatase. Statistical analysis was performed on statistical software (SPSS 22.0) and Microsoft excel. Continuous variables were presented as mean ± S.D as analysed by Student`s t-test. Statistical significance was taken at 95% confidence interval (P-value ≤0.05).Results: Serum cholecalciferol was low in cases 22.84±5.10 ng/dl compared to controls 47.09±7.65 ng/dl (p=0.0001). Mean ± SD interventricular septum and posterior wall thickness was noted as 12.39±1.82 mm in cases. Serum cholecalciferol revealed negative correlation with LVH (r= - 0.774, p=0.0001).Conclusion: Low serum cholecalciferol was found in the essential hypertension with left ventricular hypertrophy

Medical doctors\u27 offline computer-assisted digital education: Systematic review by the digital health education collaboration

Background: The widening gap between innovations in the medical field and the dissemination of such information to doctors may affect the quality of care. Offline computer-based digital education (OCDE) may be a potential solution to overcoming the geographical, financial, and temporal obstacles faced by doctors.Objective: The objectives of this systematic review were to evaluate the effectiveness of OCDE compared with face-to-face learning, no intervention, or other types of digital learning for improving medical doctors\u27 knowledge, cognitive skills, and patient-related outcomes. Secondary objectives were to assess the cost-effectiveness (CE) of OCDE and any adverse effects.Methods: We searched major bibliographic databases from 1990 to August 2017 to identify relevant articles and followed the Cochrane methodology for systematic reviews of intervention.Results: Overall, 27 randomized controlled trials (RCTs), 1 cluster RCT (cRCT), and 1 quasi-RCT were included in this review. The total number of participants was 1690 in addition to the cRCT, which included 24 practices. Due to the heterogeneity of the participants, interventions, and outcomes, meta-analysis was not feasible, and the results were presented as narrative summary. Compared with face-to-face learning, the effect of OCDE on knowledge gain is uncertain (ratio of the means [RM] range 0.95-1.17; 8 studies, 495 participants; very low grade of evidence). From the same comparison, the effect of OCDE on cognitive skill gain is uncertain (RM range 0.1-0.9; 8 studies, 375 participants; very low grade of evidence). OCDE may have little or no effect on patients\u27 outcome compared with face-to-face education (2 studies, 62 participants; low grade of evidence). Compared with no intervention, OCDE may improve knowledge gain (RM range 1.36-0.98; 4 studies, 401 participants; low grade of evidence). From the same comparison, the effect of OCDE on cognitive skill gain is uncertain (RM range 1.1-1.15; 4 trials, 495 participants; very low grade of evidence). One cRCT, involving 24 practices, investigated patients\u27 outcome in this comparison and showed no difference between the 2 groups with low-grade evidence. Compared with text-based learning, the effect of OCDE on cognitive skills gain is uncertain (RM range 0.91-1.46; 3 trials with 4 interventions; 68 participants; very low-grade evidence). No study in this comparison investigated knowledge gain or patients\u27 outcomes. One study assessed the CE and showed that OCDE was cost-effective when compared with face-to-face learning if the cost is less than or equal to Can $200. No trial evaluated the adverse effect of OCDE.Conclusions: The effect of OCDE compared with other methods of education on medical doctors\u27 knowledge and cognitive skill gain is uncertain. OCDE may improve doctors\u27 knowledge compared with no intervention but its effect on doctors\u27 cognitive skills is uncertain. OCDE may have little or no effect in improving patients\u27 outcome

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.</p

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.</p

Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases

The impact of the COVID-19 pandemic on the education of medical, dental and non-medical healthcare professionals in Bangladesh : findings and connotation

Lockdown measures in response to the COVID-19 pandemic had an appreciable impact on the education of all medical, dental, and non-medical healthcare professional (HCP) students. These included the closure of universities necessitating a rapid move to e-learning and new approaches to practical’s. However initially, there was a lack of knowledge and expertise regarding e-learning approaches and the affordability of internet bundles and equipment. We initially con-ducted two pilot studies to assess such current challenges, replaced by a two-stage approach including a full investigation involving 32 private and public universities during the early stages of the pandemic followed by a later study assessing the current environment brought about by the forced changes. Top challenges at the start of the pandemic included a lack of familiarity with e-learning approaches, cost of the internet, lack of IT equipment and the quality of the classes. Universities offered support to staff and students to a varying degree to address identified challenges. Since then, e-learning approaches have widened the possibilities for teaching and learning at convenient times. However, challenges remain. In conclusion, there were considerable challenges at the start of them pandemic. Several key issues have been addressed with hybrid learning here to stay. Remaining challenges include a lack of ICT equipment. However, new innovations will continue

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Dissecting the steps of substrate processing by the energy-dependent protease ClpXP

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2004.Includes bibliographical references.Intracellular proteolysis is carried out by self-compartmentalized, energy dependent proteases which contain a regulatory and a proteolytic component. The regulatory component, which contains ATPases, has crucial activities necessary for the mechanism of degradation. To degrade a substrate the regulatory component recognizes and binds the substrate, then processes it further for degradation by actively unfolding and translocating it into a sequestered proteolytic compartment. The substrate is degraded into small fragments, approximately 9-11 amino acids long, that are then released. Both the regulatory and proteolytic components have pores which align to form a channel through which substrates are proposed to travel. In the bacterial energy-dependent protease ClpXP, ClpX is the regulatory component and ClpP is the proteolytic component. To better understand the proteolytic activity of ClpXP we investigated the steps involved in processing of substrates by ClpXP. The aim of this thesis is to present studies that have provided information about the roles of the important features of the ClpXP complex, namely the central pore of ClpX, the N-domain of ClpX and the channel of the ClpXP protease, during processing of substrates. Using mutational analysis I have found that the central pore of ClpX is involved in processing of C-motif 1 signals, one of the five classes of recognition signals, suggesting that ClpX processes its substrates with different recognition signals in at least two distinct manners. The central pore is also involved in engagement of C-motif 1 substrates, a step following binding but prior to further processing of substrates.(cont.) I have found that the N-domain is necessary for activity of the ClpX adaptor protein RssB in degradation of [sigma]. I have also found that the N-domain plays a differential role in degradation of ClpXP substrates, it is necessary for efficient degradation of protein substrates containing all of the recognition signals except C-motif 1. The N-domain was not necessary for degradation of N-motif 1 and N-motif 2 peptide substrates, which unlike protein substrates do not need to be unfolded during degradation. Thus suggesting that the N-domain is involved in steps following binding, that is, unfolding and/or translocation. I have shown that ClpXP can efficiently degrade proteins containing a disulfide-bond. This suggests that the ClpXP channel can expand to [approx.] 20-25A [Angstroms], since translocation of an intact disulfide bond requires simultaneous translocation of two, if not three, polypeptide chains. My work has contributed to understanding how ClpXP functions by providing insights into the roles of the central pore and the N-domain of ClpX in processing substrates and by demonstrating that the ClpXP channel can be flexible to accommodate its substrates.by Samia M. Siddiqui.Ph.D