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Background: Rheumatic Heart Disease (RHD) is a disease of developing countries where it inflects significant burden dis-proportionality. We investigated the role of socio-economic and environmental risk factors for RHD. Methods: This was descriptive cross-sectional conducted at Pakistan Institute of Medical Sciences Islamabad by including the patients coming to cardiology out door patient department through convenient sampling technique. Study was approved from ethical committee of Pakistan institute of Medical Sciences Islamabad and written consent was taken prior to start the interview. Results: In this study, the average age of patient with rheumatic heart disease was 29.4 years, male predominance of patients was observed. 67% of subjects had income below Rs. 20,000. Average BMI of subjects was 22.4±4.04. It was observed that 75.25 % of people lived in houses with an area of less than 5 marla. Average area of house was found to be 5.12±2.8 marla. Overcrowding was noticed in 60.8 % of the subjects. Conclusion: There is a high prevalence of RHD and Acute Rheumatic Fever (ARF) in Pakistan. The major findings of this study were that Overcrowding, poor hygienic conditions, low socio-economic status, are major risk factors for RHD. In order to address this alarming situation, platforms like Pakistan Pediatric Cardiac Society and Pakistan Pediatric Association need to be mobilized for health promotion regarding awareness of the disease. [ABSTRACT FROM AUTHOR]

Background: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment.Design: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment.Subjects: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment.Main Measures: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment.Key Results: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment.Conclusions: Despite more women entering medicine, substantial gender disparities remain in various medical disciplines. This study explores the extent of these disparities in Canadian academic internal medicine, particularly in academic ranks, leadership positions, and research productivity.Cross-sectional.Faculty physicians within internal medicine and subspecialties.Data on faculty physicians with Medical Doctorate (MD), Doctor of Osteopathic Medicine (DO), or Bachelor of Medicine, Bachelor of Surgery (MBBS) degrees were compiled from 17 internal medicine programs listed in the Canadian Resident Matching Service (CaRMS). Research metrics were obtained using Elsevier’s Scopus, and analyses were performed with Stata v14.2.Among 5099 physician faculty members in internal medicine, 34% were women, and 66% were men. Among the faculty members holding leadership positions, 68% were men, and 32% were women. There was a significant difference in h-index between men and women physician faculty members (p ≤ 0.001), with men having a higher research output. Across all academic ranks, men faculty had higher median h-index values: Assistant Professor (12 vs. 9), Associate Professor (20 vs. 16), and Professor (40 vs. 30). Women were underrepresented in the procedural specialties, while only a few internal medicine subspecialties, such as palliative medicine and geriatrics, had a women predominance.Our study underscores existing gender disparity within academic internal medicine in Canada, aligning with global trends. Women remain disproportionately underrepresented in academic ranks, leadership positions, and research productivity. Addressing these disparities necessitates a systemic and multifaceted approach, encompassing policy reforms, mentorship, and fostering an inclusive work environment. [ABSTRACT FROM AUTHOR]

Simple Summary: Despite improvements in therapeutics, head and neck squamous cell carcinomas (HNSCC) relapse in more than 50% of cases due to the development of chemo-radiotherapy resistance during sequential treatments. Our findings provide a strong rationale which can improve potential therapeutic strategies for overcoming drug resistance in HNSCC. We demonstrated that expression of miR124-3p and miR766-3p is associated with drug resistance in HNSCC, and their blockade greatly enhances the efficacy of standard anti-HNSCC therapeutics including 5-fluorouracil and cisplatin (FP chemotherapy), as well as radiotherapy. We discovered miR124-3p and miR766-3p-mediated mechanisms of resistance involve transcriptional factors CREBRF and NR3C2 in HNSCC. These results warrant testing miR766-3p and miR124-3p as predictors of response to chemo-radiotherapy in clinical settings and as markers for selecting patients for alternative treatment approach. Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive disease with poor prognosis, which is mainly due to drug resistance. The biology determining the response to chemo-radiotherapy in HNSCC is poorly understood. Using clinical samples, we found that miR124-3p and miR766-3p are overexpressed in chemo-radiotherapy-resistant (non-responder) HNSCC, as compared to responder tumors. Our study shows that inhibition of miR124-3p and miR766-3p enhances the sensitivity of HNSCC cell lines, CAL27 and FaDu, to 5-fluorouracil and cisplatin (FP) chemotherapy and radiotherapy. In contrast, overexpression of miR766-3p and miR124-3p confers a resistance phenotype in HNSCC cells. The upregulation of miR124-3p and miR766-3p is associated with increased HNSCC cell invasion and migration. In a xenograft mouse model, inhibition of miR124-3p and miR766-3p enhanced the efficacy of chemo-radiotherapy with reduced growth of resistant HNSCC. For the first time, we identified that miR124-3p and miR766-3p attenuate expression of CREBRF and NR3C2, respectively, in HNSCC, which promotes aggressive tumor behavior by inducing the signaling axes CREB3/ATG5 and β-catenin/c-Myc. Since miR124-3p and miR766-3p affect complementary pathways, combined inhibition of these two miRNAs shows an additive effect on sensitizing cancer cells to chemo-radiotherapy. In conclusion, our study demonstrated a novel miR124-3p- and miR766-3p-based biological mechanism governing treatment-resistant HNSCC, which can be targeted to improve clinical outcomes in HNSCC. [ABSTRACT FROM AUTHOR]

Background: Severe acute respiratory syndrome coronavirus 2 infection can lead to a constellation of viral and immune symptoms called coronavirus disease 2019. Emerging literature increasingly supports the premise that severe acute respiratory syndrome coronavirus 2 promotes a prothrombotic milieu. However, to date there have been no reports of acute aortic occlusion, itself a rare phenomenon. We report a case of fatal acute aortic occlusion in a patient with coronavirus disease 2019.Case Report: A 59-year-old Caucasian male with past medical history of peripheral vascular disease presented to the emergency department for evaluation of shortness of breath, fevers, and dry cough. His symptoms started 5-7 days prior to the emergency department visit, and he received antibiotics in the outpatient setting without any effect. He was found to be febrile, tachypneic, and hypoxemic. He was placed on supplemental oxygen via a non-rebreather mask. Chest X-ray showed multifocal opacifications. Intravenous antibiotics for possible pneumonia were initiated. Hydroxychloroquine was initiated to cover possible coronavirus disease 2019 pneumonia. During the hospitalization, the patient became progressively hypoxemic, for which he was placed on bilevel positive airway pressure. D-dimer, ferritin, lactate dehydrogenase, and C-reactive protein were all elevated. Severe acute respiratory syndrome coronavirus 2 reverse transcription polymerase chain reaction was positive. On day 3, the patient was upgraded to the intensive care unit. Soon after he was intubated, he developed a mottled appearance of skin, which extended from his bilateral feet up to the level of the subumbilical plane. Bedside ultrasound revealed an absence of flow from the mid-aorta to both common iliac arteries. The patient was evaluated emergently by vascular surgery. After a discussion with the family, it was decided to proceed with comfort-directed care, and the patient died later that day.Discussion: Viral infections have been identified as a source of prothrombotic states due to direct injury of vascular tissue and inflammatory cascades. Severe acute respiratory syndrome coronavirus 2 appears to follow a similar pattern, with numerous institutions identifying elevated levels of thrombotic complications. We believe that healthcare providers should be aware of both venous and arterial thrombotic complications associated with coronavirus disease 2019, including possible fatal outcome. [ABSTRACT FROM AUTHOR]

Background: Coronary artery disease (CAD) in diabetes mellitus (DM) is a significant cause of mortality among US adults. This study investigates trends in CAD-related mortality in adults aged 25 and older with DM, focusing on geographic, gender, and racial/ethnic disparities from 1999 to 2020., Methods: A retrospective analysis was conducted using death certificate data from the CDC WONDER database from 1999 to 2020. Age-adjusted mortality rates (AAMRs), annual percent change (APC), and average annual percentage change (AAPC) were calculated per 100,000 persons, stratified by year, sex, race/ethnicity, and geographical region., Results: CAD in DM accounted for 1,462,279 deaths among US adults aged 25+. Most deaths occurred in medical facilities (44.2 %) and at home (29.3 %). The overall AAMR for CAD in DM-related deaths decreased from 36.3 in 1999 to 31.7 in 2020, with an AAPC of -0.96 (95 % CI: -1.29 to -0.77, p < 0.000001). Men had higher AAMRs (41.6) compared to women (22.6), with a more significant decrease in women (AAPC: -2.10, p < 0.000001) than in men (AAPC: -0.34, p = 0.001200). Racial/ethnic disparities showed the highest AAMRs in American Indians/Alaska Natives (43.6), followed by Blacks (37.8), Hispanics (33.8), Whites (29.7), and Asians/Pacific Islanders (22.5). The most significant decrease was in Hispanics (AAPC: -1.64, p < 0.000001). Geographically, AAMRs ranged from 13.7 in Nevada to 51.3 in West Virginia, with the highest mortality observed in the Midwest (AAMR: 34.5). Nonmetropolitan areas exhibited higher AAMRs (35.2) than metropolitan areas (29.7), with a more pronounced decrease in metropolitan areas (AAPC: -1.22, p < 0.000001) compared to nonmetropolitan areas (AAPC: -0.03, p = 0.854629)., Conclusion: The notable increase in mortality rates associated with CAD among patients with DM from 2018 to 2020 presents a substantial concern that necessitates targeted public health interventions to ensure equitable access to cardiovascular care., Competing Interests: Declaration of competing interest All authors have no conflict of interest to disclose that is related to this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To synthesize the evidence on the efficacy and safety of teclistamab in treating relapsed/refractory multiple myeloma (RRMM). A systematic search for records published from inception until June 2024 was conducted on PubMed, Web of Science, EMBASE, and Google Scholar databases. Five studies with 661 RRMM patients were included in the analysis. The pooled results showed that teclistamab led to an overall response rate (ORR) of 62.8% (95% Confidence Interval (CI): 58.6-66.8), a ≥ very good partial response or better (VGPR) of 52.1% (95% CI: 46.8-57.3), and a ≥ complete response or better (CR) of 29.5% (95% CI: 21.9-38.4). When the ORR was assessed in different subgroups, we found that patients with extramedullary disease (EMD) had considerably lower ORR than those without EMD (45% vs. 71%, p < 0.0001). The ORR was significantly lower in patients with prior (B-cell maturation antigen) BCMA-directed therapy (OR: 2.24, p = 0.002) and those with stage III disease (OR: 3.69, p = 0.0001). However, the subgroup analyses showed no considerable difference in the ORR between patients with high or standard-risk cytogenetics (OR: 1.05 p = 0.82) and those with penta-drug or triple-class-refractory disease (OR: 0.97 p = 0.89). Regarding the safety of teclistamab, the pooled results showed that the incidence of grade ≥ 3 adverse events was high (90.7%). However, grade ≥ 3 cytokine release syndrome (CRS) and neurotoxic events were low (1.5% and 2.2%, respectively). RRMM patients treated with teclistamab display good response rates., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: This study aimed to analyze two decades of consecutive mortality data to investigate cardiovascular deaths in Systemic Lupus Erythematosus (SLE) across the United States (US), identifying patterns and disparities in mortality rates., Methods: A retrospective analysis was conducted using mortality data from the CDC WONDER database spanning 1999-2020. ICD-10 codes for diseases of circulatory system (I00-I99) and for SLE (M32) were used to identify cardiovascular-related deaths in SLE among adults aged 25 years and older at the time of death. Age-adjusted mortality rates (AAMRs) per 1,000,000 persons were calculated, and trends were assessed using Average Annual Percentage Change (AAPC) and Annual Percent Change (APC) using Joinpoint. Data were stratified by year, sex, race/ethnicity, and geographical regions., Results: Between 1999 and 2020, cardiovascular-related deaths in SLE accounted for 6,548 deaths among adults aged 25 and older in the US. The overall AAMR for cardiovascular-related deaths in SLE decreased from 1.81 in 1999 to 1.53 in 2020, with an AAPC of -1.00 (95% CI: -1.91 to -0.24, p=0.025). A significant decline occurred from 1999 to 2014 with an APC of -3.20 (95% CI: -5.56 to -2.18; p=0.02), followed by a notable increase of 4.73 (95% CI: 0.41 to 18.29, p=0.23) from 2014 to 2020. Women exhibited higher AAMRs compared to men (women: 2.12, men: 0.53). The AAMR decreased for both men and women, with a steeper decline for men from 1999 to 2014 (APC: -4.85 95% CI: -15.58 to -2.62; p<0.02) compared to women in the same period (APC: -2.81 95% CI: -5.78 to -1.73; p<0.03). The Black cohort had a higher AAMR (3.54 95% CI: 3.37 to 3.70), compared to the White cohort (1.12 95% CI: 1.09 to 1.16). The highest mortality was in the Western region (AAMR: 1.60 95% CI: 1.52 to 1.68). Geographically, AAMRs ranged from 0.62 in Massachusetts to 3.11 in Oklahoma. Metropolitan areas had higher AAMRs than Non-metropolitan areas [(1.41 95% CI: 1.37 to 1.45) vs (1.29 95% CI: 1.21 to 1.37)], with a significant mortality reduction in Metropolitan area from 1999-2020 (AAPC: -1.04 95% CI: -1.95 to -0.28, p=0.0064) compared to Non-metropolitan areas in the same time frame (AAPC: -0.86, 95% CI: -2.43 to 0.33 p=0.152)., Conclusions: This analysis highlights notable differences in mortality rates related to cardiovascular deaths in SLE. The target population was adult patients aged 25 and older in the United States. These results are based on demographic and geographic factors. Initially, there was a considerable decrease, but recently the mortality rates have started to rise. This highlights the importance of patient focused interventions to address disparities and improve health outcomes., Competing Interests: Declaration of competing 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., (Copyright © 2024. Published by Elsevier Inc.)

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types and known for its suppressive effect on T cells through its interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1 + neutrophils has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1 + neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. The administration of PD-L1 monoclonal antibody did not impair PD-L1 + neutrophil function, suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by their increased plasma alanine transaminase (ALT) levels and frequencies of inflammatory leukocytes in the liver, implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for the enhanced anti-bacterial function of neutrophils. Moreover, PD-L1 + neutrophils are an indispensable population attenuating inflammatory leukocyte activities, assisting in a smooth transition into the resolution phase in MRSA infection.

Background: Balloon non-crossable stenoses represent a challenging subset of coronary artery disease (CAD). They are clinically associated with patients who are older, frailer, and with multi-morbidities, and angiographically with increased tortuosity and coronary artery calcification. Combined rotational (RA) excimer laser coronary atherectomy (ELCA), or RASER, may facilitate stent delivery and deployment in non-crossable, non-dilatable severely calcified lesions. In this study, we assessed preliminary safety and efficacy of the RASER hybrid technique., Methods: RASER feasible percutaneous coronary intervention (PCI) procedures performed at a large tertiary hospital in the northeast of England were retrospectively analyzed from September 1, 2008, to February 28, 2022. Major endpoints were in-hospital death from any cause, as well as procedural and angiographic success, defined by stent delivery with less than 50% residual stenosis and without clinical or angiographic complications, respectively., Results: From 74 unique cases, there were 28 RASER, 24 ELCA/RA, 16 balloon angioplasty ± stenting, and 6 medically treated patients. In-hospital mortality rate was 5.2%, including 1 ELCA- and 3 RASER-treated patients. Successful stent delivery was achieved in significantly more RASER-treated patients compared to ELCA/RA- or balloon-treated patients: 96.4% (27/28), 25% (6/24), and 31.3% (5/16) respectively (P less than .001)., Conclusions: In our retrospective, single-center study, patients with CAD who were deemed appropriate for RASER PCI had a high peri-procedural mortality rate. In this context, adjunctive RASER therapy provides acceptable safety and efficacy as a bailout strategy, with at least 3 out of 5 patients achieving satisfactory procedural and angiographic results. Randomized controlled trials are needed to comprehensively compare the clinical outcomes of high-risk RASER PCI vs conservative medical therapy.

The pathogenesis of atherosclerosis is defined by impaired lipid handling by macrophages which increases intracellular lipid accumulation. This dysregulation of macrophages triggers the accumulation of apoptotic cells and chronic inflammation which contributes to disease progression. We previously reported that mice with increased macrophage-specific angiotensin-converting enzyme, termed ACE10/10 mice, resist atherosclerosis in an adeno-associated virus-proprotein convertase subtilisin/kexin type 9 (AAV-PCSK9)-induced model. This is due to increased lipid metabolism by macrophages which contributes to plaque resolution. However, the importance of ACE in peripheral blood monocytes, which are the primary precursors of lesional-infiltrating macrophages, is still unknown in atherosclerosis. Here, we show that the ACE-mediated metabolic phenotype is already triggered in peripheral blood circulating monocytes and that this functional modification is directly transferred to differentiated macrophages in ACE10/10 mice. We found that Ly-6Clo monocytes were increased in atherosclerotic ACE10/10 mice. The monocytes isolated from atherosclerotic ACE10/10 mice showed enhanced lipid metabolism, elevated mitochondrial activity, and increased adenosine triphosphate (ATP) levels which implies that ACE overexpression is already altered in atherosclerosis. Furthermore, we observed increased oxygen consumption (VO2), respiratory exchange ratio (RER), and spontaneous physical activity in ACE10/10 mice compared to WT mice in atherosclerotic conditions, indicating enhanced systemic energy consumption. Thus, ACE overexpression in myeloid lineage cells modifies the metabolic function of peripheral blood circulating monocytes which differentiate to macrophages and protect against atherosclerotic lesion progression due to better lipid metabolism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cao, Saito, Xu, Fan, Li, Ahmed, Jovanovic, Shibata, Che, Bernstein, Gianni, Divakaruni, Okwan-Duodu, Khan, Riera, Chen and Bernstein.)

Background Medical education often overlooks the significance of design and innovation literacy, resulting in a knowledge gap in undergraduate medical education (UME) regarding formal training in these areas. Incorporating innovation into UME's core curriculum is crucial as future physicians will encounter evolving technologies, and fostering a transdisciplinary approach can enable collaborative problem-solving and improve patient health outcomes. Methodology We developed a comprehensive medical biodesign curriculum focused on innovation, including problem identification, prototype testing, and product commercialization. Participants were selected based on applications, interviews, and diverse criteria. A survey was conducted before and after the program to assess students' biodesign experiences and knowledge, with data analyzed using descriptive statistics and paired t-tests. Results Of the 41 participants, 24 (58.5%) completed both pre- and post-program surveys. These five-point Likert surveys showed a significant shift from pre-program to responses demonstrating increased "comfort levels in explaining and applying biodesign principles" (p < 0.0001). Specifically, the "comfort level in taking a product to market" increased from 33% to 67% (p = 0.01), while the "comfort level in applying the biodesign process" increased from 29% to 92% (p < 0.0001). Moreover, 58.3% of participants expressed interest in continuing their current projects, and 70.8% of students stated feeling confident in generating ideas and solutions with their team members. Conclusions The medical biodesign curriculum demonstrated success in exposing undergraduate medical and engineering students to the concepts of medical innovation and biodesign. The program has led to a significant improvement in students' knowledge and comfort levels in applying the biodesign process and taking a product to market. The high level of interest and participation in the program highlight the need for incorporating innovative training in UME to foster creativity and prepare future physicians to contribute to the advancements in healthcare., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Gupta et al.)

Background: Treatment of unprotected severely calcified left main coronary artery (LMCA) disease is a complex interventional procedure. Intravascular lithotripsy (IVL) and rotational atherectomy (RA) are safe and effective methods of treating coronary calcification in the non-LMCA setting. This retrospective analysis assessed the feasibility of IVL versus RA in unprotected LMCA disease., Methods: We analyzed IVL and RA procedures performed at a large tertiary hospital in the Northeast of England from January 1, 2019 to April 31, 2022. Major safety and efficacy endpoints were procedural and angiographic success, defined by stent delivery with <50 % residual stenosis and without clinical or angiographic complications, respectively. Another important clinical endpoint was the composite of major adverse cardiac events (MACE) at 1 year., Results: From 242 patients, 44 had LMCA IVL, 81 had LMCA RA and 117 had non-LMCA IVL. Patients with LMCA disease were older and more likely to have aortic stenosis. IVL was a second-line or bailout technique in 86.4 % LMCA and 92.2 % non-LMCA cases. Procedural and angiographic success rates were ≥ 84 % across all groups (p > 0.05). In 3 LMCA IVL and 3 LMCA RA cases arrhythmias and cardiac tamponade complicated the procedures respectively. At 1 year, MACE occurred in 10/44 (22.7 %) LMCA IVL, 16/81 (19.8 %) LMCA RA and 25/117 (21.4 %) cases (p > 0.05)., Conclusion: In our single center retrospective analysis, IVL is feasible in unprotected calcified LMCA as a second-line and third-line adjuvant calcium modification technique. Its use in unprotected calcified LMCA disease should be formalized with the undertaking of large randomized controlled trials., Competing Interests: Declaration of competing interest KH, FS, RA, FA, TC, MR, MM, GM, JMA: None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction is a growing public health concern, a disease with poor health outcomes, and is showing increased prevalence globally. This review paper explores the literature with a focus on the pathophysiology and microbiology of preserved ejection fraction heart failure while drawing connections between preserved and reduced ejection fraction states. The discussion teases out the cellular level changes that affect the overall dysfunction of the cardiac tissue, including the clinical manifestations, microbiological changes (endothelial cells, fibroblasts, cardiomyocytes, and excitation-contraction coupling), and the burden of structural diastolic dysfunction. The goal of this review is to summarize the pathophysiological disease state of heart failure with preserved ejection fraction to enhance understanding, knowledge, current treatment models of this pathology., Competing Interests: Declaration of Competing 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., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Value-based care, prioritizing patient outcomes over service volume, is steering a transformative course in anesthesiology in the United States. With the rise of this patient-centric approach, anesthesiologists are adopting dynamic roles to meet the demands of medical institutions, insurers, and patients for high-quality, cost-effective care. The urgency for this transition is accentuated by persistent challenges in reducing postoperative mortality rates and surgical complications, further spotlighted by the coronvirus disease 2019 (COVID-19) pandemic. Anesthesiologists engage in preoperative optimization, personalized care delivery, and evidence-based practices, bolstering their influence in the perioperative environment. Their collaboration with perioperative stakeholders propels the shift toward a value-driven healthcare landscape. This review analyzes the implementation of value-based care in American anesthesiology, assesses the significance of technology in enhancing its delivery, and outlines potential strategies for improving its application., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Ahmed et al.)

Percutaneous coronary intervention (PCI) is a widely used therapy for coronary artery disease (CAD), but it carries risks and complications. Adhering to evidence-based practice guidelines is crucial for optimal outcomes. This review compares the recommendations of the 2021 American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions (ACC/AHA/SCAI) and 2018 European Society of Cardiology (ESC) guidelines for coronary artery revascularization and discusses emerging trends and novel devices in PCI. A comprehensive literature review of mixed studies, clinical trials, and guidelines was conducted. Intravascular imaging, including intravascular ultrasound and optical coherence tomography, for stent optimization, is also recommended when feasible. However, differences reflecting variations in evidence quality interpretation and applicability were identified. Furthermore, novel devices and technologies with the potential for improving outcomes were highlighted, but their safety and efficacy compared to standard-of-care techniques require further evaluation through extensive randomized trials. Clinicians should stay updated on advancements and personalize treatment decisions based on individual patient factors. Future research should address evidence gaps and barriers to adopting innovative devices and techniques. This review provides recommendations for clinical practice, emphasizing the need to remain current with the evolving landscape of PCI to optimize patient outcomes. The discoveries provide valuable counsel for the deliberation of clinical interventions and prospective inquiries within the realm of interventional cardiology. Overall, the review underscores the importance of evidence-based practice and ongoing advancements in PCI for CAD management., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abubakar et al.)

Typhoid fever, a common enteric disease in Pakistan, caused by Salmonella typhi , is becoming an extended drug-resistant organism and is preventable through the typhoid conjugate vaccine (TCV). Public adherence to preventive measures is influenced by knowledge and attitude toward the vaccine. This study investigates the knowledge, attitudes, and practices of the general population of Pakistan toward TCV. The differences in mean scores and factors associated with typhoid conjugate vaccine knowledge, attitudes, and practices were investigated. A total of 918 responses were received with a mean age of 25.9 ± 9.6, 51% were women, and 59.6% had graduation-level education. The majority of them responded that vaccines prevent illness (85.3%) and decrease mortality and disability (92.6%), and typhoid could be prevented by vaccination (86.7%). In total, 77.7 and 80.8% considered TCV safe and effective, respectively. Of 389 participants with children, 53.47% had vaccinated children, according to the extended program on immunization (EPI). Higher family income has a higher odds ratio (OR) for willingness toward booster dose of TCV [crude odds ratio (COR) = 4.920, p -value <0.01; adjusted odds ratio (aOR) = 2.853, value of p <0.001], and negative attitude regarding the protective effect of TCV has less willingness toward the booster dose with statistical significance (COR = 0.388, value of p  = 0.017; aOR = 0.198, value of p  = 0.011). The general population of Pakistan had a good level of knowledge about the benefits of TCV, and attitude and practices are in favor of the usage of TCV. However, a few religious misconceptions are prevalent in public requiring the efforts to overcome them to promote the usage of vaccines to prevent the disease and antibiotic resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tahir, Zaman, Saffi, Asghar, Tariq, Ahmed, Islam, Farooqui, Ullah, Saqlain, Ullah and Ahmed.)

Having access to accurate and recent digital twins of infrastructure assets benefits the renovation, maintenance, condition monitoring, and construction planning of infrastructural projects. There are many cases where such a digital twin does not yet exist, such as for legacy structures. In order to create such a digital twin, a mobile laser scanner can be used to capture the geometric representation of the structure. With the aid of semantic segmentation , the scene can be decomposed into different object classes. This decomposition can then be used to retrieve cad models from a cad library to create an accurate digital twin. This study explores three deep-learning-based models for semantic segmentation of point clouds in a practical real-world setting: PointNet++, SuperPoint Graph, and Point Transformer. This study focuses on the use case of catenary arches of the Dutch railway system in collaboration with Strukton Rail, a major contractor for rail projects. A challenging, varied, high-resolution, and annotated dataset for evaluating point cloud segmentation models in railway settings is presented. The dataset contains 14 individually labelled classes and is the first of its kind to be made publicly available. A modified PointNet++ model achieved the best mean class Intersection over Union (IoU) of 71% for the semantic segmentation task on this new, diverse, and challenging dataset.

Background: During the initial phases of the COVID-19 pandemic, there was an unfounded fervor surrounding the use of hydroxychloroquine (HCQ) and tocilizumab (TCZ); however, evidence on their efficacy and safety have been controversial., Objective: The purpose of this study is to evaluate the overall clinical effectiveness of HCQ and TCZ in patients with COVID-19. We hypothesize that HCQ and TCZ use in these patients will be associated with a reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis., Methods: A retrospective cohort study was performed to determine the impact of HCQ and TCZ use on hard clinical outcomes during hospitalization. A total of 176 hospitalized patients with a confirmed COVID-19 diagnosis was included. Patients were divided into two comparison groups: (1) HCQ (n=144) vs no-HCQ (n=32) and (2) TCZ (n=32) vs no-TCZ (n=144). The mean age, baseline comorbidities, and other medications used during hospitalization were uniformly distributed among all the groups. Independent t tests and multivariate logistic regression analysis were performed to calculate mean differences and adjusted odds ratios with 95% CIs, respectively., Results: The unadjusted odds ratio for patients upgraded to a higher level of care (ie, intensive care unit) (OR 2.6, 95% CI 1.19-5.69; P=.003) and reductions in C-reactive protein (CRP) level on day 7 of hospitalization (21% vs 56%, OR 0.21, 95% CI 0.08-0.55; P=.002) were significantly higher in the TCZ group compared to the control group. There was no significant difference in the odds of in-hospital mortality, upgrade to intensive medical care, need for invasive mechanical ventilation, acute kidney failure necessitating dialysis, or discharge from the hospital after recovery in both the HCQ and TCZ groups compared to their respective control groups. Adjusted odds ratios controlled for baseline comorbidities and medications closely followed the unadjusted estimates., Conclusions: In this cohort of patients with COVID-19, neither HCQ nor TCZ offered a significant reduction in in-hospital mortality, upgrade to intensive medical care, invasive mechanical ventilation, or acute renal failure needing dialysis. These results are similar to the recently published preliminary results of the HCQ arm of the Recovery trial, which showed no clinical benefit from the use of HCQ in hospitalized patients with COVID-19 (the TCZ arm is ongoing). Double-blinded randomized controlled trials are needed to further evaluate the impact of these drugs in larger patient samples so that data-driven guidelines can be deduced to combat this global pandemic., (©Sohaib Roomi, Waqas Ullah, Faizan Ahmed, Soban Farooq, Usama Sadiq, Asad Chohan, Munnam Jafar, Maryum Saddique, Shristi Khanal, Robert Watson, Margot Boigon. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 01.09.2020.)

The current investigation reports bactericidal and cytotoxicity evaluation of bio-enzymatically formulated nano‑gold (AuNPs) using physiologically significant enzyme β galactosidase. The AuNPs were characterized using spectroscopic and microscopic techniques. The anti-pathogenic efficacy of AuNPs as a potential drug was observed against five contagious bacterial strains of Escherichia coli, Staphylococcus aureus, group B Streptococcus, Acinetobacter baumannii and Klebsiella pneumonia. The estimation of minimum bactericidal concentration, minimum inhibitory concentration, scanning electron microscopy and fluorescence microscopy conclude enhanced bactericidal effects of green AuNPs. The cytotoxicity of AuNPs against human cervical (HeLa), breast (MCF-7) and liver (Hep 3B) cancer cells was evaluated. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was adopted to analyze antitumor potential of AuNPs. Cell nuclear morphology associated with apoptosis after treatment with NPs was assessed against MCF-7 cells through 4,6-diamidino-2-phenylindole staining. Apoptotic activity of AuNPs was determined against HeLa cells using annexin V/ propidium iodide double staining by flow cytometric analysis. The AuNPs exhibited excellent efficacy against these cell lines and future prospects of usage as potential nano-drugs and drug delivery vehicles., Competing Interests: Declaration of Competing Interest The authors declare there is no conflict of interest in this work., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Atrial fibrillation (AF), and heart failure (HF) are a major cardiovascular epidemic over the last decade. The prevalence and rehospitalization of heart failure are on rising edge, and many factors are responsible for these re-exacerbations of heart failure. In this study, we sought to determine an association of a risk factor for frequent rehospitalization of heart failure at our institute. We aimed to find the re-admission rate, heart rate, and rhythm of heart failure exacerbation., Methods: We performed a single-center retrospective study at the Abington Hospital - Jefferson health and 418 patients having a history of heart failure, and AF were selected. The heart failure readmission rate (days), heart rate, and rhythm were analyzed., Results: The mean age of the included population was 82.8 years SD ± 9.2. About 53% had AF with a mean heart rate 90 SD ± 21 bpm, and 47% had normal sinus rhythm (NSR) with a mean heart rate of 78 ± 16 bpm on re-admission. This difference was statistically significant (p=0.02). The mean re-admission rate for atrial fibrillation was 27.49 days SD ± 18.97, compared to 32.68 SD ± 20.26 days for NSR, statistically significant (p=0.007) and the Pearson Chi-square was also significant P = 0.006., Conclusion: There is a significantly increased rate of re-admission in heart failure patients with atrial fibrillation with a rapid ventricular rate. Efforts should be taken to keep the patient in NSR or controlled AF to minimize the rehospitalization rate, and this, in turn, reduces the financial burden on patients and institutes., Competing Interests: None., (AJCD Copyright © 2019.)

Bedaquiline was approved by USFDA in 2012 for pulmonary MDR-TB. The IC 50 value of bedaquiline was reported to be remarkably low (25 nM), effectively inhibiting mycobacterial ATP synthase. In addition to these obvious assets of bedaquiline, the potential disadvantages of bedaquiline include inhibition of the hERG (human Ether-à-go-related gene; KCNH 2 ) potassium channel (concurrent risk of cardiac toxicity), hepatic toxicity and possibly phospholipidosis. The current review focuses primarily on the structural part of bedaquiline for the activity-toxicity optimization. This critical analysis of the structure of bedaquiline will help medicinal chemists to synthesize the better modified analouge of bedaquiline with reduced cardiotoxicity, hepatotoxicity potential and improved pharmacokinetics., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The fabrication of nanoparticles (NPs) has been a wide realm of studies focusing majorly on their dispersion and stabilization. The use of biological components as reducing agents has led to emergence of environment-friendly and cost-effective approaches of synthesis. The primary aim was synthesizing silver nanoparticles (AgNPs) mediated by enzyme β galactosidase. The surface plasmon resonance peaks of AgNPs were screened using ultraviolet-visible spectroscopy against varying time of synthesis and concentration of enzyme. The mean dimension was 12.89 ± 0.16 nm as determined by the transmission electron microscopy and selected area electron diffraction patterns. The obtained NPs were fine spherical and quasi-spherical assemblages as revealed by the scanning electron microscopy studies. Fourier transform infrared spectroscopy confirmed that β galactosidase contributed to the reduction and stabilization of the silver nanoparticles. The crystallinity and presence of elemental silver was displayed by X-ray diffraction and electron dispersive spectroscopy. The antimicrobial efficacy of these AgNPs was tested against the pathogenic bacterial strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Staphylococcus epidermidis. The minimum inhibitory concentration, minimum bactericidal concentration and biofilm inhibitory activities were reported depicting enzymatically reduced AgNPs possess an excellent bactericidal activity. An alternative approach was formulated in dye wastewater treatment where the nano-assemblages were reduced within the dye solutions leading to significant decolorization of industrially important dyes; direct, reactive and acid. The cytotoxic potential of the AgNPs was evaluated on peripheral blood lymphocytes in vitro and scanning electron microscope images obtained concluded that green synthesis fabricates benign NPs at low concentrations., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Nephrotoxicity is a severe complication in patients undergoing cisplatin (CP) chemotherapy. Previous studies in our lab have shown that administration of a single dose of CP results in decrease in the activities of brush border membrane (BBM) and free radical scavenging enzymes and induces oxidative stress in rat kidney. Nigella sativa, is one of the most revered medicinal plant known for its numerous health benefits. Nigella sativa seed/oil has been shown to improve kidney functions in animal models of acute kidney injury., Objective: The present study was undertaken to investigate whether Nigella sativa oil (NSO) can prevent the CP-induced nephrotoxic effects., Results: The effect of NSO was determined on CP induced alterations in various serum parameters and on enzymes of carbohydrate metabolism, BBM and antioxidant defense system in renal cortex and medulla. Administration of NSO (2ml/kg bwt. orally), prior to and following a single dose CP treatment (6mg/kg bwt. i.p), significantly attenuated the CP induced increase in serum creatinine (Scr) and blood urea nitrogen (BUN) and decrease in the activities of BBM enzymes in renal cortical and medullary homogenates as well as in isolated BBM vesicles (BBMV). NSO administration also precluded CP induced alterations in the activities of carbohydrate metabolism enzymes and in the enzymatic and non-enzymatic antioxidant parameters. Histopathological observations showed extensive kidney damage in CP treated animals and remarkably reduced renal injury in CP and NSO co-treated group., Conclusion: The biochemical and histological data suggest a protective effect of NSO against CP-induced acute kidney injury., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Mayer Rokitansky Kuster Hauser (MRKH) syndrome is a rare disorder, characterized by the congenital absence of uterus and associated renal tract anomalies. The case presented with primary amenorrhea and primary infertility, despite development of normal female secondary sexual characteristics. CT scan revealed absent uterus, a solitary left sided pelvic kidney and a vesicovaginal communication that, on cystoscopy, revealed urogenital sinus anomaly manifesting as a common channel formed due to absent anterior wall of vagina and posterior wall of urethra. The urogenital sinus anomaly in MRKH syndrome has not been reported earlier.