The Relationship Between GAPDH Gene Polymorphism and Risk of Acute Coronary Syndrome in South Indians with Type 2 Diabetes Mellitus.

As glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is one of the regulators of carbonyl stress, a pathogenic mechanism for diabetic complications like acute coronary syndrome (ACS), the study aimed to investigate the relationship between GAPDH gene polymorphism, GAPDH activity in red blood cell (RBC), methylglyoxal (MG) levels in plasma and ACS risk in South Indians with type 2 diabetes mellitus (T2DM). This study comprised 150 T2DM with ACS as cases and 150 T2DM without ACS as controls. The GAPDH rs1136666, rs1060620 and rs1060619 gene polymorphisms were identified by TaqMan probe assays. The RBC GAPDH activity and plasma MG levels were estimated. Cases had significantly higher plasma MG levels and lower RBC GAPDH activity than controls (P < 0.001). The distribution of rs1060620 or rs1060619 alleles and genotypes significantly differed between groups. The rs1060620 AG (OR 0.55; 95% CI 0.33-0.92; P = 0.022) or rs1060619 CT (OR 0.51; 95% CI 0.31-0.83; P = 0.007) genotype was associated with reduced ACS risk, confirmed in the over-dominant genetic model. Haplotype analyses revealed that the GAT and CGC haplotypes were associated with increased (OR 28.37; 95% CI 3.82-210.49; P = 8.51 × 10-7) and decreased (OR 0.45; 95% CI 0.24-0.86; P = 0.014) ACS risk in T2DM patients, respectively. Lower GAPDH activity was observed in the TT and CT genotypes compared to the CC genotype of rs1060619 (P < 0.001). This work established that the GAPDH rs1060620 or rs1060619 gene polymorphisms are associated with ACS risk in South Indians with T2DM.

Training in cardiothoracic surgery: The role for simulation.

Adequate cardiothoracic surgical training is essential for provision of quality care to patients. In recent years, simulation-based training has been advocated as an adjunct to traditional surgical training. Advances in simulation technology has resulted in many low- and highfidelity simulators being employed in cardiothoracic surgical training. Such models allow trainees to practice an array of realistic full-length procedures in a safe and controlled environment, with the window to make mistakes and consider them learning points. There is significant evidence to demonstrate the effectiveness of cardiothoracic surgery simulation in improving surgical skills and operating room performances in addition to building confidence among trainees. However, owing to the high financial cost of arranging it, simulation-based training is not widespread in low- and middle-income countries, including Pakistan. More work is warranted on the cost effectiveness of implementing simulation-based learning, which, in turn, would increase the uptake of simulation to enhance cardiothoracic surgical training in Pakistan.

GC-MS validation and analysis of targeted plasma metabolites related to carbonyl stress in type 2 diabetes mellitus patients with and without acute coronary syndrome.

Methylglyoxal (MG) is responsible for advanced glycation end-product formation, the mechanisms leading to diabetes pathogenesis and complications like acute coronary syndrome (ACS). Sugar metabolites, amino acids and fatty acids are possible substrates for MG. The study aimed to measure plasma MG substrate levels using a validated gas chromatography-mass spectrometry (GC-MS) method and explore their association with ACS risk in type 2 diabetes mellitus (T2DM). The study included 150 T2DM patients with ACS as cases and 150 T2DM without ACS as controls for the analysis of glucose, fructose, ribulose, sorbitol, glycerol, pyruvate, lactate, glycine, serine, threonine, C16:0, C16:1, C18:0, C18:1, C18:2, C18:3, C20:0 and C22:6 by GC-MS. Validated GC-MS methods were accurate, precise and sensitive. Cases significantly differed in plasma MG and metabolite levels except for lactate, C16:0, C18:0, C18:2, and C18:3 levels compared with controls. On multivariable logistic regression, plasma C20:0, C18:1, glycine and glycerol levels had increased odds of ACS risk. On multivariate receiver operating characteristic analysis, a model containing plasma C20:0, C16:1, C18:1, C18:2, serine, glycerol, lactate and threonine levels had the highest area under the curve value (0.932) for ACS diagnosis. In conclusion, plasma C20:0, C16:1, C18:1, glycine, glycerol and sorbitol levels were associated with ACS risk in T2DM.

Fluorescence in neurosurgery: its therapeutic and diagnostic significance - a comprehensive review.

This review provides a comprehensive overview of the therapeutic and diagnostic implications of fluorescence imaging in neurosurgery. Fluorescence imaging has become a valuable intraoperative visualization and guidance tool, facilitating precise surgical interventions. The therapeutic role of fluorescence is examined, including its application in photodynamic therapy and tumor-targeted therapy. It also explores its diagnostic capabilities in tumor detection, margin assessment, and blood-brain barrier evaluation. Drawing from clinical and preclinical studies, the review underscores the growing evidence supporting the efficacy of fluorescence imaging in neurosurgical practice. Furthermore, it discusses current limitations and future directions, emphasizing the potential for emerging technologies to enhance the utility and accessibility of fluorescence imaging, ultimately improving patient outcomes in neurosurgery.

Exploring the current and prospective role of artificial intelligence in disease diagnosis.

Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems, providing assistance in a variety of patient care and health systems. The aim of this review is to contribute valuable insights to the ongoing discourse on the transformative potential of AI in healthcare, providing a nuanced understanding of its current applications, future possibilities, and associated challenges. The authors conducted a literature search on the current role of AI in disease diagnosis and its possible future applications using PubMed, Google Scholar, and ResearchGate within 10 years. Our investigation revealed that AI, encompassing machine-learning and deep-learning techniques, has become integral to healthcare, facilitating immediate access to evidence-based guidelines, the latest medical literature, and tools for generating differential diagnoses. However, our research also acknowledges the limitations of current AI methodologies in disease diagnosis and explores uncertainties and obstacles associated with the complete integration of AI into clinical practice. This review has highlighted the critical significance of integrating AI into the medical healthcare framework and meticulously examined the evolutionary trajectory of healthcare-oriented AI from its inception, delving into the current state of development and projecting the extent of reliance on AI in the future. The authors have found that central to this study is the exploration of how the strategic integration of AI can accelerate the diagnostic process, heighten diagnostic accuracy, and enhance overall operational efficiency, concurrently relieving the burdens faced by healthcare practitioners.

Dual-chamber versus single chamber pacemakers, a systemic review and meta-analysis on sick sinus syndrome and atrioventricular block patients.

Aims: The atrioventricular block (AVB) is a conduction system problem that results from the impairment in the transmission of an impulse from the atria to the ventricle, the disease has many etiologies. This article aimed to evaluate the efficacy and safety of dual and single-chamber pacemakers in patients with SSS and AVB. Methods: An electronic search of PubMed (Medline), EMBASE, and Google Scholar was performed from 2000 till August 15th, 2022. Retrieved articles were exported to Endnote Reference Library Software, where duplicate studies were removed from the list, and only articles meeting the eligibility criteria of this study were selected. RevMan 5.4 and STATA 16 software were used for the analysis. The modified Cochrane Collaboration's risk of bias and New-castle Ottawa scale were used for quality assessment of RCTs and observational studies respectively. Results: This study is composed of 8953 patients with sick-sinus syndrome and atrioventricular block. A total of thirteen outcomes are included in this meta-analysis, out of which atrial fibrillation significantly favored dual chamber [OR = 1.29; 95 % CI = 1.05-1.59; P = 0.01 I2 = 29 %] and overall complications [OR = 0.48; 95 % CI = 0.29-0.77; p = 0.03 I2 = 0 %] and pneumothorax [OR = 0.31; 95 % CI = 0.10-0.93; p = 0.04, I2 = 0 %] were satisfied by single-chamber pacing. Conclusion: This study concluded that neither single-chamber nor dual-chamber pacemakers are superior to each other, but they are unique in their own ways as the results of this study manifest remarkable reduction in atrial fibrillation rates and pneumothorax using dual-chamber and single-chamber pacemakers respectively.

Vitamin D and preeclampsia: A systematic review and meta-analysis.

Objectives: Preeclampsia is one of the most frequent pregnancy disorders, with a global incidence of 2%-8%. Serum 25-hydroxyvitamin D is an essential mineral for human health; some studies suggest link between 25-hydroxyvitamin D deficiency and preeclampsia, while others offer contradictory findings. Thus, the goal of this study is to evaluate the relationships between maternal 25- hydroxyvitamin D concentrations and the risk of preeclampsia. In addition to this, our study also evaluates the effects of 25- hydroxyvitamin D supplementation on the incidence of preeclampsia. Therefore, assessing 25- hydroxyvitamin D's potential as a possible intervention to lower the risk of preeclampsia. Methods: The Medline database was queried from inception until July 2021 for randomized controlled trials and observational studies without any restrictions. The studies assessing the association between 25-hydroxyvitamin D deficiency and preeclampsia and the impact of 25-hydroxyvitamin D supplementation on the incidence of preeclampsia were incorporated. The results were reported using a random-effects meta-analysis and the Mantel-Haenszel odds ratio. A p-value of <0.05 was considered significant for the analysis. Results: This analysis includes 34 papers, including 10 randomized controlled trials and 24 observational studies. According to our pooled analysis, 25-hydroxyvitamin D supplementation was significantly associated with a lower risk of preeclampsia in pregnant women (OR: 0.50; 95% CI: 0.40-0.63; p = 0.00001), while 25-hydroxyvitamin D deficiency was significantly associated with an increased risk of preeclampsia (OR: 4.30; 95 % CI: 2.57-7.18; p < 0.00001, OR: 1.71; 95 % Cl: 1.27-2.32; p = 0.0005, OR 1.61; 95 % Cl: 1.21-2.16; p = 0.001). Conclusion: Results suggest that 25-hydroxyvitamin D has a significant relationship with preeclampsia as confirmed by the findings that low maternal 25-hydroxyvitamin D concentrations cause increased risk of preeclampsia while 25-hydroxyvitamin D supplementation reduces the incidence of preeclampsia. Our findings indicate that 25-hydroxyvitamin D supplementation can be used as a possible intervention strategy in preventing one of the most common causes of maternal mortality around the world, preeclampsia.

The genetic polymorphisms and activity of glyoxalase 1 as a risk factor for acute coronary syndrome in South Indians with type 2 diabetes mellitus.

OBJECTIVE: The individuals' genetic traits predispose them to a higher or lower risk of Type 2 diabetes mellitus (T2DM) and its complications, for example, acute coronary syndrome (ACS). As carbonyl stress is responsible for the pathogenesis and complications of T2DM, and glyoxalase 1 (GLO1) is the most crucial determinant of carbonyl stress, the study aimed to explore the association between GLO1 gene polymorphism, GLO1 activity in red blood cell (RBC), plasma methylglyoxal (MG) levels, and ACS risk in South Indian T2DM patients. METHODS: A total of 150 T2DM patients with ACS as cases and 150 T2DM patients without ACS as controls were recruited in a case-control study. The rs4746, rs1049346 and rs1130534 of the GLO1 gene were analysed using TaqMan allele discrimination assay. The RBC GLO1 activity and plasma MG levels were measured. RESULTS: Significantly lower RBC GLO1 activity and higher plasma MG levels were found in cases compared to controls (p < 0.001 and p = 0.008, respectively). The genotype and allele frequencies of rs1049346 significantly differed between cases and controls (p < 0.001). For rs1130534 and rs1049346, no significant difference was found. For rs1049346, the TT and CC genotypes were associated with higher (p = 0.002) and lower (p = 0.001) ACS risk, respectively, in various genetic models. The TT genotype of rs1049346 was associated with lower RBC GLO1 activity (p = 0.004) and higher MG level (p = 0.010). In haplotype analysis, higher ACS susceptibility with the TAT haplotype (p < 0.001) and lower ACS susceptibility with the TAC haplotype (p < 0.001) were observed. Also, lower RBC GLO1 activity was associated with the TAT haplotype (p = 0.002). CONCLUSIONS: The rs1049346 of the GLO1 gene may be associated with ACS risk in South Indian T2DM patients, and the T and C allele might be essential precipitating and protective factors, respectively.

Frequency and Factors of Sleep Paralysis Among Medical Students of Karachi.

INTRODUCTION: Sleep paralysis is a prevalent phenomenon characterized by suffocation, immobility, and hallucinations. Its causes remain unknown, although the neurotransmitter imbalance is suggested as a potential factor. This condition is closely associated with hallucinations and a sense of intrusion, often observed in patients with narcolepsy, hypertension, and seizures. METHODS: A cross-sectional study was conducted in various medical colleges in Karachi, involving 297 participants aged 18 to 30 years. The participants were divided into groups based on gender and year of study. They were surveyed about the frequency of sleep paralysis episodes, their beliefs about the phenomenon, sleep routines, and academic impacts. RESULTS: Among the respondents, a significant number of females (n=209, 70.3%) reported experiencing sleep paralysis. The overall mean age was 20±2.0 years. Correlation analysis revealed an insignificant relationship between depression and mental anxiety (p=0.147). Similarly, no significant association was found when comparing the occurrence of sleep paralysis (p=0.16). However, a notable finding was the significant link between sleep paralysis and its impact on academics (p=0.043). CONCLUSION: This study highlighted the frequency of sleep paralysis among medical students, particularly among females. Furthermore, it emphasizes the diverse beliefs held by individuals regarding these frightening episodes. To address this neglected issue, it is essential to conduct awareness sessions aimed at understanding and alleviating sleep paralysis in individuals' lives.

SARS-CoV-2: Has artificial intelligence stood the test of time.

ABSTRACT: Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government-public relations.

Application in medicine: Has artificial intelligence stood the test of time.

ABSTRACT: Artificial intelligence (AI) has proven time and time again to be a game-changer innovation in every walk of life, including medicine. Introduced by Dr. Gunn in 1976 to accurately diagnose acute abdominal pain and list potential differentials, AI has since come a long way. In particular, AI has been aiding in radiological diagnoses with good sensitivity and specificity by using machine learning algorithms. With the coronavirus disease 2019 pandemic, AI has proven to be more than just a tool to facilitate healthcare workers in decision making and limiting physician-patient contact during the pandemic. It has guided governments and key policymakers in formulating and implementing laws, such as lockdowns and travel restrictions, to curb the spread of this viral disease. This has been made possible by the use of social media to map severe acute respiratory syndrome coronavirus 2 hotspots, laying the basis of the "smart lockdown" strategy that has been adopted globally. However, these benefits might be accompanied with concerns regarding privacy and unconsented surveillance, necessitating authorities to develop sincere and ethical government-public relations.

Disparities in access to quality surgical care for women in resource-constrained settings: Bottlenecks and the way forward.

Women seeking surgical care are burdened with gender disparities, particularly in resource-limited settings. Such disparities can lead to women often presenting late with advanced disease and poor prognoses. The current narrative review was planned to find evidence for gender disparities, their implications, challenges faced by women seeking surgical care, and strategies to address them. Potentiating from interplay between various societal, sociocultural, and economic barriers, the main challenges included inadequate autonomy, financial constraints, transport and referral issues, lack of experienced women surgeons, privacy concerns, surgeon distrust, and higher thresholds for seeking care. While research revealed these underlying causes, much work remains for governmental healthcare bodies, the international community, surgical leadership, policymakers, surgeons, and family members of patients to act on the highlighted issues. Unrestricted access to quality surgical care for everyone is of vital importance, and can translate into a significant decrease in preventable disabilities and deaths among women in resource-constrained settings.

Perioperative registries in resource-limited settings: The way forward for Pakistan.

Capable of improving surgical quality, perioperative registries can allow performance benchmarking, reliable reporting and the development of risk-prediction models. Well established in high-income countries, perioperative registries remain limited in lower- and middle-income countries due to several challenges. First, ensuring comprehensive data entry forums to power the registries is difficult because of limited electronic medical records requiring sustained efforts to develop and integrate these into practice. Second, lack of adequate expertise and resources to develop and maintain registry software necessitates the involvement of software developers and information technology personnel. Third, case ascertainment and item completion are challenging secondary to poor-quality medical records and high loss-to-follow-up rates, requiring telemedicine initiatives as an adjunct to existing care for the assessment of post-discharge outcomes. Lastly, standardised coding of clinical terminology is warranted for ensuring interoperability of the registries for which adaptation of the existing disease and procedural codes can be a sustainable and cost-effective alternative to the development of new codes.

PakSurg: The first trainee-lead model for multicenter surgical research collaboration in Pakistan.

We describe creation and piloting of the PakSurg Collaborative, devised via integration of existing trainee-led collaborative models in the United Kingdom with the resource-limited surgical care in Pakistan. This is the first trainee-lead surgical research collaborative in Pakistan, established by the student-lead Surgery Interest Group from the Aga Khan University. The project involved creation of a model that included a steering committee comprising of five teams which worked in conjunction with collaborators from multiple hospitals. To facilitate this collaboration, a comprehensive and cost-efficient study management pathway was developed. The PakSurg Collaborative has the potential to deliver methodologically robust, high-quality, multicenter surgical evidence from Pakistan. This nationally representative data could inform evidence-based surgical guidelines, potentially translating into improved outcomes for patients undergoing surgery.

Thrombosis with Thrombocytopenia Syndrome After Administration of AZD1222 or Ad26.COV2.S Vaccine for COVID-19: A Systematic Review.

BACKGROUND: Cases of thrombosis with thrombocytopenia syndrome (TTS) have been reported following vaccination with AZD1222 or Ad26.COV2.S. This review aimed to explore the pathophysiology, epidemiology, diagnosis, management, and prognosis of TTS. METHODS: A systematic review was conducted to identify evidence on TTS till 4th September 2021. Case reports and series reporting patient-level data were included. Descriptive statistics were reported and compared across patients with different sexes, age groups, vaccines, types of thrombosis, and outcomes. FINDINGS: Sixty-two studies reporting 160 cases were included from 16 countries. Patients were predominantly females with a median age of 42.50 (22) years. AZD1222 was administered to 140 patients (87·5%). TTS onset occurred in a median of 9 (4) days after vaccination. Venous thrombosis was most common (61.0%). Most patients developed cerebral venous sinus thrombosis (CVST; 66.3%). CVST was significantly more common in female vs male patients (p = 0·001) and in patients aged <45 years vs ≥45 years (p = 0·004). The mortality rate was 36.2%, and patients with suspected TTS, venous thrombosis, CVST, pulmonary embolism, or intraneural complications, patients not managed with non-heparin anticoagulants or IVIG, patients receiving platelet transfusions, and patients requiring intensive care unit admission, mechanical ventilation, or inpatient neurosurgery were more likely to expire than recover. INTERPRETATION: These findings help to understand the pathophysiology of TTS while also recommending diagnostic and management approaches to improve prognosis in patients. FUNDING: This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Effectiveness of education and antibiotic control programme at All India Institute of Medical Sciences, New Delhi.

Background: We aimed to assess the impact of antibiotic optimization education along with understanding the antibiogram on antibiotic-prescribing practices, antibiotic consumption, antimicrobial resistance and cost of antibiotics in a tertiary care hospital in New Delhi. Methods: We divided the study into 3 phases-before and after intervention and a phase of education in between. We collected data on demographics, indication for antibiotic prescription, appropriateness or reasons for inappropriate antibiotic uses, antibiotic consumption (i.e. the rate and duration of antibiotic use), bacterial resistance and antibiotic cost. Interventions included education, introduction of an antibiogram and use of antibiotic prescription forms. Similar data were collected for the post-interventional phase. The study was conducted at the Department of Medicine, All India Institute of Medical Sciences, New Delhi, India. Results: There was an improvement in the number of patients who underwent de-escalation of antibiotics, 21/100 v. 36/100 (p = 0.019); appropriate antibiotic usage, 25/ 100 v. 46/100 (p = 0.002); switching from intravenous to oral promptly, 16/52 v. 1 9/36 (p = 0.003) and decrease in expenditure, ₹24 207.5 v. ₹16 51 7.5 per patient (p = 0.001 ); in the post-interventional phase. Significant reductions in the incidence of infections due to Acinetobacter (60% v. 31%; p<0.001) and improvement in sensitivity pattern with cephalosporin sulbactam (80% v. 100%; p<0.001) were seen. Multivariate analysis revealed that Acute Physiology and Chronic Health Evaluation (APACHE) score, hospital stay <10 days, ventilator-associated pneumonia and methicillin-resistant Staphylococcus aureus coverage were independent predictors of mortality with odds ratio of 1.14, 0.1, 9.7 and 1.14, respectively. Conclusion: Education and an antibiotic control programme constituted an effective and cost-saving strategy to optimise antibiotic use at a tertiary care centre.