A therapy for suppressing canonical and noncanonical SARS-CoV-2 viral entry and an intrinsic intrapulmonary inflammatory response.

The prevalence of "long COVID" is just one of the conundrums highlighting how little we know about the lung's response to viral infection, particularly to syndromecoronavirus-2 (SARS-CoV-2), for which the lung is the point of entry. We used an in vitro human lung system to enable a prospective, unbiased, sequential single-cell level analysis of pulmonary cell responses to infection by multiple SARS-CoV-2 strains. Starting with human induced pluripotent stem cells and emulating lung organogenesis, we generated and infected three-dimensional, multi-cell-type-containing lung organoids (LOs) and gained several unexpected insights. First, SARS-CoV-2 tropism is much broader than previously believed: Many lung cell types are infectable, if not through a canonical receptor-mediated route (e.g., via Angiotensin-converting encyme 2(ACE2)) then via a noncanonical "backdoor" route (via macropinocytosis, a form of endocytosis). Food and Drug Administration (FDA)-approved endocytosis blockers can abrogate such entry, suggesting adjunctive therapies. Regardless of the route of entry, the virus triggers a lung-autonomous, pulmonary epithelial cell-intrinsic, innate immune response involving interferons and cytokine/chemokine production in the absence of hematopoietic derivatives. The virus can spread rapidly throughout human LOs resulting in mitochondrial apoptosis mediated by the prosurvival protein Bcl-xL. This host cytopathic response to the virus may help explain persistent inflammatory signatures in a dysfunctional pulmonary environment of long COVID. The host response to the virus is, in significant part, dependent on pulmonary Surfactant Protein-B, which plays an unanticipated role in signal transduction, viral resistance, dampening of systemic inflammatory cytokine production, and minimizing apoptosis. Exogenous surfactant, in fact, can be broadly therapeutic.

Comparative speed of kill provided by lotilaner (Credelio™), sarolaner (Simparica Trio™), and afoxolaner (NexGard™) to control Amblyomma americanum infestations on dogs.

BACKGROUND: Canine acaricides with rapid onset and sustained activity can reduce pathogen transmission risk and enhance pet owner experience. This randomized, complete block design, investigator-masked study compared the speed of kill of Amblyomma americanum provided by three monthly-use isoxazoline-containing products. METHODS: Eight randomized beagles per group were treated (day 0), per label, with sarolaner (combined with moxidectin and pyrantel, Simparica Trio™), afoxolaner (NexGard™), or lotilaner (Credelio™), or remained untreated. Infestations with 50 adult A. americanum were conducted on days - 7, - 2, 21, and 28, and tick counts were performed on day - 5 (for blocking), and at 4, 8, 12, 24, 48, and 72 h following treatment and subsequent infestations. Efficacy calculations were based on geometric mean live tick counts. A linear mixed model was used for between-group comparisons. RESULTS: On day 0, only lotilaner significantly reduced an A. americanum infestation by 12 h (43.3%; P = 0.002). Efficacy of lotilaner and afoxolaner at 24 h post-treatment was 95.3% and 97.6%, respectively, both significantly different from sarolaner (74%) (P = 0.002, P < 0.001, respectively). On day 21, at 12 h postinfestation, lotilaner efficacy (59.6%) was significantly different from sarolaner (0.0%) (P < 0.001) and afoxolaner (6.3%) (P < 0.001). At 24 h, lotilaner efficacy (97.4%) was significantly different (P < 0.001) from sarolaner and afoxolaner (13.6% and 14.9%, respectively). On day 28, at 12 h postinfestation, lotilaner efficacy (47.8%) was significantly different from sarolaner (17.1%) (P = 0.020) and afoxolaner (9.0%) (P = 0.006). At 24 h, lotilaner efficacy (92.3%) was significantly different from sarolaner 4.9% (P < 0.001) and afoxolaner (0.0%) (P < 0.001). Speed of kill for sarolaner and afoxolaner, but not lotilaner, significantly declined over the study period. Following reinfestation on day 28, neither sarolaner nor afoxolaner reached 90% efficacy by 48 h. By 72 h, sarolaner efficacy was 97.4% and afoxolaner efficacy was 86.3%. Only lotilaner achieved ≥ 90% efficacy by 24 h post-treatment and 24 h postinfestation on days 21 and 28. Time to ≥ 90% efficacy following new infestations consistently occurred 24-48 h earlier for lotilaner compared with sarolaner or afoxolaner. CONCLUSIONS: Credelio (lotilaner) has a more rapid onset of acaricidal activity against A. americanum than Simparica Trio (sarolaner-moxidectin-pyrantel) and NexGard (afoxolaner). Only lotilaner's speed of tick kill is sustained throughout the dosing period.

A large-scale assessment of eastern whip-poor-will (Antrostomus vociferus) occupancy across a gradient of forest management intensity using autonomous recording units.

Conservationists spend considerable resources to create and enhance wildlife habitat. Monitoring how species respond to these efforts helps managers allocate limited resources. However, monitoring efforts often encounter logistical challenges that are exacerbated as geographic extent increases. We used autonomous recording units (ARUs) and automated acoustic classification to mitigate the challenges of assessing Eastern Whip-poor-will (Antrostomus vociferus) response to forest management across the eastern USA. We deployed 1263 ARUs in forests with varying degrees of management intensity. Recordings were processed using an automated classifier and the resulting detection data were used to assess occupancy. Whip-poor-wills were detected at 401 survey locations. Across our study region, whip-poor-will occupancy decreased with latitude and elevation. At the landscape scale, occupancy decreased with the amount of impervious cover, increased with herbaceous cover and oak and evergreen forests, and exhibited a quadratic relationship with the amount of shrub-scrub cover. At the site-level, occupancy was negatively associated with basal area and brambles (Rubus spp.) and exhibited a quadratic relationship with woody stem density. Implementation of practices that create and sustain a mosaic of forest age classes and a diverse range of canopy closure within oak (Quercus spp.) dominated landscapes will have the highest probability of hosting whip-poor-wills. The use of ARUs and a machine learning classifier helped overcome challenges associated with monitoring a nocturnal species with a short survey window across a large spatial extent. Future monitoring efforts that combine ARU-based protocols and mappable fine-resolution structural vegetation data would likely further advance our understanding of whip-poor-will response to forest management.

Food availability aligns with contrasting demographics in populations of an at-risk songbird.

Golden-winged Warblers (Vermivora chrysoptera) have become rare across much of their historic breeding range and response to conservation efforts is variable. Evidence from several recent studies suggests that breeding output is a primary driver explaining responses to conservation and it is hypothesized that differences in food availability may be driving breeding output disparity between two subpopulations of the warbler's Appalachian breeding range. Herein, we studied two subpopulations: central Pennsylvania ("central subpopulation"), where breeding productivity is relatively low, and eastern Pennsylvania ("eastern subpopulation"), where breeding productivity is relatively high. To test the food-availability hypothesis in this system, we measured density of caterpillars, plasma lipid metabolites (triglycerides [TRIG; fat deposition] and glycerol [GLYC; fat breakdown]), body mass of adults males, and acquired body mass data for fledglings at 38 sites managed for nesting habitat. Consistent with our prediction, leaf-roller caterpillar density, the group upon which Golden-winged Warblers specialize, was 45× lower in the central subpopulation than the eastern subpopulation. TRIG concentrations were highest within the eastern subpopulation during breeding grounds arrival. The change in TRIG concentrations from the breeding-grounds-arrival stage to the nestling-rearing stage was subpopulation dependent: TRIG decreased in the eastern subpopulation and was constant in the central subpopulation, resulting in similar concentrations during the nestling-rearing stage. Furthermore, GLYC concentrations were higher in the eastern subpopulation, which suggests greater energy demands in this region. Despite this, adult male warblers in the eastern subpopulation maintained a higher average body mass. Finally, fledgling body mass was 16% greater in the eastern subpopulation than the central subpopulation before and after fledging. Collectively, our results suggest that poor breeding success of Golden-winged Warblers in the central subpopulation could be driven by lower availability of primary prey during the breeding season (leaf-roller caterpillars), and this, in turn, limits their response to conservation efforts.

CT Chest Imaging Using Normalized Join-Count: Predicting Emphysema Progression in the CanCOLD Study.

Background Pre-existing emphysema is recognized as an indicator of future worsening in patients with chronic obstructive pulmonary disease (COPD) when observed through CT imaging. However, it remains uncertain whether additional factors, such as the spatial compactness of CT emphysema, might also serve as predictors of disease progression. Purpose To evaluate the relationship between the compactness of CT emphysema voxels and emphysema progression. Materials and Methods This secondary analysis uses data from the prospective Canadian Cohort Obstructive Lung Disease (CanCOLD) study, examining CT images obtained in participants with and without COPD at baseline and a 3-year follow-up time point (November 2009 to November 2018). Measurements of forced expiratory volume in first second of expiration (FEV1) and diffusing capacity of lung for carbon monoxide (DLco) were collected. The normalized join-count (NJC) measurement from baseline CT images and lung density (LD) changes were analyzed. Emphysema progression was defined as an annualized LD change of less than half an SD below the mean of the participants without COPD with no smoking history. Multivariable linear and logistic regression models were used to assess the association between baseline CT NJC measurements and the annualized change in LD, FEV1, DLco, and emphysema progression versus nonprogression. Results A total of 524 participants (mean age, 66 years ± 10 [SD]; 293 male) (FEV1 percent predicted, 88% ± 19; FEV1/FVC, 67% ± 9; DLco percent predicted, 105% ± 25) were analyzed, 187 (36%) of whom had COPD. CT NJC was associated with the annualized change in LD (P < .001), FEV1 (P = .02), and DLco (P = .01). Additionally, CT NJC predicted emphysema progression versus nonprogression (odds ratio, 2.24; 95% CI: 1.37, 3.50; P < .001). Conclusion The spatial distribution, or "compactness," of CT emphysema voxels predicted emphysema progression in individuals with and without COPD. ClinicalTrials.gov Identifier: NCT00920348 © RSNA, 2024 Supplemental material is available for this article.

Implementing Montessori approaches after training: A mixed methods study to examine staff understanding and movement toward action.

Background: This paper uses Normalization Process Theory (NPT) to examine staff impressions of Montessori-based program training and implementation at Veterans Affairs Community Living Centers (VA CLCs; nursing homes). Methods: We conducted a mixed-methods evaluation of Montessori Approaches to Person-Centered Care (MAP-VA) at eight VA CLCs. Trainings were conducted as either a live virtual course or a pre-recorded asynchronous class. Two NPT constructs, coherence building and cognitive participation, informed qualitative interview questions, surveys, and analyses focused on staff movement from knowledge to action during initial implementation. Data collection included staff-completed standardized post-training exams (N = 906), post-training evaluations (N = 761), and optional validated surveys on perceptions of Montessori training (N = 307). Champions (peer-leaders) from each CLC completed semi-structured qualitative interviews post-training (N = 22). Findings: The majority of staff (83%-90%) passed all courses. Staff evaluated the training highly (80%+ agreement) on learning relevant new knowledge and confidence applying new skills. On average, staff felt MAP-VA would become a normal part of their work (7.68/10 scale), and reported increased familiarity with Montessori approaches after training (p = .002). Qualitative interview data from staff trained in Montessori supported three themes concordant with the NPT dimensions of coherence building and cognitive participation. (1) Coherence regarding Montessori: staff demonstrated an understanding of the program and mentioned the benefits of Montessori compared to their previous usual routines. Cognitive participation or engagement with Montessori: (2) staff had positive feelings about Montessori principles/applications and demonstrated a willingness to try the Montessori approach, and (3) staff made sense of the new intervention through early rehearsal of Montessori principles/practices and recognized opportunities for using Montessori in future interactions. Conclusions: Montessori virtual training resulted in high levels of coherence and cognitive participation among multidisciplinary staff, evidenced by high knowledge, self-efficacy, and readiness to act. The asynchronous and synchronous trainings were accessible, relevant, and supported diverse learners.

Racial, Ethnic, and Age-Related Disparities in Sedation and Restraint Use for Older Adults in the Emergency Department.

OBJECTIVES: Older adults may present to the emergency department (ED) with agitation, a symptom often resulting in chemical sedation and physical restraint use which carry significant risks and side effects for the geriatric population. To date, limited literature describes the patterns of differential restraint use in this population. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: This retrospective cross-sectional study used electronic health records data from ED visits by older adults (age ≥65 years) ranging 2015-2022 across nine hospital sites in a regional hospital network. Logistic regression models were estimated to determine the association between patient-level characteristics and the primary outcomes of chemical sedation and physical restraint. RESULTS: Among 872,587 ED visits during the study period, 11,875 (1.4%) and 32,658 (3.7%) encounters involved the use of chemical sedation and physical restraints respectively. The populations aged 75-84, 85-94, 95+ years had increasingly higher odds of chemical sedation [adjusted odds ratios (AORs) 1.35 (95% CI 1.29-1.42); 1.82 (1.73-1.91); 2.35 (2.15-2.57) respectively] as well as physical restraint compared to the 65-74 group [AOR 1.31 (1.27-1.34); 1.55 (1.50-1.60); 1.69 (1.59-1.79)]. Compared to the White Non-Hispanic group, the Black Non-Hispanic and Hispanic/Latinx groups had significantly higher odds of chemical sedation [AOR 1.26 (1.18-1.35); AOR 1.22 (1.15-1.29)] and physical restraint [AOR 1.12 (95% CI 1.07-1.16); 1.22 (1.18-1.26)]. CONCLUSION: Approximately one in 20 ED visits among older adults resulted in chemical sedation or physical restraint use. Minoritized group status was associated with increasing use of chemical sedation and physical restraint, particularly among the oldest old. These results may indicate the need for further research in agitation management for historically marginalized populations in older adults.

What diagnostic tests are available for respiratory infections or pulmonary exacerbations in cystic fibrosis: A scoping literature review.

A scoping review methodological framework formed the basis of this review. A search of two electronic databases captured relevant literature published from 2013. 1184 articles were screened, 200 of which met inclusion criteria. Included studies were categorised as tests for either respiratory infections OR pulmonary exacerbations. Data were extracted to ascertain test type, sample type, and indication of use for each test type. For infection, culture is the most common testing method, particularly for bacterial infections, whereas PCR is utilised more for the diagnosis of viral infections. Spirometry tests, indicating lung function, facilitate respiratory infection diagnoses. There is no clear definition of what an exacerbation is in persons with CF. A clinical checklist with risk criteria can determine if a patient is experiencing an exacerbation event, however the diagnosis is clinician-led and will vary between individuals. Fuchs criteria are one of the most frequently used tests to assess signs and symptoms of exacerbation in persons with CF. This scoping review highlights the development of home monitoring tests to facilitate earlier and easier diagnoses, and the identification of novel biomarkers for indication of infections/exacerbations as areas of current research and development. Research is particularly prevalent regarding exhaled breath condensate and volatile organic compounds as an alternative sampling/biomarker respectively for infection diagnosis. Whilst there are a wide range of tests available for diagnosing respiratory infections and/or exacerbations, these are typically used clinically in combination to ensure a rapid, accurate diagnosis which will ultimately benefit both the patient and clinician.

Structure and Formation Mechanisms in Tantalum and Niobium Oxides in Superconducting Quantum Circuits.

Improving the qubit's lifetime (T1) is crucial for fault-tolerant quantum computing. Recent advancements have shown that replacing niobium (Nb) with tantalum (Ta) as the base metal significantly increases T1, likely due to a less lossy native surface oxide. However, understanding the formation mechanism and nature of both surface oxides is still limited. Using aberration-corrected transmission electron microscopy and electron energy loss spectroscopy, we found that Ta surface oxide has fewer suboxides than Nb oxide. We observed an abrupt oxidation state transition from Ta2O5 to Ta, as opposed to the gradual shift from Nb2O5, NbO2, and NbO to Nb, consistent with thermodynamic modeling. Additionally, amorphous Ta2O5 exhibits a closer-to-crystalline bonding nature than Nb2O5, potentially hindering H atomic diffusion toward the oxide/metal interface. Finally, we propose a loss mechanism arising from the transition between two states within the distorted octahedron in an amorphous structure, potentially causing two-level system loss. Our findings offer a deeper understanding of the differences between native amorphous Ta and Nb oxides, providing valuable insights for advancing superconducting qubits through surface oxide engineering.

Timing of Palliative Care Consultation Impacts End of Life Care Outcomes in Metastatic Non-Small Cell Lung Cancer.

CONTEXT: Early specialist palliative care (PC) involvement in metastatic non-small cell lung cancer (mNSCLC) is associated with improved quality of life, less aggressive end of life (EoL) care, and longer survival. As treatment paradigms for NSCLC have evolved, PC utilization remains low. OBJECTIVES: This work examines how the timing and extent of PC involvement impacts outcomes and the patient experience in mNSCLC in the era of immunotherapy. METHODS: This retrospective review analyzed patients with mNSCLC who initiated first-line treatment with chemotherapy, immunotherapy, or combined chemoimmunotherapy at Duke University between March 2015 and July 2019. PC consultation and outcomes data were abstracted through November 2022. EoL care variables were analyzed using descriptive statistics. RESULTS: 152 patients were stratified based on whether PC was consulted during their disease course. 80 patients (53%) never saw PC, while the 72 patients (47%) who saw PC were further stratified by time to first PC encounter and total number of PC visits. 31% were seen within two months of diagnosis (early), 33% between two and six months (intermediate), and 36% after 6 months (late). Patients who received early PC had longer median time on hospice (35 days), had lower rates of aggressive EoL care (43%), and experienced less frequent in-hospital death (14%) compared to other groups. CONCLUSION: This real-world study reveals that referrals to PC still occur late or not at all in mNSCLC despite demonstrated benefits of early PC integration. Early outpatient PC referrals resulted in longer time on hospice, lower frequency of aggressive EoL care, and lower rates of in-hospital death.

A portable inflatable soft wearable robot to assist the shoulder during industrial work.

Repetitive overhead tasks during factory work can cause shoulder injuries resulting in impaired health and productivity loss. Soft wearable upper extremity robots have the potential to be effective injury prevention tools with minimal restrictions using soft materials and active controls. We present the design and evaluation of a portable inflatable shoulder wearable robot for assisting industrial workers during shoulder-elevated tasks. The robot is worn like a shirt with integrated textile pneumatic actuators, inertial measurement units, and a portable actuation unit. It can provide up to 6.6 newton-meters of torque to support the shoulder and cycle assistance on and off at six times per minute. From human participant evaluations during simulated industrial tasks, the robot reduced agonist muscle activities (anterior, middle, and posterior deltoids and biceps brachii) by up to 40% with slight changes in joint angles of less than 7% range of motion while not increasing antagonistic muscle activity (latissimus dorsi) in current sample size. Comparison of controller parameters further highlighted that higher assistance magnitude and earlier assistance timing resulted in statistically significant muscle activity reductions. During a task circuit with dynamic transitions among the tasks, the kinematics-based controller of the robot showed robustness to misinflations (96% true negative rate and 91% true positive rate), indicating minimal disturbances to the user when assistance was not required. A preliminary evaluation of a pressure modulation profile also highlighted a trade-off between user perception and hardware demands. Finally, five automotive factory workers used the robot in a pilot manufacturing area and provided feedback.

Association between antibody responses post-vaccination and severe COVID-19 outcomes in Scotland.

Several population-level studies have described individual clinical risk factors associated with suboptimal antibody responses following COVID-19 vaccination, but none have examined multimorbidity. Others have shown that suboptimal post-vaccination responses offer reduced protection to subsequent SARS-CoV-2 infection; however, the level of protection from COVID-19 hospitalisation/death remains unconfirmed. We use national Scottish datasets to investigate the association between multimorbidity and testing antibody-negative, examining the correlation between antibody levels and subsequent COVID-19 hospitalisation/death among double-vaccinated individuals. We found that individuals with multimorbidity ( ≥ five conditions) were more likely to test antibody-negative post-vaccination and 13.37 [6.05-29.53] times more likely to be hospitalised/die from COVID-19 than individuals without conditions. We also show a dose-dependent association between post-vaccination antibody levels and COVID-19 hospitalisation or death, with those with undetectable antibody levels at a significantly higher risk (HR 9.21 [95% CI 4.63-18.29]) of these serious outcomes compared to those with high antibody levels.

Histologic Findings of Sinusoidal Dilatation and Congestion in Liver Grafts Do Not Correlate with Hepatic Venous Anastomotic Gradients.

PURPOSE: Hepatic venous transplant anastomotic pressure gradient measurement and transjugular liver biopsy are commonly used in clinical decision-making in patients with suspected anastomotic hepatic venous outflow obstruction. This investigation aimed to determine if sinusoidal dilatation and congestion on histology are predictive of hepatic venous anastomotic outflow obstruction, and if it can help select patients for hepatic vein anastomosis stenting. MATERIALS AND METHODS: This is a single-center retrospective study of 166 transjugular liver biopsies in 139 patients obtained concurrently with transplant venous anastomotic pressure gradient measurement. Demographic characteristics, laboratory parameters, procedure and clinical data, and histology of time-zero allograft biopsies were analyzed. RESULTS: No relationship was found between transplant venous anastomotic pressure gradient and sinusoidal dilatation and congestion (P = 0.92). Logistic regression analysis for sinusoidal dilatation and congestion confirmed a significant relationship with reperfusion/preservation injury and/or necrosis of the allograft at time-zero biopsy (OR 6.6 [1.3-33.1], P = 0.02). CONCLUSION: There is no relationship between histologic sinusoidal dilatation and congestion and liver transplant hepatic vein anastomotic gradient. In this study group, sinusoidal dilatation and congestion is a nonspecific histopathologic finding that is not a reliable criterion to select patients for venous anastomosis stenting.

qPCR assay for detection of Woodchuck Hepatitis Virus Post-Transcriptional Regulatory Elements from CAR-T and TCR-T cells in fresh and formalin-fixed tissue.

As adoptive cellular therapies become more commonplace in cancer care, there is a growing need to monitor site-specific localization of engineered cells-such as chimeric antigen receptor T (CAR-T) cells and T-cell receptor T (TCR-T) cells-in patients' tissues to understand treatment effectiveness as well as associated adverse events. Manufacturing CAR-T and TCR-T cells involves transduction with viral vectors commonly containing the WPRE gene sequence to enhance gene expression, providing a viable assay target unique to these engineered cells. Quantitative PCR (qPCR) is currently used clinically in fresh patient tissue samples and blood with target sequences specific to each immunotherapy product. Herein, we developed a WPRE-targeted qPCR assay that is broadly applicable for detection of engineered cell products in both fresh and archival formalin-fixed paraffin embedded (FFPE) tissues. Using both traditional PCR and SYBR Green PCR protocols, we demonstrate the use of this WPRE-targeted assay to successfully detect two CAR-T cell and two TCR-T cell products in FFPE tissue. Standard curve analysis reported a reproducible limit of detection at 100 WPRE copies per 20µL PCR reaction. This novel and inexpensive technique could provide better understanding of tissue abundance of engineered therapeutic T cells in both tumor and second-site toxicity tissues and provide quantitative assessment of immune effector cell trafficking in archival tissue.

The Use of Hematopoietic Stem Cells for Heart Failure: A Systematic Review.

The purpose of this review is to summarize the current understanding of the therapeutic effect of stem cell-based therapies, including hematopoietic stem cells, for the treatment of ischemic heart damage. Following PRISMA guidelines, we conducted electronic searches in MEDLINE, and EMBASE. We screened 592 studies, and included RCTs, observational studies, and cohort studies that examined the effect of hematopoietic stem cell therapy in adult patients with heart failure. Studies that involved pediatric patients, mesenchymal stem cell therapy, and non-heart failure (HF) studies were excluded from our review. Out of the 592 studies, 7 studies met our inclusion criteria. Overall, administration of hematopoietic stem cells (via intracoronary or myocardial infarct) led to positive cardiac outcomes such as improvements in pathological left-ventricular remodeling, perfusion following acute myocardial infarction, and NYHA symptom class. Additionally, combined death, rehospitalization for heart failure, and infarction were significantly lower in patients treated with bone marrow-derived hematopoietic stem cells. Our review demonstrates that hematopoietic stem cell administration can lead to positive cardiac outcomes for HF patients. Future studies should aim to increase female representation and non-ischemic HF patients.

Speckle-free coherent imaging through deep turbulence.

We develop and validate a model-based iterative reconstruction framework for digitally correcting coherent images corrupted by deep turbulence. In general, this framework is applicable to coherent-imaging approaches that gain access to the complex-optical field; however, we demonstrate our approach with multi-shot digital holography data. To test our image correction framework, we generate calibrated deep-turbulence conditions from our laboratory testbed. Using the resulting data, we demonstrate groundbreaking performance in terms of speckle-free image correction in deep-turbulence conditions.

Individual differences in the boldness of female zebrafish are associated with alterations in serotonin function.

One of the most prevalent axes of behavioral variation in both humans and animals is risk taking, where individuals that are more willing to take risk are characterized as bold while those that are more reserved are regarded as shy. Brain monoamines (i.e. serotonin, dopamine and noradrenaline) have been found to play a role in a variety of behaviors related to risk taking. Using zebrafish, we investigated whether there was a relationship between monoamine function and boldness behavior during exploration of a novel tank. We found a correlation between serotonin metabolism (5-HIAA:5-HT ratio) and boldness during the initial exposure to the tank in female animals. The DOPAC:DA ratio correlated with boldness behavior on the third day in male fish. There was no relationship between boldness and noradrenaline. To probe differences in serotonergic function in bold and shy fish, we administered a selective serotonin reuptake inhibitor, escitalopram, and assessed exploratory behavior. We found that escitalopram had opposing effects on thigmotaxis in bold and shy female animals: the drug caused bold fish to spend more time near the center of the tank and shy fish spent more time near the periphery. Taken together, our findings indicate that variation in serotonergic function has sex-specific contributions to individual differences in risk-taking behavior.

Natural History of Artificial Urinary Sphincter Erosion: Long-term Lower Urinary Tract Outcomes and Incontinence Management.

OBJECTIVE: To describe long-term lower urinary tract outcomes and incontinence management after AUS erosion, including risk factors associated with each outcome. METHODS: We retrospectively reviewed our prospectively maintained AUS database for men undergoing device explantation for urethral erosion from January 1, 1986 to October 10, 2023. Outcomes included development of urethral stricture and management of post-explant incontinence (eg, pads/clamp, catheter, salvage AUS, supravesical diversion). Risk factors were tested for association with stricture formation and repeat AUS erosion using logistic regression. RESULTS: Around 1943 unique patients underwent AUS implantation during the study period, and 217 (11%) had a device explantation for urethral erosion. Of these, 194 had complete records available and were included for analysis. Median follow-up from implantation was 7.5 years (IQR 2.7-13.7) and median time to erosion was 2 yrs (IQR 0-6). Ninety-six patients (49%) underwent salvage AUS placement. Of those, 38/96 (40%) were explanted for subsequent erosion. On multivariable analysis, no factors were significantly associated with risk of salvage AUS erosion. On multivariable model, pelvic radiation (OR 2.7; 95% CI 1.0-7.4) and urethral reapproximation during explant for erosion (OR 4.2; 95% CI 1.5-11.2) were significantly associated with increased risk of urethral stricture (P <.05). At the time of last follow-up, 69/194 (36%) patients had a functioning salvage AUS, including both initial and subsequent salvage implants. CONCLUSION: Following AUS erosion, radiation history and urethral reapproximation at explantation were risk factors for development of urethral stricture. Salvage AUS replacement can be performed, but has a higher rate of repeat urethral erosion.

Incidence and predictors of ipsilateral local recurrence following partial nephrectomy.

PURPOSE: Ipsilateral local recurrence (LR) after partial nephrectomy (PN) for renal cell carcinoma (RCC) may result from a metachronous tumor or PN bed recurrence. To date, literature has predominantly reported ipsilateral LRs collectively, although the pathophysiology and prognostic implications of these event may be distinct. We sought to assess variables associated with LR and evaluated associations of LR with metastasis and death from RCC. MATERIALS AND METHODS: We identified adults undergoing PN for unilateral, sporadic, localized RCC from 2000 to 2019 using a prospectively maintained, single institution registry. LR was defined as new, enhancing tumor within/near the PN bed on MRI/CT. Cox proportional hazards models were used to create a preoperative risk score for LR and to examine the association of LR with metastasis and CSS following PN among patients with clear cell RCC. RESULTS: In a cohort of 2,164 PNs, 106 true LRs were identified, for a 10-year incidence of 6.2%. A preoperative risk score for LR based on age, symptoms, solitary kidney, complex tumor necessitating open partial nephrectomy, and cT stage was created (c-index = 0.73). Postoperatively, positive margins, pT stage, and clear cell subtype were associated with LR. Notably, 21% (23/106) of patients with LR presented with synchronous metastases. Following LR, 5-year metastasis-free and cancer-specific survival were 64% and 71%, respectively. LR remained associated with metastasis (HR 6.25; P < 0.001) and death from RCC (HR 1.93; P = 0.03) on multivariable analysis. CONCLUSIONS: We developed a preoperative risk score to identify patients at risk for LR following PN. LR was an independent risk factor for metastasis and death from RCC. Further study is warranted to determine whether treatment of LR improves oncologic outcomes.

Nursing Home to Emergency Care Transition Form Has Limited Uptake But Improves Documentation.

Critical information gaps exist in nursing home-to-emergency department (NH-ED) transfer documentation. Standardization of forms may address these gaps. In a single state, a Continuity of Care Acute Care Transfer (CoC) Form was standardized and mandated to be used for all NH-ED transfers. The objective of this study was to evaluate adoption and effectiveness of the standardized CoC form. We used a random cross-sectional sample of 2019-2022 electronic health record encounter data to determine NH-ED documentation completeness after standardized CoC form implementation. Using patient characteristic adjusted linear and logistic regressions, we examined if CoC form standardization was associated with the number of key elements present on NH-ED transfer documentation and hospital admission, respectively. We then compared documentation completeness (out of 15 key data elements) to previously published pre-implementation data (2015-2016, n = 474). Of the 203 NH-ED transfer visits after CoC standardization (2019-2022), mean patient age was 81.8 years and 41.4% had dementia. Any NH-ED transfer form was present for 80.8% (n = 164) of encounters and 28.6% (n = 58) used the standardized CoC form. In comparison with the 2015-2016 data, there was an increase in documentation for functional baseline (20% to 30%), cognitive baseline (25% to 37%), and reason for transfer (25% to 82%). Post implementation, the use of the standardized CoC form was (1) associated with 2.55 (95% CI, 1.66-3.44) more key data elements documented and (2) not associated with a decreased odds of admission [odds ratio (OR), 1.06; 95% CI, 0.54-2.05] after controlling for confounders. Implementation of a statewide standardized CoC form for NH-ED transfers improved documentation of key elements, yet significant information gaps remain. Implementation evaluation is needed to identify how to achieve greater uptake of the form and improve the quality of information exchange between NHs and EDs.