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Background Greenness—or vegetative presence—has been identified as a factor in chronic disease. The present study examines the longitudinal relationship between objective measures of greenness at the residential block level and incidence of 6 cardiovascular disease conditions. Methods and Results Analyses examined the impact of consistently high versus consistently low “precision” greenness at the Census block level on the 5‐year incidence of cardiovascular disease conditions, including acute myocardial infarction, atrial fibrillation, heart failure, ischemic heart disease, stroke/transient ischemic attack, and hypertension, among 229 034 US Medicare beneficiaries in Miami‐Dade County, Florida, USA. Zero‐inflated Poisson regression was used to model the odds of developing any new cardiovascular disease and number of new cardiovascular disease conditions based on greenness tertiles computed across 2011 and 2016 Normalized Difference Vegetation Index values, adjusting for individual age, sex, race, ethnicity, baseline cardiovascular disease conditions, neighborhood income, and walkability in 2011 and 2016. When compared with individuals consistently in the low greenness tertile in 2011 and 2016, those consistently in the high greenness tertile in 2011 and 2016 had a 9% lower odds of having any new cardiovascular conditions (odds ratio [OR], 0.91 [95% CI, 0.84–0.99]; P=0.021). Conclusions Over a 5‐year period, consistently high greenness, when compared with consistently low greenness, was associated with lower odds of any new cardiovascular disease conditions. Identifying the role of greenness exposure in such a small geographic area, the Census block on which the older adult resides, allows for more precise, strategic decisions on where additional trees can be added—by selecting at‐risk blocks rather than entire neighborhoods for tree‐planting interventions.

Objective. Pulmonary hypertension is a severe and rapidly progressive disease, particularly frequent in patients with rheumatic diseases. The aims of this study were the following: to determine the prevalence of pulmonary hypertension in Italian patients with autoimmune rheumatic diseases, and to evaluate if the presence of a rheumatic disease in general, or of a specific autoimmune rheumatic disease, is a risk factor for the development of pulmonary hypertension. Patients and Methods. One hundred and thirteen Italian patients with connective tissue diseases (105 females, 8 males), aged 19 to 83 yrs, entered the study. Fifty-one had systemic sclerosis (SSc): 49 were females, 2 males, aged 34 to 83 yrs; 41 had limited cutaneous SSc, 8 diffuse cutaneous SSc, and 2 SSc sine scleroderma. Thirty-three patients had systemic lupus erythematosus (SLE): all but one were females, their age ranged from 19 to 82 yrs. Twenty-five had rheumatoid arthritis (RA): 21 females, 4 males, aged 26 to 45 yrs. Three females and one male, 51-77 yrs, had mixed connective tissue disease (MCTD). Systolic pulmonary arterial pressure (SPAP) was assessed by Doppler echocardiography. Results. Twenty three patients had pulmonary hypertension, which was more frequent in MCTD than in SLE (75% vs 6.1%, p=0.0002) or in AR (20%, p=0.0313). Pulmonary hypertension was more frequent in SSc than in SLE (25.5% vs 6.1%, p=0.0028) and in limited than in diffuse SSc(21.6% vs 3.9%). SPAP was significanly related to age (R=0.35, P=0.0275), with patients with pulmonary hypertension older than patients with normal SPAP (66±13 vs 52±16 yrs, p=0.0003). Conclusions. These data show a significant association between pulmonary hypertension and autoimmune rheumatic diseases. Therefore pulmonary hypertension assessment seems mandatory, at least in MCTD and SSc. However, more studies are needed to clarify the relationship between age and pulmonary hypertension and to verify whether the low prevalence of pulmonary hypertension we found in our SLE patients is related or not to their lower age.

Background: Despite the well-known efficacy of anti-COVID-19 vaccines in preventing morbidity and mortality, several vaccinated individuals are diagnosed with SARS-CoV-2 breakthrough infection, which might require hospitalisation. This multicentre, observational, and retrospective study aimed to investigate the clinical characteristics and outcomes of vaccinated vs. non-vaccinated patients, both hospitalised with SARS-CoV-2 infection in 3 major hospitals in Northern Italy. Methods: Data collection was retrospective, and paper and electronic medical records of adult patients with a diagnosed SARS-CoV-2 infection were pseudo-anonymised and analysed. Vaccinated and non-vaccinated individuals were manually paired, using a predetermined matching criterion (similar age, gender, and date of hospitalisation). Demographic, clinical, treatment, and outcome data were compared between groups differing by vaccination status using Pearson’s Chi-square and Mann-Whitney tests. Moreover, multiple logistic regression analyses were performed to assess the impact of vaccination status on ICU admission or intra-hospital mortality. Results: Data from 360 patients were collected. Vaccinated patients presented with a higher prevalence of relevant comorbidities, like kidney replacement therapy or haematological malignancy, despite a milder clinical presentation at the first evaluation. Non-vaccinated patients required intensive care more often than their vaccinated counterparts (8.8% vs. 1.7%, p = 0.002). Contrariwise, no difference in intra-hospital mortality was observed between the two groups (19% vs. 20%, p = 0.853). These results were confirmed by multivariable logistic regressions, which showed that vaccination was significantly associated with decreased risk of ICU admission (aOR=0.172, 95%CI: 0.039–0.542, p = 0.007), but not of intra-hospital mortality (aOR=0.996, 95%CI: 0.582–1.703, p = 0.987). Conclusions: This study provides real-world data on vaccinated patients hospitalised with COVID-19 in Northern Italy. Our results suggest that COVID-19 vaccination has a protective role in individuals with higher risk profiles, especially regarding the need for ICU admission. These findings contribute to our understanding of SARS-CoV-2 infection outcomes among vaccinated individuals and emphasise the importance of vaccination in preventing severe disease, particularly in those countries with lower first-booster uptake rates.

IntroductionAutosomal recessive osteopetrosis (ARO) is a rare genetic disease, characterized by increased bone density due to defective osteoclast function. Most of the cases are due to TCIRG1 gene mutation, leading to severe bone phenotype and death in the first years of life. The standard therapy is the hematopoietic stem cell transplantation (HSCT), but its success is limited by several constraints. Conversely, gene therapy (GT) could minimize the immune-mediated complications of allogeneic HSCT and offer a prompt treatment to these patients.MethodsThe Tcirg1-defective oc/oc mouse model displays a short lifespan and high bone density, closely mirroring the human condition. In this work, we exploited the oc/oc neonate mice to optimize the critical steps for a successful therapy.ResultsFirst, we showed that lentiviral vector GT can revert the osteopetrotic bone phenotype, allowing long-term survival and reducing extramedullary haematopoiesis. Then, we demonstrated that plerixafor-induced mobilization can further increase the high number of HSPCs circulating in peripheral blood, facilitating the collection of adequate numbers of cells for therapeutic purposes. Finally, pre-transplant non-genotoxic conditioning allowed the stable engraftment of HSPCs, albeit at lower level than conventional total body irradiation, and led to long-term survival and correction of bone phenotype, in the absence of acute toxicity.ConclusionThese results will pave the way to the implementation of an effective GT protocol, reducing the transplant-related complication risks in the very young and severely affected ARO patients.

Objectives Vasoactive drugs have exhibited clinical efficacy in addressing pulmonary arterial hypertension, manifesting a significant reduction in morbidity and mortality. Pulmonary hypertension may complicate advanced interstitial lung disease (PH-ILD) and is associated with high rates of disability, hospitalisation due to cardiac and respiratory illnesses, and mortality. Prior management hinged on treating the underlying lung disease and comorbidities. However, the INCREASE trial of inhaled treprostinil in PH-ILD has demonstrated that PH-ILD can be effectively treated with vasoactive drugs.Methods This comprehensive systematic review examines the evidence for vasoactive drugs in the management of PH-ILD.Results A total of 1442 pubblications were screened, 11 RCTs were considered for quantitative synthesis. Unfortunately, the salient studies are limited by population heterogeneity, short-term follow-up and the selection of outcomes with uncertain clinical significance.Conclusions This systematic review underscores the necessity of establishing a precision medicine-oriented strategy, directed at uncovering and addressing the intricate cellular and molecular mechanisms that underlie the pathophysiology of PH-ILD.PROSPERO registration number CRD42023457482.

Background: Patients suffering from coronavirus disease-19 (COVID-19)-related interstitial pneumonia have variable outcomes, and the risk factors for a more severe course have yet to be comprehensively identified. Cohort studies have suggested that coronary artery calcium (CAC), as estimated at chest computed tomography (CT) scan, correlated with patient outcomes. However, given that the prevalence of CAC is gender- and age-dependent, the influence of baseline confounders cannot be completely excluded. Methods: We designed a retrospective, multicenter case-control study including patients with COVID-19, with severe course cases selected based on death within 30 days or requiring invasive ventilation, whereas controls were age- and sex-matched patients surviving up to 30 days without invasive ventilation. The primary outcome was the analysis of moderate-to-severe CAC prevalence between cases and controls. Results: A total of 65 cases and 130 controls were included in the study. Cases had a significantly higher median pulmonary severity score at chest CT scan compared to controls (10 vs. 8, respectively; p = 0.0001), as well as a higher CAC score (5 vs. 2; p = 0.009). The prevalence of moderate-to-severe CAC in cases was significantly greater (41.5% vs. 23.8%; p = 0.013), a difference mainly driven by a higher prevalence in those who died within 30 days (p = 0.000), rather than those requiring invasive ventilation (p = 0.847). White blood cell count, moderate-to-severe CAC, the need for antibiotic therapy, and severe pneumonia at CT scan were independent primary endpoint predictors. Conclusions: This case-control study demonstrated that the CAC burden was higher in COVID-19 patients who did not survive 30 days or who required mechanical ventilation, and CAC played an independent prognostic role.

During the sixteenth century, a relevant number of books related to practical arithmetic were published in Spain. This paper presents a comparative study that aims to identify the object and target of five old mathematics books and the main contents of these books. In order to do so, all the contents and all the examples found in five arithmetic books written during the first half of the 16th century were identified and categorised. A historical-mathematical analysis using a content analysis technique was then applied. The results show the authors' concerns about mathematics at the time and the different contents that were included in some arithmetic books of this century.

Summary: Visual cortical plasticity is high during early life, but gradually decreases with development. This is due to the Otx2-driven maturation of intracortical inhibition that parallels the condensation of extracellular matrix components into perineuronal nets mainly around parvalbumin-positive GABAergic neurons. Repressor Element 1 Silencing Transcription (REST) epigenetically controls the expression of a plethora of neuron-specific genes. We demonstrate that the conditional knockout of REST in the primary visual cortex of adult mice induces a shift of ocular dominance after short-term monocular deprivation and promotes the recovery of vision in long-term deprived animals after reverse suture. These phenomena paralleled a reduction of perineuronal net density and increased expression of REST target genes, but not of the homeoprotein Otx2 in the visual cortex contralateral to the deprived eye. This shows that REST regulates adult visual cortical plasticity and is a potential therapeutic target to restore vision in adult amblyopia by enhancing V1 plasticity.

Abstract Interstitial lung diseases (ILDs) are complex and heterogeneous diseases. The use of traditional diagnostic classification in ILD can lead to suboptimal management, which is worsened by not considering the molecular pathways, biological complexity, and disease phenotypes. The identification of specific “treatable traits” in ILDs, which are clinically relevant and modifiable disease characteristics, may improve patient’s outcomes. Treatable traits in ILDs may be classified into four different domains (pulmonary, aetiological, comorbidities, and lifestyle), which will facilitate identification of related assessment tools, treatment options, and expected benefits. A multidisciplinary care team model is a potential way to implement a “treatable traits” strategy into clinical practice with the aim of improving patients’ outcomes. Multidisciplinary models of care, international registries, and the use of artificial intelligence may facilitate the implementation of the “treatable traits” approach into clinical practice. Prospective studies are needed to test potential therapies for a variety of treatable traits to further advance care of patients with ILD.

There is an ongoing effort to advance methodologies for culturing functional photoreceptors in vitro for retinal regenerative strategies. To support the formation of functional photoreceptors, a scaffold should replicate the native environment. The aim of this study was to optimize a sodium alginate–gelatin (SA-G) bioink to mimic the retinal properties while ensuring the printing of constructs with high shape fidelity. The optimized bioink was thoroughly characterized in terms of its physical, mechanical, and rheological properties, printability assessment, and preliminary biocompatibility. The material showed a constant degradation rate, which is crucial for effective tissue regeneration as it provides support for cell differentiation and polarization while gradually degrading to allow cell proliferation and matrix deposition. The optimized bioink displayed stiffness comparable to the native photoreceptor layer, potentially providing appropriate mechanical cues for photoreceptor maturation. Additionally, it exhibited shear-thinning behavior, the presence of yield stress, and fast recovery kinetics, which are essential for successful extrusion. The high shape fidelity of 3D-printed constructs suggested the feasibility of printing complex patterns to drive photoreceptor polarization. The preliminary cell results demonstrated homogeneous cell distribution and sustained cell viability over time. Overall, these findings indicate that the optimized bioink can provide the mechanical and topographical cues necessary for cultivating photoreceptors in vitro for retinal regeneration.

This study presents the perceptions of trainee teachers regarding the realisation of practical mathematical sessions to expand on the concepts that are taught in primary education using manipulatives. For a 4-month period, a practical session with the mentioned characteristics was carried out weekly with Year 1 students of the Primary Education Teaching Degree. After their completion of the module the students were requested to comment in writing on the utility of such practical sessions. The resulting information was analysed qualitatively through content analysis using ATLAS.ti software (Version 7.5.4). Six broad categories grouping the utilities considered by the students were found.

The objectives of this study were to (1) investigate the association between human blood type and COVID-19 in both inpatient and longitudinal populations and (2) identify the association between blood type and severity of COVID-19 via presence of cellular biomarkers of severe infection in hospitalized individuals at our institution in South Florida. This study consisted of (1) a single-center retrospective analysis of 669 out of 2741 COVID-19-positive, screened patients seen from 1 January 2020 until 31 March 2021 at the University of Miami Emergency Department (ED) who tested positive for COVID-19 and had a documented ABO blood type and (2) a longitudinal SARS-CoV-2 immunity study (“CITY”) at the University of Miami Miller School of Medicine, consisting of 185 survey participants. In an inpatient setting, blood type appeared to be associated with COVID-19 severity and mortality. Blood type O sustained less risk of COVID-19 mortality, and blood type O- demonstrated less risk of developing COVID-19 pneumonia. Inpatients with O- blood type exhibited less biomarkers of severe infection than did other blood types. In a longitudinal setting, there was no association found between blood type and SARS-CoV-2 infection.

BackgroundThe proliferation of digital disease-detection systems has led to an increase in earlier warning signals, which subsequently have resulted in swifter responses to emerging threats. Such highly sensitive systems can also produce weak signals needing additional information for action. The delays in the response to a genuine health threat are often due to the time it takes to verify a health event. It was the delay in outbreak verification that was the main impetus for creating EpiCore. ObjectiveThis paper describes the potential of crowdsourcing information through EpiCore, a network of voluntary human, animal, and environmental health professionals supporting the verification of early warning signals of potential outbreaks and informing risk assessments by monitoring ongoing threats. MethodsThis paper uses summary statistics to assess whether EpiCore is meeting its goal to accelerate the time to verification of identified potential health events for epidemic and pandemic intelligence purposes from around the world. Data from the EpiCore platform from January 2018 to December 2022 were analyzed to capture request for information response rates and verification rates. Illustrated use cases are provided to describe how EpiCore members provide information to facilitate the verification of early warning signals of potential outbreaks and for the monitoring and risk assessment of ongoing threats through EpiCore and its utilities. ResultsSince its launch in 2016, EpiCore network membership grew to over 3300 individuals during the first 2 years, consisting of professionals in human, animal, and environmental health, spanning 161 countries. The overall EpiCore response rate to requests for information increased by year between 2018 and 2022 from 65.4% to 68.8% with an initial response typically received within 24 hours (in 2022, 94% of responded requests received a first contribution within 24 h). Five illustrated use cases highlight the various uses of EpiCore. ConclusionsAs the global demand for data to facilitate disease prevention and control continues to grow, it will be crucial for traditional and nontraditional methods of disease surveillance to work together to ensure health threats are captured earlier. EpiCore is an innovative approach that can support health authorities in decision-making when used complementarily with official early detection and verification systems. EpiCore can shorten the time to verification by confirming early detection signals, informing risk-assessment activities, and monitoring ongoing events.

Introduction: The importance of Continuing Professional Education is emphasized internationally due to the widespread changes in different domains. The nursing profession plays an important role in healthcare due to the influence of nurses on patients’ and community health status. Thus, it is crucial to understand the motives for participation in Continuing Professional Education programs. This study seeks to recognize the motivational factors that affect nurses to choose Continuing Nursing Education. Material and methods: Data was collected through a self-completed questionnaire, sent in electronic form to Hellenic Nurses Associations and Institutions. The Kolmogorov—Smirnov test was used for normality analysis of the quantitative variables. Unifactorial analyses were made by using the Mann–Whitney t-test, Kruskal–Wallis test, and Spearman’s correlation coefficients to analyze the relation between the outcome variables (PRS subscales questionnaires) and the quantitative, qualitative demographic characteristics respectively. Results: The results of this study have shown that all factors explored within the 4 dimensions by Participation Reason Scale (PRS), have generated a positive response. Factors improving professional skills and patients’ services were the most common factors that affect nurses’ participation in Continuing Education. Certain demographic variables are associated with specific motivational factors, specifically with higher levels of motivation for both improving professional skills and patient services, as well as professional commitment among nurses. Conclusion: It is crucial to investigate the incentives for Continuing education in Nursing and recognize their actual training needs. When individuals' continuing education and training needs are acknowledged, it will become possible to develop training plans, promotion, and strategies that are aligned with their specific needs and objectives. Resumen: Introducción: La importancia de la Educación Profesional Continua se enfatiza a nivel internacional debido a los cambios generalizados en diferentes dominios. Dado que la enfermería juega un papel importante en el cuidado de la salud debido a su influencia en el estado de salud de los pacientes y de la comunidad, es crucial saber cuáles son las motivaciones del colectivo o si enfrentan alguna barrera con respecto a su participación en los programas de Educación Continua. Este estudio busca identificar los factores motivacionales que afectan al colectivo de enfermería para optar por la Formación Continua en Enfermería. Material y Métodos: Se trata de un diseño descriptivo, correlacional. La muestra consta de 154 enfermeras/os del personal del hospital, enfermeras/os prácticas licenciadas/asistentes de enfermería, enfermeras/os escolares, enfermeras/os geriátricas que trabajan en el sector público y privado en Grecia. Los datos se recopilaron a través de un cuestionario autocompletado, enviado en forma electrónica a las Asociaciones e Instituciones de Enfermeras Helénicas. Para el análisis de normalidad de las variables cuantitativas se utilizó la prueba de Kolmogorov-Smirnov. Se realizaron análisis unifactoriales utilizando la prueba t de Mann-Whitney, la prueba de Kruskal-Wallis y los coeficientes de correlación de Spearman para analizar la relación entre las variables de resultado (cuestionarios de subescalas PRS) y las características demográficas cuantitativas y cualitativas, respectivamente. Resultados: Los resultados de este estudio han demostrado que todos los factores explorados dentro de las cuatro dimensiones por la Escala de Razón de Participación (PRS), han generado una respuesta positiva. Los factores que mejoran las habilidades profesionales y los servicios de los pacientes fueron los factores más comunes que afectan la participación de las enfermeras/os en la Educación Continua. Ciertas variables demográficas se asocian con factores motivacionales específicos, específicamente con mayores niveles de motivación tanto para mejorar las habilidades profesionales y los servicios al paciente, así como el compromiso profesional de las enfermeras. Conclusión: Es crucial investigar los incentivos que motivan al colectivo de enfermería para la formación continua y reconocer sus necesidades reales de formación. Cuando se reconozcan las necesidades de educación y capacitación continua de las personas, será posible desarrollar planes de capacitación, promoción y estrategias alineadas con sus necesidades y objetivos específicos.

A substantial increase in broad-spectrum antibiotics as empirical therapy in patients with community-acquired pneumonia (CAP) has occurred over the last 15 years. One of the driving factors leading to that has been some evidence showing an increased incidence of drug-resistant pathogens (DRP) in patients from a community with pneumonia, including methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Research has been published attempting to identify DRP in CAP through the implementation of probabilistic approaches in clinical practice. However, recent epidemiological data showed that the incidence of DRP in CAP varies significantly according to local ecology, healthcare systems and countries where the studies were performed. Several studies also questioned whether broad-spectrum antibiotic coverage might improve outcomes in CAP, as it is widely documented that broad-spectrum antibiotics overuse is associated with increased costs, length of hospital stay, drug adverse events and resistance. The aim of this review is to analyze the different approaches used to identify DRP in CAP patients as well as the outcomes and adverse events in patients undergoing broad-spectrum antibiotics.

BackgroundGeant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing.AimsTo respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics.Materials and methodsG4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes.ResultsThis paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data.DiscussionOur results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics.ConclusionThe results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Objective: Ghrelin is an appetite-modulating peptide mainly produced in the stomach, with levels reported to be lower in Helicobacter pylori-positive subjects. This pre-post study aimed to evaluate the effect of H. pylori eradication on circulating total ghrelin, gastric histopathology, appetite, and nutritional status of dyspeptic adults. Patients and Methods: Weight, height, appetite and nutrient intake were determined using validated tools. Gastric biopsies were obtained for histopathology and H. pylori diagnosis. Fasting serum ghrelin was measured by ELISA. H. pylori-positive subjects received eradication therapy and returned ≥12 weeks later for re-evaluation. Results: Of 117 screened individuals, 47 who were H. pylori-positive were included, and the organism was eradicated in 28 (59.6%). Pathologic findings decreased significantly after treatment in subjects with eradication (p