A framework for the systematic evaluation of a novel cigarette filter technology.

Any functional change in cigarette filter design warrants a rigorous assessment to ensure comparability to existing filter functionality. This study compares the functionality of a standard CA filter with a novel cellulose-based alternative using a combination of emissions, in silico approaches, pre-clinical assessments and behavioural studies. We assess the challenges faced with a significant filtration change, the substantiation of this change and the limitations of such assessments. We explore cigarette emission chemical profiles; assess the potential toxicological impacts (in vitro and statistical modelling) of the differing chemical profiles of cigarette smoke aerosol resulting from the respective filter types; and, finally investigate the behavioural aspects associated with use of the novel filter as compared to the traditional one. The aim of the study was to establish a weight of evidence assessment framework for the comprehensive evaluation of a novel cigarette filter design as part of robust stewardship approach. The data show comparability to a standard CA filter across all assessments and highlight potential areas of investigation for future novel filter product iterations. The approach demonstrates the applicability of a comprehensive step-wise assessment framework to identify any potential increased toxicant emissions and exposures associated with using the novel filter.

aVR: The forgotten lead in acute coronary syndrome: A case series.

Lead aVR is often considered as a neglected lead or forgotten lead owing to its reciprocal location to the lateral leads. However, it has diagnostic and prognostic importance in cases of acute coronary syndromes. We present a series of four cases of acute coronary syndrome with ST elevation (STE) in aVR and critical stenosis in coronary vessels. Patients with STE in aVR have a poor prognosis with increased morbidity not limited to increased chances of heart failure at presentation, greater hemodynamic instability, and in-hospital acute kidney injury, as well as increased mortality due to large infarction areas. Thus, early revascularization is warranted in such cases.

Practical Clinical Consensus Guidelines for the Management of Cancer Associated Anemia in Low- and Middle-Income Countries.

Purvish M. ParikhCancer-associated anemia (CAA) remains a major unmet need that compromises overall survival (OS) and quality of life (QoL). Currently, available guidelines do not take into consideration the unique challenges in low- and middle-income countries (LMIC). Our CAA patients have to battle preexisting impaired nutritional status, depleted body iron stores, financial limitations, and difficulty in having easily accessible affordable healthcare. Hence, we fulfilled the need of guidelines for LMIC. A group of subject experts were put together, given background literature, met in a face-to-face discussion, voted using Delphi process, and finally agreed on the contents of this guideline document. As many as 50% of cancer patients will have significant anemia (hemoglobin < 10 g/dL) at initial diagnosis. It is most commonly seen with gastrointestinal malignancies, head and neck cancers, and acute leukemias. The hemoglobin falls further after initiation of cancer directed therapy, due to chemotherapy itself or heightened nutritional deficiency. Its evaluation should include tests for complete blood count, red blood cell morphology, reticulocyte count, Coombs test, and levels of vitamin B12 and folic acid. Iron status should be monitored using test to measure serum iron, total iron binding capacity, transferring saturation, and serum ferritin levels. A minimum of 50% of cancer patients with anemia require iron supplements. The preferred mode of therapy is with intravenous (IV) iron using ferric carboxymaltose (FCM). Most patients respond satisfactorily to single dose of 1000 mg. It is also safe and does not require use of a test dose. Significant anemia is found in at least half of all cancer patients in India, South Asian Association for Regional Cooperation region, and other LMIC countries. Its awareness among healthcare professionals will prevent it from remaining undiagnosed (in up to 70% of all cancer patients) and adversely affecting OS and QoL. The benefits of treating them with IV iron therapy are quick replenishment of iron stores, hemoglobin returning to normal, better QoL, and avoiding risk of infections/reactions with blood transfusions. Many publications have proven the value of single-dose FCM in such clinical situations. CAA has been proven to be an independent prognostic factor that adversely affects both QoL and OS in cancer patients. Use of FCM as single IV dose of 1000 mg is safe and effective in the majority of patients with CAA.

Link between Blood Cell-Associated Inflammatory Indices and Chemotherapy-Induced Hyperglycemia in Women Affected with Breast Cancer: Clinical Studies.

Krishna PrasadBackground Development of treatment-induced hyperglycemia/diabetes is a considerable problem in women undergoing chemotherapy for breast cancer. In this study, baseline levels of blood cell-associated inflammatory indices (BCAII) were analyzed to understand their role in the development of treatment-induced hyperglycemia and diabetogenesis. Materials and Methods This was a retrospective study, and information on women who were normoglycemic and nondiabetic and of women who were diabetic at the beginning of the treatment were collected from files. Demographic, pathology-related details, and complete blood profile were noted. Neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammatory index (SII) which indicate BCAII were calculated. Demographic details were subjected to frequency and percentage, while blood parameters were subjected to one-way analysis of variance followed by post hoc Bonferroni's multiple comparison tests. A p -value of <0.05 was considered significant. Results The results indicated that a significant difference in levels of total count ( p < 0.035), neutrophil, lymphocyte, and platelets ( p < 0.001) were observed. Regarding BCAII, when compared with women who were normoglycemic at the end of treatment, NLR, dNLR, PLR, and SII were significantly high for people who were known diabetics at the beginning of treatment ( p < 0.001). The dNLR ( p = 0.0008), PLR ( p < 0.001), and SII ( p < 0.001) were significant for people who developed secondary hyperglycemia/diabetes, while only dNLR was significant for people who progressed from normal to prediabetes stage ( p = 0.049) Conclusion To the best of the authors' knowledge, this is the first study that indicates difference in baseline BCAII and development of treatment-induced hyperglycemia/diabetes indicating that underlying low levels of inflammation may contribute to diabetogenesis in women affected with breast cancer.

Investigation of Autonomic Dysfunction in Alzheimer's Disease-A Computational Model-Based Approach.

(1) Background and Objective: Alzheimer's disease (AD) is commonly accompanied by autonomic dysfunction. Investigating autonomic dysfunction's occurrence patterns and severity may aid in making a distinction between different dementia subtypes, as cardiac autonomic dysfunction and AD severity are correlated. Heart rate variability (HRV) allows for a non-invasive assessment of the autonomic nervous system (ANS). AD is characterized by cholinergic depletion. A computational model of ANS based on the kinetics of acetylcholine and norepinephrine is used to simulate HRV for various autonomic states. The model has the flexibility to suitably modulate the concentration of acetylcholine corresponding to different autonomic states. (2) Methods: Twenty clinically plausible AD patients are compared to 20 age- and gender-matched healthy controls using HRV measures. Statistical analysis is performed to identify the HRV parameters that vary significantly in AD. By modulating the acetylcholine concentration in a controlled manner, different autonomic states of Alzheimer's disease are simulated using the ANS model. (3) Results: In patients with AD, there is a significant decrease in vagal activity, sympathovagal imbalance with a dominant sympathetic activity, and change in the time domain, frequency domain, and nonlinear HRV characteristics. Simulated HRV features corresponding to 10 progressive states of AD are presented. (4) Conclusions: There is a significant difference in the HRV features during AD. As cholinergic depletion and autonomic dysfunction have a common neurological basis, autonomic function assessment can help in diagnosis and assessment of AD. Quantitative models may help in better comprehending the pathophysiology of the disease and assessment of its progress.

A Treatment Dilemma: Bentall vs Transcatheter Paravalvular Leak Closure with Aortic Aneurysm Repair in a High Surgical Risk Patient.

This case presentation involves an 80-year-old male with a history of surgically repaired patent ductus arteriosus and surgical aortic valve replacement due to infective endocarditis, who presented with progressive heart failure symptoms and was found to have a severe aortic paravalvular leak (PVL) and ascending thoracic aortic aneurysm. Due to complex surgical anatomy and multiple chronic comorbidities, he was considered a poor candidate for traditional valve replacement surgery including the Bentall procedure. Instead, a multidisciplinary team opted for transcatheter paravalvular leak closure (TPLC) with an Amplatzer plug followed by planned endovascular aortic aneurysm repair. The patient showed significant improvement in symptoms and reduction in aneurysm size post-procedure leading to avoidance of the open-heart surgery. This case highlights the effectiveness of the percutaneous approach in high-risk surgical patients with PVL and complex anatomical considerations.

Primary Ovarian Non-Hodgkin's Lymphoma: An 18-year Retrospective Institutional Study and Review of Literature from India.

BACKGROUND: Primary lymphomas of the female reproductive tract are rare and the ovarian extranodal presentation of non-Hodgkin's lymphoma (NHL) accounts for only 0.5% of all NHLs and 1.5% of all ovarian malignancies. METHODS: We retrospectively reviewed the institutional medical oncology database for newly diagnosed NHL cases between 1999 and 2017. We aimed to study the clinical characteristics, pathology, and outcome of primary ovarian non-Hodgkin's lymphoma (NHL) cases presented to our institution. RESULTS: We identified three patients (3.7% of extranodal NHLs and 0.85% of all NHL patients) with primary ovarian NHL from 350 NHL patient records. They underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy followed by six to eight cycles of (rituximab, adriamycin, cyclophosphamide, vincristine, prednisolone (R-CHOP/CHOP), and they attained complete remission. CONCLUSION: Given the heterogeneity of cancer incidence in India and the absence of state-wise cancer registries, our study argues a pressing need to develop a national representative registry for NHL for accurate incidence, mortality, and survival data. Additionally, fertility preservation is an important issue that must be discussed with women of fertile age and the parents of children.

Outcomes of Neurorehabilitation Among Patients With Prolonged Disorders of Consciousness.

BACKGROUND:  The impact of neurorehabilitation on patients with prolonged disorders of consciousness (PDOC) is not well known. We assessed the range of motion (ROM), muscle girth and power, level of consciousness, development of musculoskeletal deformity, and superficial sensation. METHODS:  A retrospective observational record-based study was done, which included the data of patients diagnosed with PDOC admitted at Thumbay Physical Therapy & Rehabilitation Hospital, Ajman, UAE, between 2020 and 2022. Data on the "range of motion", "muscle girth and power", "level of consciousness", "development of musculoskeletal deformity", and "superficial sensation" were collected and analyzed. The SPSS software version 27 (IBM Corp., Armonk, NY, USA) was used for analysis. The chi-square test was used to assess association, and the t-test was used to test the mean difference. RESULTS:  We assessed the data of 21 patients with PDOC. The superficial sensation was found to have increased significantly (p<0.025). There was a decrease in the proportion of patients with musculoskeletal deformities during the follow-up period. The ROM, muscle girth, and muscle power were also preserved without significant deterioration. However, the level of consciousness measured by the Glasgow coma scale (GCS) showed no improvement. CONCLUSIONS: Our research showed that neurorehabilitation significantly improves superficial sensation and prevents the development of musculoskeletal deformities. However, the mean level of consciousness remained the same. There was also no decrease in ROM. Both muscle girth and power were preserved over two years.

Histomorphological Analysis of Ovarian Neoplasms According to the 2020 WHO Classification of Ovarian Tumors: A Distribution Pattern in a Tertiary Care Center.

BACKGROUND: In 2018, ovarian carcinoma ranked as the eighth most common cancer diagnosed and the leading cause of cancer death in women. High-grade serous carcinoma is the most common histological type seen among malignant cases. A diverse group of neoplasms is seen in the ovary with variable clinical, morphological, and histological features, so assessing the nature of ovarian neoplasms further assists in the treatment of the disease. AIM: This study was conducted to assess the different histopathological variants of ovarian neoplasms according to the latest 2020 World Health Organization (WHO) classification of ovarian tumors. Further analysis of the frequency, age, clinical features in patients, and distribution of various ovarian tumors is assessed. MATERIALS AND METHODS: A retrospective study was conducted in the Department of Pathology at Patna Medical College and Hospital (PMCH), Patna. The data of the patients from the past three years, from February 2020 to February 2023, were retrieved and assessed. Gross and microscopic findings, including clinical details of patients with ovarian masses, were analyzed from the previous records. RESULT: A total of 110 cases of ovarian neoplasms on histopathology were analyzed. The age range was 11-70 years. The types of specimens received were those of total abdominal hysterectomy, salphingoopherectomy, and unilateral or bilateral ovarian cystectomy. The most common presentation was an abdominal mass, followed by pain in the abdomen. The majority of the tumors were benign (69%), malignancy was observed in 24.5% of cases, and borderline tumors were seen in 5.4% of cases. Epithelial tumors were the commonest tumors, accounting for 70%, followed by germ cell tumors (21%). Serous cystadenoma was the commonest benign tumor, followed by mature teratoma and serous cystadenocarcinoma. High-grade serous cystadenocarcinoma was the commonest malignant ovarian tumor (9%), followed by low-grade serous cystadenocarcinoma (4.5%) and metastatic carcinoma of the ovary. Krukenberg tumor was seen in two cases, and a very rare case of sclerosing stromal tumor was seen in one of the cases. CONCLUSION: Ovarian neoplasms usually present with a variety of clinicomorphological and histological features. The most common neoplasm observed in the ovary is surface epithelial tumors, which are benign lesions that commonly affect reproductive age groups. Newer advancements like immunohistochemistry (IHC) and genetic studies have made the diagnosis easier and more precise. However, in institutes with limited resources, a histopathological study is still the gold standard in the diagnosis and prognostic evaluation of these tumors.

Comparative Expedited Regulatory Programs of U.S Food & Drug Administration and Project Orbis Partners.

Project Orbis was initiated in May 2019 by the Oncology Center of Excellence to facilitate faster patient access to innovative cancer therapies by providing a framework for concurrent submissions and review of oncology products among international partners. Since its inception, Australia's Therapeutic Goods Administration (TGA), Canada's Health Canada (HC), Singapore's Health Sciences Authority (HSA), Switzerland's Swissmedic (SMC), Brazil's National Health Surveillance Agency (ANVISA), United Kingdom's Medicines and Healthcare Products Regulatory Agency (MHRA), and most recently Israel's Ministry of Health (IMoH) Medical Technologies, Health Information, Innovation and Research (MTIIR) Directorate, have joined Project Orbis. While each country has its own expedited review pathways to bring promising therapies to patients, there are some similarities and differences in pathways and timelines. FDA's fast-track designation and MHRA's marketing authorization under exceptional circumstances (MAEC) allow non-clinical and limited clinical evidence to support approval under these programs. HC's Extraordinary Use New Drug (EUND) pathway allows granting exceptional use authorization with limited clinical evidence. ANVISA, HSA, MTIIR, and TGA do not have standard pathways that allow non-clinical evidence and limited clinical evidence. While there is no definite regulatory pathway for HSA, the current framework for approval does allow flexibility in the type of data (non-clinical or clinical) required to demonstrate the benefit-risk profile of a product. HSA may register a product if the agency is satisfied that the overall benefit outweighs the risk. All Project Orbis Partner (POP) countries have similar programs to the FDA accelerated approval program except ANVISA. Although HSA and MTIIR do not have defined pathways for accelerated approval programs, there are opportunities to request accelerated approval per these agencies. All POP countries have pathways like the FDA priority review except MHRA. Priority review timelines for new drugs range from 120 to 264 calendar days (cd). Standard review timelines for new drugs range from 180 to 365 cd.

Neuro-Cardio-Autonomic Modulations in Children with Duchenne Muscular Dystrophy.

BACKGROUND AND OBJECTIVE: Duchenne muscular dystrophy (DMD) is a degenerative X-linked muscle disease. Death frequently results from complications in cardiopulmonary systems. Preclinical/early diagnosis of cardiac autonomic abnormalities may aid initiate cardioprotective therapy and enhance prognosis. METHODS: A cross sectional, prospective study of 38 DMD boys compared with 37 age-matched healthy controls was conducted. Lead II electrocardiography and beat-to-beat blood pressure were recorded to assess heart rate variability (HRV), blood pressure variability (BPV), and baroreceptor sensitivity (BRS) in a standardized environment. Data were analysed and correlated with disease severity and genotype. RESULTS: In the DMD group, the median age at assessment was 8 years [IQR 7-9 years], the median age at disease onset was 3 years [IQR, 2-6 years], and the mean duration of illness was 4 years [IQR, 2.5-5]. DNA sequencing showed deletions in 34/38 (89.5 %) and duplications in 4/38 (10.5%) patients. The median heart rate in DMD children was significantly higher [101.19 (Range, 94.71-108.49)] /min compared to controls [81 (Range, 76.2-92.76)] /min (p < 0.05). All the assessed HRV and BPV parameters were significantly impaired in DMD cases except for the coefficient of variance of systolic blood pressure. Further, BRS parameters were also significantly reduced in DMD, excluding alpha-LF. A positive correlation was found between alpha HF with age at onset and duration of illness. CONCLUSION: This study demonstrates a distinct early impairment of neuro-cardio-autonomic regulation in DMD. Simple yet effective non-invasive techniques such as HRV, BPV, and BRS may help identify cardiac dysfunction in a pre-clinical state, paving the way for early cardio-protective therapies and limiting disease progression in DMD patients.

Evaluation of behavioural, chemical, toxicological and clinical studies of a tobacco heated product glo™ and the potential for bridging from a foundational dataset to new product iterations.

Background: Tobacco Heating Products (THPs) are tobacco products that heat rather than burn tobacco with temperatures less than 350 °C. Because of this operating principle, they produce substantially fewer and lower levels of tobacco smoke toxicants than combustible cigarette smoke produced when tobacco is burnt, which occurs at much higher temperatures of around 900 °C. This paper analyses data on a THP, glo™, and assesses whether its use would result in reduced health risks compared to the health risks of smoking cigarettes. It also looks at the possibility of bridging datasets across the different variants of the glo™ product. Methods: The approach is to consider whether datasets from behavioural, chemical, toxicological and clinical studies provide consistent findings of reductions in toxicant exposure with glo™ use by subjects who switch completely from smoking cigarettes to using glo™ and whether these reductions are similar to those who stop smoking cigarettes without switching to glo™ or any other tobacco or nicotine product. We also examine the similarities and differences of different versions of the glo™ product and benchmark it against a THP from another manufacturer. Results: The studies indicate that the use of the glo™ results in substantial and prolonged reductions in toxicant exposure for smokers who switch to glo™ completely. A long-term clinical study shows substantial reductions in toxicant exposure over a period of time, similar to reduction of some biomarkers of exposure found following smoking cessation without switching to glo™ or any other tobacco product, and biomarkers of potential harm trending in a favourable manner for both groups that switch to glo™ and that quit all tobacco and nicotine use. Data suggests that all iterations of glo™ result in substantial reductions in toxicant exposure compared to smoking cigarettes and that bridging across datasets is feasible. Conclusions: Given the accumulated scientific data summarised in this paper, and particularly the findings from a long-term clinical study, the data demonstrate that glo™ is a reduced exposure product compared to combustible cigarettes and is reasonably deemed to reduce the risk of smoking-related diseases and supports the conclusion that smokers who would have otherwise continued to smoke and instead switch entirely to THP glo™ use, will reduce their relative risk of developing smoking-related diseases as compared to continued smoking. The extent of reduction in risk compared to continuing to smoke is likely to vary by smoking-related disease and by an individuals' smoking history, other risk factors and an individual's susceptibility to disease. Use of the THP will present some level of increased health risk as compared to cessation of tobacco and nicotine products and will cause dependence. As long as the principles of heat-not-burn are maintained, THP use will result in substantially reduced exposure to smoke toxicants as compared to continued conventional cigarette smoking. It is possible to use bridging or read across to apply these conclusions to new iterations of the glo™ product, extending the utility and validity of the evidence generated through study of prior iterations.

The evolving landscape of pulmonary arterial hypertension clinical trials.

Although it is a rare disease, the number of available therapeutic options for treating pulmonary arterial hypertension has increased since the late 1990s, with multiple drugs developed that are shown to be effective in phase 3 randomised controlled trials. Despite considerable advancements in pulmonary arterial hypertension treatment, prognosis remains poor. Existing therapies target pulmonary endothelial dysfunction with vasodilation and anti-proliferative effects. Novel therapies that target proliferative vascular remodelling and affect important outcomes are urgently needed. There is need for additional innovations in clinical trial design so that all emerging candidate therapies can be rigorously studied. Pulmonary arterial hypertension trial design has shifted from short-term submaximal exercise capacity as a primary endpoint, to larger clinical event-driven trial outcomes. Event-driven pulmonary arterial hypertension trials could face feasibility and efficiency issues in the future because increasing sample sizes and longer follow-up durations are needed, which would be problematic in such a rare disease. Enrichment strategies, innovative and alternative trial designs, and novel trial endpoints are potential solutions that could improve the efficiency of future pulmonary arterial hypertension trials while maintaining robustness and clinically meaningful evidence.

Evaluation of Asymptomatic Carotid Artery Stenosis Prior to Coronary Artery Bypass Grafting - A Prospective Observational Study in North Indian Population.

Background: Carotid artery stenosis (CAS) is an established risk factor for peri-operative neurological complications in patients following coronary artery bypass grafting (CABG). However, routine pre-surgical screening for CAS is still a matter of debate. This study was conducted to study the prevalence of asymptomatic carotid artery disease in patients undergoing CABG and to determine the predictors of significant carotid stenosis in them. Methods: In this prospective observational study, 112 patients, who were planned for CABG, were enrolled, and their demographic details, risk factor profile, and coronary angiogram parameters were analyzed. Results: Carotid stenosis was observed in 75.0% of the study population with 11.6% having unilateral and 63.4% having bilateral carotid stenosis. A total of 56.2% of the patients had mild, 14.3% had moderate, and 4.5% had severe carotid stenosis. The presence of significant carotid stenosis showed a correlation with chronic stable angina (P = 0.009), significant left main (LM) disease (P = 0.001), chronic total occlusion (P = 0.043), and coronary vessel calcification (P = 0.004). Multivariate analysis of all the predictor variables in a regression model showed that significant LM disease (Odds ratio (OR):6.5, P = 0.002) and coronary artery calcification (OR: 4.3, P = 0.024) were the only independent predictors of significant CAS in the study population. Conclusion: The presence of significant carotid vessel stenosis in patients undergoing CABG in the Indian population has a stronger association with the chronicity of the coronary artery disease rather than the coronary atheroma load (as determined by the modified Gensini score). The presence of significant LM disease and coronary artery calcification may be useful in detecting high-risk patients for significant CAS during the pre-surgical workup.

Ventricular Tachycardia Storm in a Patient with an Implanted Cardioverter-Defibrillator Following COVID-19 Infection.

Severe Coronavirus disease 2019 (COVID-19) infection presents with acute respiratory distress syndrome and multiorgan dysfunction. Cardiac involvement is seen in about a quarter of patients, and it can present as acute coronary syndromes, arrhythmias, myocarditis, and thromboembolic events. Ventricular arrhythmias in the setting of COVID-19 infection are usually multifactorial in etiology. There are only a few reports of ventricular tachycardia (VT) storms in patients with COVID-19 infection. We hereby report a case of an elderly man with severe left ventricular systolic dysfunction and a stable cardiac status for the last few years who, following coronary artery bypass graft surgery and implantable cardioverter-defibrillator (ICD) implantation, experienced a VT storm after a COVID-19 infection. The VT storm was controlled using multiple ICD shocks, along with antiarrhythmic drugs. Following his recovery from COVID-19 infection, the patient was asymptomatic at a 3-month follow-up.

Hypertriglyceridemia induced acute pancreatitis: 4 years' experience from a tertiary care institute and quick literature review.

Hypertriglyceridemia (HTG) is infrequent but an established etiology that can trigger recurrent episodes of acute pancreatitis. The risk of acute pancreatitis is significant when serum triglycerides levels surpass >1000 mg/dL. Although the severity of HTG-induced acute pancreatitis (HTG-AP) may be correlated to higher HTG levels in the early stages, the overall clinical outcomes are similar to other aetiologies. The initial management also differs from the routine recommendations with additional diagnostic and therapeutic challenges. This retrospective case series includes a 4-year experience with HTG-AP at our facility and a brief literature review.

Acquired cyanosis secondary to RVOT obstruction due to pacemaker lead prolapse and vegetation in a child with ASD.

Pacemaker implantation in the paediatric population is associated with significant perioperative complications. We report a child with atrial septal defect who developed cyanosis following pacemaker implantation. An 8-year-old male child presented to us with fever of 2 months, along with cyanosis and clubbing. He underwent endocardial transvenous pacemaker implantation for congenital complete heart block. His echocardiography revealed right atrial vegetation (1 × 1 cm), moderate tricuspid regurgitation, and a prolapsed lead loop extending into the right ventricular outflow tract and pulmonary valve causing severe obstruction of pulmonary valve. He was started on empirical treatment followed by sensitive antibiotics based on culture report; however due to recurrent ventricular tachycardia he was taken for emergency surgery. He underwent closure of atrial septal defect, removal of pulse generator, removal of endocardial leads/vegetation, and pulmonary valve repair. Postoperative echocardiography revealed mild tricuspid regurgitation and resolution of pulmonic stenosis. This case presents a rare complication of severe right ventricular outflow tract obstruction following pacemaker implantation. .

Vaccine for Diabetes-Where Do We Stand?

Diabetes is an endocrinological disorder with a rapidly increasing number of patients globally. Over the last few years, the alarming status of diabetes has become a pivotal factor pertaining to morbidity and mortality among the youth as well as middle-aged people. Current developments in our understanding related to autoimmune responses leading to diabetes have developed a cause for concern in the prospective usage of immunomodulatory agents to prevent diabetes. The mechanism of action of vaccines varies greatly, such as removing autoreactive T cells and inhibiting the interactions between immune cells. Currently, most developed diabetes vaccines have been tested in animal models, while only a few human trials have been completed with positive outcomes. In this review, we investigate the undergoing clinical trial studies for the development of a prototype diabetes vaccine.

Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes.

Exposure to outer space microgravity poses a risk for the development of various pathologies including cardiovascular disease. To study this, we derived cardiomyocytes (CMs) from human-induced pluripotent stem cells and exposed them to simulated microgravity (SMG). We combined different "omics" and chromosome conformation capture technologies with live-cell imaging of various transgenic lines to discover that SMG impacts on the contractile velocity and function of CMs via the induction of senescence processes. This is linked to SMG-induced changes of reactive oxygen species (ROS) generation and energy metabolism by mitochondria. Taken together, we uncover a microgravity-controlled axis causing contractile dysfunctions to CMs. Our findings can contribute to the design of preventive and therapeutic strategies against senescence-associated disease.