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The diagnosis of pediatric pneumonia and determination of the likely pathogen are complicated as the clinical picture overlaps with other respiratory illnesses, interpretation of radiographs is subjective, and laboratory results are rarely diagnostic. This study was designed to describe the relative rates of bacterial and viral pneumonia in the pediatric Emergency Department (ED), determine the accuracy of pediatric ED physicians' ability to diagnose pneumonia and distinguish bacterial from viral etiology, and to determine clinical and laboratory predictors of bacterial pneumonia. Children 3 months to 16 years of age presenting to seven Canadian pediatric EDs before the COVID-19 pandemic with fever and cough who had a chest radiograph performed for possible pneumonia were enrolled and underwent standardized clinical investigations. An expert panel was convened and reached a Consensus Diagnosis of typical or atypical bacterial pneumonia, viral pneumonia or not pneumonia for each case. The expert panel assessed 247 cases with the Consensus Diagnosis being typical bacterial pneumonia (N = 44(18%)), atypical bacterial pneumonia (N = 18(7%)), viral pneumonia (N = 46(19%)) and no pneumonia (N = 139(56%)). Treating ED physician diagnoses were typical bacterial pneumonia (N = 126(51%)), atypical bacterial pneumonia (N = 3(1%)), viral pneumonia (N = 10(4%)) and no pneumonia (N = 108(44%)) with low agreement between a diagnosis of bacterial pneumonia by the ED physician and the panel's Consensus Diagnosis (Kappa 0.15 (95% CI 0.08, 0.21)). Cut off values that predicted bacterial pneumonia as the Consensus Diagnosis were ESR ≥ 47 mm/hour, CRP ≥ 42 mg/L and procalcitonin ≥0.85 ng/m. Age greater than 5 years and cough for 5 or more days also predict bacterial pneumonia. In this cohort, pediatric ED physicians over-diagnosed typical bacterial pneumonia and underdiagnosed viral and atypical bacterial pneumonia. Bacterial pneumonia is most likely in children over 5 years of age, with cough for 5 or more days and/or with elevated inflammatory markers.

To measure the accuracy and reliability of a portable home oximetry monitor with an automated analysis for the diagnosis of obstructive sleep apnea (OSA) in children. Prospective cohort study. Alberta Lung Association Sleep Center, Alberta Children’s Hospital Sleep Clinic. Consecutive, otherwise healthy children, aged 4 to 18 years, presenting to the Pediatric Sleep Service at the Alberta Children’s Hospital for assessment of possible OSA. All subjects underwent 2 nights of monitoring in the home with an oximetry-based portable monitor with an automatic internal scoring algorithm. A third night of monitoring was done simultaneously with computerized laboratory polysomnography according to American Thoracic Society guidelines. Both test-retest reliability of the portable monitor-based desaturation index (DI) between 2 nights at home and between laboratory and home were high using the Bland and Altman analysis (mean agreement, 0.32 and 0.64; limits of agreement, − 8.00 to 8.64 and − 0.75 to 6.50, respectively). The polysomnographic apnea-hypopnea index (AHI) agreed poorly with the portable monitor DI (mean difference, 1.27; limits of agreement, − 12.02 to 15.02). The sensitivity and specificity of the monitor for the identification of moderate sleep apnea (polysomnography AHI > 5/h) were 67% and 60%, respectively. Portable monitoring based only on oximetry alone is not adequate for the identification of OSA in otherwise healthy children.

In children, the diagnosis of narcolepsy remains underrecognized despite reported cases in the literature. The potential delays in diagnosis are related to the frequent absence of one or more of the associated features of narcolepsy, compounded by differences in expression of symptoms in children. The significance of recognizing and treating this disease in children is to prevent potentially serious psychological and academic consequences.

The association between reduced myofilament force-generating capacity (F max ) and heart failure (HF) is clear, however the underlying molecular mechanisms are poorly understood. Here, we show impaired F max arises from reduced BAG3-mediated sarcomere turnover. Myofilament BAG3 expression decreases in human HF and positively correlates with F max . We confirm this relationship using BAG3 haploinsufficient mice, which display reduced F max and increased myofilament ubiquitination, suggesting impaired protein turnover. We show cardiac BAG3 operates via chaperone-assisted selective autophagy (CASA), conserved from skeletal muscle, and confirm sarcomeric CASA complex localization is BAG3/proteotoxic stress-dependent. Using mass spectrometry, we characterize the myofilament CASA interactome in the human heart and identify eight clients of BAG3-mediated turnover. To determine if increasing BAG3 expression in HF can restore sarcomere proteostasis/F max , HF mice were treated with rAAV9-BAG3. Gene therapy fully rescued F max and CASA protein turnover after four weeks. Our findings indicate BAG3-mediated sarcomere turnover is fundamental for myofilament functional maintenance. Decreased expression of BAG3 in the heart is associated with contractile dysfunction and heart failure. Here the authors show that this is due to decreased BAG3-dependent sarcomere protein turnover, which impairs mechanical function, and that sarcomere force-generating capacity is restored with BAG3 gene therapy.

The universally conserved α-oxoaldehydes glyoxal (GO) and methylglyoxal (MGO) are toxic metabolic byproducts whose accumulation can lead to cell death. In the absence of a known, natural inducer of the GO-specific response in prokaryotes, we exploited RNA-seq to define a GO response in the bacterial pathogen Pseudomonas aeruginosa . The highest upregulated operon consisted of the known glyoxalase ( gloA2 ) and an antibiotic monooxygenase (ABM) domain of unknown function - renamed here A ldehyde r esponsive q uorum-sensing I nhibitor (ArqI). The arqI-gloA2 operon is highly specific to GO induction and ArqI protein responds by migrating to the flagellar pole. An ArqI atomic structure revealed several unique features to the ABM family, including a ‘pinwheel’ hexamer harboring a GO-derived post-translational modification on a conserved arginine residue (Arg49). Induction of ArqI abrogates production of the Pseudomonas Quinolone Signal (PQS) quorum sensing molecule and was found to directly interact with PqsA; the first enzyme in the PQS biosynthesis pathway. Finally, we use a sepsis model of infection to reveal a survival requirement for arqI-gloA2 in blood-rich organs (heart, spleen, liver and lung). Here we define a global GO response in a pathogen, identify and characterize the first GO-specific operon and implicate its role in PQS production and host survival. In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa , suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

Given the limited availability of serological testing to date, the seroprevalence of SARS-CoV-2-specific antibodies in different populations has remained unclear. Here, we report very low SARS-CoV-2 seroprevalence in two San Francisco Bay Area populations. Seroreactivity was 0.26% in 387 hospitalized patients admitted for non-respiratory indications and 0.1% in 1,000 blood donors in early April 2020. We additionally describe the longitudinal dynamics of immunoglobulin-G (IgG), immunoglobulin-M (IgM), and in vitro neutralizing antibody titers in COVID-19 patients. The median time to seroconversion ranged from 10.3–11.0 days for these 3 assays. Neutralizing antibodies rose in tandem with immunoglobulin titers following symptom onset, and positive percent agreement between detection of IgG and neutralizing titers was >93%. These findings emphasize the importance of using highly accurate tests for surveillance studies in low-prevalence populations, and provide evidence that seroreactivity using SARS-CoV-2 anti-nucleocapsid protein IgG and anti-spike IgM assays are generally predictive of in vitro neutralizing capacity. Highly accurate antibody tests for SARS-CoV-2 are needed for surveillance in low-prevalence populations. Here, the authors find seroprevalence of less than 1% in two San Francisco Bay Area populations at the beginning of April, and that seroreactivity is generally predictive of in vitro neutralising activity.

Emerging evidence suggests social, health, environmental, and economic benefits of urban agriculture (UA). However, limited work has characterized the risks from metal contaminant exposures faced by urban growers and consumers of urban-grown produce. We aimed to answer community-driven questions about the safety of UA and the consumption of urban-grown produce by measuring concentrations of nine metals in the soil, irrigation water, and urban-grown produce across urban farms and gardens in Baltimore, Maryland. We measured concentrations of 6 nonessential [arsenic (As), barium (Ba), cadmium (Cd), chromium (Cr), lead (Pb), nickel (Ni)] and three essential [copper (Cu), manganese (Mn), zinc (Zn)] metals in soil, irrigation water, and 13 types of urban-grown produce collected from 104 UA sites. We compared measured concentrations to existing public health guidelines and analyzed relationships between urban soil and produce concentrations. In the absence of guidelines for metals in produce, we compared metals concentrations in urban-grown produce with those in produce purchased from farmers markets and grocery stores (both conventionally grown and U.S. Department of Agriculture-certified organic). Mean concentrations of all measured metals in irrigation water were below public health guidelines. Mean concentrations of nonessential metals in growing area soils were below public health guidelines for Ba, Cd, Pb, and Ni and at or below background for As and Cr. Though we observed a few statistically significant differences in concentrations between urban and nonurban produce items for some combinations, no consistent or discernable patterns emerged. Screening soils for heavy metals is a critical best practice for urban growers. Given limitations in existing public health guidelines for metals in soil, irrigation water, and produce, additional exposure assessment is necessary to quantify potential human health risks associated with exposure to nonessential metals when engaging in UA and consuming urban-grown produce. Conversely, the potential health benefits of consuming essential metals in urban-grown produce also merit further research. https://doi.org/10.1289/EHP9431.

Early initiation of combination antiretroviral therapy (cART), at higher CD4 cell counts, prevents disease progression and reduces sexual transmission of human immunodeficiency virus (HIV). We describe the temporal trends in CD4 cell counts at the start of cART in adults from low-income, lower-middle-income, upper-middle-income, and high-income countries (LICs, LMICs, UMICs, and HICs, respectively). We included HIV-infected individuals aged ≥16 years who started cART between 2002 and 2015 in a clinic participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) or the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE). Missing CD4 cell counts at the start of cART were estimated through multiple imputation. Weighted mixed-effect models were used to smooth trends in median CD4 cell counts. A total of 951855 adults from 16 LICs, 11 LMICs, 9 UMICs, and 19 HICs were included. Overall, the modeled median CD4 cell count at the start of cART increased from 2002 to 2015, from 78/µL (95% confidence interval, 58-104/µL) to 287/µL (250-328/µL) in LICs, from 99/µL (71-140/µL) to 234/µL (192-285/µL) in LMICs, from 71/µL (49-104/µL) to 311/µL (255-379/µL) in UMICs, and from 161/µL (143-181/µL) to 327/µL (286-372/µL) in HICs. In LICs, LMICs, and UMICs, the increase was more pronounced in women; in HICs, the opposite was observed. Median CD4 cell counts at the start of cART increased in all income groups, but generally remained below 350/μL in 2015. Substantial additional efforts and resources are required to achieve earlier diagnosis, linkage to care, and initiation of cART.

Multiple transitions across care settings can be disruptive for older adults with dementia and their care partners, and can lead to fragmented care with adverse outcomes. This scoping review was conducted to identify and classify care trajectories across multiple settings for people with dementia, and to understand the prevalence of multiple transitions and associated factors at the individual and organizational levels. Searches of three databases, limited to peer-reviewed studies published between 2007 and 2017, provided 33 articles for inclusion. We identified 26 distinct care trajectories. Common trajectories involved hospital readmission or discharge from hospital to long-term care. Factors associated with transitions were identified mainly at the level of demographic and medical characteristics. Findings suggest a need for investing in stronger community-based systems of care that may reduce transitions. Further research is recommended to address knowledge gaps about complex and longitudinal care trajectories and trajectories experienced by sub-populations of people living with dementia.