Introduction: Rural Americans (RA) have poorer vascular health and physical activity levels than their urban counterparts; all are dementia risk factors. Dementia risk reduction among rural individuals requires a tailored approach. The purpose of this project was to examine preliminary efficacy of a community-based physical exercise and/or dementia risk factor-reduction curriculum among rural adults 50 and older.
View Article and Find Full Text PDFBackground: Currently, the United States has the largest number of reported coronavirus disease 2019 (COVID-19) cases and deaths globally. Using a geographically diverse surveillance network, we describe risk factors for severe outcomes among adults hospitalized with COVID-19.
Methods: We analyzed data from 2491 adults hospitalized with laboratory-confirmed COVID-19 between 1 March-2 May 2020, as identified through the Coronavirus Disease 2019-Associated Hospitalization Surveillance Network, which comprises 154 acute-care hospitals in 74 counties in 13 states.
The vast majority of intracellular protein targets are refractory toward small-molecule therapeutic engagement, and additional therapeutic modalities are needed to overcome this deficiency. Here, the identification and characterization of a natural product, WDB002, reveals a therapeutic modality that dramatically expands the currently accepted limits of druggability. WDB002, in complex with the FK506-binding protein (FKBP12), potently and selectively binds the human centrosomal protein 250 (CEP250), resulting in disruption of CEP250 function in cells.
View Article and Find Full Text PDFMutations in the TRIM8 gene have been described in patients with severe developmental delay, intellectual disability and epilepsy. Only six patients have been described to date. All the previous mutations were truncating variants clustered in the C-terminus of the protein.
View Article and Find Full Text PDFObjective: Pathogenic variants in SCN3A, encoding the voltage-gated sodium channel subunit Nav1.3, cause severe childhood onset epilepsy and malformation of cortical development. Here, we define the spectrum of clinical, genetic, and neuroimaging features of SCN3A-related neurodevelopmental disorder.
View Article and Find Full Text PDFBackground: Improving appropriate antibiotic use is crucial for combating antibiotic resistance and unnecessary adverse drug reactions. Acute respiratory illness (ARI) commonly causes outpatient visits and accounts for ~41% of antibiotics used in the United States. We examined the influence of influenza vaccination on reducing antibiotic prescriptions among outpatients with ARI.
View Article and Find Full Text PDFWith advances in genetic testing and improved access to such advances, whole exome sequencing is becoming a first-line investigation in clinical work-up of children with developmental delay/intellectual disability (ID). As a result, the need to understand the importance of genetic variants and its effect on the clinical phenotype is increasing. Here, we report on the largest cohort of patients with HNRNPU variants.
View Article and Find Full Text PDFSince 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).
View Article and Find Full Text PDFBackground: Several observational studies have shown decreases in measured influenza vaccine effectiveness (mVE) during influenza seasons. One study found decreases of 6-11%/month during the 2011-2012 to 2014-2015 seasons. These findings could indicate waning immunity but could also occur if vaccine effectiveness is stable and vaccine provides partial protection in all vaccinees ("leaky") rather than complete protection in a subset of vaccinees.
View Article and Find Full Text PDFEML4-ALK is an oncogenic fusion present in ∼5% of non-small cell lung cancers. However, alternative breakpoints in the gene lead to distinct variants of EML4-ALK with different patient outcomes. Here, we show that, in cell models, EML4-ALK variant 3 (V3), which is linked to accelerated metastatic spread, causes microtubule stabilization, formation of extended cytoplasmic protrusions and increased cell migration.
View Article and Find Full Text PDFTwo 1p36 contiguous gene deletion syndromes are known so far: the terminal 1p36 deletion syndrome and a 1p36 deletion syndrome with a critical region located more proximal at 1p36.23-1p36.22.
View Article and Find Full Text PDFIn December 2019, an outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, began in Wuhan, China (1). The disease spread widely in China, and, as of February 26, 2020, COVID-19 cases had been identified in 36 other countries and territories, including the United States. Person-to-person transmission has been widely documented, and a limited number of countries have reported sustained person-to-person spread.
View Article and Find Full Text PDFWe report experimental results on the diffractive imaging of three-dimensionally aligned 2,5-diiodothiophene molecules. The molecules were aligned by chirped near-infrared laser pulses, and their structure was probed at a photon energy of 9.5 keV (λ ≈ 130 pm) provided by the Linac Coherent Light Source.
View Article and Find Full Text PDFBackground: Annual United States (US) estimates of influenza vaccine effectiveness (VE) in children typically measure protection against outpatient medically attended influenza illness, with limited data evaluating VE against influenza hospitalizations. We estimated VE for preventing laboratory-confirmed influenza hospitalization among US children.
Methods: We included children aged 6 months-17 years with acute respiratory illness enrolled in the New Vaccine Surveillance Network during the 2015-2016 influenza season.
Pathogenic variants in ZMYND11, which acts as a transcriptional repressor, have been associated with intellectual disability, behavioral abnormalities, and seizures. Only 11 affected individuals have been reported to date, and the phenotype associated with pathogenic variants in this gene have not been fully defined. Here, we present 16 additional patients with predicted pathogenic heterozygous variants in including four individuals from the same family, to further delineate and expand the genotypic and phenotypic spectrum of ZMYND11-related syndromic intellectual disability.
View Article and Find Full Text PDFDuring the 2019-20 influenza season, influenza-like illness (ILI)* activity first exceeded the national baseline during the week ending November 9, 2019, signaling the earliest start to the influenza season since the 2009 influenza A(H1N1) pandemic. Activity remains elevated as of mid-February 2020. In the United States, annual vaccination against seasonal influenza is recommended for all persons aged ≥6 months (1).
View Article and Find Full Text PDFMMWR Morb Mortal Wkly Rep
February 2020
In December 2019, a cluster of cases of pneumonia emerged in Wuhan City in central China's Hubei Province. Genetic sequencing of isolates obtained from patients with pneumonia identified a novel coronavirus (2019-nCoV) as the etiology (1). As of February 4, 2020, approximately 20,000 confirmed cases had been identified in China and an additional 159 confirmed cases in 23 other countries, including 11 in the United States (2,3).
View Article and Find Full Text PDFBackground: Since 2013, quadrivalent influenza vaccines containing 2 B viruses gradually replaced trivalent vaccines in the United States. We compared the vaccine effectiveness of quadrivalent to trivalent inactivated vaccines (IIV4 to IIV3, respectively) against illness due to influenza B during the transition, when IIV4 use increased rapidly.
Methods: The US Influenza Vaccine Effectiveness (Flu VE) Network analyzed 25 019 of 42 600 outpatients aged ≥6 months who enrolled within 7 days of illness onset during 6 seasons from 2011-2012.
Purpose: To evaluate whether the 8th staging system is a better discriminator of overall survival (OS) than the 7th edition for oropharyngeal cancer patients after definitive (chemo)radiotherapy (CRT).
Material And Methods: Data from oropharyngeal cancer patients treated with CRT with curative intent between 2010 and 2016 at Guy's and St Thomas' Hospitals were reviewed. Human papillomavirus (HPV) status was ascertained in all cases.
Multiple genetically distinct influenza B/Victoria lineage viruses have cocirculated in the United States recently, circulating sporadically during the 2018-19 season and more frequently early during the 2019-20 season (1). The beginning of the 2019-20 influenza season in Louisiana was unusually early and intense, with infections primarily caused by influenza B/Victoria lineage viruses. One large pediatric health care facility in New Orleans (facility A) reported 1,268 laboratory-confirmed influenza B virus infections, including 23 hospitalizations from July 31 to November 21, 2019, a time when influenza activity is typically low.
View Article and Find Full Text PDFBackground: Multivalent influenza vaccine products provide protection against influenza A(H1N1)pdm09, A(H3N2), and B lineage viruses. The 2018-2019 influenza season in the United States included prolonged circulation of A(H1N1)pdm09 viruses well-matched to the vaccine strain and A(H3N2) viruses, the majority of which were mismatched to the vaccine. We estimated the number of vaccine-prevented influenza-associated illnesses, medical visits, hospitalizations, and deaths for the season.
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