27941 research outputs found
Sort by
Review of studies that examine the role of advanced practice registered nurses and physician associates in mass shooting incidents
No full textBACKGROUND: A mass shooting incident (MSI) occurs where four or more people are shot and injured or killed. Mass shooting incidents have increased in frequency since the 1960s with 2,700 injured and 600 individuals killed in 2022. Advanced Practice Registered Nurses (APRNs) and Physician Associates (PAs) are front-line caregivers, who may engage with victims, their families, perpetrators, and potential perpetrators. Advanced Practice Registered Nurses and PAs provide care to these people across care settings.
OBJECTIVE: Identify the pertinent literature describing the roles, responsibilities, and skills that APRNs and PAs must possess surrounding MSIs.
DATA SOURCE: An integrative review was completed using Covidence. Search engines included Ovid Medline, Ovid Emcare, PsycInfo (Ovid), CINAHL (EBSCO), Scopus (Elsevier), and Cochrane Central Register of Controlled Trials (Wiley). Two team members independently reviewed each citation, and a third member resolved conflicts.
CONCLUSIONS: Eleven studies met inclusion criteria. Four phases of the Federal Emergency Management Agency framework (Prevention, Preparedness, Response, Recovery) were represented, and, in some studies, more than one phase was discussed. The review showed strong support for APRN and PA roles in prevention and preparedness of an MSI, and less support surrounding the response and recovery phases of an MSI. Additional research is needed to further define the distinct role that APRNs and PAs can have encompassing MSIs.
IMPLICATIONS FOR PRACTICE: Advanced Practice Registered Nurses and PAs possess the skills to intervene in prevention, preparedness, response, and recovery surrounding an MSI. Although some evidence exists to define the role APRNs and PAs can assume, the focus was primarily on prevention with screening for access to firearms and safe storage.No embarg
A new framework for pulmonary nodules: how terminology impacts management
No full textThe Fleischner Society recently updated its Glossary of Terms of Thoracic Imaging, proposing a new approach in the assessment of pulmonary nodules. These updates include changes in terminology regarding the definition of nodule size, as well as inclusive terminology to provide a more flexible framework in the assessment of pulmonary nodule morphology. The broad categories "simple" and "complex" are introduced for more versatile characterization to encompass the wide nodule structure and morphology we see in clinical practice, beyond the classic trichotomy of solid, subsolid, and part-solid. Another key aspect in the assessment of pulmonary nodules includes longitudinal evaluation, a small part of which is growth, namely changes in nodule size. While there is a strong focus on changes in size, other features, such as changes in components, also play a key role in nodule assessment. These include transition in morphology and structure: from simple to complex, and complex to simple; in regard not only to the core of the nodule, but also to borders and contours. This paper examines how the updated terminology aligns with and impacts management within the current nodule management paradigms. KEY POINTS: Question The updated Fleischner Society Glossary of Terms introduces a new definition for nodule size and terminology regarding nodule morphology, and these features are tied to management. Findings Nodule size and morphology are important factors in characterizing and assessing the malignant potential of pulmonary nodules. Clinical relevance The increased threshold for nodule size aims to decrease the workup of small, likely benign nodules. New terminology on morphology allows more flexible characterization to address the broad range seen in clinical practice and offers an opportunity for incorporation in nodule management systems.No embarg
HSD17B13 Couples Hepatocellular Lipid Dysregulation to Stellate Cell Activation through a TGFβ-1–Dependent Mechanism
Full text linkMetabolic dysfunction–associated steatohepatitis (MASH) is a progressive liver disease characterized by hepatocellular lipid overload, inflammatory activation, and hepatic stellate cell (HSC)–mediated fibrogenesis. Human genetic studies have identified loss-of-function (LoF) variants in 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) that confer robust protection against advanced fibrosis and cirrhosis, establishing HSD17B13 as a critical modifier of MASH severity. However, the mechanisms linking HSD17B13 activity to fibrogenesis remain incompletely understood. Here, we demonstrate that both native and catalytically deficient HSD17B13 (mHSD) localize to lipid droplets (LDs) in human hepatocytes. Only catalytically active HSD17B13 enhances lipid storage and markedly upregulates the lipogenic transcriptional regulator carbohydrate-responsive element–binding protein (ChREBP). This HSD17B13–driven lipogenic program promotes activation of human LX2 stellate cells both in direct co-culture and upon exposure to hepatocyte-conditioned medium (CM). Screening of candidate signaling mediators revealed that transforming growth factor β-1 (TGFβ-1) is uniquely and robustly induced by HSD17B13 expression, whereas mHSD elicits minimal induction. Notably, siRNA-mediated TGFB1 knockdown or antibody neutralization of active TGFβ-1 effectively abrogates CM-induced LX2 activation and collagen synthesis. Collectively, these findings delineate an HSD17B13–TGFβ-1 signaling pathway that mechanistically couples hepatocellular lipid dysregulation to stellate cell-mediated fibrogenesis. This work reveals a dual metabolic and profibrotic role for HSD17B13 and underscores its therapeutic potential as a target for mitigating the transition from simple steatosis to steatohepatitis.Translational ScienceNo embarg
Investigating the Role of Apolipoprotein E and Neuroinflammatory Modulation in Alzheimer's Disease
No full textAlzheimer’s disease (AD) is the most prevalent neurodegenerative disease diagnosed today, characterized by significant cognitive decline with few disease-modifying options available. Molecular AD pathology consists of extracellular amyloid plaques subsequently followed by intracellular neurofibrillary tau tangles, both of which lead to substantial inflammation and degeneration. The gene encoding apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor of AD, known to seed amyloid plaques. Previous work has demonstrated that mouse Apoe-targeting siRNA induces a hyperinflammatory signature in 5xFAD mice, an AD model recapitulating human amyloid burden. This work uses therapeutically-relevant siRNA technology to probe the dual role of ApoE and neuroinflammation by targeting both Apoe and Jak1, a master regulator of interferon signaling relevant to destructive AD neuroinflammation. Although inflammatory signaling, primarily by microglia, plays an important role in clearing AD pathology, overactive inflammatory signaling is detrimental to the brain, leading to worsening degeneration. Therefore, we hypothesized that Jak1 modulation would reduce hyperactive inflammation while Apoe modulation would improve amyloid clearance. 5xFAD mice were treated with a single injection of Apoe and Jak1-targeting siRNAs over two months to evaluate molecular markers and amyloid pathology. Amyloid burden was significantly reduced in both Apoe and dual-targeting Apoe+Jak1 groups, demonstrating that JAK1 signaling is not required for microglial-mediated plaque clearance. This provides a proof-of-concept for further investigation of dual-targeting Apoe and Jak1 as a disease-modifying treatment option.MD/PhD2 years2028-01-1
Multi-omic Longitudinal Analysis of Canine Osteosarcoma Identifies Inter-Patient Heterogeneity and Immune Enrichment in Metastatic Lesions [preprint]
Full text linkThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Osteosarcoma (OS) exhibits substantial genomic complexity and inter-patient heterogeneity, necessitating longitudinal, patient-matched analyses to understand acquired features of tumor evolution. However, most published OS data is limited to primary tumor samples, limiting insight into patient-specific resistance mechanisms. To address this, we characterized the genomic landscape of paired primary and metastatic tumor samples from dogs with spontaneous OS. Whole-genome and single-cell RNA sequencing reveal mutation and gene expression profiles that are predominantly organized by patient identity. Mutational burden and pathway alterations such as those involving PI3K, NOTCH, TP53, MAPK, RAS and epigenetic regulation differ between primary and metastatic samples. Variants present in tumor tissue are readily detectable in paired cfDNA samples, demonstrating the utility of this assay for identifying tumor-specific alterations associated with treatment resistance. Analysis of bulk RNA-seq data to estimate cell-type composition shows greater immune cell representation in metastases, underscoring the importance of immune signaling pathways in OS. These findings exemplify the presence of patient-specific alterations in genomic architecture over the course of tumor progression, linking CNV amplification, pathway reprogramming, and immune evasion in metastatic OS.No embarg
Relationship between substance use and socio-behavioral drivers of poor ART adherence among young people with HIV in Zambia
No full textDespite improved access to antiretroviral therapy (ART) in Zambia, adherence among young people with HIV (YPHIV) remains suboptimal, compromising treatment effectiveness. YPHIV face unique developmental and socio-behavioral challenges including HIV-related stigma, depression and substance use, which further undermine consistent ART adherence. Alcohol and drug use impair cognitive and emotional functioning, increasing the likelihood of disrupted medication routines. This study applied the Hierarchical Model of Medication Adherence (HMMA) to examine how individual, social and structural factors influence ART adherence among YPHIV in Zambia. A qualitative descriptive design was employed using six focus group discussions (FGDs) with 48 purposively selected participants aged 18-24 years, all reporting <80% adherence and recent substance use. Data were audio-recorded, transcribed verbatim and thematically analyzed. HIV-related stigma, mental health distress and negative healthcare experiences were key drivers of substance use. Substance use impaired adherence by causing forgetfulness and other factors. Depression and emotional exhaustion also emerged as major contributors to substance use and poor adherence. The study offers novel, context-specific insights into the multilevel drivers of poor adherence among Zambian youth aged 18-24. Findings highlight the need for youth-centred interventions that address stigma, mental health and substance use to improve ART adherence and health outcomes.No embarg
Association of vaginal IL-4, IL-6, IL-8, IL-17, IFN-γ, and dietary intake with IBD status and vaginal microbiota in pregnant individuals
Full text linkBACKGROUND: Pregnant individuals with inflammatory bowel diseases (IBD) exhibit gut inflammation and dysbiosis; however, there is limited knowledge about their vaginal environment. This is important as vaginal inflammation and high vaginal microbiota diversity are associated with adverse pregnancy outcomes.
OBJECTIVES: We aimed to compare vaginal inflammatory markers and microbiota diversity of pregnant individuals with and without IBD in their third trimester of pregnancy and determine the role of diet in the vaginal microbiota diversity.
METHODS: We recruited pregnant individuals who provided vaginal swabs at 27-29 weeks of pregnancy. We characterized the vaginal microbiota by sequencing the V3-V4 region of the 16S rRNA and surveyed nine key pro and anti-inflammatory cytokines by qRT-PCR from the vaginal mucosa. Participants completed three validated interviewer-led nutrition assessments of 24-hour dietary intake around the same time as the collection of vaginal samples. The nutritional assessments were used to estimate dietary quality using the validated Healthy Eating Index (HEI-2015).
RESULTS: The cohort included 23 pregnant individuals with IBD (18 with Crohn's disease and 5 with ulcerative colitis) and 25 healthy controls (HC); 56.5% of the IBD cases were in remission. Vaginal microbiota diversity and composition did not differ significantly between individuals with IBD and HC. However, the vaginal mucosa of the IBD individuals showed increased expression of Th17 pro-inflammatory cytokines (i.e., IL-6, IL-8, IL-17) and decreased expression of Th1 (IFN-γ) and Th2 (IL-4) compared to HC. Expression of IL-6 and TNF- α correlated positively with vaginal microbial diversity. The beneficial Lactobacillus crispatus dominated the vaginal microbiota of individuals with either high dietary quality or those consuming more vegetables or low added sugar, regardless of IBD status. In IBD cases, consumption of vegetables and added sugars were associated with reduced expression of the pro-inflammatory IFN-γ and an increased expression of anti-inflammatory IL-4.
CONCLUSION: The vaginal microbiome did not differ between individuals with IBD and HC; however, IBD cases exhibit a pro-inflammatory tone in the vagina (high IL-6) that is associated with higher vaginal microbial diversity. Regardless of IBD status, healthier diets are positively associated with an increased abundance of the beneficial L. crispatus in the vagina.No embarg
A data-driven respiratory motion correction for pediatric DMSA renal SPECT imaging: A simulation study
No full textBACKGROUND: Technetium-99 m-dimercaptosuccinic acid (DMSA) renal cortical scintigraphy is commonly used in the evaluation of children with urinary tract infections. Pyelonephritis and post-pyelonephritic scarring manifest as renal cortical defects on DMSA renal scintigraphy, including DMSA Single Photon Emission Computed Tomography (SPECT) imaging. SPECT image quality can be degraded by blurring related to respiratory motion. Thus we hypothesize that image quality will be improved with estimation and correction of respiratory motion.
PURPOSE: The purpose of this study is to develop and evaluate a data-driven methodology that estimates surrogate respiratory signals and then employs these surrogate signals in correction of respiratory-motion in pediatric DMSA renal SPECT imaging.
METHODS: The XCAT digital anthropomorphic phantom was used with SPECT Monte Carlo simulation to form a population of 100 ms projections of DMSA renal SPECT imaging acquired with clinically relevant count-levels. These 100 ms projections emulated the framing of list-mode acquisitions at Boston Children's Hospital (BCH). The axial (superior/inferior) center-of-count-mass (aCOM) approach was utilized to estimate a surrogate respiratory signal for combining the 100 ms projections into seven respiratory-motion states with each having different extents of motion. The motion-states were then reconstructed and rigid-body respiratory-motion of the kidneys between the three motion-states on either side of the center state versus the center state was estimated by rigid-body registration. This estimated motion was then used to correct respiratory motion as part of a second pass through reconstruction of the projections of the motion states. To evaluate the surrogate signal, Pearson's correlation coefficient was calculated between the true respiratory signals used in creating the XCAT projection data and the surrogate respiratory signals. The respiratory motion corrected reconstructions and the images reconstructed without respiratory motion compensation were quantitatively compared to the ground truth images (where no respiratory motion was simulated) using the Normalized Root Mean Square Error (NRMSE) as a measure of fidelity.
RESULTS: The average over our entire population of XCAT phantoms of Pearson's correlation coefficient (r) between the aCOM estimated surrogate respiratory and the actual average motion simulated for each of the 100 ms time intervals was 0.76. The average standard error of the estimate (SEE) for this r-value was 3.06 mm. For the group of XCAT phantoms with a simulated average amplitude of motion between 6-10 mm, there were no significant differences in the NRMSE versus ground truth reconstructions for the reconstructions with either the estimated or true motion correction methods compared against reconstructions without motion correction. For the groups with simulated average amplitudes of motion between 10-14 mm, 14-18 mm, and >18 mm, there were significant differences in the NRMSE for the reconstructions with motion with either the estimated and true motion correction applied in comparison to reconstructions without motion correction.
CONCLUSION: Respiratory motion correction in pediatric renal SPECT imaging using a data-driven approach can improve image quality, with potential for improved diagnostic accuracy for studies with a moderate amount of motion.No embarg
Lessons in IR: Management of Radial Artery Pseudoaneurysm with Extended Hemostatic Band Compression
No full textNo embarg
Expanding Access to Care: Qualitative Insights from a Nationwide Home-Based Test-to-Treat Program for COVID-19 and Influenza [preprint]
No full textThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.The COVID-19 pandemic and subsequent influenza outbreaks highlighted disparities in timely access to tests and treatments. To address this gap, a nationwide Home Test to Treat (HTTT) program was launched to provide home test kits, telehealth consultations, and medication delivery for COVID-19 and influenza. This study explored participant experiences, factors influencing satisfaction levels, and recommendations for future programs. Methods In-depth interviews were conducted with 48 participants enrolled in the HTTT program. Purposive sampling was used to obtain experiences from diverse backgrounds. Content analysis was used to extract the final coding scheme. Results Interviewees reported a range of experiences, from positive to negative. Many of them were satisfied with efficient communication with telehealth providers, timely and convenient access to resources, and a seamless transition from enrollment to prescription. However, some interviewees noted limited interactions with telehealth providers, delayed access to treatment and cost challenges, and navigation and coordination challenges. For a future home-based Teat to Treat program, interviewees recommended improving inclusivity, offering more comprehensive consultation, enhancing user-friendliness, and increasing awareness through diverse platforms Discussion This study highlights a home-based Test to Treat program as a feasible way to improve access to COVID-19 and influenza care. Enhancing interactions with providers, comprehensive care, and support for marginalized populations may further expand the program and reduce disparities in access to tests and treatments.No embarg