Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.

Acute respiratory distress syndrome (ARDS) is a life-threatening lung injury that currently lacks effective clinical treatments. Evidence highlights the potential role of glycogen synthase kinase-3 (GSK-3) inhibition in mitigating severe inflammation. The inhibition of GSK-3α/ß by CHIR99021 promoted fetal lung progenitor proliferation and maturation of alveolar epithelial cells (AECs). The precise impact of CHIR99021 in lung repair and regeneration during acute lung injury (ALI) remains unexplored. This study intends to elucidate the influence of CHIR99021 on AEC behaviour during the peak of the inflammatory phase of ALI and, after its attenuation, during the repair and regeneration stage. Furthermore, a long-term evaluation was conducted post CHIR99021 treatment at a late phase of the disease. Our results disclosed the role of GSK-3α/ß inhibition in promoting AECI and AECII proliferation. Later administration of CHIR99021 during ALI progression contributed to the transdifferentiation of AECII into AECI and an AECI/AECII increase, suggesting its contribution to the renewal of the alveolar epithelial population and lung regeneration. This effect was confirmed to be maintained histologically in the long term. These findings underscore the potential of targeted therapies that modulate GSK-3α/ß inhibition, offering innovative approaches for managing acute lung diseases, mostly in later stages where no treatment is available.

Neurodevelopment outcomes in the first 5 years of the life of children with transposition of the great arteries surgically corrected in the neonatal period: systematic review and meta-analysis.

OBJECTIVES: In patients with transposition of the great arteries, surgical correction may achieve definitive treatment, so a thorough knowledge of the long-term outcomes, particularly neurodevelopment outcomes, is essential. Therefore, we conducted a systematic review and meta-analysis to study the neurodevelopment outcomes in the first 5 years of the life of children submitted to corrective surgery for transposition of the great arteries in the neonatal period. METHODS: A total of 17 studies from 18 reports were included, assessing 809 individuals with surgically corrected transposition of the great arteries. The neurodevelopmental outcomes were assessed with the Bayley Scales of Infant and Toddler Development (BSID) and the Wechsler Intelligence Scale for Children (WISC). RESULTS: Mean Mental Development Index (MDI) and Psychomotor Development Index (PDI) were within the average values from 1 to 3 years of age, although the proportion of children scoring more than 1 standard deviation below the mean in PDI, MDI, motor, and language composite scores was significantly higher than in the general population. From 4 to 5 years, mean full-scale global intelligence quotient (IQ), verbal IQ, and performance IQ scores did not differ significantly from the general population. CONCLUSION: This study revealed neurodevelopment scores within the normal range at 5 years of age in children submitted to corrective surgery for transposition of the great arteries in the neonatal period. However, these early outcomes may not adequately predict long-term outcomes. Further studies are needed to identify specific risk factors and early markers of later impairment to guide the establishment of early interventions.

Experiencia de adultos mayores «PT4Ageing». Un programa de autogestión de enfermedades crónicas / Older person's experience of PT4Ageing—A programme on self-management «support» in chronic illness

Objetivo: Este estudio buscó describir la experiencia de un grupo de adultos mayores que participaron en un programa de autogestión de enfermedades crónicas. Métodos: El estudio empleó un enfoque fenomenológico cualitativo. Los participantes fueron ocho ancianos y los datos se recogieron mediante entrevistas semiestructuradas. Los datos se analizaron mediante análisis temático. Resultados: Del análisis surgieron cinco temas: 1) Consejos para mejorar nuestra vida diaria, 2) siempre estaba motivado, 3) compartir y ayuda mutua, 4) nos hicieron creer que éramos capaces, 5) sería estupendo que esto no acabara aquí. Globalmente, los participantes en el programa describieron su experiencia como muy positiva. Identificaron beneficios derivados de la participación en el programa, como el aprendizaje de estrategias que les ayudarán a afrontar sus problemas de salud, la mejora de su capacidad para gestionar sus enfermedades de forma más autónoma y el refuerzo del apoyo social, que incluso persistieron tras la conclusión de la intervención. Conclusiones: Los resultados de este estudio proporcionan una visión de cómo los adultos mayores experimentan un programa para la autogestión de enfermedades crónicas. Para el desarrollo de futuros programas, debe tenerse en cuenta la creación de apoyo. Los adultos mayores que participan en programas de autogestión muestran una mayor autoeficacia con relación a la gestión de sus enfermedades crónicas y una mayor autonomía en el autocuidado.(AU)

Objective: This study sought to describe the experience of a group of older adults who participated in a chronic illness self-management programme. Methods: The study employed a qualitative phenomenological approach. Participants were eight elders and data collected using semi-structured interviews. Data was analysed using thematic analysis. Results: Five themes emerged from the analysis: 1) tips to improve our daily lives, 2) I was always motivated, 3) sharing and mutual help, 4) they made us believe we were capable, 5) It would be great if it did not end here. Globally, the participants of the programme described their experience as very positive. They identified gains from participating in the programme, such as learning strategies to help them cope with their health problems, improving their ability to manage their illnesses more autonomously and building social support, that even persisted after the conclusion of the intervention. Conclusion: The findings of this study provide insight into how older adults experience a programme for the self-management of chronic illness. For the development of future programmes, support building must be considered. Older adults who participate in self-management programmes exhibit improved self-efficacy in relation to the management their chronic illnesses and greater autonomy in self-care.(AU)

Older person's experience of PT4Ageing-A programme on self-management «support¼ in chronic illness.

OBJECTIVE: This study sought to describe the experience of a group of older adults who participated in a chronic illness self-management program. METHODS: The study employed a qualitative phenomenological approach. Participants were eight elders and data collected using semi-structured interviews Data was analysed using thematic analysis. RESULTS: Five themes emerged from the analysis: (1) Tips to improve our daily lives, (2) I was always motivated, (3) Sharing and mutual help, (4) They made us believe we were capable (5). It would be great if it did not end here. Globally, the participants of the program described their experience as very positive. They identified gains from participating in the program, such as learning strategies to help them cope with their health problems, improving their ability to manage their illnesses more autonomously and building social support, that even persisted after the conclusion of the intervention. CONCLUSION: The findings of this study provide insight into how older adults experience a program for the self-management of chronic illness. For the development of future programs, support building must be considered. Older adults who participate in self-management programmes exhibit improved self-efficacy in relation to the management their chronic illnesses and greater autonomy in self-care.

Strategies Used by Nurses to Maintain Person-Family Communication during the COVID-19 Pandemic: A Scoping Review.

Background: The COVID-19 pandemic made nurse-patient-family communication more difficult, reducing the understanding of the patient's wishes and current care history. COVID-19 challenged healthcare teams to develop strategies to address these changes and provide more integrated care using the technology at their disposal. So, this study aims to map the strategies used by nurses to maintain communication between the person hospitalized with COVID-19 and the family to understand which communication technologies were most used to maintain communication between the person and the family. Methods: A Scoping Review, according to the recommendations of the Joanna Briggs Institute [JBI] with the Preferred Reporting Items for Scoping Review extension (PRISMA-ScR), research conducted between September 2022 and January 2023. The search was conducted in the databases: Latin American and Caribbean Literature in Health Sciences (LILACS); Cumulative Index of Nursing and Allied Health Literature (CINAHL); Scientific Electronic Library Online (SciELO); Medical Literature Analysis and Retrieval System Online (Medline), using the descriptors: family, communication, nurses, hospitals and COVID-19, and the Boolean operators "AND". The inclusion criteria were: original articles, in Portuguese, English, and Spanish, published from 2020 onwards, with access to full and free text. Results: It was found that most of the communication was unstructured with the family. The technologies most used by nurses were the telephone with video calls from the patients themselves and even from health professionals to maintain communication between the patient and the family. Conclusions: Communication between patients and families became essential during the pandemic, as it became a vital lifeline of human connection that supported the mental health of patients and their families. This study was not registered.

Emotional sounds in space: asymmetrical representation within early-stage auditory areas.

Evidence from behavioral studies suggests that the spatial origin of sounds may influence the perception of emotional valence. Using 7T fMRI we have investigated the impact of the categories of sound (vocalizations; non-vocalizations), emotional valence (positive, neutral, negative) and spatial origin (left, center, right) on the encoding in early-stage auditory areas and in the voice area. The combination of these different characteristics resulted in a total of 18 conditions (2 categories x 3 valences x 3 lateralizations), which were presented in a pseudo-randomized order in blocks of 11 different sounds (of the same condition) in 12 distinct runs of 6 min. In addition, two localizers, i.e., tonotopy mapping; human vocalizations, were used to define regions of interest. A three-way repeated measure ANOVA on the BOLD responses revealed bilateral significant effects and interactions in the primary auditory cortex, the lateral early-stage auditory areas, and the voice area. Positive vocalizations presented on the left side yielded greater activity in the ipsilateral and contralateral primary auditory cortex than did neutral or negative vocalizations or any other stimuli at any of the three positions. Right, but not left area L3 responded more strongly to (i) positive vocalizations presented ipsi- or contralaterally than to neutral or negative vocalizations presented at the same positions; and (ii) to neutral than positive or negative non-vocalizations presented contralaterally. Furthermore, comparison with a previous study indicates that spatial cues may render emotional valence more salient within the early-stage auditory areas.

Improving timely transfers from acute care to the local palliative care unit for patients at the end of life.

BACKGROUND: Despite evidence showing that nearly two thirds of the Canadian population prefer to die at home, the majority die in hospital. Honoring a patient's wish for their preferred location of death is an essential component in end-of-life care. Therefore, for those patients admitted to acute care whose choice is to transfer to a palliative care unit for end-of-life care, it is imperative that this occurs in a safe and timely manner. The General Internal Medicine ward at this local tertiary care academic center, did not have a standardized process for transferring patients at the end-of-life to the local palliative care unit. With bed calls made between Monday to Saturday at 8 am, weekday and weekend transfer times ranged between 1 to 6 hours. The aim of this project was to establish a standardized, safe and efficient patient transfer from acute care to the palliative care unit for a daily standard arrival time. METHODS: A multidisciplinary quality improvement team was formed to analyze the transfer process. Several Plan Do Study Act cycles were tested, targeting all steps of the transfer process and turnaround time. An outcome measure aiming for a turnaround time of two hours was set as the target. RESULTS: A total of fourteen patient transfers were included. Average transfer time during the weekday was reduced from a baseline average of 180.2 to 128.3 min. This change was found to be statistically significant and sustained (P<0.003). The average transfer time on weekends remained stable at 234 min. The outcome target of a 10:00 am arrival time to the palliative care unit was achieved 42% of the time. CONCLUSIONS: This project remains on-going and early data is encouraging as it met the targeted transfer time 42% of the time. Fidelity in the process measures helped to meet the targeted turnaround time of two hours for a safe and efficient transfer to the palliative care unit and ensured patients got to their preferred location for end of life care. The goal is to expand this project to other general internal medicine wards across the organization.

Evaluation of Molecular Methods to Identify Chagas Disease and Leishmaniasis in Blood Donation Candidates in Two Brazilian Centers.

In Brazil, blood donation is regulated by the Brazilian Ministry of Health, and all States follow the same protocol for clinical and laboratory screening. Brazil is an endemic country for Chagas disease (CD), caused by Trypanosoma cruzi, and for leishmaniasis, caused by a species of Leishmania spp. Screening for leishmaniosis is not routinely performed by blood banks. Given the antigenic similarity between T. cruzi and Leishmania spp., cross-reactions in serological tests can occur, and inconclusive results for CD have been found. The objective of this study was to apply molecular techniques, e.g., nPCR, PCR, and qPCR, to clarify cases of blood donation candidates with non-negative serology for CD and to analyze the difference between the melting temperature during real-time PCR using SYBR Green. Thirty-seven cases that showed non-negative results for CD using chemiluminescent microparticle immunoassay (CMIA) tests from blood banks in Campo Grande, MS, and Campinas, SP, were analyzed. In the serum samples, 35 samples were evaluated by ELISA, and 24.3% (9/35) showed positive results for CD. nPCR was able to detect 12 positive results in 35 samples (34.28%). qPCR for T. cruzi was quantifiable in the samples that showed a value ≥0.002 par eq/mL (parasite equivalents per milliliter), and in 35 samples, 11 (31.42%) were positive. Of all evaluated samples using the described tests (CMIA, ELISA, nPCR, and qPCR), 18 (48.6%) were positive for CD. For MCA by qPCR, the melting temperature was 82.06 °C ± 0.46 for T. cruzi and 81.9 °C ± 0.24 for Leishmania infantum. The Mann-Whitney test showed a significant value of p < 0.0001. However, the differentiation between T. cruzi and L. infantum could not be considered due to temperature overlap. For leishmaniasis, of the 35 samples with non-negative serology for CD tested by the indirect fluorescent antibody test (IFAT), only one sample (2.85%) was positive (1:80). The PCR for Leishmania spp. was performed on 36 blood samples from donation candidates, and all were negative. qPCR for L. infantum showed 37 negative results for the 37 analyzed samples. The data presented here show the importance of performing two different tests in CD screening at blood banks. Molecular tests should be used for confirmation, thereby improving the blood donation system.

Interstitial Macrophages Lead Early Stages of Bleomycin-Induced Lung Fibrosis and Induce Fibroblasts Activation.

A progressive fibrosing phenotype is critical in several lung diseases. It is irreversible and associated with early patient mortality. Growing evidence has revealed pulmonary macrophages' role as modulators of the fibrotic processes. The proportion, phenotype, and function of alveolar (AM) and interstitial macrophages (IM) at the early stages of bleomycin-induced pulmonary fibrosis have not been clearly described. In this way, our study aimed to characterize these macrophage populations and investigate the effect on fibroblast activation. C57BL/6 mice were intratracheally injected with bleomycin and were sacrificed at day 3, 5, and 7 for the performance of flow cytometry and fluorescent-activated cell sorting analysis for protein and gene expression quantification. After bleomycin administration, the proportion of IM was significantly higher than that of AM, which showed a decay during the inflammatory phase, and peaked at day 7. At day 7 of the inflammatory phase, AM started shifting their phenotype from M1-like towards M2, while IM showed a M2-like phenotype. Conditioned medium derived from IM sorted at day 7 induced fibroblast activation and differentiation in myofibroblasts in vitro. Our findings indicate that IM are the largest macrophage population at the early stages of experimental pulmonary fibrosis and are secreted mediators able to activate fibroblasts, pointing to macrophage modulation as a potential therapeutic strategy to restrain progressive fibrosing lung disorders.

fMRIflows: A Consortium of Fully Automatic Univariate and Multivariate fMRI Processing Pipelines.

How functional magnetic resonance imaging (fMRI) data are analyzed depends on the researcher and the toolbox used. It is not uncommon that the processing pipeline is rewritten for each new dataset. Consequently, code transparency, quality control and objective analysis pipelines are important for improving reproducibility in neuroimaging studies. Toolboxes, such as Nipype and fMRIPrep, have documented the need for and interest in automated pre-processing analysis pipelines. Recent developments in data-driven models combined with high resolution neuroimaging dataset have strengthened the need not only for a standardized preprocessing workflow, but also for a reliable and comparable statistical pipeline. Here, we introduce fMRIflows: a consortium of fully automatic neuroimaging pipelines for fMRI analysis, which performs standard preprocessing, as well as 1st- and 2nd-level univariate and multivariate analyses. In addition to the standardized pre-processing pipelines, fMRIflows provides flexible temporal and spatial filtering to account for datasets with increasingly high temporal resolution and to help appropriately prepare data for advanced machine learning analyses, improving signal decoding accuracy and reliability. This paper first describes fMRIflows' structure and functionality, then explains its infrastructure and access, and lastly validates the toolbox by comparing it to other neuroimaging processing pipelines such as fMRIPrep, FSL and SPM. This validation was performed on three datasets with varying temporal sampling and acquisition parameters to prove its flexibility and robustness. fMRIflows is a fully automatic fMRI processing pipeline which uniquely offers univariate and multivariate single-subject and group analyses as well as pre-processing.

Television, Brands, and the Pandemic: How Spanish TV Channels Treated the Brands Most Valued for Their CSR During the COVID-19 Lockdown.

Due to the COVID-19 pandemic, in March 2020, the Spanish Government announced a total lockdown of the population and the interruption of all nonessential economic activity. From this point, televisions adapted their programming schedules by reducing their usual informative content, such as sport or economic segments. In this context, it would be reasonable to assume that the overall television coverage devoted to the main Spanish brands would decrease, but what about those considered to be most active in the field of corporate social responsibility (CSR)? In this work, we analyze the presence of the Spanish brands that are most valued for their CSR on the four main television channels with the highest audience over the two months of total lockdown, and also in the online press. The study confirms that the television coverage of these brands was not only reduced but was also mostly positive during the pandemic, so it reveals the CSR importance in crisis periods.

Perception of nurses about nursing teleconsultation in primary care / Percepción de los enfermeros en relación la teleconsulta de enfermería en la atención inicial / Percepção dos enfermeiros sobre teleconsulta de enfermagem na atenção primária

ABSTRACT Objective analyze the nurse's perception about nursing teleconsultation in Primary Health Care through the workflows characterization, potential, challenges and teleconsultation in nursing feasibility. Method exploratory-descriptive study with a qualitative approach. Data were collected, between the months of May and June 2021, with 19 nurses from four health districts of a capital in south of Brazil, using digital questionnaire. Data were systematized in Microsoft ExcelⓇ and analyzed following the criteria of the Discourse of the Collective Subject. This process was carried out with the support of the DSCsoftⓇ Program. Results the results were organized into five thematic categories: Nursing teleconsultation flow in Primary Health Care; Teleconsultation process; Instruments used during the teleconsultation; Potentialities and challenges identified during the teleconsultation in the Primary Health Care; and, Applicability: services that can be resolved through teleconsultation. Among the challenges are the inherent problems of communication and internet connectivity and the distrust of users in relation to this new consultation modality. Conclusion telecare in nursing is a recent technological innovation, with several challenges as: the possible failure in communication between the professional and the user; internet connection problems; lack of ability to travel from new tools; lack of privacy and excessive noise and distrust of users about the service provided. With the teleconsultation, there was an extension of the users' access to the health services, there was greater agility and efficiency in the services provided to the population.

RESUMEN Objetivo analizar la percepción de los enfermeros en relación a la teleconsulta de enfermería en la atención inicial de salud a través de la caracterización de los flujos de trabajo, potenciales, desafíos y la viabilidad de la teleconsulta en enfermería. Método estudio exploratório-descriptivo, con abordaje cualitativa. Los datos son colectados con 19 enfermeros que actúan en cuatro distritos sanitarios de una capital del sur del Brasil, utilizando un cuestionario digital. La colecta de los datos fue realizada entre los meses de mayo a junio de 2021 de forma totalmente online; los datos fueron sistematizados en el Microsoft Excel y analizados según los criterios del Discurso del sujeto colectivo, que utiliza las representaciones sociales y el senso común retratado la manifestación o posicionamento de cada individuo y posibilita agrupamientos de pensamientos y/o opiniones individuales sobre determinado asunto. Ese proceso fue realizado con el apoyo del Programa DSCsoft. Resultados los resultados fueron organizados en cinco categorías temáticas: Flujo de la teleconsulta de enfermería en la Atención Inicial de Salud; Proceso de realización de la teleconsulta; Instrumentos utilizados a lo largo de la realización de la teleconsulta; Potencialidades y desafíos identificados a lo largo de la teleconsulta en la Atención Inicial de Salud; y, Aplicabilidad: atendimientos pasibles de resoluciones por medio de la teleconsulta. Entre los desafíos están los problemas inherente a la comunicación y la conectividad con la internet y la desconfianza de los usuarios en relación a esta nueva modalidad de consulta: Conclusión el teleatendimiento en la área de la enfermería es una innovación tecnológica reciente, con diversos desafíos, como: la posible falla en la comunicación entre el profesional y el usuário; problemas de la conexión con la internet; falta de habilidad para manejo de las nuevas herramientas; falta de privacidad, exceso de ruidos y desconfianza de los usuarios a los servicios de salud, ocurre mayor agilidad y eficacia de los atendimientos realizados a la población.

RESUMO Objetivo analisar a percepção dos enfermeiros sobre teleconsulta de enfermagem na Atenção Primária de Saúde através da caracterização dos fluxos de trabalhos, potenciais, desafios e viabilidade da teleconsulta em enfermagem. Método estudo exploratório-descritivo, com abordagem qualitativa. Os dados foram coletados, entre os meses de maio a junho de 2021, com 19 enfermeiros que atuam em quatro distritos sanitários de uma capital do Sul do Brasil, utilizando um questionário digital. Os dados foram sistematizados no Microsoft Excel Ⓡ e analisados segundo os critérios do Discurso do Sujeito Coletivo. Esse processo foi realizado com o apoio do Programa DSCsoftⓇ. Resultados os resultados foram organizados em cinco categorias temáticas: Fluxo da teleconsulta de enfermagem na Atenção Primária à Saúde; Processo de realização da teleconsulta; Instrumentos utilizados durante a realização da teleconsulta; Potencialidades e desafios identificados durante a teleconsulta na Atenção Primária à Saúde; e, Aplicabilidade: atendimentos passíveis de resolução por meio da teleconsulta. Entre os desafios estão os problemas inerentes à comunicação e à conectividade com a internet e a desconfiança dos usuários em relação a esta nova modalidade de consulta. Conclusão o teleatendimento na área da enfermagem é uma inovação tecnológica recente, com diversos desafios, como: a possível falha na comunicação entre o profissional e o usuário; problemas de conexão com a internet; falta de habilidade para manuseio das novas ferramentas; falta de privacidade, excesso de ruídos e desconfiança dos usuários sobre o atendimento realizado. Com a teleconsulta ocorreu a ampliação do acesso dos usuários aos serviços de saúde, houve maior agilidade e eficácia dos atendimentos realizados à população.

Factors that Delay Transfers from Acute Care to a Local Palliative Care Unit.

For patients desiring end-of-life care in a palliative care unit, ensuring a safe and timely transfer while reducing length of stay in acute care is optimal. A chart review of 130 patients was completed on those who either died in acute care or were transferred to a palliative care unit. In all, 31% of patients died in acute care and 69% were transferred to a palliative care unit. Barriers impacting a timely transfer included disposition planning, behavioural changes requiring monitoring, imminently dying patients and those awaiting medical assistance in dying. This article makes clinical recommendations to address these barriers.

Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.

Chronic pulmonary aspergillosis (CPA) is a devastating disease with increasing prevalence worldwide. The characteristic granulomatous-like inflammation poses as the major setback to effective antifungal therapies by limiting drug access to fungi. These inflammatory lung structures are reported to be severely hypoxic; nevertheless, the underlying mechanisms whereby these processes contribute to fungal persistence remain largely unknown. Hypoxia-inducible factor 1 alpha (HIF-1α), besides being the major cellular response regulator to hypoxia, is a known central immune modulator. Here, we used a model of Aspergillus fumigatus airway infection in myeloid-restricted HIF-1α knock-out (mHif1α-/- ) mice to replicate the complex structures resembling fungal granulomas and evaluate the contribution of HIF-1α to antifungal immunity and disease development. We found that fungal-elicited granulomas in mHif1α-/- mice had significantly smaller areas, along with extensive hyphal growth and increased lung fungal burden. This phenotype was associated with defective neutrophil recruitment and an increased neutrophil death, therefore highlighting a central role for HIF-1α-mediated regulation of neutrophil function in the pathogenesis of chronic fungal infection. These results hold the promise of an improved capacity to manage the progression of chronic fungal disease and open new avenues for additional therapeutic targets and niches of intervention.

Comparison Between Continuous Positive Airway Pressure and High-Flow Nasal Cannula as Postextubation Respiratory Support in Neonates: A Systematic Review and Meta-Analysis.

OBJECTIVE: The interest in noninvasive respiratory support has been increasing, including continuous positive airway pressure and recent respiratory methods, namely high-flow nasal cannula. It is discussed if high-flow nasal cannula can reduce continuous positive airway pressure or invasive ventilation use. This systematic review and meta-analysis aimed to compare continuous positive airway pressure and high-flow nasal cannula as postextubation respiratory support in neonates. MATERIALS AND METHODS: A literature search, based on Preferred Reporting of Items of Systematic Reviews and Meta-Analyses guidelines, was conducted across MEDLINE (through PubMed), Scopus, and Web of Science in 15 years (2006-2021) assessing randomized controlled trials that compared continuous positive airway pressure with high-flow nasal cannula as postextubation interventions in neonates. The primary outcome was extubation failure at 72 hours and/or at 7 days and the secondary outcomes included air leak syndrome, pneumothorax, bronchopulmonary dysplasia, nasal trauma, abdominal distension, and mortality. RESULTS: Seven studies were included, comprising 1044 neonates. No statistically significant differences were found between high-flow nasal cannula and continuous positive airway pressure in extubation failure (at 72 hours and 7 days), air leak syndrome, pneumothorax, bronchopulmonary dysplasia, abdominal distension, and mortality. High-flow nasal cannula was associated with a lower incidence of nasal trauma (odds ratio = 0.21; 95% CI 0.08-0.52; P = .0008). Studies assessing extreme premature infants (<28 weeks) raised some efficacy and safety concerns. CONCLUSION: High-flow nasal cannula may be as effective and safe as continuous positive airway pressure, with similar extubation failure and risk of air leak syndrome, pneumothorax, bronchopulmonary dysplasia, abdominal distension, and mortality with the advantage of less nasal trauma. High-flow nasal cannula should be considered as an alternative to continuous positive airway pressure in postextubation settings in neonates. Further studies are needed to establish efficacy and safety in lower gestational ages.

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Quantification of forensic genetic evidence: Comparison of results obtained by qualitative and quantitative software for real casework samples.

To overcome the multifactorial complexity associated with the analysis and interpretation of the capillary electrophoresis results of forensic mixture samples, probabilistic genotyping methods have been developed and implemented as software, based on either qualitative or quantitative models. The former considers the electropherograms' qualitative information (detected alleles), whilst the latter also takes into account the associated quantitative information (height of allele peaks). Both models then quantify the genetic evidence through the computation of a likelihood ratio (LR), comparing the probabilities of the observations given two alternative and mutually exclusive hypotheses. In this study, the results obtained through the qualitative software LRmix Studio (v.2.1.3), and the quantitative ones: STRmix™ (v.2.7) and EuroForMix (v.3.4.0), were compared considering real casework samples. A set of 156 irreversibly anonymized sample pairs (GeneMapper files), obtained under the scope of former cases of the Portuguese Scientific Police Laboratory, Judiciary Police (LPC-PJ), were independently analyzed using each software. Sample pairs were composed by (i) a mixture profile with either two or three estimated contributors, and (ii) a single contributor profile associated. In most cases, information on 21 short tandem repeat (STR) autosomal markers were considered, and the majority of the single-source samples could not be a priori excluded as belonging to a contributor to the paired mixture sample. This inter-software analysis shows the differences between the probative values obtained through different qualitative and quantitative tools, for the same input samples. LR values computed in this work by quantitative tools showed to be generally higher than those obtained by the qualitative. Although the differences between the LR values computed by both quantitative software showed to be much smaller, STRmix™ generated LRs are generally higher than those from EuroForMix. As expected, mixtures with three estimated contributors showed generally lower LR values than those obtained for mixtures with two estimated contributors. Different software products are based on different approaches and mathematical or statistical models, which necessarily result in the computation of different LR values. The understanding by the forensic experts of the models and their differences among available software is therefore crucial. The better the expert understands the methodology, the better he/she will be able to support and/or explain the results in court or any other area of scrutiny.

Parasite load evaluation by qPCR and blood culture in Chagas disease and HIV co-infected patients under antiretroviral therapy.

Chagas disease also known as American trypanosomiasis, is caused by Trypanosoma cruzi and transmitted by triatominae-contaminated feces. It is considered a neglected tropical disease that affects 6 to 7 million people worldwide. The reactivation of Chagas disease occurs when the chronically infected hosts are not able to control T. cruzi infection, generating recurrence of the acute phase. HIV is the main immunosuppressive infection that can lead to the reactivation of chronic Chagas disease in AIDS conditions. In co-infected patients, the reactivation of Chagas disease is related to their high parasite load, high HIV viral load, and CD4 T-cell counting less than 200/mm3, which may evolve to meningoencephalitis and myocarditis. Eight T. cruzi/HIV co-infected patients under antiretroviral therapy (ART) and ten Chagas disease patients without HIV infection that attended at Study Group of Chagas Disease, Hospital de Clínicas, University of Campinas (GEdoCh/HC/UNICAMP-SP) and Pontifical Catholic University of Campinas SP (PUCC/SP) were evaluated. Tests for Chagas disease were performed, such as qPCR and T. cruzi blood culture. The patient's medical records were analyzed to verify clinical and epidemiological data, viral load, and CD4 T-cell counting since the outset of ART. For both groups, we found no statically significant differences between parasite load via blood culture and qPCR. In T. cruzi/HIV co-infected subjects, we observed a significant increase of CD4 T-cells counting and viral load decrease, which became undetectable over the years after ART. Parasites isolated from the patient's blood culture were genotyped, being the majority of them infected with TcII and one case of mixed infection (TcII and TcV/TcVI). These results were expected according to the region of origin of the patients. We suggest that the parasite load be monitored through qPCR in T.cruzi/HIV co-infected patients. We conclude that ART in people living with HIV improves infection and immunosuppression control, enabling the natural evolution of the American trypanosomiasis.

Correlação entre medidas ecocardiográficas e hemodinâmicas na avaliação do átrio direito e ventrículo direito em pacientes com hipertensão pulmonar / Correlation between echocardiographic and hemodynamic measurements in right atrium and right ventricle assessments of patients with pulmonary hypertension

Introdução: Hipertensão Pulmonar (HP), uma condição clínica grave, pode levar à disfunção sistólica do ventrículo direto (DSVD), com implicações prognósticas. Pacientes com suspeita de HP devem ser submetidos ao ecocardiograma transtorácico (ECOTT) para diagnóstico e avaliação, colocando-o como o principal exame de triagem e acompanhamento. Objetivo: Verificar a associação e a concordância das medidas referentes à pressão média no átrio direito (AD) e à disfunção sistólica do ventrículo direto (DSVD) ao (ECOTT) e ao cateterismo de câmaras direitas (CCD) em pacientes com (HP). Métodos: Foram incluídos indivíduos com diagnóstico de (HP). Todos os pacientes foram submetidos ao ECOTT e CCD. Avaliou-se pelo ECOTT: área do átrio direito (AAD), pressão média do átrio direito (AD) através por meio do diâmetro e da colapsabilidade da veia cava inferior (PMADECOTT ), strain AD (SAD), TAPSE (excursão sistólica do plano anular tricúspide), MAF (mudança da área fracional), SPLVD (strain da parede livre do VD) e onda s´ tricuspídea. Pelo CCD avaliaram-se pressão média do (PMADCCD ) e índice cardíaco (IC). Resultados: Dos 16 pacientes, 13 eram do sexo feminino. A idade média foi de 44,4 anos (±14,9). Constataram-se associação entre pressão média do átrio direito PMADCCD com área do átrio direito, PMADECOTT pressão média do átrio direito e SAD strain do átrio direito (r=0,845, r=0,621 e r=-0,523, respectivamente; p< 0,05). Verificou-se associação entre as categorias de risco de mortalidade, mensuradas pelas medidas AAD da área do átrio direito e pressão média do átrio direito PMADCCD (X2=10,42; p=0,003), com concordância moderada (k=0,44; p=0,012). DSVD A disfunção sistólica do ventrículo direto estava presente em dez pacientes. Houve associação entre disfunção sistólica do ventrículo direto DSVD (presente ou ausente) e índice cardíaco IC (r=0,522; p=0,04), com concordância moderada (k=0,43; p=0,037). Conclusão: As medidas do ecocardiograma transtorácico (ECOTT) e cateterismo de câmara direita (CCD) demostraram associação na avaliação da pressão média do átrio direito com melhor associação entre área do átrio direito AAD e pressão média do átrio direito (PMADCCD) . Houve associação com concordância moderada quanto à disfunção sistólica do ventrículo direto (DSVD) entre métodos. (AU)

Introduction: Pulmonary hypertension (PH), a serious clinical condition, can lead to right ventricular systolic dysfunction (RVSD) with prognostic implications. Patients with suspected PH should undergo transthoracic echocardiography (TTE) for diagnosis and evaluation as the main screening and follow-up exam. Objective: To verify the associations of and agreement between measurements of mean pressure in the right atrium (RA) and RVSD with TTE Method: Individuals diagnosed with PH were included. All patients underwent TTE and RCC. The following were evaluated by TTE: right atrial area (RAA), mean right atrial pressure through the diameter and collapsibility of the inferior vena cava (RMAPTTE), RA strain (RAS), tricuspid annular plane systolic excursion, fractional area change, RV free wall strain, and tricuspid s' wave. Mean RA pressure (RMAPRCC) and cardiac index (CI) were evaluated through the RCC. Results: Of the 16 patients, 13 were female. The mean patient age was 44.4 (±14.9) years. An association was found between RMAPRCC and AAD, RMAPTTE, and RAS (r=0.845, r=0.621, and r=-0.523, respectively; p<0.05). There was an association between the mortality risk categories measured by the RAA and RMAPRCC measures (X2=10.42; p=0.003), with moderate agreement (k=0.44; p=0.012). RVSDJ was present in 10 patients. There was an association between RVSD (present or absent) and CI (r=0.522; p=0.04) with moderate agreement (k=0.43; p=0.037). Conclusion: The TTE and RCC measurements showed an association in the assessment of mean right atrial pressure, especially between RAA and RMAPRCC. An association with RVSD and moderate agreement between methods were also noted. (AU)

Evaluation of Trypanosoma cruzi parasitic load by real-time PCR and blood culture in long-term kidney transplant recipients.

INTRODUCTION: Acute Chagas disease involving reactivation can occur after organ transplant, and follow-up by direct parasitological or molecular methods is essential for monitoring the parasitic load in such patients. In contrast, there is a little data on the parasitic load in long-term organ recipients. In this study, we examined the parasitic load in long-term kidney transplant patients and assessed the possibility of late Chagas disease reactivation. METHODOLOGY: Blood cultures and real-time PCR were used to assess the parasitic load in four immunosuppressed patients who underwent kidney transplants (between 1996 and 2014) and were also treated for parasites. RESULTS: There were no positive blood culture or real-time PCR results in Chagas disease patients who received kidney transplants. The real-time PCR presented detection limit of 0.1 parasite equivalent/mL. The time interval between the transplant and sample collection varied from one to 19 years. CONCLUSIONS: No parasites were detected in the evaluated patients. The use of benznidazole and immunosuppressive therapy may have contributed to control the T. cruzi infection. In transplanted patients with Chagas disease, the use of methods such real-time PCR and blood culture can monitor the parasitic load and prevent disease reactivation.