NAT8L mRNA oxidation is linked to neurodegeneration in multiple sclerosis.

RNA oxidation has been implicated in neurodegeneration, but the underlying mechanism for such effects is unclear. Extensive RNA oxidation occurs within the neurons in multiple sclerosis (MS) brains. Here, we identified selectively oxidized mRNAs in neuronal cells that pertained to neuropathological pathways. N-acetyl aspartate transferase 8 like (NAT8L) is one such transcript, whose translation product enzymatically synthesizes N-acetyl aspartic acid (NAA), a neuronal metabolite important for myelin synthesis. We reasoned that impediment of translation of an oxidized NAT8L mRNA will result in a reduction in its cognate protein, thus lowering the NAA level. This hypothesis is supported by our studies on cells, an animal model, and postmortem human MS brain. Reduced brain NAA level hampers myelin integrity making neuronal axons more susceptible to damage, which contributes to MS neurodegeneration. Overall, this work provides a framework for a mechanistic understanding of the link between RNA oxidation and neurodegeneration.

Reversible Bronchial Obstruction in Primary Ciliary Dyskinesia.

BACKGROUND: Inhaled bronchodilators are frequently used among patients with primary ciliary dyskinesia (PCD), although neither the effectiveness nor the prevalence of their use is known, due to the paucity of relevant studies. METHODS: This is a retrospective analysis of pre- and post-bronchodilator spirometry results, of patients with PCD from two centers. Correlations were examined of bronchodilator response, with asthma and atopy markers. RESULTS: Of 115 patients, 46 (40%) completed spirometry pre- and post-bronchodilation. Of these, 26 (56.5%) demonstrated reversible airway obstruction (increase in %FEV1 predicted ≥ 10%). Obstruction reversibility was not found to be associated with a family history of asthma, blood eosinophil level, elevated IgE, or atopy symptoms. Of the 46 patients who completed bronchodilator spirometry, 29 (63%) were regularly using bronchodilators and inhaled corticosteroids. CONCLUSIONS: More than half of patients with PCD presented with reversible airway obstruction, without any correlation to markers of personal or familial atopy. Inhaled bronchodilators and corticosteroid therapies are commonly used for treating PCD. Evaluating bronchodilator response should be considered, and its effectiveness should be further studied.

Pose-gait analysis for cetacean biologging tag data.

Biologging tags are a key enabling tool for investigating cetacean behavior and locomotion in their natural habitat. Identifying and then parameterizing gait from movement sensor data is critical for these investigations, but how best to characterize gait from tag data remains an open question. Further, the location and orientation of a tag on an animal in the field are variable and can change multiple times during a deployment. As a result, the relative orientation of the tag with respect to (wrt) the animal must be determined for analysis. Currently, custom scripts that involve species-specific heuristics tend to be used in the literature. These methods require a level of knowledge and experience that can affect the reliability and repeatability of the analysis. Swimming gait is composed of a sequence of body poses that have a specific spatial pattern, and tag-based measurements of this pattern can be utilized to determine the relative orientation of the tag. This work presents an automated data processing pipeline (and software) that takes advantage of these patterns to 1) Identify relative motion between the tag and animal; 2) Estimate the relative orientation of the tag wrt the animal using a data-driven approach; and 3) Calculate gait parameters that are stable and invariant to animal pose. Validation results from bottlenose dolphin tag data show that the average relative orientation error (tag wrt the body) after processing was within 11 degrees in roll, pitch, and yaw directions. The average precision and recall for detecting instances of relative motion in the dolphin data were 0.87 and 0.89, respectively. Tag data from humpback and beluga whales were then used to demonstrate how the gait analysis can be used to enhance tag-based investigations of movement and behavior. The MATLAB source code and data presented in the paper are publicly available (https://github.com/ding-z/cetacean-pose-gait-analysis.git), along with suggested best practices.

Treatment Variability and Complications Associated With Pediatric Lateral Ankle Injuries: A POSNA Quality, Safety, and Value Initiative Survey.

Background: Isolated pediatric lateral ankle injuries, including ankle sprain (AS) and nondisplaced Salter-Harris type 1 (SH-1) distal fibular fracture, are common orthopaedic sports-related injuries. Variability in treatment is suspected among pediatric orthopaedic surgeons. Complications from medical treatment or lack thereof have not been reported in this population. Purpose: The purpose of this study was to investigate treatment variability and associated complications after pediatric AS and SH-1 via a survey of members of the Pediatric Orthopaedic Society of North American (POSNA). Study Design: Cross-sectional study. Level of evidence, 5. Methods: A voluntary, anonymous survey was distributed to POSNA membership (approximately 1400 members) via email. Survey questions, specific to both grade 1 or 2 AS and nondisplaced or minimally displaced SH-1 injuries in skeletally immature patients, focused on initial evaluation, immobilization, return to sports, and complications. We analyzed variability both in treatment between AS and SH-1 injury and in respondent characteristics. For statistical analysis, chi-square or Fisher exact test was used for categorical variables, and analysis of variance was used for continuous variables. Results: The survey response rate was 16.4% (229/1400). Of the respondents, 27.7% used examination only to distinguish between AS and SH-1, whereas 18.7% performed serial radiography to aid with diagnosis. A controlled ankle motion boot or walking boot was the most common immobilization technique for both AS (46.3%) and SH-1 (55.6%); the second most common technique was bracing in AS (33.5%) and casting in SH-1 (34.7%). Approximately one-third of all respondents recommended either outpatient or home physical therapy for AS, whereas only 11.4% recommended physical therapy for SH-1 (P < .01). Results showed that 81.2% of respondents reported no complications for SH-1 treatment and 87.8% reported no complications for AS treatment. Cast complications were reported by 9.6% for SH-1 and 5.2% for AS. Rare SH-1 complications included distal fibular growth arrest, infection, nonunion, late fracture displacement, and recurrent fracture. Conclusion: Significant variability was found in primary treatment of pediatric AS and SH-1 injuries. Rare complications from injury, treatment, and neglected treatment after SH-1 and AS were reported.

Decay of Piwi-Interacting RNAs in Human Cells Is Primarily Mediated by 5' to 3' Exoribonucleases.

Piwi-interacting RNAs (piRNAs) are a group of small noncoding RNA molecules that regulate the activity of transposons and control gene expression. The cellular concentration of RNAs is generally maintained by their rates of biogenesis and degradation. Although the biogenesis pathways of piRNAs have been well defined, their degradation mechanism is still unknown. Here, we show that degradation of human piRNAs is mostly dependent on the 5'-3' exoribonuclease pathway. The presence of 3'-end 2'-O-methylation in piRNAs significantly reduced their degradation through the exosome-mediated decay pathway. The accumulation of piRNAs in XRN1 and XRN2 exoribonuclease-depleted cells further supports the 5'-3' exoribonuclease-mediated decay of piRNAs. Moreover, formation of stable secondary structures in piRNAs slows the rate of XRN1-mediated degradation. Our findings establish a framework for the piRNA degradation mechanism in cells and thus provide crucial information about how the basal level concentration of piRNAs is maintained in cells.

Cell models for Down syndrome-Alzheimer's disease research.

Down syndrome (DS) is the most common chromosomal abnormality and leads to intellectual disability, increased risk of cardiac defects, and an altered immune response. Individuals with DS have an extra full or partial copy of chromosome 21 (trisomy 21) and are more likely to develop early-onset Alzheimer's disease (AD) than the general population. Changes in expression of human chromosome 21 (Hsa21)-encoded genes, such as amyloid precursor protein (APP), play an important role in the pathogenesis of AD in DS (DS-AD). However, the mechanisms of DS-AD remain poorly understood. To date, several mouse models with an extra copy of genes syntenic to Hsa21 have been developed to characterise DS-AD-related phenotypes. Nonetheless, due to genetic and physiological differences between mouse and human, mouse models cannot faithfully recapitulate all features of DS-AD. Cells differentiated from human-induced pluripotent stem cells (iPSCs), isolated from individuals with genetic diseases, can be used to model disease-related cellular and molecular pathologies, including DS. In this review, we will discuss the limitations of mouse models of DS and how these can be addressed using recent advancements in modelling DS using human iPSCs and iPSC-mouse chimeras, and potential applications of iPSCs in preclinical studies for DS-AD.

Census tract socioeconomic indicators and COVID-19-associated hospitalization rates-COVID-NET surveillance areas in 14 states, March 1-April 30, 2020.

OBJECTIVES: Some studies suggested more COVID-19-associated hospitalizations among racial and ethnic minorities. To inform public health practice, the COVID-19-associated Hospitalization Surveillance Network (COVID-NET) quantified associations between race/ethnicity, census tract socioeconomic indicators, and COVID-19-associated hospitalization rates. METHODS: Using data from COVID-NET population-based surveillance reported during March 1-April 30, 2020 along with socioeconomic and denominator data from the US Census Bureau, we calculated COVID-19-associated hospitalization rates by racial/ethnic and census tract-level socioeconomic strata. RESULTS: Among 16,000 COVID-19-associated hospitalizations, 34.8% occurred among non-Hispanic White (White) persons, 36.3% among non-Hispanic Black (Black) persons, and 18.2% among Hispanic or Latino (Hispanic) persons. Age-adjusted COVID-19-associated hospitalization rate were 151.6 (95% Confidence Interval (CI): 147.1-156.1) in census tracts with >15.2%-83.2% of persons living below the federal poverty level (high-poverty census tracts) and 75.5 (95% CI: 72.9-78.1) in census tracts with 0%-4.9% of persons living below the federal poverty level (low-poverty census tracts). Among White, Black, and Hispanic persons living in high-poverty census tracts, age-adjusted hospitalization rates were 120.3 (95% CI: 112.3-128.2), 252.2 (95% CI: 241.4-263.0), and 341.1 (95% CI: 317.3-365.0), respectively, compared with 58.2 (95% CI: 55.4-61.1), 304.0 (95%: 282.4-325.6), and 540.3 (95% CI: 477.0-603.6), respectively, in low-poverty census tracts. CONCLUSIONS: Overall, COVID-19-associated hospitalization rates were highest in high-poverty census tracts, but rates among Black and Hispanic persons were high regardless of poverty level. Public health practitioners must ensure mitigation measures and vaccination campaigns address needs of racial/ethnic minority groups and people living in high-poverty census tracts.

Corrigendum: Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer's Disease.

[This corrects the article DOI: 10.3389/fnagi.2021.703876.].

Basal Forebrain Cholinergic Neurons: Linking Down Syndrome and Alzheimer's Disease.

Down syndrome (DS, trisomy 21) is characterized by intellectual impairment at birth and Alzheimer's disease (AD) pathology in middle age. As individuals with DS age, their cognitive functions decline as they develop AD pathology. The susceptibility to degeneration of a subset of neurons, known as basal forebrain cholinergic neurons (BFCNs), in DS and AD is a critical link between cognitive impairment and neurodegeneration in both disorders. BFCNs are the primary source of cholinergic innervation to the cerebral cortex and hippocampus, as well as the amygdala. They play a critical role in the processing of information related to cognitive function and are directly engaged in regulating circuits of attention and memory throughout the lifespan. Given the importance of BFCNs in attention and memory, it is not surprising that these neurons contribute to dysfunctional neuronal circuitry in DS and are vulnerable in adults with DS and AD, where their degeneration leads to memory loss and disturbance in language. BFCNs are thus a relevant cell target for therapeutics for both DS and AD but, despite some success, efforts in this area have waned. There are gaps in our knowledge of BFCN vulnerability that preclude our ability to effectively design interventions. Here, we review the role of BFCN function and degeneration in AD and DS and identify under-studied aspects of BFCN biology. The current gaps in BFCN relevant imaging studies, therapeutics, and human models limit our insight into the mechanistic vulnerability of BFCNs in individuals with DS and AD.

The BHMT-betaine methylation pathway epigenetically modulates oligodendrocyte maturation.

Research into the epigenome is of growing importance as a loss of epigenetic control has been implicated in the development of neurodegenerative diseases. Previous studies have implicated aberrant DNA and histone methylation in multiple sclerosis (MS) disease pathogenesis. We have previously reported that the methyl donor betaine is depleted in MS and is linked to changes in histone H3 trimethylation (H3K4me3) in neurons. We have also shown that betaine increases histone methyltransferase activity by activating chromatin bound betaine homocysteine S-methyltransferase (BHMT). Here, we investigated the role of the BHMT-betaine methylation pathway in oligodendrocytes. Immunocytochemistry in the human MO3.13 cell line, primary rat oligodendrocytes, and tissue from MS postmortem brain confirmed the presence of the BHMT enzyme in the nucleus in oligodendrocytes. BHMT expression is increased 2-fold following oxidative insult, and qRT-PCR demonstrated that betaine can promote an increase in expression of oligodendrocyte maturation genes SOX10 and NKX-2.2 under oxidative conditions. Chromatin fractionation provided evidence of a direct interaction of BHMT on chromatin and co-IP analysis indicates an interaction between BHMT and DNMT3a. Our data show that both histone and DNA methyltransferase activity are increased following betaine administration. Betaine effects were shown to be dependent on BHMT expression following siRNA knockdown of BHMT. This is the first report of BHMT expression in oligodendrocytes and suggests that betaine acts through BHMT to modulate histone and DNA methyltransferase activity on chromatin. These data suggest that methyl donor availability can impact epigenetic changes and maturation in oligodendrocytes.

Gender and Socioeconomic Factors Affect Adolescent Patient and Guardian Preferences in Sports Medicine Physician Characteristics and Medical Decision Making.

INTRODUCTION: Diversity has increased within youth sports. It is unknown whether these demographic or socioeconomic factors affect adolescent patients' and their guardians' preferences of sports medicine physicians and involvement in medial decision making. Demographic and socioeconomic factors may affect adolescent patient and guardian preferences for sports medicine physicians. METHODS: Patients, age 10 to 18 years, and their guardians presenting to two sports medicine offices were asked to complete matched, anonymous surveys assessing their preferences for medical decision making, sports medicine physician gender, and personality characteristics. Analysis of demographic and socioeconomic effects on preferences was completed. RESULTS: Matched survey responses were collected from 353 patients and 325 corresponding guardians. Patient average age was 14.6 years (SD 2.1), with 43% female. Guardian average age was 43.4 years (SD 8.3), with 79% female. For both patients and guardians, the highest valued physician characteristic was being a good listener. Overall, 21% of patients and 17% of guardians reported a physician gender preference that matched the gender of the patient. Among all female patients, 32% preferred a female physician. Among all male patients, 12% preferred a male physician (P < 0.001). Ninety-two percent of patients reported wanting to be involved, and 93% of guardians thought that their child should be involved in the decision-making process. Hispanic, non-White, non-English speaking, government or no insurance, or less than college level of education patients and guardians reported a significantly greater importance of the physician independently determining the treatment plan (P < 0.001). CONCLUSIONS: Demographic and socioeconomic factors do affect adolescent patient and guardian preferences for sports medicine physicians. Young patients have a desire to be included in the medical decision-making process. Female adolescent patients may have a same-gender preference for their sports medicine physician. STUDY DESIGN: This is a prospective, cohort study.

An integrated comparative physiology and molecular approach pinpoints mediators of breath-hold capacity in dolphins.

BACKGROUND AND OBJECTIVES: Ischemic events, such as ischemic heart disease and stroke, are the number one cause of death globally. Ischemia prevents blood, carrying essential nutrients and oxygen, from reaching tissues, leading to cell and tissue death, and eventual organ failure. While humans are relatively intolerant to ischemic events, other species, such as marine mammals, have evolved a unique tolerance to chronic ischemia/reperfusion during apneic diving. To identify possible molecular features of an increased tolerance for apnea, we examined changes in gene expression in breath-holding dolphins. METHODOLOGY: Here, we capitalized on the adaptations possesed by bottlenose dolphins (Tursiops truncatus) for diving as a comparative model of ischemic stress and hypoxia tolerance to identify molecular features associated with breath holding. Given that signals in the blood may influence physiological changes during diving, we used RNA-Seq and enzyme assays to examine time-dependent changes in gene expression in the blood of breath-holding dolphins. RESULTS: We observed time-dependent upregulation of the arachidonate 5-lipoxygenase (ALOX5) gene and increased lipoxygenase activity during breath holding. ALOX5 has been shown to be activated during hypoxia in rodent models, and its metabolites, leukotrienes, induce vasoconstriction. CONCLUSIONS AND IMPLICATIONS: The upregulation of ALOX5 mRNA occurred within the calculated aerobic dive limit of the species, suggesting that ALOX5 may play a role in the dolphin's physiological response to diving, particularly in a pro-inflammatory response to ischemia and in promoting vasoconstriction. These observations pinpoint a potential molecular mechanism by which dolphins, and perhaps other marine mammals, respond to the prolonged breath holds associated with diving.

Trochlear Morphology Development: Study of Normal Pediatric Knee MRIs.

INTRODUCTION: Trochlear dysplasia is a known risk factor for patellar dislocations yet normal trochlea development is not well described. This study will define the articular cartilage (AC) and subchondral trochlear morphology development in pediatric patients using magnetic resonance imaging (MRI) evaluation. METHODS: A retrospective knee MRI review included patients aged 3 to 16 years with nonpatellofemoral-related diagnoses. International classification of diseases-9/International classification of diseases-10 codes were used to identify eligible study patients. Measurements of the trochlea were made on the basis of previously established methods using the axial MRI just distal to the physis at the deepest portion of the trochlear groove. Three linear [lateral trochlear height (LTH), medial trochlear height (MTH), and central trochlear height (CTH)] and 3 angular [sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS)] were made at AC and subchondral bone (SCB). The 12 measurements were made independently by 2 study authors. Inter-rater reliability was assessed using an interclass correlation coefficient for absolute agreement to the average of the scores. Trochlea measurements were summarized across age quartiles defined as first quartile (age, 5.1 to 8.3 y), second quartile (8.3 to 11.5 y), third quartile (11.5 to 14.3 y), fourth quartile (14.3to 16.9 y). Associations between age and trochlea measures were assessed using linear regression with Huber-White-adjusted SEs to account for clustering from a small number of patients (N=16) with >1 MRI. RESULTS: In total, 246 knee MRIs from 230 patients were included in this study; 113 patients (51%) were female, whereas 117 (49%) were male. A total of 116 MRIs (47%) were of the left knee and 130 (53%) were right knee. The average patient age was 11.4±3.4 years. Inter-rater agreement was high across all measures with interclass correlation coefficient values >0.7. Mean values for measurements are presented by age quartiles. LTH, MTH, and CTH showed a linear increase with age (range, 2 to 2.6 cm/y; P<0.001). SA, LTS, MTS measured at AC showed no change with age (P>0.05); however, LTS and MTS measured at SCB showed significant increases with age (0.6 and 0.9 degrees/y; P<0.001), whereas SA showed a decrease with age (-1.4 degrees/y; P<0.001). There were no significant differences found in the age associations by laterality, left versus right. There were no sex differences in the age associations for SA, LTS (P>0.05); however, for MTH, LTH, and CTH, males were found to have a significantly greater growth rate (P<0.001). CONCLUSIONS: This study found an increase in AC and SCB MTH, LTH, and CTH over time, as well as an increase in SCB LTS and MTS, with a decrease in SA. However, AC of the LTS and SA remained constant, with no significant change throughout growth. This normative data indicate that the LTS and SA of AC are predictors of final trochlea shape in normal development. Final trochlear morphologic development is nearly complete around age 12 years, with no significant changes occurring thereafter.

COVID-19-Associated Hospitalizations Among Health Care Personnel - COVID-NET, 13 States, March 1-May 31, 2020.

Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.

Characteristics and Maternal and Birth Outcomes of Hospitalized Pregnant Women with Laboratory-Confirmed COVID-19 - COVID-NET, 13 States, March 1-August 22, 2020.

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.

Delays in Obtaining Knee MRI in Pediatric Sports Medicine: Impact of Insurance Type.

BACKGROUND: Increased enrollment in government-based insurance plans has been reported. With youth sports injuries on the rise, increased ordering of advanced imaging such as magnetic resonance imaging (MRI) has occurred. This study sought to report on the impact of insurance type on access to and results of knee MRI in pediatric sports medicine patients. METHODS: A retrospective review of 178 consecutive pediatric sports medicine clinics was completed. INCLUSION CRITERIA: patients younger than 18 years, routine knee MRI ordered, sports medicine diagnosis, and insurance. Data included basic demographics, injury date, date and location (urgent care vs. clinic) of the first presentation, details of MRI ordering and approval, date and location of MRI follow-up, MRI results (negative, minor findings, major findings), and eventual treatment required. RESULTS: A total of 168 charts underwent a complete review. The patients' average age was 14±3 years and 54% (N=90) were female. Ninety-eight had government insurance and 70 had commercial insurance. The time between injury and MRI completion was significantly longer with government insurance (34 vs. 67 d, P<0.01). Government insurance had increased wait time between the first visit and MRI completion (11 vs. 40 d, P<0.001) as well as MRI order and completion (9 vs. 16.5 d, P<0.001). There was no significant difference in positive findings on MRI between insurance groups, including both major and minor findings nor in the proportion receiving eventual operative treatment. CONCLUSION: Pediatric sports medicine patients with government insurance have delays in obtaining knee MRI, despite there being no difference in the rate of positive findings and subsequent operative treatments. LEVEL OF EVIDENCE: Level III-case-control study.

Hospitalization Rates and Characteristics of Children Aged <18 Years Hospitalized with Laboratory-Confirmed COVID-19 - COVID-NET, 14 States, March 1-July 25, 2020.

Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.

Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020.

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.

Applying infectious disease forecasting to public health: a path forward using influenza forecasting examples.

BACKGROUND: Infectious disease forecasting aims to predict characteristics of both seasonal epidemics and future pandemics. Accurate and timely infectious disease forecasts could aid public health responses by informing key preparation and mitigation efforts. MAIN BODY: For forecasts to be fully integrated into public health decision-making, federal, state, and local officials must understand how forecasts were made, how to interpret forecasts, and how well the forecasts have performed in the past. Since the 2013-14 influenza season, the Influenza Division at the Centers for Disease Control and Prevention (CDC) has hosted collaborative challenges to forecast the timing, intensity, and short-term trajectory of influenza-like illness in the United States. Additional efforts to advance forecasting science have included influenza initiatives focused on state-level and hospitalization forecasts, as well as other infectious diseases. Using CDC influenza forecasting challenges as an example, this paper provides an overview of infectious disease forecasting; applications of forecasting to public health; and current work to develop best practices for forecast methodology, applications, and communication. CONCLUSIONS: These efforts, along with other infectious disease forecasting initiatives, can foster the continued advancement of forecasting science.

A secondary structure within a human piRNA modulates its functionality.

The piwi-interacting RNAs (piRNAs) are small non-coding RNAs, mostly 24-32 nucleotides in length. The piRNAs are not known to have any conserved secondary structure or sequence motifs. Using bioinformatics analysis, we discovered the presence of putative G-quadruplex (GQ) forming sequences in human piRNAs. We studied human piR-48164/piR-GQ containing a potential GQ forming sequence and using biochemical and biophysical techniques confirmed its ability to form a GQ. Using EMSA, we discovered that the formation of GQ structure led to inhibition of the piRNA binding to the HIWI-PAZ domain as well as the complementary base pairing to a target RNA. The inability of the piR-GQ to interact with the PIWI protein might be detrimental to the function of the piRNA. To investigate if the formation of a GQ structure in piRNA prevents its target gene silencing in vivo, we used a reporter assay. The piR-GQ failed to inhibit the reporter gene expression while a mutated version that lacked the ability to form GQ inhibited reporter gene expression indicating that the presence of GQ in piRNA is detrimental to its function. These studies unraveled the dependence of a piRNA's functionality on an RNA secondary structure and added a new layer of regulation to their function.