Graves' Disease Associated With Pulmonary Hypertension and Cardiac Arrest.

Thyrotoxicosis has been associated with several cardiac conditions including atrial fibrillation, congestive heart failure due to left ventricular dysfunction, and cardiomyopathy. However, few cases of ventricular fibrillation as a complication of thyrotoxicosis have been reported. Our case described a 45-year-old male with a history of hypertension and Graves' disease, who presented with 1 week of left-sided chest pain associated with shortness of breath on exertion and occasional palpitations. His workup revealed acute diastolic congestive heart failure secondary to thyrotoxicosis, causing pulmonary hypertension, which led to ventricular fibrillation and cardiac arrest. After being treated with methimazole and metoprolol, the patient's symptoms improved. This case underscores the significance of assertive medical interventions alongside both invasive and non-invasive cardiac procedures. Addressing thyrotoxicosis and ventricular arrhythmia in hyperthyroid patients is crucial to prevent potentially life-threatening complications.

The Impact of Tofacitinib on Quality of Life in Patients with Moderate-to-Severe Psoriasis- An Observational Study.

Background: Global phase III trials have established the effectiveness and the safety profile of 5 and 10 mg twice-daily regimens of Tofacitinib for the management of psoriasis. Aims and Objectives: This study was aimed at assessing the improvement in quality of life in patients suffering from moderate-to-severe psoriasis following 12-week Tofacitinib therapy. Materials and Methods: 50 adults with moderate to severe plaque psoriasis enrolled with informed consent. Tofacitinib was given orally for 12 weeks, as 5 mg or 10 mg twice daily based on weight. Improvement in PASI and DLQI was recorded. Results: We observed a statistically significant improvement in PASI (p-value < 0.001) and DLQI (p-value < 0.001) following Tofacitinib therapy. The 3 domains of DLQI with the most significant improvement were symptoms and feelings (items 1 and 2) (p-value-0.001), daily activities (items 3 and 4) (p-value-0.0001), and treatment (item 10) (p-value-0.0001). Conclusion: Tofacitinib demonstrated a significant improvement in psoriasis disease severity and symptoms with 12 weeks' therapy.

Effectiveness of Omeprazole in Acid Peptic Disease: A Real-World, Patient-Reported Outcome Measures Study.

Objectives This prospective study assessed the effectiveness and patient satisfaction of four-week omeprazole therapy in acid peptic disease (APD). Methods This was an observational, post-marketing, real-world evidence, patient-reported outcome (PRO) measures study. Patients visiting the five study sites across India with symptoms of APD, and who were prescribed oral omeprazole (20/40 mg per day) for at least four weeks were enrolled after obtaining informed consent. Study assessments included frequency and severity of symptoms and overall satisfaction reported by the patients using the Patient Assessment of Gastrointestinal Disorder Symptom Severity Index (PAGI-SYM) questionnaire. The satisfaction with therapy was reported by the patients using the Treatment Satisfaction Questionnaire for Medication (TSQM) questionnaire. Both PAGI-SYM and TSQM were reported by patients on days 14 and 28. Omeprazole safety was assessed based on the adverse events reported by the patients. Results A total of 96 (62 males and 34 females) patients were included in the study, of which 38.54% had significant findings related to APD at baseline. The proportion of patients with symptoms reduced to 16.67% on day 14 and 8.33% on day 28 with omeprazole therapy. The PAGI-SYM total scores at baseline were 41.32 (15.487), which reduced to 20.86 (11.620) on day 14 (p < 0.0001), and to 8.93 (8.361) on day 28 (p < 0.0001). Significant reductions were also seen in individual symptom scores. The TSQM total scores increased to 36.67 (range: 13 to 63) on day 28 from 34.69 (range: 12 to 58) on day 14. Improvement in scores for all domains of TSQM (effectiveness, convenience, and global satisfaction) was seen on day 28. Improvement in reflux symptoms was reported by 46.74% and 68.48% of patients on day 14 and day 28, respectively. Four (4.17%) patients reported adverse events, which were of mild severity and were unrelated to omeprazole. Conclusions Omeprazole provides significant improvement in PAGI-SYM and TSQM questionnaires on day 14 and day 28. Patients reported the omeprazole-based therapy as effective, convenient, and satisfactory. Omeprazole therapy is safe and effective for the treatment of APD and shows good improvement in APD in patients suffering from duodenal ulcers, gastric ulcers, and reflux oesophagitis.

Inhibiting de novo ceramide synthesis restores mitochondrial and protein homeostasis in muscle aging.

Disruption of mitochondrial function and protein homeostasis plays a central role in aging. However, how these processes interact and what governs their failure in aging remain poorly understood. Here, we showed that ceramide biosynthesis controls the decline in mitochondrial and protein homeostasis during muscle aging. Analysis of transcriptome datasets derived from muscle biopsies obtained from both aged individuals and patients with a diverse range of muscle disorders revealed that changes in ceramide biosynthesis, as well as disturbances in mitochondrial and protein homeostasis pathways, are prevalent features in these conditions. By performing targeted lipidomics analyses, we found that ceramides accumulated in skeletal muscle with increasing age across Caenorhabditis elegans, mice, and humans. Inhibition of serine palmitoyltransferase (SPT), the rate-limiting enzyme of the ceramide de novo synthesis, by gene silencing or by treatment with myriocin restored proteostasis and mitochondrial function in human myoblasts, in C. elegans, and in the skeletal muscles of mice during aging. Restoration of these age-related processes improved health and life span in the nematode and muscle health and fitness in mice. Collectively, our data implicate pharmacological and genetic suppression of ceramide biosynthesis as potential therapeutic approaches to delay muscle aging and to manage related proteinopathies via mitochondrial and proteostasis remodeling.

Hand Foot Mouth Disease During the SARS-CoV-2 Pandemic: A Multicentric Study.

OBJECTIVES: This prospective observational study aimed to identify the current trend of the circulating viral strains responsible for HFMD outbreak in four tertiary care centers in Rajasthan, amidst the COVID-19 pandemic (April-October 2022). METHODS: Cases with suspected HFMD, presenting to our skin outpatient department were assessed clinically and serologically (IgM antibodies against coxsackie virus (CV) A6, A16 and enterovirus 71) for evidence of the disease. RESULTS: We identified 718 new HFMD patients (161 adults) with peaks in May and August, 2022. Male:female ratio decreased with increasing age. Most children were asymptomatic. A total of 385/409 patients assessed serologically, were found positive, most commonly against CV-A6. CONCLUSION: Though HFMD typically affects young children, an unusually higher proportion of adults were affected during the current pandemic. There were some subtle differences between pediatric and adult presentation of HFMD.

Making drug supply chain secure traceable and efficient: a Blockchain and smart contract based implementation.

The healthcare supply chain involves obtaining resources, managing supplies, and delivering goods and services to patients across multiple teams, stakeholders, and geographical boundaries. With such a complex structure, the healthcare supply chain is vulnerable to fraud, inaccurate data, and lack of transparency. These misdeeds cost businesses money and harm health. To address these issues, the health care supply chain needs an end-to-end decentralized track-and-trace system. Most centralized systems risk drug and data safety. This paper presents an Ethereum blockchain-based solution for a health care supply chain track-and-trace mechanism that uses smart contracts and data immutability. Hash functions store data in a public distributed ledger. This protects and discloses data. Smart contracts automate agreement execution so all parties know the outcome instantly, without an intermediary or time loss. It also outlined decentralized healthcare supply chain application architecture and algorithms. This paper proposes a system to address the lack of transparency and tracking in traditional supply chains. The blockchain-based method proposed in this paper runs on Solidity smart contracts. The system's algorithms and methods are tested against a variety of inputs, and the results are presented as an average gas cost for specific functionality. The proposed system tracks goods' histories (medicine). The average gas cost for all accounts is 18,027.2. Overall, log gas costs 48,118.6 to buy medicine, gas costs 229,607.5, and to log out 14,275.The results of the proposed system are compared to state-of-the-art methods. Thus, the presented work allows a seamless flow of medicines via blockchain and smart contracts without intermediaries. Finally, it addresses building a secure pharma supply chain application for blockchain 4.0.

Indole-3-carbinol in vitro antiviral activity against SARS-Cov-2 virus and in vivo toxicity.

The effects of indole-3-carbinol (I3C) compound have been described deeply as antitumor drug in multiple cancers. Herein, I3C compound was tested for toxicity and antiviral activity against SARS-CoV-2 infection. Antiviral activity was assessed in vitro in both in VeroE6 cell line and human Lung Organoids (hLORGs) where I3C exhibited a direct anti-SARS-CoV-2 replication activity with an antiviral effect and a modulation of the expression of genes implicated in innate immunity and inflammatory response was observed at 16.67 µM. Importantly, we further show the I3C is also effective against the SARS-CoV-2 Omicron variant. In mouse model, instead, we assessed possible toxicity effects of I3C through two different routes of administration: intragastrically (i.g.) and intraperitoneally (i.p.). The LD50 (lethal dose 50%) values in mice were estimated to be: 1410 and 1759 mg/kg i.g.; while estimated values for i.p. administration were: 444.5 mg/kg and 375 mg/kg in male and female mice, respectively. Below these values, I3C (in particular at 550 mg/kg for i.g. and 250 mg/kg for i.p.) induces neither death, nor abnormal toxic symptoms as well as no histopathological lesions of the tissues analysed. These tolerated doses are much higher than those already proven effective in pre-clinical cancer models and in vitro experiments. In conclusion, I3C exhibits a significant antiviral activity, and no toxicity effects were recorded for this compound at the indicated doses, characterizing it as a safe and potential antiviral compound. The results presented in this study could provide experimental pre-clinical data necessary for the start of human clinical trials with I3C for the treatment of SARS-CoV-2 and beyond.

Intralesional Purified Protein Derivative of Tuberculin Versus Intralesional Mycobacterium W Vaccine in Treatment of Recalcitrant Extragenital Warts: A Randomized, Single-Blinded, Comparative Study.

Introduction: Of late, immunotherapy has emerged as a promising therapeutic modality for the treatment of recalcitrant and difficult to treat warts. Purified protein derivative of tuberculin (PDD) and mycobacterium w (Mw) vaccine hold promising prospects for the treatment of verruca, especially in a country like ours where a majority of the population is already sensitized to mycobacterium tuberculosis both due to disease endemicity and Bacillus Calmette-Guérin (BCG) vaccination. Aims and Objectives: We aimed at evaluating the treatment outcome of intralesional PPD tuberculin and Mw vaccine in the treatment of recalcitrant extragenital warts in immunocompetent subjects. Materials and Methods: The patients included immunocompetent subjects between the ages of 16 and 65 years with two or more extragenital warts. The patients were randomized into two groups, namely A (PPD Tuberculin) and B (Mw vaccine). In both groups, 0.1 mL of active intralesional immunogen was injected at the base of the largest wart. The doses were repeated at 4 weeks' intervals for a maximum of 5 injections. Additionally, the improvement in quality of life was measured using the Hindi-validated version of the Dermatology Quality of Life Index (DLQI) questionnaire. Results: Ninety-seven patients completed the study, with 46 in group A and 51 in group B. In group A, 24 (52.17%) patients had complete clearance in all warts, and in group B, 32 (62.75%) (P = 0.38). The most common adverse event in patients of group A was transient injection site erythema and swelling, whereas that in group B was mild transient fever. None of the patients showed any signs of recurrence in the ensuing follow-up period. There was a statistically significant improvement in the mean DLQI scores after treatment in both groups (P < 0.0001). Conclusion: Both PPD Tuberculin and Mw vaccine are effective in the treatment of recalcitrant warts with minimal recurrence rate. The safety profile of PPD is superior to Mw vaccine. We suggest both to be used as first-line therapy in the treatment of difficult to treat warts.

Health impact assessment of Delhi's outdoor workers exposed to air pollution and extreme weather events: an integrated epidemiology approach.

This study is an assessment of the effects of outdoor air pollution and extreme weather events on the health of outdoor workers in Delhi, including auto rickshaw drivers, street vendors, and sweepers. To carry it out, a cross-sectional and perception-based epidemiological research design was used, and the primary tool used for data collection was a questionnaire. Two hundred twenty-eight people participated in the survey, and a pulmonary function test (PFT) was performed on 63 participants. Most of the respondents from different occupational groups complained about headaches/giddiness, nausea, and muscular cramps during extreme heat events due to the physically demanding nature of their jobs in the outdoor environment. Furthermore, autorickshaw drivers reported the highest prevalence of ophthalmic symptoms, such as eye redness (44%) and eye irritation (36%). In comparison, vendors reported a higher prevalence of headaches (43%) and eye redness (40%) due to increased exposure to vehicular emissions. Among sweepers, musculoskeletal problems like joint pain (40%), backache (38%), and shoulder pain (35%) were most prevalent due to occupation-related ergonomic factors. In addition, the majority of autorickshaw drivers (47%), vendors (47%), and sweepers (48%) considered that air quality had a severe impact on their health. PFT results showed that most respondents had restricted lung function. Binary logistic regression analysis showed that lung function impairment had a significant association with smoking (p = 0.023) and age (0.019). The odds ratio for smoking, which was around 4, indicated that respondents who smoked had a nearly four times greater risk of developing lung impairment. The study also highlighted the need for using personal protective equipment and developing guidelines to reduce their exposure level.

Sphingolipids accumulate in aged muscle, and their reduction counteracts sarcopenia.

Age-related muscle dysfunction and sarcopenia are major causes of physical incapacitation in older adults and currently lack viable treatment strategies. Here we find that sphingolipids accumulate in mouse skeletal muscle upon aging and that both genetic and pharmacological inhibition of sphingolipid synthesis prevent age-related decline in muscle mass while enhancing strength and exercise capacity. Inhibition of sphingolipid synthesis confers increased myogenic potential and promotes protein synthesis. Within the sphingolipid pathway, we show that accumulation of dihydroceramides is the culprit disturbing myofibrillar homeostasis. The relevance of sphingolipid pathways in human aging is demonstrated in two cohorts, the UK Biobank and Helsinki Birth Cohort Study in which gene expression-reducing variants of SPTLC1 and DEGS1 are associated with improved and reduced fitness of older individuals, respectively. These findings identify sphingolipid synthesis inhibition as an attractive therapeutic strategy for age-related sarcopenia and co-occurring pathologies.

Health impact assessment of auto rickshaw and cab drivers due to exposure to vehicular pollution in Delhi: an integrated approach.

Vehicular emission is an important contributor to air pollution in the urban environment and impacts the health of commuters as well as drivers. The in-vehicle concentration of pollutants is known to be higher than the ambient environment and varies with the mode of transport. Thus, this study attempts to assess the health impacts of air pollution exposure on auto rickshaws and cab drivers. The study was conducted in Delhi using a triangular approach involving a health perception survey, lung function test and in-vehicle monitoring of particulate matter (PM1, PM2.5, PM10) concentration to assess the health impacts of air pollution on auto rickshaw and cab drivers. A total of 150 respondents (75 from each occupation) were surveyed, and spirometry was performed for 40 respondents (20 from each occupation). Binary logistic regression showed auto rickshaw drivers were exposed to significantly higher in-vehicle PM concentrations in summers and winters and, thus, had a significantly higher risk of developing respiratory, ophthalmic and dermatological health symptoms (p< 0.05 and relative risk >1). Pulmonary function test showed obstructive lung impairment was reported only among auto rickshaw drivers (6%) and restrictive lung impairment was also more prevalent among auto rickshaw drivers (48%) than cab drivers (33%), suggesting a greater vulnerability of auto rickshaw drivers to respiratory health issues. Lung function impairment was associated with age (p= 0.002). The health and well-being of individuals is a matter of global concern, also highlighted in sustainable development goal no. 3. However, it was observed that neither auto rickshaw drivers nor cab drivers used formal/standard protective measures mainly due to unawareness or unaffordability. The study suggests increasing awareness and formulating guidelines to highlight the use of proper protective measures by these vulnerable groups and specific policy measures to protect outdoor workers like auto rickshaw drivers.

Evaluation of the Efficacy of Intralesional Measles, Mumps, and Rubella Vaccine with Intralesional Vitamin D3 as Immunotherapies in the Treatment of Recalcitrant Cutaneous Warts in Adult- A Randomized Placebo-Controlled Study.

INTRODUCTION: Currently, various destructive and ablative treatment options are conventionally used for warts, but all of them are limited in some form by their adverse effects, high recurrences, suboptimal effectiveness, and the need to treat every wart. Lately, immunotherapy has emerged as a safe treatment relying on biological substances that modulate the immune system to achieve disease control. AIMS AND OBJECTIVES: We aimed at conducting a placebo-controlled study to compare the rate of efficacy of intralesional MMR vaccine with vitamin D3 in the management of recalcitrant extragenital warts in immune-competent adults. Follow-up was done at third and sixth month. MATERIALS AND METHODS: Patients were divided into three groups, namely, group A, B, and C. Groups A, B, and C received intralesional MMR vaccine, vitamin D3 and normal saline, respectively, in the largest wart. The injections were repeated every 2 weeks, for a maximum of four injections. RESULTS: Among injected warts, in group A, complete clearance was seen in 29 (87.8%) patients, partial clearance in two (6.1%) and no response in two (6.1%) patients. In group B, 24 (77.4%) patients, five (16.1%) patients, and two (6.5%) patients showed signs of complete, partial, and no clearance, respectively, in injected warts. Complete response in distant warts was seen in 25 (75.7%) patients in group A and 20 (64.5%) patients in group B. There was no statistically significant difference between responses of the two groups. In group C, only three (12.5%) patients had complete clearance in injected warts, and none in distant warts. Recurrence was seen in two (6.4%) patients, each in group B and C. However, for management of verruca plana MMR was found to be superior to vitamin D3. LIMITATIONS: Our study was limited by a small sample size, absence of immunological analysis, and limited follow-up period. CONCLUSION: MMR vaccine and vitamin D3 are equally effective and safe treatment option for multiple, recalcitrant warts, as well as warts on difficult to treat sites with minimal recurrence.