438 research outputs found

    Development and pilot evaluation of a personalized decision support intervention for low risk prostate cancer patients.

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    ObjectivesDevelopment and pilot evaluation of a personalized decision support intervention to help men with early-stage prostate cancer choose among active surveillance, surgery, and radiation.MethodsWe developed a decision aid featuring long-term survival and side effects data, based on focus group input and stakeholder endorsement. We trained premedical students to administer the intervention to newly diagnosed men with low-risk prostate cancer seen at the University of California, San Francisco. Before the intervention, and after the consultation with a urologist, we administered the Decision Quality Instrument for Prostate Cancer (DQI-PC). We hypothesized increases in two knowledge items from the DQI-PC: How many men diagnosed with early-stage prostate cancer will eventually die of prostate cancer? How much would waiting 3 months to make a treatment decision affect chances of survival? Correct answers were: "Most will die of something else" and "A little or not at all."ResultsThe development phase involved 6 patients, 1 family member, 2 physicians, and 5 other health care providers. In our pilot test, 57 men consented, and 44 received the decision support intervention and completed knowledge surveys at both timepoints. Regarding the two knowledge items of interest, before the intervention, 35/56 (63%) answered both correctly, compared to 36/44 (82%) after the medical consultation (P = .04 by chi-square test).ConclusionsThe intervention was associated with increased patient knowledge. Data from this pilot have guided the development of a larger scale randomized clinical trial to improve decision quality in men with prostate cancer being treated in community settings

    The scale of genetic differentiation in the Dunes Sagebrush-Lizard (Sceloporus arenicolus), an endemic habitat specialist

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    Abstract The Dunes Sagebrush-Lizard (Sceloporus arenicolus) is a North American species endemic to sandshinnery oak habitats of the Mescalero and Monahans sand dunes in eastern New Mexico and western Texas. This lizard is listed as Endangered in New Mexico and exhibits habitat specificity at several geographic scales. Dunes Sagebrush-Lizards are only found in topographically complex shinnery oak (Quercus havardii) dominated landscapes within their small geographic distribution and are not found in surrounding human-altered landscapes. Within suitable sand-shinnery oak habitat, individuals predominantly occupy non-vegetated sand dune blowouts and utilize blowouts with particular physical characteristics due to thermoregulatory, reproduction, and foraging requirements. Here, we examined historical and contemporary patterns of genetic differentiation with respect to the current distribution of suitable habitat at multiple spatial scales using mitochondrial DNA sequences and microsatellite data from individuals throughout the entire range. We found three genetic clusters of individuals generally concordant with geographic regions and low sequence divergence at mitochondrial loci suggesting a recent origin of these populations. We also found high levels of genetic structure at microsatellite loci among populations within each of these groups indicating restricted gene flow at intermediate scales. Despite high habitat specificity, we did not detect genetic structure among sand blowouts at finer spatial scales. Within each population, matrices comprised of both sand blowouts and vegetated shinnery oak patches are necessary for genetic connectivity, but the fine scale spatial arrangement of blowouts may not be as critical. We discuss our results with respect to the scale of landscape heterogeneity and habitat connectivity and consider the conservation implications for this threatened taxon

    Microvascular significance of TGF-β axis activation in COVID-19

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    As 2023 approaches, the COVID-19 pandemic has killed millions. While vaccines have been a crucial intervention, only a few effective medications exist for prevention and treatment of COVID-19 in breakthrough cases or in unvaccinated or immunocompromised patients. SARS-CoV-2 displays early and unusual features of micro-thrombosis and immune dysregulation that target endothelial beds of the lungs, skin, and other organs. Notably, anticoagulation improves outcomes in some COVID-19 patients. The protein transforming growth factor-beta (TGF-β1) has constitutive roles in maintaining a healthy microvasculature through its roles in regulating inflammation, clotting, and wound healing. However, after infection (including viral infection) TGF-β1 activation may augment coagulation, cause immune dysregulation, and direct a path toward tissue fibrosis. Dysregulation of TGF-β signaling in immune cells and its localization in areas of microvascular injury are now well-described in COVID-19, and such events may contribute to the acute respiratory distress syndrome and skin micro-thrombosis outcomes frequently seen in severe COVID-19. The high concentration of TGF-β in platelets and in other cells within microvascular thrombi, its ability to activate the clotting cascade and dysregulate immune pathways, and its pro-fibrotic properties all contribute to a unique milieu in the COVID-19 microvasculature. This unique environment allows for propagation of microvascular clotting and immune dysregulation. In this review we summarize the physiological functions of TGF-β and detail the evidence for its effects on the microvasculature in COVID-19. In addition, we explore the potential role of existing TGF-β inhibitors for the prevention and treatment of COVID-19 associated microvascular thrombosis and immune dysregulation

    The Environmental Conditions, Treatments, and Exposures Ontology (ECTO): connecting toxicology and exposure to human health and beyond.

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    BACKGROUND: Evaluating the impact of environmental exposures on organism health is a key goal of modern biomedicine and is critically important in an age of greater pollution and chemicals in our environment. Environmental health utilizes many different research methods and generates a variety of data types. However, to date, no comprehensive database represents the full spectrum of environmental health data. Due to a lack of interoperability between databases, tools for integrating these resources are needed. In this manuscript we present the Environmental Conditions, Treatments, and Exposures Ontology (ECTO), a species-agnostic ontology focused on exposure events that occur as a result of natural and experimental processes, such as diet, work, or research activities. ECTO is intended for use in harmonizing environmental health data resources to support cross-study integration and inference for mechanism discovery. METHODS AND FINDINGS: ECTO is an ontology designed for describing organismal exposures such as toxicological research, environmental variables, dietary features, and patient-reported data from surveys. ECTO utilizes the base model established within the Exposure Ontology (ExO). ECTO is developed using a combination of manual curation and Dead Simple OWL Design Patterns (DOSDP), and contains over 2700 environmental exposure terms, and incorporates chemical and environmental ontologies. ECTO is an Open Biological and Biomedical Ontology (OBO) Foundry ontology that is designed for interoperability, reuse, and axiomatization with other ontologies. ECTO terms have been utilized in axioms within the Mondo Disease Ontology to represent diseases caused or influenced by environmental factors, as well as for survey encoding for the Personalized Environment and Genes Study (PEGS). CONCLUSIONS: We constructed ECTO to meet Open Biological and Biomedical Ontology (OBO) Foundry principles to increase translation opportunities between environmental health and other areas of biology. ECTO has a growing community of contributors consisting of toxicologists, public health epidemiologists, and health care providers to provide the necessary expertise for areas that have been identified previously as gaps

    AbGRI4, a novel antibiotic resistance island in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates.

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    OBJECTIVES: To investigate the genomic context of a novel resistance island (RI) in multiply antibiotic-resistant Acinetobacter baumannii clinical isolates and global isolates. METHODS: Using a combination of long and short reads generated from the Oxford Nanopore and Illumina platforms, contiguous chromosomes and plasmid sequences were determined. BLAST-based analysis was used to identify the RI insertion target. RESULTS: Genomes of four multiply antibiotic-resistant A. baumannii clinical strains, from a US hospital system, belonging to prevalent MLST ST2 (Pasteur scheme) and ST281 (Oxford scheme) clade F isolates were sequenced to completion. A class 1 integron carrying aadB (tobramycin resistance) and aadA2 (streptomycin/spectinomycin resistance) was identified. The class 1 integron was 6.8 kb, bounded by IS26 at both ends, and embedded in a new target location between an α/β-hydrolase and a reductase. Due to its novel insertion site and unique RI composition, we suggest naming this novel RI AbGRI4. Molecular analysis of global A. baumannii isolates identified multiple AbGRI4 RI variants in non-ST2 clonal lineages, including variations in the resistance gene cassettes, integron backbone and insertion breakpoints at the hydrolase gene. CONCLUSIONS: A novel RI insertion target harbouring a class 1 integron was identified in a subgroup of ST2/ST281 clinical isolates. Variants of the RI suggested evolution and horizontal transfer of the RI across clonal lineages. Long- and short-read hybrid assembly technology completely resolved the genomic context of IS-bounded RIs, which was not possible using short reads alone

    Unusual presentation of cactus spines in the flank of an elderly man: a case report

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    <p>Abstract</p> <p>Introduction</p> <p>Splinters and spines of plant matter are common foreign bodies in skin wounds of the extremities, and often present embedded in the dermis or subcutaneous tissue. Vegetative foreign bodies are highly inflammatory and, if not completely removed, can cause infection, toxic reactions, or granuloma formation. Older patients are at increased risk for infection from untreated plant foreign bodies. The most common error in plant splinter and spine management is failure to detect their presence.</p> <p>Case presentation</p> <p>Here we report a case of cactus spines in an 84-year-old Caucasian man presenting on the right flank as multiple, red papules with spiny extensions. This presentation was unusual both in location and the spinous character of the lesions, and only after punch biopsy analysis was a diagnosis of cactus matter spines made.</p> <p>Conclusions</p> <p>Our patient presented with an unusual case of cactus spines that required histopathology for identification. Skin lesions with neglected foreign bodies are a common cause of malpractice claims. If not removed, foreign bodies of the skin, particularly in elderly individuals, can result in inflammatory and infectious sequela. This report underscores the importance of thoroughly evaluating penetrating skin lesions for the presence of foreign bodies, such as splinters and spines.</p

    Monitoring Prevalence, Treatment, and Control Of Metabolic Conditions In New York City Adults Using 2013 Primary Care Electronic Health Records: A Surveillance Validation Study

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    Introduction: Electronic health records (EHRs) can potentially extend chronic disease surveillance, but few EHR-based initiatives tracking population-based metrics have been validated for accuracy. We designed a new EHR-based population health surveillance system for New York City (NYC) known as NYC Macroscope. This report is the third in a 3-part series describing the development and validation of that system. The first report describes governance and technical infrastructure underlying the NYC Macroscope. The second report describes validation methods and presents validation results for estimates of obesity, smoking, depression and influenza vaccination. In this third paper we present validation findings for metabolic indicators (hypertension, hyperlipidemia, diabetes). Methods:We compared EHR-based estimates to those from a gold standard surveillance source – the 2013-2014 NYC Health and Nutrition Examination Survey (NYC HANES) – overall and stratified by sex and age group, using the two one-sided test of equivalence and other validation criteria. Results: EHR-based hypertension prevalence estimates were highly concordant with NYC HANES estimates. Diabetes prevalence estimates were highly concordant when measuring diagnosed diabetes but less so when incorporating laboratory results. Hypercholesterolemia prevalence estimates were less concordant overall. Measures to assess treatment and control of the 3 metabolic conditions performed poorly. Discussion:While indicator performance was variable, findings here confirm that a carefully constructed EHR-based surveillance system can generate prevalence estimates comparable to those from gold-standard examination surveys for certain metabolic conditions such as hypertension and diabetes. Conclusions: Standardized EHR metrics have potential utility for surveillance at lower annual costs than surveys, especially as representativeness of contributing clinical practices to EHR-based surveillance systems increases

    Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies

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    A lack of prospective studies has been a major barrier for assessing the role of the microbiome in human health and disease on a population-wide scale. To address this significant knowledge gap, we have launched a large-scale collection targeting fecal and oral microbiome specimens from 20,000 women within the Nurses’ Health Study II cohort (the Microbiome Among Nurses study, or Micro-N). Leveraging the rich epidemiologic data that have been repeatedly collected from this cohort since 1989; the established biorepository of archived blood, urine, buccal cell, and tumor tissue specimens; the available genetic and biomarker data; the cohort’s ongoing follow-up; and the BIOM-Mass microbiome research platform, Micro-N furnishes unparalleled resources for future prospective studies to interrogate the interplay between host, environmental factors, and the microbiome in human health. These prospectively collected materials will provide much-needed evidence to infer causality in microbiome-associated outcomes, paving the way toward development of microbiota-targeted modulators, preventives, diagnostics and therapeutics. Here, we describe a generalizable, scalable and cost-effective platform used for stool and oral microbiome specimen and metadata collection in the Micro-N study as an example of how prospective studies of the microbiome may be carried out
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