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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]

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]

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]

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 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 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]

Non-coding RNAs have distinct regulatory roles in the pathogenesis of joint diseases including osteoarthritis (OA) and rheumatoid arthritis (RA). As the amount of high-throughput profiling studies and mechanistic investigations of microRNAs, long non-coding RNAs and circular RNAs in joint tissues and biofluids has increased, data have emerged that suggest complex interactions among non-coding RNAs that are often overlooked as critical regulators of gene expression. Identifying these non-coding RNAs and their interactions is useful for understanding both joint health and disease. Non-coding RNAs regulate signalling pathways and biological processes that are important for normal joint development but, when dysregulated, can contribute to disease. The specific expression profiles of non-coding RNAs in various disease states support their roles as promising candidate biomarkers, mediators of pathogenic mechanisms and potential therapeutic targets. This Review synthesizes literature published in the past 2 years on the role of non-coding RNAs in OA and RA with a focus on inflammation, cell death, cell proliferation and extracellular matrix dysregulation. Research to date makes it apparent that 'non-coding' does not mean 'non-essential' and that non-coding RNAs are important parts of a complex interactome that underlies OA and RA. [ABSTRACT FROM AUTHOR]

Objective: To study the neuroprotective effect of curcumin against tartrazine-induced neurobiochemical and histopathological changes in the gray matter of motor cortex of rat brain. Study Design: Lab-based experimental study. Place and Duration of Study: Department of Anatomy, Islamic International Medical College, from Sep 2019 to Sep 2020. Methodology: Forty five adult male albino rats (250-300 gm) were divided randomly into three groups (n=15). Group A, rats were given standard rat diet. Group B, rats were given tartrazine orally by dissolving in tap water in the dose of 7.5 mg/kg body weight. Group C, rats were given 200 mg/kg of curcumin along with tartrazine orally by dissolving in tap water, daily for 28 consecutive days. At the end, all animals were dissected and their brain were removed. The neurobiochemical parameters including lipid peroxidation marker level along with microscopic changes widening of Virchow's robin space and neuropil vacuolation in neurovascular unit were observed. Results were analyzed using SPSS version 21. Results: The curcumin administration significantly improved the MDA levels (p-value <0.001 on intergroup comparison) and widening of Virchow's robin space (group A=3.57 ± 0.78 μm, group B=19.39 ± 0.68 μm, group C12.1 ± 0.83 μm; p-value <0.001). Neuropil vacuolation was reduced to negligible in 60% rats of curcumin treated group. Conclusion: Curcumin displayed a neuroprotective role in improving the tartrazine induced neurobiochemical and histopathological changes in the motor cortex of rat brain. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the chondroprotective effect of piroxicam in post-traumatic osteoarthritis model of rat. Study Design: Laboratory based experimental study. Place and Duration of Study: Pharmacology department, Army Medical College, Rawalpindi, from Apr to Jun 2019. Methodology: Project included sixteen rats of Sprague Dawley breed. Osteoarthritis was induced in anesthetized rats by surgical removal of medial meniscus and anterior cruciate ligament resection. After that rats were randomly allocated in two groups with eight rats in each group. Rats of group I were positive control that received 0.2 ml saline intra articularly once weekly for four weeks. Meanwhile rats of group II (treatment group) received 50 µl piroxicam intra articularly once weekly for four weeks. One week after the drug intervention, radiograph of the right knee joint of all rats were taken. Animals were then sacrificed with inhaled chloroform and part of proximal tibia was obtained for histopathological analysis. Results: Comparison of radiographs of both groups depicted a significant p-value of <0.01. Meanwhile mean histopathological score of control group and treatment group were 11.50 ± 1.195 and 6.50 ± 1.195 respectively with a p-value of <0.01. Conclusion: Intra articular administration of piroxicam in post-traumatic Osteoarthritis model of rats resulted in improvement in radiographic grades and histopathology scores. [ABSTRACT FROM AUTHOR]

Objective: Objective: Considerable variations exist in geometry of proximal femur across populations, which play an important role in total hip replacement surgeries. However, a rigorous characterization of femoral geometry across different geographical localities in Pakistan has not been performed. We aimed to assess the variations of the proximal femoral geometry in dry human femur bones from two different regions of Pakistan. Study type settings & duration: A descriptive study was carried out at Islamic International Medical College, Rawalpindi and at three different Medical Colleges in Peshawar from October 2018 to July 2019. Methodology: After obtaining ethical approvals, complete, fully ossified bones without additional paint or visible pathology from Rawalpindi (N = 98) and Peshawar (N = 112) were included for measurements of neck shaft angle (NSA), vertical head diameter and femoral neck length. NSA was measured from sketches of bones by using goniometer placed parallel to the shaft axis, while regular scale was used for measuring vertical head diameter and neck length. Unpaired T test was performed to compare the variations of femoral geometry in a side- and region-specific manner from Rawalpindi and Peshawar regions of Pakistan. Results: Means and SD values of NSA, vertical diameter of head and neck length of all bones were 125.85°± 7.35, 42.17±4.25 mm and 54.2±6mm, respectively. Significant differences (p value <0.001) were observed for NSA, vertical diameter of head and neck length between bones from the two regions. The femoral geometry was similar between right and left side bones, except for NSA in Peshawar which was differed significantly. Conclusion: Significant differences exist in the proximal femoral geometry between the Peshawar and Rawalpindi regions with higher values of NSA, femoral head diameter and femur neck length recorded in Peshawar. [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. [ABSTRACT FROM AUTHOR]

Stigma plays an important role in understanding successful interventions to control the opioid epidemic in the United States. Stigma has been described both as an agent to incentivize positive health behavior and as an agent of marginalization contributing to poorer health. Past scholarship has argued that stigma has positively motivated public health changes, for example, among tobacco users; it has also been associated with discrimination against vulnerable individuals, resulting in increasingly poorer health behaviors, for example in relation to HIV-prevention messaging. The discourse on stigma may conflate the denormalization of unhealthy behaviors with wholesale rejection of individual identities. More effective interventions would counter stigma against people who use opioids in general and specifically denormalize opioid misuse. These interventions might alter the effect of public health messaging and ultimately improve outcomes. We argue that public health educators and communication campaigns can contribute to positive social norm change and motivate healthy behaviors by incorporating strategies that attempt to disentangle unhealthy behaviors from identity. [ABSTRACT FROM AUTHOR]

Objective: The present study investigated withdrawal effects of caffeinated energy drink on renal histological and biochemical parameters of adult albino rats. Material and method: Thirty adult male rats weighing 250±10gm were equally divided into 3 groups. Rats in control group I received normal diet and water for 8 weeks. Rats in energy drink group II received 3.57ml/kg body weight red bull daily by gavage for 8 weeks. Withdrawal group III received 3.57ml/kg body weight red bull for 4weeks daily, followed by normal diet and water for next 4 weeks. Blood samples were taken through tail vein at end of 4 and 8 weeks for determination of serum urea and creatinine levels. After completion of 8 weeks' rats were sacrificed, kidneys were removed and slides were prepared using Periodic acid-Schiff stain. Readings were taken through image j software and results were analyzed by SPSS. Results: On histological examination decrease in diameter of glomerulus along with widening of bowman capsule space was observed. In withdrawal group, the histological changes were not reverted to normal since no significant difference was observed when compared to energy drink group with P=0.05. Amongst the biochemical parameters, serum urea levels were increased significantly in the energy drink group. In the withdrawal group, serum urea levels were not reduced at the end of 8 weeks, results were significant when compared with control group with p value 0.000. The results were not significant in case of serum creatinine levels. Conclusion: Histological and biochemical changes in adult albino rats kidneys are not reversible after withdrawal of caffeinated energy drinks. [ABSTRACT FROM AUTHOR]

Objective: To analyze the ameliorative effects of vitamin E on vancomycin-induced nephrotoxicity in rabbits. Study Design: Laboratory based experimental study. Place and Duration of Study: National Institute of Health, Islamabad and Department of Pharmacology and Therapeutics, Army Medical College, Rawalpindi, from Jul to Aug 2017. Methodology: Study included seventy adult, male and female, rabbits weighing 1-2 kg. Group A served as a control group (n=10), group B (n=30) received vancomycin, 200mg/kg I/p dissolved in normal saline twice a day for seven days while group C (n=30) received oral vitamin E, 500mg/kg 5 days prior to vancomycin administration and for seven days after 200mg/kgI/p vancomycin administration. On the eighth day animals were sacrificed. Blood samples were drawn on day 0 and day 8. Estimation of kidney damage was assessed via serum urea, creatinine, sodium and potassium levels. Kidneys were assessed for histopathological examination. Results: Vitamin E administration was buoyant in alleviating marked nephrotoxicity imposed by vancomycin (group B) by significantly decreasing serum urea (p<0.001), creatinine, (p<0.001), serum sodium (p<0.001) and serum potassium levels (p<0.001). Improvement in the renal morphology was also witnessed in group C. Conclusion: Vitamin E successfully ameliorated the nephrotoxicity induced by vancomycin administration. This implicates the therapeutic importance of vitamin E as a nephroprotective agent. [ABSTRACT FROM AUTHOR]

Objective: To explore use of metacognitive skills by medical teachers in relation to Zimmerman’s model of self-regulation. Methods: A qualitative phenomenological study was conducted at Riphah International University from February 2017 to August 2017. A semi structured interview of ten medical teachers was planned to uncover the lived experiences of selected teachers to demonstrate how these teachers use metacognitive strategies in different phases of learning. Data was collected by asking five open ended questions after expert validation. Data was analyzed by using N-Vivo software. Results: Total eight themes were extracted. For prediction and planning three themes, brainstorming, making concept map and sufficient time required were isolated while teachers selected learning objectives and level of students for resource selection while for motivation theme selected was previous experience. Two themes, self-questioning to improve the learning and extra effort required to meet the timeline were isolated for monitoring and reflection during and after learning for evaluation of learning process. Conclusion: During forethought phase, medical teachers predict their learning process through learning objectives and plan after brainstorming to make a concept map and use suitable learning resources. During learning, they monitor learning process through self-questioning and put extra-effort to meet the deadlines. During and after learning, teachers reflect on their performance. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the ameliorative effect of olive oil on gross and qualitative histological changes induced by arsenic in liver of albino rats. Study Design: An experimental/observational study Place and Duration: Department of Anatomy, Islamic International Medical College, Riphah International University, Islamabad from 1st November, 2017 to 18th April, 2018. Methodology: A total of 45 adult albino rats were selected and fifteen out of 45 rats were placed in each of three cages. Rats of group I(control group) were given distilled water, group II received sodium arsenite (40 mg per kg per day) and group III were given 0.2 ml per day of olive oil along with sodium arsenite for 30 days. Rats were dissected after 30 days to observe gross and qualitative histological changes in liver i.e. appearance, colour, consistency and weight along with histological changes like necrosis, congestion and hemorrhage. Results: Among gross parameters all rats in group I (control) showes spongy appearance, dark brown colour and firm consistency. Group II rats shows white necrosed appearance, soft consistency and all rats in group III have normal spongy, pale brown liver with few white patches and soft to firm consistency. Group II livers showed increased mean weight of 10.19 grams as compare to group I liver (7.83 grams) and mean liver weight of group II rats was 7.83 grams. Among qualitative histological parameters, necrosis, congestion and haemorrhage were observed.None of rats in control group I showed these changes, in group II 100% of rats showed necrosis and congestion whereas 46% of rats showed haemorrhage. The use of olive oil has significantly reduced necrosis to 53.3 % and congestion to 46.7% of rats in group III, whereas no haemorrhage was observed in group III rats. Conclusion: The olive oil improves gross and qualitative histological changes induced by arsenic in liver which include appearance, colour, consistency, weight, congestion, necrosis and haemorrhage. [ABSTRACT FROM AUTHOR]

Excessive Hedgehog (Hh) signaling in chondrocytes is sufficient to cause formation of enchondroma-like lesions which can progress to chondrosarcoma. To elucidate potential underlying mechanisms, we identified GLI1 and GLI2 target genes in human chondrosarcoma. Using chromatin immunoprecipitation (ChIP) sequencing and microarray data, in silico analyses were conducted to identify and characterize unique and overlapping GLI1 and GLI2 binding regions in neoplastic chondrocytes. After overlaying microarray data from human chondrosarcoma, 204 upregulated and 106 downregulated genes were identified as Hh-responsive Gli binding targets. After overlaying published Gli ChIP-on-chip data from mouse, 48 genes were identified as potential direct downstream targets of Hedgehog signaling with shared GLI binding regions in evolutionarily conserved DNA elements. Among these was BMP2, pointing to potential cross-talk between TGF beta signaling and Hh signaling. Our identification of potential target genes that are unique and common to GLI1 and GLI2 in neoplastic chondrocytes contributes to elucidating potential pathways through which Hh signaling impacts cartilage tumor biology. [ABSTRACT FROM AUTHOR]

Objective: To explore the nephropreventive effects of melatonin on vancomycin-induced nephrotoxicity in rabbits. Study Design: Laboratory based randomized controlled trial. Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College, Rawalpindi, from May 2017 to June 2017. Material and Methods: Seventy rabbits were divided into three groups. Group A served as a control group (n=10), group B (n=30) received I/P vancomycin 200mg/kg twice a day for seven days while group C (n=30) received I/P melatonin 10mg/kg 30 minutes prior to vancomycin administration for seven days. Animals were sacrificed on the eighth day. Biochemical analysis was done for serum urea, creatinine, sodium and potassium on day 0 and day 8. Kidneys were sent for histopathology. Statistical analysis was carried out by using Microsoft Office Excel 2010 and SPSS version 21. One way ANOVA, followed by 'Post Hoc Tukey' test was used for biochemical parameters. Results: Vancomycin induced massive renal damage (grade III) and led to elevation in biochemical parameters, while melatonin pretreatment prevented the renal damage and the biochemical parameters were also significantly reduced with a p-value of <0.001 for serum urea, creatinine and potassium but had insignificant p-value for serum sodium levels. Conclusion: The study outcome indicates the potential of melatonin to prevent Vancomycin induced nephrotoxicity by virtue of its antioxidant property. [ABSTRACT FROM AUTHOR]

Objective: To assess whether diclofenac sodium interferes with the anti-platelet effect of low dose aspirin. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College and Armed Forces Institute of Pathology Rawalpindi. Material and Methods: Eighteen healthy volunteers, divided into three groups, between the ages of 22-50 years, after written informed consent were selected according to a set criterion. They were given aspirin (150mg) once a day and diclofenac sodium 50mg three times a day for six consecutive days while use of any other drug was prohibited. Blood samples were taken from the study subjects on two occasions, before starting drugs and then on the seventh day. Blood samples were analyzed for platelet aggregation (ADP and collagen induced) and serum thromboxane B2 levels. Results: When a single daily dose of 150mg aspirin is taken with three daily doses of diclofenac sodium (50mg), results show that the anti-platelet effect of aspirin still remains. The mean platelet aggregation with ADP was reduced to 55.83 ± 5.38 percent from a baseline value of 71.67 ± 5.27 percent. Similarly if collagen was used as a reagent the aggregation of platelets was markedly reduced to 40.83 ± 6.63 from a baseline of 66.67 ± 6.54 percent. Results showed a prominent inhibition of aggregation of 22.10% for ADP and 38.75% for collagen. Also, mean thromboxane B2 levels reduced markedly from 971.11 ± 128.91 pg/ml to 702.99 ± 101.59 pg/ml. Conclusion: It is safe to use diclofenac sodium with aspirin, as the anti-platelet effect of the latter is not attenuated. [ABSTRACT FROM AUTHOR]

With the prevalence of osteoarthritis (OA) increasing internationally, there is a need to study the impact of this disease on culturally diverse populations. Individuals of Asian descent make up more than 60% of the world population, yet comprehensive information on the cultural factors that impact OA care is not available. Scoping review methodology using directed content analysis was employed to identify and analyze existing research on OA care for Asians. A categorization matrix was developed using the six care areas from the OA clinical practice guidelines along with an additional three non-clinical areas (cross-cultural adaptation of clinical tools; psychological well-being; family systems and informal care) identified in an initial scan resulting in a total of nine OA care areas to guide initial coding. A full scoping review was conducted across five databases resulting in 656 abstracts screened. All text was coded using the categorization matrix and resulting subthemes were identified. A total of 74 articles were analyzed with 23 subthemes identified across the nine categories. Four new perspectives emerged to support OA care for Asian populations: (1) the importance of family and peer assistance, (2) the importance of culturally specific activities, (3) distrust in western medicine, and (4) impact of positive coping mechanisms on health appraisals. While Asians are more susceptible to knee and hand OA because of their cultural lifestyle factors (e.g. squatting for chores, hygiene and religious activities), and traditional beliefs on OA management (e.g. traditional diet, topical oils, physical therapy), many do not present themselves for conventional treatments (e.g. surgery) until all traditional treatments are exhausted. The results suggest that cultural factors influence the uptake of OA management practices among Asians. Greater awareness of these cultural factors may improve diagnosis, treatment, and management of OA among Asian patients. [ABSTRACT FROM AUTHOR]

Systematic reviews of self-management programs for osteoarthritis suggest minimal evidence of benefit and indicate substantial heterogeneity in interventions. The purpose of this scoping review was to describe the nature of self-management interventions provided to patients with osteoarthritis focusing on the inclusion and type of education and social support components. We searched PsycINFO, EMBASE, MEDLINE, and Cochrane Library databases from 1990 to 2016 to identify studies addressing community-based management strategies for osteoarthritis that included aspects of disease-specific education and ongoing social support. Results are presented as a narrative synthesis to facilitate integration of diverse evidence. Data were extracted from 23 studies that met our inclusion and exclusion criteria, describing complex, multicomponent interventions for osteoarthritis. All studies included education components, and 18 of these were osteoarthritis-specific. Social support was most often offered through peers and health care professionals, but also through exercise trainers/instructors and researchers, and lasted between 5 and 52 weeks. We charted positive social interaction offered by peers in group settings and emotional/informational support offered by health care professionals. Overall, descriptions of self-management provided limited documentation of the rationale or content of the programs. This suggests that more precise definitions of the theoretical underpinnings, components, and mechanisms would be useful for greater insight into best practices for osteoarthritis self-management programs. [ABSTRACT FROM AUTHOR]

Objectives. Among the challenges in health research is translating interventions from controlled experimental settings to clinical and community settings where chronic disease is managed daily. Pragmatic trials offer a method for testing interventions in real-world settings but are seldom used in OA research. The aim of this study was to evaluate the literature on pragmatic trials in OA research up to August 2016 in order to identify strengths and weaknesses in the design and reporting of these trials. Methods. We used established guidelines to assess the degree to which 61 OA studies complied with pragmatic trial design and reporting. We assessed design according to the pragmatic-explanatory continuum indicator summary and reporting according to the pragmatic trials extension of the CONsolidated Standards of Reporting Trials guidelines. Results. None of the pragmatic trials met all 11 criteria evaluated and most of the trials met between 5 and 8 of the criteria. Criteria most often unmet pertained to practitioner expertise (by requiring specialists) and criteria most often met pertained to primary outcome analysis (by using intention-to-treat analysis). Conclusion. Our results suggest a lack of highly pragmatic trials in OA research. We identify this as a point of opportunity to improve research translation, since optimizing the design and reporting of pragmatic trials can facilitate implementation of evidence-based interventions for OA care. [ABSTRACT FROM AUTHOR]

Objective With no effective therapies to attenuate cartilage degeneration in osteoarthritis (OA), the result is pain and disability. Activation of hedgehog (HH) signaling causes changes related to the progression of OA, with higher levels of Gli-mediated transcriptional activation associated with increased disease severity. To elucidate the mechanism through which this occurs, this study sought to identify genes regulated by HH signaling in human OA chondrocytes. Methods Using human OA cartilage samples, microarray analyses were performed to detect changes in gene expression when the HH pathway was modulated. Results were analyzed for differentially expressed genes, grouped into functional networks, and validated in independent samples. To investigate the effects of chondrocyte-specific sterol accumulation, we generated mice lacking Insig1 and Insig2, which are major negative regulators of cholesterol homeostasis, under Col2a1 regulatory elements. Results HH signaling was found to regulate genes that govern cholesterol homeostasis, and this led to alterations in cholesterol accumulation in chondrocytes. A higher level of Gli-mediated transcription resulted in accumulation of intracellular cholesterol. In genetically modified mice, chondrocyte-specific cholesterol accumulation was associated with an OA phenotype. Reducing cholesterol accumulation attenuated the severity of OA in mice in vivo and decreased the expression of proteases in human OA cartilage in vitro. Conclusion HH signaling regulates cholesterol homeostasis in chondrocytes, and intracellular cholesterol accumulation contributes to the severity of OA. Our findings have therapeutic implications, since reduction of HH signaling reversed cholesterol accumulation and statin treatment attenuated cartilage degeneration. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of transition of summative assessment from frequent modular to combined block assessment and its role on learning of medical students. Methods: A descriptive study was carried out at Islamic International Medical College. A questionnaire comprizing of 8 questions with Likert scale (1-5) was designed for 3rd year students. The questions were grouped in three categories which included learning acquired, personal development and efficacy of assessment tools used in combined block assessment and frequent modular exam separately. Results of end of year exams were analyzed for difference in performance of students in two exams. The received data was analyzed by using SPPS 21. Results: About 60% students agreed that they need to study regularly in frequent modular exams. Combined block assessment promoted more indepth studies and multiple revisions 51% and 55% students respectively. About 42% students, in comparison with 33%, agreed that CBA helped in their personal development while 42% students agreed to assessment tools used in CBA while only 28% students to those used in frequent modular exam. About 47% students agreed that assessment tools in CBA were useful for deep learningand 47% students agreed that time given in CBA was enough in exam preparation. Comparison of all results (x 2 tests) was statistically significant. The comparison of end of year performance showed improvement in the mean of total marks obtained and decrease in the number of failed students in combined block assessment. Conclusion: Transition from frequent to combined block assessment with regular formative assessment has positive effect on learning, personal grooming and performance in summative assessment. [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 GroupD, 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]

Introduction: Spina bifida is an important developmental defect of vertebral column. There are various types of spina bifida. The commonest one is spina bifida occulta (SBO), in which patients do not show any sign and symptoms as there is no herniation of spinal canal contents. This lesion is present at birth. Incidence of spina bifida decreases with age. The prevalence of spina bifida is related to various factors. Genetic predispositions, environmental factors and teratogenic effects of the drugs are important. It may be caused by the prenatal use of drugs like valproic acid. Sacral hiatus is used for caudal epidural block. We conducted this cross sectional study to find out the incidence of SBO in our population. Methodology: This was an observational descriptive study. This study was carried out in Islamic International Medical College Rawalpindi. The duration of study was six months. Bones were studied in five different medical colleges of Rawalpindi with the consent of the concerned authorities. A total of 200 sacra were selected. The damaged and defective bones were excluded. All the studied bones were complete. All bones were studied for prevalence of SBO in our population. Bones having apex of sacral hiatus till S4 were considered normal. The remaining bones were divided into four grades according to level of failure of closure of sacral laminae. Bones with partial closure between two or more adjacent sacral vertebrae (incomplete spina bifida) were included in Grade I and II. Bone with sacral hiatus extending beyond S4 ( long hiatus)were included in grade III and all bones with open dorsal wall representing the complete failure of fusion of the laminae from S1-S5 were included in grade VI. Results were analyzed by SPSS 17. Results: The spina bifida was found in 69 bones with an overall incidence of 34.5% among 200 bones. Out of 69 variants, bones were grouped in two groups; one having complete and incomplete SBO among adjacent vertebrae, other having long hiatus. Prevalence of grade-1 SBO was 5.5% while it was 4.5% for grade-IV SBO. Region between S1-2 was the most common site for grade-1 anomaly. Incidence of long hiatus from S5-3 was higher i.e., 46 (23%) while 2 sacra had hiatus ending at S2. Conclusion: Presence of spina bifida occulta should always be kept in mind while dealing with patients of backache, urinary and neurological symptoms. It may also be the cause of failure of caudal epidural block. Studies with larger sample size and including different ethnic groups from different regions of Pakistan are required to note the regional and ethnic disparities in the anatomy of the sacral hiatuses. [ABSTRACT FROM AUTHOR]

Background: Artemether-lumefantrine is one of the most widely used anti-malarial drug combinations in the world with excellent tolerability and cure rates in adult and paediatric patients with uncomplicated falciparum malaria. The aim of this study was to evaluate the pharmacokinetics of artemether and its active metabolite, dihydroartemisinin, in healthy Pakistani volunteers. Methods: Twelve healthy male Pakistani subjects, aged 20 to 50, were recruited into the study. A fixed oral combination of artemether-lumefantrine (80-480 mg) was given as a single oral dose. Frequent blood samples were collected and artemether and dihydroartemisinin were quantified in human plasma using solid-phase extraction and liquid chromatography coupled with tandem mass spectrometry. Drug concentration-time data were evaluated with non-compartmental analysis. Results: Observed maximum concentrations (mean ± SD) of artemether and dihydroartemisinin were 184 ± 100 ng/mL and 126 ± 46 ng/mL, respectively. These concentrations were reached at 1.56 ± 0.68 hr and 1.69 ± 0.59 hr, respectively, after drug intake. The terminal elimination half-life of artemether and dihydroartemisinin were 2.00 ± 0.71 hr and 1.80 ± 0.31 hr, respectively. Apparent volume of distribution and oral clearance for artemether were estimated to 666 ± 220 L and 257 ± 140 L/hr. The same parameters were estimated to 702 ± 220 L and 269 ± 57 L/hr for dihydroartemisinin. Conclusions: The overall pharmacokinetic properties of artemether and dihydroartemisinin in healthy Pakistani subjects are comparable to healthy subjects and patients from other populations. [ABSTRACT FROM AUTHOR]

Abstract: We report an optimized method for RNA extraction from human articular cartilage that does not require the use of specialized equipment or column purification. To maximize RNA yield while minimizing degradation and contamination, chondrocytes are isolated from the extracellular matrix and the traditional TRIzol protocol is modified to include two RNA–DNA–protein phase separations. We compared RNA extracted using this modified method with the traditional TRIzol method by spectrophotometry, Bioanalyzer, and real-time polymerase chain reaction (PCR). With the modified method, RNA recovery is increased by nearly 1μg per 100mg of cartilage, and RNA integrity number (RIN) is improved from 2.0 to 7.5. [Copyright &y& Elsevier]

Osteoarthritis (OA) is a debilitating disease with no approved disease-modifying therapies. Among the challenges for developing treatment is achieving targeted drug delivery to affected joints. This has contributed to the failure of several drug candidates for the treatment of OA. Over the past 20 years, significant advances have been made in antisense oligonucleotide (ASO) technology for achieving targeted delivery to tissues and cells both in vitro and in vivo. Since ASOs are able to bind specific gene regions and regulate protein translation, they are useful for correcting aberrant endogenous mechanisms associated with certain diseases. ASOs can be delivered locally through intra-articular injection, and can enter cells through natural cellular uptake mechanisms. Despite this, ASOs have yet to be successfully tested in clinical trials for the treatment of OA. Recent chemical modification to ASOs have further improved cellular uptake and reduced toxicity. Among these are locked nucleic acid (LNA)-based ASOs, which have shown promising results in clinical trials for diseases such as hepatitis and dyslipidemia. Recently, LNA-based ASOs have been tested both in vitro and in vivo for their therapeutic potential in OA, and some have shown promising joint-protective effects in preclinical OA animal models. In order to accelerate the testing of ASO therapies in a clinical trial setting for OA, further investigation into delivery mechanisms is required. In this review article, we discuss opportunities for viral-, particle-, biomaterial-, and chemical modification-based therapies, which are currently in preclinical testing. We also address potential roadblocks in the clinical translation of ASO-based therapies for the treatment of OA, such as the limitations associated with OA animal models and the challenges with drug toxicity. Taken together, we review what is known and what would be useful to accelerate translation of ASO-based therapies for the treatment of OA. • Currently, there are no approved disease modifying drugs for osteoarthritis (OA). • Antisense oligonucleotides (ASOs) bind specific gene sequences to regulate translation. • ASO technology is advancing toward targeted delivery to tissues and cells. • Some locked nucleic acid (LNA)-based ASOs show promise in OA animal models. • Challenges (e.g. targeted drug delivery, safety profile) remain prior to OA clinical trials. [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]

This community based Cross-sectional Observational study was carried out in Skardu city and its adjoining areas, in order to determine the frequency of intestinal parasitic infections and its relation with the nutritional status of pre-school children. A sample of 300 preschool children was selected through convenience sampling. Stool samples were tested for presence of ova/cysts of intestinal parasites. Anthropometric data was obtained using standard tools. Ascaris Lumbricoides, Cryptosporidium, Hymenolepis Nana and Giardia had frequency of 22.33%, 14%, 9.3% and 8.0% respectively. 47 (15.7%) Preschool children were found to be wasted. Out of wasted children, majority (35 children) were infested with some kind of intestinal parasites (p-value 0.001845). Significant relation was found between intestinal parasitic infestation and wasting. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the overall impact of using e-learning resources by Riphah faculty members in terms of their satisfaction and its usefulness for student learning. Study Design: Cross-sectional survey. Place and Duration of Study: Conducted in Islamic International Medical College, from 24th Jun to 28th Jun 2020. Methodology: There were a total of 160 respondents of Riphah faculty of Medical College (n=100), Dental College (n=30) and Rehab Sciences (n=30). Results: A total of 58.8% of the faculty agreed that online education is convenient for their working and the concept of online mode of teaching was acceptable to 65.6%. Faculty-development workshops were appreciated by 60%. About 70% disagreed that face-face lectures can be replaced by online lectures. Regarding Perception of student online teaching and assessment 66.9% disagreed that they are attentive during the online lectures. As far as the preparedness towards online learning was concerned 33.8% agreed that preparation for online lectures requires a lot of effort. 52.5% agreed that learning of online technologies is difficult to learn. Major challenges faced were those of network issues 56.3% lack of computer skills 64.4%. According to Kirk Patricks’ evaluation level-1 regarding the reaction of faculty 96.3% were satisfied with the faculty development program. Conclusion: Reaction of the employees is recorded to identify aspects, which can be used to make improvements in the training programs. A very high percentage of faculty members were satisfied with the training activities and strengths and weaknesses were elaborated along with the factors, which promote and hinder the students learning activities. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of vitamin D3 supplementation on HbA1c in individuals with pre-diabetes Study Design: Quasi experimental study. Place and Duration of Study: Study was executed in department of Pharmacology and Therapeutics, Army Medical College, Rawalpindi in collaboration with Chemical Pathology department, Army Medical College and Armed Forces Institute of Pathology (AFIP), Rawalpindi Pakistan, from Jan to Dec 2019. Methodology: One hundred and forty individuals with pre-diabetes and co-existing hypovitaminosis D3 were selected, with serum 25(OH) D (<50 nmol/L) and elevated glycosylated hemoglobin (HbA1c) (5.7-6.4%). Individuals were randomly assigned to receive 2000000 IU of vitamin D3 (Vit D3; n=70) or placebo (n=70) one stat at the beginning of study and one after one month. The primary outcome was amelioration of HbA1c. Results of HbA1c and vitamin D3 were compared after completion of study with the initial values. Results: A considerable inverse association was found between vitamin D3 and HbA1c in individuals with prediabetes. Median with inter-quartile range of baseline serum 25(OH) D3 was 43 and 41 nmol/L in the Vitamin D3 and placebo group, respectively. Post treatment serum 25(OH) D3 was significantly increased to 54nmol/L (p<0.0001) in the Vitamin D3 group. HbA1c level was decreased in the vitamin D3 group. Conclusion: This study evaluated the correlation between vitamin D3 in individuals with pre-diabetes. A statistically significant improvement in Glycosylated hemoglobin (HbA1c) was observed in the patients selected in the pre-diabetic range. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are a promising cell source for cartilage tissue regeneration in animals and humans but with large interdonor variation in their in vitro chondrogenic differentiation potential. Underlying molecular mechanisms responsible for culture-expanded MSC heterogeneity remain poorly understood. In this study, we sought to identify variations in microRNA (miRNA) signatures associated with cultured equine MSC chondrogenic differentiation potential from different donors. Neocartilage tissue generated from equine cord blood-derived MSCs was categorized as having either high or low chondrogenic potential (LCP) based on their histological appearance and quantification of glycosaminoglycan deposition. Using next-generation sequencing, we identified 30 differentially expressed miRNAs among undifferentiated MSC cultures that corresponded with their chondrogenic potential. Of note, MSCs with LCP upregulated miR-146a and miR-487b-3p, which was also observed by quantitative real-time polymerase chain reaction. Our findings suggest that miRNA profiling of equine MSC cultures may have prognostic value in selecting MSC donors with regard to their chondrogenic differentiation potential. [ABSTRACT FROM AUTHOR]

Objective: To compare protective potential of cinnamon extract and green tea against Bisphenol A induced changes in tubular histology of rat kidney. Design of Study: Randomized controlled trial. Place and Duration of Study: Duration of study was six months and was conducted in Islamic International Medical College in collaboration with NIH. Material and Methods: Sixty adult male rats of Sprague Dawley strain were placed in 4 cages having 15 rats each. Experimental duration was 30 days. Rats in control group A were subcutaneously injected with distilled water. Rats in experimental group B were given subcutaneous injections of BPA at dose of 30mg/kg/day. Rats in group C were given cinnamon (200mg/kg/day) orally along with s/c injection of BPA while group D rats were given green tea orally along with s/c BPA injections. All rats were dissected after 30 days and right kidneys were taken out to examine histological changes in proximal and distal convoluted tubules. Results: Histological parameters of proximal and distal convoluted tubules were observed in experimental and control groups. Marked deterioration of tubular structure was observed in group B as compared to control group. Although both groups C and D showed nephroprotection against tubular histological changes but group D offered greater nephroprotection than group C. Conclusion: Green tea was more effective than cinnamon in combating the oxidative stress induced neprotoxicity caused by BPA. Co-administration of cinnamon and green tea with BPA reduced the histological damage in proximal and distal convoluted tubules of nephrons in rats caused by Bisphenol A. [ABSTRACT FROM AUTHOR]

Objective: To explore the effect of genetic polymorphism -100_-102AAG deletion in the 5-hydroxytryptamine type 3B (5-HT3B) gene on the incidence of post-operative vomiting (POV). Study Design: A prospective, clinical trial. Place and Duration of study: Clinical data collection and blood sampling was carried out at Combined Military Hospital, Rawalpindi. Genetic analysis was carried out at Institute of Biomedical and Genetic Engineering, Islamabad from 01 Aug 2012 to 22 Sep 2013. Methods: This study included two hundred and sixty patients planned for elective laparoscopic cholecystectomy. 4 mg ondansetron was administered intravenously thirty minutes before the end of surgery. A total of 140 patients with the complaints of vomiting and 120 patients without vomiting were analyzed for -100_-102delAAG deletion polymorphism with the help of direct sequencing method. Results: A significant association was found between the incidence of vomiting and the -100_-102AAG insertion/deletion polymorphism of the 5-HT3B gene at 2 hours after surgery. Conclusion: The -100_-102AAG deletion variant of the 5-HT3B gene may affect POV and predict the responsiveness to ondansetron. [ABSTRACT FROM AUTHOR]

Objective: To determine the effectiveness and safety of preoperative gabapentin administration on post-operative pain after laparoscopic cholecystectomy. Methodology: Ninety patients undergoing laparoscopic cholecystectomy were divided into two groups. Group A received gabapentin in a dose of 300 mg two hours before surgery; and group B received placebo capsules in the same size and shape as gabapentin capsules. The pain scores, consumption of analgesics and adverse effects were compared between the two groups postoperatively at 2 hours, 6 hours, 12 hours and 24 hours after recovery. Results: Group A had statistically less pain scores as compared to group B at 2, 6, 12 and 24 hours after recovery (p values were 0.0001, <0.0001, 0.0004, <0.0001 respectively). The requirement of analgesics was statistically lower in group A in comparison to group B at all the time intervals (p <0.0001). Both groups had no difference in the frequency of adverse effects except for vomiting which was significantly higher in group B (p =0.04). Conclusion: Post-operative pain and the requirement for postoperative analgesics were significantly reduced in patients with administration of gabapentin before surgery and its use was found to be safe following laparoscopic cholecystectomy. [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]

Post-operative nausea and vomiting is the most annoying and at the same time a dangerous side effect of general anaesthesia. Ondansetron is a routinely used anti emetic drug which is being administered by the trial and error principle. Though it did revolutionized the management of this condition but by and large failed to completely eliminate the problem. Recently an important factor possibly elucidating this failure is said to be the differing expression of genes controlling proteins that are involved in transport and receptors related to this drug. Quite surprisingly these transporter and receptor pathways have been found to be polymorphic and at the same time shown to be related to efficacy of the drug. The differentiation between those responding to treatment and those not responding may pave a way to individualize treatment for emesis to a greater extent. This review highlights the pharmacogenetics related to this commonly used anti-emetic drug in anaesthesia. It is visualized as a promising way to achieve the target of individualized therapy. It seems obvious that pharmacogenetics will become an important field of anaesthesia research in the future. [ABSTRACT FROM AUTHOR]

Ultrasound-promoted reaction of substituted 2,4-dichloroquinolines ( 1) with ethyl 4-(3-hydroxyphenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate ( 2) in the presence of KCO as mild base at moderate temperatures leads to 2-chloroquinolin-4-pyrimidine carboxylate derivatives ( 3) with high regioselectivity. All the compounds synthesized were characterized by use of spectral data and screened for their antibacterial activity against two Gram-positive ( Staphylococcus aureus, Bacillus cereus) and two Gram-negative ( Escherichia coli and Pseudomonas aeruginosa) bacteria. Activity was moderate. [ABSTRACT FROM AUTHOR]

The disruption of K+ transport and accumulation is symptomatic of NH4+ toxicity in plants. In this study, the influence of K+ supply (0.02–40 mM) and nitrogen source (10 mM NH4+ or NO3–) on root plasma membrane K+ fluxes and cytosolic K+ pools, plant growth, and whole-plant K+ distribution in the NH4+-tolerant plant species rice (Oryza sativa L.) was examined. Using the radiotracer 42K+, tissue mineral analysis, and growth data, it is shown that rice is affected by NH4+ toxicity under high-affinity K+ transport conditions. Substantial recovery of growth was seen as [K+]ext was increased from 0.02 mM to 0.1 mM, and, at 1.5 mM, growth was superior on NH4+. Growth recovery at these concentrations was accompanied by greater influx of K+ into root cells, translocation of K+ to the shoot, and tissue K+. Elevating the K+ supply also resulted in a significant reduction of NH4+ influx, as measured by 13N radiotracing. In the low-affinity K+ transport range, NH4+ stimulated K+ influx relative to NO3– controls. It is concluded that rice, despite its well-known tolerance to NH4+, nevertheless displays considerable growth suppression and disruption of K+ homeostasis under this N regime at low [K+]ext, but displays efficient recovery from NH4+ inhibition, and indeed a stimulation of K+ acquisition, when [K+]ext is increased in the presence of NH4+. [ABSTRACT FROM PUBLISHER]

Objective: To assess the role of pregabalin as premedication for preoperative sedation and anxiolysis with two different doses in laparoscopic cholecystectomy patients. Study Design: Quasi-experimental study. Place and Duration of Study: Department of Pharmacology and Therapeutics, Army Medical College, Rawalpindi in collaboration with Department of Anesthesiology, Combined Military Hospital, Rawalpindi, from Feb to Jul 2019. Methodology: A total 96 patients of either gender, aged between 18-60 years with American Society of Anesthesiologists (ASA) grade I-II, undergoing elective laparoscopic cholecystectomy were enrolled in this study. They were randomly divided into three groups having 32 patients each. Group 1 received oral placebo drug, group 2 received oral pregabalin 150 mg, whereas group 3 received oral pregabalin 300mg with sip of water 90 mins before the induction of general anesthesia. The effects of drugs on the patient’s level of sedation and anxiety were evaluated at baseline and before the induction of anesthesia using Ramsay Sedation Score and Beck Anxiety Inventory respectively. Results: Premedication with pregabalin 150mg and 300mg significantly produced sedation as compared to placebo. Though, Pregabalin (300mg) exhibited more sedation than Pregabalin (150mg) but the difference between them was statistically insignificant (p=0.33). Preoperative administration of pregabalin was related with anxiolysis, with the most prominent results shown by pregabalin 300mg (p<0.00) whereas pregabalin 150mg could not alleviate anxiety and the results were statistically insignificant (p=0.05). Conclusion: Premedication with Pregabalin 300mg, 90 mins before the induction of general anesthesia is an effective regimen to alleviate preoperative anxiety and sedation. [ABSTRACT FROM AUTHOR]

BACKGROUND & OBJECTIVE: Osteoarthritis (OA) is one of the most common joint diseases afflicting human, characterized by progressive degeneration of articular cartilage in which chondrocytes fails to repair adequately. The objective of this study isto evaluate the chondroprotection treated by triamcinolone in osteoarthritis induced rat model. METHODOLOGY: This laboratory-based experimental study was conducted inthe Department of Pharmacology, Army Medical College, Rawalpindi, in collaboration with the National Institute of Health, Islamabad, from May-July2019.Osteoarthritis was induced by surgical removal of the medial meniscus and anterior cruciate ligament resection in the right knee joint of Sixteen (16) anesthetized rats of Sprague Dawley breed. They were divided into two (02) groups, with eight (08) rats in each group. Group-I was disease control in which 0.2 ml Intraarticular saline was administered for three weeks. While in group-II, a treatment group was treated with 70 µl intraarticular triamcinolone once weekly for three weeks. After that gait pattern of rats was scored. Animals were euthanized with overdosage of inhaled chloroform and a sample of proximal tibia was taken for histopathological analysis. RESULTS: The mean gait score of the control group and treatment group was 3.25±.707 and 2.25±.463 with a p-value of 0.006 that is statistically significant. While mean histopathological modified Mankin score of the control and treatment group was 11.5±1.195 and 8.5±1.195, respectively, with a significant p<0.001. CONCLUSION: Intraarticular administration of triamcinolone in osteoarthritis-induced rats resulted in improvement in gait pattern and histopathology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the clinical efficacy of Ascorbic acid in relieving pain and inflammation following surgical removal of the third molar. Study Design: Quasi-experimental study. Place and Duration of Study: Armed Forces Institute of Dentistry, Rawalpindi Pakistan, from Jan to Mar 2023. Methodology: Sixty participants who required surgical extraction of the impacted third molar were included and segregated equally into two groups. Group-A received Amoxicillin with Clavulanic acid (625 mg) thrice a day and Metronidazole (400 mg) twice daily, while Group-B received Amoxicillin with Clavulanic acid (625 mg) thrice daily, Ascorbic acid (500 mg) twice daily and Metronidazole (400 mg) twice daily. Both the groups received Naproxen Sodium as per requirement (550 mg). Pain, trismus, facial swelling, and requirement of analgesic consumption were evaluated on the seventh post-operative day. Results: There was a statistically significant difference in reducing the intensity of pain (p<0.01), severity of facial swelling and trismus (p<0.01) and requirement of analgesic consumption between Group A and B (p<0.001). Conclusion: Our study concluded that Ascorbic acid after surgery effectively reduces pain intensity, the severity of facial swelling and trismus, and the requirement for analgesic consumption so that ascorbic acid may be used as an adjuvant therapy with other conventional drugs. [ABSTRACT FROM AUTHOR]

Objective: MicroRNA‐34a‐5p (miR‐34a‐5p) expression is elevated in the synovial fluid of patients with late‐stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR‐34a‐5p in OA pathogenesis. Methods: Expression of miR‐34a‐5p was determined in joint tissues and human plasma (n = 71). Experiments using miR‐34a‐5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast‐like synoviocytes (FLS) (n = 7–9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high‐fat diet and subjected to DMM (n = 11). Wild‐type (WT) mice (n = 9) and miR‐34a–knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t‐test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes. Results: Expression of miR‐34a‐5p was significantly increased in the plasma, cartilage, and synovium of patients with late‐stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR‐34a‐5p expression was significantly increased in obese patients with late‐stage OA, and in the plasma and knee joints of mice fed a high‐fat diet. In human OA chondrocytes and FLS, miR‐34a‐5p mimic increased key OA pathology markers, while miR‐34a‐5p ASO improved cellular gene expression. Intraarticular miR‐34a‐5p mimic injection induced an OA‐like phenotype. Conversely, miR‐34a‐5p ASO injection imparted cartilage‐protective effects in the DMM and high‐fat diet/DMM models. The miR‐34a–KO mice exhibited protection against DMM‐induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR‐34a‐5p signaling network. Conclusion: Our findings provide comprehensive evidence of the role and therapeutic potential of miR‐34a‐5p in OA. [ABSTRACT FROM AUTHOR]