Patient and immunological factors associated with delayed clearance of mucosal SARS-CoV-2 RNA and symptom persistence.

Serial blood and mucosal samples were characterized for 102 participants enrolled a median of 7.0 days post-COVID-19 diagnosis. Mucosal RNA was detectable a median 31.5 (95% CI 20.5 - 63.5) days, with persistence ≥1 month associated with obesity (BMI ≥30, OR 3.9, 95% CI 1.2 - 13.8) but not age, sex, or chronic conditions. Fifteen participants had likely reinfection; lower serum anti-S IgG levels were associated with reinfection risk. Nearly half of participants (47%) reported symptoms lasting ≥2-3 months; persistence ≥3 months was associated with BMI ≥30 (OR = 4.2 95% CI 1.1 - 12.8) and peak anti-S and anti-NC antibody levels.

Vaccine Effectiveness Against SARS-CoV-2 Related Hospitalizations in People who had Experienced Homelessness or Incarceration - Findings from the Minnesota EHR Consortium.

COVID-19 disproportionately affects people experiencing homelessness or incarceration. While homelessness or incarceration alone may not impact vaccine effectiveness, medical comorbidities along with social conditions associated with homelessness or incarceration may impact estimated vaccine effectiveness. COVID-19 vaccines reduce rates of hospitalization and death; vaccine effectiveness (VE) against severe outcomes in people experiencing homelessness or incarceration is unknown. We conducted a retrospective, observational cohort study evaluating COVID-19 vaccine VE against SARS-CoV-2 related hospitalization (positive SARS-CoV-2 molecular test same week or within 3 weeks prior to hospital admission) among patients who had experienced homelessness or incarceration. We utilized data from 8 health systems in the Minnesota Electronic Health Record Consortium linked to data from Minnesota's immunization information system, Homeless Management Information System, and Department of Corrections. We included patients 18 years and older with a history of experiencing homelessness or incarceration. VE and 95% Confidence Intervals (CI) against SARS-CoV-2 hospitalization were estimated for primary series and one booster dose from Cox proportional hazard models as 100*(1-Hazard Ratio) during August 26, 2021, through October 8, 2022 adjusting for patient age, sex, comorbid medical conditions, and race/ethnicity. We included 80,051 individuals who had experienced homelessness or incarceration. Adjusted VE was 52% (95% CI, 41-60%) among those 22 weeks or more since their primary series, 66% (95% CI, 53-75%) among those less than 22 weeks since their primary series, and 69% (95% CI: 60-76%) among those with one booster. VE estimates were consistently lower during the Omicron predominance period compared with the combined Omicron and Delta periods. Despite higher exposure risk, COVID-19 vaccines provided good effectiveness against SARS-CoV-2 related hospitalizations in persons who have experienced homelessness or incarceration.

Number needed to vaccinate with a COVID-19 booster to prevent a COVID-19-associated hospitalization during SARS-CoV-2 Omicron BA.1 variant predominance, December 2021-February 2022, VISION Network: a retrospective cohort study.

Background: Understanding the usefulness of additional COVID-19 vaccine doses-particularly given varying disease incidence-is needed to support public health policy. We characterize the benefits of COVID-19 booster doses using number needed to vaccinate (NNV) to prevent one COVID-19-associated hospitalization or emergency department encounter. Methods: We conducted a retrospective cohort study of immunocompetent adults at five health systems in four U.S. states during SARS-CoV-2 Omicron BA.1 predominance (December 2021-February 2022). Included patients completed a primary mRNA COVID-19 vaccine series and were either eligible to or received a booster dose. NNV were estimated using hazard ratios for each outcome (hospitalization and emergency department encounters), with results stratified by three 25-day periods and site. Findings: 1,285,032 patients contributed 938 hospitalizations and 2076 emergency department encounters. 555,729 (43.2%) patients were aged 18-49 years, 363,299 (28.3%) 50-64 years, and 366,004 (28.5%) ≥65 years. Most patients were female (n = 765,728, 59.6%), White (n = 990,224, 77.1%), and non-Hispanic (n = 1,063,964, 82.8%). 37.2% of patients received a booster and 62.8% received only two doses. Median estimated NNV to prevent one hospitalization was 205 (range 44-615) and NNV was lower across study periods for adults aged ≥65 years (110, 46, and 88, respectively) and those with underlying medical conditions (163, 69, and 131, respectively). Median estimated NNV to prevent one emergency department encounter was 156 (range 75-592). Interpretation: The number of patients needed to receive a booster dose was highly dependent on local disease incidence, outcome severity, and patient risk factors for moderate-to-severe disease. Funding: Funding was provided by the Centers for Disease Control and Prevention though contract 75D30120C07986 to Westat, Inc. and contract 75D30120C07765 to Kaiser Foundation Hospitals.

Welcome to the lab.

Having a formal onboarding procedure for new lab members can lead to a happier and more productive working environment.

Glial Cells Promote Myelin Formation and Elimination.

Building a functional nervous system requires the coordinated actions of many glial cells. In the vertebrate central nervous system (CNS), oligodendrocytes myelinate neuronal axons to increase conduction velocity and provide trophic support. Myelination can be modified by local signaling at the axon-myelin interface, potentially adapting sheaths to support the metabolic needs and physiology of individual neurons. However, neurons and oligodendrocytes are not wholly responsible for crafting the myelination patterns seen in vivo. Other cell types of the CNS, including microglia and astrocytes, modify myelination. In this review, I cover the contributions of non-neuronal, non-oligodendroglial cells to the formation, maintenance, and pruning of myelin sheaths. I address ways that these cell types interact with the oligodendrocyte lineage throughout development to modify myelination. Additionally, I discuss mechanisms by which these cells may indirectly tune myelination by regulating neuronal activity. Understanding how glial-glial interactions regulate myelination is essential for understanding how the brain functions as a whole and for developing strategies to repair myelin in disease.

Microglia phagocytose myelin sheaths to modify developmental myelination.

During development, oligodendrocytes contact and wrap neuronal axons with myelin. Similarly to neurons and synapses, excess myelin sheaths are produced and selectively eliminated, but how elimination occurs is unknown. Microglia, the resident immune cells of the central nervous system, engulf surplus neurons and synapses. To determine whether microglia also prune myelin sheaths, we used zebrafish to visualize and manipulate interactions between microglia, oligodendrocytes, and neurons during development. We found that microglia closely associate with oligodendrocytes and specifically phagocytose myelin sheaths. By using a combination of optical, genetic, chemogenetic, and behavioral approaches, we reveal that neuronal activity bidirectionally balances microglial association with neuronal cell bodies and myelin phagocytosis in the optic tectum. Furthermore, multiple strategies to deplete microglia resulted in oligodendrocytes maintaining excessive and ectopic myelin. Our work reveals a neuronal activity-regulated role for microglia in modifying developmental myelin targeting by oligodendrocytes.

Oligodendrocytes express synaptic proteins that modulate myelin sheath formation.

Vesicular release from neurons promotes myelin sheath growth on axons. Oligodendrocytes express proteins that allow dendrites to respond to vesicular release at synapses, suggesting that axon-myelin contacts use similar communication mechanisms as synapses to form myelin sheaths. To test this, we used fusion proteins to track synaptic vesicle localization and membrane fusion in zebrafish during developmental myelination and investigated expression and localization of PSD95, a dendritic post-synaptic protein, within oligodendrocytes. Synaptic vesicles accumulate and exocytose at ensheathment sites with variable patterning and most sheaths localize PSD95 with patterning similar to exocytosis site location. Disruption of candidate PDZ-binding transsynaptic adhesion proteins in oligodendrocytes cause variable effects on sheath length and number. One candidate, Cadm1b, localizes to myelin sheaths where both PDZ binding and extracellular adhesion to axons mediate sheath growth. Our work raises the possibility that axon-glial communication contributes to myelin plasticity, providing new targets for mechanistic unraveling of developmental myelination.

Endoplasmic Reticulum Stress and Unfolded Protein Response in Cartilage Pathophysiology; Contributing Factors to Apoptosis and Osteoarthritis.

Chondrocytes of the growth plate undergo apoptosis during the process of endochondral ossification, as well as during the progression of osteoarthritis. Although the regulation of this process is not completely understood, alterations in the precisely orchestrated programmed cell death during development can have catastrophic results, as exemplified by several chondrodystrophies which are frequently accompanied by early onset osteoarthritis. Understanding the mechanisms that underlie chondrocyte apoptosis during endochondral ossification in the growth plate has the potential to impact the development of therapeutic applications for chondrodystrophies and associated early onset osteoarthritis. In recent years, several chondrodysplasias and collagenopathies have been recognized as protein-folding diseases that lead to endoplasmic reticulum stress, endoplasmic reticulum associated degradation, and the unfolded protein response. Under conditions of prolonged endoplasmic reticulum stress in which the protein folding load outweighs the folding capacity of the endoplasmic reticulum, cellular dysfunction and death often occur. However, unfolded protein response (UPR) signaling is also required for the normal maturation of chondrocytes and osteoblasts. Understanding how UPR signaling may contribute to cartilage pathophysiology is an essential step toward therapeutic modulation of skeletal disorders that lead to osteoarthritis.

The use of Theory in Family Therapy Research: Content Analysis and Update.

In this study, we evaluated 275 empirical studies from Journal of Marital and Family Therapy and Family Process from 2010 to 2015 on their use of theory, and compared our findings to those of a similar previous analysis (Hawley & Geske, 2000). Overall, theory seems to have become much better incorporated in empirical family therapy research, with only 16.4% of the articles not using theory in either their introductory or discussion sections. Theory appeared better incorporated in the introductory sections than in the discussion sections. Systems theory remained the most commonly used conceptual framework, followed by attachment theory. We discuss areas for improving theory incorporation in family therapy research, and offer suggestions for both family therapy researchers and educators.

A lipid-rich gestational diet predisposes offspring to nonalcoholic fatty liver disease: a potential sequence of events.

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%-30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered ß-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review suggests a mechanism that integrates outcomes reported by a variety of studies conducted in an analysis of fetal hepatic metabolic capacity amid the maternal consumption of a high-fat diet. Potential preventive measures and therapies for use both as part of prenatal nutrition and for those at risk for the development of NAFLD are also discussed.