Impact of COVID-19 on patients undergoing scheduled procedures for chronic venous disease.

OBJECTIVE: The COVID-19 pandemic has drastically altered the medical landscape. Various strategies have been employed to preserve hospital beds, personal protective equipment, and other resources to accommodate the surges of COVID-19 positive patients, hospital overcapacities, and staffing shortages. This has had a dramatic effect on vascular surgical practice. The objective of this study is to analyze the impact of the COVID-19 pandemic on surgical delays and adverse outcomes for patients with chronic venous disease scheduled to undergo elective operations. METHODS: The Vascular Surgery COVID-19 Collaborative (VASCC) was founded in March 2020 to evaluate the outcomes of patients with vascular disease whose operations were delayed. Modules were developed by vascular surgeon working groups and tested before implementation. A data analysis of outcomes of patients with chronic venous disease whose surgeries were postponed during the COVID-19 pandemic from March 2020 through February 2021 was performed for this study. RESULTS: A total of 150 patients from 12 institutions in the United States were included in the study. Indications for venous intervention were: 85.3% varicose veins, 10.7% varicose veins with venous ulceration, and 4.0% lipodermatosclerosis. One hundred two surgeries had successfully been completed at the time of data entry. The average length of the delay was 91 days, with a median of 78 days. Delays for venous ulceration procedures ranged from 38 to 208 days. No patients required an emergent intervention due to their venous disease, and no patients experienced major adverse events following their delayed surgeries. CONCLUSIONS: Interventions may be safely delayed for patients with venous disease requiring elective surgical intervention during the COVID-19 pandemic. This finding supports the American College of Surgeons' recommendations for the management of elective vascular surgical procedures. Office-based labs may be safe locations for continued treatment when resources are limited. Although the interventions can be safely postponed, the negative impact on quality of life warrants further investigation.

Carotid endarterectomy is safe for octogenarians.

BACKGROUND: Carotid endarterectomy (CEA) has demonstrated superior results in stroke risk reduction for patients with symptomatic and asymptomatic high-grade carotid stenosis. However, this benefit has long been questioned for the elderly and high-risk populations. In the present study, we aimed to provide high-volume, single-institution data with long-term follow-up examining the risk factors for postoperative stroke and stroke-free survival stratified by age for asymptomatic and symptomatic patients undergoing CEA. METHODS: A single-institution retrospective review of 840 consecutive patients who had undergone CEA from 2011 to 2018 was performed, inclusive of both symptomatic and asymptomatic operative indications. The primary end point was perioperative stroke within 30 days of surgery. The secondary end points were late stroke, death, and myocardial infarction. Patients aged >80 years were compared with those aged <80 years to examine freedom from stroke and death. Statistically significant differences were defined as those with P < .05. RESULTS: A total of 840 patients were evaluated with a median follow-up of 416 ± 1244 days. Of the 840 patients, 499 (59%) were men, and 604 (72%) were White. The mean age was 72 ± 9 years, with 202 (24%) aged ≥80 years. CEA was performed for symptomatic disease in 305 patients (36%), of whom 143 (47%) had had strokes and 162 (53%) had had transient ischemic attacks. The overall 30-day postoperative stroke rate was 1.0% (eight patients; 0.6% for asymptomatic and 1.6% for symptomatic; P = .147). Compared with younger patients, octogenarians had had a similar stroke rate after CEA (1.5% vs 0.8%; P = .407). Hispanic race was an independent risk factor for postoperative stroke. White race and preoperative statin use both appeared to be protective. Kaplan-Meier survival curves demonstrated decreased a 5-year stroke-free survival in patients aged ≥80 years (P = .031). However, overall, the estimated 5-year survival was similar to the U.S. general population across both age groups. CONCLUSIONS: CEA for octogenarians is safe and effective for both symptomatic and asymptomatic populations with excellent 30-day outcomes and long-term survival mirroring that of the general population.

Effectiveness of a Multi-component Delirium Prevention Program Implemented on General Medicine Hospital Units: an Interrupted Time Series Analysis.

BACKGROUND: Delirium is among the most prevalent harmful events in hospitals that is associated with an elevated risk for severe outcomes such as functional decline, falls, longer length of stay, and increased mortality. OBJECTIVE: To evaluate the impact of the implementation of a multi-component delirium program on the prevalence of delirium and the incidence of falls among patients staying on general medicine inpatient hospital units. DESIGN: A pre-post intervention study using retrospective chart abstraction and interrupted time series analysis. COHORT: Patients were selected from adult patients that stayed at least 1 day on one of the five general medicine units in a large community hospital in Ontario, Canada. A total of 16 random samples of 50 patients per month for 8 consecutive months pre-intervention (October 2017 to May 2018) and 8 months post intervention (January 2019 to August 2019) were selected for a total of 800 patients. There were no exclusion criteria. INTERVENTION: The delirium program included multiple components: education of staff and hospital leadership, twice per day bed-side screen for delirium, non-pharmacological and pharmacological prevention, and intervention strategies and a delirium consultation team. MEASUREMENT: Delirium prevalence was assessed using the evidence-based delirium chart abstraction method, CHART-del. Demographic data as well as fall incidence were also collected. RESULT: Our evaluation showed that the implementation of a multicomponent delirium program led to a reduction in delirium prevalence and fall incidences. The reduction in both delirium and falls was the largest for patients in the ages between 72 and 83 years old and varied across inpatient units. CONCLUSION: A multi-component delirium program to improve the prevention, recognition, and management of delirium reduces the prevalence of delirium and fall incidence among patients in general medicine units.

Rapid-response surveillance of the first US test market for VLN cigarettes.

INTRODUCTION: VLN King menthol and non-menthol are the first combustible cigarettes to receive US Food and Drug Administration (FDA) authorisation as modified risk tobacco products. Focusing on the first retail test market, this study characterised VLN advertising, product placement, discounts and price. METHODS: All Chicago-area Circle K stores (n=133) were telephoned to assess whether they sold VLN. Single-pack price of non-menthol was obtained in 57 of 100 stores that sold VLN. In fall 2022, trained data collectors visited those 57 stores to assess VLN product placement, advertising, discounts and prices. Paired t-tests compared observed VLN price with telephone price and to price of other cigarette brands. RESULTS: Nearly all stores (91.1%) displayed exterior advertisements for VLN, and 41.1% displayed interior advertising, with 8.9% of stores advertising VLN in the power wall but never in the header row. VLN cigarettes were displayed in the power wall exclusively and among high-nicotine cigarettes. Some VLN marketing claims were not FDA-authorised. VLN advertised a sweepstakes offer and rewards programme. Most stores (85.7%) offered VLN discounts. VLN was priced like a premium brand (mean=$10.90, SD=$1.53), and prices obtained by telephone did not differ from observed prices several months later. CONCLUSIONS: Retail marketing strategies for VLN mimic those for high-nicotine cigarettes. Deviations from FDA-authorised marketing claims were evident. Surveillance in future test markets is recommended to assess compliance with marketing claims and examine relative price and discount offers. Of interest is how premium-priced, low-nicotine cigarettes stand to compete in a market dominated by cheaper high-nicotine cigarettes.

Type IV Hypersensitivity Reaction after Cyanoacrylate Venous Closure.

BACKGROUND: Nonthermal endovenous closure techniques are routinely utilized to treat superficial axial venous reflux. Cyanoacrylate closure is a safe and effective modality implemented for truncal closure. However, an adverse reaction of type IV hypersensitivity (T4H), unique to cyanoacrylate, is a known risk. This study aims to evaluate the real-world incidence of T4H and examine risk factors that may predispose its development. METHODS: A retrospective review between 2012- and 2022 was performed at four tertiary US institutions to examine patients who underwent cyanoacrylate vein closure of their saphenous veins. Patient demographics, comorbidities, CEAP (Clinical [C], Etiological [E], Anatomical [A], and Pathophysiological [P]) classification, and periprocedural outcomes were included. The primary endpoint was development of T4H post procedure. Logistic regression analysis for risk factors predictive of T4H was performed. Variables with a P-value of <0.05 were deemed significant. RESULTS: 595 patients underwent 881 cyanoacrylate venous closures. Mean age was 66.2 ± 14.9, and 66% of patients were female. There were 92 (10.4%) T4H events in 79 (13%) patients. Oral steroids were administered to 23% for persistent and/or severe symptoms. There were no systemic allergic reactions to cyanoacrylate. Multivariate analysis revealed younger age (P = 0.015), active smoking status (P = 0.033), and CEAP 3 (P < 0.001) and 4 (P = 0.005) classifications as independent risk factors associated with development of T4H. CONCLUSIONS: This real-world multicenter study shows the overall incidence of T4H to be 10%. CEAP 3 and 4 patients of younger age and smokers predicted a higher risk of T4H to cyanoacrylate.

The effects of Yakson touch and gentle human touch on preterm infants: A systematic review and meta-analysis.

We aim to collect the evidence of efficacy of Gentle Guman Touch (GHT) and Yakson Touch in preterm neonates as pain relief, heart rate, oxygen saturation, and urine cortisol level. We made our search through PubMed, Web of Science, Scopus, and Cochrane by the mid of March 2023. Randomized control trials (RCTs) were included, and the Cochrane risk of bias tool was utilized to assess their quality. Using Review Manager software, a meta-analysis was conducted. We computed the mean difference (MD) with a 95% confidence interval (CI) for the continuous data. During the examination, the Neonatal Infant Pain Scale (NIPS) was significantly reduced in the touch group compared to the control group (MD = -3.40, 95% CI [-4.15 to -2.64], P-value= 0.00001). After the examination, the NIPS score was also reduced by both Yakson touch and GHT compared to the control (MD = -2.14, 95% CI [-3.42 to -0.85], P-value <0.00001). Yakson touch and GHT are non-pharmacological, easy, and safe methods that can be used for painful interventions to reduce the pain experience of preterm infants from variable interventions. Both methods improved infant sleep and behavior. Preterm infants' heart rates and oxygen saturation were unaffected by Yakson touch or GHT.

U"AI" Testing: User Interface and Usability Testing of a Chest X-ray AI Tool in a Simulated Real-World Workflow.

Purpose: To observe interactions of practicing radiologists with a chest x-ray AI tool and evaluate its usability and impact on workflow efficiency. Methods: Using a simulated clinical workflow and remote multi-monitor screensharing, we prospectively assessed the interactions of 10 staff radiologists (5-33 years of experience) with a PACS-embedded, regulatory-approved chest x-ray AI tool. Qualitatively, we collected feedback using a think-aloud method and post-testing semi-structured interview; transcript themes were categorized by: (1) AI tool features, (2) deployment considerations, and (3) broad human-AI interactions. Quantitatively, we used time-stamped video recordings to compare reporting and decision-making efficiency with and without AI assistance. Results: For AI tool features, radiologists appreciated the simple binary classification (normal vs abnormal) and found the heatmap essential to understand what the AI considered abnormal; users were uncertain of how to interpret confidence values. Regarding deployment considerations, radiologists thought the tool would be especially helpful for identifying subtle diagnoses; opinions were mixed on whether the tool impacted perceived efficiency, accuracy, and confidence. Considering general human-AI interactions, radiologists shared concerns about automation bias especially when relying on an automated triage function. Regarding decision-making and workflow efficiency, participants began dictating 5 seconds later (42% increase, P = .02) and took 14 seconds longer to complete cases (33% increase, P = .09) with AI assistance. Conclusions: Radiologist usability testing provided insights into effective AI tool features, deployment considerations, and human-AI interactions that can guide successful AI deployment. Early AI adoption may increase radiologists' decision-making and total reporting time but improves with experience.

A comprehensive review on clinical and mechanistic pathophysiological aspects of COVID-19 Malady: How far have we come?

Since its outbreak in 2019, the coronavirus disease (COVID-19) has become a pandemic, affecting more than 52 million people and causing more than 1 million mortalities globally till date. Current research reveals a wide array of disease manifestations and behaviors encompassing multiple organ systems in body and immense systemic inflammation, which have been summarized in this review. Data from a number of scientific reviews, research articles, case series, observational studies, and case reports were retrieved by utilizing online search engines such as Cochrane, PubMed, and Scopus from December 2019 to November 2020. The data for prevalence of signs and symptoms, underlying disease mechanisms and comorbidities were analyzed using SPSS version 25. This review will discuss a wide range of COVID-19 clinical presentations recorded till date, and the current understanding of both the underlying general as well as system specific pathophysiologic, and pathogenetic pathways. These include direct viral penetration into host cells through ACE2 receptors, induction of inflammosomes and immune response through viral proteins, and the initiation of system-wide inflammation and cytokine production. Moreover, peripheral organ damage and underlying comorbid diseases which can lead to short term and long term, reversible and irreversible damage to the body have also been studied. We concluded that underlying comorbidities and their pathological effects on the body contributed immensely and determine the resultant disease severity and mortality of the patients. Presently there is no drug approved for treatment of COVID-19, however multiple vaccines are now in use and research for more is underway.

All together: Integrated care for youth with type 1 diabetes.

OBJECTIVE: We describe the implementation and evaluation of an integrated, stepped care model aimed to identify and address the concerns of adolescents with type 1 diabetes (T1D) associated with diabetes-related quality of life (DRQoL), emotional well-being, and depression. RESEARCH DESIGN AND METHODS: The care model with 4 steps: (1) Systematic identification and discussion of concerns salient to adolescents; (2) Secondary screening for depressive symptoms when indicated; (3) Developing collaborative treatment plans with joint physical and mental health goals; and (4) Psychiatric assessment and embedded mental health treatment; was implemented into an ambulatory pediatric diabetes clinic and evaluated using quantitative and qualitative methods. RESULTS: There were 236 adolescents (aged 13-18 years) with T1D that were enrolled in the care model. On average adolescents identified three concerns associated with their DRQoL and 25% indicated low emotional well-being. Fifteen adolescents received a psychiatric assessment and embedded mental health treatment. Both adolescents and caregivers were appreciative of a broader, more holistic approach to their diabetes care and to the greater focus of the care model on adolescents, who were encouraged to self-direct the conversation. Parents also appreciated the extra level of support and the ability to receive mental health care for their adolescents from their own diabetes care team. CONCLUSION: The initial findings from this project indicate the acceptability and, to limited extent, the feasibility of an integrated stepped care model embedded in an ambulatory pediatric diabetes clinic led by an interdisciplinary care team. The care model facilitated the identification and discussion of concerns salient to youth and provided a more holistic approach.

Correction: Samad, N., et al. Behavioral and Biochemical Effects of Mukia madrespatana Following Single Immobilization Stress in Rats. Medicina 2020, 56, 350.

We would like to change the funding part of paper [...].

Behavioral and Biochemical Effects of Mukia madrespatana Following Single Immobilization Stress on Rats.

BACKGROUND AND OBJECTIVES: Elevated oxidative stress has been shown to play an important role in the diagnosis and prognosis of stress and memory-related complications. Mukia madrespatana (M. madrespatana) has been reported to have various biological and antioxidant properties. We intended to evaluate the effect of M. madrespatana peel on single immobilization stress-induced behavioral deficits and memory changes in rats. Materials and Methods: M. madrespatana peel (2000 mg/kg/day, orally) was administered to control and immobilize stressed animals for 4 weeks. Anxiolytic, antidepressant, and memory-enhancing effects of M. madrespatana were observed in both unstressed and stressed animals. Results: Lipid peroxidation was decreased while antioxidant enzymes were increased in both unstressed and stressed animals. Acetylcholine level was increased while acetylcholinesterase activity was decreased in both M. madrespatana treated unstressed and stressed rats. There was also an improvement in memory function. Serotonin neurotransmission was also regulated in M. madrespatana treated rats following immobilization stress with anxiolytic and anti-depressive effects. Conclusion: Based on the current study, it is suggested that M. madrespatana has strong antioxidant properties and may be beneficial as dietary supplementation in stress and memory-related conditions.

Adoption of evidence-based novel therapies in the treatment of gastric cancer: A national observational study.

BACKGROUND: The adoption of novel and effective gastric cancer therapies into general clinical practice has crucial implications for patient outcomes. The current study explored trends in treatment use and overall survival in patients with gastric cancer in the United States. METHODS: Patients with adenocarcinoma of the gastric cardia and noncardia were identified in the National Cancer Data Base between 2006 and 2014. Tumor stages were divided into early (IA), locally advanced (IB-IIIC), and metastatic (IV) stage. Treatment use was examined according to tumor stage and location. Time trend analyses of treatment use and overall survival were conducted. RESULTS: A total of 89,098 patients with gastric adenocarcinoma were identified. In those with early-stage cancer, endoscopic treatment increased over time in patients with cardia and noncardia disease. In patients with locally advanced cardia disease, preoperative therapy use increased over time (2013-2014 [vs 2006-2008]: odds ratio [OR], 3.09; 95% confidence interval [95% CI], 2.80-3.41). In patients with locally advanced noncardia disease, the use of preoperative therapy also increased (2013-2014: OR, 3.32; 95% CI, 2.88-3.82) as did the use of perioperative therapy (2013-2014: OR, 4.21; 95% CI, 3.52-5.03) in lieu of postoperative treatment (2013-2014: OR, 0.66; 95% CI, 0.60-0.71). In patients with metastatic disease, approximately 34% of patients with cardia and 40% of patients with noncardia cancer did not receive treatment. Stage-specific and location-specific overall survival was found to improve over the study period. CONCLUSIONS: Practice patterns for the treatment of gastric cancer in the United States reflect the increased adoption of evidence-based therapies, including endoscopic resection of early-stage cancer and preoperative therapy for patients with locally advanced disease. Treatment for metastatic disease remains markedly underused. Cancer 2018;124:1122-31. © 2017 American Cancer Society.

Fructans Exacerbate Symptoms in a Subset of Children With Irritable Bowel Syndrome.

BACKGROUND & AIMS: Dietary fructans exacerbate symptoms in some, but not all, adults with irritable bowel syndrome (IBS). We sought to determine whether fructans worsen symptoms in children with IBS and whether clinical and psychosocial factors, and/or gas production, can identify those who are fructan sensitive. METHODS: We performed a double-blind placebo-controlled (maltodextrin) cross-over trial of 23 children with IBS, based on pediatric Rome III criteria, from September 2014 through December 2016. At baseline, participants completed 1-week pain and stool diaries and a 3-day food record and psychosocial factors (depression, anxiety, and somatization) were measured. Subjects were randomly assigned to groups that were provided meals for 72 hours containing either fructans or maltodextrin (0.5 g/kg; maximum, 19 g). Following a washout period of 10 days or more, the subjects received the meal they were not given during the first study period (crossed over). Gastrointestinal symptoms and breath hydrogen and methane production were captured during each meal period. Fructan sensitivity was defined as an increase of 30% or more in abdominal pain frequency following fructan ingestion. RESULTS: Subjects had more mean episodes of abdominal pain/day during the fructan-containing diet (3.4 ± 2.6) vs the maltodextrin-containing diet (2.4 ± 1.7) (P < .01), along with more severe bloating (P < .05) and flatulence (P = .01). Hydrogen (but not methane) production was greater while subjects were on the fructan-containing diet (617 ± 305 ppm∗h) than the maltodextrin-containing diet (136 ± 78 ppm*h) (P < .001). Eighteen subjects (78.2%) had more frequent abdominal pain while on the fructan-containing diet and 12 (52.2%) qualified as fructan sensitive. We found no difference between fructan-sensitive and fructan-insensitive subjects in baseline abdominal pain or bowel movement characteristics, dietary intake, psychosocial parameters, IBS subtype, or gas production. CONCLUSIONS: In a randomized controlled trial of children with IBS, we found fructans to exacerbate several symptoms. However, fructan sensitivity cannot be identified based on baseline gastrointestinal symptoms, dietary intake, psychosocial factors, or gas production. Clinicaltrials.gov no: NCT02842281.

Antioxidant activity, acetylcholinesterase inhibitory potential and phytochemical analysis of Sarcocephalus latifolius Sm. bark used in traditional medicine in Sudan.

BACKGROUND: Sarcocephalus latifolius is used as a traditional medicine for curing many diseases in Sudan. The main objective of the current study was to determine the antioxidant activity and acetylcholinesterase inhibition (AChEI) of S. latifolius, and to estimate its total phenolic and flavonoid contents. METHODS: Antioxidant activity of the tested plant extracts was carried out by determining their ability to scavenge the 2,2-diphenyl-1-picryl hydrazyl (DPPH) free radical. On the other hand, AChE inhibitory activity was determined spectrophotometrically using the Ellman's colorimetric method. The levels of total phenols and flavonoids were determined quantitatively using spectrophotometric methods. MTT assay was consumed to assess the cytotoxic effect of the most active fractions. These fractions were subjected to phytochemical analysis using GC-MS techniques to determine thier chemical composition. RESULTS: Hexane and chloroform fractions exhibited the highest antioxidant activity with IC50 values of (0.098 ± 0.08 and 0.099 ± 0.029 mg/ml) respectively. Standard propyl gallate had the lowest IC50 value of 0.0414 ± 0.11 mg/ml. The ethanolic crude extract showed low AChEI activity with 40.2 ± 0.10%. High concentrations of phenolic and flavonoid contents were observed. GCMS revealed the presence of well-known antioxidants compounds e.g. Vitamin E and caffeic acid. CONCLUSION: The ethanolic extract of bark of S. latifolius showed potent antioxidant effects and low AChEI activity, high phenolic and flavonoid contents and presence of pharmacologically active compounds. These findings explain its wide usages in traditional medicine.

Amidation inhibitors 4-phenyl-3-butenoic acid and 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester are novel HDAC inhibitors with anti-tumorigenic properties.

4-Phenyl-3-butenoic acid (PBA) is an inhibitor of peptidylglycine alpha-amidating monooxygenase with anti-inflammatory properties that has been shown to inhibit the growth of ras-mutated epithelial and human lung carcinoma cells. In this report, we show that PBA also increases the acetylation levels of selected histone subtypes in a dose and time dependent manner, an effect that is attributable to the inhibition of histone deacetylase (HDAC) enzymes. Comparison studies with the known HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) using high resolution two-dimensional polyacrylamide gels and Western analysis provide evidence that PBA acts as an HDAC inhibitor within cells. PBA and a more potent amidation inhibitor, 5-(acetylamino)-4-oxo-6-phenyl-2-hexenoic acid methyl ester (AOPHA-Me), inhibit HDAC enzymes in vitro at micromolar concentrations, with IC50 values approximately 30 fold lower for AOPHA-Me than PBA for selected HDAC isoforms. Overall, these results indicate that PBA and AOPHA-Me are novel anti-tumorigenic HDAC inhibitors.

Unveiling the nexus between perceived overqualification and knowledge hiding: Moderated mediation analysis of job crafting and job boredom.

Purpose: Grounding on relative deprivation theory, this study aimed to investigate the relationship between perceived overqualification (POQ) and knowledge hiding. Furthermore, this study investigated the mediating role of job boredom and the moderating effect of job crafting. Design: /Methodology/Approach: This study employs Hayes' PROCESS model to analyze data obtained from 374 employees working in the hospitality and tourism industry. Findings: The results indicate a positive relationship between POQ, job boredom, and knowledge hiding. These findings suggest that job boredom mediates the relationship between POQ and knowledge hiding. Furthermore, the study showed a moderated mediation path wherein the interaction effect of POQ and job crafting on knowledge hiding was mediated by job boredom. Research limitations/implications: Data were collected from the hospitality and tourism industry, limiting the generalizability of the findings to other sectors. Additionally, the study relied on self-reported measures, which may have resulted in a bias. Practical implications: Conduct thorough job fit assessments during the hiring process to ensure that candidates' qualifications align closely with job requirements. By matching employees' skills and experiences to their job, organizations can reduce perceived overqualification, which may lower job boredom and knowledge hiding tendencies. Originality/value: This study's focus on person-job misfits adds a new layer of insight into employee experiences in the workplace. By examining how mismatches between individuals and their roles contribute to job boredom and knowledge hiding, this study highlights the importance of aligning job responsibilities with employee skills, qualifications, and preferences.

Fractal Pattern in the Premature Graying of Hair: A Case Report.

Premature graying of hair (PGH) is a multifactorial condition defined by the graying of hair before the age of 20 in Caucasians and before the age of 30 in African Americans. Although the etiology remains unknown, it has been associated with genetic predisposition, oxidative stress, nutritional deficiencies, and autoimmune diseases. Current treatment options are limited but can include anti-inflammatory medications, vitamins, and hair colorants for symptom control. In this report, we present a case of premature graying in a 32-year-old male, onset at age 15, exhibiting a distinctive fractal pattern. This case represents a unique instance of PGH characterized by an unusual pattern, necessitating further investigation into potential etiological factors and underlying pathophysiological mechanisms.

Comparing machine learning screening approaches using clinical data and cytokine profiles for COVID-19 in resource-limited and resource-abundant settings.

Accurate screening of COVID-19 infection status for symptomatic patients is a critical public health task. Although molecular and antigen tests now exist for COVID-19, in resource-limited settings, screening tests are often not available. Furthermore, during the early stages of the pandemic tests were not available in any capacity. We utilized an automated machine learning (ML) approach to train and evaluate thousands of models on a clinical dataset consisting of commonly available clinical and laboratory data, along with cytokine profiles for patients (n = 150). These models were then further tested for generalizability on an out-of-sample secondary dataset (n = 120). We were able to develop a ML model for rapid and reliable screening of patients as COVID-19 positive or negative using three approaches: commonly available clinical and laboratory data, a cytokine profile, and a combination of the common data and cytokine profile. Of the tens of thousands of models automatically tested for the three approaches, all three approaches demonstrated > 92% sensitivity and > 88 specificity while our highest performing model achieved 95.6% sensitivity and 98.1% specificity. These models represent a potential effective deployable solution for COVID-19 status classification for symptomatic patients in resource-limited settings and provide proof-of-concept for rapid development of screening tools for novel emerging infectious diseases.

Dual modulation of JNK and Akt signaling pathways by chaetoglobosin K in human lung carcinoma and ras-transformed epithelial cells.

Chaetoglobosin K (ChK) is a natural product that inhibits anchorage-dependent and anchorage-independent growth of ras-transformed cells, prevents tumor-promoter disruption of cell-cell communication, and reduces Akt activation in tumorigenic cells. This study demonstrates how ChK modulates the JNK pathway in ras-transformed and human lung carcinoma cells and investigates regulatory mechanisms controlling ChK's effect on the Akt and JNK signaling pathways. Human lung carcinoma and ras-transformed epithelial cell lines treated with ChK or vehicle for varying times were assayed for cell growth or extracted for total proteins for western blot analysis using phosphorylation site-specific antibodies to monitor changes in activation of JNK, Akt, and other signaling enzymes. Results show that ChK inhibited both Akt and JNK phosphorylation at key activation sites in ras-transformed cells as well as human lung carcinoma cells. Downstream effectors of both kinases were accordingly affected. Direct upstream kinases of JNK were not affected by ChK. Wortmannin and LY294002, two PI3 kinase inhibitors, inhibited Akt but not JNK phosphorylation in ras-transformed cells. This report establishes the dual inhibitory effect of ChK on both the Akt and JNK signaling pathways in ras-transformed epithelial and human carcinoma cells. The unique effect of ChK on these two key pathways involved in carcinogenesis earmarks ChK for further studies to determine its molecular target(s) and in vivo anti-tumor potential.