Osteoprotegerin genetic polymorphisms and their influence on therapeutic response to ibandronate in postmenopausal osteoporotic females.

OBJECTIVES: The present study investigated osteoprotegerin (OPG) genetic polymorphisms and their influence on the therapeutic response to ibandronate in postmenopausal osteoporotic females. METHODS: This case-control study included 135 postmenopausal females (89 osteoporotic females and 46 non-osteoporotic females). Each osteoporotic patient received a monthly 150 mg ibandronate tablet for six months, and blood samples were taken before and after treatment. Bone mineral density (BMD) was measured using DEXA Scan. Three SNPs (A163G, T245G, and G1181C) of the OPG gene were selected for analysis. RESULTS: Serum OPG levels were significantly lower in osteoporotic subjects than in the control group. The percentage changes in OPG levels in the osteoporotic group before and after treatment with ibandronate were significant (p < .001). After six months of therapy with ibandronate, the percentage changes in OPG levels with AA, TT, TC, GC, and GG genotypes were significant. Following six months of ibandronate treatment, the AA genotype of rs3134069, TT, TC genotypes of rs3102735, GG, and GC genotypes of rs2073618 SNP showed a significant increase in OPG levels. Age, BMI, and GC polymorphism (rs2073618 (G/C) G1181C) were inversely associated with low BMD. Adjusted odds ratios (OR) showed that BMI, GC, GG polymorphism (rs2073618 (G/C) G1181C) and TC polymorphism (rs3102735 (T/C) A163G) were inversely associated with low BMD. CONCLUSION: The inverse association of rs2073618 and rs3102735 with low BMD indicates the protective role of these SNPs in our population. More research is needed to replicate these results in another cohort and to determine the molecular processes by which such SNPs may influence BMD.

Point prevalence probing of antimicrobial prescription patterns from a developing country.

BACKGROUND: Irrational use of antibiotics intensifies resistance and jeopardizes advances made in modern medicine. We aimed to conduct a baseline gap analysis survey on antibiotic prescription practices across Pakistan. RESEARCH DESIGN AND METHODS: This multi-centered cross-sectional survey was conducted at six public sector tertiary care hospitals from February 2021 to March 2021. Data related to various variables including hospital infrastructure, policies and practices, monitoring and feedback, and epidemiological, clinical, and antibiotic prescription for surveyed patients was collected using World Health Organization (WHO) Point Prevalence Survey (PPS) methodology. RESULTS: In a survey of 837 inpatients, 78.5% were prescribed antibiotics. Most commonly prescribed antimicrobial was ceftriaxone (21.7%), followed by metronidazole (17.3%), cefoperazone-sulbactam (8.4%), amoxicillin-clavulanate (6.3%), and piperacillin/tazobactam (5.9%). Surgical prophylaxis (36.7%) and community-acquired infections (24.7%) were the main reasons for antibiotic prescriptions. Single antibiotics were given to 46.7% of patients, 39.9% received a combination of two antibiotics, and 12.5% were prescribed three or more antibiotics. Among six hospitals surveyed, two had drug and therapeutic committees, three had infection prevention and control committees, and one had an antibiotic formulary. CONCLUSION: Findings demonstrate high consumption of broad-spectrum antimicrobials and emphasize the importance of expanding antimicrobial stewardship programs among hospitals. Mentoring clinical teams could help rationalize antimicrobial use.

Factors leading to delayed and challenging presentation of benign breast lumps in young females.

Background and Objective: A delayed presentation of benign breast diseases may lead to a therapeutic challenge when they enlarge enormously or become multiple. Aim of this study was to evaluate the factors leading to delayed presentation of benign breast lumps. Methods: This cross-sectional study was conducted at Madinah Teaching Hospital and Allied Hospital, Faisalabad from January 2019 to October 2021. One hundred and forty five female patients were selected by non-probability purposive sampling. Patients with large size (>5cm) or multiple benign breast lumps were included. An interview was conducted using structured questionnaire translated in Urdu. Factors leading to delayed presentation and social impact scale for stigma were evaluated. Results: Patients had a mean age of 26.52 ± 6.90 years. The average delay of seeking medical care was 8.48 ± 8.41 months. Factors leading to delayed presentation were; lack of knowledge n=112 (77.2%) and parda (religious issues) n=112 (77.2%), followed by poverty n=109 (75.2%), and fear of cancer n=90 (62.1%). All the sub-scales of stigma, i.e., social rejection, financial insecurity, internalized shame and social isolation were high in late presenters, though, only financial insecurity was significantly high in late presenters (p=0.03). Conclusion: Lack of awareness, socioeconomic factors and disease related stigma were the main factors related to delayed presentation in young females with benign breast diseases. Addressing these factors may improve timely diagnosis and management of delayed and challenging cases.

Association of serum levels of Visfatin, Intelectin-1, RARRES2 and their genetic variants with bone mineral density in postmenopausal females.

Background: Adipokines are engaged in bone physiology and regulate bone mineral density (BMD) by playing protective or cynical role in bone metabolism. The study is designed to measure and compare BMD, adipokines (retinoic acid receptor responder protein-2 RARRES2, visfatin and Intelectin-1) and their genetic variants in postmenopausal osteoporotic, osteopenic and non-osteoporotic females. Methods: This comparative study included postmenopausal non-osteoporotic (n=72), osteopenic (n=72) and osteoporotic (n=100) females with two years of amenorrhea and age between 50 to 70 years. Gold standard DXA was used to measure BMD. Hardy-Weinberg equilibrium was established. Kruskal-Wallis test for comparisons, logistic and multivariate regression analysis were used to rule out the predictors of BMD. Results: On comparing the three groups, significant differences were observed in serum RARRES2 (p <0.001) and serum visfatin (p=0.050). The significant positive predictor of BMD at lumbar spine and total hip was serum visfatin. BMD at right and left femoral neck was predicted negatively by serum chemerin while BMD at left femoral neck was also predicted positively by serum calcium levels. There was significant difference in BMD at right femoral neck (p = 0.033) between rs7806429 genotypes. The odds of having low BMD increases with increasing serum levels of chemerin and decreasing serum levels of visfatin and calcium. Conclusion: The adipokines RARRES2 and visfatin are associated with BMD. RARRES2 is an independent negative and visfatin is positive predictor of BMD in postmenopausal females. BMD at right femoral neck was significantly low in RARRES2 rs7806429 TC heterozygotes.

Serum Resistin Levels and Related Genetic Variants Are Associated With Bone Mineral Density in Postmenopausal Women.

Background: Osteoporosis is a multifactorial disorder and a number of genetic variants or loci responsible for bone mineral density (BMD) have been identified. Resistin, a novel adipokine has diverse role in human body including its function in bone remodeling. The objective of this study was to see the association of serum resistin levels and related genetic variants (rs3931020, rs13144478) with BMD in postmenopausal females. Methods: This comparative analytical study was conducted on postmenopausal osteoporotic (n=101), osteopenic (n=77) and non-osteoporotic (n=74) females. For comparison and correlational analysis, Kruskal-Wallis test and Spearman's rho correlation were used respectively. Hardy-Weinberg equilibrium (HWE) was calculated by using Chi-square test (χ2). Results: There was significant difference in the serum levels of resistin (p <0.001), among the three groups. Significant negative correlation of resistin was observed with BMD at various sites. Serum resistin levels were significantly low in the rs3931020 AA homozygous genotype (p = 0.010), and significantly high in the rs13144478 AT heterozygous genotype (p = 0.020), BMD at all sites except left femoral neck was significantly high in rs3931020 AA genotype, while BMD at lumbar spine, left hip and total BMD were significantly low in the rs13144478 TT homozygotes. Conclusion: High serum resistin levels are associated with low BMD and single nucleotide variation in rs3931020 and rs13144478 may lead to high serum resistin levels and low bone mineral density. Resistin can serve as a new genetic marker, potential therapeutic target and predictor of osteoporosis.

Rasagiline Pharmacokinetics in CYP1A2 Variant Healthy Smokers & Non-smokers in Different Doses.

Objectives: Rasagiline, a drug for Parkinson's disease is metabolized by CYP1A2 enzyme. The objective of the study was to investigate the influence of cytochrome P450 1A2 variants and smoking status of healthy individuals on the pharmacokinetics of rasagiline. Methods: A comparative, open label, interventional, single oral dose, pharmacokinetic study was performed on 108 healthy volunteers in UHS & UVAS, Lahore. Data collection was initiated in June 2016 and ended in January 2018. It was divided in three phases with 1, 2 and 5mg of rasagiline given to a group of 36 volunteers in each phase. Volunteers were sub-divided into six groups of AA smokers, AA non-smokers, AC smokers, AC non-smokers, CC smokers & CC non-smokers on the basis of genotyping and smoking status. Serial blood sampling was performed at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8 & 12 hours after administration of rasagiline tablets. Plasma concentrations were determined using High Performance Liquid Chromatography (HPLC) method. Pharmacokinetic (PK) parameters were calculated using software (APO) pharmacological analysis. Results: Analysis of variance (ANOVA) showed significant difference between AA and CC groups. Multiple group comparison with post hoc Tukey's revealed that AA-smokers had significantly less tmax (p<0.001), t1/2 (p<0.012), AUC (p<0.008) and highest Cl (p<0.001) as compared to CC-smokers. The trend was same across all three doses. Conclusion: The study concludes that the systemic metabolism of rasagiline is significantly increased in CYP1A2*AA variants while smoking status did not show consistent difference in PK parameters.

Evaluation of Bone Mineral Density, Serum Osteocalcin, and Osteopontin Levels in Postmenopausal Women with Type 2 Diabetes Mellitus, with/without Osteoporosis.

OBJECTIVE: Osteoporosis (OP) is a worldwide ailment; we aim to establish new biomarkers in diagnosis by determining the levels of serum osteocalcin and osteopontin along with bone mineral density (BMD) and lumbar T-score, in postmenopausal women with type 2 diabetes mellitus (T2DM) with or without OP. METHODS: This observational study included 160 postmenopausal women who were an attendee at outpatient clinics in Al-Hussein Hospital, Thi-Qar province; subdivided into 3 groups based on their T-score testing: Group I (n = 40) comprised postmenopausal women without T2DM as controls, Group II (n = 60) comprised postmenopausal women with T2DM but without OP, and Group III (n = 60) comprised postmenopausal women with T2DM with OP. The dual-energy X-ray absorptiometry was used to measure the BMD (total body, lumbar spine, and femoral) and T-score for lumbar spine and femoral. Glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), osteocalcin, and osteopontin levels were assessed in all three groups. RESULTS: Compared with controls, Group III demonstrated significantly lower BMD (total body, lumbar spine, and femoral), T-score for lumbar spine and femoral, serum osteocalcin, and osteopontin levels than Group II and Group I (P < 0.001). FBG and HbA1c levels were significantly higher in Group III than in Groups I and II (P < 0.001). A negative correlation was proved between HbA1c levels with BMD, osteocalcin levels, and osteopontin levels in the three groups. CONCLUSIONS: Iraqi postmenopausal women with T2DM had a significantly lower bone mineral density, serum osteocalcin, and osteopontin levels. These results may serve as adjuvants in screening for OP, particularly among diabetic patients.

Effect of Ibandronate Therapy on Serum Chemerin, Vaspin, Omentin-1 and Osteoprotegerin (OPG) in Postmenopausal Osteoporotic Females.

Osteoporosis is a condition in which bone mineral density is reduced due to altered bone microstructure, which results in increased skeletal fragility and incidence of various types of fractures. Adipokines such as chemerin, vaspin, omentin-1 and osteoprotegerin are involved in bone remodeling. The current study was designed to determine the changes in circulating chemerin, vaspin, omentin-1, and osteoprotegerin levels after treatment with oral ibandronate 150 mg in postmenopausal osteoporotic females. The present study enrolled 107 postmenopausal osteoporotic females from a tertiary care hospital in Faisalabad, Pakistan, based on stringent inclusion and exclusion criteria. Sixty-six healthy postmenopausal, non-osteoporotic females with no systemic illness were chosen from the general population. The assessment of bone mineral density (BMD) was done using a DEXA scan. Serum levels of chemerin, vaspin, omentin-1 and osteoprotegerin were estimated using commercially available enzyme-linked immunosorbent assay kits. The collected data were analyzed with the Statistical Package for Social Sciences (SPSS) version 24. Following 6 months of ibandronate treatment, there was a significant decrease of 24.24% (p < .033) in serum chemerin levels, as well as a significant increase in serum vaspin levels 343.32% (p < .001) and osteoprotegerin levels 19.57% (p < .001), with no significant change in omentin-1 levels. Thus, an increase in serum chemerin levels and a decrease in serum vaspin and osteoprotegerin levels could be implicated in osteoporosis.

Psychosocial, cultural, and academic challenges to Saudi Arabian students in Australia.

OBJECTIVES: This study investigated the perceptions of Saudi Arabian medical disciplines students undergoing training in various institutes of Australia regarding psychosocial, cultural, and academic challenges. METHODS: This cross-sectional study was from March 15 to June 15, 2019. Data were collected by an online questionnaire. It consisted of questions regarding demographic, psychosocial, cultural, and academic challenges. Two hundred nineteen students studying in Australia responded to our questionnaire. RESULTS: Of the total 219 students, 13(6.0%) were undergraduate, 167(76%) were postgraduate, and 39(18%) were Ph.D. students. For most students (171[79.2%]), Australia was the country of choice for studying. Most of them were satisfied with their academic performance and adjustment to the Australian way of living. Most of the students (180[82.2%]) showed satisfaction over the availability of fair chances of their religious practices in Australia. Few of them faced difficulties coping with the Australian climate (25[11.4%]), homesickness (59[26.9%]), and food and dietary sources (44[20.1%]). Students were overall satisfied with the student advisory system (156[71.2%]), university assessments (147[67.2%]), and available research facilities (170[77.6%]). Among participants, 77 (35.1%), 119(54.3%), and 23(10.5%) students indicated that they wished to stay in Australia only until completion of their studies, temporarily and permanently, respectively. CONCLUSIONS: Our findings showed that Saudi students in Australia had strong psychosocial well-being, cultural integration, and academic success. Most of them were satisfied and adjusted well to Australian culture.

Knowledge, Awareness, and Practices Regarding the Novel Coronavirus Among a Sample of a Pakistani Population: A Cross-Sectional Study.

OBJECTIVES: We aimed to investigate knowledge, attitudes, and practices regarding the new coronavirus in a sample of the general Pakistani population. METHODS: This survey was carried out through The University of Faisalabad (TUF), Pakistan, between February 2020 and April 2020. The questionnaire was circulated on various online platforms to gather information. The data were analyzed on SPSS-22. RESULTS: Out of 2121 respondents (13.7% were male, and 86.3% were females), 7.4% were married, 4.5% had a high income, and 5.8% had fewer family members. Coronavirus disease (COVID-19) knowledge scores were significantly low in the < 21 years age group as compared to the 21 to 25 years age group (P < 0.001) and > 25 years age group (P < 0.001). The males, married community, high income people, and few family members groups had significantly higher coronavirus knowledge than their respective groups (P = 0.033; P = 0.001; P < 0.001; P = 0.042, respectively). CONCLUSION: Our findings suggest that the knowledge score among our study population was not up to the mark. However, a positive correlation between the correct knowledge and appropriate attitude and practice was found among study participants. Older age groups and the high income group were associated with adequate knowledge scores.

Social Media Use, Psychological Distress and Knowledge, Attitude, and Practices Regarding the COVID-19 Among a Sample of the Population of Pakistan.

This study was conducted to assess social media (SM) use, psychological distress, and knowledge, attitude, and practices (KAP) regarding the coronavirus disease 2019 (COVID-19) among a sample of the population of Pakistan. A cross-sectional study was conducted in Multan, Pakistan between April and May 2020. Demographics details, SM use, psychological distress, and KAP on the COVID-19 were investigated. A total of 800 respondents were analyzed out of which 33.5% (n = 268) were women. No gender-wise difference was found in the terms of SM use and duration of SM use. Women were prone to have psychological disorders such as anxiety, depression, and stress than men in the current COVID-19 pandemic. The mean knowledge score of men was significantly higher compared to women (18.69 ± 4.20 vs. 16.89 ± 3.04, p < 0.001), while the mean score of the attitude and practices on the COVID-19 prevention measures was significantly better in women (p = 0.012 and p < 0.001, respectively). The psychological problems such as anxiety (p < 0.001) and depression scores (p = 0.033) were higher among women than men. The stress score was also higher in women but not significantly higher (p = 0.079). The knowledge was significantly correlated with attitude, anxiety, depression, and stress. The regression analysis showed that the COVID-19-related KAPs are the predictors of psychological suffering of an individual. The female gender was positively associated with anxiety and depression. The SM use was the predictor of the stress. Male respondents had significantly more knowledge of the COVID-19 than female respondents, but women had significantly better attitudes and practiced the COVID-19 prevention measures. Gender is a significant determinant of psychological distress and KAP about the COVID-19. The government has already taken significant steps to limit the spread of the disease; however, much more effort is required to tackle this COVID-19 pandemic.

Association of serum chemerin with calcium, alkaline phosphatase and bone mineral density in postmenopausal females.

OBJECTIVES: To investigate the association of serum chemerin with calcium, alkaline phosphatase and bone mineral density in postmenopausal non-osteoporotic and osteoporotic females. METHODS: This cross-section analysis was carried out at the orthopedic department of Madina Teaching Hospital, Faisalabad, Pakistan, in the year 2017-2019. Postmenopausal females were divided into two groups according to their bone mineral density (BMD). All osteoporotic females had a T-score of -2.5 or less. Data were analyzed on SPSS-24. RESULTS: A total of 140 women were included in our study (80 osteoporotic and 60 non-osteoporotic). Non significant difference in age and BMI was observed between osteoporotic and non-osteoporotic subjects (p=0.152) and (p=0.291) respectively. There was a significant difference found in total BMD, serum chemerin levels between osteoporotic and non-osteoporotic subjects p<0.001 in both parameters. No significant correlation of serum chemerin was found with serum calcium, serum alkaline phosphatase and BMD in postmenopausal osteoporotic females (p=0.907), (p=0.318) (p=0.664) respectively. A significant negative correlation was found between serum alkaline phosphatase levels and total BMD in postmenopausal osteoporotic females (p=- 0.039). Linear regression analysis of serum alkaline phosphatase levels with total BMD showed no association between BMD and serum alkaline phosphatase levels (p=0.869). CONCLUSION: There is no association of serum chemerin with calcium, ALP and bone mineral density in non-osteoporotic and osteoporotic postmenopausal females.

Relationship of BMI with Junk Food, sleep pattern, exam performance and awareness about its ill health effects in healthy teenagers.

OBJECTIVE: To evaluate the relationship of body mass index of healthy teenagers with junk food, sleep pattern, exam performance and awareness about its ill effects. METHODS: The cross-sectional study was conducted from March to June 2017 at University Medical and Dental College, University of Faisalabad, Faisalabad, Pakistan, and comprised subjects aged 13-19. Data was collected using face-to-face interviews, getting the examnation results from respective educational insititutions and calculating the body mass index, Data was analysed using SPSS 22. RESULTS: Of the 226 subjects, 96(42.5%) were boys with a mean age of 15.68 ±1.83 years, and 130(57.5%) were girls with a mean age of 17.00±1.74 years. Based on body mass index, 35(15.5%) subjects were underweight, 88(39%) were normal, 28(12.4%) overweight, 56(24.7%) pre-obese and 19(8.4%) were obese. The independent predictors of body mass index were higher consumption of soft drinks in males and higher consumption of soft drinks and salt in females (p<0.05). CONCLUSION: Teenagers were found to be well aware of the ill effects of junk food, but they were found to be happy with their dietary habits and unwilling to change it.

Emotional intelligence and academic performance of students.

The medical profession deals with 'humanism' which involves interactions with people, the ability to think about them, care for them, and to provide positive reinforcement in clinical follow-ups. Emotional intelligence integrates the significant features of personal relationships to promote self-management skills, like adaptability, control of temperaments and reduction of tension, which can improve performance of individuals. This has led to increasing interest in the importance of emotional intelligence for effective academic growth, professional experiences and clinical practice. There are many studies examining the correlation between emotional intelligence and academic achievement at different education levels, signifying its importance to predict students who need guided intervention. With proven relationship between emotional intelligence and academic success, the assessment of emotional intelligence can be introduced in entrance exams of medical schools to recognise students who might need directed intermediation. With the agreement of all stakeholders, emotional intelligence training workshops and awareness sessions can be introduced for educators and students.

Serum resistin levels as predictor of low bone mineral density in postmenopausal women.

Resistin, a novel adipokine may play an important role in bone metabolism. The study is designed to discover the association of bone mineral density (BMD) with serum resistin levels, anthropometric measures and to elucidate serum resistin as a predictor of BMD in postmenopausal women. Postmenopausal women (n = 160) were recruited and divided into two groups, non-osteoporotic (n = 70) and osteoporotic (n = 90). BMD was evaluated by DXA scan. High serum resistin levels and low weight are independent contributors to low BMD and can influence BMD at lumbar spine, right femoral neck, right hip, left femoral neck, and left hip in postmenopausal women.

Association of serum osteoprotegerin with severity of chronic liver disease in female patients: A potential biomarker.

OBJECTIVE: To determine the association of serum osteoprotegerin (OPG) with the severity of chronic liver disease in female patients. METHODS: This case-control study was conducted in Madina Teaching Hospital from 2019-2020.An institutional review board of University Medical and Dental College, The University of Faisalabad gave the approval to conduct the study. Only female patients of age group 40 to 60 years having CLD were included in this study. Total 80 participants were enrolled after fulfilling the inclusion and exclusion criteria. Serum OPG levels were measured by enzyme linked immunosorbant assay (ELISA) supplied by ELAB Sciences, USA. The severity of disease was assessed by Child-Pugh classification. RESULTS: OPG levels were significantly different between the three Child-Pugh classes. OPG levels were significantly high in class C indicating increased level of this cytokine in CLD as compared to class A (p = <0.05). There was a positive association of OPG with splenomegaly (OR = 2.10, p = <0.001), hepatomegaly (OR = 4.41, (p = <0.05), skin pigmentation (OR = 2.06, p = <0.05), malena (OR = 1.87, p = <0.05) and prolonged bleeding (OR = 1.86, p = <0.05). CONCLUSION: The levels of serum Osteoprotegerin is increased in severe form of chronic liver disease (Class C) of Child-Pughs classification as compared to mild (Class A) and moderate (Class B) forms of Child-Pughs classification.

Venetoclax in the Treatment of Chronic Lymphocytic Leukemia: Evidence, Expectations, and Future Prospects.

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the western adult population; it is also prevalent worldwide. The B cell lymphoma-2 (BCL-2) family proteins play a key role in regulating intrinsic apoptosis and, in many cancers, are the main culprits behind tumor survival and therapy resistance. Hence, the role of BCL-2 inhibitors is very beneficial in the treatment of CLL. Venetoclax is the first selective, orally bioavailable BCL-2 inhibitor. This review article discusses factors such as the pharmacokinetics, pharmacodynamics, acquired resistance to venetoclax, responders vs. non-responders in venetoclax monotherapy, and the synergistic role of venetoclax with other drugs in detail. Venetoclax is the first BH3 mimetic drug and selective BCL-2 inhibitor that has received FDA approval. This drug has proved to provide good therapeutic responses in CLL patients irrespective of the presence of adverse clinical or genetic features, including in patients with relapsed or refractory forms of CLL. We anticipate that novel combination therapies, including venetoclax and immunotherapy, will further alter the treatment landscape for patients with relapsed CLL, particularly for those with deletion 17p (del 17p) CLL, which carries a very poor prognosis.