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Background: Post-operative sore throat (POST) can be a cause of great discomfort after endotracheal intubation with an incidence of up to 65%. While there are studies demonstrating the efficacy of prophylactic zinc lozenges in decreasing POST in patients intubated using MacIntosh laryngoscope, similar studies with King Vision video laryngoscope (KVVL) are lacking. Hence, we conducted this study to assess whether similar beneficial effects can be seen in South Indian patients. Aims and Objectives: The primary objective was to evaluate the efficacy of prophylactic zinc lozenges for the prevention of POST in patients intubated using channeled KVVL. The Secondary objectives were to assess the severity of POST, the duration of laryngoscopy, and the number of intubation attempts and their effect on POST. Materials and Methods: In this prospective comparative trial, 94 American Society of Anesthesiologists physical status one and two patients, randomized into two groups received either 40 mg of a zinc lozenge or a placebo, 30 min before endotracheal intubation POST was evaluated after surgery at 0, 2, 4, 6, and 24 h. Results: The overall incidence of POST in the zinc group was 13.18% and in the placebo group was 26.37% resulting in an almost 50% reduction in the overall incidence of POST. Conclusion: The administration of zinc lozenge 30 min preoperatively is effective to reduce the incidence of POST in the immediate and early post-operative period.

Abstract Background Germline genetic testing is recommended for an increasing number of conditions with underlying genetic etiologies, the results of which impact medical management. However, genetic testing is underutilized in clinics due to system, clinician, and patient level barriers. Behavioral economics provides a framework to create implementation strategies, such as nudges, to address these multi-level barriers and increase the uptake of genetic testing for conditions where the results impact medical management. Methods Patients meeting eligibility for germline genetic testing for a group of conditions will be identified using electronic phenotyping algorithms. A pragmatic, type 3 hybrid cluster randomization study will test nudges to patients and/or clinicians, or neither. Clinicians who receive nudges will be prompted to either refer their patient to genetics or order genetic testing themselves. We will use rapid cycle approaches informed by clinician and patient experiences, health equity, and behavioral economics to optimize these nudges before trial initiation. The primary implementation outcome is uptake of germline genetic testing for the pre-selected health conditions. Patient data collected through the electronic health record (e.g. demographics, geocoded address) will be examined as moderators of the effect of nudges. Discussion This study will be one of the first randomized trials to examine the effects of patient- and clinician-directed nudges informed by behavioral economics on uptake of genetic testing. The pragmatic design will facilitate a large and diverse patient sample, allow for the assessment of genetic testing uptake, and provide comparison of the effect of different nudge combinations. This trial also involves optimization of patient identification, test selection, ordering, and result reporting in an electronic health record-based infrastructure to further address clinician-level barriers to utilizing genomic medicine. The findings may help determine the impact of low-cost, sustainable implementation strategies that can be integrated into health care systems to improve the use of genomic medicine. Trial registration ClinicalTrials.gov. NCT06377033. Registered on March 31, 2024. https://clinicaltrials.gov/study/NCT06377033?term=NCT06377033&rank=1

Precision medicine, which among other aspects includes an individual's genomic data in diagnosis and management, has become the standard‐of‐care for Mendelian cardiovascular disease (CVD). However, early identification and management of asymptomatic patients with potentially lethal and manageable Mendelian CVD through screening, which is the promise of precision health, remains an unsolved challenge. The reduced costs of genomic sequencing have enabled the creation of biobanks containing in‐depth genetic and health information, which have facilitated the understanding of genetic variation, penetrance, and expressivity, moving us closer to the genotype‐first screening of asymptomatic individuals for Mendelian CVD. This approach could transform health care by diagnostic refinement and facilitating prevention or therapeutic interventions. Yet, potential benefits must be weighed against the potential risks, which include evolving variant pathogenicity assertion or identification of variants with low disease penetrance; costly, stressful, and inappropriate diagnostic evaluations; negative psychological impact; disqualification for employment or of competitive sports; and denial of insurance. Furthermore, the natural history of Mendelian CVD is often unpredictable, making identification of those who will benefit from preventive measures a priority. Currently, there is insufficient evidence that population‐based genetic screening for Mendelian CVD can reduce adverse outcomes at a reasonable cost to an extent that outweighs the harms of true‐positive and false‐positive results. Besides technical, clinical, and financial burdens, ethical and legal aspects pose unprecedented challenges. This review highlights key developments in the field of genotype‐first approaches to Mendelian CVD and summarizes challenges with potential solutions that can pave the way for implementing this approach for clinical care.

Mavacamten is the first and only cardiac myosin inhibitor approved in 5 continents for the treatment of adults with symptomatic New York Heart Association class II and III obstructive hypertrophic cardiomyopathy. An evidence‐based rationale was used to develop individualized mavacamten dosing, guided by commonly used clinical parameters. Echocardiography is recommended as part of routine clinical assessment of patients with hypertrophic cardiomyopathy, and left ventricular (LV) outflow tract gradient and LV ejection fraction are parameters that can be readily assessed and monitored by echocardiography. Therefore, an echocardiography‐based, clinically guided dose‐titration strategy was developed to optimize patient benefit from mavacamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy while minimizing the risk of LV ejection fraction reduction. Results from clinical trials paired with extensive modeling and simulation analyses support a dose‐titration and monitoring strategy based on serial echocardiographic measures of Valsalva LV outflow tract gradient and LV ejection fraction. This dosing approach allows for the identification of the lowest individualized mavacamten dose and exposure required to provide improvements in LV outflow tract obstruction, functional capacity, and symptoms. Mavacamten is primarily metabolized by CYP2C19 (cytochrome P450 2C19), and CYP2C19 metabolizer phenotype has an effect on mavacamten exposure. Therefore, this approach has also been demonstrated to provide a favorable safety profile irrespective of patients' CYP2C19 metabolizer status. The dose‐titration strategy includes additional considerations for the potential onset of systolic dysfunction in the context of intercurrent illness, and for the potential of drug–drug interactions with inhibitors and substrates of cytochrome P450 enzymes. This posology is reflected in the mavacamten US prescribing information.

Background Aficamten, a novel cardiac myosin inhibitor, reversibly reduces cardiac hypercontractility in obstructive hypertrophic cardiomyopathy. We present a prespecified analysis of the pharmacokinetics, pharmacodynamics, and safety of aficamten in SEQUOIA‐HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM). Methods and Results A total of 282 patients with obstructive hypertrophic cardiomyopathy were randomized 1:1 to daily aficamten (5–20 mg) or placebo between February 1, 2022, and May 15, 2023. Aficamten dosing targeted the lowest effective dose for achieving site‐interpreted Valsalva left ventricular outflow tract gradient

Whitefly infestations have posed a severe threats to cotton crops in recent years, affecting farmers globally. These little insects consume food on cotton plants, causing leaf damage and lower crop yields. In response to this agricultural dilemma, we developed a novel method for detecting whitefly infestations in cotton fields. To improve pest detection accuracy, we use the combined efficiency of visual transformers and low-cost acoustic sensors. We train the vision transformer with a large dataset of cotton fields with and without whitefly infestations. Our studies yielded encouraging results, with the vision transformer obtaining an amazing 99% accuracy. Surprisingly, this high degree of accuracy is reached after only 10-20 training epochs, outperforming benchmark approaches, which normally give accuracies ranging from 80% to 90%. These outcomes underline the cost-effective potential of the vision transformer in detecting whitefly attacks on cotton crops. Moreover, the successful integration of acoustic sensors and vision transformers opens doors for further research and advancements in the domain of cotton pest detection, promising more robust and efficient solutions for farmers facing the challenges of whitefly infestations.

Background: Cervical cancer is the common cancer cause of death among women in developing countries. High Dose Rate (HDR) intracavitary brachytherapy that is given with or sequential after EBRT, is an integral component in the treatment of carcinoma of the cervix. In recent years, High Dose Rate (HDR) brachytherapy in combination with External Beam Radiotherapy (EBRT) has been popular in the management of carcinoma of the cervix. Objectives: To evaluate treatment response post 3 and 6 months after treatment completion and treatment-related toxicities during treatment in weekly v/s biweekly HDR intracavitary brachytherapy after concomitant chemoradiation in squamous cell carcinoma cervix patients. Methods: A total of 60 cervical cancer patients fulfilling the inclusion criteria were selected. Patients were randomly assigned to the weekly and Biweekly HDR ICBT using the chit-box method with replacement. Arm A (Study arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/m2) followed by HDR-ICBT 5 Gy * 5 fractions biweekly after completion of EBRT. Arm B (Control arm): 30 patients with concurrent EBRT (50 Gy/25 fractions with 2 Gy per fraction) with weekly cisplatin (35 mg/ m2) followed by HDR - ICBT 7.5 Gy * 3 fractions weekly after completion of EBRT. Results: Patients were assessed at 3 and 6 months to determine the local disease response and the incidence of any toxicities assessed during the treatment. All responses were graded as either CR (complete response), PR (partial response), SD (stable disease), or PD (progressive disease). 30 patients were assessed for therapy response using the WHO criteria. At 3 months arm A showed 86% CR and arm B showed 90% CR. 2 patients in arm A and 1 patient in arm B had PR. In both arms 2 patients had progressive disease. At 6 months 1 patient in both arms who had progressive disease converted into partial response after taking post RT chemotherapy. Conclusions: To sum up, brachytherapy is a vital aspect of the process of treating cervical cancer. Several centers have experimented with various doses and fractionation regimes. Patients in the current trial reported no safety concerns or intolerability issues across any treatment protocol. Arm A had treatment completion before arm B with comparable disease response and toxicities. Therefore, the choice of treatment plan depends on the individual patient’s circumstances and the institution’s demands. nonetheless, longer follow-ups and a bigger patient sample are needed for a solid evaluation of disease response and toxicity.

Background Annual heart transplant (HT) volumes have increased, as have post‐HT outpatient care needs. Data on HT‐related emergency department (ED) visits are limited. Methods and Results A retrospective analysis of 177 450 HT patient ED visits from the 2009 to 2018 Nationwide Emergency Department Sample was conducted. HT recipients, primary diagnoses, and comorbidities associated with ED visits were identified via International Classification of Diseases, Ninth Revision (ICD‐9) and International Classification of Diseases, Tenth Revision (ICD‐10) codes. Multivariable logistic regression was used to predict outcomes of hospital admission and death. HT volumes and HT‐related ED visits increased from 2009 to 2018. Infection was the most common primary diagnosis (24%), and cardiac primary diagnoses represented 10% of encounters. Hospital admissions occurred in 48% of visits, but overall mortality was low (1.6%). Length of stay was 3.1 days (interquartile range, 1.6–5.9 days), and comorbidity burden was high: 42% had hypertension, 38% had diabetes, and 31% had ≥2 comorbidities. Those aged ≥65 years had significantly higher odds of admission (odds ratio [OR], 2.14 [95% CI, 1.97–2.33]) and death (OR, 2.06 [95% CI, 1.61–2.62]). Comorbidities increased odds of admission (OR, 1.62 [95% CI, 1.51–1.75]) but not death. Renal primary diagnosis had the highest risk of admission (OR, 4.1 [95% CI, 3.6–4.6]), but cardiac primary diagnosis had the highest odds of death (OR, 11.6 [95% CI, 9.1–14.8]). Conclusions HT‐related ED visits increased from 2009 to 2018 with high admission rates but low in‐hospital mortality, suggesting an opportunity to improve prehospital care. Older patients and those with cardiac primary diagnoses had the highest risk of death. The observed contrast between predictors of admission and mortality signals a need for further study to improve risk stratification and outpatient care strategies.

Pathogenic mutations in LAMIN A/C (LMNA) cause abnormal nuclear structure and laminopathies. These diseases have myriad tissue-specific phenotypes, including dilated cardiomyopathy (DCM), but how LMNA mutations result in tissue-restricted disease phenotypes remains unclear. We introduced LMNA mutations from individuals with DCM into human induced pluripotent stem cells (hiPSCs) and found that hiPSC-derived cardiomyocytes, in contrast to hepatocytes or adipocytes, exhibit aberrant nuclear morphology and specific disruptions in peripheral chromatin. Disrupted regions were enriched for transcriptionally active genes and regions with lower LAMIN B1 contact frequency. The lamina-chromatin interactions disrupted in mutant cardiomyocytes were enriched for genes associated with non-myocyte lineages and correlated with higher expression of those genes. Myocardium from individuals with LMNA variants similarly showed aberrant expression of non-myocyte pathways. We propose that the lamina network safeguards cellular identity and that pathogenic LMNA variants disrupt peripheral chromatin with specific epigenetic and molecular characteristics, causing misexpression of genes normally expressed in other cell types.

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.