Enhancing Maturation and Translatability of Human Pluripotent Stem Cell-Derived Cardiomyocytes through a Novel Medium Containing Acetyl-CoA Carboxylase 2 Inhibitor.

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) constitute an appealing tool for drug discovery, disease modeling, and cardiotoxicity screening. However, their physiological immaturity, resembling CMs in the late fetal stage, limits their utility. Herein, we have developed a novel, scalable cell culture medium designed to enhance the maturation of hPSC-CMs. This medium facilitates a metabolic shift towards fatty acid utilization and augments mitochondrial function by targeting Acetyl-CoA carboxylase 2 (ACC2) with a specific small molecule inhibitor. Our findings demonstrate that this maturation protocol significantly advances the metabolic, structural, molecular and functional maturity of hPSC-CMs at various stages of differentiation. Furthermore, it enables the creation of cardiac microtissues with superior structural integrity and contractile properties. Notably, hPSC-CMs cultured in this optimized maturation medium display increased accuracy in modeling a hypertrophic cardiac phenotype following acute endothelin-1 induction and show a strong correlation between in vitro and in vivo target engagement in drug screening efforts. This approach holds promise for improving the utility and translatability of hPSC-CMs in cardiac disease modeling and drug discovery.

The Combination of Vascular Endothelial Growth Factor A (VEGF-A) and Fibroblast Growth Factor 1 (FGF1) Modified mRNA Improves Wound Healing in Diabetic Mice: An Ex Vivo and In Vivo Investigation.

BACKGROUND: Diabetic foot ulcers (DFU) pose a significant health risk in diabetic patients, with insufficient revascularization during wound healing being the primary cause. This study aimed to assess microvessel sprouting and wound healing capabilities using vascular endothelial growth factor (VEGF-A) and a modified fibroblast growth factor (FGF1). METHODS: An ex vivo aortic ring rodent model and an in vivo wound healing model in diabetic mice were employed to evaluate the microvessel sprouting and wound healing capabilities of VEGF-A and a modified FGF1 both as monotherapies and in combination. RESULTS: The combination of VEGF-A and FGF1 demonstrated increased vascular sprouting in the ex vivo mouse aortic ring model, and topical administration of a combination of VEGF-A and FGF1 mRNAs formulated in lipid nanoparticles (LNPs) in mouse skin wounds promoted faster wound closure and increased neovascularization seven days post-surgical wound creation. RNA-sequencing analysis of skin samples at day three post-wound creation revealed a strong transcriptional response of the wound healing process, with the combined treatment showing significant enrichment of genes linked to skin growth. CONCLUSION: f-LNPs encapsulating VEGF-A and FGF1 mRNAs present a promising approach to improving the scarring process in DFU.

Valorization of kiwi waste through composting.

Kiwi waste from the calibration process is a major environmental problem of kiwi production due to landfill deposition. This work aims to contribute to the agronomic use of recycled kiwi waste through composting. With this objective, a composting experiment was carried out with kiwi fruit waste mixed with 5%, 10% and 20% (fresh weight) of wheat straw from bundles used to protect kiwifruit trunks from frost, as abulking agent to increase aeration, in the piles 5S, 10S and 20S, respectively. The highest temperatures for piles 5S and 10S were above 60°C, whereas the temperature did not reach 40°C in the pile with the highest straw content (20S) because the aeration increased heat loss in addition to increased C/N ratio of this pile. Also, the amount of organic matter mineralized decreased with increasing amount of straw because of the high C/N ratio of the straw. The highest total N (29.7 g kg-1) and the lowest C/N ratio (13) of the compost with 5% of straw is important from the agricultural point of view to promote N availability. In contrast, the high electrical conductivity (4.6 dS m-1) of this compost increases the risk of salt accumulation in the soil. Our results show that the compost with 10% straw, with high degree of maturation, absence of poor hygiene indicators as coliforms and pathogens as Salmonella sp., high organic matter content and rich in nutrients, together with the adequate compost pH and low electrical conductivity improves compost quality.

Toxic Shock Syndrome: Eighteen Years of Experience in a Pediatric Intensive Care Unit.

Introduction Toxic shock syndrome (TSS) is a life-threatening disease usually caused by a Staphylococcus aureus or group Aß-hemolytic Streptococcus infection. Methods In this retrospective study, we included patients with TSS admitted to a tertiary hospital's pediatric intensive care unit (PICU) over the last 18 years. We compared the staphylococcal TSS (Staph-TSS) and streptococcal TSS (Strep-TSS) groups. Results We included 17 patients (64.7% male), with a median age of 6.1 years (3.0 years for streptococcal TSS versus 13.3 years for staphylococcal TSS, p = 0.040), a median of 3.0 days from symptom onset to diagnosis, and a median of 6.0 days of hospitalization. Ten patients met the Centers for Disease Control and Prevention (CDC) criteria for staphylococcal TSS (one menstrual-related) and seven met the criteria for streptococcal TSS (four of them occurring since the COVID-19 pandemic was declared). Fifteen patients had identified risk factors, primarily cutaneous lesions (29.4%). In 15 patients, at least three organs or systems were affected, with fever, rash, and hypotension as universal findings. Mucous membrane hyperemia was present in 16 patients, gastrointestinal symptoms in 14 patients, and desquamation in nine. Muscular involvement was present in seven patients, all with staphylococcal TSS (p = 0.010). All patients received two or more antibiotics, including a protein synthesis inhibitor (except for one), and required fluid resuscitation and vasoactive amines (median three days). Six patients needed invasive mechanical ventilation (median seven days). Albumin infusion was necessary in six patients, significantly more frequently in patients with streptococcal TSS (p = 0.035). Two patients with staphylococcal TSS died, while the seven patients with streptococcal TSS survived hospital discharge. There were no recurrent cases. Conclusions Our study revealed TSS severity and multiorgan involvement, emphasizing the importance of early diagnosis and intervention. Risk factors were prevalent, and we noted an increased frequency of group A streptococcal (GAS) TSS post-COVID-19 pandemic.

Adaptação transcultural do Instrumento de Rastreio para a Disfonia (IRD-Br) para o Português Europeu (PE) / Cross-cultural adaptation of the Dysphonia Screening Tool (DST-Br) for European Portuguese (EP)

RESUMO Objetivo Realizar a adaptação transcultural do Instrumento de Rastreio para a Disfonia (IRD-Br) para o Português Europeu (PE). Métodos Foi realizada a adaptação transcultural do IRD-Br para o PE de acordo com as seguintes etapas: tradução, retrotradução, análise de um comitê de especialistas e pré-teste. Na etapa de pré-teste, participaram 30 indivíduos disfônicos com idades entre os 18 e 87 anos, sendo 24 do sexo feminino e 6 do sexo masculino. Resultados Foi necessária a inserção de um enunciado na versão em PE do instrumento. Houve divergência na retrotradução do título, sendo resolvida na análise do comitê de especialistas. Um item apresentou divergência na tradução e na retrotradução, sendo definida a versão final na análise do comitê de especialistas. Um item e a chave de resposta apresentaram consenso em todas as etapas. No pré-teste, todos os itens receberam 100% de respostas sim ou não, e nenhum recebeu resposta não aplicável. Conclusão A adaptação do IRD-Br para o PE foi bem sucedida. A versão para o português europeu do instrumento foi denominada de Instrumento de Rastreio para a Disfonia em português europeu - IRD-PT.

ABSTRACT Purpose To perform a cross-cultural adaptation of the Brazilian Dysphonia Screening Tool (DST-Br) for European Portuguese (EP). Methods The cross-cultural adaptation of the DST-Br for EP was carried out in four stages: translation, back-translation, expert committee review, and pre-testing. The pre-testing involved 30 dysphonic individuals (24 women and 6 men) aged between 18 and 87 years old. Results An additional statement was required in the EP version of the instrument. Disagreement in the back-translation of the title was resolved through an expert committee review. One item presented discrepancies in the translation and back-translation, with the final version determined through an expert committee review. One item and the answer key reached a consensus in all stages. During pre-testing, all items received 100% "yes" or "no" responses, and none were marked as "not applicable". Conclusion The cross-cultural adaptation of DST-Br for use in EP was successfully carried out. The European Portuguese version of the instrument was named the Instrumento de Rastreio para a Disfonia em português europeu (IRD-PT) / Dysphonia Screening Tool in European Portuguese.

Cross-cultural adaptation of the Dysphonia Screening Tool (DST-Br) for European Portuguese (EP). / Adaptação transcultural do Instrumento de Rastreio para a Disfonia (IRD-Br) para o Português Europeu (PE).

PURPOSE: To perform a cross-cultural adaptation of the Brazilian Dysphonia Screening Tool (DST-Br) for European Portuguese (EP). METHODS: The cross-cultural adaptation of the DST-Br for EP was carried out in four stages: translation, back-translation, expert committee review, and pre-testing. The pre-testing involved 30 dysphonic individuals (24 women and 6 men) aged between 18 and 87 years old. RESULTS: An additional statement was required in the EP version of the instrument. Disagreement in the back-translation of the title was resolved through an expert committee review. One item presented discrepancies in the translation and back-translation, with the final version determined through an expert committee review. One item and the answer key reached a consensus in all stages. During pre-testing, all items received 100% "yes" or "no" responses, and none were marked as "not applicable". CONCLUSION: The cross-cultural adaptation of DST-Br for use in EP was successfully carried out. The European Portuguese version of the instrument was named the Instrumento de Rastreio para a Disfonia em português europeu (IRD-PT) / Dysphonia Screening Tool in European Portuguese.

OBJETIVO: Realizar a adaptação transcultural do Instrumento de Rastreio para a Disfonia (IRD-Br) para o Português Europeu (PE). MÉTODOS: Foi realizada a adaptação transcultural do IRD-Br para o PE de acordo com as seguintes etapas: tradução, retrotradução, análise de um comitê de especialistas e pré-teste. Na etapa de pré-teste, participaram 30 indivíduos disfônicos com idades entre os 18 e 87 anos, sendo 24 do sexo feminino e 6 do sexo masculino. RESULTADOS: Foi necessária a inserção de um enunciado na versão em PE do instrumento. Houve divergência na retrotradução do título, sendo resolvida na análise do comitê de especialistas. Um item apresentou divergência na tradução e na retrotradução, sendo definida a versão final na análise do comitê de especialistas. Um item e a chave de resposta apresentaram consenso em todas as etapas. No pré-teste, todos os itens receberam 100% de respostas sim ou não, e nenhum recebeu resposta não aplicável. CONCLUSÃO: A adaptação do IRD-Br para o PE foi bem sucedida. A versão para o português europeu do instrumento foi denominada de Instrumento de Rastreio para a Disfonia em português europeu - IRD-PT.

Factors associated with changes in inpatients' smoking pattern during hospitalization and one month after discharge: A cohort study.

INTRODUCTION: Smokers are frequent users of healthcare services. Admissions to hospital can serve as a "teachable moment" for quitting smoking. Clinical guidelines recommend initiating smoking cessation services during hospitalization; however, in Southern European countries less than 5% of inpatients receive a brief intervention for smoking cessation. OBJECTIVES: The aims of this study were (i) to examine rates of smoking abstinence during and after hospitalization; (ii) to measure changes in smoking patterns among persons who continued smoking after discharge; and (iii) to identify predictors of abstinence during hospitalization and after discharge. METHODS: A cohort study of a representative sample of current adult smokers hospitalized in two Spanish and two Portuguese hospitals. We surveyed smokers during hospitalization and recontacted them one month after discharge. We used a 25-item ad hoc questionnaire regarding their smoking pattern, the smoking cessation intervention they have received during hospitalization, and hospital and sociodemographic characteristics. We performed a descriptive analysis using the chi-square test and a multivariate logistic regression to characterize the participant, hospital, and smoking cessation intervention (5As model) characteristics associated with smoking abstinence. RESULTS: Smoking patients from both countries presented high abstinence rates during hospitalization (Spain: 76.4%; Portugal: 70.2%); however, after discharge, their abstinence rates decreased to 55.3% and 46.8%, respectively. In Spain, smokers who tried to quit before hospital admission showed higher abstinence rates, and those who continued smoking reduced a mean of five cigarettes the number of cigarettes per day (p ≤ 0.001). In Portugal, abstinence rates were higher among women (p = 0.030), those not living with a smoker (p = 0.008), those admitted to medical-surgical wards (p = 0.035), who consumed their first cigarette within 60 min after waking (p = 0.006), and those who were trying to quit before hospitalization (p = 0.043). CONCLUSIONS: Half of the smokers admitted into the Spanish hospitals are abstinent one month after discharge or have reduced their cigarettes per day. Nevertheless, success rates could be increased by implementing evidence-based tobacco cessation programs at the organizational-level, including post-discharge active quitting smoking support. CLINICAL RELEVANCE: Three-quarters of the inpatients who smoke remain abstinent during hospitalization and over half achieve to maintain their abstinence or at least reduce their consumption one month after discharge, proving that admission to hospitals is an excellent teachable moment to quit smoking.

Unraveling the Metabolic Derangements Occurring in Non-infarcted Areas of Pig Hearts With Chronic Heart Failure.

Objective: After myocardial infarction (MI), the non-infarcted left ventricle (LV) ensures appropriate contractile function of the heart. Metabolic disturbance in this region greatly exacerbates post-MI heart failure (HF) pathology. This study aimed to provide a comprehensive understanding of the metabolic derangements occurring in the non-infarcted LV that could trigger cardiovascular deterioration. Methods and Results: We used a pig model that progressed into chronic HF over 3 months following MI induction. Integrated gene and metabolite signatures revealed region-specific perturbations in amino acid- and lipid metabolism, insulin signaling and, oxidative stress response. Remote LV, in particular, showed impaired glutamine and arginine metabolism, altered synthesis of lipids, glucose metabolism disorder, and increased insulin resistance. LPIN1, PPP1R3C, PTPN1, CREM, and NR0B2 were identified as the main effectors in metabolism dysregulation in the remote zone and were found differentially expressed also in the myocardium of patients with ischemic and/or dilated cardiomyopathy. In addition, a simultaneous significant decrease in arginine levels and altered PRCP, PTPN1, and ARF6 expression suggest alterations in vascular function in remote area. Conclusions: This study unravels an array of dysregulated genes and metabolites putatively involved in maladaptive metabolic and vascular remodeling in the non-infarcted myocardium and may contribute to the development of more precise therapies to mitigate progression of chronic HF post-MI.

Congenital central hypoventilation syndrome: a life-threatening cause of neonatal apnoea.

Congenital central hypoventilation syndrome (CCHS) is an uncommon genetic disease characterised by an autonomic nervous system dysfunction that affects ventilatory homeostasis. Involvement of other systems is also described, mainly cardiovascular, gastrointestinal and central nervous systems. We describe a rare case of CCHS diagnosed in a term newborn who presented with persistent apnoea in the first hours of life. After an exhaustive aetiological study excluding primary pulmonary, cardiac, metabolic and neurological diseases, this diagnosis was confirmed by a paired-like homeobox 2B gene sequence analysis. During hospitalisation, ventilation was optimised and multidisciplinary follow-up was initiated, including genetic counselling. At 2 months old, the child was discharged under non-invasive ventilation during sleep. This case illustrates the importance of early diagnosis, including genetic study and advances in home ventilation. These factors allow early hospital discharge and timely multidisciplinary intervention, which is crucial for patients' quality of life and outcome optimisation.

4,4,16-Trifluoropalmitate: Design, Synthesis, Tritiation, Radiofluorination and Preclinical PET Imaging Studies on Myocardial Fatty Acid Oxidation.

Fatty acid oxidation (FAO) produces most of the ATP used to sustain the cardiac contractile work, although glycolysis is a secondary source of ATP under normal physiological conditions. FAO impairment has been reported in the advanced stages of heart failure (HF) and is strongly linked to disease progression and severity. Thus, from a clinical perspective, FAO dysregulation provides prognostic value for HF progression, the assessment of which could be used to improve patient monitoring and the effectiveness of therapy. Positron emission tomography (PET) imaging represents a powerful tool for the assessment and quantification of metabolic pathways in vivo. Several FAO PET tracers have been reported in the literature, but none of them is in routine clinical use yet. Metabolically trapped tracers are particularly interesting because they undergo FAO to generate a radioactive metabolite that is subsequently trapped in the mitochondria, thus providing a quantitative means of measuring FAO in vivo. Herein, we describe the design, synthesis, tritium labelling and radiofluorination of 4,4,16-trifluoro-palmitate (1) as a novel potential metabolically trapped FAO tracer. Preliminary PET-CT studies on [18 F]1 in rats showed rapid blood clearance, good metabolic stability - confirmed by using [3 H]1 in vitro - and resistance towards defluorination. However, cardiac uptake in rats was modest (0.24±0.04 % ID/g), and kinetic analysis showed reversible uptake, thus indicating that [18 F]1 is not irreversibly trapped.

Metabolic Maturation of Human Pluripotent Stem Cell-Derived Cardiomyocytes by Inhibition of HIF1α and LDHA.

RATIONALE: Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) are a readily available, robustly reproducible, and physiologically appropriate human cell source for cardiac disease modeling, drug discovery, and toxicity screenings in vitro. However, unlike adult myocardial cells in vivo, hPSC-CMs cultured in vitro maintain an immature metabolic phenotype, where majority of ATP is produced through aerobic glycolysis instead of oxidative phosphorylation in the mitochondria. Little is known about the underlying signaling pathways controlling hPSC-CMs' metabolic and functional maturation. OBJECTIVE: To define the molecular pathways controlling cardiomyocytes' metabolic pathway selections and improve cardiomyocyte metabolic and functional maturation. METHODS AND RESULTS: We cultured hPSC-CMs in different media compositions including glucose-containing media, glucose-containing media supplemented with fatty acids, and glucose-free media with fatty acids as the primary carbon source. We found that cardiomyocytes cultured in the presence of glucose used primarily aerobic glycolysis and aberrantly upregulated HIF1α (hypoxia-inducible factor 1α) and its downstream target lactate dehydrogenase A. Conversely, glucose deprivation promoted oxidative phosphorylation and repressed HIF1α. Small molecule inhibition of HIF1α or lactate dehydrogenase A resulted in a switch from aerobic glycolysis to oxidative phosphorylation. Likewise, siRNA inhibition of HIF1α stimulated oxidative phosphorylation while inhibiting aerobic glycolysis. This metabolic shift was accompanied by an increase in mitochondrial content and cellular ATP levels. Furthermore, functional gene expressions, sarcomere length, and contractility were improved by HIF1α/lactate dehydrogenase A inhibition. CONCLUSIONS: We show that under standard culture conditions, the HIF1α-lactate dehydrogenase A axis is aberrantly upregulated in hPSC-CMs, preventing their metabolic maturation. Chemical or siRNA inhibition of this pathway results in an appropriate metabolic shift from aerobic glycolysis to oxidative phosphorylation. This in turn improves metabolic and functional maturation of hPSC-CMs. These findings provide key insight into molecular control of hPSC-CMs' metabolism and may be used to generate more physiologically mature cardiomyocytes for drug screening, disease modeling, and therapeutic purposes.

The first reported case of factor V Leiden mutation with agenesis of superior vena cava: A case report.

RATIONALE: Total absence of superior vena cava (ASVC) is a very rare anomaly, and the patient usually suffers from superior vena cava syndrome (SVCS) or conduction disturbances. PATIENT CONCERNS: We report a 36-year-old white male, born and living in Brazil, without comorbidities presented to hematologist thrombotic episodes even under anticoagulant therapy. On his first hematologic appointment, he had no active complaints except by the fullness after meals, and his physical examination presented remarkable collateral circulation in the chest. DIAGNOSES: Congenital ASVC associated with factor V Leiden mutation. OUTCOMES: In his magnetic resonance angiography of the thorax, a great amount of collateral circulation and communication of the azygos and hemiazygos veins with inferior vena cava were evident, as well as the absence of the upper cava vein. Furthermore, heterozygous genetic mutation was found for Leiden factor V. LESSONS: This case gives us the lesson that we need to include ASVC in the differential diagnosis of SVCS. The importance of the V-Leiden factor as a joint risk with this congenital defect for venous thromboembolism episodes was also highlighted.

Evolución de la epidemia tabáquica en adolescentes escolarizados portugueses y europeos, por sexo, entre 1998 y 2014 / Evolution of smoking epidemic in Portuguese and European school adolescents by gender between 1998 and 2014

Objetivos: Analizar el estado actual y la evolución de la epidemia de tabaquismo en los adolescentes escolarizados portugueses y europeos, por sexo. Pacientes y método: El consumo de tabaco y su evoución se obtuvieron de la base de datos de los informes del Health Behavior in School-Aged Children (HBSC) entre 1997/1998 y 2013/2014. Resultados: En Portugal, según el último informe de HBSC, el 12% de los chicos y el 10% de las chicas de 15 años fumaban al menos un cigarrillo a la semana, que es similar a la media de prevalencia europea. En cuanto a la evolución del consumo de tabaco en Portugal entre 1997/1998 y 2013/2014, la prevalencia a los 15 años se redujo del 19 al 12% en chicos y del 14 al 10% en las chicas; a los 13 años, disminuyó del 5% en chicos y el 4% en chicas al 3% en chicos y chicas; a los 11 años, la prevalencia disminuyó del 2 al 1% en los chicos y del 1 al 0% en las chicas. Conclusiones: La evolución del consumo de tabaco en Portugal y Europa muestra un descenso en los adolescentes, con diferencias por género. Las diferencias existentes entre los sexos apuntan a la necesidad de intensificar y adecuar las intervenciones para la prevención de la experimentación del tabaco en adolescentes por género

Objectives: To analyze the current status and evolution of the smoking epidemic in Portuguese and European school adolescents by gender. Patients and methods: Tobacco use and its evolution were obtained from the data base of the reports of the Health Behavior in School-Aged Children (HBSC) between 1997/1998 and 2013/2014. Results: In Portugal, according to the last report of the HBSC, 12% of 15-year old boys and 10% of girls smoked at least one cigarette a week, which is similar to the mean European prevalence. Regarding the evolution of tobacco use in Portugal between 1997/1998 and 2013/2014, prevalence at 15 years of age decreased from 19 to 12% in boys and from 14 to 10% in girls; at 13 years, it decreases from 5% in boys and from 4% in girls to 3% in boys and girls; at 11 years, the prevalence decreased from 2 to 1% in boys and from 1 to 0% in girls. Conclusions: The evolution of tobacco use in Portugal and Europe demonstrates a decrease in adolescents, with differences by gender. The existing differences between genders indicate the need to intensify and adapt the interventions for the prevention of experimenting with tobacco in adolescents by gender

Inherited thrombotic thrombocytopenic purpura mimicking immune thrombocytopenic purpura during pregnancy: a case report.

BACKGROUND: Thrombotic thrombocytopenic purpura is a very rare hereditary blood deficiency disorder of ADAMTS13 (von Willebrand factor-cleaving protease) and a life-threatening thrombotic microangiopathy characterized by thrombocytopenia and microangiopathic hemolytic anemia. The deficiency in ADAMTS13 metalloprotease, which cleaves the von Willebrand factor, may be congenital or acquired. The congenital form is caused by inherited mutations in the ADAMTS13 gene. The diagnosis is challenging due to the nonspecific signs and symptoms, as well as the rarity of the disease. CASE PRESENTATION: We present an unusual case of a 20-year-old feoderm woman from northeast region of Brazil who manifested thrombocytopenia during her pregnancy which was believed to be immune thrombocytopenic purpura. CONCLUSIONS: Considering the importance of a differential diagnosis of thrombotic microangiopathic disorders, congenital thrombotic thrombocytopenic purpura may mimic the signs and symptoms of pre-eclampsia/eclampsia, hemolysis with elevated liver enzymes and low platelet count syndrome, and atypical hemolytic-uremic syndrome. It should be considered in suspect cases in patients with an ADAMTS13 activity at 5% without ADAMTS13 antibodies.

Respiratory morbidity in late preterm infants.

BACKGROUND: Late preterm delivery (74% of all preterm births) increases the incidence of respiratory pathology, namely respiratory distress syndrome (RDS), transient tachypnea of the newborn (TTN) and the need of ventilator support when compared to term delivery. The aim is to evaluate the respiratory morbimortality in late preterm infants and the risk factors associated with RDS and TTN. METHODS: Descriptive retrospective study of all newborns of 34+0 to 36+6 weeks of gestational age, born at our center between September 1, 2012 and August 31, 2015. Those with major malformations, chromosomopathies, hydrops fetalis and congenital TORCH infection were excluded. RESULTS: A total of 498 newborns were studied, 44 (8.83%) of them with either RDS or TTN. Respiratory morbidity was significantly associated with lower gestational age, male gender, caesarean section, exposure to peripartum antibiotics, overweighed and nulliparous mothers. RDS newborns had a significantly higher need for resuscitation, endotracheal intubation, oxygen therapy, early invasive ventilation, parenteral nutrition and a longer NICU stay when compared to newborns with TTN. 55% of the patients with RDS had 35+0 to 36+6 weeks of gestational age, moderate or severe RDS and required mechanical ventilation; six needed surfactant. Caesarean section and resuscitation with ETT were independent risk factors for respiratory morbidity. CONCLUSIONS: Late preterm remain at risk for adverse respiratory outcomes, particularly newborns delivered after 35 weeks, whose mothers are not given ACS and still have considerable morbidity. Growing evidence supports the possibility of extending the management window further into the LPT period. Caesarean section was an independent risk factor for respiratory morbidity and efforts should be undertaken to reduce the procedure rate.

3D aggregate culture improves metabolic maturation of human pluripotent stem cell derived cardiomyocytes.

Three-dimensional (3D) cultures of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) hold great promise for drug discovery, providing a better approximation to the in vivo physiology over standard two-dimensional (2D) monolayer cultures. However, the transition of CM differentiation protocols from 2D to 3D cultures is not straightforward. In this work, we relied on the aggregation of hPSC-derived cardiac progenitors and their culture under agitated conditions to generate highly pure cardiomyocyte aggregates. Whole-transcriptome analysis and 13 C-metabolic flux analysis allowed to demonstrate at both molecular and fluxome levels that such 3D culture environment enhances metabolic maturation of hiPSC-CMs. When compared to 2D, 3D cultures of hiPSC-CMs displayed down-regulation of genes involved in glycolysis and lipid biosynthesis and increased expression of genes involved in OXPHOS. Accordingly, 3D cultures of hiPSC-CMs had lower fluxes through glycolysis and fatty acid synthesis and increased TCA-cycle activity. Importantly, we demonstrated that the 3D culture environment reproducibly improved both CM purity and metabolic maturation across different hPSC lines, thereby providing a robust strategy to derive enriched hPSC-CMs with metabolic features closer to that of adult CMs.

Distinct carbon sources affect structural and functional maturation of cardiomyocytes derived from human pluripotent stem cells.

The immature phenotype of human pluripotent stem cell derived cardiomyocytes (hPSC-CMs) constrains their potential in cell therapy and drug testing. In this study, we report that shifting hPSC-CMs from glucose-containing to galactose- and fatty acid-containing medium promotes their fast maturation into adult-like CMs with higher oxidative metabolism, transcriptional signatures closer to those of adult ventricular tissue, higher myofibril density and alignment, improved calcium handling, enhanced contractility, and more physiological action potential kinetics. Integrated "-Omics" analyses showed that addition of galactose to culture medium improves total oxidative capacity of the cells and ameliorates fatty acid oxidation avoiding the lipotoxicity that results from cell exposure to high fatty acid levels. This study provides an important link between substrate utilization and functional maturation of hPSC-CMs facilitating the application of this promising cell type in clinical and preclinical applications.

The genus Senna Mill. (Leguminosae: Caesalpinioideae) in a fragment of the Ecological Station Raso da Catarina, Bahia, Brazil / O gênero Senna Mill. (Leguminosae: Caesalpinioideae) em um fragmento da Estação Ecológica Raso da Catarina, Bahia, Brasil

Senna comprises about 300 species with circuntropical distribution, widely represented in the Americas, also occurring in Africa, Australia, Asia and Oceania. The Brazil includes 80 species, of which 27 are endemic, 50 reported from Bahia and 22 recorded from the Caatinga. The floristic survey of Senna in the Ecological Station Raso da Catarina included analysis of specimens collected March 2010 to October 2011. The analyses were supplemented with dried collections from the following herbaria: ALCB, EAC, HRB, HUEFS and MBM. Seven taxa were recorded. The most representative taxa in the area were Senna rizzinii H.S.Irwin & Barneby and S. acuruensis (Benth.) H.S.Irwin & Barneby var. acuruensis. The genus can be found in a variety of environments from preserved to degraded areas and in sandy, sandy-clayey or rocky soils. The taxonomic treatment includes anidentification key, descriptions, illustrations, photos, data of the geographical distribution, reproductive phenology and comments about the taxa.

Senna inclui cerca de 300 espécies com distribuição circuntropical, amplamente representada nas Américas, ocorrendo ainda na África, Austrália, Ásia e Oceania. O Brasil inclui 80 espécies, dentre estas 27 são endêmicas, 50 são registradas para Bahia e 22 para Caatinga. O levantamento florístico de Senna na Estação Ecológica Raso da Catarina incluiu a análise de espécimes coletados de março de 2010 a outubro de 2011. As análises foram complementadas com coleções dos seguintes herbários: ALCB, EAC, HRB, HUEFS e MBM. Sete táxons foram registrados. Os táxons mais representativos na área foram Senna rizzinii H.S.Irwin & Barneby e S. acuruensis (Benth.) H.S.Irwin & Barneby var. acuruensis. O gênero pode ser encontrado em uma variedade de ambientes de preservados até áreas degradadas e em solos arenosos, argilo-arenosos ou rochosos. O tratamento taxonômico inclui uma chave de identificação, descrições, ilustrações, fotografias, dados de distribuição geográfica, fenologia reprodutiva e comentários sobre os táxons.

The genus Chamaecrista Moench in a fragment of the Ecological Station Raso da Catarina, Bahia, Brazil / O gênero Chamaecrista Moench em um fragmento da Estação Ecológica Raso da Catarina, Bahia, Brasil

Abstract Chamaecrista has a Pantropical distribution, with some occurrences in Australia and temperate areas, and includes about 330 species, of which 266 occur in the Americas. The genus is represented in Brazil by 256 species, of which 97 are cited for the northeast Region. The Ecological Station Raso da Catarina (ESRC) is one of the largest areas of protected Caatinga and occupies about 105,282.00 ha., delimited by the coordinates 09°39’0.30” to 09°50’98.2” S and 38°26’57.5” to 38°29’32.6” W. The floristic survey of Chamaecrista in the ESRC included analysis of specimens collected from March 2010 and October 2011. The analyses were supplemented with dried collections from the following herbaria: ALCB, EAC, HRB, HUEFS and MBM. The genus is represented in the study area by ten taxa. The most representative taxa in the area were Chamaecrista repens (Vogel) H.S.Irwin & Barneby var. multijuga (Benth.) H.S.Irwin & Barneby, C. brevicalyx (Benth.) H.S.Irwin & Barneby var. brevicalyx, C. belemii (H.S.Irwin & Barneby) H.S.Irwin & Barneby var. belemii, wich are directly related to sandy soils common in the region. The taxonomic treatment includes a key for the identification, descriptions, illustrations, photos, data geographical distribution, reproductive phenology and comments about the taxa.

Resumo Chamaecrista possui uma distribuição Pantropical, com algumas ocorrências na Austrália e em áreas temperadas, inclui cerca de 330 espécies, das quais 266 ocorrem nas Américas. O gênero está representado no Brasil por 256 espécies, das quais 97 são citadas para a região nordeste. A Estação Ecológica Raso da Catarina (ECRC) é uma das maiores áreas protegidas de Caatinga e ocupa cerca de 105.282.00 ha., delimitada pelas coordenadas 09°39’0,30” a 09°50’98,2” S e 38°26’57,5” a 38°29’32,6” W. O levantamento florístico de Chamaecrista na ECRC incluiu análises de espécimes coletados de março 2010 a outubro de 2011. As análises foram complementadas com coleções dos seguintes herbários: ALCB, EAC, HRB, HUEFS e MBM. O gênero está representado na área de estudo por dez táxons, onde os mais representativos foram: Chamaecrista repens (Vogel) H.S.Irwin & Barneby var. multijuga (Benth.) H.S.Irwin & Barneby, C. brevicalyx (Benth.) H.S.Irwin & Barneby var. brevicalyx, C. belemii (H.S.Irwin & Barneby) H.S.Irwin & Barneby var. belemii, estando diretamente relacionados com solos arenosos comuns na região. O tratamento taxonômico inclui uma chave para a identificação, descrições, ilustrações, fotografias, dados de distribuição geográfica, fenologia reprodutiva e comentários sobre os táxons.

HLA and Delayed Drug-Induced Hypersensitivity.

Delayed drug allergy reactions (DDAR) are potentially fatal. Certain human leukocyte antigen (HLA) alleles have been associated with delayed allergy reactions following the administration of particular drugs. Examples are HLA-B*57:01 (abacavir), HLA-B*15:02/HLA-A*31:01 (carbamazepine), and HLA-B*58:01 (allopurinol). Based on the identification of these associations, it may now be possible to prevent certain allergy reactions that were, until recently, considered unpredictable. In this review, we will focus on the pharmacogenetics of the best-studied associations between specific HLA alleles and delayed allergy reactions and describe the pathogenesis models proposed so far. Finally, we will evaluate the genetic screening strategies available and discuss the clinical relevance of a better understanding of the immunogenetics and mechanisms involved in DDAR.