Potentially harmful advantage to athletes: a putative connection between UGT2B17 gene deletion polymorphism and renal disorders with prolonged use of anabolic androgenic steroids

ABSTRACT: BACKGROUND AND OBJECTIVE: With prolonged use of anabolic androgenic steroids (AAS), occasional incidents of renal disorders have been observed. Independently, it has also been established that there are considerable inter-individual and inter-ethnic differences, in particular with reference to the uridine diphosphate-glucuronosyltransferase 2B17 (UGT2B17) gene, in metabolising these compounds. This report postulates the association of deletion polymorphism in the UGT2B17 gene with the occurrence of renal disorders on chronic exposure to AAS. PRESENTATION OF THE HYPOTHESIS: The major deactivation and elimination pathway of AASs is through glucuronide conjugation, chiefly catalyzed by the UGT2B17 enzyme, followed by excretion in urine. Excretion of steroids is affected in individuals with a deletion mutation in the UGT2B17 gene. We hypothesize that UGT2B17 deficient individuals are more vulnerable to developing renal disorders with prolonged use of AAS owing to increases in body mass index and possible direct toxic effects of steroids on the kidneys. Elevated serum levels of biologically active steroids due to inadequate elimination can lead to prolonged muscle build up. An increase in body mass index may cause renal injuries due to sustained elevated glomerular pressure and flow rate. TESTING THE HYPOTHESIS: In the absence of controlled clinical trials in humans, observational studies can be carried out. Real time PCR with allelic discrimination should be employed to examine the prevalence of different UGT2B17 genotypes in patients with impaired renal function and AAS abuse. In individuals with the UGT2B17 deletion polymorphism, blood tests, biofluid analyses, urinalysis, and hair analyses following the administration of an anabolic steroid can be used to determine the fate of the substance once in the body. IMPLICATIONS OF THE HYPOTHESIS: If the hypothesis is upheld, anabolic steroid users with a deletion mutation in the UGT2B17 gene may be exposed to an increased risk of developing renal disorders. In the current detecting - sanctioning anti-doping system, athletes motivated by the potential to evade detection owing to their unique genetic make-up could subject themselves to a serious health consequence. More research on AAS metabolism in the presence of UGT2B17 gene deletion is required. Benefit - harm evaluations in therapeutic use of anabolic steroids should also consider this potential link between UGT2B17 gene deletion polymorphism and renal disorders

Impact of diabetes-related knowledge and medication adherence on quality of life among type 2 diabetes patients in a tertiary health facility in Multan, Pakistan

Purpose: To assess the impact of drug adherence and diabetes-related knowledge on the quality of life (QoL) of type 2 diabetes patients in a hospital in Pakistan.Methods: A cross-sectional study was conducted in City Hospital, Multan, Pakistan between March and September 2020. A total of 151 patients diagnosed with type 2 diabetes mellitus (T2DM) were recruited. Medication adherence, diabetes-related knowledge, and QoL were assessed by Drug attitude inventory-10 (DAI-10), the Michigan Diabetes Knowledge Test (MDKT), and EQ-5D-3L tools, respectively. The association between sociodemographic data and study variables was assessed by independent t-test and one-way ANOVA.Results: Among the 151 patients, 53 % were males. The mean MDKT score was 0.33 ± 0.18, indicating poor knowledge of diabetes. An overall moderate level of adherence was observed among the participants (mean adherence score, 6.14 ± 1.39). Mean QoL score was 1.31 ± 0.28, and the Visual Analog Scale score (VAS) was 59.6 ± 12.21, indicating a good to moderate QoL among the study participants. Study participants with a longer duration of diabetes and poor adherence to their medications showed poor QoL (p = 0.01, p = 0.004 respectively).Conclusion: Overall, the patients reported poor knowledge, moderate adherence, and good to moderate QoL. Moreover, patients with poor adherence to medication, longer duration of diabetes, and poorly controlled HbA1c showed poor QoL

Assessment of medication prescription errors and their contributory factors in major cities of Punjab Province, Pakistan: A cross-sectional survey

Purpose: To evaluate the prescription errors and their contributory factors in Punjab, Pakistan.Methods: An observational, cross-sectional study was conducted in 12 major cities of Punjab, Pakistan. A total of 1,184 prescriptions were collected from patients using a convenient sampling method from homes, pharmacies, clinics, and hospitals. The data were presented in frequency and percentage using descriptive statistics. To determine the association between the variables assessed, Chi-square (X2) test was used.Results: A total of 1,184 prescriptions were analyzed; 432 of them (36.5 %) were from prescribers who are graduate degree holders, and 752 (63.5 %) from prescribers who are post-graduate degree holders. The most commonly missing parameters in the prescriptions were the age of the patients (835 representing 29.4 %), signatures of the prescribers (755 representing 26.5 %), and prefix (622 representing 21.9 %). The number of prescription errors was significantly correlated to prescriber qualification (p = 0.001). The prescription errors were more common in age groups of prescribers: 21 - 30 years (654 representing 23.0 %), and 31 - 40 years (1,012 representing 35.6 %) (p = 0.001). The higher number of prescription errors by post-graduate prescribers working in teaching hospitals can be attributed to the higher patient load and lack of continuing medical education programs for the prescribers.Conclusion: The government should take necessary measures for the implementation of electronic prescribing systems, and devise mechanisms for the uniform distribution of patient load amongst the prescribers working in different hospitals. Keywords: Prescription error, Prescribers, Patient load, Continuing medical education, Electronic prescribin

Assessing Knowledge and Perception Regarding Antimicrobial Stewardship and Antimicrobial Resistance in University Students of Pakistan: Findings and Implications

The irrational use of antimicrobials has enormously contributed to antimicrobial resistance (AMR) globally and especially in the developing world. To assess the knowledge and perception regarding AMR and antimicrobial stewardship (AMS), a descriptive cross-sectional study was carried out in university students enrolled in pharmacy, veterinary, and biology programs by using an online self-administered questionnaire. The Chi-square and Fisher exact tests (where applicable) were performed to assess the association of the demographics with the students’ knowledge and perception regarding AMR and AMS. A total of 496 students completed the questionnaire, among which, 85.7% of the participants were familiar with the term AMR and 79.4% of the participants correctly identified a poorly designed dosing regimen as a contributing factor towards AMR. The majority of participants (57.9%) were familiar with the term AMS and 86.5% were aware of the aim of AMS. The participants showed good knowledge regarding AMR and AMS, but to further improve student knowledge and perception of AMS and AMR, it is suggested that dedicated modules on antibiotic use and AMS should be incorporated into the curricula of these undergraduate and postgraduate programs

Virtue or pretense? Looking behind self-declared innocence in doping

BACKGROUND: Social science studies of doping practices in sport rely predominantly on self-reports. Studies of psychoactive drug use indicate that self-reporting is characterised by under-reporting. Likewise doping practice is likely to be equally under-reported, if not more so. This calls for more sophisticated methods for such reporting and for independent, objective validation of its results. The aims of this study were: i) to contrast self-reported doping use with objective results from chemical hair analysis and ii) to investigate the influence of the discrepancy on doping attitudes, social projection, descriptive norms and perceived pressure to use doping. METHODOLOGY/PRINCIPAL FINDINGS: A doping attitudes questionnaire was developed and combined with a response latency-based implicit association test and hair sample analysis for key doping substances in 14 athletes selected from a larger sample (N = 82) to form contrast comparison groups. Results indicate that patterns of group differences in social projection, explicit attitude about and perceived pressure to use doping, vary depending on whether the user and non-user groups are defined by self-report or objectively verified through hair analysis. Thus, self-confessed users scored higher on social projection, explicit attitude to doping and perceived pressure. However, when a doping substance was detected in the hair of an athlete who denied doping use, their self-report evidenced extreme social desirability (negative attitude, low projection and low perceived pressure) and contrasted sharply with a more positive estimate of their implicit doping attitude. CONCLUSIONS/SIGNIFICANCE: Hair analysis for performance enhancing substances has shown considerable potential in validating athletes' doping attitude estimations and admissions of use. Results not only confirm the need for improved self-report methodology for future research in socially-sensitive domains but also indicate where the improvements are likely to come from: as chemical validation remains expensive, a more realistic promise for large scale studies and online data collection efforts is held by measures of implicit social cognition

Comparison of Cross-Entropy Based MCDM Approach for Selection of Material in Sugar Industry

One of the major problems faced in engineering is the selection of the material which is most suitable for the product. Material selection from a large number with diverse mechanical, physical and chemical properties and choosing the best material which is the most satisfying for making the job is a very complex process. Material selection is important as it determines durability, reliability and cost of the product. Selection of suitable material which gives maximum performance with minimum cost is often observed to be a multi-criterion decision-making (MCDM) problem with different objectives. This chapter presents an integrated approach to select the suitable material to be used as base of induction cookware which can give maximum performance with minimum cost. In the integrated approach the weights of the criteria are computed using the cross-entropy method and ranking of the alternatives is done using the different MCDM methods. The methods are further illustrated with an example and the result obtained from different cross-entropy MCDM methods are compared for finding the most suitable method for serving the purpose