Serum metabolome profiling in patients with mild cognitive impairment reveals sex differences in lipid metabolism.

Alzheimer's disease (AD) affects more women than men. Although women live longer than men, it is not longevity alone, but other factors, including metabolic changes, that contribute to the higher risk of AD in women. Metabolic pathways have been implicated in AD progression, but studies to date examined targeted pathways, leaving many metabolites unmeasured.

The Contribution of Neutrophil Extracellular Traps to Coagulopathy in Patients with COVID-19-Related Thrombosis.

COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is associated with hypercoagulability and increased incidence of thrombotic events. In this study, we investigated the levels of neutrophil extracellular trap biomarkers and von Willebrand factor to assess if these could predict the occurrence of a thrombotic event in COVID-19 patients. We enrolled 202 patients hospitalized with symptomatic COVID-19 infection.

Alphavirus nsP3 organizes into tubular scaffolds essential for infection and the cytoplasmic granule architecture.

Alphaviruses, such as chikungunya virus (CHIKV), are mosquito-borne viruses that represent a significant threat to human health due to the current context of global warming. Efficient alphavirus infection relies on the activity of the non-structural protein 3 (nsP3), a puzzling multifunctional molecule whose role in infection remains largely unknown. NsP3 is a component of the plasma membrane-bound viral RNA replication complex (vRC) essential for RNA amplification and is also found in large cytoplasmic aggregates of unknown function Here, we report the cryo-electron microscopy (cryo-EM) structure of the CHIKV nsP3 at 2.

Genome-Wide CRISPR-Cas9 Screening for the Identification of Host Dependency Factors of Emerging Viruses.

Like all the RNA viruses, Rift Valley fever virus (RVFV) encodes only few viral proteins and relies heavily on the host cellular machinery for productive infection. This dependence creates a potential "Achille's heel" that may be exploited to develop new approaches to treat RVFV infection. The recent development of lentiviral sgRNAs pool has enabled the creation of genome-scale CRISPR-Cas9 knockout libraries that has been used to identify host factors required for virus replication.

Seeking American Society of Clinical Oncology-Quality Oncology Practice Initiative (ASCO-QOPI) certification in a northern New England rural health system and cancer care network.

In 2006 following several years of preliminary study, the American Society of Clinical Oncology (ASCO) launched the Quality Oncology Practice Initiative (QOPI). This cancer-focused quality initiative evolved considerably over the next decade-and-a-half and is expanding globally. QOPI is undoubtedly the leading standard-bearer for quality cancer care and contemporary medical oncology practice.

Lactobacilli decrease the susceptibility of Typhimurium to azithromycin.

Bacteria are involved in numerous interactions during infection and among host-associated microbial populations. serovar Typhimurium is a foodborne pathogen of great importance as well as a model organism to study interactions within a microbial community. In this study, we found that .

Multidisciplinary Approach to Management of Hypertrophic Cardiomyopathy With Severe Left Ventricular Outflow Obstruction in Pregnancy.

Pregnancy can worsen symptoms of hypertrophic cardiomyopathy and increase the risk of complications. Severe left ventricular outflow tract obstruction with gradient >100 mm Hg poses a high risk of deterioration during pregnancy. We present a patient with hypertrophic obstructive cardiomyopathy in the third trimester of pregnancy with a left ventricular outflow tract gradient >100 mm Hg and discuss successful interdisciplinary management.

Restoring a balanced pool of host-derived and microbiota-derived ligands of the aryl hydrocarbon receptor is beneficial after stroke.

Background: Stroke is a major cause of morbidity and mortality, and its incidence increases with age. While acute therapies for stroke are currently limited to intravenous thrombolytics and endovascular thrombectomy, recent studies have implicated an important role for the gut microbiome in post-stroke neuroinflammation. After stroke, several immuno-regulatory pathways, including the aryl hydrocarbon receptor (AHR) pathway, become activated.

The Information Sharing Behaviors of Dietitians and Twitter Users in the Nutrition and COVID-19 Infodemic: Content Analysis Study of Tweets.

Background: The COVID-19 pandemic has generated an infodemic, an overabundance of online and offline information. In this context, accurate information as well as misinformation and disinformation about the links between nutrition and COVID-19 have circulated on Twitter since the onset of the pandemic.

Objective: The purpose of this study was to compare tweets on nutrition in times of COVID-19 published by 2 groups, namely, a preidentified group of dietitians and a group of general users of Twitter, in terms of themes, content accuracy, use of behavior change factors, and user engagement, in order to contrast their information sharing behaviors during the pandemic.

Sex differences in global metabolomic profiles of COVID-19 patients.

Coronavirus disease (COVID-19), caused by SARS-CoV-2, leads to symptoms ranging from asymptomatic disease to death. Although males are more susceptible to severe symptoms and higher mortality due to COVID-19, patient sex has rarely been examined. Sex-associated metabolic changes may implicate novel biomarkers and therapeutic targets to treat COVID-19.

RACK1 Associates with RNA-Binding Proteins Vigilin and SERBP1 to Facilitate Dengue Virus Replication.

Dengue virus (DENV) is a mosquito-borne flavivirus responsible for dengue disease, a major human health concern for which no effective treatment is available. DENV relies heavily on the host cellular machinery for productive infection. Here, we show that the scaffold protein RACK1, which is part of the DENV replication complex, mediates infection by binding to the 40S ribosomal subunit.

Perceptions on barriers, facilitators, and recommendations related to mental health service delivery during the COVID-19 pandemic in Quebec, Canada: a qualitative descriptive study.

Background: There was an increase in self-reported mental health needs during the COVID-19 pandemic in Canada, with research showing reduced access to mental health services in comparison to pre-pandemic levels. This paper explores 1) barriers and facilitating factors associated with mental health service delivery via primary care settings during the first two pandemic waves in Quebec, Canada, and 2) recommendations to addressing these barriers.

Methods: A qualitative descriptive study design was used.

MR Imaging Differences in the Circle of Willis between Healthy Children and Adults.

Background And Purpose: Asymmetries in the circle of Willis have been associated with several conditions, including migraines and stroke, but they may also be age-dependent. This study examined the impact of age and age-dependent changes in cerebral perfusion on circle of Willis anatomy in healthy children and adults.

Materials And Methods: We performed an observational, cross-sectional study of bright and black-blood imaging of the proximal cerebral vasculature using TOF-MRA and T2 sampling perfection with application-optimized contrasts by using different flip angle evolution (T2-SPACE) imaging at the level of the circle of Willis in 23 healthy children and 43 healthy adults (4-74 years of age).

Spatiotemporal relationship between subthreshold amyloid accumulation and aerobic glycolysis in the human brain.

In Alzheimer's disease, brain amyloid deposition has a distinct topography that correlates with aerobic glycolysis (AG), that is, the use of glucose beyond that predicted by oxygen consumption. The causes for this relationship remain unclear but might provide crucialinsight into how amyloid deposition begins. Here we develop methods to study the earliest topography of amyloid deposition based on amyloid imaging and investigate its spatiotemporal evolution with respect to the topography of AG in adults.

Phosphorus Consumption Within 1 Hour Prior to Blood Work and Associated Serum Levels of Phosphate, Calcium, and PTH in Adult Patients Receiving Hemodialysis Treatment.

Background: While dietary intake is known to influence serum markers of chronic kidney disease-mineral and bone disorder (CKD-MBD), the effects of recent food and beverage intake, particularly phosphorus consumption on these serum markers (phosphate, calcium, and parathyroid hormone [PTH]), are unknown in hemodialysis patients. An understanding of these effects could have direct and important implications on the management of CKD-MBD.

Objective: To determine whether serum phosphate, calcium, and PTH levels were higher in hemodialysis patients who had consumed dietary phosphorus within 1 hour prior to their routine dialysis-related blood work (non-phosphorus-fasted) compared with patients who did not (phosphorus-fasted).

The Heart and Kidney: Abnormal Phosphate Homeostasis Is Associated With Atherosclerosis.

Context: Phosphate has gained recognition as a risk factor for adverse cardiovascular outcomes, potentially due to accelerated vascular calcification. Fibroblast growth factor-23 (FGF-23) is a counter-regulatory hormone that increases renal phosphate excretion to maintain normal levels.

Objective: The purpose of the study was to determine the association of phosphate and FGF-23 to atherosclerosis.

Circulating Gas6 is associated with reduced human carotid atherosclerotic plaque burden in high risk cardiac patients.

Objective: Pre-clinical studies suggest that growth arrest-specific protein 6 (Gas6), a member of the vitamin K dependent family of proteins, is implicated in atherosclerosis. A role for Gas6 in stabilizing atherosclerotic plaque has been suggested. Our aim was to determine the association between Gas6 and measures of carotid artery atherosclerosis in humans undergoing elective coronary angiography.

Human embryonic stem cell-derived cardiomyocytes restore function in infarcted hearts of non-human primates.

Pluripotent stem cell-derived cardiomyocyte grafts can remuscularize substantial amounts of infarcted myocardium and beat in synchrony with the heart, but in some settings cause ventricular arrhythmias. It is unknown whether human cardiomyocytes can restore cardiac function in a physiologically relevant large animal model. Here we show that transplantation of ∼750 million cryopreserved human embryonic stem cell-derived cardiomyocytes (hESC-CMs) enhances cardiac function in macaque monkeys with large myocardial infarctions.

Aerobic glycolysis and tau deposition in preclinical Alzheimer's disease.

Research of the human brain metabolism in vivo has largely focused on total glucose use (via fluorodeoxyglucose positron emission tomography) and, until recently, did not examine the use of glucose outside oxidative phosphorylation, which is known as aerobic glycolysis (AG). AG supports important functions including biosynthesis and neuroprotection but decreases dramatically with aging. This multitracer positron emission tomography study evaluated the relationship between AG, total glucose use (CMRGlc), oxygen metabolism (CMRO), tau, and amyloid deposition in 42 individuals, including those at preclinical and symptomatic stages of Alzheimer's disease.

Passive Stretch Induces Structural and Functional Maturation of Engineered Heart Muscle as Predicted by Computational Modeling.

The ability to differentiate human pluripotent stem cells (hPSCs) into cardiomyocytes (CMs) makes them an attractive source for repairing injured myocardium, disease modeling, and drug testing. Although current differentiation protocols yield hPSC-CMs to >90% efficiency, hPSC-CMs exhibit immature characteristics. With the goal of overcoming this limitation, we tested the effects of varying passive stretch on engineered heart muscle (EHM) structural and functional maturation, guided by computational modeling.

Defined Engineered Human Myocardium With Advanced Maturation for Applications in Heart Failure Modeling and Repair.

Background: Advancing structural and functional maturation of stem cell-derived cardiomyocytes remains a key challenge for applications in disease modeling, drug screening, and heart repair. Here, we sought to advance cardiomyocyte maturation in engineered human myocardium (EHM) toward an adult phenotype under defined conditions.

Methods: We systematically investigated cell composition, matrix, and media conditions to generate EHM from embryonic and induced pluripotent stem cell-derived cardiomyocytes and fibroblasts with organotypic functionality under serum-free conditions.