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Background Metformin has antiviral activity against RNA viruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The mechanism appears to be suppression of protein translation via targeting the host mechanistic target of rapamycin pathway. In the COVID-OUT randomized trial for outpatient coronavirus disease 2019 (COVID-19), metformin reduced the odds of hospitalizations/death through 28 days by 58%, of emergency department visits/hospitalizations/death through 14 days by 42%, and of long COVID through 10 months by 42%. Methods COVID-OUT was a 2 × 3 randomized, placebo-controlled, double-blind trial that assessed metformin, fluvoxamine, and ivermectin; 999 participants self-collected anterior nasal swabs on day 1 (n = 945), day 5 (n = 871), and day 10 (n = 775). Viral load was quantified using reverse-transcription quantitative polymerase chain reaction. Results The mean SARS-CoV-2 viral load was reduced 3.6-fold with metformin relative to placebo (−0.56 log10 copies/mL; 95% confidence interval [CI], −1.05 to −.06; P =.027). Those who received metformin were less likely to have a detectable viral load than placebo at day 5 or day 10 (odds ratio [OR], 0.72; 95% CI,.55 to.94). Viral rebound, defined as a higher viral load at day 10 than day 5, was less frequent with metformin (3.28%) than placebo (5.95%; OR, 0.68; 95% CI,.36 to 1.29). The metformin effect was consistent across subgroups and increased over time. Neither ivermectin nor fluvoxamine showed effect over placebo. Conclusions In this randomized, placebo-controlled trial of outpatient treatment of SARS-CoV-2, metformin significantly reduced SARS-CoV-2 viral load, which may explain the clinical benefits in this trial. Metformin is pleiotropic with other actions that are relevant to COVID-19 pathophysiology. Clinical Trials Registration NCT04510194. [ABSTRACT FROM AUTHOR]

Purpose: Physical therapy (PT) and conservative care are recommended first-line treatments for musculoskeletal (MSK) pain. While essential to high-quality care, these solutions often do not provide immediate or sufficient pain relief. Traditional transcutaneous electronic nerve stimulation (TENS) devices are often recommended; however, there is mixed evidence behind their effectiveness. A novel approach called hybrid form impulse therapy (HFIT) incorporates a priming pulse with a traditional TENS pulse width and frequency. This randomized controlled trial (RCT) aimed to compare the effectiveness of HFIT versus traditional TENS versus usual care among members of a digital MSK program. Patients and Methods: A three-arm RCT comparing HFIT versus TENS versus usual care was conducted. A total of 325 people with chronic back or knee pain who were members of a digital MSK program consisting of PT-guided exercise therapy, education, and coaching were randomized. Outcomes including pain, function, anxiety, and depression were examined at 1, 2, and 4 weeks (primary endpoint). Engagement was measured through exercise therapy (ET) sessions completed. Unadjusted and adjusted logistic generalized estimating equations were conducted. Results: Adjusted per-protocol results at 4 weeks showed significantly lower odds of achieving pain improvement for both TENS (OR: 0.42, 95% CI: [0.19, 0.92]) and usual care (OR: 0.35, 95% CI: [0.17, 0.72]) groups, compared to HFIT group. Both HFIT and usual care users had significantly higher engagement than the TENS users (p=0.026 and p=0.002, respectively). No adverse events were reported throughout the study. Conclusion: More participants of a digital MSK program who were randomized to the HFIT group experienced meaningful pain improvement at 4 weeks than participants who used TENS and usual care. HFIT can be an effective, non-pharmaceutical solution for relief as a complement to first-line treatments for patients with chronic back and knee pain. [ABSTRACT FROM AUTHOR]

This study describes decentralized recruitment and enrollment for a COVID-19 treatment trial, while comparing 5 primary recruitment methods: search engine ads, paid advertising within a national testing company, paid advertising within a regional testing company, electronic health record messages, and word of mouth. These are compared across patient demographics, efficiency, and cost. Clinical Trials Registration NCT04510194. [ABSTRACT FROM AUTHOR]

Background Data conflict on whether vaccination decreases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load. The objective of this analysis was to compare baseline viral load and symptoms between vaccinated and unvaccinated adults enrolled in a randomized trial of outpatient coronavirus disease 2019 (COVID-19) treatment. Methods Baseline data from the first 433 sequential participants enrolling into the COVID-OUT trial were analyzed. Adults aged 30–85 with a body mass index (BMI) ≥25 kg/m2 were eligible within 3 days of a positive SARS-CoV-2 test and <7 days of symptoms. Log10 polymerase chain reaction viral loads were normalized to human RNase P by vaccination status, by time from vaccination, and by symptoms. Results Two hundred seventy-four participants with known vaccination status contributed optional nasal swabs for viral load measurement: median age, 46 years; median (interquartile range) BMI 31.2 (27.4–36.4) kg/m2. Overall, 159 (58%) were women, and 217 (80%) were White. The mean relative log10 viral load for those vaccinated <6 months from the date of enrollment was 0.11 (95% CI, –0.48 to 0.71), which was significantly lower than the unvaccinated group (P  = .01). Those vaccinated ≥6 months before enrollment did not differ from the unvaccinated with respect to viral load (mean, 0.99; 95% CI, –0.41 to 2.40; P  = .85). The vaccinated group had fewer moderate/severe symptoms of subjective fever, chills, myalgias, nausea, and diarrhea (all P  < .05). Conclusions These data suggest that vaccination within 6 months of infection is associated with a lower viral load, and vaccination was associated with a lower likelihood of having systemic symptoms. [ABSTRACT FROM AUTHOR]

Observational studies suggest outpatient metformin use is associated with reduced mortality from coronavirus disease‐2019 (COVID‐19). Metformin is known to decrease interleukin‐6 and tumor‐necrosis factor‐α, which appear to contribute to morbidity in COVID‐19. We sought to understand whether outpatient metformin use was associated with reduced odds of severe COVID‐19 disease in a large US healthcare data set. Retrospective cohort analysis of electronic health record (EHR) data that was pooled across multiple EHR systems from 12 hospitals and 60 primary care clinics in the Midwest between March 4, 2020 and December 4, 2020. Inclusion criteria: data for body mass index (BMI) > 25 kg/m2 and a positive SARS‐CoV‐2 polymerase chain reaction test; age ≥ 30 and ≤85 years. Exclusion criteria: patient opt‐out of research. Metformin is the exposure of interest, and death, admission, and intensive care unit admission are the outcomes of interest. Metformin was associated with a decrease in mortality from COVID‐19, OR 0.32 (0.15, 0.66; p =.002), and in the propensity‐matched cohorts, OR 0.38 (0.16, 0.91; p =.030). Metformin was associated with a nonsignificant decrease in hospital admission for COVID‐19 in the overall cohort, OR 0.78 (0.58–1.04, p =.087). Among the subgroup with a hemoglobin HbA1c available (n = 1193), the adjusted odds of hospitalization (including adjustment for HbA1c) for metformin users was OR 0.75 (0.53–1.06, p =.105). Outpatient metformin use was associated with lower mortality and a trend towards decreased admission for COVID‐19. Given metformin's low cost, established safety, and the mounting evidence of reduced severity of COVID‐19 disease, metformin should be prospectively assessed for outpatient treatment of COVID‐19. Highlights: Oral outpatient therapies for SARS‐CoV‐2 infection are desperately needed.Metformin has a history of anti‐inflammatory and anti‐viral effects.In this retrospective cohort analysis in persons with overweight or obesity outpatient metformin use was associated with lower lower mortality. There was no significant association with reduced hospitalization. [ABSTRACT FROM AUTHOR]

Over the past two decades, there have been a lot of advances in the field of pattern analyses for biomedical signals, which have helped in both medical diagnoses and in furthering our understanding of the human body. A relatively recent area of interest is the utility of biomedical signals in the field of biometrics, i.e., for user identification. Seminal work in this domain has already been done using electrocardiograph (ECG) signals. In this paper, we discuss our ongoing work in using a relatively recent modality of biomedical signals—a cardio-synchronous waveform measured using a Radio-Frequency Impedance-Interrogation (RFII) device for the purpose of user identification. Compared to an ECG setup, this device is noninvasive and measurements can be obtained easily and quickly. Here, we discuss the feasibility of reducing the dimensions of these signals by projecting onto various subspaces while still preserving interuser discriminating information. We compare the classification performance using classical dimensionality reduction methods such as principal component analysis (PCA), independent component analysis (ICA), random projections, with more recent techniques such as K-SVD-based dictionary learning. We also report the reconstruction accuracies in these subspaces. Our results show that the dimensionality of the measured signals can be reduced by 60 fold while maintaining high user identification rates. [ABSTRACT FROM PUBLISHER]

Computed Tomography (CT) and Magnetic Resonance Imaging (MRI) are arguably the most prominent and most widely used healthcare diagnostic modalities for a wide range of applications. There are certain specific applications for which a particular modality is specifically used or has been adopted over a period of time because of reasons like good diagnostic accuracy, fast diagnosis, etc. One such application for CT has been "Spinal Fracture Diagnosis" and for MRI has been "Brain Tumor Detection". This study presents case studies from different time periods to demonstrate the evolution of these respective applications and emphasizes the role of Artificial Intelligence (AI) based techniques like machine learning, deep learning, etc. for advancements in the diagnostic process. The case studies will enable the new researchers to understand the background and the work done in the respective time period. The time period of the studies referred to is between the years 2000 and 2023 (Present date). The purpose of this study is to enlighten the reader about the evolution of spinal fractures and brain tumor diagnosis which are understood to be primary applications of CT and MRI, respectively and, encourage further study into topics pertaining to AI-based tools used in diagnostic modalities for applications like automatic detection and prediction, smart decision making, early detection, etc. [ABSTRACT FROM AUTHOR]

Design Credit: Andy Grams. B Back Cover Caption b : The cover image is based on the Research Article I Outpatient metformin use is associated with reduced severity of COVID-19 disease in adults with overweight or obesity i by Carolyn T. Bramante et al., https://doi.org/10.1002/jmv.26873. [Extracted from the article]

In the early seventeenth century, the amount of meat available in Rome increased exponentially, with consumption reaching a pound per person per day in the 1630s. There were cultural and political reasons for this surge: in the wake of the Reformation, a series of popes sought to turn the city of Rome into a model "city on a hill," representing the ideal of a Catholic state under a powerful ruler. However, to bring such large amounts of food from the countryside to Roman tables required enormous efforts on the part of a variety of bureaucrats and local artisans working for the papal regime. This essay will briefly examine the efforts of two of those groups that helped create Rome's "meat moment": the contatori who inspected and distributed animals brought from the countryside to Rome and the butchers in the city. In the end, the dramatic increase in supply was not sustainable and would result in both political and ecological upheaval. [ABSTRACT FROM AUTHOR]

We propose and test a catering theory of nominal stock prices. The theory predicts that when investors place higher valuations on low-price firms, managers respond by supplying shares at lower price levels, and vice versa. We confirm these predictions in time-series and firm-level data using several measures of time-varying catering incentives. More generally, the results provide unusually clean evidence that catering influences corporate decisions, because the process of targeting nominal share prices is not well explained by alternative theories. [ABSTRACT FROM AUTHOR]

Background: Mycoplasma mastitis is increasingly posing significant impact on dairy industry. Although the effects of major conventional mastitis pathogens on milk components has been widely addressed in the literature, limited data on the effects of different Mycoplasma and Acholeplasma spp. on milk quality and quantity is available. The aim of this study was to determine the casual relationship of Mycoplasma spp. and A. laidlawii to mastitis and compare them to subclinical mastitis caused by conventional mastitis pathogens from a single dairy herd in South Australia; Mycoplasma spp. and A. laidlawii were detected using PCR applied directly to milk samples. The herd had mastitis problem with high somatic cell count and low response rate to conventional antimicrobial therapy. A total of 288 cow-level milk samples were collected aseptically and used in this study. Results: Conventional culture showed a predominance of coagulase-negative staphylococci, followed by coagulasepositive staphylococci, Streptococcus spp., Enterococcus spp., E. coli, and Klebsiella spp. PCR results showed a high prevalence of mycoplasmas (76.7%), including A. laidlawii (10.8%), M. bovis (6.2%), M. bovirhinis (5.6%), M. arginini (2%), and (52.1%) of cows were co-infected with two or more Mycoplasma and Acholeplasma species. Mycoplasma co-infection significantly increased somatic cell counts (SCC) similar to conventional mastitis pathogens and compared to non-infected cows with 389.3, 550.3 and 67.3 respectively; and decreased the milk yield with 29.0, 29.9 and 34.4 l, respectively. Mycoplasma co-infection caused significant increase in protein percentage, and significant decrease in fat percentage and total milk solids, similar to other conventional mastitis pathogens. In contrast, changes in milk composition and yield caused by various individual Mycoplasma species were non-significant. Conclusions: Mycoplasma mastitis had on-farm economic consequences similar to common conventional mastitis pathogens. Results of our study indicate that co-infection Mycoplasma mastitis caused similar effect on milk composition to other mastitis pathogens and we hope these findings raise the awareness of the importance of their detection on routine diagnostic panels.e [ABSTRACT FROM AUTHOR]

This paper was originally presented at the British Psychological Society's Transpersonal Psychology Section's 19th annual conference - 'Psychedelics, Psychology and Spirituality'. It was my intention, in the best spirit of academic debate and inquiry, to offer some critical perspectives and considerations related to the use of psychedelics in relation to the origins and development of Transpersonal Psychology. To this end I reflected on the work and lives of some influential counter-culture figures including Albert Hofmann, Abraham Maslow, Ram Dass and others - each of whom raised particular concerns and doubts in relation to the potential risks associated with psychedelics, which I will argue still resonate today. Where appropriate I have also included some of the varied positions one might encounter in relation to spiritual traditions and psychedelics (specifically Buddhism, Judaism, Daoism and Hinduism). [ABSTRACT FROM AUTHOR]