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Objective: To assess the impact of post-protamine neutralisation activated clotting time (ACT) values on postoperative outcomes including chest drain output, transfusion requirements, and CICU stay, in patients undergoing cardiac surgery., Study Design: Observational comparative study. Place and Duration of the Study: Department of Anaesthesiology, The Aga Khan University Hospital, Karachi, Pakistan, from February to August 2023., Methodology: Ethical approval was obtained to collect data from elective cardiac surgery patients' charts. A sequential sampling approach analysed the baseline and post-protamine neutralisation ACT values, categorising patients into two groups. Group A maintained ACT within 10% of baseline, while Group B deviated. The outcomes measured included transfusion needs, chest drain output, additional protamine, cardiac intensive care unit (CICU) stay, and postoperative reopening. Statistical analysis included mean, median, frequency, t-test / Mann-Whitney U test, and Chi-square test., Results: The study comprised 101 patients (39 in Group A, 62 in Group B), with similar baseline health. No significant differences were found in tranexamic acid use, CICU stay, chest drain output, or transfusion rates between the groups (p >0.05)., Conclusion: Maintaining ACT within 10% of baseline post-protamine neutralisation results in similar intraoperative and postoperative outcomes, suggesting potential benefits in avoiding the aggressive protamine therapy and ensuring haemostasis in cardiac surgery., Key Words: Coronary Artery bypass grafting, Cardiopulmonary bypass, Activated clotting time (ACT), Heparin, Postoperative bleeding, Blood transfusions.

Objective: The implications of saline flushing of the radial sheath have not been studied in terms of radial artery occlusion. We aimed to investigate radial artery patency outcomes after the saline flush of the radial sheath., Methods: In this prospective observational study, patients were selected to receive either radial sheath flushing with 10 mL of saline after pulling the sheath to one-third of its length (Group 1) or standard care (Group 2) after removal of the catheter sheath as per physician discretion. Radial artery patency was assessed by Doppler ultrasound at 24 h and 30 days after the procedure., Results: A total of 2877 patients were enrolled in the study, with 1340 receiving radial sheath flushing and 1537 receiving standard care. At 24 h after the procedure, the incidence of radial artery occlusion was significantly lower in the radial sheath flushing group compared to the standard care group (4.4% vs 12.6%, p  = 0.027). This difference persisted 30 days after the procedure (6.1% vs 15.8%, p  = 0.015). Radial sheath flushing was independently associated with a lower risk of radial artery occlusion 30 days after the procedure, after adjusting for potential confounders (OR 0.375, 95% CI 0.18-0.77, p  = 0.008)., Conclusion: In conclusion, this prospective study provides evidence to support the use of radial sheath flushing after coronary intervention via the radial artery as a simple and effective strategy for reducing the risk of radial artery occlusion without increasing the risk of other adverse outcomes., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

In today's era of modern healthcare, the intersection between medical practices and environmental responsibility has gained significant attention. One such area of focus is the practice of anesthesia, which plays a crucial role in various surgical procedures. Anesthetics such as nitrous oxide and volatile halogenated ethers (desflurane, isoflurane, sevoflurane) are examples of medical gases that are strong greenhouse gases that contribute to global warming. During medical procedures, most of these anesthetic agents are released into the atmosphere, which exacerbates their influence on the environment. Also anesthesia delivery systems have traditionally utilized high flow rates of gases, leading to not only excessive consumption but also a considerable environmental impact in terms of greenhouse gas emissions. However, the emergence of low-flow anesthesia (LFA) presents a promising solution for achieving emission reduction and cost savings, thereby aligning healthcare practices with sustainability goals. Understanding LFA involves the administration of anesthetic gases to patients at reduced flow rates compared to conventional high-flow methods. This practice requires precision in gas delivery, often incorporating advanced monitoring and control systems. By optimizing gas flow to match the patient's requirements, LFA minimizes wastage and excessive gas release into the environment, subsequently curbing the carbon footprint associated with healthcare operations. Decreasing volatile anesthetic delivery provides safe and effective strategies for anesthesia providers to decrease costs and reduce environmental pollution. Current literature support in favor of LFA represents an area of cost containment and an opportunity to lessen the environmental impact of anesthesia. This article will cover the concept of LFA, the distinctions between low flow and minimal flow, and the potential advantages of LFA, such as those related to patient safety, the environment, and the economy., (Copyright © 2024 Copyright: © 2024 Medical Gas Research.)

Acute leukemia is a group of aggressive hematological malignancies, with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) being the most common types. The biology of acute leukemia involves complex genetic and epigenetic alterations that lead to uncontrolled cell proliferation and resistance to apoptosis. Mitochondrial dysfunction is a feature of acute leukemia that results in altered energy production, unregulated cell death pathways, and increased cancer cell survival. Apoptosis, particularly via the mitochondrial pathway, is crucial for cellular homeostasis and cancer prevention. In acute leukemia, disruption of apoptosis is pivotal in disease development and progression, with elevated levels of anti-apoptotic proteins conferring a survival advantage to leukemia cells and promoting resistance to conventional therapies. Targeting mitochondrial apoptosis using BH3 mimetics and anti-apoptotic protein inhibitors is a viable therapeutic strategy. Alterations in the mitochondrial membrane potential, metabolism, and dynamics also contribute to the pathogenesis of acute leukemia. Continued research is vital for developing novel therapies and enhancing survival outcomes in patients with acute leukemia while minimizing the long-term adverse effects of treatment. In this narrative review, we provide a birds-eye view of the available scientific literature on the importance of mitochondria in acute leukemia, and discuss the role of BH3 mimetics in targeting the mitochondrial internal apoptotic machinery.

SF3B1 mutations frequently occur in cancer yet lack targeted therapies. Clinical trials of XPO1 inhibitors, selinexor and eltanexor, in high-risk myelodysplastic neoplasms (MDS) revealed responders were enriched with SF3B1 mutations. Given that XPO1 (Exportin-1) is a nuclear exporter responsible for the export of proteins and multiple RNA species, this led to the hypothesis that SF3B1-mutant cells are sensitive to XPO1 inhibition, potentially due to altered splicing. Subsequent RNA sequencing after XPO1 inhibition in SF3B1 wildtype and mutant cells showed increased nuclear retention of RNA transcripts and increased alternative splicing in the SF3B1 mutant cells particularly of genes that impact apoptotic pathways. To identify novel drug combinations that synergize with XPO1 inhibition, a forward genetic screen was performed with eltanexor treatment implicating anti-apoptotic targets BCL2 and BCLXL, which were validated by functional testing in vitro and in vivo. These targets were tested in vivo using Sf3b1 K700E conditional knock-in mice, which showed that the combination of eltanexor and venetoclax (BCL2 inhibitor) had a preferential sensitivity for SF3B1 mutant cells without excessive toxicity. In this study, we unveil the mechanisms underlying sensitization to XPO1 inhibition in SF3B1-mutant MDS and preclinically rationalize the combination of eltanexor and venetoclax for high-risk MDS., (© 2024. The Author(s).)

Introduction and Importance: Redo aortic valve replacement in twin pregnancy presents significant challenges because of the elevated risks for both maternal and fetal health. Mortality rates range from 12 % to 21 % in specialised centres, with previous cardiac surgeries further elevating the risk. Pregnancy complicates cardiac surgery, with fetal mortality rates as high as 16-33 %., Presentation of Case: A 31-year-old woman, 15 weeks pregnant with twins and with a history of mechanical aortic valve replacement, presented with worsening breathlessness and grade III dyspnoea. Echocardiography revealed severe valve obstruction, necessitating redo-aortic valve replacement and posterior aortic root enlargement. Despite intraoperative challenges, including ventricular fibrillation and postoperative heart block, she underwent successful surgery and pacemaker implantation, with both mother and fetuses remaining stable., Discussion: Optimal timing of surgery is crucial, considering fetal developmental vulnerability in the first trimester and maternal cardiac workload in the third trimester. Second-trimester risks are comparable to non-pregnant patients. A limited understanding of fetal-placental perfusion during bypass necessitates cautious management strategies, with emerging techniques like pulsatile perfusion showing promise. Anaesthesia selection prioritises fetal safety while monitoring fetal distress during surgery remains challenging. To achieve successful outcomes for both mother and babies in a twin pregnancy undergoing a redo aortic valve replacement, careful timing, appropriate surgical techniques, and meticulous perioperative care are essential., Conclusion: A multidisciplinary approach is crucial for managing twin pregnancy following redo aortic valve surgery. Careful planning, close monitoring, and specialised surgical and anaesthetic techniques are key to minimising risks to both mother and fetus., Competing Interests: Conflict of interest statement Nothing to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Inflammatory myofibroblastic tumors (IMTs) are one of the most complex and rare neoplasms that have been discovered, with varying behavior in different cases. They mostly arise in the thoracic and abdominal cavity, the lungs, retroperitoneum, and extremities. They can also be detected in the head and neck area. IMTs have no age or gender preference which makes them tougher to anticipate. Head and neck IMTs are benign neoplasms with locally aggressive behavior and a low risk of metastatic spread. They have an unknown etiology, and they resemble malignant lesions radiologically. In this case report, we will review the case of a 40-year-old woman with an unusual IMT in the maxillary sinus that presented as a challenge in diagnosis and management., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

This study aims to improve the biopharmaceutical, mechanical, and tableting properties of a poorly soluble drug, ibuprofen (IBP), by preparing amorphous solid dispersion (ASD) followed by a sustained-release tablet formulation. A suitable polymer to develop an ASD system was chosen by utilizing the apparent solubility of IBP in various polymer solutions. ASDs containing various ratios of IBP and selected polymer were prepared by the melt fusion (MF) method. ASD containing optimized drug-polymer ratio prepared by freeze-drying (FD) method was characterized and compared physicochemically. The solubility of IBP in water increased 28-fold and 35-fold when formulated as ASD by MF and FD, respectively. Precise formulations showed amorphization of IBP and increased surface area, improving solubility. The dissolution pattern of optimized ASD-IBP in pH 6.8 phosphate buffer after 60 min in MF and FD was enhanced 3-fold. In addition, direct compression tablets comprising optimized ASD granules from MF and FD were made and assessed using compendial and noncompendial methods. ASD-IBP/MF and ASD-IBP/FD formulations showed a similar drug release profile. In addition, 12 h of sustained IBP release from the ASD-IBP-containing tablets was obtained in a phosphate buffer with a pH of 6.8. From the dissolution kinetics analysis, the Weibull model fitted well. The drug release pattern indicated minimal variations between tablets formed using ASD-IBP prepared by both procedures; however, pre- and postcompression assessment parameters differed. From these findings, the application of ASD and sustained-release polymers in matrix formation might be beneficial in improving the solubility and absorption of poorly soluble drugs such as IBP., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Ajam Uddin et al.)

In many cancers, mortality is associated with the emergence of relapse with multidrug resistance (MDR). Thus far, the investigation of cancer relapse mechanisms has largely focused on acquired genetic mutations. Using acute myeloid leukemia (AML) patient-derived xenografts (PDX), we systematically elucidated a basis of MDR and identified drug sensitivity in relapsed AML. We derived pharmacologic sensitivity for 22 AML PDX models using dynamic BH3 profiling (DBP), together with genomics and transcriptomics. Using in vivo acquired resistant PDXs, we found that resistance to unrelated, narrowly targeted agents in distinct PDXs was accompanied by broad resistance to drugs with disparate mechanisms. Moreover, baseline mitochondrial apoptotic priming was consistently reduced regardless of the class of drug-inducing selection. By applying DBP, we identified drugs showing effective in vivo activity in resistant models. This study implies evasion of apoptosis drives drug resistance and demonstrates the feasibility of the DBP approach to identify active drugs for patients with relapsed AML., Significance: Acquired resistance to targeted therapy remains challenging in AML. We found that reduction in mitochondrial priming and common transcriptomic signatures was a conserved mechanism of acquired resistance across different drug classes in vivo. Drugs active in vivo can be identified even in the multidrug resistant state by DBP., (©2024 American Association for Cancer Research.)

Objective: The objective of our study is to compare the success rate, duration, and incidence of complications of a right internal jugular vein (IJV) cannulation by using three different techniques., Methodology: A randomised controlled trial was conducted at a tertiary care teaching hospital. A total of 201 patients were randomly allocated to one of the following three groups (67 in each group). Techniques were categorised as anatomical landmark technique group (Group ALT), ultrasound guided pre-location group (Group USG-Pre), and real-time ultrasound-guided technique group (Group USG-RT)., Interventions: Central venous catheter insertion via three techniques., Results: In 138 (73.01%) patients' IJV canulated in the first attempt, USG-RT, USG-Pre, and ALT were 51 (83.6%), 44 (72.1%), and 43 (64.2%), respectively. On the other hand, 37 (19.57%) patients were required in the second attempt, while only 14 (7.40%) patients were required in the third attempt for successful IJV cannulation. The success rates, as defined in our study, were only 138 (73%) as, in 51 (27%), we cannulated in more than a single attempt or switched to another technique. We found a significant difference in preparation time in all techniques as P-value <0.05, but no significant difference was found in venous access time, cannulation time, and duration of the procedure., Conclusions: Any technique can be used for IJV cannulation, but the most acceptable is the real-time US technique. However, no difference in the overall procedure time among all three techniques was noted, and no major incidence of complication was found., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Ahmed et al.)

Orodispersible films (ODFs) are thin, mechanically strong, and flexible polymeric films that are designed to dissolve or disintegrate rapidly in the oral cavity for local and/or systemic drug delivery. This review examines various aspects of ODFs and their potential as a drug delivery system. Recent advancements, including the detailed exploration of formulation components, such as polymers and plasticizers, are briefed. The review highlights the versatility of preparation methods, particularly the solvent-casting production process, and novel 3D printing techniques that bring inherent flexibility. Three-dimensional printing technology not only diversifies active compounds but also enables a multilayer approach, effectively segregating incompatible drugs. The integration of nanoparticles into ODF formulations marks a significant breakthrough, thus enhancing the efficiency of oral drug delivery and broadening the scope of the drugs amenable to this route. This review also sheds light on the diverse in vitro evaluation methods utilized to characterize ODFs, ongoing clinical trials, approved marketed products, and recent patents, providing a comprehensive outlook of the evolving landscape of orodispersible drug delivery. Current patient-centric approaches involve developing ODFs with patient-friendly attributes, such as improved taste masking, ease of administration, and enhanced patient compliance, along with the personalization of ODF formulations to meet individual patient needs. Investigating novel functional excipients with the potential to enhance the permeation of high-molecular-weight polar drugs, fragile proteins, and oligonucleotides is crucial for rapid progress in the advancing domain of orodispersible drug delivery.

Introduction Surgery patients frequently experience sleep deprivation, which is regarded as a stress factor during the perioperative period and can cause physical discomfort, exhaustion, and even postoperative pain. There is a dearth of information on preoperative sleep habits and the consequences that may result. There are both subjective and objective ways to rate the quality of your sleep. We chose the Pittsburgh Sleep Quality Index (PSQI), which employs a questionnaire to provide crucial information on issues like sleep length, efficiency, and interruption. Lower sleep quality is correlated with higher PSQI scores. Study objective Our study aimed to assess the changes in the sleep pattern of cardiac disease patients before cardiac surgery and compare these changes with baseline sleep patterns. Methods This prospective survey was carried out after ethical review committee approval at the Department of Anesthesia, Aga Khan University Hospital. Consent was obtained from all patients undergoing cardiac surgery. Strict inclusion and exclusion criteria were followed. All patients aged 25 to 65 who came from home for elective cardiac surgery under general anesthesia were included. At the same time, patient demographics were noted. Additionally, a printed PSQI questionnaire was distributed to each participant. The native Urdu language was also translated into this questionnaire. The patient was given an explanation of this form by a medical professional. This questionnaire was filled out by the patients on the surgical floor or preoperative area before premedication. The PSQI questionnaire was used to assess baseline sleeping patterns, and then the same questions were asked about the period between decisions for the date of surgery and the time of admission for surgery. Results A total of 83 patients participated in the study. The mean age of the patient was 57 ( ± 13.0), out of which 67 (80.7%) were males and 16 (19.3%) were females. The most common surgeries were coronary artery bypass (CABG) surgery 63 (77.8%), followed by valve replacement nine (11.1%). The overall mean PSQI score was higher (5.27) once the surgery date was decided as compared to the baseline (4.84), but it did not reach the statistically significant level (p-value 0.411). Sleep latency (time to fall asleep while in bed) was the only variable statistically significant between baseline (26.1 (±35.0) and after the surgery date has been finalized (36.1 (±46.6)). No significant differences were found in other variables like sleep quality (feeling of being well-rested), sleep duration (hours of actual sleep), sleep efficiency (sleep efficiency is the ratio of the amount of total time asleep versus the total time in bed), and sleep disturbance (problem initiating and maintaining sleep). Total bedtime was also reduced at night before surgery but did not achieve a significant level. The logistic regression model demonstrated that age, gender, and type of surgery did not influence sleep quality. Conclusion In the present study, lower sleep quality was observed before cardiac surgery, but it did not reach a statistically significant level when compared with baseline. Sleep latency (time to fall asleep while in bed) was significantly prolonged compared to baseline. We could not find any association between quality of sleep and variables like age, gender, and type of surgery., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ahmed et al.)

Background: The multisystem inflammatory syndrome in adults (MIS-A) has emerged, similar to those in children associated with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) [multisystem inflammatory syndrome in children (MIS-C)]. This review aimed to analyze the risk factors, clinical course, and prognosis of MIS-A., Methods: A comprehensive literature search was conducted using several databases for cases reporting MIS-A from 1 December 2019 till 9 September 2021. The case definitions used to identify potential cases were those recommended by the World Health Organization, Center for Disease Control, and individual country/physician classification. The meta-analysis was performed using Comprehensive Meta-Analysis (CMA) 2.2.027 and Review Manager (RevMan) 5.4.1, employing 95% confidence intervals (CI)., Results: Seventy studies were assessed for full-text eligibility, out of which 37 were included. The mean age of the study population was 32.52±10.29 years. The most common symptoms were fever (89.8%, 95% CI: 77.7-95.7%) and diarrhea (49%, 95% CI: 35.4-62.7%). Ventricular tachycardia (57.1%, 95% CI: 43.1-70.1%) was the most common electro-cardiac abnormality. The most common inflammatory marker was elevated C-reactive protein (89.8%, 95% CI: 77.7-95.7%). Abnormal echocardiogram was the most common imaging test result (commonly, ventricular dysfunction and arrhythmias), while steroids were the most administered treatment. Severe cases had a higher need for vasopressor and inotropic support and antibiotic therapy compared to the non-severe cases. One death was reported due to cardiovascular failure., Conclusion: Our collated findings will help clinicians identify the typical presenting symptoms and optimal management of MIS-A. Further research is required to understand the long-term prognosis and the correlation between coronavirus disease 2019 (COVID-19) and MIS-A to understand its pathogenesis and clinical spectrum., Competing Interests: All authors declare no conflicts of interest.Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Postgraduate medical training has increasingly adapted to competency-based medical education (CBME). In an endeavour to stay abreast with the new trends in medical education and adapt to CBME frameworks, an in-depth review and revision of the Anaesthesiology training curriculum were conducted. The authors worked on the task from December 2020 to December 2021. Learning outcomes were defined and corresponding competencies were identified and relevant teaching, learning and assessment strategies were aligned with each learning outcome. Additionally, lists were devised for topics to be covered through didactic lectures and simulation-based workshops. The revised curriculum is currently being implemented in a phased manner. Formative workplace-based assessment tools are being introduced to complement CBME. Moreover, daily clinical assessments, entrustable professional activity (EPA), simulation-based workshops and assessments have been introduced. Key Words: Anaesthesiology, Postgraduate training, Curriculum revision, Competency-based medical education, Low-middle income country, Simulation-based training.

This paper presents an ontological review of the global research on access to geriatric disability care and a roadmap for future research to address the problem in India. First, the dominant research focus is on resources (human, financial, and spatial) that affect access to disability care; there is little focus on informational and technological resources. Second, functional disabilities are the dominant focus of the research, followed by cognitive, mental, and locomotor disabilities; there is little focus on speech, hearing, and visual disabilities. Third, barriers, inhibitors, and catalysts of physical access are the dominant focus, with relatively less focus on virtual access; there is very little emphasis on the drivers to access. Fourth, the primary, although not dominant, focus is on access for urban and rural populations; there is very little focus on access for underserved and indigenous populations. Future research must address these gaps systematically to improve access. This paper adds: (a) a systemic framework for the study of an important, complex, emerging problem; (b) a systematic review of the global research on the problem; and (c) a research roadmap to address the emerging problem in India.

Knowing the state of mental health research in adolescents and youth can be an important tool for decision-making, especially in contexts of limited resources. The aim of this study is to map the scientific research on adolescent and youth mental health in Chile using an ontological framework. We have mapped the population of research articles on mental health of adolescents and youth in Chile in Scopus, Web of Science, and SciELO databases onto the ontology. The PRISMA reporting guidelines were used to screen the 1688 items based on relevance, duplication, and version. The corpus of 346 articles was coded into the ontology through an iterative process among the seven authors. This ontological mapping shows isolated research efforts that have been carried out in Chile to explain the whole state of mental health in adolescents and youth. There is a lack of coordination between the priorities established by the decision-makers and the researchers. Our results coincide with the need to strengthen mental health research in the country, and to prioritizing those topics that contribute to decision-making based on the needs of the population.

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., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

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., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Background: Due to the Novel Coronavirus Disease, medical education has transformed from a physical to an online-medium. The importance of physical education in low-and-middle-income countries (LMICs), where online education can be challenging there is a need to explore the factors that affect online education. This study assesses the perspective and mental health of students whose medical education has been impacted by the pandemic., Methods: An online-questionnaire was distributed through social media platforms from October-to-December 2020 through Google-Forms among medical students across Pakistan. Two grading-scales were used to score anxiety and depression. Descriptive statistics and a logistic regression analysis were used to identify factors associated with anxiety and depression among medical students. p<0.05 was considered as significant. Data was analyzed using STATA v.15., Results: Total of 433 medical students participated in the study where 68.1% had some form of depression and 10.9% had anxiety. Around 65%-participants disagreed with the preference for online-classes. Seventy percent agreed on "Has the thought of the pandemic made you worry about your academic future" being associated with COVID-19 related-depression (OR: 2.03, 95%CI: 1.32-3.11). Multivariate analysis showed agreeing to "COVID affected my educational performance" was associated with anxiety (OR:1.45, 95%CI: 1.03-2.06) and depression (OR: 1.27, 95%CI: 1.03-1.56)., Conclusions: Being part of the Low- and-Middle-Income Countries (LMIC), online-education itself becomes a challenge. Given the continued shutdown of universities across the country and the growing anxiety and depression amongst the students, adequate measures should be taken to help in coping up with the current challenge.

Background: Spontaneous Adverse drug reactions (ADRs) reporting is a cornerstone for a successful pharmacovigilance program as under-reporting of ADRs remains a major issue around the globe. The current study aimed to assess the knowledge attitude and practices of health care professionals regarding pharmacovigilance along with barriers and factors to encourage ADR reporting at tertiary care hospitals of Khyber-Pakhtunkhwa, Pakistan., Methods: A questionnaire-based cross-sectional survey was conducted, using the convenience sampling method to collect the data from doctors, nurses, and pharmacists working in seven tertiary care hospitals from seven districts of Khyber-Pakhtunkhwa province, Pakistan, between July 2019 and March 2020., Results: During the study, a total of 830 questionnaires were distributed, out of which 669 were returned (response rate 80.6%). Overall, Healthcare professionals exhibited poor knowledge (79.5%) about ADR reporting and pharmacovigilance however, 73.5% of pharmacists were more knowledgeable as compared to 18.7% doctors and 13.8% nurses ( p  < .001). Moreover, poor reporting practices were displayed by 95.6% doctors, 94.4% nurses, 94.4 and 75.5% pharmacists ( p  < .001). However, the majority of healthcare professionals showed an overall positive attitude (94%) toward ADR reporting. The most frequently cited barriers were unavailability of reporting forms (92.5%), absence of a professional environment to discuss ADRs (82.5%), and lack of training (81.8%) whereas, most common factors to encourage ADR reporting were obligatory reporting (85.9%) and provision of ADR management guidelines and training (84.3%). A significant relation was found between the healthcare professionals and their professional status with the overall knowledge, attitude, and practice (KAP) scores ( p  < .001) whereas a medium, positive correlation was found between the knowledge and practice of pharmacovigilance and ADR reporting by the healthcare professionals ( r  = 0.321, n  = 669, p  < .001)., Conclusion: There is an overall lack of knowledge and poor reporting practices among health care professionals on ADR reporting and pharmacovigilance. Hence the study suggests that strategies should be devised by all the stakeholders to properly educate and train the healthcare professionals in this area to enhance overall patient safety and safe use of medicines.

Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Cardiac surgery is typically attributed with a significant risk of intraoperative blood loss and allogeneic blood transfusions. Intraoperative blood loss, allogenic blood transfusions, high dose anticoagulation requirement, and interactions with cardiopulmonary bypass (CPB) have all been linked to cardiac surgeries. To reduce unnecessary transfusions and their negative effects, it is recommended to follow evidence-based multidisciplinary strategies, which are collectively termed patient blood management (PBM). This review highlights the most recent blood conservation strategies in adult cardiac surgery, which can be employed pre-operatively, intra-operatively, and postoperatively, to enhance red cell mass and attenuate the utilization of packed red blood cells (PRBCs) and other blood products., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Yousuf et al.)

Background: Left Atril Appendage(LAA) is one of the most contractile structure of the heart. Elevated Left atrial pressure (LAP) can change the flow profile in and out of LAA. There is little data on the effect of LAP on LAA flow velocities for patients in sinus rhythm, and it's not properly known that by evaluation of LAA flow spectra and its velocities, the LAP can be predicted. We tried to find the relationship between LAA flow velocities and LAP, with the premise that LAA flow velocities can be used as a surrogate for measuring LAP, by obtaining a regression equation in this prospective observational study., Methods: In forty patients with normal systolic and diastolic heart function undergoing elective off pump coronary artery bypass (OPCAB) under general anaesthesia, TEE based LAA flow velocities were measured and simultaneous direct measurements of LAP was done by the surgeon. We also studied the relation between the ratio of early mitral inflow velocity (E) and mitral lateral annular early diastolic velocity (E'), that is, (E/E') in all patients., Results: We found significant correlation between E/E' and LAP (r = 0.424, p = 0.024) however there was no significant correlation between LAA flow velocities and LAP., Conclusion: LAA flow profile can not be used under anaesthesia to evaluate LAP however E/E' shows a strong correlation with directly measured LAP., Competing Interests: None

Measles infection, caused by the "Rubeola" virus is a highly contagious disease with outrageously fatal consequences. Initiating with a variety of symptoms including fever, cough, conjunctivitis, and runny nose, it can lead to more severe sequelae including sub-acute sclerosing pan-encephalitis which is a potentially fatal and serious complication of measles. The lackluster vaccination processes in underdeveloped areas of the world due to suboptimal immunization programs, scarce resources, and insufficient political constancy still leads to increased cases of measles and its complications. A variety of management programs including the use of several medications have been introduced according to the literature in order to counter this dreadful disease. In this review article, we focus on assessment of the previous literature and discussing the possible treatment modalities of this currently irremediable disease., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

Objective: To assess different anaesthesia-related quality indicators during adult cardiac surgery., Methods: The prospective clinical audit was conducted at the Aga Khan University Hospital, Karachi, from October 2016 to March 2017, and comprised all adult patients scheduled for cardiac surgery. Different anaesthesia-related quality indicators were observed during the pre-induction phase, before the cardiopulmonary bypass, during the procedure, and post-surgery till the transfer from the operating room to the cardiac intensive care unit. Data was analysed using SPSS 19., Results: Of the 264 patients, 217(82.2%) had complete record; 160(73.7%) males and 57(26.3%) females. The overall mean age was 56.56±12.46 years. In the pre-induction phase, difficult intravenous and invasive line access was seen in 42(19.3%) patients. Inappropriate information in the preoperative form was found in 6(2.8%) patients, and preoperative drugs for anxiolysis were used in 145(66.8%) patients. Haemodynamic issues were significant during the surgery in 15(6.9%) patients. In the post-surgery period, abnormal activated clotting time was found in 17(7.8%) patients, while monitoring problems were faced in 7(3.2%) cases during transfer to cardiac intensive care unit., Conclusions: It will help to develop quality improvement policies to enhance patient safety, satisfaction and better outcome.

The objective of the present study was to assess the perceptions, knowledge, and awareness of self-medication practice among the university students in Nepal. This descriptive cross-sectional, questionnaire-based study was conducted on randomly selected 620 students from three different universities in Nepal. The study results revealed that 95.4% of students had reported self-medication, among which analgesics and antipyretic medications were mostly used (66 %); followed by anti-ulcerants (35.3%), antibiotics (33.9%), anti-allergic preparations (20%), and other categories (10.3%) of drugs. Study results also showed that, the major cause of self-medication was minor illness, and the prescriptions which were previously used to treat the similar disease conditions were the main source of motivation to do so. A significant portion of the respondents believed that self-medication might be acceptable to treat minor illness. Furthermore, students demonstrated variable responses regarding the doses, safety, toxicities, and health hazards towards self-medication without having appropriate knowledge of drugs. The findings of this study revealed the necessity of building awareness and strict implementation of the jurisdiction to minimize the practice of self-medication., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s).)

Objective: To highlight the prevalence and epidemiology of New Delhi metallo-ß-lactamase-1. producers in pus samples., Methods: The cross-sectional study was conducted from April to August 2018 at the Biotechnology Laboratory, Balochistan University of Information Technology Engineering and Management Sciences, Quetta, Hi-tech Laboratory, Centre for Advance Studies in Vaccinology and Biotechnology, University of Balochistan, Quetta and Microbiology Laboratory, Bolan Medical Complex Hospital, Quetta, Pakistan. Biochemical and molecular approaches were used for the identification of the isolates and Modified Hodge Test for the phenotypic detection of class-A carbapenemase activity. Minimum Inhibitory Concentration was performed using E-test and broth microdilution method. Molecular basis of carbapenemase activity was ascertained by the recognition of blaNDM-1 gene in the isolates., Results: Of the 300 pus samples taken from surgical/burn units, 6(2%) blaNDM-1 harbouring isolates were found; 3(50%) each being Klebsiella pneumoniae and Pseudomonas aeruginosa. Klebsiella. pneumoniae isolates were extensively drug-resistant. The Pseudomonas aeruginosa isolates displayed resistance against 21 antibiotics of tetracyclines, quinolones, b-lactams, aminoglycosides, monobactams, sulphonamides, macrolides, cephalosporins, phosphonic acid and polypeptide groups, suggesting pan-drug resistance., Conclusions: The resistance pattern of the bacterial isolates poses a significant clinical threat in the region.

Objective: To compare open reduction with internal fixation of mandibular subcondylar fracture with closed reduction in terms of adequate mouth opening., Methodology: The randomised clinical trial was conducted from March 2014 to February 2015 at the Oral and Maxillofacial Surgery Department, King Edward Medical University and Allied Hospitals, Lahore, Pakistan, and comprised patients who presented with unilateral subcondylar fractures. The patients were randomly divided into 2 groups. Group-A patients were treated with closed reduction and immobilisation and were discharged the same day, while Group-B patients were treated by open reduction with internal fixation and retained in ward for 1 day. Both were recalled for periodic follow-ups, and were compared in terms of achieving adequate mouth opening. Data was analysed using SPSS 20., Results: Of the 70 patients, 35(50%) were in each of the two groups. The mean age in Group-A was 28.88±11.86 years compared to 28.22±10.80 years in Group-B (p>0.05). Mean mouth opening in the two groups were consistently positive, and significant at the last two follow ups(p<0.001)., Conclusions: The difference in results of both treatment modalities was significant, indicating that open reduction and internal fixation should be the preferred treatment.

Bone regeneration after trauma, pathologic and surgical procedures is considered a major medical challenge. Due to limitations in using conventional approaches, cell based regenerative strategies may provide an alternative option to address such issues. In the current study, we sought to determine the osteogenic potential of dental pulp stem cells (DPSCs) isolated from impacted 3 rd molars. DPSCs were isolated from human dental pulp tissue (n=6) using explant culture. Growth characteristics of DPSCs were determined using plating efficiency, and the number and time of population doublings. After characterization, DPSCs were induced to differentiate into osteoblasts and were assessed using polymerase chain reactions (PCR) and histological analysis. Results indicated that DPSCs can be isolated from impacted human third molars, and that DPSCs exhibited typical fibroblastic morphology and excellent proliferative potential. In addition, morphological changes, histological analysis and expression of lineage specific genes confirmed osteogenic differentiation of DPSCs. In conclusion, DPSCs isolated from impacted 3rd molars have high proliferative potential and ability to differentiate into osteoblasts., Competing Interests: Conflict of interest: Authors state no conflict of interest., (© 2020 Sadia Awais, et al. published by De Gruyter.)

Background: Pancreatoblastoma is a rare malignancy that occurs predominantly in children. Less than 50 adult cases, including 17 patients with metastatic disease, have been published to date. Recent outcome data from children with advanced-stage disease suggest an intensive multimodal treatment approach; however, little is known about the most beneficial therapy in adults. Molecular characterization of pancreatoblastoma is limited to a small number of pediatric cases and revealed few recurrent genetic events without immediate clinical relevance., Methods: Patients were treated between 2013 and 2018 at a high-volume German university cancer center. Molecular analyses included whole genome, exome, transcriptome, and fusion gene panel sequencing. Molecularly guided treatment recommendations were discussed within a dedicated molecular tumor board (MTB) embedded in a precision oncology program (NCT MASTER)., Results: We identified four adult patients with metastatic pancreatoblastoma. In three patients, local approaches were combined with systemic treatment. Oxaliplatin-containing protocols showed an acceptable tumor control as well as an adequate toxicity profile. Overall survival was 15, 17, 18 and 24 months, respectively. Three tumors harbored genetic alterations involving the FGFR pathway that included an oncogenic FGFR2 fusion., Conclusion: Oxaliplatin-containing chemotherapy seems to be a reasonable approach in adult patients with advanced pancreatoblastoma, whereas the benefit of intensified treatment including local ablative techniques or surgical resection remains unclear. Our finding of FGFR alterations in three of four cases indicates a potential role of FGFR signaling in adult pancreatoblastoma whose clinical significance warrants further study., (Copyright © 2020. Published by Elsevier B.V.)

Rationale: Patients with obsessive-compulsive disorder (OCD) have been found to show exaggerated error responses and prediction error learning signals in a variety of EEG and fMRI tasks, with data converging on the anterior cingulate cortex as a key locus of dysfunction. Considerable evidence has linked prediction error processing to dopaminergic function., Objective: In this study, we investigate potential dopaminergic dysfunction during reward processing in the context of OCD., Methods: We studied OCD patients (n = 18) and controls (n = 18) whilst they learned probabilistic associations between abstract stimuli and monetary rewards in the fMRI scanner involving administration (on separate visits) of a dopamine receptor agonist, pramipexole 0.5 mg; a dopamine receptor antagonist, amisulpride 400 mg; and placebo. We fitted a Q-learning computational model to fMRI prediction error responses; group differences were examined in anterior cingulate and nucleus accumbens regions of interest., Results: There were no significant group, drug, or interaction effects in the number of correct choices; computational modeling suggested a marginally significant difference in learning rates between groups (p = 0.089, partial ƞ 2  = 0.1). In the imaging results, there was a significant interaction of group by drug (p = 0.013, partial ƞ 2  = 0.13). OCD patients showed abnormally strong cingulate signaling of prediction errors during omission of an expected reward, with unexpected reduction by both pramipexole and amisulpride (p = 0.014, partial ƞ 2  = 0.26, 1-β error probability = 0.94). Exaggerated cingulate prediction error signaling to omitted reward in placebo was related to trait subjective difficulty in self-regulating behavior in OCD., Conclusions: Our data support cingulate dysfunction during reward processing in OCD, and bidirectional remediation by dopaminergic modulation, suggesting that exaggerated cingulate error signals in OCD may be of dopaminergic origin. The results help to illuminate the mechanisms through which dopamine receptor antagonists achieve therapeutic benefit in OCD. Further research is needed to disentangle the different functions of dopamine receptor agonists and antagonists during bidirectional modulation of cingulate activation.

Regulation of the Wnt pathway in stem cells and primary tissues is still poorly understood. Here we report that Usp16, a negative regulator of Bmi1/PRC1 function, modulates the Wnt pathway in mammary epithelia, primary human fibroblasts and MEFs, affecting their expansion and self-renewal potential. In mammary glands, reduced levels of Usp16 increase tissue responsiveness to Wnt, resulting in upregulation of the downstream Wnt target Axin2, expansion of the basal compartment and increased in vitro and in vivo epithelial regeneration. Usp16 regulation of the Wnt pathway in mouse and human tissues is at least in part mediated by activation of Cdkn2a, a regulator of senescence. At the molecular level, Usp16 affects Rspo-mediated phosphorylation of LRP6. In Down's Syndrome (DS), triplication of Usp16 dampens the activation of the Wnt pathway. Usp16 copy number normalization restores normal Wnt activation in Ts65Dn mice models. Genetic upregulation of the Wnt pathway in Ts65Dn mice rescues the proliferation defect observed in mammary epithelial cells. All together, these findings link important stem cell regulators like Bmi1/Usp16 and Cdkn2a to Wnt signaling, and have implications for designing therapies for conditions, like DS, aging or degenerative diseases, where the Wnt pathway is hampered.

Ultrasound-guided central venous cannulation is now considered as the standard of care, and this has largely replaced blind central venous cannulation using anatomical landmarks. We are reporting a case of inadvertent placement of central venous catheter in the right common carotid artery with the use of ultrasound guidance during emergency surgery for the total correction of Tetralogy of Fallot (ToF). This patient luckily had a favourable outcome despite this inadvertent catheter placement which was not recognised even after completion of surgery .The patient also received drug infusions of inotropes and vasopressors through this malplaced central line into the aorta. The possible mechanism, consequences, prevention and management of this inadvertent cannulation are discussed in this report.

Objective: To compare the intravenous boluses and intravenous continuous infusion of tranexamic acid (TXA) to reduce postoperative bleeding in cyanotic congenital heart disease surgeries., Study Design: Single-blinded randomised clinical trial., Place and Duration of Study: Anaesthesia Department, The Aga Khan University Hospital, Karachi, from July 2016 to April 2017., Methodology: Sixty patients of cyanotic congenital heart disease, undergoing either palliative or corrective surgery involving cardiopulmonary bypass (CPB), were recruited. These 60 patients were divided randomly into two groups. The infusion group received intravenous infusion of TXA at 5 mg/kg/hour while the bolus group received three intravenous boluses of 10 mg/kg after induction, after going to bypass and after protamine reversal. Data was collected through predesigned proforma. There were two primary outcomes: postoperative bleeding in the first 24 hours, and chest closure time., Results: Postoperative bleeding was 13.94 (10.27-20.18) ml/kg in the first 24 hours in infusion group and 15.05 (9.0423.50) ml/kg in the bolus group. Chest closure time was 38.5 (25-45) in infusion group and 30 (20-46.25) minutes in the bolus group. There was no statistically significant and clinical difference between both groups regarding postoperative bleeding in the first 24 hours and chest closure time., Conclusion: These infusion and bolus groups had comparable postoperative bleeding and chest closure time.

Plant cells respond to stresses and exogenous environmental stimuli. Production of altered levels of reactive oxygen species (ROS) is one of a typical cellular responses against such stimuli. These responses are detectable through various techniques including luminol-based bioassays. Luminol-based bioassays provide an excellent opportunity for detection of ROS in plant leaf tissue when challenged with some exogenous stimuli like phytohormones, cytokinins, auxins, ABA, etc. The luminol-based protocol in point aims at measuring changes in the H 2 O 2 levels of Arabidopsis leaf discs when exposed to phytohormone cytokinins. However, utility of the luminol-based ROS determination protocol is quite wide. We specifically optimized this protocol to quantify the effect of cytokinins on ROS production by Arabidopsis leaves.

Objectives: The aim of this study was to evaluate whether the foramen magnum (FM) dimensions could be used for sex determination using the Cone Beam Computed Tomography (CBCT)., Methods: Two hundred and sixty six CBCT full Field Of View (FOV) scans (111 males and 115 female subjects) of the skull were retrospectively selected and the FM length, width measured on reconstructed axial cross section by two observers using the CS 3D imaging software at a slice thickness of 300 μm and the FM area subsequently calculated using two established formulae by Routal and Teixeira. All data were subjected to descriptive and discriminant functional analysis to validate the expression of sexual dimorphism in the metric parameters of FM., Results: Using the FM dimensions the overall accuracy rate of sex determination was 66.4%. Out of these, 70.3% of males and 62.6% of females were sexed correctly. The best parameter for sex determination was the Area of the FM. In addition, the accuracy rate of sex prediction using the Area dimensions (Teixeira's formula) was 66.4%, same as that of all the four FM parameters used together., Conclusion: This study validates that there is statistically significant expression of sexual differences in the foramen magnum region, which may prove useful and reliable in predicting sex in partial skull remains by discriminant function analysis when other methods tend to be inconclusive. It suggests the reliability, usability and accuracy of CBCT in forensic identification., (Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

Background: Patients presenting for cardiac surgery have unstable cardiovascular disease and haemodynamics with multiple coexisting diseases. Optimal monitoring in the perioperative period is very important for best perioperative outcome. The introduction of the flow-directed pulmonary artery catheter (PAC) into clinical practice is one of the most important and popular advances in the field of cardiac anaesthesia. The objective of the study was to determine the frequency, indications and complications of pulmonary artery catheter insertion in adult open-heart surgery patients., Methods: A Prospective observational study was conducted at cardiac operating rooms and Cardiac Intensive care unit (CICU) of Aga Khan University Hospital for a period of six months from Nov 2015 to April 2016.Two hundred and seven patients were included in this study. PAC was inserted through right/left internal jugular vein or subclavian vein. Complications noted were arrhythmias (atrial and ventricular), right bundle branch block, coiling and knotting, pulmonary artery rupture, and infection up to 72 hours of PAC insertion. Frequency and percentage were computed for gender, comorbids (Hypertension, Diabetes, Chronic kidney disease, Chronic Obstructive Pulmonary Disease) and PAC frequency of insertion, indications and complications were noted., Results: The frequency of PAC insertion was 47.83%. Major indications for PAC insertion were poor left ventricular function, acute coronary syndrome, cardiogenic shock, significant left main disease and valvular heart disease patients. Minor complications were found in 23.22% cases, which included arrhythmia in 19.2% cases and coiling in 4.02%., Conclusions: TPulmonary artery catheter insertion is a safe technique with useful clinical application in the management of high-risk cardiac surgical patients. The PAC insertion rationale must be standardized to confirm the judicious use.

Introduction: Female sexual dysfunction (FSD) is a common problem, and many self-report questionnaires are available for its evaluation. Pakistani women with sexual problems feel shy to consult with their physician. A validated self-report questionnaire, in the local language with modest expressions is required for these women., Aim: The aim of this study was to translate, cross-culturally adapt, and perform a psychometric validation of an Urdu translation of the Female Sexual Function Index (FSFI)., Methods: The FSFI was translated in Urdu, and its precision was ascertained through reverse translation. It was pretested on 22 bilingual women and refined again to reach at a reliable Urdu version of the questionnaire FSFI-U. One hundred sixteen bilingual women, in a stable sexual relationship over the previous 6 months were finally asked to fill out the FSFI and FSFI-U. Their sexual function was then clinically evaluated and responses were compared with the clinical assessment as well as with each other., Main Outcome Measures: The responses were analyzed through descriptive statistics for reliability, face validity, agreement between the responses to the original English version and to the FSFI-U, and also for test-retest consistency. The data were analyzed statistically using Cronbach's alpha analysis, Intraclass correlation coefficients, Pearson correlation, and Student's t-test., Results: FSFI was found to be easily understandable and capable of adequately evaluating and measuring various aspects of female sexual function. A high degree of internal consistency was demonstrated on Cronbach's alpha analysis. Cronbach's α coefficient for various domains was sufficiently high ranging from 0.84 to 0.97. The clinical assessment of the presence and severity of FSD also matched with the self-report questionnaire. Similarly, various domains of FSFI had high degree of correlation in the Urdu version of FSFI (P < 0.001)., Conclusion: The Urdu translation version of FSFI is valid and reliable for use in the literate population of Pakistan. Rehman KU, Asif Mahmood M, Sheikh SS, Sultan T, Khan MA. The Female Sexual Function Index (FSFI): Translation, Validation, and Cross-Cultural Adaptation of an Urdu Version "FSFI-U". Sex Med 2015;3:244-250.

Background: Smoking plays a key role in increasing the inflammatory marker C-reactive protein (CRP)., Aims: To examine inverse correlation between CRP and magnesium levels in smokers and nonsmokers., Materials and Methods: A total of 192 healthy adult male subjects were included in the present study, out of which 96 were smokers and the remaining 96 were nonsmokers having age range from 20 to 40 years, and all the subjects belonged to District Matyari of Hyderabad. Serum CRP was measured by NycoCard standard kit method and magnesium levels by DiaSys standard kit method in smokers and nonsmokers., Results: The levels of serum CRP in smokers (14.62 ± 0.16 mg/L) is high as compared to nonsmokers (4.81 ± 0.38 mg/L), which is highly significant (P < 0.001). However, inverse results were seen for serum magnesium levels which were significantly higher (P < 0.001) in nonsmokers (2.52 ± 0.18 mg/L) as compared to the smokers (1.09 ± 0.38 mg/dL). A significant (P < 0.001) inverse relationship between serum CRP and magnesium concentrations were seen in smokers., Conclusion: This result shows that smoking increases serum CRP, an inflammatory marker parallel to decrease in serum magnesium levels in smokers having 20-40 years of age.

Objective: To examine the effect of smoking on complete blood count, serum C-reactive protein and magnesium levels in male smokers., Methods: The prospective case-control study was conducted in two villages of Matiari district in rural Sindh, Pakistan, from July to December 2013, and comprised healthy adult male smokers and an equal number of matching non-smokers as controls.The complete blood count, serum C-reactive protein and magnesium levels in all the subjects were measured to assess the effect of smoking on these parameters., Results: The two groups had 48 subjects each with an overall age range of 20-40 years. The results of complete blood count were comparable except for lymphocyte, which was significantly higher (p<0.001), and neutrophil, which was lower (p<0.001) in smokers than in the non-smokers. Serum C-reactive protein concentrations among the cases (14.62±0.16mg/L) compared to the controls (4.81±0.38mg/L) were significantly higher (p<0.001). However, reverse was true for serum magnesium levels which were significantly higher (p<0.001) in the controls (2.52±0.18mg/L) as against the cases (1.09±0.38mg/dl).Serum C-reactive protein-to-magnesium ratio was significantly higher (p<0.001) in smokers than in the non-smokers., Conclusion: Lymphocyte count was higher while neutrophil count was lower in smokers. Smoking also caused significant increase in serum C-reactive protein concentration concomitant to decrease in magnesium concentration in the smokers.

Objective: To evaluate the effect of smoking on blood levels of xanthine oxidase and malondialdehyde in acute myocardial infarction patients., Methods: The cross-sectional study was conducted from June to November 2013 and comprised myocardial infarction in-patients at Liaquat University of Medical and Health Sciences Hospital, Jamshoro, and Isra University Hospital, Hyderabad. Serum samples from age and gender matched smoking and non-smoking patients were investigated for the levels of xanthine oxidase and malondialdehyde by kit methods., Results: Of the 88 serum samples investigated, 68(77.3%) belonged to men and 20(22.7%) to women. Among the 44 smokers, 35(79.5%) were men and 9(20.5%) were women.The overall mean age of the group was 49.6±8.0 years. Among the 44 non-smokers, 33(75%) were men and 11(25%) women. The overall mean age of the group was 50.9±8.4 Years. Smokers compared to non-smokers had significantly raised mean serum xanthine oxidase (0.31±0.05 vs 0.28±0.03mg/dl; p<0.05) and malondialdehyde (32.29±3.30 vs 30.30±2.87 µmol/L; p<0.04) levels., Conclusion: Smokers as against the non-smokers were at higher risk of developing acute myocardial infarction owing to increased level of oxidative stress caused by smoking.

There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Compulsivity is a hallmark of drug addiction and in animal models is measured by consecutive incorrect responses to a previously rewarded stimulus during reversal learning. The aim of this study was to measure behavioral and neural markers of compulsivity in stimulant-dependent individuals and to test whether these markers could be modulated by treatment with drugs targeting the dopamine system., Methods: In a randomized, double-blind, placebo-controlled, crossover design, stimulant-dependent individuals (SDIs; n = 18) and healthy volunteers (n = 18) received single doses of dopamine D(2/3) receptor antagonist (amisulpride, 400 mg) and agonist (pramipexole, 0.5 mg) drugs. To examine compulsivity and its dopaminergic modulation more generally, patients with obsessive-compulsive disorder (OCD; n = 18) were also included in the study., Results: SDIs made significantly more perseverative responses to the previously correct stimulus immediately following reversal, compared with both healthy volunteers and patients with OCD. Across all participants, the number of perseverative errors was negatively correlated with functional activation in right fronto-striato-parietal networks-in particular, the right caudate nucleus. In SDIs, perseveration-related caudate activation was abnormally reduced in the placebo condition, but the dopamine D(2/3) agonist pramipexole normalized both perseverative responding and related activation of the right caudate., Conclusions: Perseveration during reversal learning was associated specifically with stimulant dependence rather than with compulsive behaviors more generally. The beneficial effects of a dopamine agonist drug challenge on both behavior and associated brain activation in SDIs may indicate new avenues for pharmacologic treatment in stimulant dependence., (Copyright © 2011 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Context: There are no effective pharmacotherapies for stimulant dependence but there are many plausible targets for development of novel therapeutics. We hypothesized that dopamine-related targets are relevant for treatment of stimulant dependence, and there will likely be individual differences in response to dopaminergic challenges., Objective: To measure behavioral and brain functional markers of drug-related attentional bias in stimulant-dependent individuals studied repeatedly after short-term dosing with dopamine D(2)/D(3) receptor antagonist and agonist challenges., Design: Randomized, double-blind, placebo-controlled, parallel-groups, crossover design using pharmacological functional magnetic resonance imaging., Setting: Clinical research unit (GlaxoSmithKline) and local community in Cambridge, England., Participants: Stimulant-dependent individuals (n = 18) and healthy volunteers (n = 18)., Interventions: Amisulpride (400 mg), pramipexole dihydrochloride (0.5 mg), or placebo were administered in counterbalanced order at each of 3 repeated testing sessions., Main Outcome Measures: Attentional bias for stimulant-related words was measured during functional magnetic resonance imaging by a drug-word Stroop paradigm; trait impulsivity and compulsivity of dependence were assessed at baseline by questionnaire., Results: Drug users demonstrated significant attentional bias for drug-related words, which was correlated with greater activation of the left prefrontal and right cerebellar cortex. Attentional bias was greater in people with highly compulsive patterns of stimulant abuse; the effects of dopaminergic challenges on attentional interference and related frontocerebellar activation were different between high- and low-compulsivity subgroups., Conclusions: Greater attentional bias for and greater prefrontal activation by stimulant-related words constitute a candidate neurocognitive marker for dependence. Individual differences in compulsivity of stimulant dependence had significant effects on attentional bias, its brain functional representation, and its short-term modulation by dopaminergic challenges.

Hepatic encephalopathy (HE) constitutes a neuropsychiatric syndrome which remains a major clinical problem in patients with cirrhosis. In the severest form of HE, cirrhotic patients may develop varying degrees of confusion and coma. Ammonia has been regarded as the key precipitating factor in HE, and astrocytes have been the most commonly affected cells neuropathologically. Although the evidence base supporting a pivotal role of ammonia is robust, in everyday clinical practice a consistent correlation between the concentration of ammonia in the blood and the manifest symptoms of HE is not observed. More recently the synergistic role of inflammation and infection in modulating the cerebral effects of ammonia has been shown to be important. Furthermore, it has been recognized that infection impairs brain function both in the presence and absence of liver disease. Thus it could be postulated that in the presence of ammonia, the brain is sensitized to a systemic inflammatory stimulus and is able to elicit an inflammatory response involving both proinflammatory and neurotransmitter pathways. Ammonia is not only directly toxic to astrocytes but induces neutrophil dysfunction with the release of reactive oxygen species, which contribute to oxidative stress and systemic inflammation. This may further exacerbate the cerebral effects of ammonia and potentially reduce the capacity of the neutrophil to fight microbial attack, thus inducing a vicious circle. This evidence supports the neutrophil in addition to ammonia as being culpable in the pathogenesis of HE, making the neutrophil a target for future anti-inflammatory therapeutic strategies in addition to ammonia lowering therapies.