Integrated behavioral health can improve primary care and mental health outcomes. Access to behavioral health and primary care services in Texas is in crisis because of high uninsurance rates, regulatory restrictions, and lack of workforce. To address gaps in access to care, a partnership formed among a large local mental health authority in central Texas, a federally designated rural health clinic, and the Texas A&M University School of Nursing to create an interprofessional team-based health care delivery model led by nurse practitioners in rural and medically underserved areas of central Texas.
View Article and Find Full Text PDFBackground: Sero-surveillance of SARS-CoV-2 is crucial to monitoring levels of population exposure and informing public health responses, but may be influenced by variability in performance between available assays.
Methods: Five commercial immunoassays and a neutralising activity assay were used to detect antibodies to SARS-CoV-2 in routine primary care and paediatric samples collected during the first wave of the pandemic in NHS Lothian, Scotland as part of ongoing surveillance efforts. For each assay, sensitivity and specificity was calculated relative to consensus results (majority of immunoassays positive = overall positive) and neutralising activity.
Emerging zoonotic viral pathogens threaten global health, and there is an urgent need to discover host and viral determinants influencing infection. We performed a loss-of-function genome-wide CRISPR screen in a human lung cell line using HCoV-OC43, a human betacoronavirus. One candidate gene, VPS29, a component of the retromer complex, was required for infection by HCoV-OC43, SARS-CoV-2, other endemic- and pandemic-threat coronaviruses, as well as ebolavirus.
View Article and Find Full Text PDFThe number and variability of the neutralizing epitopes targeted by polyclonal antibodies in individuals who are SARS-CoV-2 convalescent and vaccinated are key determinants of neutralization breadth and the genetic barrier to viral escape. Using HIV-1 pseudotypes and plasma selection experiments with vesicular stomatitis virus/SARS-CoV-2 chimaeras, here we show that multiple neutralizing epitopes, within and outside the receptor-binding domain, are variably targeted by human polyclonal antibodies. Antibody targets coincide with spike sequences that are enriched for diversity in natural SARS-CoV-2 populations.
View Article and Find Full Text PDFBackground: A critical step in the HIV-1 replication cycle is the assembly of Gag proteins to form virions at the plasma membrane. Virion assembly and maturation are facilitated by the cellular polyanion inositol hexaphosphate (IP), which is proposed to stabilize both the immature Gag lattice and the mature capsid lattice by binding to rings of primary amines at the center of Gag or capsid protein (CA) hexamers. The amino acids comprising these rings are critical for proper virion formation and their substitution results in assembly deficits or impaired infectiousness.
View Article and Find Full Text PDFAntibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options.
View Article and Find Full Text PDFMonoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated.
View Article and Find Full Text PDFAntibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on the properties of SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibodies, we analyzed six independent antibody lineages. As well as increased neutralization potency, antibody evolution changed pathways for acquisition of resistance and, in some cases, restricted the range of neutralization escape options.
View Article and Find Full Text PDFMonoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasma, including plasma from individuals from whom some of the antibodies were isolated.
View Article and Find Full Text PDFCross-reactive immune responses elicited by seasonal coronaviruses might affect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and disease outcomes. We measured neutralizing activity against SARS-CoV-2 in prepandemic sera from patients with prior polymerase chain reaction scan-confirmed seasonal coronavirus infection. Although neutralizing activity against seasonal coronaviruses was detected in nearly all sera, cross-reactive neutralizing activity against SARS-CoV-2 was undetectable.
View Article and Find Full Text PDFNeutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear.
View Article and Find Full Text PDFCross-reactive immune responses elicited by seasonal coronaviruses might impact SARS-CoV-2 susceptibility and disease outcomes. We measured neutralizing activity against SARS-CoV-2 in pre-pandemic sera from patients with prior PCR-confirmed seasonal coronavirus infection. While neutralizing activity against seasonal coronaviruses was detected in nearly all sera, cross-reactive neutralizing activity against SARS-CoV-2 was undetectable.
View Article and Find Full Text PDFNeutralizing antibodies elicited by prior infection or vaccination are likely to be key for future protection of individuals and populations against SARS-CoV-2. Moreover, passively administered antibodies are among the most promising therapeutic and prophylactic anti-SARS-CoV-2 agents. However, the degree to which SARS-CoV-2 will adapt to evade neutralizing antibodies is unclear.
View Article and Find Full Text PDFSon preference has existed for centuries in many cultures and societies. In some Asian countries, including China and India, the sex ratio at birth (SRB, number of male infants divided by number of female infants times 100) is elevated above the worldwide biological norm of about 105. We investigate whether this ratio is elevated in the U.
View Article and Find Full Text PDFHistone deacetylase (HDAC) inhibitors are efficacious epigenetic-based therapies for some cancers and neurological disorders; however, each of these drugs inhibits multiple HDACs and has detrimental effects on the skeleton. To better understand how HDAC inhibitors affect endochondral bone formation, we conditionally deleted one of their targets, Hdac3, pre- and postnatally in type II collagen α1 (Col2α1)-expressing chondrocytes. Embryonic deletion was lethal, but postnatal deletion of Hdac3 delayed secondary ossification center formation, altered maturation of growth plate chondrocytes, and increased osteoclast activity in the primary spongiosa.
View Article and Find Full Text PDFBackground: The purpose of this study was to evaluate the relationship of calorie and protein intake to the severity of oral mucositis in patients with head and neck cancer receiving radiation therapy.
Methods: Patients with head and neck cancer undergoing ≥60 Gy of radiation were eligible. Weekly data were collected for oral mucositis grade and protein and calorie intake.
In the context of intraparenchymal delivery of therapeutic agents into brain parenchyma for the purpose of treating serious brain diseases, we present the scientific and medical need for infusion from a single source to cover a large area of the cerebral cortex, which we refer to as 'surface-contoured distributions' (SCD). The designs of two devices suitable for obtaining such SCD's are described, and the results of preliminary experimental studies with prototypes of them are reported. The studies were done in ex vivo samples of mammalian brain tissues, and histological sections of the brains confirmed that we had covered the large surface area desired.
View Article and Find Full Text PDFSelf-determination, choice, and preference have become important issues in vocational rehabilitation and have long been staples of social work practice. This article provides an overview of a model, the self-determined career development model, which is designed to enable people with disabilities to self-direct planning that leads to employment. Specifically, this model is applied to young women with intellectual and developmental disabilities to obtain nontraditional employment through self-regulated, customized employment planning.
View Article and Find Full Text PDFThis paper examines the effect of climate on migration. We examine whether climate is an influential factor in internal migration. We assume that most persons tend to avoid exposure to bitter and cold winters, and excessively hot and humid summers, preferring climates between these extremes.
View Article and Find Full Text PDFExperiments were conducted to determine (1) dose response of glyphosate-resistant (GR) and -susceptible (non-GR) soybean [Glycine max (L.) Merr.] and canola (Brassica napus L.
View Article and Find Full Text PDFJ Intellect Disabil Res
December 2006
Background: Family quality of life (FQOL), as a family outcome measure of early intervention and other services, has increasingly drawn attention of researchers, policymakers and service providers. Developing an index of family QOL requires a measure suitable for use with multiple family members. The purpose of this study was to test whether mothers and fathers similarly view the conceptual model of FQOL embodied in one measure.
View Article and Find Full Text PDFThis paper examines the effect of age at menarche on children ever born (CEB). We use data from the 1997 Sample Survey of Population and Reproductive Health conducted by the China Population Information and Research Center and the State Family Planning Commission. Poisson regression models are estimated for 10,919 ever married Chinese Han women.
View Article and Find Full Text PDFBackground: Increasing emphasis on family-centred approaches to services and supports for families of children with disabilities has surfaced the issue of accountability for family outcomes. We present a review of literature about the impacts of children with disabilities on families as a backdrop to proposing family quality of life as a concept that encompasses impacts of disability and one that can be used to assess the impact of supports and services on families.
Method: We briefly introduce the Beach Center Family Quality of Life Scale, providing information about its factor structure, reliability and convergent validity.