Association between baseline insulin resistance and hospital mortality in moderate-to-severe coronavirus disease 2019 patients without diabetes mellitus: An observational study.

Background: Insulin resistance is often implicated as a risk factor of cell-mediated immune dysfunction in sepsis patients and results in poor clinical outcome. However, it is unclear whether early insulin resistance is contributory to T-cell dysfunction and poor clinical outcome in coronavirus disease 2019 (COVID-19) patients. Methods: Adult patients with moderate-to-severe or critically ill COVID-19 infection were included in this study. Serum samples were collected at the time of diagnosis for fasting plasma glucose, serum insulin, serum cortisol, and serum glucagon measurements, and the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated. Results: One hundred and twenty-six subjects with a mean (standard deviation) age of 49.6 (16.3) years were recruited in this study, and 62.4% (78 of 125 patients) were male. HOMA-IR was a predictor of inhospital mortality with the area under the receiver operating characteristics curve (AUROC) (95% confidence interval [CI] of 0.61 [0.49-0.73]). With a cutoff value of 1.91, sensitivity was 75.5% and specificity was 45.2%. Higher serum insulin was associated with higher survival with AUROC (95% CI) of 0.65 (0.53-0.76), and the best cutoff was 7.15, with a sensitivity and specificity of 62.1% and 64.5%. Serum cortisol was also a predictor of inhospital mortality with an AUROC (95% CI) of 0.67 (0.56-0.77). Conclusion: An independent association between baseline serum cortisol and poor outcome in moderate-to-severe COVID-19 patients was observed. Hyperglycemia and HOMA-IR can also predict poor outcome in these patients with some accuracy.

Transforming Medicinal Oil into Advanced Gel: An Update on Advancements.

The present study delves into the evolution of traditional Ayurvedic oil preparations through innovative strategies to develop advanced gel formulations, aiming at amplifying their therapeutic efficacy. Ayurvedic oils have a rich historical context in healing practices, yet their conversion into contemporary gel-based formulations represents a revolutionary approach to augment their medicinal potential. The primary objective of this transformation is to leverage scientific advancements and modern pharmaceutical techniques to enhance the application, absorption, and overall therapeutic impact of these traditional remedies. By encapsulating the essential constituents of Ayurvedic oils within gel matrices, these novel strategies endeavor to improve their stability, bioavailability, and targeted delivery mechanisms. This review highlights the fusion of traditional Ayurvedic wisdom with cutting-edge pharmaceutical technology, paving the way for more effective and accessible utilization of these revered remedies in modern healthcare.

Validation of machine learning models for estimation of left ventricular ejection fraction on point-of-care ultrasound: insights on features that impact performance.

BACKGROUND: Machine learning (ML) algorithms can accurately estimate left ventricular ejection fraction (LVEF) from echocardiography, but their performance on cardiac point-of-care ultrasound (POCUS) is not well understood. OBJECTIVES: We evaluate the performance of an ML model for estimation of LVEF on cardiac POCUS compared with Level III echocardiographers' interpretation and formal echo reported LVEF. METHODS: Clinicians at a tertiary care heart failure clinic prospectively scanned 138 participants using hand-carried devices. Video data were analyzed offline by an ML model for LVEF. We compared the ML model's performance with Level III echocardiographers' interpretation and echo reported LVEF. RESULTS: There were 138 participants scanned, yielding 1257 videos. The ML model generated LVEF predictions on 341 videos. We observed a good intraclass correlation (ICC) between the ML model's predictions and the reference standards (ICC = 0.77-0.84). When comparing LVEF estimates for randomized single POCUS videos, the ICC between the ML model and Level III echocardiographers' estimates was 0.772, and it was 0.778 for videos where quantitative LVEF was feasible. When the Level III echocardiographer reviewed all POCUS videos for a participant, the ICC improved to 0.794 and 0.843 when only accounting for studies that could be segmented. The ML model's LVEF estimates also correlated well with LVEF derived from formal echocardiogram reports (ICC = 0.798). CONCLUSION: Our results suggest that clinician-driven cardiac POCUS produces ML model LVEF estimates that correlate well with expert interpretation and echo reported LVEF.

Genome-wide association study identifies human genetic variants associated with fatal outcome from Lassa fever.

Infection with Lassa virus (LASV) can cause Lassa fever, a haemorrhagic illness with an estimated fatality rate of 29.7%, but causes no or mild symptoms in many individuals. Here, to investigate whether human genetic variation underlies the heterogeneity of LASV infection, we carried out genome-wide association studies (GWAS) as well as seroprevalence surveys, human leukocyte antigen typing and high-throughput variant functional characterization assays. We analysed Lassa fever susceptibility and fatal outcomes in 533 cases of Lassa fever and 1,986 population controls recruited over a 7 year period in Nigeria and Sierra Leone. We detected genome-wide significant variant associations with Lassa fever fatal outcomes near GRM7 and LIF in the Nigerian cohort. We also show that a haplotype bearing signatures of positive selection and overlapping LARGE1, a required LASV entry factor, is associated with decreased risk of Lassa fever in the Nigerian cohort but not in the Sierra Leone cohort. Overall, we identified variants and genes that may impact the risk of severe Lassa fever, demonstrating how GWAS can provide insight into viral pathogenesis.

Automated Atrial Fibrillation Diagnosis by Echocardiography without ECG: Accuracy and Applications of a New Deep Learning Approach.

BACKGROUND: Automated rhythm detection on echocardiography through artificial intelligence (AI) has yet to be fully realized. We propose an AI model trained to identify atrial fibrillation (AF) using apical 4-chamber (AP4) cines without requiring electrocardiogram (ECG) data. METHODS: Transthoracic echocardiography studies of consecutive patients ≥ 18 years old at our tertiary care centre were retrospectively reviewed for AF and sinus rhythm. The study was first interpreted by level III-trained echocardiography cardiologists as the gold standard for rhythm diagnosis based on ECG rhythm strip and imaging assessment, which was also verified with a 12-lead ECG around the time of the study. AP4 cines with three cardiac cycles were then extracted from these studies with the rhythm strip and Doppler information removed and introduced to the deep learning model ResNet(2+1)D with an 80:10:10 training-validation-test split ratio. RESULTS: 634 patient studies (1205 cines) were included. After training, the AI model achieved high accuracy on validation for detection of both AF and sinus rhythm (mean F1-score = 0.92; AUROC = 0.95). Performance was consistent on the test dataset (mean F1-score = 0.94, AUROC = 0.98) when using the cardiologist's assessment of the ECG rhythm strip as the gold standard, who had access to the full study and external ECG data, while the AI model did not. CONCLUSIONS: AF detection by AI on echocardiography without ECG appears accurate when compared to an echocardiography cardiologist's assessment of the ECG rhythm strip as the gold standard. This has potential clinical implications in point-of-care ultrasound and stroke risk stratification.

Radical pair model for magnetic field effects on NMDA receptor activity.

The N-methyl-D-aspartate receptor is a prominent player in brain development and functioning. Perturbations to its functioning through external stimuli like magnetic fields can potentially affect the brain in numerous ways. Various studies have shown that magnetic fields of varying strengths affect these receptors. We propose that the radical pair mechanism, a quantum mechanical process, could explain some of these field effects. Radicals of the form [Formula: see text], where R is a protein residue that can be Serine or Tyrosine, are considered for this study. The variation in the singlet fractional yield of the radical pairs, as a function of magnetic field strength, is calculated to understand how the magnetic field affects the products of the radical pair reactions. Based on the results, the radical pair mechanism is a likely candidate for explaining the magnetic field effects observed on the receptor activity. The model predicts changes in the behaviour of the system as magnetic field strength is varied and also predicts certain isotope effects. The results further suggest that similar effects on radical pairs could be a plausible explanation for various magnetic field effects within the brain.

Detecting early-stage Parkinson's disease from gait data.

Parkinson's disease is a chronic and progressive neurodegenerative disorder with an estimated 10 million people worldwide living with PD. Since early signs are benign, many patients go undiagnosed until the symptoms get severe and the treatment becomes more difficult. The symptoms start intermittently and gradually become continuous as the disease progresses. In order to detect and classify these minute differences between gaits in early PD patients, we propose to use dynamic time warping (DTW). For a given set of gait data from a patient, the DTW algorithm computes the difference between any two gait cycles in the form of a warping path, which reveals small time differences between gait cycles. Once the time-warping information between all possible pairs of gait cycles is used as the main source of gait features, K-means clustering is used to extract the final features. These final features are fed to a simple logistic regression to easily and successfully detect early PD symptoms, which was reported as challenging using conventional statistical features. In addition, the use of DTW ensures that the obtained results are not affected by the differences in the style and speed of walking of a subject. Our approach is validated for the gait data from 83 subjects at early stages of PD, 10 subjects at moderate stages of PD, and 73 controls using the Leave-One-Out and N-fold cross-validation techniques, with a detection accuracy of over 98%. The high classification accuracy validated from a large data set suggests that these new features from DTW can be effectively used to help clinicians diagnose the disease at the earliest. Even though PD is not completely curable, early diagnosis would help clinicians to start the treatment from the beginning thereby reducing the intensity of symptoms at later stages.

Subphenotypes of SARS-CoV-2-Associated ARDS Overlap Each Other: A Retrospective Analysis.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-associated pneumonia and acute respiratory distress syndrome (ARDS) were often associated with hyperinflammation and elevation of several serum inflammatory markers but usually less than what is observed in non-coronavirus disease (COVID) ARDS. Elevated inflammatory markers such as C-reactive protein, interleukin (IL)-6, etc., are associated with severe infection. This study identified subphenotypes of COVID-19 ARDS patients by latent profile analysis in a cohort of Indian patients. Methods Data of n = 233 adult Indian patients with laboratory-confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital were analyzed in this retrospective study. Only patients with acute respiratory failure (defined by partial pressure of oxygen/fraction of inspired oxygen ratio < 200 mm Hg) and chest X-ray showing bilateral infiltrates were included. Results The patients' mean (standard deviation) age was 53.3 (14.9) years, and 62% were male. A two subphenotypic model was formulated based on the lowest Bayesian information criterion. Neutrophil-to-lymphocyte ratio and serum IL-6 were latent variables in that model (entropy 0.91). The second phenotype (hyperinflammatory) had lower platelet count ( p = 0.02), higher serum creatinine ( p = 0.004), higher C-reactive protein ( p = 0.001), higher ferritin ( p < 0.001), and serum lactate dehydrogenase ( p = 0.009). Age-adjusted hospital mortality ( p = 0.007), duration of hospital stay ( p < 0.001), and duration of intensive care unit stay ( p < 0.001) were significantly higher in the second subphenotype. Conclusion Two distinct but overlapping subphenotypes were identified in SARS-CoV-2-associated respiratory failure. Hyperinflammatory subphenotype was associated with significantly poor short-term outcomes.

Metagenomic surveillance uncovers diverse and novel viral taxa in febrile patients from Nigeria.

Effective infectious disease surveillance in high-risk regions is critical for clinical care and pandemic preemption; however, few clinical diagnostics are available for the wide range of potential human pathogens. Here, we conduct unbiased metagenomic sequencing of 593 samples from febrile Nigerian patients collected in three settings: i) population-level surveillance of individuals presenting with symptoms consistent with Lassa Fever (LF); ii) real-time investigations of outbreaks with suspected infectious etiologies; and iii) undiagnosed clinically challenging cases. We identify 13 distinct viruses, including the second and third documented cases of human blood-associated dicistrovirus, and a highly divergent, unclassified dicistrovirus that we name human blood-associated dicistrovirus 2. We show that pegivirus C is a common co-infection in individuals with LF and is associated with lower Lassa viral loads and favorable outcomes. We help uncover the causes of three outbreaks as yellow fever virus, monkeypox virus, and a noninfectious cause, the latter ultimately determined to be pesticide poisoning. We demonstrate that a local, Nigerian-driven metagenomics response to complex public health scenarios generates accurate, real-time differential diagnoses, yielding insights that inform policy.

Cardiac Phenotyping of SARS-CoV-2 in British Columbia: A Prospective Echo Study With Strain Imaging.

BACKGROUND: There is limited data on the residual echocardiographic findings including strain analysis among post-coronavirus disease (COVID) patients. The aim of our study is to prospectively phenotype post-COVID patients. METHODS: All patients discharged following acute COVID infection were systematically followed in the post-COVID-19 Recovery Clinic at Vancouver General Hospital and St. Paul's Hospital. At 4-18 weeks post diagnosis, patients underwent comprehensive echocardiographic assessment. Left ventricular ejection fraction (LVEF) was assessed by 3D, 2D Biplane Simpson's, or visual estimate. LV global longitudinal strain (GLS) was measured using a vendor-independent 2D speckle-tracking software (TomTec). RESULTS: A total of 127 patients (53% female, mean age 58 years) were included in our analyses. At baseline, cardiac conditions were present in 58% of the patients (15% coronary artery disease, 4% heart failure, 44% hypertension, 10% atrial fibrillation) while the remainder were free of cardiac conditions. COVID-19 serious complications were present in 79% of the patients (76% pneumonia, 37% intensive care unit admission, 21% intubation, 1% myocarditis). Normal LVEF was seen in 96% of the cohort and 97% had normal right ventricular systolic function. A high proportion (53%) had abnormal LV GLS defined as < 18%. Average LV GLS of septal and inferior segments were lower compared to that of other segments. Among patients without pre-existing cardiac conditions, LVEF was abnormal in only 1.9%, but LV GLS was abnormal in 46% of the patients. CONCLUSIONS: Most post-COVID patients had normal LVEF at 4-18 weeks post diagnosis, but over half had abnormal LV GLS.

Effect of Deferasirox on Shunt Fraction During Thoracic Surgery With One-Lung Ventilation: A Randomized Controlled Study.

Context Deferasirox, an iron chelator, can potentially reduce intraoperative right-to-left shunt and improve oxygenation in patients undergoing thoracic surgery requiring one-lung ventilation (OLV) by potentiating hypoxic pulmonary vasoconstriction (HPV). Aim The aim was to determine the effect of deferasirox on the intraoperative shunt fraction (SF) of patients undergoing thoracic surgery using OLV. Study design and settings This was a prospective, single-blind, randomized, controlled study. The study was conducted at a tertiary-care hospital. Methods Before surgery, 64 patients were allocated to two groups comprising 32 patients each. Group D patients were administered deferasirox, while those in group C were given a placebo. We included patients with the American Society of Anesthesiologists physical status III or IV, aged 18-60 years, undergoing elective thoracic surgery needing OLV. SF was the primary outcome variable. Secondary outcome variables were arterial oxygen tension (PaO2), peripheral oxygen saturation (SpO2), the ratio of PaO2 and inspired oxygen concentration (P/F), and complications such as desaturation episodes, hypotension, and tachycardia. Results Baseline and postoperative values of outcome variables were statistically similar in both groups. Intraoperative values of SF were lower and PaO2, SpO2, and P/F were higher in group D. The incidence of intraoperative desaturation was lower in group D. Conclusion We conclude that pre-treatment with deferasirox reduces intraoperative SF and improves oxygenation during thoracic surgery using OLV.

Machine learning derived echocardiographic image quality in patients with left ventricular systolic dysfunction: insights on the echo views of greatest image quality.

We sought to determine the cardiac ultrasound view of greatest quality using a machine learning (ML) approach on a cohort of transthoracic echocardiograms (TTE) with abnormal left ventricular (LV) systolic function. We utilize an ML model to determine the TTE view of highest quality when scanned by sonographers. A random sample of TTEs with reported LV dysfunction from 09/25/2017-01/15/2019 were downloaded from the regional database. Component video files were analyzed using ML models that jointly classified view and image quality. The model consisted of convolutional layers for extracting spatial features and Long Short-term Memory units to temporally aggregate the frame-wise spatial embeddings. We report the view-specific quality scores for each TTE. Pair-wise comparisons amongst views were performed with Wilcoxon signed-rank test. Of 1,145 TTEs analyzed by the ML model, 74.5% were from males and mean LV ejection fraction was 43.1 ± 9.9%. Maximum quality score was best for the apical 4 chamber (AP4) view (70.6 ± 13.9%, p<0.001 compared to all other views) and worst for the apical 2 chamber (AP2) view (60.4 ± 15.4%, p<0.001 for all views except parasternal short-axis view at mitral/papillary muscle level, PSAX M/PM). In TTEs scanned by professional sonographers, the view with greatest ML-derived quality was the AP4 view.

Quantification of pleural effusions by two-dimensional transthoracic echocardiography.

PURPOSE: There is lack of validated methods for quantifying the size of pleural effusion from standard transthoracic (TTE) windows. The purpose of this study is to determine whether pleural effusion (Peff) measured from routine two-dimensional (2D) TTE views correlate with chest radiograph (CXR). MATERIALS AND METHODS: We retrospectively identified all inpatients who underwent a TTE and CXR within 2 days in a large tertiary care center. Peff was measured on TTE from parasternal long axis (PLAX), apical four-chamber (A4C), and subcostal views and on CXR. Logistic regression models were used determine optimal cut points to predict moderate or greater Peff. RESULTS: In 200 patients (mean age 69.3 ± 14.3 years, 49.5% female), we found statistically significant associations between Peff size assessed by all TTE views and CXR, with weak to moderate correlation (PLAX length: 0.21 (95% CI [0.05, 0.35]); PLAX depth: 0.21 (95% CI [0.05, 0.35]); A4C left: 0.31 (95% CI [0.13, 0.46]); A4C right: 0.39 (95% CI [0.17, 0.57]); subcostal: 0.38 (95% CI [0.07, 0.61]). The best TTE thresholds for predicting moderate or greater left-sided Peff on CXR was PLAX length left > = 8.6 cm (sensitivity 78%, specificity 54%, PPV 26%, and NPV 92%). The best TTE thresholds for predicting moderate or greater right-sided Peff on CXR was A4C right > = 2.6 cm (sensitivity 87%, specificity 60%, PPV 37%, and NPV 94%). CONCLUSIONS: We identified statistically significant associations with Peff size measured on TTE and CXR. The predictive ability of TTE to identify moderate or large pleural effusion is limited.

Effect of positive end expiratory pressure on atelectasis in patients undergoing major upper abdominal surgery under general anaesthesia: A lung ultrasonography study.

Postoperative pulmonary complications vary in major upper abdominal surgery. The objective of this study was to assess the effect of positive end expiratory pressure on the incidence of atelectasis in patients undergoing major upper abdominal surgery under general anaesthesia using lung ultrasound. The patients were randomised into receiving either no positive end expiratory pressure (Group I) or positive end expiratory pressure of 5cm H2O (Group II). Lung ultrasound was performed at various time points - baseline, 10 minutes, 2 hours after induction, during closure of skin and 30 minutes post extubation. The lung aeration as assessed by Total Modified Lung Ultrasound Score was worse in the Group I as compared to the Group II at 2 hours post induction. Driving pressure in Group II was significantly reduced compared to Group I. Application of positive end expiratory pressure, as minimal as 5cm H2O, as a single intervention, helps in significantly reducing the Total Modified Lung Ultrasound Score after a duration of more than 2 hours and also attaining low driving pressures during intraoperative mechanical ventilation.

Early Introduction and Rise of the Omicron Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variant in Highly Vaccinated University Populations.

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly transmissible in vaccinated and unvaccinated populations. The dynamics that govern its establishment and propensity toward fixation (reaching 100% frequency in the SARS-CoV-2 population) in communities remain unknown. Here, we describe the dynamics of Omicron at 3 institutions of higher education (IHEs) in the greater Boston area. METHODS: We use diagnostic and variant-specifying molecular assays and epidemiological analytical approaches to describe the rapid dominance of Omicron following its introduction into 3 IHEs with asymptomatic surveillance programs. RESULTS: We show that the establishment of Omicron at IHEs precedes that of the state and region and that the time to fixation is shorter at IHEs (9.5-12.5 days) than in the state (14.8 days) or region. We show that the trajectory of Omicron fixation among university employees resembles that of students, with a 2- to 3-day delay. Finally, we compare cycle threshold values in Omicron vs Delta variant cases on college campuses and identify lower viral loads among college affiliates who harbor Omicron infections. CONCLUSIONS: We document the rapid takeover of the Omicron variant at IHEs, reaching near-fixation within the span of 9.5-12.5 days despite lower viral loads, on average, than the previously dominant Delta variant. These findings highlight the transmissibility of Omicron, its propensity to rapidly dominate small populations, and the ability of robust asymptomatic surveillance programs to offer early insights into the dynamics of pathogen arrival and spread.

Multimodal surveillance of SARS-CoV-2 at a university enables development of a robust outbreak response framework.

BACKGROUND: Universities are vulnerable to infectious disease outbreaks, making them ideal environments to study transmission dynamics and evaluate mitigation and surveillance measures. Here, we analyze multimodal COVID-19-associated data collected during the 2020-2021 academic year at Colorado Mesa University and introduce a SARS-CoV-2 surveillance and response framework. METHODS: We analyzed epidemiological and sociobehavioral data (demographics, contact tracing, and WiFi-based co-location data) alongside pathogen surveillance data (wastewater and diagnostic testing, and viral genomic sequencing of wastewater and clinical specimens) to characterize outbreak dynamics and inform policy. We applied relative risk, multiple linear regression, and social network assortativity to identify attributes or behaviors associated with contracting SARS-CoV-2. To characterize SARS-CoV-2 transmission, we used viral sequencing, phylogenomic tools, and functional assays. FINDINGS: Athletes, particularly those on high-contact teams, had the highest risk of testing positive. On average, individuals who tested positive had more contacts and longer interaction durations than individuals who never tested positive. The distribution of contacts per individual was overdispersed, although not as overdispersed as the distribution of phylogenomic descendants. Corroboration via technical replicates was essential for identification of wastewater mutations. CONCLUSIONS: Based on our findings, we formulate a framework that combines tools into an integrated disease surveillance program that can be implemented in other congregate settings with limited resources. FUNDING: This work was supported by the National Science Foundation, the Hertz Foundation, the National Institutes of Health, the Centers for Disease Control and Prevention, the Massachusetts Consortium on Pathogen Readiness, the Howard Hughes Medical Institute, the Flu Lab, and the Audacious Project.

Effects of radiation exposure on brain health: a state of the art and new challenges.

Good brain health refers to a condition in which a person may fully realize their talents and improve their psychological, emotional, cognitive, and behavioral functioning to cope with life's challenges. Various causes of CNS diseases are now being investigated. Radiation is one of the factors that affects the brain and causes a variety of problems. The emission or transmission of energy in the form of waves or particles via space or a material medium is known as radiation. Particle beams and electromagnetic waves are two types of ionizing radiation that have the potential to ionize atoms in a material (separating them into positively charged ions and negatively charged electrons). Radiation to the CNS can induce delayed puberty, which can lead to hyperprolactinemia, and the hypothalamic-pituitary axis can lead to gonadotropin deficit if the hypothalamic-pituitary axis is involved in the radiation field. Ionizing radiation is the most common kind of radiation. Here, we focus on the different effects of radiation on brain health. In this article, we will look at a variety of CNS diseases and how radiation affects each one, as well as how it affects the brain's numerous processes.