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BackgroundClinical trials have evaluated the efficacy of intravenous mesenchymal stem cells (MSCs) for acute and subacute ischemic stroke. Therefore, we conducted this meta-analysis to investigate the efficacy and safety of intravenous MSC treatments compared to placebo for acute and subacute ischemic stroke patients.MethodsWe searched PubMed, SCOPUS, Web of Science, and Cochrane CENTRAL for randomized controlled trials evaluating any clinical trials of intravenous MSCs for acute and subacute ischemic stroke patients. The efficacy outcomes of this study were the rates of improvement in National Institutes of Health Stroke Scale (NIHSS) scores, good scores on the modified Rankin Scale (mRS), and Barthel Index (BI) scores, while the safety outcomes were the rates of mortality and stroke recurrence. We compared intravenous MSC and placebo treatments on a fixed-effect meta-analysis model in R software.ResultsFour randomized controlled studies involving 97 patients were included in the analysis. In the meta-analysis, MSC treatments were superior to placebo treatments in good mRS (MD −0.95, 95% CI [−1.39, −0.52]) or BI (MD 21.36, 95% CI [9.96, 32.75]) scores, and MSC treatments were not superior to placebo treatments in the rate of improvement of the NIHSS scores (MD −1.81, 95% CI [−4.123, 0.494]). MSCs were associated with neither decreased mortality nor stroke recurrence (risk ratio 0.58 and 0.59, respectively; p-value = 0.51 and p-value = 0.533, respectively).ConclusionFor patients with acute and subacute ischemic stroke who are eligible for further damage to neural tissue, MSCs achieve high efficacy and acceptable safety.Systematic review registrationProspero, unique ID: CRD42023457655.

Objective: This study provides histological evidence of the combined effects of L-Carnitine, and Coenzyme Q10 on gliosis and anhedonia in a rat model of multiple sclerosis (MS). Methods: Fifty male Sprague Dawley rats were randomly divided into 5 groups of 10 rats each. Group 1 was the control group. The rest of the groups were disease models and were given 0.2% cuprizone w/w to induce MS. After 4 weeks, Group 3 started receiving L-Carnitine, Group 4 was given Coenzyme Q10, and Group 5 received both, while cuprizone poisoning continued. After 12 weeks sucrose preference test and tail suspension test were performed for anhedonia. Rats were euthanized and brains were dissected, and assessed for astrocytes, oligodendrocytes, and microglial count. Results: A significant increase in oligodendrocyte count, while a reduction in astrocyte and microglial count was seen in the synergistic group (p < 0.05). Synergism could not be proved in anhedonia. Conclusion: The combination of Coenzyme Q10 and L-Carnitine has a synergistic effect in controlling gliosis in a rat model of MS, but synergism could not be demonstrated on anhedonia. [ABSTRACT FROM AUTHOR]

Purpose: Palliative care is regarded as fundamental to human dignity and falls under the definition of basic human rights. One considerable community of color whose needs are poorly understood consists of Asian Americans, including distinct priorities, expectations, and decision-making processes by diverse subgroups. The purpose of this work was to understand whether and to what extent unique considerations are understood among Asian American subgroups. Method: A scoping review was conducted among major scientific and academic databases. Broad search terms surrounding end-of-life care were combined with individual racial and ethnic identifiers encompassing Asian American subgroups. Results: Twenty-two articles met inclusion criteria and reflected diverse arrays of worldviews surrounding access to, utilization of, and desired outcomes from palliative care. Most articles focused on social orientations prioritizing family in disease disclosure and avenues of interventions sought with distinct patterns among subgroups. Discussion/Conclusion: A human rights framework emphasizing palliative and other end-of-life approaches to care may be inadequate to address unique considerations among diverse Asian American subgroups. Theorists and practitioners should incorporate practices of collectivist orientations and family contexts commonly found among these diverse communities.

Online learning has grown productive and vital for delivering asynchronous instruction to undergraduate medical students. We explored the factors that affect the learning of undergraduate medical students in an online asynchronous Forensic Medicine course through focus group discussions. These factors were identified in three components of theoretical framework: learner, design, and environment. The promoting factors in the learner component were regulation of learning, internal motivation, metacognition, interaction with peers, and social interaction. Hampering factors were poor self-regulation, losing motivation, and less use of discussion forums. In the environment component students' engagement, external motivation, and lack of physical interaction hampered the learning. In design: course content, links, extra material, pre-recorded lectures, assessment, time limitation, and flexibility promoted the learning, while lack of training in asynchronous mode, losing motivation, loss of attention, and less interaction hampered learning. These identified factors will assist online educators and instructors in designing better online asynchronous courses. [ABSTRACT FROM AUTHOR]

Background and Aims: The polycystic ovarian syndrome is a menacing metabolic condition with high prevalence rate in Asian countries involving women of reproductive age. This study was commenced to assess favorable effects of Lycopene--a dietary component in letrozole-induced PCOS rat model. Materials and Methods: Fifty adult female Sprague Dawley rats were divided into five groups, ten rats each for a study of 5weeks. Control group A was given standard rat diet. Rats of experimental group B were given 1mg/kg of Letrozole to induce PCO model. Group C was given 1mg/kg of letrozole+15mg/kg/day of lycopene. Group D was given 1mg/kg of letrozole+ 500 mg/kg/day metformin. Group E was given 1mg/kg of letrozole +combination of Lycopene and metformin together. Relative body weight was taken on the day1, day21 and end of experiment. Antioxidant activity was tested using CAT, SOD and MDA. Ovaries were removed for H&E staining and studied under light microscopy. Statical analysis was carried out for result interpretations. Results: The results showed, reduced rat weight by use of Lycopene. Histological architecture of ovary showed better count of secondary and graafian follicles towards normal values which was quite reduced in group B proved by significant p-value<0.001. While raised number of atretic follicles in group B 6±1.6 was reduced to 3±0.9, 4±0.6, 4±0.7 in group C, D &E respectively. Overall improvement in distorted/cystic ovaries was noted by treatment therapy, evident by significant p-value. Group B showed mean count of cyst 7±1.0, which was brought to 2±0.5, 3±0.8, 2±0.7 in groups C, D &E. Elevated Oxidative markers (ROS) were also reduced. Conclusion: Dietary intake Lycopene can ameliorate histological and oxidative damage in polycystic ovaries. [ABSTRACT FROM AUTHOR]

Background: Helicobacter pylori (H. pylori) is a gram-negative bacterium which usually resides in the mucoid lining of the stomach and may cause different gastric pathologies e.g., Gastritis, peptic ulcer disease, adenocarcinoma of the gastric system and mucoid associated lymphoma (MALT). The Objective was to compare the effect of 7-days Vonoprazan based triple therapy and 14-days Esomeprazole based triple therapy on eradication rate, compliance and cost effectiveness in Helicobacter pylori infected patients. Methods: This clinical trial was performed in the Department of Pharmacology Army Medical College, National University of Medical Sciences (NUMS) in collaboration with the Gastroenterology Department, Pak Emirates Military Hospital (PEMH) Rawalpindi from December 2022 to March 2023. A total of one hundred and twenty-two patients with dyspepsia symptoms and yielding lab results positive for Helicobacter pylori by stool antigen test were enrolled in the study. They were randomly allocated into two groups. The Esomeprazole group received 14 days of triple therapy orally with Esomeprazole 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. The comparative Vonoprazan group was given 7-days triple therapy orally with Vonoprazan 20 mg twice a day; Amoxicillin 1000 mg twice a day; and Levofloxacin 500 mg one time a day. Eradication success was evaluated by stool antigen test four weeks later, as counted from the start of treatment. compliance and cost-effectiveness of both therapies were also assessed. Results: The eradication rate was (95.1%) in the Vonoprazan group with 58 out of 61 patients negative for H. pylori and (93.1%) in Esomeprazole group with 54 patients out of 58 yielding a negative result demonstrating p-value of 0.64. Compliance was 95.0% in the Esomeprazole group with p-value of 0.07. Cost effective ratio for Vonoprazan triple therapy was lower (731.8PKR) than the Esomeprazole group. Conclusion: One two-week Vonoprazan regimen demonstrated improved eradication rate, good compliance, and better tolerability in patients with less cost and a half duration of treatment in comparison with two weeks Esomeprazole regimen, attesting that one week Vonoprazan therapy is more cost efficacious in producing better results. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) is a new class of medication for the treatment of type 2 diabetes mellitus. Additionally, they have been found to have beneficial effects on heart failure outcomes, convincingly reducing the morbidity and mortality in heart failure. Although the medical data indicates SGLT2i to be safe and cardio-protective, very little attention has been given to the impact of these agents on electrolyte balance particularly in acute heart failure (AHF). We aimed to evaluate the effect of SGLT2i, and dapagliflozin on serum sodium, potassium and creatinine in AHF. Methods: Overall, 160 adult patients of either gender, admitted with AHF were selected for the study. Selected individuals were randomly assigned to receive dapagliflozin 10 mg orally added to standard medical treatment (n=80) or were in reception of standard medical therapy only (n=80). Serum electrolytes and serum creatinine were collected on admission and day 7 or on discharge whichever happened earlier. Results: The mean level of serum electrolytes displayed insignificant differences among both groups on admission. The mean level of serum potassium was higher in the dapagliflozin group compared with the control group (p<0.001) on day 7/discharge. Mean serum sodium level was comparable and showed significant differences between the two groups following treatment (pvalue= 0.021). Significant higher levels of serum creatinine were observed following treatment in both groups. However, on intergroup comparison, they were statistically insignificant. Conclusion: Dapagliflozin is an effective treatment of heart failure and is not associated with deterioration of serum electrolyte levels and renal functioning when used as add-on therapy in AHF. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the influence of dapagliflozin on renal functions and diuretics use in patients with acute heart failure (AHF). Methods: This comparative analytical study was conducted at Armed Forces Institute of Cardiology, Rawalpindi from July 2022 to November 2022. Patients were distributed equally in two groups i.e. Dapagliflozin and Conventional Groups, where patients received dapagliflozin added to conventional therapy for AHF and, only conventional therapy for AHF respectively. Estimated glomerular filtration rate (eGFR), serum creatinine were measured and compared on admission, after 48 hours and on discharge. Weight loss during hospitalization, daily dose of furosemide and length of hospital stay was also recorded. Quantitative parameters were analyzed using t-test or Mann Whitney U test accordingly. Results: There were no significant baseline differences in renal functions. A modest decline in eGFR was observed in both groups after 48 hours. However, the variation in values of eGFR remained similar among both groups after 48 hours (p-value 0.365) and on discharge (p-value 0.768). Whereas, patients subjected to dapagliflozin treatment exhibited a more profound diuretic response expressed as greater weight loss (p-value < 0.001), achieved at comparatively lower doses of loop diuretics. Moreover, they also had a shorter duration of hospital stay (six vs eight days, p-value <0.001). Conclusion: Institution of dapagliflozin did not cause any significant deterioration of renal functions, whereas; it was associated with improved diuretic response as depicted by more pronounced weight loss at comparatively lower doses of loop diuretics. [ABSTRACT FROM AUTHOR]

Background: Shivering is one of the most common adverse outcomes associated with the administration of spinal anaesthesia, which, when clinically relevant, leads to numerous detrimental effects on the human body. Hence, its management becomes imperative. Meperidine, an opioid analgesic, is the drug of choice for this condition. However, the use of meperidine is controversial, as it carries the devastating adverse effect of respiratory depression. We explored the role of granisetron, a 5HT3 antagonist and a commonly used antiemetic premedication, in minimising the incidence of post-spinal shivering and decreasing the use of meperidine as a rescue drug. Methods: Overall, 160 parturient patients, between the ages 18-50, undergoing uncomplicated, elective caesarean section, were enrolled in the study, and randomized into two groups with 80 participants each: Group A received 3ml of normal saline, and Group B was administered 3 mg granisetron, 15 minutes before spinal anaesthesia institution. Incidence of clinically relevant shivering (score of 3 or more) was noted, and it was recorded whether meperidine was used or not. Results: 67.5% of participants in Group A, and 32.5% of patients in Group B, experienced clinically relevant shivering, with 62.5% of patients in Group A and 28.75% in Group B warranting the use of meperidine. There was a statistically significant difference between the two groups in terms of incidence of clinically relevant shivering, and meperidine consumption (p-value <0.001). Conclusion: Premedication with 3 mg granisetron effectively attenuates the occurrence of post-spinal shivering and, hence, lowers the requirement of meperidine as rescue medication. [ABSTRACT FROM AUTHOR]

Background: Abstraction of wisdom teeth or impacted third molar under local anaesthesia is one of the most frequent interventions by an oral and maxillofacial surgeon. The abstraction of the third molar is usually followed by the release of liberation and consequent trismus, pain, and swelling due to the area of the third molar being highly vascularized and rich in loose connective tissue. Objective of the study was to evaluate the anti-inflammatory effect of ascorbic acid following surgical extraction of the third molar. Methods: The current study was carried out Armed Forces Institute of Dentistry, Rawalpindi, from October to December 2022. This was a cross-sectional observational study. Fifty participants who required surgical extraction of the impacted third molar were included in the study via non-probability purposive sampling and were segregated equally into two groups, i.e., Group A and Group B, comprising twenty-five participants in each group. Group A received amoxicillin with clavulanic acid (625 mg) thrice a day and metronidazole (400 mg) twice daily. In comparison, Group B received amoxicillin with clavulanic acid (625 mg) thrice daily, ascorbic acid (500 mg) twice daily, and metronidazole (400 mg) twice daily. Both groups received naproxen sodium as per requirement (550 mg). Pain, facial swelling, and C reactive protein concentration were evaluated until the 7th postoperative day. Results: There was a reduction in pain and facial swelling in both groups, but in the ascorbic acid group, there was more reduction in pain and facial swelling compared to the control group. However, the difference between the two groups in reducing pain and facial swelling was statistically significant (p<0.01). There was a reduction in CRP in both groups, but in the ascorbic acid group, there was more reduction in CRP 2.35 (1.60-5.30) compared to the control group 2.6 (0.86-5.03). However, the difference between the two groups in reducing C reactive protein concentration was statistically insignificant (p>0.05). Conclusion: Our study concluded that ascorbic acid significantly reduced inflammation and C reactive protein, so ascorbic acid should be used as an adjuvant supplement with other conventional drugs. [ABSTRACT FROM AUTHOR]

Background: This study aimed to evaluate the impact of Insulin Degludec Aspart on daily insulin dose in comparison with premixed insulin aspart. Methods: It was a Quasi-Experimental study conducted in the Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi and the Department of Medicine, Pak Emirates Military Hospital, Rawalpindi. One hundred and twenty participants with documented type 2 diabetes, taking premixed insulin aspart therapy were enrolled in the study. Sixty participants were substituted with insulin degludec aspart from premixed insulin aspart. Daily units of insulin were recorded for 12 weeks and compared for both groups. SPSS version 26 was used for analysing the study results. Results: Participants of the insulin degludec aspart group showed a significant reduction in the daily insulin dose compared to the premixed insulin aspart group. Fifty-two units per day were administered in the participants of the premixed insulin aspart patients while insulin degludec aspart participants received 40 units of median daily insulin dose (p-value<0.001). Conclusion: Insulin degludec aspart proved superior to premixed insulin aspart in a reduction in the daily dose of insulin with insulin degludec aspart. [ABSTRACT FROM AUTHOR]

Introduction: To study the protective effect of extra virgin olive oil (EVOO) on histopathological changes induced by arsenic in the kidneys of albino rats. Randomized control trial. November 1, 2017-November 30, 2017 at National Institute of Health. Material and Methods: Forty-five male adult albino rats were placed in three cages having 15 rats each. Distilled water was given to the rats of control Group I for 30 days. The dose of sodium arsenite given to rats was 40 mg per kg per day dissolved in drinking water for 30 days. Olive oil of 0.2 ml per day was only given to Group III rats for 30 days along with sodium arsenite. In dissection was done after 30 days and their kidneys were approached and dissected out for histological changes. Results: EVOO has ameliorated the microscopic quantitative and qualitative histological changes induced by arsenic on both kidneys of albino rats. Olive oil had significantly prevented the increase in the diameter of the proximal convoluted tubule (PCT). Discussion and Conclusion: The present study demonstrates that EVOO prevents the quantitative and qualitative histological changes caused by arsenic on kidneys which include the diameter of PCT and distal convoluted tubule, the diameter of glomeruli, width of bowman's space, and loss of brush border. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the effect of nicorandil in prevention of reperfusion injury during primary percutaneous coronary intervention by thrombolysis in myocardial infarction flow grade scoring. Methods: A total of 140 patients from Rawalpindi Institute of Cardiology were enrolled in this study conducted from 7th September to 10th of October 2021. These participants were allocated into two major groups. Control group received conventional acute coronary syndrome protocol regimen only whereas experimental group was given nicorandil along with conventional acute coronary syndrome protocol. During primary percutaneous coronary intervention, thrombolysis in myocardial infarction flow grade scoring was analyzed and compared. Results: Majority of participants in nicorandil group achieved thrombolysis in myocardial infarction Grade-3 scoring which indicated reduced rate of no reflow phenomenon as compared to control group. A statistically significant difference was noted in score of both groups (p value = 0.001) signifying prophylactic use of nicorandil before primary percutaneous coronary intervention along with conventional acute coronary syndrome protocol is superior to only conventional acute coronary syndrome protocol regimen to cases in the control group. Conclusion: Use of nicorandil in ST elevated myocardial infarction patients before primary percutaneous coronary intervention prevents reperfusion injury thus decreasing the risk of post percutaneous coronary intervention complications and reducing mortality rate in cardiac patients suggesting its significant cardio protective role. [ABSTRACT FROM AUTHOR]

Objective: Synovial fibrosis contributes to osteoarthritis (OA) pathology, but the underlying mechanisms remain unknown. We have observed increased microRNA‐27b‐3p (miR‐27b‐3p) levels in synovial fluid of patients with late‐stage radiographic knee OA. Here, we investigated the contribution of miR‐27b‐3p to synovial fibrosis in patients with severe knee OA and in a mouse model of knee OA. Methods: We stained synovium sections obtained from patients with radiographic knee OA scored according to the Kellgren/Lawrence scale and mice that underwent destabilization of the medial meniscus (DMM) for miR‐27b‐3p using in situ hybridization. We examined the effects of intraarticular injection of miR‐27b‐3p mimic into naive mouse knee joints and intraarticular injection of a miR‐27b‐3p inhibitor into mouse knee joints after DMM. We performed transfection with miR‐27b‐3p mimic and miR‐27b‐3p inhibitor in human OA fibroblast‐like synoviocytes (FLS) using reverse transcriptase–quantitative polymerase chain reaction (RT‐qPCR) array, RNA sequencing, RT‐qPCR, Western blotting, immunofluorescence, and migration assays. Results: We observed increased miR‐27b‐3p expression in the synovium from patients with knee OA and in mice with DMM‐induced arthritis. Injection of the miR‐27b‐3p mimic in mouse knee joints induced a synovial fibrosis‐like phenotype, increased synovitis scores, and increased COL1A1 and α‐smooth muscle actin (α‐SMA) expression. In the mouse model of DMM‐induced arthritis, injection of the miR‐27b‐3p inhibitor decreased α‐SMA but did not change COL1A1 expression levels or synovitis scores. Transfection with the miR‐27b‐3p mimic in human OA FLS induced profibrotic responses, including increased migration and expression of key extracellular matrix (ECM) genes, but transfection with the miR‐27b‐3p inhibitor had the opposite effects. RNA sequencing identified a PPARG/ADAMTS8 signaling axis regulated by miR‐27b‐3p in OA FLS. Human OA FLS transfected with miR‐27b‐3p mimic and then treated with the PPARG agonist rosiglitazone or with ADAMTS8 small interfering RNA exhibited altered expression of select ECM genes. Conclusion: Our findings demonstrate that miR‐27b‐3p has a key role in ECM regulation associated with synovial fibrosis during OA. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate and compare the Ondansetron and Granisetron in preventing spinal anaesthesia induced hemodynamic instability in obstetric patients Methods: The comparative analytical study was conducted at Combined Military Hospital, Rawalpindi, from September to October, 2021. One hundred and twenty pregnant women undergoing cesarean section, were enrolled in the study via non probability convenience sampling, and divided into three groups containing 40 participants each based on the type of antiemetic premedication they received, if any: Group N were those not requiring antiemetic premedication, Group O consisted of those given ondansetron 4mg, and Group G had those receiving 3mg granisetron, 15 minutes prior to administration of spinal anaesthesia. Systolic blood pressures and heart rates were recorded before and at multiple intervals after spinal anaesthesia was administered. Episodes of hypotension and bradycardia were recorded. Requirement of phenylephrine and atropine as rescue drugs was recorded for each participant. Results: There was a statistically significant difference in incidence of hypotension among the three groups (p value <0.001), with both drugs being superior to the control group (p value <0.001 for both), and 3mg granisetron being superior to 4mg ondansetron (p value <0.001). As for incidence of bradycardia, ondansetron and granisetron were superior to control group (p value 0.03 and <0.001 respectively), but there was no significant difference between the two drug groups (p value 0.094). Conclusion: High dose granisetron (3mg) is superior to low dose ondansetron (4mg) in preventing hemodynamic fluctuations induced by spinal anaesthesia. [ABSTRACT FROM AUTHOR]

Objective: To compare the efficacy of Selenium and Zinc in improving histological features on DEHP-induced toxicity in the thyroid gland of rats. Design of study: Laboratory based experimental study. Place and Duration of Study: Anatomy Department of Islamic International Medical College with the National Institute of Health (NIH), Islamabad Pakistan cooperation from Sep 2019 to Sep 2020. Methodology: Forty, eight weeks old rats were divided into four groups, each containing ten male rats. In control, Group-A rats were on the standard diet. In Group-B, rats were given orally 500mg/kg/day DEHP. In Group-C rats were given 500mg/kg/day DEHP and 1mg/kg/day Selenium orally. In Group-D rats were given 500mg/kg/day DEHP and 5mg/kg/day Zinc orally. After 28 days, rats were dissected, and the thyroid gland was removed. Histological parameters, vacuolization and number of follicular cells were observed with H and E stining among control and experimental groups. Results: In Group-B, 50% of rats showed severe vacuolization. In Group-C, 60% of rats showed minimal vacuolization. In Group-D, 40% of rats showed minimally, and 40% of rats showed mild vacuolization. Among quantitative parameters, the number of follicular cells was conserved more by Selenium than Zinc. Conclusion: Selenium and Zinc have a protective effect on thyroid histological changes caused by DEHP, but Selenium shows better conservation than zinc on thyroid histology. [ABSTRACT FROM AUTHOR]

Objective: To study the teratogenic effects of Bisphenol A exposure during maternal pregnancy and lactation on the testicular histology of developing rat pups. Design of Study: Laboratory-based experimental study. Place and Duration of Study: Department of Anatomy, Islamic International Medical College Rawalpindi in collaboration with the National Institute of Health (NIH) Islamabad Pakistan from Sep 2018 to Sep 2019. Methodology: Eight weeks old, ten pregnant female rats were divided into groups, each comprising five pregnant rats. Pups were born by spontaneous vaginal delivery. Control group A consisted of 15 male rat pups delivered from 5 pregnant rats, fed on a standard diet during pregnancy and lactation till the 21st day. Experimental group B consisted of 15 male rat pups delivered from 5 pregnant female rats who were administered subcutaneous Bisphenol A at a dose of during their pregnancy and lactation till the 21st day. Results: Significant deterioration of quantitative parameters in testes of the experimental group was seen. The seminiferous tubule diameter in group B was 81.99 ± 10.88 compared to group A which was 111.59 ± 8.36. The germinal epithelial height in group B was 10.47 ± 2.34 compared to 30.41 ± 2.43 in group A. The number of Leydig cells in group B was 17 ± 3.45 compared to 47 ± 4.44 in group A. The number of rounded spermatids in group B was 10 ± 3.74 compared to 38 ± 4.02 in group A. Conclusion: Bisphenol A has teratogenic effects on testicular histology of developing rats when exposed to mothers during pregnancy and lactation. This may deteriorate male fertility by adverse effects on spermatogenesis. [ABSTRACT FROM AUTHOR]

Objective: To evaluate and compare the preventive role of Nebivolol and Alpha Tocopherol on testosterone-induced benign prostatic hyperplasia in rats. Study Design: Laboratory-based experimental study. Place and Duration of Study: Department of Pharmacology and Pathology, Army Medical College, Rawalpindi, in collaboration with National Institute of Health (NIH), Islamabad Pakistan, from Dec 2021 to Jun 2022. Methodology: One hundred fifty healthy male Sprague-Dawley rats were procured from the NIH, Islamabad. They were placed into five groups, each with 30 rats. Results: Out of a total 150 sample of five groups, the mean prostatic index in Group-A, Group-B, Group-C, Group-D, and Group-E were 1.49±0.09, 2.35±0.48, 1.87±0.11, 1.72±0.04 and 1.68±0.08 respectively (p-value<0.001). Mean Prostate Specific Antigen in Group-A, Group-B, Group-C, Group-D and Group-E was 0.19±0.02, 0.23±0.01, 0.18±0.02, 0.18±0.02 and 0.16±0.02 respectively (p-value<0.001). On gross examination, in Group-A, all (100%) prostate samples were normal-sized. In Group-B, all (100%) prostate samples were enlarged. In Group-C, 53.3% were mild, and 47.7% of samples were moderately enlarged. In Group-D, 73.3% of samples were mildly enlarged, and 26.7% were moderately enlarged. In Group E, 26.7% of samples were normal, and 73.3% were mildly enlarged (p-value<0.001). Conclusion: Prostatic index is markedly declined following treatment with the combination of Nebivolol and AlphaTocopherol. There is also a declining trend in Prostate Specific Antigen following treatment with a combination of Nebivolol and Alpha-Tocopherol. [ABSTRACT FROM AUTHOR]

Objective: To determine whether Insulin Degludec Aspart is associated with a reduced risk of hypoglycemia as compared to premixed Insulin aspart therapy in type-2 diabetes mellitus patients. Study Design: Quasi-experimental study Place and Duration of Study: Department of Pharmacology, Army Medical College, National University of Medical Sciences, Rawalpindi and Department of Medicine, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Sep to Dec 2021. Methodology: One hundred twenty participants with documented type 2 diabetes, taking premixed Insulin Aspart therapy, were enrolled in the study. The participants were divided into two groups. Group-A participants were continued on Premixed Insulin Aspart therapy, and Group-B participants were substituted with Insulin Degludec Aspart. The symptomatic hypoglycemic episodes were recorded for 12 weeks as confirmed hypoglycemia, nocturnal hypoglycemia, and severe hypoglycemia. Results: Among the Premixed Insulin Aspart-Group, 49(81.6%) participants and in the Insulin Degludec Aspart-Group, 26(43.3%) participants reported 160 and 40 episodes of confirmed total hypoglycemia, respectively (p-value<0.001). 43(71.6%) participants in the Premixed Insulin Aspart-Group and 11(18.3%) participants in the Insulin Degludec Aspart-Group reported 73 and 12 episodes of confirmed nocturnal hypoglycemia, respectively (p-value<0.001). No severe hypoglycemic episodes were recorded in both groups after 12 weeks. Conclusion: The use of Degludec Aspart is associated with a reduced incidence of hypoglycemia, offering improved treatment compliance among the Pakistani population with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study is to identify circulating microRNAs that distinguish fast-progressing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative cohort by applying microRNA-sequencing. Methods: Participants with Kellgren–Lawrence (KL) grade 0/1 at baseline were included (N = 106). Fast-progressors were defined by an increase to KL 3/4 by 4-year follow-up (N = 20), whereas slow-progressors showed an increase to KL 2/3/4 only at 8-year follow-up (N = 35). Non-progressors remained at KL 0/1 by 8-year follow-up (N = 51). MicroRNA-sequencing was performed on plasma collected at baseline and 4-year follow-up from the same participants. Negative binomial models were fitted to identify differentially expressed (DE) microRNAs. Penalized logistic regression (PLR) analyses were performed to select combinations of DE microRNAs that distinguished fast-progressors. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate predictive ability. Results: DE analyses revealed 48 microRNAs at baseline and 2 microRNAs at 4-year follow-up [false discovery rate (FDR) < 0.05] comparing fast-progressors with both slow-progressors and non-progressors. Among these were hsa-miR-320b, hsa-miR-320c, hsa-miR-320d, and hsa-miR-320e, which were predicted to target gene families, including members of the 14-3-3 gene family, involved in signal transduction. PLR models included miR-320 members as top predictors of fast-progressors and yielded AUC ranging from 82.6 to 91.9, representing good accuracy. Conclusion: The miR-320 family is associated with fast-progressing radiographic knee OA and merits further investigation as potential biomarkers and mechanistic drivers of knee OA. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the chondroprotective effects of hyaluronic acid in a rat model of osteoarthritis. Study Design: Laboratory based experimental study. Place and Duration of Study: Department of Pharmacology, Army Medical College, Rawalpindi, in alliance with National Institute of health, Islamabad and Department of Pathology, Army Medical College Rawalpindi, from Apr to Jun 2019. Methodology: Sixteen (16) rats of Sprague Dawley breed were procured in this study. Osteoarthritis was induced in right knee joint of rats by surgical resection of medial meniscus and anterior cruciate ligament. They were allocated into two (02) groups with eight (8) rats in both groups. Group-I was control group that was treated with 0.2 ml intra articular saline once weekly for four weeks. While group-II was treatment group that was intra particularly administered with 0.2ml hyaluronic acid once weekly for four weeks. One week after the last dosage, gait pattern of the animals was scored. Then animals were sacrificed and a part of proximal tibia was obtained for histopathologic analysis. Results: Mean gait score of control group and treatment group was 3.25 ± 0.707 and 1.00 ± 0.756 respectively with a statistically significant p-value of <0.001, while mean histopathological Modified Mankin score of control and treatment group was 11.5 ± 1.195 and 5.50 ± 1.195 respectively with a significant p-value of <0.001. Conclusion: Intra articular viscosupplementation of hyaluronic acid in rat model of osteoarthritis resulted in improved gait pattern and histopathology. [ABSTRACT FROM AUTHOR]

Discovery of non-coding RNAs continues to provide new insights into some of the key molecular drivers of musculoskeletal diseases. Among these, microRNAs have received widespread attention for their roles in osteoarthritis and rheumatoid arthritis. With evidence to suggest that long non-coding RNAs and circular RNAs function as competing endogenous RNAs to sponge microRNAs, the net effect on gene expression in specific disease contexts can be elusive. Studies to date have focused on elucidating individual long non-coding-microRNA-gene target axes and circular RNA-microRNA-gene target axes, with a paucity of data integrating experimentally validated effects of non-coding RNAs. To address this gap, we curated recent studies reporting non-coding RNA axes in chondrocytes from human osteoarthritis and in fibroblast-like synoviocytes from human rheumatoid arthritis. Using an integrative computational biology approach, we then combined the findings into cell- and disease-specific networks for in-depth interpretation. We highlight some challenges to data integration, including non-existent naming conventions and out-of-date databases for non-coding RNAs, and some successes exemplified by the International Molecular Exchange Consortium for protein interactions. In this perspective article, we suggest that data integration is a useful in silico approach for creating non-coding RNA networks in arthritis and prioritizing interactions for further in vitro and in vivo experimentation in translational research. [ABSTRACT FROM AUTHOR]