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It is now well known that the severe acute respiratory syndrome (SARS-CoV-2) originated in the Wuhan province of Hubei, China in 2019. Having spread across different countries of the world, this highly contagious disease has posed many challenges for the healthcare workers to work without endangering themselves and their patients' wellbeing. Several things are yet not clear about the virus and the presence or absence of the virus in the cerebrospinal fluid (CSF) is currently a debated topic. This article reports the perioperative management of two coronavirus disease-19 positive cases, one of whom was a pregnant patient. Their CSF samples, which were collected during the administration of spinal anesthesia, tested to be negative for viral reverse transcription polymerase chain reaction (RT-PCR) test. We wish to highlight from these cases, that during spinal anesthesia, CSF in mildly symptomatic COVID-19 cases probably does not pose a risk of transmission to the anesthesiologist. However, we suggest that due to the varied presentations of the virus, health care personnel, especially anesthesiologists have to be careful during the perioperative management of such cases. [ABSTRACT FROM AUTHOR]

Efforts to find a better adjuvant in regional anaesthesia are underway since long. Aims and objectives are to compare the efficacy and clinical profile of two α-2 adrenergic agonists, dexmedetomidine and clonidine, in epidural anaesthesia with special emphasis on their sedative properties and an ability to provide smooth intra-operative and post-operative analgesia. A prospective randomized study was carried out which included 50 adult female patients between the ages of 44 and 65 years of (American Society of Anaesthesiologists) ASAI/II grade who underwent vaginal hysterectomies. The patients were randomly allocated into two groups; ropivacaine + dexmedetomidine (RD) and ropivacaine + clonidine (RC), comprising of 25 patients each. Group RD was administered 17 ml of 0.75% epidural ropivacaine and 1.5 μg/kg of dexmedetomidine, while group RC received admixture of 17 ml of 0.75% ropivacaine and 2 μg/kg of clonidine. Onset of analgesia, sensory and motor block levels, sedation, duration of analgesia and side effects were observed. The data obtained was subjected to statistical computation with analysis of variance and chi-square test using statistical package for social science (SPSS) version 10.0 for windows and value of P < 0.05 was considered significant and P < 0.0001 as highly significant. The demographic profile, initial and post-operative block characteristics and cardio-respiratory parameters were comparable and statistically nonsignificant in both the groups. However, sedation scores with dexmedetomidine were better than clonidine and turned out to be statistically significant (P < 0.05). The side effect profile was also comparable with a little higher incidence of nausea and dry mouth in both the groups which was again a non-significant entity (P > 0.05). Dexmedetomidine is a better neuraxial adjuvant compared to clonidine for providing early onset of sensory analgesia, adequate sedation and a prolonged post-operative analgesia. [ABSTRACT FROM AUTHOR]

Background: Postoperative nausea and vomiting (PONV) is one of the complications which hamper the successful implementation of day care surgical procedure in spite of the availability of so many antiemetic drugs and regimens for its prevention. The aim was to compare the prophylactic effects of intravenously (IV) administered ondansetron and palonosetron on PONV prevention in patients undergoing laparoscopic gynecological surgery under general anesthesia. Methods: A prospective double-blind study comprised of 60 ASAI/II female patients between the age group of 25 and 40 years was carried out in the Departments of Anesthesiology and Obstetrics and Gynecology of our institute. Patients were randomly divided into two groups of 30 patients each in a double-blind manner. Group I received 8 mg of inj. ondansetron IV while group II received inj. palonosetron 0.075 mg IV 5 minutes before the induction of anesthesia. The need for rescue antiemetics, episodes of PONV and other side effects were observed for 6 hours in the postanesthesia care unit and thereafter complaints were received on phone after the discharge. At the end of study, results were compiled and statistical data was subjected to statistical analysis using Student two-tailed 't' and χ2 test and value of P<0.05 was considered significant. Results: The demographical profile of the patients was comparable. Twenty and 13.33% of the patients in group I had nausea and vomiting episodes postoperatively as compared to 6.67% and 3.33%, respectively, in group II which was statistically significant (P<0.05). Twenty percent of the patients in group I experienced significant post-op headache as compared to 6.67% in group II. The mean rescue dose of antiemetic was significantly higher (10.6 mg) in the group I as compared to group II (6.4 mg) (P=0.036). The rest of parameters were comparable and statistically nonsignificant. Conclusions: Palonosetron is a comparatively better drug to prevent the PONV in patients undergoing day care surgical procedures as compared to ondansetron as it has got a prolonged duration of action and favorable side-effects profile. [ABSTRACT FROM AUTHOR]

The global changes have occurred throughout the 20th century and there is no reason to believe that they will slow down their pace in this millennium. The disintegration of the Soviet Union with its defeat in the Cold War and the terrorist attacks of September 11 have changed geopolitical environment and generated new forms of instability in the world and particularly in South Asia. These events also damaged those traditional international security arrangements that were evolved after the World War II. This paper will examine the major challenges and trends in Pakistan's foreign policy after the terrorist attacks of September 11, 2001 that caused major shift in the US policy towards the region and the issues pertaining to the US-led global war that has much significance for Pakistan. [ABSTRACT FROM AUTHOR]

Pyrexia can be extremely threatening during the normal progression of pregnancy if it occurs during the early phase of gestation as compared to the latter half of pregnancy. The degree of temperature rise, stage of pregnancy, and duration of the underlying illness are the important determinants for the outcome of pregnancy. Fever, resulting from the intrauterine infections, can be extremely hazardous for the newborn. Any history of fever (>24 h) during pregnancy mandate a complete clinical examination and thorough investigations. We report successful management of a rare case of prolonged high-grade pyrexia with unusual cause during mid-pregnancy. [ABSTRACT FROM AUTHOR]

Background: Bleeding disorder of unknown cause (BDUC) is a diagnostic category encompassing patients with a clear bleeding phenotype but without identifiable abnormality on hemostatic testing. The optimal management of hemostasis in BDUC patients prior to invasive procedures and childbirth is uncertain., Objectives: Our objective was to characterize periprocedural hemostatic prophylaxis and bleeding outcomes in patients with BDUC., Methods: We conducted a retrospective cohort study of adult patients with BDUC at 2 academic medical centers. Following diagnosis of BDUC, subsequent surgical procedures and childbirths were analyzed using a combination of registry data and manual chart review., Results: We identified 127 patients with mean age of 39.9 years (SD = 16.6); the majority of patients were female (91.3%). Forty-eight major procedures, 70 minor procedures, and 19 childbirths were analyzed. Antifibrinolytic monotherapy was advised for 57% of major procedures, 59% of minor procedures, and 67% of childbirths. Perioperative platelet transfusion was recommended in 26% of major procedures and 9% of minor procedures in combination with other hemostatic agents. Major or clinically relevant nonmajor bleeding occurred in 4.1% (4/98) of procedures with prophylaxis and 10% (2/20) of procedures without prophylaxis. Postpartum hemorrhage occurred in 26% (5/19) of deliveries., Conclusion: In this multiinstitution experience, we found overall low rates of hemostatic complications in procedures completed with hemostatic prophylaxis, although preventing hemorrhage in childbirth and gynecologic procedures remain unmet needs., (© 2024 The Authors.)

Purulent pericarditis is a rare and potentially life-threatening condition characterized by infection of the pericardial space. We describe a case of purulent bacterial pericarditis in a 41-year-old male with no significant medical or surgical history who had concomitant pulmonary Histoplasma infection. Streptococcus intermedius was the bacteria directly responsible for the pericardial infection, though co-infection with histoplasmosis likely predisposed him to develop purulent pericarditis. We hypothesize histoplasmosis caused mediastinal lymphadenopathy, facilitating contact between a necrotic lymph node and the pericardium and contiguous suppuration of bacteria to the pericardial space. We treated S. intermedius and Histoplasma capsulatum with ceftriaxone and amphotericin B, respectively. Additionally, the patient presented in cardiac tamponade requiring emergent pericardiocentesis and drain placement. His course was also complicated by pericardial constriction. Cardiac magnetic resonance confirmed this, showing inflamed pericardium and abnormal septal motion with inspiration, and he had symptoms refractory to antimicrobials and anti-inflammatories. As such, he required pericardiectomy. This case demonstrates maintaining suspicion for secondary infectious foci as a contributor to the pathogenesis of purulent pericarditis is important, as pulmonary histoplasmosis played a pivotal role in allowing S. intermedius to spread to the pericardium but was not the primary infection. It also highlights the multifaceted evaluation and management of purulent pericarditis, highlighting the role of echocardiography and emergent pericardial drainage if cardiac tamponade is present, the importance of targeted antimicrobial therapy, the superior ability of cardiac magnetic resonance to identify pericardial constriction as a sequela of purulent pericarditis, and indications for pericardiectomy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Christian-Miller et al.)

This review aims to explore the potential of artificial intelligence (AI) in coronary CT angiography (CCTA), a key tool for diagnosing coronary artery disease (CAD). Because CAD is still a major cause of death worldwide, effective and accurate diagnostic methods are required to identify and manage the condition. CCTA certainly is a noninvasive alternative for diagnosing CAD, but it requires a large amount of data as input. We intend to discuss the idea of incorporating AI into CCTA, which enhances its diagnostic accuracy and operational efficiency. Using such AI technologies as machine learning (ML) and deep learning (DL) tools, CCTA images are automated to perfection and the analysis is significantly refined. It enables the characterization of a plaque, assesses the severity of the stenosis, and makes more accurate risk stratifications than traditional methods, with pinpoint accuracy. Automating routine tasks through AI-driven CCTA will reduce the radiologists' workload considerably, which is a standard benefit of such technologies. More importantly, it would enable radiologists to allocate more time and expertise to complex cases, thereby improving overall patient care. However, the field of AI in CCTA is not without its challenges, which include data protection, algorithm transparency, as well as criteria for standardization encoding. Despite such obstacles, it appears that the integration of AI technology into CCTA in the future holds great promise for keeping CAD itself in check, thereby aiding the fight against this disease and begetting better clinical outcomes and more optimized modes of healthcare. Future research on AI algorithms for CCTA, making ethical use of AI, and thereby overcoming the technical and clinical barriers to widespread adoption of this new tool, will hopefully pave the way for profound AI-driven transformations in healthcare., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Thribhuvan Reddy et al.)

Objective: We assessed the effectiveness of oral Hydroxychloroquine (HC), Azithromycin (AZ) and Oseltamivir (OS), alone or combined, among patients hospitalized with mildly symptomatic coronavirus infectious disease (COVID-19)., Methods: Following the approval of the National Bioethics Committee and prospective registration (clinicaltrials.gov NCT04338698), a multicenter randomized clinical trial of adaptive design was conducted at 10 multispecialty hospitals in Pakistan. Patients were randomized into seven treatment groups. Starting April 15, 2020, consenting, eligible, otherwise healthy adult patients or those with co-morbidities under control, were recruited if they presented with mildly symptomatic COVID-19 (scored 3 on a 7-point ordinal scale anchored between 1 = not hospitalized, able to undertake normal activities, to 7 = death) confirmed by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). Two primary outcomes were assessed by day seven: Turning qRT-PCR negative; and clinical improvement of two points from the baseline. Outcome rates were compared using a chi-square test. Multiple imputations were applied to handle missing data. An interim data analysis was carried out on July 19, 2020, following which the study continued without treatment group changes. Data Safety and Monitoring Board advised to stop recruitment due to its futility on January 18, 2021., Results: Of 471 patients randomized, a total of 426 (90.4%) completed the follow-up for primary outcomes. Based on imputed data analyses at day seven: Total qRT-PCR negative cases were 137/471 (29%, 95% CI 25.0 - 33.4). By day seven, a total of 111/471 (23.5%, 95% CI 19.8 - 27.6) showed clinical improvement. No serious or non-serious adverse event was reported., Conclusions: Among patients with mild COVID-19, there was no statistically significant difference in the effectiveness of oral antimalarial, antiviral, or antibiotic treatments. Clinicaltrials.gov ID: NCT04338698., (Copyright: © Pakistan Journal of Medical Sciences.)

Fatty acid handling and complex lipid synthesis are altered in the kidney cortex of diabetic patients. We recently showed that inhibition of the renin-angiotensin system without changes in glycemia can reverse diabetic kidney disease (DKD) and restore the lipid metabolic network in the kidney cortex of diabetic (db/db) mice, raising the possibility that lipid remodeling may play a central role in DKD. However, the roles of specific enzymes involved in lipid remodeling in DKD have not been elucidated. In the present study, we used this diabetic mouse model and a proximal tubule epithelial cell line (HK2) to investigate the potential relationship between long-chain acyl-CoA synthetase 1 (ACSL1) and lipid metabolism in response to fatty acid exposure and inflammatory signals. We found ACSL1 expression was significantly increased in the kidney cortex of db/db mice, and exposure to palmitate or tumor necrosis factor-α significantly increased Acsl1 mRNA expression in HK-2 cells. In addition, palmitate treatment significantly increased the levels of long-chain acylcarnitines and fatty acyl CoAs in HK2 cells, and these increases were abolished in HK2 cell lines with specific deletion of Acsl1(Acsl1KO cells), suggesting a key role for ACSL1 in fatty acid β-oxidation. In contrast, tumor necrosis factor-α treatment significantly increased the levels of short-chain acylcarnitines and long-chain fatty acyl CoAs in HK2 cells but not in Acsl1KO cells, consistent with fatty acid channeling to complex lipids. Taken together, our data demonstrate a key role for ACSL1 in regulating lipid metabolism, fatty acid partitioning, and inflammation., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

This paper presents a data-driven discrepancy modeling method that variationally embeds measured data in the modeling and analysis framework. The proposed method exploits the residual between the first-principles theory and sensor-based measurements from the dynamical system, and it augments the physics-based model with a variationally derived loss function that is comprised of this residual. The method was first developed in the context of linear elasticity (Masud and Goraya, J. Appl. Mech. 89 (11), 111001 (2022)) wherein the relation between the discrepancy model and loss terms was derived to show that the data embedding terms behave like residual-based least-squares regression functions. An interpretation of the stabilization tensor as a kernel function was formally established and its role in assimilating a-priori knowledge of the problem in the modeling method was highlighted. The present paper employs linear elastodynamics as a model problem where the Data-Driven Variational (DDV) method incorporates high-fidelity data into the forward simulations, thereby driving the problem with not only the boundary and initial conditions, but also by measurement data that is taken at only a small subset of the total domain. The effect of the loss function on the time-dependent response of the system is investigated under a variety of loading conditions and model discrepancies. The energy and Morlet wavelet analyses reveal that the problem with embedded data recovers the energy and the fundamental frequency band of the target system. Time histories of strain energy and kinetic energy of a cantilever beam undergoing damped oscillations are recovered by including known data in an undamped model to highlight the data-driven discrepancy modeling feature of the method under the combined effect of parameter and model discrepancy., Competing Interests: Declaration of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Physics Informed Neural Networks (PINNs) are shown to be a promising method for the approximation of partial differential equations (PDEs). PINNs approximate the PDE solution by minimizing physics-based loss functions over a given domain. Despite substantial progress in the application of PINNs to a range of problem classes, investigation of error estimation and convergence properties of PINNs, which is important for establishing the rationale behind their good empirical performance, has been lacking. This paper presents convergence analysis and error estimates of PINNs for a multi-physics problem of thermally coupled incompressible Navier-Stokes equations. Through a model problem of Beltrami flow it is shown that a small training error implies a small generalization error. Posteriori convergence rates of total error with respect to the training residual and collocation points are presented. This is of practical significance in determining appropriate number of training parameters and training residual thresholds to get good PINNs prediction of thermally coupled steady state laminar flows. These convergence rates are then generalized to different spatial geometries as well as to different flow parameters that lie in the laminar regime. A pressure stabilization term in the form of pressure Poisson equation is added to the PDE residuals for PINNs. This physics informed augmentation is shown to improve accuracy of the pressure field by an order of magnitude as compared to the case without augmentation. Results from PINNs are compared to the ones obtained from stabilized finite element method and good properties of PINNs are highlighted., Competing Interests: Declarations Conflicts of interest Authors have no competing interests.

Background: Breast cancer risk estimates for atypical lesions are based primarily on case-control studies of patients with open biopsies. The authors report the cumulative breast cancer incidence after a core biopsy diagnosis of atypical hyperplasia (ductal or lobular) or lobular carcinoma in situ., Methods: A cohort study with central pathology review was conducted on 393 patients who had core biopsy diagnoses of atypical hyperplasia and lobular carcinoma in situ from 1995 through 2010. Follow-up was available for 255 of 264 patients (97%) at a median of 87 months (range, 3-236 months)., Results: There were 212 patients (54%) who were not upgraded on excision and had no personal history of breast cancer. Of these, 21 of 212 (9.9%) developed breast cancer, including 15 invasive carcinomas, 4 ductal carcinomas in situ, 1 pleomorphic lobular carcinoma in situ, and 1 unknown type. The prior core biopsy diagnoses were atypical ductal hyperplasia for 11 patients (52%) and atypical lobular hyperplasia/lobular carcinoma in situ in the remaining 10 patients (48%). The number of atypical foci in the core biopsy was not significantly associated with the subsequent development of breast cancer (P = .42). Of the 15 invasive carcinomas, 11 (73%) were ipsilateral, 11 (73%) were pathologic T1 tumors, 5 (33%) were pathologic N1 tumors, 13 (87%) were estrogen receptor-positive, and 1 (7%) was amplified for human epidermal growth factor receptor 2., Conclusions: In patients who had an initial diagnosis of atypical hyperplasia or lobular carcinoma in situ on core biopsy, the 7-year cumulative breast cancer incidence was 9.9%. Most tumors were ipsilateral, stage I, estrogen receptor-positive, invasive carcinomas. The current data support close clinical and radiologic follow-up for more than 5 years in this patient population. Cancer 2018;124:459-65. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Purpose: To report a novel technique for endovascular retrieval of a maldeployed vascular closure device, obviating the need for a femoral cutdown., Technique: To remove a 6-F Angio-Seal device that embolized to the superficial femoral artery, the contralateral common femoral artery was accessed, and an 8-F, 65-cm-long sheath was inserted just proximal to the embolus. A second semistiff 0.035-inch buddy wire was advanced past the lesion along the sheath. A 0.014-inch wire was advanced past the embolus, and a SpiderFX embolic protection device was deployed 1 cm past the embolized Angio-Seal device. The sheath was advanced so as to push the embolus into the filter. The sheath and the filter containing the Angio-Seal device were then removed., Conclusion: Endovascular retrieval of an embolized Angio-Seal device can be done using an embolic filter device, restoring arterial flow to the limb., (© The Author(s) 2015.)