Concordance between risk scales for venous thromboembolism in patients treated in emergency departments. / Concordancia entre las escalas de valoración del riesgo de tromboembolismo venoso en pacientes con patología médica en urgencias.

OBJECTIVE: To evaluate agreement between risk-assessment models for venous thromboembolism (VTE) in patients hospitalized for medical conditions and to analyze variables associated with the decision to prescribe pharmacological thromboprophylaxis in hospital emergency departments (EDs). Conclusions. METHODS: Prospective observational multicenter cohort study. We included adults attended in 15 hospital EDs who were hospitalized for medical conditions, calculating VTE risk according to the International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) score, the Padua Prediction Score (PPS), and the National Institute for Health and Care Excellence (NICE) score. In addition to assessing interscore concordance, we analyzed variables associated with the prescription of thromboprophylaxis in the ED. RESULTS: A total of 1203 patients were included. The PADUA, IMPROVE, and NICE scales assigned high risk scores for 68.7%, 47.4%, and 69.5% of the patients, respectively. The κ statistic for agreement between the PADUA and NICE scores was 0.80 (95% CI, 0.76-0.84); 102 patients (8.5%) had discordant scores. The κ statistics for agreement between the IMPROVE score and the PADUA and NICE classifications were 0.47 (95% CI, 0.43-0.52) and 0.37 (95% CI, 0.33-0.42), respectively; 322 (26.8%) and 384 patients (31.9%), respectively, had discordant scores. Variables associated with starting thromboprophylaxis in the ED were a diagnosis of acute myocardial infarction or stroke (adjusted odds ratio [aOR], 4.26), immobility in the last 2 months (aOR, 2.19), chronic obstructive pulmonary disease (aOR, 1.97), ischemic heart disease (aOR, 1.51), reduced mobility of 3 days or longer (aOR, 1.14), body mass index (aOR, 1.04), age (aOR, 1.02), recent trauma or surgery (aOR, 0.40), and risk for bleeding (aOR, 0.56). CONCLUSIONS: There is disagreement among the recommended models for predicting risk for VTE in patients hospitalized for medical conditions. The basis for emergency physicians' clinical judgment regarding thromboprophylaxis extends beyond risk scales to include multiple risk factors for VTE and bleeding.

OBJETIVO: Evaluar la concordancia entre las escalas de riesgo de enfermedad tromboembólica venosa (ETV) de pacientes médicos hospitalizados y analizar las variables asociadas a la decisión de instaurar tromboprofilaxis farmacológica en los servicios de ur gencias(SUH). METODO: Se trata de un estudio de cohorte observacional prospectivo multicéntrico que incluyó pacientes adultos atendidos en 15 SUH españoles que requerían ingreso por patología médica. Se calculó la puntuación según las escalas IMPROVE, PADUA y NICE. Se evaluó la concordancia entre ellas, y las variables asociadas a la indicación de tromboprofilaxis en urgencias. RESULTADOS: Se incluyeron 1.203 pacientes. Las escalas PADUA, IMPROVE y NICE clasificaron de riesgo alto al 68,7%, 47,4% y 69,5% de los pacientes, respectivamente. PADUA y NICE mostraron un índice Kappa de 0,80 (IC 95%: 0,76-0,84) y discordancia del 8,5% (102 pacientes). IMPROVE con PADUA y NICE mostró un índice Kappa de 0,47 (IC 95%:0,43-0,52) y 0,37 (0,33-0,42), con una discordancia del 26,8% (322 pacientes) y 31,9% (384 pacientes), respectivamente. Las variables asociadas con la instauración de tromboprofilaxis fueron infarto agudo de miocardio o ictus (odss ratio ajustada ­ORa­ 4,26), inmovilidad 2 meses previos (ORa 2,19), enfermedad pulmonar obstructiva crónica (ORa 1,97), cardiopatía isquémica (ORa 1,51), movilidad reducida $ 3 días (ORa 1,14), índice masa corporal (ORa 1,04), edad (ORa 1,02), trauma o cirugía recientes (ORa 0,40) y factores de riesgo hemorrágicos (ORa 0,56). CONCLUSIONES: Existe disconcordancia entre las escalas recomendadas para valorar el riesgo de ETV en pacientes médicos hospitalizados. El juicio clínico del urgenciólogo para decidir la tromboprofilaxis se basa en la presencia de múltiples factores de riesgo de ETV y sangrado, más allá de las escalas.

Impact of an emergency department nurse training intervention on the adequacy of thromboprophylaxis for venous thromboembolism: the PROTESU III study. / Impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la profilaxis de la enfermedad tromboembólica venosa: estudio PROTESU III.

OBJECTIVE: Objectives. To assess the impact of training for emergency department (ED) nurses on adequate thromboprophylaxis for patients admitted to hospital from the ED for medical conditions. Methods. Multicenter quasiexperimental pre-post study of an ED nurse training intervention in 8 hospitals. Patients were recruited from January 2022 through May 2023 in 3 phases: before nurse training, in the first month after training, and in the sixth month after training. Included were patients attended in the ED for medical conditions. Adequate thromboprophylaxis was defined as 1) use of prophylactic drugs in patients at high risk for venousthromboembolism according to the Padua Prediction Score (PPS), and 2) nonuse in patients at low risk. We compared the percentage of adequate prophylaxis in the first phase to the percentages in the second and third phases. Results. A total of 928 patients were included (326 in phase 1, 295 in phase 2, and 307 in phase 3). PPS scores indicated that 238 (73%) of the patients were at high risk in phase 1 vs 189 (64.1%, P = .016) in phase 2 and 207 (67.4%, P = .125) in phase 3. A total of 187 patients (57.4%, 95% CI, 51.8%-62.8%) were adequatelythromboprophylaxed in phase 1 vs 178 (60.%, 95% CI, 54.5%-66%) in phase 2 (absolute difference in proportions, 3.0% (95% CI, -4.8% to 10.6%; P = .462)]. In phase 3, 166 patients (54.1%, 95% CI, 48.3%-59.7%) received adequate prophylaxis (difference, -3.3% (95% CI, -11.0% to 4.4%; P = .405). Conclusions. A training intervention for ED nurses, implemented as an isolated strategy, had no impact on the adequacy of thromboprophylaxis in patients admitted from the ED for medical conditions.

OBJETIVO: Objetivos. Evaluar el impacto de una intervención formativa en enfermería de urgencias sobre la adecuación de la tromboprofilaxis farmacológica de los pacientes ingresados por patología médica. Método. Estudio cuasiexperimental, multicéntrico (8 hospitales), pre y posintervención, con 3 fases de reclutamiento (enero 2022-mayo 2023): primera,preintervención; segunda, en el primer mes tras la intervención; y tercera, al sexto mes. Se incluyeron los pacientes atendidos en urgencias que requirieron ingreso por enfermedad médica. La adecuación de la tromboprofilaxis farmacológica se definió como: 1) la utilización en pacientes clasificados en el grupo de riesgo alto por la Escala de Padua (PPS); o 2) la no utilización en pacientes clasificados de riesgo bajo. Se compararon los porcentajes de adecuación de las fases 2 y 3 frente a la fase 1. Resultados. Se incluyeron 928 pacientes: 326 en la fase 1; 295 en la fase 2; y 307 en la fase 3. En la fase 1, 238 pacientes (73%) fueron clasificados de riesgo alto por PPS; en la fase 2, 189 (64,1%) (p = 0,016); y en la fase 3, 207 (67,4%) (p = 0,125). La tromboprofilaxis farmacológica fue adecuada en 187 pacientes (57,4%, IC 95% 51,8-62,8%) de la fase 1; en 178 (60,3%, IC 95% 54,5 66%) de la fase 2 [diferencia absoluta proporciones (DAP) 3,0% (IC 95% de ­4,8 a +10,6%), p = 0,462], y en 166 (54,1%, IC 95% 48,3-59,7%) de la fase 3 [DAP 3,3% (IC 95% de ­11,0 a +4,4%, p = 0,405]. Conclusiones. Una intervención formativa aislada en la enfermería de urgencias no tuvo impacto sobre la adecuación de la tromboprofilaxis farmacológica en urgencias de los pacientes que ingresan por enfermedad médica.

Harnessing the therapeutic effects of nature for chronic Pain: A role for immersive virtual reality? A narrative review.

BACKGROUND AND OBJECTIVE: There is a growing interest in the relationship between nature and pain relief. Evidence from environmental psychology, neuroscience and physiology-based studies point towards analgesic effects of nature being mediated through various cognitive, affective and/or autonomic factors. Being able to harness these therapeutic effects using immersive virtual reality (VR) could help to optimize and improve accessibility of nature-based environments as part of chronic pain management plans. In this narrative review, we present evidence supporting a new theoretical framework for nature-based analgesia and suggest ways for applying this through immersive VR. DATABASES AND DATA TREATMENT: We provide an overview of the evidence on (1) the therapeutic effects of nature on pain, (2) environmental psychology theory that underpins the health benefits of nature, (3) key mechanistic evidence from nature neuroimaging and physiology-based studies, (4) previous studies that have used VR-based nature in pain research and (5) how to design effective VR interventions that can be used to integrate nature into immersive 360 environments. RESULTS: We have demonstrated how environmental psychology, neuroscience and physiology-based research can be used to form a novel theoretical framework for nature-based analgesia. Using this framework, we identify how key aspects of nature can act as analgesic and how this can be harnessed using immersive VR. CONCLUSIONS: Through developing this theoretical framework, we have provided a foundation on which to guide future experimental and clinical studies as well as helping to improve the accessibility of nature for chronic pain patients through immersive VR technologies. SIGNIFICANCE: This review article summarizes key multidisciplinary evidence to help understand how nature exerts beneficial effects on pain processing. The use of this theoretical framework alongside advances in immersive VR technologies provides a springboard for future research and can be used to help develop new nature-based therapeutics using VR.

Prophylaxis of venous thromboembolism in hospitalized patients admitted from Spanish emergency departments: the PROTESU II study. / Profilaxis de la enfermedad tromboembólica venosa en pacientes hospitalizados por patología médica desde los servicios de urgencias españoles: estudio PROTESU II.

OBJECTIVE: To estimate the prevalence of inappropriate use of prophylaxis to prevent venous thromboembolism (VTE) in patients with medical diseases admitted to hospital from the emergency department. To explore variables associated with inappropriate thromboprophylaxis. METHODS: Prospective multicenter cohort study in 15 hospital emergency departments. We included patients admitted for a medical condition during 7 days in the first quarter of 2022. We assessed risk for VTE with the Padua Prediction Score (PPS). Inappropriate thromboprophylaxis was defined by failure to prescribe prophylaxis in patients with a high-risk PPS assessment unless there were absolute contraindications (active bleeding or severe thrombopenia) or, alternatively, the prescription of prophylaxis in patients with a low-risk PPS assessment or absolute contraindications. A logistic regression model was adjusted for risk level to identify variables associated with inappropriate use of thromboprophylaxis. RESULTS: Of a total of 630 patients included, 450 (71.4%) had PPS scores indicating high risk for VTE; 180 patients were at low risk. Thromboprophylaxis was inappropriate in 248 patients (39.4%): 165 high-risk patients who received no prophylaxis, 82 low-risk patients who were nonetheless treated, and 1 patient who was treated in spite of severe thrombopenia. Odds ratios (ORs) revealed that the variables associated with inappropriate use of thromboprophylaxis were trauma or recent surgery (OR, 5.53; 95% CI, 1.58-19.34), presence of factors indicating risk for bleeding (OR, 2.61; 95% CI, 1.44-4.73), and hospital admission for either urinary tract infection (OR, 2.29; 95% CI, 1.07-4.87) or gastrointestinal disease (OR, 4.30; 95% CI, 1.71-10.85). CONCLUSIONS: The inappropriate use of thromboprophylaxis in Spanish emergency departments is high and associated with certain clinical characteristics.

OBJETIVO: Evaluar la inadecuación de la tromboprofilaxis farmacológica, según la escala Padua (PPS), para prevenir la enfermedad tromboembólica venosa (ETV) entre los pacientes que ingresan desde el servicio de urgencias hospitalario (SUH) por patología médica, así como las variables asociadas a su uso inadecuado. METODO: Estudio de cohortes, prospectivo, multicéntrico donde participaron 15 SUH. Se incluyeron los pacientes atendidos que requirieron ingreso por enfermedad médica durante 7 días del primer trimestre de 2022. La inadecuación de la tromboprofilaxis farmacológica se definió como la no utilización en pacientes clasificados por PPS de alto riesgo sin contraindicaciones absolutas para su uso (hemorragia activa o trombopenia grave) o su utilización en pacientes de riesgo bajo o con contraindicaciones absolutas. Se ajustó, para cada grupo de riesgo, un modelo de regresión logística para identificar las variables asociadas a la inadecuación. RESULTADOS: Se incluyeron 630 pacientes, 450 (71,4%) tenían riesgo alto y 180 (28,6%) riesgo bajo para ETV según la PPS. De ellos, la tromboprofilaxis fue inadecuada en 248 pacientes (39,4%) (165 tenían riesgo alto pero no recibieron tromboprofilaxis, 1 la recibió teniendo trombopenia grave y 82 tenían riesgo bajo pero recibieron tromboprofilaxis). Las variables asociadas con la inadecuación en pacientes de alto riesgo fueron trauma o cirugía recientes con odds ratio (OR) de OR 5,53 (IC 95%: 1,58-19,34), presencia de factores de riesgo hemorrágico con OR de 2,61 (IC 95%: 1,44-4,73), e infección del tracto urinario con OR de 2,29 (IC 95%: 1,07-4,87) y enfermedad gastrointestinal con OR de 4,30 (IC 95%: 1,71-10,85) como motivos de ingreso. CONCLUSIONES: En los SUH españoles, el uso inadecuado de la tromboprofilaxis farmacológica es elevado. Algunas características clínicas se asocian al uso inadecuado de dicha tromboprofilaxis.

Evaluation of the safety of medication-use systems in hospital emergency services. / Evaluación de la seguridad del sistema de utilización de los medicamentos en los servicios de urgencias hospitalarios.

INTRODUCTION: The aim of this study was to assess the implementation of safe medication practices in hospital emergency services, in order to understand the points of greatest risk as well as the safety challenges faced by these departments, and to plan collaboratively improvement initiatives. METHOD: Multicentric and descriptive study based on completion of the "Medication safety self-assessment of emergency services" from 5/16/2023 to 11/16/2023, at voluntarily participating emergency services. The survey contained 93 items grouped into 10 key elements. Mean score and mean percentages based on the maximum possible values for the overall survey, for the key elements and for each individual item of evaluation, were assessed. RESULTS: A total of 72 emergency services completed the questionnaire. The mean score obtained for the overall questionnaire was 428.3 points (51.1% of the maximum score). Results showed a large variation among the scores of the participating services (range: 164-620.5). Four key elements had values below 50%, corresponding to competence and training of professionals in safety practices (38.4%); incorporation of pharmacists in emergency departments (42.1%), availability and accessibility of information about patients (43.1%), and patient education (48.1%). The highest values corresponded to labeling, packaging, and naming of medications (69.2%) and communication of prescriptions and other medication information (64%). No differences were found between emergency services in the key elements according to the dependency or size of the hospital, or the type of service, except for the item referring to the incorporation of pharmacists in the emergency service, where differences were observed between hospitals with less than 200 beds (28.9%) and those with more than 500 (52.2%). CONCLUSION: The application of the specific self-assessment questionnaire has made it possible to identify safety practices that are insufficiently implemented into emergency services in our country and to identify critical points for improvement for which planning collaborative initiatives to reduce medication errors in these departments should become a priority.

Description of B abesia coryicola sp. nov. from Florida pumas (Puma concolor coryi) from southern Florida, USA.

Previously, a high prevalence of piroplasms has been reported from Florida pumas (Puma concolor coryi) from southern Florida. In the current study, we describe the biological characteristics of a novel Babesia species in Florida pumas. Ring-stage trophozoites were morphologically similar to trophozoites of numerous small babesids of felids including B. leo, B. felis, and Cytauxzoon felis. Parasitemias in Florida pumas were very low (<1%) and hematologic values of 25 Babesia-infected Florida pumas were within normal ranges for P. concolor. Phylogenetic analysis of near full-length 18S rRNA gene, ß-tubulin, cytochrome c oxidase subunit I, cytochrome c oxidase subunit III, and cytochrome b gene sequences indicated that this Babesia species is a member of the Babesia sensu stricto clade and is related to groups of Babesia spp. from carnivores or ungulates, although the closest group varied by gene target. Internal transcribed spacer (ITS)-1 region sequences from this Babesia sp. from 19 Florida pumas were 85.7-99.5% similar to each other and ∼88% similar to B. odocoilei. Similarly, an ITS-2 sequence from one puma was 96% similar to B. bigemina and 92% similar to a Babesia sp. from a red panda (Ailurus fulgens). Infected pumas were positive for antibodies that reacted with B. odocoilei, B. canis, and B. bovis antigens with titers of 1:256, 1:128, and 1:128, respectively. No serologic reactivity was noted for Theileria equi. No molecular evidence of congenital infection was detected in 24 kittens born to 11 Babesia-infected female pumas. Pumas from other populations in the United States [Louisiana (n = 1), North Dakota (n = 5) and Texas (n = 28)], British Columbia, Canada (n = 9), and Costa Rica (n = 2) were negative for this Babesia sp. Collectively, these data provide morphologic, serologic, genetic, and natural history data for this novel Babesia sp. which we propose the name Babesia coryicola sp. nov. sp. This is the first description of a felid-associated Babesia species in North America.

Single-cell analysis reveals lasting immunological consequences of influenza infection and respiratory immunization in the pig lung.

The pig is a natural host for influenza viruses and integrally involved in virus evolution through interspecies transmissions between humans and swine. Swine have many physiological, anatomical, and immunological similarities to humans, and are an excellent model for human influenza. Here, we employed single cell RNA-sequencing (scRNA-seq) and flow cytometry to characterize the major leukocyte subsets in bronchoalveolar lavage (BAL), twenty-one days after H1N1pdm09 infection or respiratory immunization with an adenoviral vector vaccine expressing hemagglutinin and nucleoprotein with or without IL-1ß. Mapping scRNA-seq clusters from BAL onto those previously described in peripheral blood facilitated annotation and highlighted differences between tissue resident and circulating immune cells. ScRNA-seq data and functional assays revealed lasting impacts of immune challenge on BAL populations. First, mucosal administration of IL-1ß reduced the number of functionally active Treg cells. Second, influenza infection upregulated IFI6 in BAL cells and decreased their susceptibility to virus replication in vitro. Our data provide a reference map of porcine BAL cells and reveal lasting immunological consequences of influenza infection and respiratory immunization in a highly relevant large animal model for respiratory virus infection.

The origin of ovarian Leydig cells: a possibly solved enigma?

Over the years, the origin of ovarian Leydig cells has been, and still is, a topic subject to deep debate. Seven years ago, we proposed that this origin resided in intraneural elements that came from a possible reservoir of neural crest cells, a reservoir that may be located in the ganglia of the celiac plexus. We believe we have found the evidence necessary to prove this hypothesis.

Generation and External Validation of a Histologic Transformation Risk Model for Patients with Follicular Lymphoma.

Follicular lymphoma (FL) is the most frequent indolent lymphoma. Some patients (10%-15%) experience histologic transformation (HT) to a more aggressive lymphoma, usually diffuse large B-cell lymphoma (DLBCL). This study aimed to validate and improve a genetic risk model to predict HT at diagnosis.We collected mutational data from diagnosis biopsies of 64 FL patients. We combined them with the data from a previously published cohort (total n = 104; 62 from nontransformed and 42 from patients who did transform to DLBCL). This combined cohort was used to develop a nomogram to estimate the risk of HT. Prognostic mutated genes and clinical variables were assessed using Cox regression analysis to generate a risk model. The model was internally validated by bootstrapping and externally validated in an independent cohort. Its performance was evaluated using a concordance index and a calibration curve. The clinicogenetic nomogram included the mutational status of 3 genes (HIST1HE1, KMT2D, and TNFSR14) and high-risk Follicular Lymphoma International Prognostic Index and predicted HT with a concordance index of 0.746. Patients were classified as being at low or high risk of transformation. The probability HT function at 24 months was 0.90 in the low-risk group vs 0.51 in the high-risk group and, at 60 months, 0.71 vs 0.15, respectively. In the external validation cohort, the probability HT function in the low-risk group was 0.86 vs 0.54 in the high-risk group at 24 months, and 0.71 vs 0.32 at 60 months. The concordance index in the external cohort was 0.552. In conclusion, we propose a clinicogenetic risk model to predict FL HT to DLBLC, combining genetic alterations in HIST1H1E, KMT2D, and TNFRSF14 genes and clinical features (Follicular Lymphoma International Prognostic Index) at diagnosis. This model could improve the management of FL patients and allow treatment strategies that would prevent or delay transformation.

Mercury Exposure Is Associated with Urbanization but not Salmonella Status in White Ibis (Eudocimus albus).

Mercury (Hg) is a ubiquitous contaminant in wetlands that can cause immunosuppression in birds, which may increase susceptibility to colonization with Salmonella spp. Previously, we found that White Ibis (Eudocimus albus), a recently urbanized wading bird, shed Salmonella spp. at a higher prevalence when captured at urban sites, compared with natural sites. In this study, we sought to determine if Hg burdens in ibis are related to Salmonella status or degree of urbanization or both. We analyzed feathers from 94 ibis in Palm Beach County, Florida, USA, along an urbanization gradient (0-68% urbanization) and from individuals with confirmed Salmonella spp. status (shedding or not shedding). We detected Hg in all ibis feathers (0.22-8.47 mg/kg; mean=1.96 mg/kg; SD=1.94). The Hg concentration was not significantly correlated to Salmonella spp. shedding status (Wilcoxon rank sum test, W=1170; P=0.596) but was negatively associated with capture site urbanization level (R2=0.327; P=0.026). Our findings may suggest that the immunosuppressive effects of Hg do not affect Salmonella shedding in the ibis or that Hg burdens were too low to affect Salmonella shedding status. Further, ibis that were captured in high urbanization sites appeared to have a lower risk of Hg exposure than ibis that were captured within low urbanization sites.

IgG4-related disease and B-cell malignancy due to an IKZF1 gain-of-function variant.

BACKGROUND: Monoallelic loss-of-function IKZF1 (IKAROS) variants cause B-cell deficiency or combined immunodeficiency, whereas monoallelic gain-of-function (GOF) IKZF1 variants have recently been reported to cause hypergammaglobulinemia, abnormal plasma cell differentiation, autoimmune and allergic manifestations, and infections. OBJECTIVE: We studied 7 relatives with autoimmune/inflammatory and lymphoproliferative manifestations to identify the immunologic disturbances and the genetic cause of their disease. METHODS: We analyzed biopsy results and performed whole-exome sequencing and immunologic studies. RESULTS: Disease onset occurred at a mean age of 25.2 years (range, 10-64, years). Six patients suffered from autoimmune/inflammatory diseases, 4 had confirmed IG4-related disease (IgG4-RD), and 5 developed B-cell malignancies: lymphoma in 4 and multiple myeloma in the remaining patient. Patients without immunosuppression were not particularly prone to infectious diseases. Three patients suffered from life-threatening coronavirus disease 2019 pneumonia, of whom 1 had autoantibodies neutralizing IFN-α. The recently described IKZF1 GOF p.R183H variant was found in the 5 affected relatives tested and in a 6-year-old asymptomatic girl. Immunologic analysis revealed hypergammaglobulinemia and high frequencies of certain lymphocyte subsets (exhausted B cells, effector memory CD4 T cells, effector memory CD4 T cells that have regained surface expression of CD45RA and CD28-CD57+ CD4+ and CD8+ T cells, TH2, and Tfh2 cells) attesting to immune dysregulation. Partial clinical responses to rituximab and corticosteroids were observed, and treatment with lenalidomide, which promotes IKAROS degradation, was initiated in 3 patients. CONCLUSIONS: Heterozygosity for GOF IKZF1 variants underlies autoimmunity/inflammatory diseases, IgG4-RD, and B-cell malignancies, the onset of which may occur in adulthood. Clinical and immunologic data are similar to those for patients with unexplained IgG4-RD. Patients may therefore benefit from treatments inhibiting pathways displaying IKAROS-mediated overactivity.

The impact of the COVID-19 pandemic on the mood and family relationships of runners.

Introduction: The aim of this study was to analyze the impact of the COVID-19 lockdown on the mood of amateur runners and on their relationships with their partners and families. Methods: Adult runners 18 years or older (N = 260) completed an online survey that included demographic information, standardized psychological assessments of Exercise Dependence (EDS-R) and mood (POMS), and, to measure relationship functioning, either the Dyadic Adjustment Scale (DAS) if they did not have children, or the Basic Family Evaluation Questionnaire (CERFB), measuring conjugal and parental relationships. Participants also answered questions about their exercise habits and the coping strategies they adopted during lockdown. Results: The results suggest that runners who saw the largest reductions in time spent exercising during lockdown tended to feel significantly less energetic (p < 0.05) and friendly (p < 0.01). In addition, they recorded significantly lower scores in marital satisfaction with their peers (p < 0.05). The runners with a higher degree of dependence on physical exercise registered significantly higher levels of depression, tension and anger than non-dependent runners (p < 0.001). Runners whose partners were physically active and did not have children had significantly higher scores marital satisfaction than runners whose partners were not physically active and had children (p < 0.05). Discussion: These findings seem to indicate that the psychological approach to athletes in the context of crises such as the pandemic should consider not only individual aspects, but also include the family perspective.

Development of Convolutional Neural Network to Segment Ultrasound Images of Histotripsy Ablation.

OBJECTIVE: Histotripsy is a focused ultrasound therapy that ablates tissue via the action of bubble clouds. It is under investigation to treat a number of ailments, including renal tumors. Ultrasound imaging is used to monitor histotripsy, though there remains a lack of definitive imaging metrics to confirm successful treatment outcomes. In this study, a convolutional neural network (CNN) was developed to segment ablation on ultrasound images. METHODS: A transfer learning approach was used to replace classification layers of the residual network ResNet-18. Inputs to the classification layers were based on ultrasound images of ablated red blood cell phantoms. Digital photographs served as the ground truth. The efficacy of the CNN was compared to subtraction imaging, and manual segmentation of images by two board-certified radiologists. RESULTS: The CNN had a similar performance to manual segmentation, though was improved relative to segmentation with subtraction imaging. Predictions of the network improved over the course of treatment, with the Dice similarity coefficient less than 20% for fewer than 500 applied pulses, but 85% for more than 750 applied pulses. The network was also applied to ultrasound images of ex vivo kidney exposed to histotripsy, which indicated a morphological shift in the treatment profile relative to the phantoms. These findings were consistent with histology that confirmed ablation of the targeted tissue. CONCLUSION: Overall, the CNN showed promise as a rapid means to assess outcomes of histotripsy and automate treatment. SIGNIFICANCE: Data collected in this study indicate integration of CNN image segmentation to gauge outcomes for histotripsy ablation holds promise for automating treatment procedures.

Understanding Cognitive Deficits in People with High Blood Pressure.

High blood pressure is associated with an elevated risk of dementia. However, much less is known about how high blood pressure is related to cognitive deficits in domains including episodic memory, semantic verbal fluency, fluid reasoning, and numerical ability. By analyzing data from 337 participants (57.39% female) with a history of clinical high blood pressure diagnosis with a mean age of 48.78 ± 17.06 years and 26,707 healthy controls (58.75% female) with a mean age of 45.30 ± 15.92 years using a predictive normative modeling approach and one-sample t-tests, the current study found that people with high blood pressure have impaired immediate (t(259) = -4.71, p < 0.01, Cohen's d = -0.08, 95% C.I. [-0.11, -0.05]) and delayed word recall (t(259) = -7.21, p < 0.01, Cohen's d = -0.11, 95% C.I. [-0.15, -0.08]) performance. Moreover, people with high blood pressure also exhibited impaired performance in the animal naming task (t(259) = -6.61, p < 0.0001, Cohen's d = -0.11, 95% C.I. [-0.15, -0.08]), and number series (t(259) = -4.76, p < 0.01, Cohen's d = -0.08, 95% C.I. [-0.11, -0.05]) and numeracy tasks (t(259) = -4.16, p < 0.01, Cohen's d = -0.06, 95% C.I. [-0.09, -0.03]) after controlling for demographic characteristics. Clinicians and health professionals should consider including these tasks as part of the neuropsychological assessment for people with high blood pressure, to detect their cognitive deficits. Moreover, they should also come up with ways to improve cognitive performance in people with high blood pressure.

Human Salmonellosis Outbreak Linked to Salmonella Typhimurium Epidemic in Wild Songbirds, United States, 2020-2021.

Salmonella infection causes epidemic death in wild songbirds, with potential to spread to humans. In February 2021, public health officials in Oregon and Washington, USA, isolated a strain of Salmonella enterica serovar Typhimurium from humans and a wild songbird. Investigation by public health partners ultimately identified 30 illnesses in 12 states linked to an epidemic of Salmonella Typhimurium in songbirds. We report a multistate outbreak of human salmonellosis associated with songbirds, resulting from direct handling of sick and dead birds or indirect contact with contaminated birdfeeders. Companion animals might have contributed to the spread of Salmonella between songbirds and patients; the outbreak strain was detected in 1 ill dog, and a cat became ill after contact with a wild bird. This outbreak highlights a One Health issue where actions like regular cleaning of birdfeeders might reduce the health risk to wildlife, companion animals, and humans.

A single Haemoproteus plataleae haplotype is widespread in white ibis (Eudocimus albus) from urban and rural sites in southern Florida.

The American white ibis (Eudocimus albus), a common bird species in Florida, has become increasingly urban, with many populations relying heavily on urban and suburban habitats, which may alter parasite transmission. Parasites of ibis, especially haemosporidians, are understudied. Avian haemosporidia can have a wide range of impacts on birds, including decreased reproductive success or increased mortality. Because southern Florida is subtropical and has a high diversity of potential vectors for haemosporidia, we hypothesized that there will be a high prevalence and genetic diversity of haemosporidia in white ibis. A total of 636 ibis from South Florida were sampled from 2010 to 2022, and blood samples were tested for haemosporidia by examination of Giemsa-stained thin blood smears and/or nested PCRs targeting the cytochrome b gene. A total of 400 (62.9%, 95% CI 59-66.7%) ibis were positive for parasites that were morphologically identified as Haemoproteus plataleae. Sequences of 302 positives revealed a single haplotype of Haemoproteus (EUDRUB01), which was previously reported from white ibis in South Florida and captive scarlet ibis (E. ruber) in Brazil. No Plasmodium or Leucocytozoon infections were detected. Parasitemias of the 400 positive birds were very low (average 0.084%, range 0.001%-2.16% [although only 2 birds had parasitemias >1%]). Prevalence and parasitemias were similar for males and females (68% vs. 61.6% and 0.081% vs. 0.071%, respectively). Prevalence in juveniles was lower compared with adults (52% vs. 67.4%) but parasitemias were higher in juveniles (0.117% vs. 0.065%). This data shows that H. plataleae is common in ibis in South Florida. Although parasitemias were generally low, additional research is needed to determine if this parasite has subclinical effects on ibis, if additional haplotypes or parasite species infect ibis in other regions of their range, or if H. plataleae is pathogenic for other sympatric avian species.

Using GHQ-12 to Screen Mental Health Issues in People with Emphysema.

Although previous studies have investigated the presence of psychometric comorbidities in individuals with emphysema, our understanding of the impact of emphysema on general mental health and specific dimensions of mental health, such as social dysfunction and anhedonia, depression and anxiety, and loss of confidence, remains limited. This research aims to examine the influence of emphysema on general mental health and its dimensions using the GHQ-12 assessment. By employing confirmatory factor analysis (CFA), the predictive normative approach, and one-sample t-test, we analyzed data from Understanding Society: the UK Household Longitudinal Study (UKHLS), including 97 individuals clinically diagnosed with emphysema and 8980 individuals without a clinical diagnosis of emphysema. The findings of this study indicate that individuals with clinically diagnosed emphysema experience poorer general mental health (t(96) = 8.41, p < 0.001, Cohen's d = 0.12, 95% C.I. [0.09, 0.15]), increased levels of social dysfunction and anhedonia (t(96) = 6.02, p < 0.001, Cohen's d = 0.09, 95% C.I. [0.06, 0.11]), heightened depression and anxiety (t(96) = 7.26, p < 0.001, Cohen's d = 0.11, 95% C.I. [0.08, 0.14]), as well as elevated loss of confidence (t(96) = 6.40, p < 0.001, Cohen's d = 0.09, 95% C.I. [0.07, 0.12]). These findings suggest the need for intervention programs aimed at improving the mental health of individuals with emphysema.

An Acute Mortality Event Associated with Novel Macrorhabdus ornithogaster Infection and Underlying Factors in a Newly-Established Captive Group of American White Ibis (Eudocimus albus) Nestlings.

Twenty-four American white ibis (Eudocimus albus) nestlings were collected in Florida (USA) on 17 April 2017 to establish a captive flock. On 7 May 2017, three birds died suddenly, following severe lethargy, hemorrhaging from the mouth and nares, anorexia, and production of bright-green colored feces. An additional ibis with delayed growth and pathological fractures was euthanized 18 May 2017. Severe ventriculitis associated with Macrorhabdus ornithogaster was noted in all four birds, bacterial sepsis was confirmed in one bird by culture and histologic examination, and bacterial endotoxemia was suspected in two birds based on gross and histologic examination, but no bacteria were isolated from these birds. Birds also had vitamin E liver levels consistent with coagulopathy previously described in pelicans. We sampled feces from 91 adult, free-living, healthy ibis in Florida in July 2017 and found 71% were shedding organisms with morphologic characteristics consistent with Macrorhabdus sp. Molecular characterization of the ibis-origin M. ornithogaster showed it was phylogenetically related to numerous M. ornithogaster sequences. It is unknown if M. ornithogaster infection resulted in clinical disease as a result of dietary or stress-related dysbiosis, or other factors. Macrorhabdus-associated disease has not previously been confirmed in wading birds. We discuss potential associations of gastric M. ornithogaster infection with morbidity and mortality in these cases and highlight the need for additional studies on this pathogen in free-living birds.

Histotripsy induces apoptosis and reduces hypoxia in a neuroblastoma xenograft model.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumor of childhood, and high-risk disease is resistant to intensive treatment. Histotripsy is a focused ultrasound therapy under development for tissue ablation via bubble activity. The goal of this study was to assess outcomes of histotripsy ablation in a xenograft model of high-risk NB. METHODS: Female NCr nude mice received NGP-luciferase cells intrarenally. Under ultrasound image guidance, histotripsy pulses were applied over a distance of 4-6 mm within the tumors. Bioluminescence indicative of tumor viability was quantified before, immediately after, and 24 h after histotripsy exposure. Tumors were immunostained to assess apoptosis (TUNEL), endothelium (endomucin), pericytes (αSMA), hypoxia (pimonidazole), vascular endothelial growth factor A (VEGFA), and platelet-derived growth factor-B (PDGF-B). The apoptotic cytokine TNFα and its downstream effector cleaved caspase-3 (c-casp-3) were assessed with SDS-PAGE. RESULTS: Histotripsy induced a 50% reduction in bioluminescence compared to untreated controls, with an absence of nuclei in the treatment core surrounded by a dense rim of TUNEL-positive cells. Tumor regions not targeted by histotripsy also showed an increase in TUNEL staining density. Increased apoptosis in histotripsy samples was consistent with increases in TNFα and c-casp-3 relative to controls. Treated tumors exhibited a decrease in hypoxia, VEGF, PDGF-B, and pericyte coverage of vasculature compared to control samples. Further, increases in vasodilation were found in histotripsy-treated specimens. CONCLUSIONS: In addition to ablative effects, histotripsy was found to drive tumor apoptosis through intrinsic pathways, altering blood vessel architecture, and reducing hypoxia.

Non-viral nitric oxide-based gene therapy improves perfusion and liposomal doxorubicin sonopermeation in neuroblastoma models.

Neuroblastoma (NB) is a pediatric malignancy that accounts for 15% of cancer-related childhood mortality. High-risk NB requires an aggressive chemoradiotherapy regimen that causes significant off-target toxicity. Despite this invasive treatment, many patients either relapse or do not respond adequately. Recent studies suggest that improving tumor perfusion can enhance drug accumulation and distribution within the tumor tissue, potentially augmenting treatment effects without inflicting systemic toxicity. Accordingly, methods that transiently increase tumor perfusion prior to treatment may help combat this disease. Here, we show the use of gene therapy to confer inducible nitric oxide synthase (iNOS) expression solely in the tumor space, using focused ultrasound targeting. NOS catalyzes the reaction that generates nitric oxide (NO), a potent endogenous vasodilator. This study reports the development of a targeted non-viral image-guided platform to deliver iNOS-expressing plasmid DNA (pDNA) to vascular endothelial cells encasing tumor blood vessels. Following transfection, longitudinal quantitative contrast-enhanced ultrasound (qCEUS) imaging revealed an increase in tumor perfusion over 72 h, attributed to elevated intratumoral iNOS expression. Methods: To construct a gene delivery vector, cationic ultrasound-responsive agents (known as "microbubbles") were employed to carry pDNA in circulation and transfect tumor vascular endothelial cells in vivo using focused ultrasound (FUS) energy. This was followed by liposomal doxorubicin (L-DOX) treatment. The post-transfection tumor response was monitored longitudinally using qCEUS imaging to determine relative changes in blood volumes and perfusion rates. After therapy, ex vivo analysis of tumors was performed to examine the bioeffects associated with iNOS expression. Results: By combining FUS therapy with cationic ultrasound contrast agents (UCAs), we achieved selective intratumoral transfection of pDNA encoding the iNOS enzyme. While transitory, the degree of expression was sufficient to induce significant increases in tumoral perfusion, to appreciably enhance the chemotherapeutic payload and to extend survival time in an orthotopic xenograft model. Conclusion: We have demonstrated the ability of a novel targeted non-viral gene therapy strategy to enhance tumor perfusion and improve L-DOX delivery to NB xenografts. While our results demonstrate that transiently increasing tumor perfusion improves liposome-encapsulated chemotherapeutic uptake and distribution, we expect that our iNOS gene delivery paradigm can also significantly improve radio and immunotherapies by increasing the delivery of radiosensitizers and immunomodulators, potentially improving upon current NB treatment without concomitant adverse effects. Our findings further suggest that qCEUS imaging can effectively monitor changes in tumor perfusion in vivo, allowing the identification of an ideal time-point to administer therapy.