Insights Into Cystic Fibrosis Gene Mutation Frequency, Clinical Findings, and Complications Among Pakistani Patients.

Background Cystic fibrosis (CF) is a genetic disorder with diverse symptoms. Understanding its genetic basis and prevalence is crucial for effective management and treatment. Objective The study aimed to provide comprehensive insights into the frequency of CF gene mutations, clinical presentations, and complications among the Pakistani population. Methodology A cohort comprising 892 patients, ranging in age from 18 to more than 40 years, was selected on the basis of clinical and genetic criteria for the diagnosis of CF. Polymerase chain reaction (PCR) was used to look for 34 variants in the CFTR gene in blood samples. Statistical analysis, which included figuring out the number of mutations, the average age of diagnosis, and the genetic diversity of the samples, was performed to analyze the percentage of patients with specific mutations, offering insights into the genetic diversity. Results In our comprehensive analysis of 892 patient samples, 77.47% (n=691) displayed consanguinity, indicating a family history. The prevailing symptoms included chronic cough (88.67%; n=791), recurrent respiratory infections (76.68%; n=684), and fatigue (73.76%; n=658). The major complications comprised pulmonary infections (22%; n=197), cystic fibrosis-related diabetes (21%; n=187), and malabsorption (20%: n=178). A paired t-test revealed a mean difference of 5.750 with a standard deviation of 9.147, a 95% confidence interval from -0.061 to 11.561, a t-value of 2.178 with 11 degrees of freedom, and a two-tailed p-value of 0.052, suggesting a potential trend towards significance. Nevertheless, the asymptotic significance values of 1.000 and 0.998 for both groups indicate no significant difference. Furthermore, the study identified 12 cystic fibrosis gene mutations, with F508del and N1303K being the most prevalent. Conclusion This research revealed significant consanguinity, confirmed typical CF symptoms, and identified common complications and prevalent CFTR gene mutations (with F508del and N1303K being the most common), providing insights for genetic guidance and treatment in the Pakistani community.

A Comparative Study of the Efficacy and Safety of Oral Misoprostol, Intravenous Oxytocin, and Intravaginal Dinoprostone for Labor Induction in Pakistani Women.

INTRODUCTION: A frequent medical procedure to accelerate labor is the induction of labor. There are different methods of labor induction, including the use of medications such as misoprostol, oxytocin, and dinoprostone. OBJECTIVE: This research compared the effectiveness and safety of oral misoprostol, intravenous oxytocin, and intravaginal dinoprostone for labor induction in Pakistani women. METHODOLOGY: A study was conducted in the Department of Obstetrics and Gynaecology, Hayatabad Medical Complex-Medical Teaching Institute (MTI) and Lady Reading Hospital-MTI, Peshawar, Pakistan, over two years. It included 378 women between 38 and 42 gestational weeks, divided into three groups of 126 women each. The oral misoprostol group was given a maximum of six doses of a 25 µg oral misoprostol solution (oral misoprostol tablet of 200 µg dissolved in 200 ml) at intervals of two hours. The drip rate for the intravenous oxytocin group ranged from 6 mIU/minute to 37 mIU/minute. The intravaginal dinoprostone group received a controlled-release vaginal insert containing 10mg of intravaginal dinoprostone, which was left in place for 12 hours. RESULTS: More women in the oral misoprostol group (n=94; 74.6%) had successful inductions when compared to the intravaginal dinoprostone (n=83; 65.9%) and intravenous oxytocin (n = 77; 64.71%) groups. Oral misoprostol had the greatest proportion of normal vaginal deliveries (n=62; 65.95%), followed by intravaginal dinoprostone (n=47; 56.63%), and intravenous oxytocin had the lowest rate (n=33; 42.85%). Cesarean section rates were greatest in the intravenous oxytocin group (n=31; 40.26%), followed by the intravaginal dinoprostone group (n=29; 34.94%), and lowest in the oral misoprostol group (n=24; 25.53%). CONCLUSION: Oral misoprostol induces labor in women safely and effectively, resulting in the lowest percentage of cesarean deliveries and the highest percentage of normal vaginal deliveries, respectively. Intravaginal dinoprostone showed the lowest rate of side effects, followed by oral misoprostol while intravenous oxytocin had the highest rate of side effects.

The functions and molecular mechanisms of Tribbles homolog 3 (TRIB3) implicated in the pathophysiology of cancer.

Currently, cancer ranks as the second leading cause of death worldwide, and at the same time, the burden of cancer continues to increase. The underlying molecular pathways involved in the initiation and development of cancer are the subject of considerable research worldwide. Further understanding of these pathways may lead to new cancer treatments. Growing data suggest that Tribble's homolog 3 (TRIB3) is essential in oncogenesis in many types of cancer. The mammalian tribbles family's proteins regulate various cellular and physiological functions, such as the cell cycle, stress response, signal transduction, propagation, development, differentiation, immunity, inflammatory processes, and metabolism. To exert their activities, Tribbles proteins must alter key signaling pathways, including the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3 kinase (PI3K)/AKT pathways. Recent evidence supports that TRIB3 dysregulation has been linked to various diseases, including tumor development and chemoresistance. It has been speculated that TRIB3 may either promote or inhibit the onset and development of cancer. However, it is still unclear how TRIB3 performs this dual function in cancer. In this review, we present and discuss the most recent data on the role of TRIB3 in cancer pathophysiology and chemoresistance. Furthermore, we describe in detail the molecular mechanism TRIB3 regulates in cancer.