The Personalization of Clopidogrel Antiplatelet Therapy: The Role of Integrative Pharmacogenetics and Pharmacometabolomics

Dual antiplatelet therapy of aspirin and clopidogrel is pivotal for patients undergoing percutaneous coronary intervention. However, the variable platelets reactivity response to clopidogrel may lead to outcome failure and recurrence of cardiovascular events. Although many genetic and nongenetic factors are known, great portion of clopidogrel variable platelets reactivity remain unexplained which challenges the personalization of clopidogrel therapy. Current methods for clopidogrel personalization include CYP2C19 genotyping, pharmacokinetics, and platelets function testing. However, these methods lack precise prediction of clopidogrel outcome, often leading to insufficient prediction. Pharmacometabolomics which is an approach to identify novel biomarkers of drug response or toxicity in biofluids has been investigated to predict drug response. The advantage of pharmacometabolomics is that it does not only predict the response but also provide extensive information on the metabolic pathways implicated with the response. Integrating pharmacogenetics with pharmacometabolomics can give insight on unknown genetic and nongenetic factors associated with the response.This review aimed to review the literature on factors associated with the variable platelets reactivity response to clopidogrel, as well as appraising current methods for the personalization of clopidogrel therapy. We also aimed to review the literature on using pharmacometabolomics approach to predict drug response, as well as discussing the plausibility of using it to predict clopidogrel outcome

Evaluating Social Participation among the People with Spinal Cord Injury of Dhaka District in Bangladesh

Introduction: People with spinal cord injuries (SCI) have faced many challenges in their community life after completing their rehabilitation. Some of them can engage in their social events in a modifying way, but many of them can not engage in their social events properly. It also restricts their ability and quality of life. This study identified the level of participation among people with SCI in the community of Dhaka district. The purpose of this study was to evaluate the social participation among people living with spinal cord injury. Materials and Methods: The study was conducted through cross-sectional design in the quantitative study among 70 participants whose age was 18-70 years who completed the rehabilitation program. By using a purposive sampling technique participants were selected for the study based on the inclusion criteria. Data were collected using a structured socio-demographic profile sheet and the Participation Scale (P-scale). Data were collected by face-to-face interviews and also used the “Participation scale”. Results: The findings reveal that 29% of respondents reported no significant restriction in participation, 44% experienced mild restriction, 19% had moderate restriction, 7% had severe restriction, and 1% faced extreme restriction. A substantial proportion of participants (80%) reported secondary complications, including pain (24%), pressure sores (19%) and urinary tract infections (20%). Adequate financial resources and social support were identified as key facilitators of participation, while physical environment, unsupportive social attitudes, and mental health issues were significant barriers. Conclusion: The study highlights the urgent need for specific interventions and supports to enhance social participation for individuals with SCI. Recommendations include improving accessibility, increasing resources and training for healthcare professionals, implementing public awareness campaigns to reduce stigma, and fostering collaboration between government and non-governmental organizations to create a more inclusive environment that supports participation and enhances the quality of life for people with SCI.&nbsp

Shear capacity evaluation of reinforced concrete beams: finite element simulation

The shear performance of reinforced concrete beams with rectangle cross-section and two different continuous rectangular spiral shear reinforcement under monotonous loading is numerically evaluated. Further, the behaviour of two continuous shear reinforcement systems named, “Single Square Spring Shear Resistance System” (SSSSRS) and “Double Square Spring Shear Resistance System” (DSSSRS) as transverse reinforcements are compared with conventional discontinuous system “Stirrups”. The finite element study includes three (3) beams. The results clearly show that the application of continuous shear reinforcement system delivered improved shear behaviour and enhanced bearing capacity in beams. Beams with Single Square Spring Shear Resistance System (SSSSRS) and Double Square Spring Shear Resistance System (DSSSRS) exhibited 14.4% and 19.8% increased shear performance in comparison with conventional control beam. It was concluded that under the same deflection higher forces was achieved for “Single Square Spring Shear Resistance System” (SSSSRS) and “Double Square Spring Shear Resistance System” (DSSSRS) compared to control specimens

Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91 462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 × 10-8).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee

Anonymity preserving and lightweight multi-medical server authentication protocol for telecare medical information system

Electronic health systems, such as Telecare Medical Information System (TMIS), allow patients to exchange their health information with a medical center/doctor for diagnosis in real-time, and across borders. Given the sensitive nature of health information/medical data, ensuring the security of such systems is crucial. In this paper, we revisit Das et al.'s authentication protocol, which is designed to ensure patient anonymity and untraceability. Then, we demonstrate that the security claims are invalid, by showing how both security features (i.e., patient anonymity and untraceability) can be compromised. We also demonstrate that the protocol suffers from smartcard launch attacks. To mitigate such design flaws, we propose a new lightweight authentication protocol using the cryptographic hash function for TMIS. We then analyze the security of the proposed protocol using AVISPA and Scyther, two widely used formal specification tools. The performance analysis demonstrates that our protocol is more efficient than other competing protocols

Critical success factors of the financial performance of commercial private banks: A study in a developing nation

This study’s objective is to examine the impact of employee innovativeness, readiness to change, employee creativity, and learning capability on the financial performance of private banks in Bangladesh. The study involved 334 bank employees from three prominent private banks in Bangladesh. Those banks were selected with better ratings by the central bank and have several branches across the country. First, branch managers were contacted about this study and collected employee emails from each branch information desk. Then, email invitations were sent to each employee of the selected bank branches. This study involved branch managers, senior officers, officers, and junior bank executives. Past studies also considered senior and junior bank officers as they directly contribute to a bank’s performance. The study utilized a methodical questionnaire to assess the three independent variables: employee innovativeness, readiness to change, and learning capability. The dependent variable in this study was financial performance, which was assessed through key financial indicators such as profitability and sales growth over three years. SPSS was utilized to conduct hypothesis testing by considering 95% confidence interval. Correlation results show that all three independent variables were significantly correlated with the bank’s financial performance. The study’s regression results suggest that bank employees’ readiness to change (β value = 0.393) significantly impacts the bank’s financial performance, followed by employee innovativeness (β value = 0.338). On the other hand, employees’ learning capability (β value = 0.202) has the least significant impact on financial performance. Moreover, three independent variables explain 42.9% variance in bank financial performance

GWAS for executive function and processing speed suggests involvement of the CADM2 gene

To identify common variants contributing to normal variation in two specific domains of cognitive functioning, we conducted a genome-wide association study (GWAS) of executive functioning and information processing speed in non-demented older adults from the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) consortium. Neuropsychological testing was available for 5429-32 070 subjects of European ancestry aged 45 years or older, free of dementia and clinical stroke at the time of cognitive testing from 20 cohorts in the discovery phase. We analyzed performance on the Trail Making Test parts A and B, the Letter Digit Substitution Test (LDST), the Digit Symbol Substitution Task (DSST), semantic and phonemic fluency tests, and the Stroop Color and Word Test. Replication was sought in 1311-21860 subjects from 20 independent cohorts. A significant association was observed in the discovery cohorts for the single-nucleotide polymorphism (SNP) rs17518584 (discovery P-value=3.12 × 10(-8)) and in the joint discovery and replication meta-analysis (P-value=3.28 × 10(-9) after adjustment for age, gender and education) in an intron of the gene cell adhesion molecule 2 (CADM2) for performance on the LDST/DSST. Rs17518584 is located about 170 kb upstream of the transcription start site of the major transcript for the CADM2 gene, but is within an intron of a variant transcript that includes an alternative first exon. The variant is associated with expression of CADM2 in the cingulate cortex (P-value=4 × 10(-4)). The protein encoded by CADM2 is involved in glutamate signaling (P-value=7.22 × 10(-15)), gamma-aminobutyric acid (GABA) transport (P-value=1.36 × 10(-11)) and neuron cell-cell adhesion (P-value=1.48 × 10(-13)). Our findings suggest that genetic variation in the CADM2 gene is associated with individual differences in information processing speed.Molecular Psychiatry advance online publication, 14 April 2015; doi:10.1038/mp.2015.37

Proportion and Risk Factors of Internet Addiction among Medical Students in A Medical College in A Non-Metropolitan City in West Bengal

Introduction: Internet addiction (IA) is an emerging public health problem worldwide, especially among adolescents and young adults. Medical students, due to high academic pressure and easy access to digital platforms, are particularly vulnerable. This study aimed to determine the prevalence of internet addiction and factors associated with moderate to severe internet addiction among undergraduate medical students in a government medical college of West Bengal. Materials and Methods: A descriptive cross-sectional study was conducted June to August 2024 among 63 second-year MBBS students at Jalpaiguri Government Medical College. Data were collected using a pretested questionnaire and the Young’s Internet Addiction Test (IAT). Sociodemographic variables and internet use patterns were assessed. Univariate logistic regression was used to identify predictors of moderate to severe internet addiction. Results: The mean age of participants was 21.9 (±1.5) years; 69.8% were male. Overall, 41.3% showed some level of internet addiction—23.8% mild, 14.3% moderate, and 3.2% severe. On univariate analysis, using more than one gadget for internet access (OR=3.7, 95% CI:1.0–13.9), internet use >6 hours/day (OR=13.2, 95% CI:1.2–140.7), and father’s postgraduate education (OR=6.6, 95% CI:1.5–28.5) were significant predictors. Initiating internet use at 16–20 years was protective (OR=0.22, 95% CI:0.07–0.69). Conclusion: A substantial proportion of medical undergraduates were affected by internet addiction. Longer screen time, access via multiple devices, and socio-familial factors were strongly associated with higher odds of moderate to severe addiction.

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics