Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) comprises a group of heterogenous disorders characterized by childhood-onset chronic joint inflammation. It is the most common rheumatologic disease in the pediatric population and an important cause of chronic illness in children. Early recognition and treatment are vital to prevent sequelae of uncontrolled inflammation on the developing skeleton. JIA can have significant complications that general pediatricians should be aware of, especially uveitis, which can be insidious and asymptomatic in very young children, and macrophage activation syndrome, which can be life-threatening if not recognized and appropriately treated. Although advances have been made in the past few decades, the etiology of JIA remains incompletely understood. Efforts are underway to refine the classification of JIA. The currently accepted classification scheme identifies subsets of JIA that are important clinically in terms of prognosis and tailoring treatment approaches. However, it is limited in identifying homogenous groups of children with early childhood onset and antinuclear antibody positivity, which may have different pathogenic mechanisms that could be important in developing more targeted and effective treatment approaches in the future. Treatment strategies for JIA have changed significantly in recent years with the availability of multiple newer targeted therapies, often modeled after medications used in adult-onset forms of arthritis. These treatments, and likely many others to come, have markedly improved symptom control and reduced complications in patients with JIA.

Diversity of Viruses Infecting Eukaryotic Algae.

Algae are photosynthetic organisms that drive aquatic ecosystems, e.g. fuelling food webs or forming harmful blooms. The discovery of viruses that infect eukaryotic algae has raised many questions about their influence on aquatic primary production and their role in algal ecology and evolution. Although the full extent of algal virus diversity is still being discovered, this review summarizes current knowledge of this topic. Where possible, formal taxonomic classifications are referenced from the International Committee on Taxonomy of Viruses (ICTV); since the pace of virus discovery has far surpassed the rate of formal classification, however, numerous unclassified viruses are discussed along with their classified relatives. In total, we recognized 61 distinct algal virus taxa with highly variable morphologies that include dsDNA, ssDNA, dsRNA, and ssRNA genomes ranging from approximately 4.4 to 560 kb, with virion sizes from approximately 20 to 210nm in diameter. These viruses infect a broad range of algae and, although there are a few exceptions, they are generally lytic and highly species or strain specific. Dedicated research efforts have led to the appreciation of algal viruses as diverse, dynamic, and ecologically important members of the biosphere, and future investigations will continue to reveal the full extent of their diversity and impact.

Turning up the volume to address biases in predicted healthcare-associated infections and enhance U.S. hospital rankings: A data-driven approach.

OBJECTIVES: To examine potential biases in standardized infection ratio (SIR) metrics due to static U.S. Centers for Disease Control and Prevention (CDC) parameters and non-linearity of infection outcomes with volume. Correspondingly, to enhance the CDC predictions by incorporating additional information from volume metrics and explore an alternative approach to more fairly rank hospitals to address the SIR=0 problem. METHODS: This population-based study uses publicly available 2019 healthcare-associated infections (HAI) data from 3096 acute care U.S. hospitals. HAI-specific Poisson generalized additive models illustrate the recalibration of CDC predictions, using volume-based spline functions to adjust for biases. Implied cumulative distribution functions (CDF) were derived, and HAI-facility-specific probabilities were calculated. Hospital rankings implied from these HAI-stratified probabilities were calculated. RESULTS: Calibration plots demonstrate existing biases associated with CDC infection over-predictions. Volume-based spline functions were significant for all HAIs (P<.0004). CDF-based rankings resulted in larger discrimination across hospitals based on strength of evidence, especially among SIR=0 facilities. National maps depict ranking differences by HAI and state. CONCLUSION: Adjustment of SIR biases, which differ by facility volume, is needed to produce more accurate and fairer hospital rankings.

Microbial Ecology of Oxygen Minimum Zones Amidst Ocean Deoxygenation.

Oxygen minimum zones (OMZs) have substantial effects on the global ecology and biogeochemical processes of marine microbes. However, the diversity and activity of OMZ microbes and their trophic interactions are only starting to be documented, especially in regard to the potential roles of viruses and protists. OMZs have expanded over the past 60 years and are predicted to expand due to anthropogenic climate change, furthering the need to understand these regions. This review summarizes the current knowledge of OMZ formation, the biotic and abiotic factors involved in OMZ expansion, and the microbial ecology of OMZs, emphasizing the importance of bacteria, archaea, viruses, and protists. We describe the recognized roles of OMZ microbes in carbon, nitrogen, and sulfur cycling, the potential of viruses in altering host metabolisms involved in these cycles, and the control of microbial populations by grazers and viruses. Further, we highlight the microbial community composition and roles of these organisms in oxic and anoxic depths within the water column and how these differences potentially inform how microbial communities will respond to deoxygenation. Additionally, the current literature on the alteration of microbial communities by other key climate change parameters such as temperature and pH are considered regarding how OMZ microbes might respond to these pressures. Finally, we discuss what knowledge gaps are present in understanding OMZ microbial communities and propose directions that will begin to close these gaps.

Benchmarking microbial growth rate predictions from metagenomes.

Growth rates are central to understanding microbial interactions and community dynamics. Metagenomic growth estimators have been developed, specifically codon usage bias (CUB) for maximum growth rates and "peak-to-trough ratio" (PTR) for in situ rates. Both were originally tested with pure cultures, but natural populations are more heterogeneous, especially in individual cell histories pertinent to PTR. To test these methods, we compared predictors with observed growth rates of freshly collected marine prokaryotes in unamended seawater. We prefiltered and diluted samples to remove grazers and greatly reduce virus infection, so net growth approximated gross growth. We sampled over 44 h for abundances and metagenomes, generating 101 metagenome-assembled genomes (MAGs), including Actinobacteria, Verrucomicrobia, SAR406, MGII archaea, etc. We tracked each MAG population by cell-abundance-normalized read recruitment, finding growth rates of 0 to 5.99 per day, the first reported rates for several groups, and used these rates as benchmarks. PTR, calculated by three methods, rarely correlated to growth (r ~-0.26-0.08), except for rapidly growing γ-Proteobacteria (r ~0.63-0.92), while CUB correlated moderately well to observed maximum growth rates (r = 0.57). This suggests that current PTR approaches poorly predict actual growth of most marine bacterial populations, but maximum growth rates can be approximated from genomic characteristics.

Seasonal determinations of algal virus decay rates reveal overwintering in a temperate freshwater pond.

To address questions about algal virus persistence (i.e., continued existence) in the environment, rates of decay of infectivity for two viruses that infect Chlorella-like algae, ATCV-1 and CVM-1, and a virus that infects the prymnesiophyte Chrysochromulina parva, CpV-BQ1, were estimated from in situ incubations in a temperate, seasonally frozen pond. A series of experiments were conducted to estimate rates of decay of infectivity in all four seasons with incubations lasting 21 days in spring, summer and autumn, and 126 days in winter. Decay rates observed across this study were relatively low compared with previous estimates obtained for other algal viruses, and ranged from 0.012 to 11% h(-1). Overall, the virus CpV-BQ1 decayed most rapidly whereas ATCV-1 decayed most slowly, but for all viruses the highest decay rates were observed during the summer and the lowest were observed during the winter. Furthermore, the winter incubations revealed the ability of each virus to overwinter under ice as ATCV-1, CVM-1 and CpV-BQ1 retained up to 48%, 19% and 9% of their infectivity after 126 days, respectively. The observed resilience of algal viruses in a seasonally frozen freshwater pond provides a mechanism that can support the maintenance of viral seed banks in nature. However, the high rates of decay observed in the summer demonstrate that virus survival and therefore environmental persistence can be subject to seasonal bottlenecks.