Islet Dysfunction In Diabetes

Type 2 Diabetes [T2DM] is a chronic condition resulting from gradual failure of pancreatic beta cells to synthesize and secrete sufficient insulin to meet the metabolic demands and the inability of tissues [muscle, adipose and liver] to efficiently utilize the secreted insulin leading to an overall increase in blood glucose levels [hyperglycemia]. As indicated by recent estimates from the International Diabetes Federation, the prevalence of the disease in the year 2014 has risen to a record 387 million worldwide. The main objective of my project was to study the mechanisms involved in pancreatic beta cell dysfunction in diabetes, specifically in elucidating the role of endoplasmic reticulum [ER] - mitochondria axis, executioner caspases and their target substrates; specifically nuclear lamins. Results obtained from our studies in pure beta cells [INS-1 832/13], primary rodent and human islets strongly suggest that glucotoxicity induced pancreatic beta cell damage involves the degradation of nuclear lamins A and B, via ER stress-mediated activation of executioner caspases 3 and 6. We confirmed this by employing pharmacological approaches [inhibitors of -ER stress, -caspase activation and calcium channel activation] to gain mechanistic insights into beta cell dysfunction under the duress of chronic hyperglycemia. Further, we were able to corroborate these findings in the ZDF rat, an animal model for T2DM and in islets obtained from human donors with T2DM. Also, our findings revealed significant attenuation of glucose-stimulated insulin secretion [GSIS] in beta cells exposed to glucotoxic conditions suggesting cellular dysfunction under these conditions. Post-translational prenylation of lamins is important for their localization into the nuclear membrane, and subsequent interaction with other proteins. Our results indicate that inhibition of prenylation by simvastatin and a site-specific inhibitor of protein farnesylation [FTI-277], promoted mitochondrial and nuclear defects as evidenced by caspase activation and lamin degradation in INS-1 832/13 cells and normal rodent islets. Our findings also suggest that inhibition of protein prenylation leads to increase in stress kinase [p38 kinase] and inhibition of ERK1/2, known for its cell survival roles. Collectively, these alterations in cell signaling pathways could promote intracellular stress and demise. We hope that data accrued in these studies will provide fresh insights into the identification of the intracellular mechanisms involved in beta cell malfunction in nutrient overload and metabolic stress. These studies will also aid in the identification of potential drug targets for the management and/or prevention of diabetes

Assessment of Endometrial Thickness by TVS for Detection of Endometrial Carcinoma in Women with Post-Menopausal Bleeding

Objective: The aim of this study is to evaluate the role of endometrial thickness for detection of endometrial carcinoma in women with post-menopausal bleeding by use of Transvaginal ultrasound. Method: In this systematic review database by Medline, PubMed, science direct and Obsgyne online library were queried for studies published between 2005 to 2020 by using specific MeSH terms. Abstract from original peer-reviewed prospective Cohort studies that shows endometrial thickness with postmenopausal bleeding by specific ultrasound findings were included in this study. Results: Clinical data were extracted from 14 studies in which approx. 2500 women included with post-menopausal bleeding and 215(8.6%) cases were diagnose with endometrial carcinoma that shows endometrial thickness greater than 10mm on Transvaginal ultrasound. The prevalence of endometrial cancer was high in patients who had endometrial thickness >9.5 mm. Women with PMB that diagnose with EC had ET was 10 to 16mm.Women with PMB less than 4mm ET not diagnosed with EC. Conclusion: In this reviewed study we concluded that women with PMB showing ET greater than 10mm on Transvaginal ultrasound diagnosed with Endometrial carcinoma. Keywords: Endometrial Thickness (ET), Endometrial carcinoma (EC), Post-menopausal bleeding (PMB), Transvaginal Ultrasound (TVS). DOI: 10.7176/JHMN/82-11 Publication date: November 30th 2020

Risk of Ovarian Cancer After Treatment for Infertility

Background: Ovarian cancer is the most frequent cause of death from gynecologic malignancies in the world. Ovarian cancer is predominantly a disease of postmenopausal period, with a median age at diagnosis of 59 years. In recent years, there have been many debates about the relationship between fertility medication and cancer. Due to the lack of comprehensive study of this matter, and as understanding the relationship between the use of fertility drugs and cancer is of importance, the present study was conducted to investigate the relationship between infertility drugs and cancer in women. Objective: To determine the risk of ovarian cancer after treatment of infertility.  Study Selection: Multiple articles were reviewed. Prospective studies and case reports were excluded from the data. Retrospective studies were included in the study. Methods and Materials: A review of the scientific literature concerning the association between the use of fertility treatments and the risk of ovarian cancer was done. In this study, digital databases including PubMed, EMBASE and Google scholar were searched. The survey was carried out using keywords such as “infertility”, “ ovarian cancer risk”, “gynecological cancer”, “gynecological cancer risk”, “cancer risk”, “in vitro fertilization”, “progesterone”, “fertility drugs”, “infertility treatment”, variously associated together. Results: Using the search criteria, 25 researches were examined based on the title and abstract. All the 25 studies were considered in their full versions. Of these works, including literature reviews or meta-analysis reports, it was concluded that infertility treatment has a positive relationship with ovarian cancer. Conclusion: The results of this study suggest that fertility drug usage significantly contribute to overall risk of ovarian cancer when adjusting for known confounding factors. In the next years, the incidence of female infertility is expected to increase. A lot of new drugs are under investigation while other recent drugs are already in current use. More study can be done so that the mortality and mobility could be reduced in the society. Keywords: infertility, fertility drugs, ovarian cancer, infertility treatment DOI: 10.7176/JHMN/82-09 Publication date: November 30th 202

Role of Ultrasound in the Diagnosis of Endometritis- A Systemic Review

Endometritis is the most sustainable disease of the endometrium that leads to infertility in premenopausal women and many other pathologies in postmenopausal women. The role of ultrasound in the diagnosis of endometritis is indefinite, the sonographic signs of endometritis are most helpful for early detection and management. The aim to the study was to evaluate the role of ultrasound, as a diagnostic tool, for the diagnosis and management of endometritis. For this purpose, the literature of 2005-2020 from different search engines includes PubMed, Google Scholar, Science Direct, MEDLINE, Embase, and ResearchGate were studied and reviewed using MeSH (medical subject heading). Different retrospective studies were included, which had the same and diverse criteria for the diagnosis, to compare and find the accuracy of sonography as a first line tool. The exclusion criteria were not to include any prospective study, case-control study, and study former than 2005. The results of this systematic review indicated that the transvaginal ultrasound, hysterosonography, and abdominal ultrasonography can be used as a basic tool of investigation because of its availability and non-invasive technique. The other methods of molecular microbiology aided the diagnosis by confirming and to indicate the pathogens which cause endometritis. Hence, it is concluded that although the importance of ultrasound cannot be neglected but shouldn’t be limited to it. The other techniques used together provide much more authentic results. Keywords: Endometritis, Ultrasonography, Infertility. DOI: 10.7176/JHMN/84-04 Publication date: December 31st 202

Risk factors leading to pulmonary exacerbation in patients with cystic fibrosis: A systematic review

Objective: To ascertain major risk factors associated with pulmonary exacerbation and pulmonary function decline in cystic fibrosis.Methods: The systematic review was conducted at Aga Khan University, Karachi, in September 2018, and comprised electronic search of PubMed, Ovid, Science Direct and Cumulative Index of Nursing and Allied Health Literature databases of studies conducted from January 1990 to September 2018 which were categorised into 3 sets; 1990-98, 1999-2007 and 2008-18. Studies included for review focussed on articles with pulmonary exacerbation as the health outcome indicator, and had diagnosis of cystic fibrosis as the inclusion criteria, while risk factors were the exposure terms used in the search process. References in bibliographies of the included studies were also systematically searched for relevant documents.Results: Of the 60 studies obtained, 31(51.7%) were selected; 2(6.45%) from 1990-98, 7(22.58%) from 1999-2007 and 22(70.96%) from 2008-18. Overall, 17(54.83%) were cohort studies, 7(22.5%) were cross-sectional studies, 3(9.6%) were case-control studies, 3(9.6%) were randomised controlled trials and 1(3.2%) was systematic review and meta-analysis. In terms of major risk factors, genetic mutations were cited by 4(12.9%) studies, infections and inflammatory biomarkers by 15(48.4%), nutritional deficiencies by 9(29%) and geographical and socioeconomic status by 3(9.6%) studies.Conclusions: Early identification and recognition of risk factors associated with pulmonary exacerbation can have an explicit impact on its management, leading to decreased morbidity and mortality burden in cystic fibrosis cases

Vitamin D status and pulmonary exacerbations in children and adolescents with cystic fibrosis: Experience from a tertiary care center

Background: The function of Vitamin D in preventing inflammation and infection has been studied previously for different pathologies in different populations globally. Relationships between serum Vitamin D levels and its effect on pulmonary exacerbations in the cystic fibrosis (CF) population are not well studied in our part of the world. Therefore, we aimed to ascertain the Vitamin D status in pediatric and adolescent CF patients and its association with pulmonary exacerbations.Materials and methods: A retrospective study was conducted at The Aga Khan University Hospital from 2015 to 2018. Patients of CF with sweat chloride value \u3e60 mmol/l and who had at least one measurement of 25 hydroxy Vitamin D (25 OHD) were included in the study. Annual serum Vitamin D levels were documented for enrolled patients and their past 1-year data were analyzed for pulmonary exacerbations, average length of stay, and tracheal/airway colonization with organisms.Results: 69 patients were included in the study. 28 patients (40.57%) were found to be Vitamin D deficient, 22 patients (31.88%) were Vitamin D insufficient and 19 patients (27.53%) were labeled as Vitamin D insufficient. The average number of exacerbations per year was significantly high in Vitamin D deficient group (3.71 ± 0.96) in comparison with insufficient (3.18 ± 1.09) and sufficient groups (2.26 ± 0.93) (P \u3c 0.001).Conclusion: Vitamin D deficiency is related to an increased number of annual pulmonary exacerbations and pseudomonas infections

The Evolving Role of Saline Infusion Sonography (SIS) in Infertality- Systemic Review

Background: To perform a systematic review to examine all the available literature reporting to describe the Structural intrauterine abnormalities are an important cause of infertility, recurrent pregnancy loss and bleeding or pain associated with a poor reproductive outcome. Various diagnostic methods have been applied to detect these lesions such as hysterosalpingography, hysteroscopy and Sonohysterography.Materials and methods: In this systematic review data extracted by Medline, PubMed, science direct and Obs gyne online library that were queried for studies published between 2000 to 2020 by using specific MeSH terms. In this reviewed article we extracted data from 15 retrospective Cohort studies in which 3800 infertile women underwent SIS procedure. Infertile women were screened for possible uterine pathologies.Results: In this systematic review we reviewed 15 article that was published between 2000 to2020.  Extracted data from these reviewed articles showed Two thousand infertile patients examined by saline infusion Sonography. From these 2000 patients 1400 women diagnose with abnormalities.Conclusion:Saline infusion sono-hysterography was found to be a more reliable method of diagnosing tubal or uterine pathologies in infertile patients.it is cost effective and gold standard. Keywords: Intrauterine, Pathology, Sonohysterography, Saline infusion sonography DOI: 10.7176/JHMN/90-03 Publication date:June 30th 202

Impact of a digital health literacy intervention and risk predictors for multimorbidity among poor women of reproductive years: Results of a randomized-controlled trial

Objective: The objective of this study was to deliver an intervention to improve health awareness for infection prevention, hygiene, and sanitation to assess its impact. Furthermore, it aimed to identify the risk of multimorbidity in women of reproductive years from low socio-economic background. Methods: A randomized control trial was conducted in Pakistan among women aged 15–45 years. Overall, 820 women participated in the baseline survey; 388 women were part of the control group and 360 of the intervention group. A digital health literacy intervention was delivered by 91 trained community health workers. Data were analyzed using descriptive statistics and multivariate logistic regression. Results: About 35.9% of women suffered from multimorbidity. The intervention group showed higher odds of confidence in managing health with respect to skill and technique acquisition (AOR = 2.21; 95% CI 1.01–4.84), self-monitoring and insight (AOR = 2.97; 95% CI 1.29–6.80) as well as sanitation and hygiene (AOR = 1.42; 95% CI 1.07–1.93). Two primary outcomes related to hand hygiene and protective behavior against infection did not show any significant improvement. The secondary outcomes of the study related to impact on overall health-related quality of life, social integration and support, and emotional well-being also did not show any significant improvement. Conclusions: Digital health literacy interventions and multimorbidity management for women of reproductive years at the primary level are a way forward to alleviate communicable and non-communicable disease burden in developing countries like Pakistan. These efforts are also critical to improve maternal and child health in developing regions

Impact of a digital health literacy intervention and risk predictors for multimorbidity among poor women of reproductive years: Results of a randomized-controlled trial

OBJECTIVE: The objective of this study was to deliver an intervention to improve health awareness for infection prevention, hygiene, and sanitation to assess its impact. Furthermore, it aimed to identify the risk of multimorbidity in women of reproductive years from low socio-economic background. METHODS: A randomized control trial was conducted in Pakistan among women aged 15–45 years. Overall, 820 women participated in the baseline survey; 388 women were part of the control group and 360 of the intervention group. A digital health literacy intervention was delivered by 91 trained community health workers. Data were analyzed using descriptive statistics and multivariate logistic regression. RESULTS: About 35.9% of women suffered from multimorbidity. The intervention group showed higher odds of confidence in managing health with respect to skill and technique acquisition (AOR = 2.21; 95% CI 1.01–4.84), self-monitoring and insight (AOR = 2.97; 95% CI 1.29–6.80) as well as sanitation and hygiene (AOR = 1.42; 95% CI 1.07–1.93). Two primary outcomes related to hand hygiene and protective behavior against infection did not show any significant improvement. The secondary outcomes of the study related to impact on overall health-related quality of life, social integration and support, and emotional well-being also did not show any significant improvement. CONCLUSIONS: Digital health literacy interventions and multimorbidity management for women of reproductive years at the primary level are a way forward to alleviate communicable and non-communicable disease burden in developing countries like Pakistan. These efforts are also critical to improve maternal and child health in developing regions

Role of Ultrasound for the Diagnosis of Uterine Prolapse in Women: A Systemic Review

Background: Uterine prolapse is the herniation of the uterus into or beyond the vagina as a result of failure of the ligamentous and fascia supports. It often coexists with prolapse of the vaginal walls, involving the bladder or rectum. Objective: The aim of this study is to evaluate the role of ultrasound for the diagnosis of uterine prolapse in young women. Methodology: In this systematic review data extracted by Medline, PubMed, science direct and Obs-gyne online library that were queried for studies published between 2000 to 2021 by using specific MeSH terms. In this systematic article we reviewed 10 retrospective style analytical studies for the collection of data. Results: 10 studies conducted between the years 2000 to 2021 were included in this systematic review. The total sample size was 2500 women aged between 10-60 years. All subjects were examined by trans-perineal three-dimensional ultrasound for the detection of uterine prolapse. Out of 2500 patient almost 1000 determine with uterine prolapse on ultrasound. Ultrasound findings had excellent predictive value for the diagnosis of clinical uterine prolapse. An eye‐ shaped vaginal canal with an antero-posterior diameter of greater than 10 mm in the rendered axial plane was a sign of uterine prolapse. This sign may be helpful for detecting concealed uterine prolapse in complex pelvic organ prolapse. In fact, uterine prolapse can often be more prominent on imaging than on clinical examination. This may be due to the fact that the functional anatomy of the levator hiatus seems to matter most for uterine descent. Conclusion: From this systematic reviewed study we concluded that Ultrasound is the most appropriate form of imaging in uro-gynecology for reasons of low cost, access and performance, and due to the fact that it provides information in real time. Trans-perineal three-dimensional 2 ultrasound can evaluate the morphological changes of levator hiatus in patients with uterine prolapse, and the area of levator hiatus has high diagnostic value for uterine prolapse. Keywords: Pelvic organ prolapse; Trans-perineal Ultrasound; Uterine Prolapse; levator ani muscles. DOI: 10.7176/JHMN/92-05 Publication date:August 31st 2021