Diazotroph Activity in Surface Narragansett Bay Sediments in Summer is Stimulated by Hypoxia and Organic Matter Delivery

Bacteria that carry out many processes of the nitrogen cycle inhabit estuarine sediments. Denitrification is known to be a dominant process causing estuarine sediments to behave as net nitrogen sinks. However, measurements of nitrogen fluxes in the sediments of Narragansett Bay, Rhode Island, USA, have at times revealed high rates of net nitrogen (N2) fixation. Whereas changes in primary production, in magnitude and phenology, within Narragansett Bay have been identified as possible causes for these changes in nitrogen cycling within the benthos, a factor that has not been examined thus far is seasonal hypoxia. Since anaerobic diazotrophs figure so prominently within the sediments of Narragansett Bay, we hypothesized that dissolved oxygen concentrations in the bottom waters affect their activity. In order to explore this relationship, we measured the activity of diazotrophs in the surface sediments of 3 study areas during the summers of 2013 and 2014 using the acetylene reduction assay. We explored the effects of several water quality parameters on nitrogenase activity including, among others, dissolved oxygen and chlorophyll concentrations. Our measurements of nitrogenase activity were generally low, ranging between 2 and 5 nmol ethylene g-1 d-1 but spiked to 16 nmol ethylene g-1 d-1 at an area experiencing severe hypoxia in July 2013. Our data suggest that diazotrophy in estuarine sediments is enhanced when the benthos experiences very low dissolved oxygen in conjunction with recent influxes of autochthonous organic matter. Experiments with sediment core incubations conducted in the laboratory support our hypothesis that low dissolved oxygen and organic matter additions promote N2 fixation

Early Diffusion of SARS-CoV-2 Infection in the Inner Area of the Italian Sardinia Island

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the coronavirus disease 2019 (COVID-19) pandemic, which started as a severe pneumonia outbreak in Wuhan, China, in December 2019. Italy has been the first European country affected by the pandemic, registering a total of 300,363 cases and 35,741 deaths until September 24, 2020. The geographical distribution of SARS-CoV-2 in Italy during early 2020 has not been homogeneous, including regions severely affected as well as administrative areas being only slightly interested by the infection. Among the latter, Sardinia represents one of the lowest incidence areas likely due to its insular nature. Methods: Next-generation sequencing of a small number of complete viral genomes from clinical samples and their virologic and phylogenetic characterization was performed. Results: We provide a first overview of the SARS-CoV-2 genomic diversity in Sardinia in the early phase of the March–May 2020 pandemic based on viral genomes isolated in the most inner regional hospital of the island. Our analysis revealed a remarkable genetic diversity in local SARS-CoV-2 viral genomes, showing the presence of at least four different clusters that can be distinguished by specific amino acid substitutions. Based on epidemiological information, these sequences can be linked to at least eight different clusters of infection, four of which likely originates from imported cases. In addition, the presence of amino acid substitutions that were not previously reported in Italian patients has been observed, asking for further investigations in a wider population to assess their prevalence and dynamics of emergence during the pandemic. Conclusion: The present study provides a snapshot of the initial phases of the SARS-CoV-2 infection in inner area of the Sardinia Island, showing an unexpected genomic diversity

Painful swollen leg – think beyond deep vein thrombosis or Baker's cyst

<p>Abstract</p> <p>Background</p> <p>The diagnosis of deep vein thrombosis of leg is very common in clinical practice. Not infrequently a range of pathologies are diagnosed after excluding a thrombosis, often after a period of anticoagulation.</p> <p>Case presentation</p> <p>This is a report of three patients who presented with a painful swollen leg and were initially treated as a deep vein thrombosis or a baker's cyst, but later diagnosed as a pleomorphic sarcoma, a malignant giant cell tumor of the muscle and a myxoid liposarcoma. A brief review of such similar reports and the relevant literature is presented.</p> <p>Conclusion</p> <p>A painful swollen leg is a common clinical scenario and though rare, tumors must be thought of without any delay, in a duplex negative, low risk deep vein thrombosis situation.</p

The Fungal Exopolysaccharide Galactosaminogalactan Mediates Virulence by Enhancing Resistance to Neutrophil Extracellular Traps

Of the over 250 Aspergillus species, Aspergillus fumigatus accounts for up to 80% of invasive human infections. A. fumigatus produces galactosaminogalactan (GAG), an exopolysaccharide composed of galactose and N-acetyl-galactosamine (GalNAc) that mediates adherence and is required for full virulence. Less pathogenic Aspergillus species were found to produce GAG with a lower GalNAc content than A. fumigatus and expressed minimal amounts of cell wall-bound GAG. Increasing the GalNAc content of GAG of the minimally pathogenic A. nidulans, either through overexpression of the A. nidulans epimerase UgeB or by heterologous expression of the A. fumigatus epimerase Uge3 increased the amount of cell wall bound GAG, augmented adherence in vitro and enhanced virulence in corticosteroid-treated mice to levels similar to A. fumigatus. The enhanced virulence of the overexpression strain of A. nidulans was associated with increased resistance to NADPH oxidase-dependent neutrophil extracellular traps (NETs) in vitro, and was not observed in neutropenic mice or mice deficient in NADPH-oxidase that are unable to form NETs. Collectively, these data suggest that cell wall-bound GAG enhances virulence through mediating resistance to NETs

A Powerful Paradigm for Cardiovascular Risk Stratification Using Multiclass, Multi-Label, and Ensemble-Based Machine Learning Paradigms: A Narrative Review

Background and Motivation: Cardiovascular disease (CVD) causes the highest mortality globally. With escalating healthcare costs, early non-invasive CVD risk assessment is vital. Conventional methods have shown poor performance compared to more recent and fast-evolving Artificial Intelligence (AI) methods. The proposed study reviews the three most recent paradigms for CVD risk assessment, namely multiclass, multi-label, and ensemble-based methods in (i) office-based and (ii) stress-test laboratories. Methods: A total of 265 CVD-based studies were selected using the preferred reporting items for systematic reviews and meta-analyses (PRISMA) model. Due to its popularity and recent development, the study analyzed the above three paradigms using machine learning (ML) frameworks. We review comprehensively these three methods using attributes, such as architecture, applications, pro-and-cons, scientific validation, clinical evaluation, and AI risk-of-bias (RoB) in the CVD framework. These ML techniques were then extended under mobile and cloud-based infrastructure. Findings: Most popular biomarkers used were office-based, laboratory-based, image-based phenotypes, and medication usage. Surrogate carotid scanning for coronary artery risk prediction had shown promising results. Ground truth (GT) selection for AI-based training along with scientific and clinical validation is very important for CVD stratification to avoid RoB. It was observed that the most popular classification paradigm is multiclass followed by the ensemble, and multi-label. The use of deep learning techniques in CVD risk stratification is in a very early stage of development. Mobile and cloud-based AI technologies are more likely to be the future. Conclusions: AI-based methods for CVD risk assessment are most promising and successful. Choice of GT is most vital in AI-based models to prevent the RoB. The amalgamation of image-based strategies with conventional risk factors provides the highest stability when using the three CVD paradigms in non-cloud and cloud-based frameworks

User fees in private non-for-profit hospitals in Uganda: a survey and intervention for equity

BACKGROUND: In developing countries, user fees may represent an important source of revenues for private-non-for-profit hospitals, but they may also affect access, use and equity. METHODS: This survey was conducted in ten hospitals of the Uganda Catholic Medical Bureau to assess differences in user fees policies and to propose changes that would better fit with the social concern explicitly pursued by the Bureau. Through a review of relevant hospital documents and reports, and through interviews with key informants, health workers and users, hospital and non-hospital cost was calculated, as well as overall expenditure and revenues. Lower fees were applied in some pilot hospitals after the survey. RESULTS: The percentage of revenues from user fees varied between 6% and 89% (average 40%). Some hospitals were more successful than others in getting external aid and government subsidies. These hospitals were applying lower fees and flat rates, and were offering free essential services to encourage access, as opposed to the fee-for-service policies implemented in less successful hospitals. The wide variation in user fees among hospitals was not justified by differences in case mix. None of the hospitals had a policy for exemption of the poor; the few users that actually got exempted were not really poor. To pay hospital and non-hospital expenses, about one third of users had to borrow money or sell goods and property. The fee system applied after the survey, based on flat and lower rates, brought about an increase in access and use of hospital services. CONCLUSION: Our results confirm that user fees represent an unfair mechanism of financing for health services because they exclude the poor and the sick. To mitigate this effect, flat rates and lower fees for the most vulnerable users were introduced to replace the fee-for-service system in some hospitals after the survey. The results are encouraging: hospital use, especially for pregnancy, childbirth and childhood illness, increased immediately, with no detrimental effect on overall revenues. A more equitable user fees system is possible

Allosteric “beta-blocker” isolated from a DNA-encoded small molecule library

The present study reports the discovery of a small-molecule negative allosteric modulator for the β2-adrenergic receptor (β2AR) via in vitro affinity-based iterative selection of highly diverse DNA-encoded small-molecule libraries. Characterization of the compound demonstrates its selectivity for the β2AR and that it negatively modulates a wide range of receptor functions. More importantly, our findings establish a generally applicable, proof-of-concept strategy for screening DNA-encoded small-molecule libraries against purified G-protein–coupled receptors (GPCRs), which holds great potential for discovering therapeutic molecules

Nutrition, atherosclerosis, arterial imaging, cardiovascular risk stratification, and manifestations in COVID-19 framework: a narrative review.

Background: Atherosclerosis is the primary cause of the cardiovascular disease (CVD). Several risk factors lead to atherosclerosis, and altered nutrition is one among those. Nutrition has been ignored quite often in the process of CVD risk assessment. Altered nutrition along with carotid ultrasound imaging-driven atherosclerotic plaque features can help in understanding and banishing the problems associated with the late diagnosis of CVD. Artificial intelligence (AI) is another promisingly adopted technology for CVD risk assessment and management. Therefore, we hypothesize that the risk of atherosclerotic CVD can be accurately monitored using carotid ultrasound imaging, predicted using AI-based algorithms, and reduced with the help of proper nutrition. Layout: The review presents a pathophysiological link between nutrition and atherosclerosis by gaining a deep insight into the processes involved at each stage of plaque development. After targeting the causes and finding out results by low-cost, user-friendly, ultrasound-based arterial imaging, it is important to (i) stratify the risks and (ii) monitor them by measuring plaque burden and computing risk score as part of the preventive framework. Artificial intelligence (AI)-based strategies are used to provide efficient CVD risk assessments. Finally, the review presents the role of AI for CVD risk assessment during COVID-19. Conclusions: By studying the mechanism of low-density lipoprotein formation, saturated and trans fat, and other dietary components that lead to plaque formation, we demonstrate the use of CVD risk assessment due to nutrition and atherosclerosis disease formation during normal and COVID times. Further, nutrition if included, as a part of the associated risk factors can benefit from atherosclerotic disease progression and its management using AI-based CVD risk assessment

Early Planet Formation in Embedded Disks (eDisk) III: A first high-resolution view of sub-mm continuum and molecular line emission toward the Class 0 protostar L1527 IRS

Studying the physical and chemical conditions of young embedded disks is crucial to constrain the initial conditions for planet formation. Here, we present Atacama Large Millimeter/submillimeter Array (ALMA) observations of dust continuum at $\sim$0.06" (8 au) resolution and molecular line emission at $\sim$0.17" (24 au) resolution toward the Class 0 protostar L1527 IRS from the Large Program eDisk (Early Planet Formation in Embedded Disks). The continuum emission is smooth without substructures, but asymmetric along both the major and minor axes of the disk as previously observed. The detected lines of $^{12}$CO, $^{13}$CO, C$^{18}$O, H$_2$CO, c-C$_3$H$_2$, SO, SiO, and DCN trace different components of the protostellar system, with a disk wind potentially visible in $^{12}$CO. The $^{13}$CO brightness temperature and the H$_2$CO line ratio confirm that the disk is too warm for CO freeze out, with the snowline located at $\sim$350 au in the envelope. Both molecules show potential evidence of a temperature increase around the disk-envelope interface. SO seems to originate predominantly in UV-irradiated regions such as the disk surface and the outflow cavity walls rather than at the disk-envelope interface as previously suggested. Finally, the continuum asymmetry along the minor axis is consistent with the inclination derived from the large-scale (100" or 14,000 au) outflow, but opposite to that based on the molecular jet and envelope emission, suggesting a misalignment in the system. Overall, these results highlight the importance of observing multiple molecular species in multiple transitions to characterize the physical and chemical environment of young disks.Comment: 27 pages, 16 figures, 2 tables, 10 pages appendix with 12 figures. Accepted for publication in ApJ as one of the first-look papers of the eDisk ALMA Large Progra