Background: Chronic obstructive pulmonary disease (COPD) is highly prevalent among nursing home residents; however, few studies have focused on the psychological impact of this clinically significant condition on nursing home residents. Objective: We examine the prevalence of, and factors associated with, anxiety and depression in nursing home residents with COPD. Methods: Using the US 2018 Minimum Dataset (MDS), we conducted a cross-sectional study among 239,615 residents aged ≥50 years old in US Medicare/Medicaid certified nursing homes with COPD. Anxiety and depression were diagnosed based on clinical diagnoses, physical examination findings, and treatment orders. Multivariable adjusted Poisson models with a generalized estimating equations approach account for the clustering among residents within nursing homes. Results: The average age of the study population was 79 years (SD: 10.6), 62.0% were women, and 43.7% had five or more comorbid conditions. In this population, 37.2% had anxiety, 57.6% had depression, and 27.5% had both mental health conditions. Women, current tobacco users, persons 50-64 years old, those who reported having moderate or severe pain, and nursing home residents with multimorbidity were more likely to have anxiety or depression than respective comparison groups. Conclusion: Anxiety and depression are common among US nursing home residents with COPD. Women, medically complex patients, and those who report having moderate-to-severe pain appear to be more likely to have anxiety and depression. Clinical teams should be aware of these findings when managing nursing home residents with COPD and use various nonpharmacological and medical interventions for the effective management of anxiety and depression. Longitudinal studies evaluating how anxiety and depression affect the management of COPD and related outcomes, and how best to improve the quality of life of nursing home residents with COPD, are warranted.

The worldwide decline in malaria incidence is revealing the extensive burden of non-malarial febrile illness (NMFI), which remains poorly understood and difficult to diagnose. To characterize NMFI in Senegal, we collected venous blood and clinical metadata from febrile patients and healthy controls in a low malaria burden area. Using 16S and unbiased sequencing, we detected viral, bacterial, or eukaryotic pathogens in 29% of NMFI cases. Bacteria were the most common, with relapsing fever Borrelia and spotted fever Rickettsia found in 15% and 3.7% of cases, respectively. Four viral pathogens were found in a total of 7 febrile cases (3.5%). Sequencing also detected undiagnosed Plasmodium, including one putative P. ovale infection. We developed a logistic regression model to distinguish Borrelia from NMFIs with similar presentation based on symptoms and vital signs. These results highlight the challenge and importance of improved diagnostics, especially for Borrelia, to support diagnosis and surveillance.

Relapse remains a major barrier to the successful treatment of children with T-cell acute lymphoblastic leukemia (T-ALL) and may represent a failure to eliminate leukemia-initiating cells (L-ICs) that possess distinguishing biological features from the bulk leukemic population. TAL1 and LMO2 are often coordinately misexpressed in T-ALL patients and their ectopic expression cooperates to transform thymic progenitors in mice. In this model, double negative-3 (DN3) stage thymic progenitors harbor L-ICs, yet only a subset of DN3 leukemic cells have L-IC activity. We interrogated L-IC heterogeneity in our Tal1/Lmo2 mouse T-ALL model using a combination of single cell RNA-sequencing (scRNA-seq) and H2B-GFP nucleosome labeling. We identified a cell cycle restricted DN3 subpopulation with high Notch1 activity and enrichment of Tal1/Lmo2 targets and T-cell quiescence genes. This dormant DN3 population significantly increased during leukemogenesis, exhibited chemotolerance and was enriched for genes associated with patient minimal residual disease (MRD). In vivo studies using the Tet-inducible H2B-GFP model revealed that Tal1 and Lmo2 cooperate to promote quiescence in DN3 cells. Examination of TAL1/LMO patient samples revealed that the L-IC enriched CD7+CD1a- thymic progenitors (hL-IC) were also chemotolerant and were also variably associated with quiescence. Collectively, our results document the emergence of dormant and chemotolerant L-ICs during Tal1/Lmo2-induced leukemogenesis in mice and relapsed T-ALL patients.

Translational control of maternal mRNAs is a major form of gene regulation during germline development and embryogenesis. C. elegans Notch homolog glp-1 maternal gene is necessary for germ cell proliferation, and embryonic fate determination. The RNA binding proteins POS-1 and GLD-1 directly regulate the translation of GLP-1 protein by binding to the specific elements within the glp-1 3’ UTR. When POS-1 or GLD-1 binding is disrupted by mutation of their respective elements, the expression pattern of a glp-1 3’ UTR reporter transgene changes in both the germline and in embryos. The mechanism by which POS-1 and GLD-1 mediate translation repression is not well understood. Previous work showed that loss of pos-1 increases the average polyA tail length of endogenous glp-1 transcripts in embryos. In this dissertation, we show that mutation of either the GLD-1 or POS-1 binding motifs in transgenic reporters does not change polyA site selection. This result rules out alternative polyA site selection as a mechanism of regulation. We also show that wild-type glp-1 transgenic reporter embryos have a shorter average polyA tail length compared to transgenic reporters with mutated GLD-1 or POS-1 binding motifs. We have studied the effect of cytoplasmic polymerases, deadenylases and translation initiation factors on our transgenic reporters. Our RNAi experiments show that two cytoplasmic polyA polymerases, GLD-2 and GLD-4, have strikingly different effects on the expression of reporter transgenes harboring GLD-1 or POS-1 binding motif mutations. By contrast, none of the deadenylases affect the transgenic reporter expression. We also observed strong derepression of all reporters upon reduction of the translation initiation factor ife-3. The results reveal that POS-1 and GLD-1 exert their repressive effects in different ways through cytoplasmic polyA polymerase activity, while IFE-3 mediated translation repression is independent of both POS-1 and GLD-1. Lastly, we have examined the biological significance of glp-1 3’UTR to the worm reproduction by using CRISPR/Cas9 mutagenesis to generate glp-1 3’UTR mutations in the endogenous locus. Characterization of a 71 base pair mutation that deletes the GLD-1 and POS-1 binding sites in the glp-1 3’UTR reveals a 2-fold reduction in the number of embryos produced and a 4-fold reduction in the hatch rate. Imaging results show that the mutant embryos appear to have patterning defects. Together, our results show that the glp-1 3’UTR contributes to reproductive health but is not essential to fertility.

PURPOSE: To describe the pre-licensure nursing educational experience of integration and inclusion among RNs with a physical disability during their education. SPECIFIC AIMS: 1) Describe the access RNs with a physical disability had to academic and social opportunities during their prelicensure education program that contributed to academic and social integration (inclusion). 2). Explore perceptions of RNs with a physical disability regarding inclusion and acceptance of their disability as a valued component of student diversity during their prelicensure education program. 3). Describe the contextual factors and key aspects of connection during the pre-licensure educational experiences of RNs who had a physical disability as positive (Disability-Diversity Connect) or negative and disintegrated (Disability-Diversity Disconnect). FRAMEWORK: This study was guided by The Disability-Diversity Disconnect (DDDM) by Aquino (2016). DESIGN: This study design used was qualitative description. It included semi-structured interviews using an interview guide based on the DDDM. RESULTS: 16 individuals with 14 different physical disabilities participated in this study. During data analysis four themes emerged: I Saved My Energy for Learning, Determination, Wanting to Find My People and Secrets, Living a Double Life which has a subtheme, Fear of Judgement. CONCLUSION: : Identification of factors related to inclusion within the academic environment provides insight for future work to examine the needs of prelicensure nursing students with physical disabilities and the potential to improve their future educational experiences.

Background: Intrasaccular flow-disrupting devices are a safe and effective treatment strategy for intracranial aneurysms. We utilized high-frequency optical coherence tomography (HF-OCT) and digital subtraction angiography (DSA) to evaluate SEAL Arc, a new intrasaccular device, and compare the findings with the well-established Woven EndoBridge (WEB) device in an animal model of saccular aneurysms. Methods: In a rabbit model, elastase-induced aneurysms were treated with SEAL Arc (n=11) devices. HF-OCT and DSA were performed after implant and repeated after 12 weeks. Device protrusion and malapposition were assessed at implant time and scored on a binary system. Aneurysm occlusion was assessed at 12 weeks with the WEB Occlusion Scale and dichotomized to complete (A and B) or incomplete (C and D) occlusion. The percentage of neointimal coverage after 12 weeks was quantified using HF-OCT. We compared these data to previously published historical controls treated with the gold-standard WEB device (n=24) in the same model. Results: Aneurysm size and device placement were not significantly different between the two groups. Complete occlusion was demonstrated in 80% of the SEAL Arc devices, which compared favorably to the 21% of the aneurysms treated with WEB devices (P=0.002). Neointimal coverage across SEAL Arc devices was 86±15% compared with 49±27% for WEB (P=0.001). Protruding devices had significantly less neointimal coverage (P<0.001) as did incompletely occluded aneurysms (P<0.001). Histologically, all aneurysms treated with SEAL Arc devices were completely healed. Conclusion: Complete early aneurysm occlusion was frequently observed in the SEAL Arc treated aneurysms, with significant neointimal coverage after 12 weeks.

Chimeric antigen receptor-T (CAR-T) therapies represent a major breakthrough in cancer medicine, given the ex vivo-based technology that harnesses the power of one's own immune system. These therapeutics have demonstrated remarkable success for relapsed/refractory B-cell lymphomas. Although more than a decade has passed since the initial introduction of CAR-T therapeutics for patients with leukaemia and lymphoma, there is still significant debate as to where CAR-T therapeutics fit into the management paradigm, as consensus guidelines are limited. Competing interventions deployed in subsequent lines of therapy for aggressive lymphoma include novel targeted agents, bispecific antibodies, and time-honoured stem cell transplant. In this focused review, we discuss the major obstacles to advancing the therapeutic reach for CAR-T products in early lines of therapy. Such barriers include antigen escape, "cold" tumour microenvironments, host inflammation and CAR-T cell exhaustion. We highlight solutions including point-of-care CAR-T manufacturing and early T lymphopheresis. We review the evidence basis for early CAR-T deployment for B-cell lymphomas in light of the recent Food and Drug Administration (FDA) approval of three first-in-class anti-CD3/CD20 bispecific antibodies-mosunetuzumab, epcoritamab and glofitamab. We propose practical recommendations for 2024.

Mainstays of opioid overdose prevention include medications for opioid use disorder (e.g., methadone or buprenorphine) and naloxone distribution. Inadequate access to buprenorphine limits its uptake, especially in communities of color, and people with opioid use disorders encounter multiple barriers to obtaining necessary medications including insurance, transportation, and consistent availability of telephones. UMass Memorial Medical Center and our community partners sought to alleviate these barriers to treatment through the deployment of a mobile addiction service, called the Road to Care. Using this approach, multidisciplinary and interprofessional providers deliver holistic addiction care by centering our patients' needs with respect to scheduling, location, and convenience. This program also extends access to buprenorphine and naloxone among people experiencing homelessness. Additional systemic and individualized barriers encountered are identified, as well as potential solutions for future mobile addiction service utilization. Over a two-year period, we have cared for 1,121 individuals who have accessed our mobile addiction service in over 4,567 encounters. We prescribed buprenorphine/naloxone (Suboxone®) to 330 individuals (29.4% of all patients). We have distributed nearly 250 naloxone kits directly on-site or and more than 300 kits via prescriptions to local pharmacies. To date, 74 naloxone rescue attempts have been reported back to us. We have demonstrated that a community-based mobile addiction service, anchored within a major medical center, can provide high-volume and high-quality overdose prevention services that facilitate engagement with additional treatment. Our experience is described as a case study below.

Allergic contact dermatitis is one of the most common inflammatory skin diseases, yet identification of environmental triggers can be challenging, and treatment options are limited for patients with frequent exposures. The chemical patch test has been used for over a century to diagnose patient-specific allergen sensitivities; however, limited test sensitivity and subjective interpretability motivates the use of modern scientific tools to improve the patch test diagnostic process. Additionally complicating diagnosis, chemical patch application can cause skin inflammation through both allergic sensitivity as well as nonspecific irritation. To discover allergy-specific biomarkers, I induced both irritant and allergic contact dermatitis in human volunteers, sampled skin lesions by non-scarring methods, and quantified transcriptomic and proteomic changes. Using single cell RNA sequencing together with a newly adapted method for ligand-receptor cell signaling estimation, I identified allergy-specific, irritant-specific, and allergy/irritant-shared cell responses of estimated disease significance. Quantification of inflammatory proteins within skin interstitial fluid also identified several biomarkers that were capable of distinguishing allergic from irritant contact dermatitis with 100% specificity and over 80% sensitivity.

Developmental venous anomalies (DVAs) are characterized by many radially oriented medullary veins surrounding a central draining vessel. When the imaging plane is perpendicular to the central vessel, these medullary veins resemble Medusa's head of snakes. Medusa's head sign, or caput medusae, can be appreciated on contrast enhanced CT scans and MRIs of the brain and is highly indicative of a DVA.