Machine learning for prediction of ventricular arrhythmia episodes from intracardiac electrograms of automatic implantable cardioverter-defibrillators.

BACKGROUND: Despite effectiveness of the implantable cardioverter-defibrillator (ICD) in saving patients with life-threatening ventricular arrhythmias (VAs), the temporal occurrence of VA after ICD implantation is unpredictable. OBJECTIVE: The study aimed to apply machine learning (ML) to intracardiac electrograms (IEGMs) recorded by ICDs as a unique biomarker for predicting impending VAs. METHODS: The study included 13,516 patients who received Biotronik ICDs and enrolled in the CERTITUDE registry between January 1, 2010, and December 31, 2020. Database extraction included IEGMs from standard quarterly transmissions and VA event episodes. The processed IEGM data were pulled from device transmissions stored in a centralized Home Monitoring Service Center and reformatted into an analyzable format. Long-range (baseline or first scheduled remote recording), mid-range (scheduled remote recording every 90 days), or short-range predictions (IEGM within 5 seconds before the VA onset) were used to determine whether ML-processed IEGMs predicted impending VA events. Convolutional neural network classifiers using ResNet architecture were employed. RESULTS: Of 13,516 patients (male, 72%; age, 67.5 ± 11.9 years), 301,647 IEGM recordings were collected; 27,845 episodes of sustained ventricular tachycardia or ventricular fibrillation were observed in 4467 patients (33.0%). Neural networks based on convolutional neural networks using ResNet-like architectures on far-field IEGMs yielded an area under the curve of 0.83 with a 95% confidence interval of 0.79-0.87 in the short term, whereas the long-range and mid-range analyses had minimal predictive value for VA events. CONCLUSION: In this study, applying ML to ICD-acquired IEGMs predicted impending ventricular tachycardia or ventricular fibrillation events seconds before they occurred, whereas midterm to long-term predictions were not successful. This could have important implications for future device therapies.

Análise comparativa de ecotoxicidade aguda em Biomphalaria glabrata e Lymnaea stagnalis (mollusca: gastropoda) expostas ao cloreto de cádmio

Cadmium chloride (CdCl2) is a salt that has high solubility in water and is frequently adopted as a reference substance in laboratory ecotoxicological assays. Several institutions have been standardizing tests to define toxicity thresholds to protect organisms and ecosystems. Invertebrates are frequently used in these evaluations, and mollusks, the second largest animal group, are suggested as appropriate models. Standardizing ecotoxicological assays with native species is necessary, since in the majority of cases, they are more susceptible to environmental contamination than exotic species, and thus, validating tests with ecological and environmental representativeness in different countries is essential. The objective of this study was to compare and evaluate the sensitivity of the Brazilian native freshwater snail Biomphalaria glabrata (Say, 1818) and the European standard species Lymnaea stagnalis (Linnaeus, 1758), by analyzing the acute toxic effect of CdCl2. The survival of adult’s snails of the species B. glabrata and L. stagnalis was evaluated through 24- hour exposure to concentrations of 0.00; 0.12; 0.25; 0.50; 1.00 and 2.00 mg L-1 of CdCl2. The lethal concentration (LC50) for adult organisms was 0.48 mg L-1 for B. glabrata and 0.33 mg L-1 for L. stagnalis. With the ecotoxicological assays carried out, it was possible to establish physical-chemical parameters and comparatively evaluate the sensitivity of L. stagnalis and B. glabrata, it was possible to show that B. glabrata was responsive and had similar results to L. stagnalis. For standardization procedures in countries that require the regulation of new tests, the comparison between organisms already validated worldwide is an additional motivation to employ them for the implementation of tests with endemic species in countries such as Brazil.

O cloreto de cádmio (CdCl2) é um sal que apresenta alta solubilidade em água e frequentemente utilizado como substância de referência em avaliações ecotoxicológicas laboratoriais. Diversas instituições têm padronizado testes para definir limiares de periculosidade de produtos químicos, bem como a qualidade da água e dos efluentes, que visam proteger os organismos e os ecossistemas. Invertebrados são frequentemente utilizados nessas avaliações, sendo que os moluscos por serem o segundo maior grupo animal são sugeridos como modelos responsivos para diferentes abordagens. O incentivo ao uso de espécies nativas, é devido ao fato de que na maioria dos casos, são organismos mais sensíveis aos poluentes ambientais do que espécies invasoras, desse modo, validar testes com representatividade ecológica e ambiental em diferentes países é essencial. O objetivo deste trabalho foi avaliar comparativamente a sensibilidade do caramujo de água doce nativo Biomphalaria glabrata (Say, 1818) com a espécie holártica normatizada na Europa para ensaios ecotoxicológicos, Lymnaea stagnalis (Linnaeus, 1758), por meio da análise do efeito tóxico agudo da substância de referência CdCl2. Para isso, foram avaliadas a sobrevivência de caramujos adultos das espécies B. glabrata e L. stagnalis através de exposições por 24 horas às concentrações de 0,00; 0,12; 0,25; 0,50; 1,00 e 2,00 mg L-1 de CdCl2. A concentração letal média (CL50) para os organismos adultos foi de 0,48 mg L-1 em B. glabrata e 0,33 mg L-1 em L. stagnalis. Com os ensaios ecotoxicológicos realizados foi possível estabelecer parâmetros físico-químicos e avaliar comparativamente a sensibilidade da espécie L. stagnalis com a espécie B. glabrata e demonstrar que a B. glabrata se mostrou responsiva e com resultados similares aos observados com L. stagnalis. Para os procedimentos de padronização e normatização em países que necessitam de regulamentação de novos ensaios, a comparação entre organismos já validados mundialmente, corroboram com informações para a implementação de ensaios com espécies endêmicas em países como o Brasil.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005-2013).

Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

MTSS2-related neurodevelopmental disorder: Further delineation of the phenotype.

MTSS2-related neurodevelopmental disorder (MTSS2-related NDD) (MIM 620086) is characterized by intellectual developmental disorder with ocular anomalies and distinctive facial features (IDDOF). The only existing report to date described five individuals who exhibited an identical de novo c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. Herein, we report a new case of MTSS2-related NND in a male dizygotic twin who presented with IDDOF and severe intellectual disability. This patient also displayed additional clinical features, including low functioning autism, hypothyroidism, duodenal obstruction secondary to Ladd's bands, inguinal hernias, cryptorchidism, transient subperiosteal new bone formation, and short stature with delayed bone age, which had not been previously reported in association with the MTSS2-related NDD. Exome sequencing identified the recurrent c.2011C>T (p.Arg671Trp) variant in the MTSS2 gene. The mother and the other twin tested negative for the pathogenic variant, while the father's participation in the study was unavailable. This case confirms that the MTSS2-related NDD is caused by the recurrent MTSS2 missense variant p.Arg671Trp. The novel findings identified in our patient expand the phenotypic spectrum associated with this new autosomal dominant entity, but further studies on its genetic and clinical manifestations are still needed.

Clinical insights from an unusual Turner syndrome manifestation: Congenital cutis verticis gyrata.

Cutis verticis gyrata (CVG) is classified as primary or secondary according to the absence or presence of underlying soft tissue abnormalities. We report an infant with Turner syndrome (TS) who in addition presented with CVG on the scalp. The skin biopsy revealed a hamartoma-like lesion. We reviewed the clinical and histopathological findings of the 13 reported cases of congenital CVG in patients with TS, including ours. In 11 of them, CVG was localized on the skin of the scalp, mainly on the parietal region, and in two, on the forehead. Clinically, CVG had a flesh-colored aspect, with absent or sparse hair, and was not progressive. CVG was classified as primary in four patients who had skin biopsy and it was attributed to the intrauterine lymphedema of TS. However, histopathology in two of these patients identified dermal hamartoma as a secondary cause of CVG, and in three others, including ours, there were hamartomatous changes. Although further studies are required, previous findings support the proposal that some CVG may instead be dermal hamartomas. This report alerts clinicians to recognize CVG as a low-frequency manifestation of TS, but also to consider the possible co-occurrence of TS in all female infants with CVG.

Comunicação efetiva e segurança do paciente: relato de experiência do PET-Saúde / Effective communication and patient safety: PET-Saúde experience report / Comunicación efectiva y seguridad del paciente: informe de experiencia PET-Saúde

Objetivo: Relatar a experiência de um grupo tutorial do PET-Saúde Gestão e Assistência, na elaboração e execução das atividades educativas, visando a prevenção e controle da Diabetes Mellitus. Método: Trata-se de um relato de experiência sobre as atividades de educação em saúde e educação permanente, desenvolvidas no Centro Especializado de Atenção ao Diabético e Hipertenso (CADH), no município de Feira de Santana-BA, pelo grupo tutorial I do PET-Saúde Gestão e Assistência, da Universidade Estadual de Feira de Santana. Foram desenvolvidas atividades referentes ao Dia do Idoso, Dia Mundial do Diabetes, curso de atualização em Diabetes e em feridas, com participação de bolsistas, tutores e preceptores do programa, usuários e equipe da unidade. Resultados: A educação em saúde auxilia as pessoas com diabetes no entendimento sobre a doença, seus fatores de risco e formas de controle. Isso inclui informações sobre alimentação saudável, exercícios físicos, monitoramento da glicemia e uso correto de medicamentos. A educação continuada dos profissionais é imprescindível para o desenvolvimento das atividades educativas e cuidado ao paciente com diabetes. Conclusão: As atividades desenvolvidas propiciaram uma experiência enriquecedora aos profissionais, usuários e estudantes, sendo avaliadas como positiva pelos participantes, contribuindo para a melhoria da saúde da população assistida no CADH.

Objective: To report the experience of a tutorial group from PET-Health Management and Assistance, in the elaboration and execution of educational activities, aiming at the prevention and control of Diabetes Mellitus. Method: This is an experience report on health education and permanent education activities, developed at the Specialized Center for Attention to Diabetics and Hypertension (CADH), in the city of Feira de Santana-BA, by the tutorial group I of PET -Health Management and Assistance, from the State University of Feira de Santana. Activities related to the Day of the Elderly, World Diabetes Day, an update course on Diabetes and wounds were carried out, with the participation of scholarship holders, tutors and preceptors of the program, users and the unit's staff. Results: Health education helps people with diabetes to un derstand the disease, its risk factors and ways of controlling it. This includes information on healthy eating, exercise, blood glucose monitoring and correct medication use. The continuing education of professionals is essential for the development of educational activities and care for patients with diabetes. Conclusion: The activities developed provided an enriching experience for professionals, users and students, being evaluated as positive by the participants, contributing to the improvement of the health of the population assisted in the CADH.

Objetivo: Relatar la experiencia de un grupo tutorial del PET-Saúde Gestão e Assistência, en la elaboración y ejecución de actividades educativas, visando la prevención y el control de la Diabetes Mellitus. Método: Se trata de un relato de experiencia sobre educación en salud y actividades de educación permanente, desarrollado en el Centro Especializado de Atención a Diabéticos e Hipertensivos (CADH), en la ciudad de Feira de Santana-BA, por el grupo tutorial I del PET -Gestión en Salud y Asistencia, de la Universidad Estatal de Feira de Santana. Se realizaron actividades relacionadas con el Día del Adulto Mayor, Día Mundial de la Diabetes, curso de actualización en Diabetes y heridas, con la participación de becarios, tutores y preceptores del programa, usuarios y personal de la unidad. Resultados: La educación en salud ayuda a las personas con diabetes a comprender la enfermedad, sus factores de riesgo y las formas de controlarla. Esto incluye información sobre alimentación saludable, ejercicio, control de glucosa en sangre y uso correcto de medicamentos. La educación continua de los profesionales es fundamental para el desarrollo de actividades educativas y de atención a los pacientes con diabetes. Conclusión: Las actividades desarrolladas proporcionaron una experiencia enriquecedora para profesionales, usuarios y estudiantes, siendo evaluadas como positivas por los participantes, contribuyendo para la mejora de la salud de la población atendida en el CADH.

Comparative analysis of Respiratory Syncytial Virus frequency rates and viral load in different patient cohorts in a University Hospital in São Paulo, Brazil, over an eight-year period (2005-2013)

Abstract Respiratory Syncytial Virus (RSV) poses a global health concern, particularly affecting young children, the elderly, and immunosuppressed individuals. RSV viral load is essential for understanding transmission, disease severity, prevention, and treatment. This retrospective study aimed to analyze the frequency rates and viral loads of RSV infections in different patient cohorts and age groups over an eight-year period in a university hospital in São Paulo, Brazil. This study analyzed 1380 Immunocompetent (IC) and Immunosuppressed (IS) patients with acute respiratory tract infections. IC included patients with chronic Heart Disease (HD), Primary Care service recipients (PC), and a subgroup suspected of having Severe Acute Respiratory Syndrome caused by Influenza A (H1N1)pdm09 virus (SARS H1N1). IS comprised transplant patients and those with HIV infection. Respiratory samples were collected between February 2005 and October 2013, with RSV detection and viral load quantification (Log10 copies of RNA/mL) using RT-qPCR. Overall RSV infection rate was 17.3 %, with higher rates in children (23.9 %) than in adults (12.9 %), particularly in children under two years of age (28.2 %). Children in the SARS H1N1 and PC subgroups had higher infection rates (16.4 % and 34.9 %, respectively), with the highest rate in PC children aged 1 to < 2 years (45.45 %). Adults with HD had a significantly higher frequency rate (27.83 %) than those in the SARS H1N1 (2.65 %) and IS (15.16 %) subgroups and higher hospitalization rate among adults under 65 years. RSV viral load ranged from 2.43 to 10.15 Log10 RNA copies/mL (mean ± SD 5.82 ± 2.19), with hospitalized patients exhibiting significantly higher viral loads (7.34 ± 1.9) than outpatients (4.38 ± 1.89). Elderly bone marrow transplant patients also had significantly higher viral loads (7.57 ± 2.41) than younger adults (5.12 ± 1.87). This study provides insights into the RSV infection patterns in different patient cohorts in Brazil. Further investigations are needed to understand susceptibility and risk factors associated with RSV infection. In conclusion, high RSV viral load among hospitalized patients could serve as a surrogate marker of disease severity. Additionally, patients with chronic heart disease deserve greater attention regarding complications associated with RSV infection.

Three-Dimensional Printing Technologies for Drug Delivery Applications: Processes, Materials, and Effects.

Since the 1930s, new methods of drug delivery, such as implantable devices with drug release control, have been developed. However, manufacturing techniques require bulk due to high initial production costs. Three-dimensional (3D) printing, also known as additive manufacturing or rapid prototyping, allows the fabrication of personalized drug delivery that uses different materials and complex geometries with multiple release profiles, thereby eradicating high initial costs. Different studies have been developed showing the extensive potential of 3D printing for the pharmaceutical industry, and despite in-depth discussions that have been published, there is no comprehensive review of processes, materials, and effects in drug delivery applications thus far. This review aims to fill this gap by presenting the use of 3D printing technology for drug delivery, exposing the different variations of the technique according to the characteristics, material, and dosage form sought. There are seven main categories of 3D printing according to the standards jointly developed by International Organization for Standardization and American Society for Testing and Materials: material jetting, binder jetting, material extrusion, vat photopolymerization, powder bed fusion, sheet lamination, and directed energy deposition. There are different 3D fabrication processes used for drug delivery applications depending on the dosage form and material applied. In this context, polymers, glasses, and hydrogels represent the most frequent materials used. 3D printing allows different forms of drug dosage. Oral, topical, rectal and vaginal, parental and implantable are discussed in this paper, presenting the identification of the type of 3D printing technology, the active pharmaceutical ingredient, formulation, and pharmaceutical effect. The main aim of this paper is to offer insights to people from academy and industry who are interested in the advancement of drug delivery and in knowing the future directions in the development of 3D printing applications in this area.

Respiratory syncytial virus: viral load, viral decay, and disease progression in children with bronchiolitis.

Acute viral bronchiolitis is the major cause of hospital admissions in children under 2 years of age, and respiratory syncytial virus (RSV) can be responsible for up to 80% of these infections. We aimed to describe RSV dynamics among hospitalized children with bronchiolitis. Upper respiratory samples of 101 hospitalized patients were collected and submitted to RSV detection by a quantitative real-time RT-PCR to assess viral load (Log10 RNA copies/mL). Seventy-two patients were positive for RSV infection, of which 38 (52.7%) could be followed up until RSV was no longer detected. The first RSV RT-qPCR was carried out on average on the 5th day of symptom onset. Thirty-six patients (94.7%) were still shedding RSV after 7 days, and 9 (23.6%) after 14 days of symptoms onset. Only 2 patients (5.2%) were still shedding RSV after 21 days. Only 7 of the followed patients (18.9%) were submitted to intubation. There was no difference between the viral load of the first collected sample and the viral persistence of patients with comorbidities, who needed intensive care unit and who needed intubation. These data could help understand RSV dynamics and future studies and treatments to come.

Comparative Therapeutic Potential of Cardioactive Glycosides in Doxorubicin Model of Heart Failure.

In the present study, we investigated the cardioactive glycosides oleandrin and ouabain, and compared them to digoxin in a model of cardiotoxicity induced by doxorubicin. Adult rats were distributed into four experimental groups. Each group was challenged with a single intraperitoneal application of doxorubicin at a dose of 12 mg/kg. Then, they were treated with saline solution and the glycosides oleandrin, ouabain, and digoxin at a dose of 50 µg/kg, for 7 days. They underwent echocardiography, electrocardiography, hematologic, biochemical tests, and microscopic evaluation of the heart. All animals presented congestive heart failure, which was verified by a reduction in the ejection fraction. Oleandrin and digoxin were able to significantly reduce (p < 0.05) the eccentric remodeling caused by doxorubicin. Oleandrin and digoxin were significantly lower (p < 0.05) than the control group in maintaining systolic volume and left ventricular volume in diastole. Other parameters evaluated did not show significant statistical differences. All animals showed an increase in erythrocyte count, and an increase in the duration of the QRS complex on the ECG and myocardial necrosis at the histopathological analysis. It is concluded that the glycosides oleandrin, ouabain, and digoxin in the used dosage do not present therapeutic potential for the treatment of congestive heart failure caused by doxorubicin.

Processo de passagem de plantão: o olhar de enfermeiras nas unidades de terapia intensiva / Procedimiento de paso de guardia: la mirada de las enfermeras en las unidades de cuidados intensivos / Procedure for the handover: nurses' perspective in intensive care units

Objetivo: compreender o processo de passagem de plantão das enfermeiras nas Unidades de Terapia Intensiva Adulto. Método: estudo com abordagem qualitativa, cuja coleta de dados foi realizada entre outubro e dezembro de 2020, por meio de observação não participativa e entrevista semiestruturada realizada em cinco unidades intensivas de hospital público do estado da Bahia, Brasil. Resultados: emergiram duas categorias principais: Práxis da passagem de plantão para melhoria do cuidado e Barreiras que prejudicam a comunicação durante a passagem de plantão. Foi possível compreender o processo de passagem de plantão, com base nos olhares das enfermeiras intensivistas, as quais dispõem de elementos estruturais para comunicação efetiva que reverberam na continuidade da assistência. Considerações finais: no processo de passagem de plantão das enfermeiras, condições estruturais e ambientais, tais como conversas paralelas, dispersão, falta de atenção, interrupções, saídas antecipadas e ruídos foram caracterizadas como barreiras que causavam falhas e interferiam no processo de comunicação.

Objetivo: comprender el proceso de paso de guardia de las enfermeras en las Unidades de Terapia Intensiva Adulto. Método: estudio con enfoque cualitativo, cuya recopilación de datos fue realizada entre octubre y diciembre de 2020, por medio de observación no participativa y entrevista semiestructurada realizada en cinco unidades intensivas de hospital público del estado de Bahía, Brasil. Resultados: surgieron dos categorías principales: Praxis del paso de guardia para mejora del cuidado y Barreras que perjudican la comunicación durante el paso de guardia. Fue posible comprender el proceso de paso de guardia, con base en las miradas de las enfermeras intensivistas, las cuales disponen de elementos estructurales para comunicación efectiva que reverberan en la continuidad de la asistencia. Consideraciones finales: en el proceso de paso de guardia de las enfermeras, condiciones estructurales y ambientales, tales como conversaciones paralelas, dispersión, falta de atención, Las interrupciones, salidas anticipadas y ruidos fueron caracterizadas como barreras que causaban fallas e interferían en el proceso de comunicación.

Objective: to understand the process of handover of nurses in Adult Intensive Care Units. Method: study with a qualitative approach, whose data collection was performed between October and December 2020, through non-participant observation and semi-structured interview conducted in five intensive care units of a public hospital in the state of Bahia, Brazil. Results: two main categories emerged: Praxis of the handover to improve care and barriers that impair communication during the handover. It was possible to understand the process of shift, based on the looks of intensive nurses, which have structural elements for effective communication that reverberate in the continuity of care. Final considerations: in the process of handover of nurses, structural and environmental conditions, such as parallel conversations, dispersion, lack of attention, interruptions, anticipated egress and noise were characterized as barriers that caused failures and interfered in the communication process.

Hepatitis E virus infection among patients with altered levels of alanine aminotransferase.

Hepatitis E virus (HEV) affects 20 million people worldwide, with 3.3 million cases and 56,000 deaths. The transmission is mainly by the fecal-oral route. Several studies have reported increased alanine aminotransferase (ALT) levels in association with viral hepatitis. This study evaluated the diagnosis of HEV infection among patients attending the emergency room (ER) of Hospital Beneficência Portuguesa (HBP) and Hospital São Paulo (HSP) in São Paulo, Brazil increased ALT levels (≥ 200 IU/L). From October 2018 to July 2019, 400 sera samples were collected from patients treated at the ER of HBP (n=200) and HSP (n=200). All samples were screened for HEV by RT-qPCR. 200 samples from HSP were tested for IgM of anti-Hepatitis A (HAV) and B (HBV) viruses, and total antibodies of Hepatitis C virus (HCV). Ninety samples (45 from each hospital), were tested for anti-HEV IgM antibodies. Patients aged under 1 to 91 years (mean = 46.29 ± 24.17, median = 48). ALT levels varied from 200 to 8,974 IU/l. 16 patients (4%) turned out positive for HEV by RT-qPCR (ALT levels = 299 to 698 IU/L). Of the 200 HSP patients, 18 (9%) were anti-HAV IgM reactive, 9 (4.5%) for anti-HBV IgM, and 7 (3.5%) for anti-HCV antibodies (ALT levels = 833 to 1918 IU/L). Two of 90 BPH patients (2.22%) were anti-HEV IgM reactive (ALT levels = 1502 to 3831 IU/L). This is the first Brazilian study evaluating patients with suspected HEV infection with increased ALT levels, which were higher than 12 and 60 times the normal upper limit, in the acute phase or for patients reactive for antibody detection, respectively. Liver damage could be minimized by implementing molecular diagnostic tests in the hospital routine.

cAMP Receptor Protein Positively Regulates the Expression of Genes Involved in the Biosynthesis of Klebsiella oxytoca Tilivalline Cytotoxin.

Klebsiella oxytoca is a resident of the human gut. However, certain K. oxytoca toxigenic strains exist that secrete the nonribosomal peptide tilivalline (TV) cytotoxin. TV is a pyrrolobenzodiazepine that causes antibiotic-associated hemorrhagic colitis (AAHC). The biosynthesis of TV is driven by enzymes encoded by the aroX and NRPS operons. In this study, we determined the effect of environmental signals such as carbon sources, osmolarity, and divalent cations on the transcription of both TV biosynthetic operons. Gene expression was enhanced when bacteria were cultivated in tryptone lactose broth. Glucose, high osmolarity, and depletion of calcium and magnesium diminished gene expression, whereas glycerol increased transcription of both TV biosynthetic operons. The cAMP receptor protein (CRP) is a major transcriptional regulator in bacteria that plays a key role in metabolic regulation. To investigate the role of CRP on the cytotoxicity of K. oxytoca, we compared levels of expression of TV biosynthetic operons and synthesis of TV in wild-type strain MIT 09-7231 and a Δcrp isogenic mutant. In summary, we found that CRP directly activates the transcription of the aroX and NRPS operons and that the absence of CRP reduced cytotoxicity of K. oxytoca on HeLa cells, due to a significant reduction in TV production. This study highlights the importance of the CRP protein in the regulation of virulence genes in enteric bacteria and broadens our knowledge on the regulatory mechanisms of the TV cytotoxin.

Disordered Eating Behaviors Are Associated with Gestational Weight Gain in Adolescents.

Disordered eating behaviors (DEBs) and adolescent pregnancy are public health problems. Among adolescents, there is little evidence concerning the relationship of DEB with gestational weight gain (GWG) and the birth weight and length of their offspring. We aimed to determine the association between DEB with GWG and the weight and length of adolescents' offspring. We conducted a study with 379 participants. To evaluate DEB, we applied a validated scale. We identified three factors from DEB by factorial analysis: restrictive, compensatory, and binge-purge behaviors. The main events were GWG and offspring's birth weight and length. We performed linear regression models. We found that 50% of adolescents have at least one DEB. Excessive and insufficient GWG were 37 and 34%, respectively. The median GWG was 13 kg; adolescents with restrictive behaviors had higher GWG (13 vs. 12 kg, p = 0.023). After adjusting for pregestational body mass index and other covariables, the restrictive (ß = 0.67, p = 0.039), compensatory (ß = 0.65, p = 0.044), and binge-purge behaviors (ß = 0.54, p = 0.013) were associated with higher GWG. We did not find an association between the birth weight and length of newborns with DEB, and suggest that DEB is associated with GWG but not with the birth weight or length of the offspring.

Rapid Exclusion of COVID Infection With the Artificial Intelligence Electrocardiogram.

OBJECTIVE: To rapidly exclude severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using artificial intelligence applied to the electrocardiogram (ECG). METHODS: A global, volunteer consortium from 4 continents identified patients with ECGs obtained around the time of polymerase chain reaction-confirmed COVID-19 diagnosis and age- and sex-matched controls from the same sites. Clinical characteristics, polymerase chain reaction results, and raw electrocardiographic data were collected. A convolutional neural network was trained using 26,153 ECGs (33.2% COVID positive), validated with 3826 ECGs (33.3% positive), and tested on 7870 ECGs not included in other sets (32.7% positive). Performance under different prevalence values was tested by adding control ECGs from a single high-volume site. RESULTS: The area under the curve for detection of acute COVID-19 infection in the test group was 0.767 (95% CI, 0.756 to 0.778; sensitivity, 98%; specificity, 10%; positive predictive value, 37%; negative predictive value, 91%). To more accurately reflect a real-world population, 50,905 normal controls were added to adjust the COVID prevalence to approximately 5% (2657/58,555), resulting in an area under the curve of 0.780 (95% CI, 0.771 to 0.790) with a specificity of 12.1% and a negative predictive value of 99.2%. CONCLUSION: Infection with SARS-CoV-2 results in electrocardiographic changes that permit the artificial intelligence-enhanced ECG to be used as a rapid screening test with a high negative predictive value (99.2%). This may permit the development of electrocardiography-based tools to rapidly screen individuals for pandemic control.

Cattle In Vitro Induced Pluripotent Stem Cells Generated and Maintained in 5 or 20% Oxygen and Different Supplementation.

The event of cellular reprogramming into pluripotency is influenced by several factors, such as in vitro culture conditions (e.g., culture medium and oxygen concentration). Herein, bovine iPSCs (biPSCs) were generated in different levels of oxygen tension (5% or 20% of oxygen) and supplementation (bFGF or bFGF + LIF + 2i-bFL2i) to evaluate the efficiency of pluripotency induction and maintenance in vitro. Initial reprogramming was observed in all groups and bFL2i supplementation initially resulted in a superior number of colonies. However, bFL2i supplementation in low oxygen led to a loss of self-renewal and pluripotency maintenance. All clonal lines were positive for alkaline phosphatase; they expressed endogenous pluripotency-related genes SOX2, OCT4 and STELLA. However, expression was decreased throughout the passages without the influence of oxygen tension. GLUT1 and GLUT3 were upregulated by low oxygen. The biPSCs were immunofluorescence-positive stained for OCT4 and SOX2 and they formed embryoid bodies which differentiated in ectoderm and mesoderm (all groups), as well as endoderm (one line from bFL2i in high oxygen). Our study is the first to compare high and low oxygen environments during and after induced reprogramming in cattle. In our conditions, a low oxygen environment did not favor the pluripotency maintenance of biPSCs.

Differentiation of Porcine Induced Pluripotent Stem Cells (piPSCs) into Neural Progenitor Cells (NPCs).

iPSC-derived neurons are attractive in vitro models to study neurogenesis and early phenotypic changes in mental illness, mainly when most animal models used in pre-clinical research, such as rodents, are not able to meet the criteria to translate the findings to the clinic. Non-human primates, canines, and porcine are considered more adequate models for biomedical research and drug development purposes, mainly due to their physiological, genetic, and anatomical similarities to humans. The swine model has gained particular interest in translational neuroscience, enabling safety and allotransplantation testing. Herein the generation of porcine iPSCs is described along with its further differentiation into neural progenitor cells (NPCs). The generated cells expressed NPC markers Nestin and GFAP, confirmed by RT-qPCR, and were positive for Nestin, b-Tubulin III, and Vimentin by immunofluorescence. These results show the evidence for the generation of NPC-like cells after in vitro induction with chemical inhibitors from a large animal model, an interesting and adequate model for regenerative and translational medicine research.

Viral load of respiratory syncytial virus among children from primary care and hospital settings admitted to a university hospital in Brazil (2009-2013).

Respiratory syncytial virus (RSV) is a relevant cause of acute respiratory infection among children. Viral replication and immune conditions may account for severity. RSV viral load (VL) was assessed in 486 children (290 hospitalized and 196 from primary care) attended at São Paulo Hospital from 2009 to 2013. VL was calculated by real-time reverse transcription-polymerase chain reaction and expressed in Log10 RNA copies/mL. Coinfection with rhinovirus (RV) and influenza A virus was also tested. Young children (<1 year of age) had a higher mean VL than older children at primary care (6.35 and 4.34 Log10 RNA copies/mL, respectively; P = .0006). Conversely, hospitalized children ≥2 years of age, presented higher mean VL compared with the same age children of primary care (6.10 and 4.26, respectively; P = .0024). RV was the most codetected virus in RSV positive patients (20% from primary care and 14% in hospitalized), and influenza A virus was found in 11% of primary care and 0.4% in hospitalized children with RSV, without RSV VL association (P = .2903). These findings may guide future therapies and immunization policies considering the role of viral load on clinical presentation among older hospitalized children and also the change of infection transmissions.

Food insecurity & dietary restraint in a diverse urban population.

The primary aim of this study was to investigate self-reported reasons for engaging in dietary restraint (DR) in a food insecure urban population. It also tested whether DR was associated with increased eating disorder (ED) pathology when DR was broadly assessed. The initial sample (N = 503) consisted of adult clients visiting food pantries who completed the Eating Disorder Diagnostic Scale for DSM 5, the Radimer Cornell Food Insecurity Measure, and three items from the DR subscale of Eating Disorder Examination Questionnaire (EDE-Q); EDE-Q items were modified to allow participants to explain why they restricted. Analyses included participants (N = 259) who responded to one of the modified EDE-Q questions. Results indicated that participants engaged in DR for several reasons, including minimizing the effect of hunger for other family members (i.e., children), "stretching" food to make it last longer, and prioritizing medical expenses. Intentional efforts to limit food intake in this sample were correlated with increased ED pathology. Although it is not surprising that adults experiencing food insecurity engage in intentional DR, this study adds important information about why food insecure adults engage in DR and highlights the importance of assessing DR for reasons other than weight and shape concerns.

A preceptoria em enfermagem na pandemia do COVID-19: relato de experiência em uma Unidade Básica de Saúde em Cacoal/RO / Nursing Preceptory in COVID-19 Pandemic: Experience Report in a Basic Health Unit in Cacoal/RO

No Brasil, a Atenção Básica em Saúde (ABS) é uma das portas de entrada para pessoas com suspeita ou confirmação da COVID-19, sendo responsável pela coordenação do cuidado e monitoramento dos casos que apresentem sintomas leves. ABS é também campo de ensino prático em enfermagem. Buscamos através do relato de experiência de um estágio supervisionado em enfermagem, numa cidade da Amazônia, estado de Rondônia, fazer alguns apontamentos dos tempos que vivemos. O retorno da atividade da preceptoria no período de pandemia foi uma significativa oportunidade de aprendizagem. O momento nos faz pensar sobre o desconhecido, as incertezas, a ansiedade que se apresenta aos usuários, trabalhadores e estudantes no cotidiano dos serviços. A vivência proporcionou a acadêmicos e à preceptoria, uma visão diferenciada da Atenção Básica e da própria profissão. Desse modo, podemos dizer que a realização de um estágio e a preceptoria permitiu a reflexão sobre alguns aspectos que envolvem a pandemia: processos de trabalho, orientações sanitárias, educação permanente em saúde e os processos formativos.