Fiocruz in Antarctica - health and environmental surveillance facing the challenges of the 21st century.

FioAntar, FIOCRUZ's research project in Antarctica, is based on the One Health approach. FioAntar aims to generate relevant information that will help reduce the risk of future pandemics and improve the search for chemical compounds and new biological molecules. After four expeditions to Antarctica under the scope of PROANTAR, Fiocruz has identified Influenza H11N2 virus in environmental fecal samples, as well as Histoplasma capsulatum and Bacillus cereus in soil samples. In addition, in a prospective virome analysis from different lakes in the South Shetland Islands, six viral orders were described, supporting future research related to the biodiversity and viral ecology in this extreme ecosystem. Our findings of environmental pathogens of public health importance are a warning about the urgency of establishing a surveillance agenda on zoonoses in Antarctica due to the imminent risks that ongoing environmental and climate changes impose on human health across the planet. FioAntar strives to establish a comprehensive surveillance program across Antarctica, monitoring circulation of pathogens with the potential to transcend continent boundaries, thereby mitigating potential spread. For Fiocruz, Antarctica signifies a new frontier, teeming with opportunities to explore novel techniques, refine established methodologies, and cultivate invaluable knowledge.

The Complexity of Tobacco Smoke-Induced Mutagenesis in Head and Neck Cancer.

Tobacco smoke, alone or combined with alcohol, is the predominant cause of head and neck cancer (HNC). Here, we further explore how tobacco exposure contributes to cancer development by mutational signature analysis of 265 whole-genome sequenced HNC from eight countries. Six tobacco-associated mutational signatures were detected, including some not previously reported. Differences in HNC incidence between countries corresponded with differences in mutation burdens of tobacco-associated signatures, consistent with the dominant role of tobacco in HNC causation. Differences were found in the burden of tobacco-associated signatures between anatomical subsites, suggesting that tissue-specific factors modulate mutagenesis. We identified an association between tobacco smoking and three additional alcohol-related signatures indicating synergism between the two exposures. Tobacco smoking was associated with differences in the mutational spectra and repertoire of driver mutations in cancer genes, and in patterns of copy number change. Together, the results demonstrate the multiple pathways by which tobacco smoke can influence the evolution of cancer cell clones.

The descriptive epidemiology of melanoma in Italy has changed - for the better.

A recent research project using data from a total of 40 cancer registries has provided new epidemiologic insights into the results of efforts for melanoma control in Italy between the 1990s and the last decade. In this article, the authors present a summary and a commentary of their findings. Incidence increased significantly throughout the study period in both sexes. However, the rates showed a stabilization or a decrease in men and women aged below 35 years. The risk of disease increased for successive cohorts born until 1973 (women) and 1975 (men) while subsequently tending to decline. The trend towards decreasing tumor thickness and increasing survival has continued, but a novel favorable prognostic factor has emerged since 2013 for patients - particularly for males - with thick melanoma, most likely represented by molecular targeted therapies and immune checkpoint inhibitors. Due to this, the survival gap between males and females has been filled out. In the meanwhile, and despite the incidence increase, dermatologists have not lowered their threshold to perform skin biopsy. Skin biopsy rate has increased because of the increasingly greater volume of dermatologic office visits, but the proportion of skin biopsies out of dermatologic office visits has remained constant. In summary, an important breakthrough in melanoma control in Italy has taken place. Effective interventions have been implemented across the full scope of care, which involve many large local populations - virtually the whole national population. The strategies adopted during the last three decades represent a valuable basis for further steps ahead in melanoma control in Italy.

A High-Efficiency Capacitor-Based Battery Equalizer for Electric Vehicles.

Technology in electric vehicles has increased substantially in the past decade. Moreover, it is projected to grow at record highs in the coming years since these vehicles are needed to reduce the contamination related to the transportation sector. One of the essential elements of an electric car is its battery, due to its cost. Batteries comprise parallel and series-connected cell arrangements to meet the power system requirements. Therefore, they require a cell equalizer circuit to preserve their safety and correct operation. These circuits keep a specific variable of all cells, such as the voltage, within a particular range. Within cell equalizers, capacitor-based ones are very common as they have many desirable characteristics of the ideal equalizer. In this work, an equalizer based on the switched-capacitor is proposed. A switch is added to this technology that allows the disconnection of the capacitor from the circuit. In this way, an equalization process can be achieved without excess transfers. Therefore, a more efficient and faster process can be completed. In addition, it allows another equalization variable to be used, such as the state of charge. This paper studies the operation, power design, and controller design of the converter. Moreover, the proposed equalizer was compared to other capacitor-based architectures. Finally, simulation results were presented to validate the theoretical analysis.

Hipertensión pulmonar: señalización mediada por canales de calcio, dianas farmacológicas presentes y futuras

La hipertensión arterial pulmonar se caracteriza por una presión arterial pulmonar media y resistencia vascular pulmonar elevadas y remodelado patológico de las arterias pulmonares. La entrada de calcio desde el espacio extracelular al intracelular a través de canales dependientes e independientes de voltaje juega un rol fundamental en el aumento de la contractilidad de las arterias pulmonares y la pérdida de regulación del comportamiento proliferativo de las células de las distintas capas de la pared de las arterias pulmonares. De esta manera, estos canales contribuyen con la vasoconstricción exacerbada de las arterias pulmonares y a su remodelado patológico. El objetivo de esta revisión es recapitular la evidencia obtenida desde modelos celulares y animales respecto a la contribución de los principales canales de calcio de membrana plasmática en estos mecanismos fisiopatológicos claves en el desarrollo de la hipertensión pulmonar, discutiendo su valor potencial como diana farmacológica para terapias presentes y futuras.

Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990-2015).

(1) Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990-2001 to 81.9% in 2009-2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70-79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003-2015 versus 1990-2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level.

Temporal Trend, Causes, and Timing of Neonatal Mortality of Moderate and Late Preterm Infants in São Paulo State, Brazil: A Population-Based Study.

Moderate and late preterm newborns comprise around 85% of live births < 37 weeks gestation. Data on their neonatal mortality in middle-income countries is limited. This study aims to analyze the temporal trend, causes and timing of neonatal mortality of infants with 320/7-366/7 weeks gestation without congenital anomalies from 2004-2015 in the population of São Paulo State, Brazil. A database was built by deterministic linkage of birth and death certificates. Causes of death were classified by ICD-10 codes. Among 7,317,611 live births in the period, there were 545,606 infants with 320/7-366/7 weeks gestation without congenital anomalies, and 5782 of them died between 0 and 27 days. The neonatal mortality rate decreased from 16.4 in 2004 to 7.6 per thousand live births in 2015 (7.47% annual decrease by Prais-Winsten model). Perinatal asphyxia, respiratory disorders and infections were responsible, respectively, for 14%, 27% and 44% of the 5782 deaths. Median time to death was 24, 53 and 168 h, respectively, for perinatal asphyxia, respiratory disorders, and infections. Bottlenecks in perinatal health care are probably associated with the results that indicate the need for policies to reduce preventable neonatal deaths of moderate and late preterm infants in the most developed state of Brazil.

A 7-Week Summer Camp in Antarctica Induces Fluctuations on Human Oral Microbiome, Pro-Inflammatory Markers and Metabolic Hormones Profile.

Antarctic camps pose psychophysiological challenges related to isolated, confined, and extreme (ICE) conditions, including meals composed of sealed food. ICE conditions can influence the microbiome and inflammatory responses. Seven expeditioners took part in a 7-week Antarctic summer camp (Nelson Island) and were evaluated at Pre-Camp (i.e., at the beginning of the ship travel), Camp-Initial (i.e., 4th and 5th day in camp), Camp-Middle (i.e., 19th-20th, and 33rd-34th days), Camp-Final (i.e., 45th-46th day), and at the Post-Camp (on the ship). At the Pre-Camp, Camp-Initial, and Camp-Final, we assessed microbiome and inflammatory markers. Catecholamines were accessed Pre- and Post-Camp. Heart rate variability (HRV), leptin, thyroid stimulating hormone (TSH), and thyroxine (T4) were accessed at all time points. Students' t-tests or repeated-measures analysis of variance (one or two-way ANOVA) followed by Student-Newman-Keuls (post hoc) were used for parametric analysis. Kruskal-Wallis test was applied for non-parametric analysis. Microbiome analysis showed a predominance of Pseudomonadota (34.01%), Bacillota (29.82%), and Bacteroidota (18.54%), followed by Actinomycetota (5.85%), and Fusobacteria (5.74%). Staying in a long-term Antarctic camp resulted in microbiome fluctuations with a reduction in Pseudomonadota-a "microbial signature" of disease. However, the pro-inflammatory marker leptin and IL-8 tended to increase, and the angiogenic factor VEGF was reduced during camp. These results suggest that distinct Antarctic natural environments and behavioral factors modulate oral microbiome and inflammation.

Brentuximab vedotin in ALK-negative anaplastic large cell lymphoma presenting with alar mass: A case report

@#Anaplastic large cell lymphoma (ALCL) is a rare subtype of T-cell non-Hodgkin lymphoma (NHL) primarily involving the lymph nodes; however, extra-nodal manifestations are also common. Diagnosis can be confirmed by a combination of histopathology and immunohistochemical staining. Complete workup and staging include imaging and bone marrow examination. This presents a case of a 55-year-old male with anaplastic lymphoma kinase (ALK) - negative ALCL presenting with an alar mass. ALCL patients often present with rapidly progressing lymphadenopathy. Extra-nodal manifestations commonly involve the skin, liver, lung, and gastrointestinal tract. Biopsy of the mass showed small to medium-sized anaplastic lymphoid cells that stained positive for CD30, LCA (CD45), CD99, and negative for CD20, ALK (CD246), neuron-specific enolase, CD34, CD5, PAX5, TdT, MPO, CD138, EMA, pancytokeratin, CD3 and synaptophysin. These findings were most compatible with an ALK-negative ALCL. The patient was started on a combination of brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (BV + CHP) every 21 days for 6 cycles. There was a progressive decrease in the size of the mass, and a resolution was noted after the 5th cycle. FDG-PET/CT scan was done after the 6th cycle of chemotherapy and 6 months after completion of treatment. Both scans showed no evidence of metabolically active nodal or extra-nodal lymphomatous disease. This case showed a unique extra-nodal manifestation of an ALK-negative ALCL presenting as an alar mass with a good response to BV + CHP. However, more evidence is necessary to further establish the role of BV as the first-line treatment regimen for CD30-positive peripheral T-cell lymphoma (PTCL), including ALK-negative ALCL.

[Pulmonary hypertension: calcium channel-mediated signaling, present and future pharmacological targets]. / Hipertensión pulmonar: señalización mediada por canales de calcio, dianas farmacológicas presentes y futuras.

Pulmonary arterial hypertension is characterized by increased mean pulmonary arterial pressure, resistance, and pathological remodeling of pulmonary arteries. Calcium entry from the extracellular to the intracellular space through voltage-dependent and -independent channels play a major role in the increase of contractility of pulmonary arteries and in the loss of regulation of the proliferative behavior of the cells from the different layers of the pulmonary arterial wall. In doing so, these channels contribute to enhanced vasoconstriction of pulmonary arteries and their pathological remodeling. This review aims to summarize the evidence obtained from animal and cellular models regarding the involvement of the main plasma membrane calcium channels in these key pathophysiological processes for pulmonary arterial hypertension, discussing the potential value as pharmacological targets for therapies in the present and the future.

Antarctic fungi with antibiotic potential isolated from Fort William Point, Antarctica.

The Antarctic continent is one of the most inhospitable places on earth, where living creatures, mostly represented by microorganisms, have specific physiological characteristics that allow them to adapt to the extreme environmental conditions. These physiological adaptations can result in the production of unique secondary metabolites with potential biotechnological applications. The current study presents a genetic and antibacterial characterization of four Antarctic fungi isolated from soil samples collected in Pedro Vicente Maldonado Scientific Station, at Fort William Point, Greenwich Island, Antarctica. Based on the sequences of the internal transcribed spacer (ITS) region, the fungi were identified as Antarctomyces sp., Thelebolus sp., Penicillium sp., and Cryptococcus gilvescens. The antibacterial activity was assessed against four clinical bacterial strains: Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, and Staphylococcus aureus, by a modified bacterial growth inhibition assay on agar plates. Results showed that C. gilvescens and Penicillium sp. have potential antibiotic activity against all bacterial strains. Interestingly, Thelebolus sp. showed potential antibiotic activity only against E. coli. In contrast, Antarctomyces sp. did not show antibiotic activity against any of the bacteria tested under our experimental conditions. This study highlights the importance of conservation of Antarctica as a source of metabolites with important biomedical applications.

Left ventricular assist device implantation via lateral thoracotomy: A systematic review and meta-analysis.

BACKGROUND: Left ventricular assist device (LVAD) implantation via lateral thoracotomy can offer similar effectiveness to conventional approaches with less perioperative adverse events. We performed a systematic review and meta-analysis to determine the potential benefits of lateral thoracotomy (LT) for LVAD implantation compared to median sternotomy. METHODS: We searched MEDLINE and Embase databases for studies comparing continuous-flow LVAD implantation using LT with conventional sternotomy. Main outcomes were perioperative mortality and complications. RESULTS: Twenty-five observational studies enrolling 3072 patients were included with a median follow-up of 10 months. Perioperative mortality (30 day or in-hospital) was 7% (LT) and 14% (sternotomy); however, mortality differences were no longer statistically significant in matched/adjusted studies (RR:0.86; 95%CI:0.52-1.44; p = 0.58). LT was associated with decreased need for blood product transfusions (mean difference[MD]: -4.7; 95%CI: -7.2 to -2.3 units; p < 0.001), reoperation for bleeding (RR:0.34; 95%CI:0.22-0.54; p < 0.001), postoperative RVAD implantation (RR:0.53; 95%CI:0.36-0.77; p < 0.001), days requiring inotropes (MD: -1.1; 95%CI: -2.1 to -0.03 inotrope days; p = 0.04), ICU (MD: -3.3; 95%CI: -6.0 to -0.7 ICU days; p = 0.01), and hospital length of stay (MD: -5.1; 95%CI: -10.1 to -0.1 hospital days; p = 0.04) in matched/adjusted studies. Overall mortality during follow-up was significantly lower for LT in unmatched/unadjusted studies but not statistically significantly lower in matched/adjusted studies (Hazard Ratio:0.82; 95%CI:0.59-1.14; p = 0.24). CONCLUSION: LVAD implantation via LT was associated with significantly decreased need for blood products, reoperation for bleeding, and postoperative RVAD implantation. Furthermore, days on inotropic support were also lower, likely contributing to the shorter length of stay. These findings support greater use of a LT approach for carefully selected patients.

Heart rate variability, thyroid hormone concentration, and neuropsychological responses in Brazilian navy divers: a case report of diving in Antarctic freezing waters.

Open-water diving in a polar environment is a psychophysiological challenge to the human organism. We evaluated the effect of short-term diving (i.e., 10 min) in Antarctic waters on autonomic cardiac control, thyroid hormone concentration, body temperatures, mood, and neuropsychological responses (working memory and sleepiness). Data collection was carried out at baseline, before, and after diving in four individuals divided into the supporting (n=2) and diving (n=2) groups. In the latter group, autonomic cardiac control (by measuring heart rate variability) was also assessed during diving. Diving decreased thyroid-stimulating hormone (effect size = 1.6) and thyroxine (effect size = 2.1) concentrations; these responses were not observed for the supporting group. Diving also reduced both the parasympathetic (effect size = 2.6) and sympathetic activities to the heart (ES > 3.0). Besides, diving reduced auricular (effect size > 3.0), skin [i.e., hand (effect size = 1.2) and face (effect size = 1.5)] temperatures compared to pre-dive and reduced sleepiness state (effect size = 1.3) compared to basal, without changing performance in the working memory test. In conclusion, short-term diving in icy waters affects the hypothalamic-pituitary-thyroid axis, modulates autonomic cardiac control, and reduces body temperature, which seems to decrease sleepiness.

Cinaciguat (BAY-582667) Modifies Cardiopulmonary and Systemic Circulation in Chronically Hypoxic and Pulmonary Hypertensive Neonatal Lambs in the Alto Andino.

Neonatal pulmonary hypertension (NPHT) is produced by sustained pulmonary vasoconstriction and increased vascular remodeling. Soluble guanylyl cyclase (sGC) participates in signaling pathways that induce vascular vasodilation and reduce vascular remodeling. However, when sGC is oxidized and/or loses its heme group, it does not respond to nitric oxide (NO), losing its vasodilating effects. sGC protein expression and function is reduced in hypertensive neonatal lambs. Currently, NPHT is treated with NO inhalation therapy; however, new treatments are needed for improved outcomes. We used Cinaciguat (BAY-582667), which activates oxidized and/or without heme group sGC in pulmonary hypertensive lambs studied at 3,600 m. Our study included 6 Cinaciguat-treated (35 ug kg-1 day-1 x 7 days) and 6 Control neonates. We measured acute and chronic basal cardiovascular variables in pulmonary and systemic circulation, cardiovascular variables during a superimposed episode of acute hypoxia, remodeling of pulmonary arteries and changes in the right ventricle weight, vasoactive functions in small pulmonary arteries, and expression of NO-sGC-cGMP signaling pathway proteins involved in vasodilation. We observed a decrease in pulmonary arterial pressure and vascular resistance during the acute treatment. In contrast, the pulmonary pressure did not change in the chronic study due to increased cardiac output, resulting in lower pulmonary vascular resistance in the last 2 days of chronic study. The latter may have had a role in decreasing right ventricular hypertrophy, although the direct effect of Cinaciguat on the heart should also be considered. During acute hypoxia, the pulmonary vascular resistance remained low compared to the Control lambs. We observed a higher lung artery density, accompanied by reduced smooth muscle and adventitia layers in the pulmonary arteries. Additionally, vasodilator function was increased, and vasoconstrictor function was decreased, with modifications in the expression of proteins linked to pulmonary vasodilation, consistent with low pulmonary vascular resistance. In summary, Cinaciguat, an activator of sGC, induces cardiopulmonary modifications in chronically hypoxic and pulmonary hypertensive newborn lambs. Therefore, Cinaciguat is a potential therapeutic tool for reducing pulmonary vascular remodeling and/or right ventricular hypertrophy in pulmonary arterial hypertension syndrome.

Large-Animal Model of Donation after Circulatory Death and Normothermic Regional Perfusion for Cardiac Assessment.

The increase in demand for cardiac transplantation throughout the years has fueled interest in donation after circulatory death (DCD) to expand the organ donor pool. However, the DCD process is associated with the risk of cardiac tissue injury due to the inevitable period of warm ischemia. Normothermic regional perfusion (NRP) allows for an in situ organ assessment, allowing the procurement of hearts determined to be viable. Here, we describe a clinically relevant large-animal model of DCD followed by NRP. Circulatory death is established in anesthetized pigs by stopping mechanical ventilation. After a preset warm ischemia period, an extracorporeal membrane oxygenator (ECMO) is used for a NRP period lasting at least 30 min. During this reperfusion period, the model allows the collection of various myocardial biopsies and blood samples for initial cardiac evaluation. Once NRP is weaned, biochemical, hemodynamic, and echocardiographic assessments of cardiac function and metabolism can be performed before organ procurement. This protocol closely simulates the clinical scenario previously described for DCD and NRP in heart transplantation and has the potential to facilitate studies aimed at decreasing ischemia-reperfusion injury and enhance cardiac functional preservation and recovery.

Perfil dos pacientes acometidos por Insuficiência Cardíaca na cidade de Anápolis/GO / Profile of patients affected by heart failure in the city of Anápolis, Brazil

Objetivo: Avaliar o perfil das internações por insuficiência cardíaca (IC) na cidade de Anápolis/GO. Métodos: Os dados foram obtidos no DATASUS, referentes ao período de agosto/2016 a agosto/2019. Foram avaliados: a incidência de internações hospitalares gerais e por IC, a média de permanência, a mortalidade e o custo hospitalar, estratificados por sexo, faixa etária. Resultados: No período estudado, ocorreram 6773 internações hospitalares por doenças do aparelho circulatório, sendo 14,6% por IC (994 internações em números absolutos). Pacientes do sexo masculino corresponderam a 51,85%. A média de permanência global foi de 8,1 dias. A taxa de mortalidade esteve em ascensão, iniciando com 15,52% em 2016 e chegando a 23,86% em 2019. O custo da AIH média aumentou de R$ 1.831,99 em 2016 para R$ 2.406,88 em 2019 (aumento de 31,3%). Conclusão: a Insuficiência Cardíaca é uma síndrome de elevado custo para o Sistema Único de Saúde, e existe a necessidade de conscientização por parte do poder público municipal para este problema saúde.

Objective: To evaluate the profile of patients hospitalized for heart failure (HF) in the city of Anápolis, state of Goiás, Brazil. Methods: Data were obtained from the Brazilian Unified Health System Database (DATASUS) from August 2016 to August 2019. We evaluated the incidence of general and HF hospitalizations, mean length of stay, mortality, and hospital costs. The data were stratified by sex and age group. Results: In the study period, there were 6,773 hospitalizations due to circulatory system diseases, 14.6% of which were due to HF (994 hospitalizations in absolute numbers). Male patients accounted for 51.85% of the sample. Overall mean length of stay was 8.1 days. The mortality rate increased from 15.52% in 2016 to 23.86% in 2019. Mean inpatient hospital authorization costs increased from R$ 1,831.99 in 2016 to R$ 2,406.88 in 2019 (31.3% increase). Conclusions: HF is a costly disease for the Brazilian Unified Health System, and the municipal government should raise awareness of this health problem.

Melatonin treatment during chronic hypoxic gestation improves neonatal cerebrovascular function.

BACKGROUND: Fetal chronic hypoxia is associated with blood flow redistribution and oxidative damage in the brain, leading to increased perinatal morbimortality. Melatonin reduces oxidative stress, improves vascular function, and has neuroprotective effects. OBJECTIVES: This study aimed to determine the effects of an oral melatonin treatment to pregnant ewes at high-altitude, on the cerebrovascular function of their neonates. STUDY DESIGN: Ten high-altitude pregnant sheep received either vehicle or melatonin (10 mg/d) during the last third of gestation until delivery. Postnatal daily hemodynamic measurements were recorded from lambs until 12 days old. In addition, lambs were submitted to a graded oxygenation protocol to assess cerebrovascular responses. Subsequently, lambs were euthanized, and middle cerebral arteries (MCA) were collected for vascular function, protein levels, and morphostructural analyses. RESULTS: Antenatal treatment doubled plasma levels of melatonin in pregnant ewes. Melatonin increased carotid flow and decreased carotid vascular resistance in the lambs by the end of the first week. Furthermore, melatonin increased MCA's maximal vasoconstrictor and vasodilator responses, associated with nitric oxide-dependent and independent mechanisms. CONCLUSIONS: An oral treatment with melatonin during pregnancy promotes postnatal cerebral perfusion in chronically hypoxic neonates. Melatonin is a potential treatment for cerebrovascular dysfunction due to perinatal chronic hypoxia.

Detección de ARN del SARS-CoV-2 por PCR en una serie de cadáveres remitidos para autopsia / Detection of SARS-CoV-2 RNA by PCR in a series of corpses sent for autopsy

A partir de la emergencia del SARS-CoV-2 en el mundo se desató la pandemia por COVID-19 que afectó a 185 países; aparecieron numerosas publicaciones científicas presentando datos epidemiológicos, clínicos, estadísticos y microbiológicos. La elevada mortalidad ha implicado la necesidad de contar con datos cada vez más precisos con relación al virus y a su comportamiento en el medio y, por otro lado, enfrentó a los equipos de salud con un grave problema con relación al manejo seguro de cadáveres y a los riesgos de transmisión que ello implica. El objetivo del presente estudio ha sido detectar la presencia de ARN del SARS-CoV-2 en cadáveres remitidos a la Morgue Judicial de la Nación que no estuvieran comprendidos en la definición de caso sospechoso propuesta por el Ministerio de Salud de la Nación de la República Argentina. Se realizaron hisopados nasofaríngeos a 101 cadáveres elegidos aleatoriamente y basándose en criterios de inclusión para la detección de ARN viral mediante técnica RT-PCR. Se detectó ARN viral en el 16,8% de los cadáveres incluidos en el estudio. (AU)

Following the emergence of SARS-CoV-2 in the world, the COVID-19 pandemic broke out, affecting 185 countries. There have been numerous scientific publications presenting epidemiological, clinical, statistical, and microbiological data. The high mortality has implied the need for increasingly accurate data regarding the virus and its behaviour in the environment and, on the other hand, faced health teams with a serious problem in relation to the safe handling of corpses and the risks of transmission that this implies. The objective of this study was to detect the presence of SARS-CoV-2 RNA in corpses sent to the National Judicial Morgue that were not included in the definition of a suspected case submitted by the Argentine Ministry of Health. Nasopharyngeal and oropharyngeal swabs were taken from 101 cadavers chosen randomly and based on inclusion criteria for detection of viral RNA using the RT-PCR technique. Of the cadavers included in the study, 16.8%, not classified as suspected cases of COVID-19, were tested for the presence of viral RNA in the samples collected. (AU)

To explain or not to explain?-Artificial intelligence explainability in clinical decision support systems.

Explainability for artificial intelligence (AI) in medicine is a hotly debated topic. Our paper presents a review of the key arguments in favor and against explainability for AI-powered Clinical Decision Support System (CDSS) applied to a concrete use case, namely an AI-powered CDSS currently used in the emergency call setting to identify patients with life-threatening cardiac arrest. More specifically, we performed a normative analysis using socio-technical scenarios to provide a nuanced account of the role of explainability for CDSSs for the concrete use case, allowing for abstractions to a more general level. Our analysis focused on three layers: technical considerations, human factors, and the designated system role in decision-making. Our findings suggest that whether explainability can provide added value to CDSS depends on several key questions: technical feasibility, the level of validation in case of explainable algorithms, the characteristics of the context in which the system is implemented, the designated role in the decision-making process, and the key user group(s). Thus, each CDSS will require an individualized assessment of explainability needs and we provide an example of how such an assessment could look like in practice.