The ETA-ESE statement on the European Chemicals Agency opinion on iodine as an endocrine disruptor.

In 2022, the European Chemicals Agency (ECHA) made a statement concluding that iodine is an endocrine disruptor (ED). "We stress the fact that the ECHA opinion ECHA/BPC/357/2022 is based on their misguidedly zooming in on exclusively the biocidal products (e.g., hand disinfectants, disinfection of animals' teats/udder, embalming fluids before cremation, etc.) that contain molecular iodine (I2), entirely neglecting [see the 2013 ECHA Regulation (EU) n°528/2012 describing iodine as being of "great importance for human health". Clearly, the current sweeping and erroneous classification of "iodine" as an endocrine disruptor is ill-advised. We moreover call upon the scientific and medical community at large to use the accurate scientific nomenclature, i.e., iodide or iodate instead of "iodine" when referring to iodized salts and food prepared there with. Drugs, diagnostic agents, and synthetic chemicals containing the element iodine in the form of covalent bonds must be correctly labelled ''iodinated'', if possible, using each time their distinctive and accurate chemical or pharmacological name.

Intestinal P-gp activity is reduced in postmenopausal women under breast cancer therapy.

Intestinal P-glycoprotein (P-gp) activity plays a crucial role in modulating the oral bioavailability of its substrates. Fexofenadine has commonly been used as a P-gp probe, although it is important to note the involvement of other drug transporters like, OATP1B1, OATP1B3, and OATP2B1. In vitro studies demonstrated an upregulation of P-gp protein in response to exposure to pregnancy-related hormones. The objective of this study was to investigate how intestinal P-gp activity is impacted by menopausal status. This study sampled fexofenadine plasma concentrations over 0-12 h after probe drug administration from two groups of patients with breast cancer: premenopausal (n = 20) and postmenopausal (n = 20). Fexofenadine plasma concentrations were quantified using liquid-chromatography tandem mass spectrometry. Area under the plasma concentration-time curve from zero to infinity (AUCinf ) was calculated through limited sampling strategies equation. Multiple linear regression was applied on AUCinf , maximum plasma concentration (Cmax ), and time to Cmax . Postmenopausal patients showed a significant increase in Cmax (geometric mean and 95% confidence interval [CI] 143.54, 110.95-176.13 vs. 223.54 ng/mL, 161.02-286.06 and in AUCinf 685.55, 534.98-878.50 vs. 933.54 ng·h/mL 735.45-1184.99) compared to premenopausal patients. The carriers of the ABCB1 3435 allele T displayed higher Cmax values of 166.59 (95% CI: 129.44-214.39) compared to the wild type at 147.47 ng/mL (95% CI: 111.91-194.34, p = 0.02). In postmenopausal individuals, the decrease in P-gp activity of ~40% may lead to an increased plasma exposure of orally administered P-gp substrates.

Oropharyngeal colostrum administration in neonates with gastroschisis: a randomized clinical trial.

OBJECTIVE: To evaluate the effect of colostrum therapy on days to start a suckling diet in newborns diagnosed with simple gastroschisis. METHODS: Randomized clinical trial with newborns diagnosed with simple gastroschisis at a federal hospital in Rio de Janeiro who were randomized to receive oropharyngeal administration of 0.2mL of colostrum or a "sham procedure" during the first 3 days of life. The analysis included clinical outcomes such as days without food, days with parenteral feeding, days until the start of enteral feeding, days to reach complete enteral feeding, sepsis and length of hospital stay. RESULTS: The onset of oral feeding (suction) in patients with simple gastroschisis in both groups occurred at a median of 15 days. CONCLUSION: The present study showed that there were no significant differences in the use of colostrum therapy and the number of days to the start of enteral feeding and suction diet between groups of newborns with simple gastroschisis.

Determination of furosemide and its glucuronide metabolite in plasma, plasma ultrafiltrate and urine by HPLC-MS/MS with application to secretion and metabolite formation clearances in non-pregnant and pregnant women.

Furosemide (FUR) has been used in probe drugs cocktails for in vivo evaluation of the renal transporters OAT1 and OAT3 activities in studies of drug-drug interactions (generally using probenecid as an inhibitor) and drug-disease interactions. The objective of this study was to develop and validate methods for FUR and its glucuronide metabolite (FUR-GLU) analysis in plasma, plasma ultrafiltrate and urine for application in pharmacokinetics studies: a pilot drug-drug interaction study in pregnant women (n = 2), who received a single oral dose of FUR (40 mg) and in another occasion a single oral dose of probenecid (750 mg) before a single oral dose of FUR (40 mg), and in non-pregnant women participants (n = 12), who only received a single oral dose of FUR (40 mg). The samples preparation for FUR in 50 µL of plasma and plasma lysate were carried by acidified liquid-liquid extraction, while 50 µL of urine and 200 µL of plasma ultrafiltrate were simply diluted with the mobile phase. The methods presented linearities in the range of 0.50 - 2500 ng/mL of plasma and plasma lysate, 0.125 - 250 ng/mL of plasma ultrafiltrate, and 50 - 20,000 ng/mL of urine. FUR-GLU methods presented linearities in the range of 0.125 - 250 ng/mL of plasma ultrafiltrate and 50 - 20,000 ng/mL of urine. Precision and accuracy evaluations showed coefficients of variation and relative errors < 15%. In the pregnant women participants, the mean values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU and CLnon-renal were all reduced when probenecid was administered with FUR (8.24 vs 2.89 L/h, 8.15 vs 2.80 L/h, 3.86 vs 1.75 L/h, 48.26 vs 22.10 L/h, respectively). Non-pregnant women presented similar values of FUR CLrenal, CLsecretion, CLformation. FUR-GLU to the pregnant women who received FUR only. Finally, FUR fraction unbound (fu) resulted in values of approximately 1% in pregnant women and to 0.22% in non-pregnant women. These developed and validated methods for FUR and FUR-GLU quantification in multiple matrices can allow the further investigation of UGT1A9/1A1 and the fu when FUR is administered as an OAT 1 and 3 in vivo probe.

Total, Unbound, Renal, and Hepatic Clearances of Raltegravir and the Formation and Elimination Clearances of Raltegravir Glucuronide in Pregnant Women.

This work aimed to evaluate the total, unbound, renal, and hepatic clearances of raltegravir (RAL) and the formation and elimination clearances of raltegravir glucuronide (RAL GLU) in pregnant women living with HIV. The participants received RAL 400 mg twice daily during the third trimester (n = 15) of gestation, delivery (n = 15), and the postpartum period (n = 8). Pharmacokinetic parameter values were calculated on the basis of plasma and urine data using noncompartmental methods. RAL clearances for the third trimester of gestation were as follows: total clearance: geometric mean, 63.63 L/h (95% CI, 47.5-85.25); renal clearance: geometric mean, 2.56 L/h (95% CI, 1.96-3.34); hepatic clearance: geometric mean, 60.52 L/h (95% CI, 44.65-82.04); and unbound clearance: geometric mean, 281.14 L/h (95% CI, 203.68-388.05). RAL GLU formation and elimination clearances for the third trimester of gestation were 7.57 L/h (95% CI, 4.94-11.6) and 8.71 L/h (95% CI, 6.71-11.32), respectively. No differences were observed in RAL GLU pharmacokinetic parameters between the third trimester of gestation and the postpartum period, except for higher formation (7.57 vs 4.03 L/h) and elimination (8.71 vs 4.92 L/h) clearances during the third trimester. The findings based on plasma and urine data are consistent with an increase in the hepatic uridine 5' diphospho-glucuronosyltransferase isoenzymes activities involved in RAL metabolism during pregnancy, and the formation of RAL GLU is a minor route of RAL elimination. Compared to the postpartum period, in the third trimester of gestation, the similar RAL plasma exposure in pregnant women reinforces the maintenance of an RAL regimen including a 400-mg oral dose twice daily during pregnancy.

Effect of Chronic Hepatitis C on the Activity of the Membrane Transporters P-gp and OATP1B1/BCRP on Patients With Different Stages of Hepatic Fibrosis.

The activity of the membrane transporters organic anion-transporting polypeptide 1B1 (OATP1B1) & breast cancer resistance protein (BCRP) (rosuvastatin) and P-glycoprotein (P-gp) (fexofenadine) was evaluated in patients with chronic hepatitis C virus (HCV) infection (n = 28), genotypes 1 and 3, investigated before the treatment with direct-acting antiviral agents (Phase 1) and up to 30 days after the assessment of the virologic response (Phase 2). Participants allocated in Groups 1 (n = 15; F0/F1 and F2, mild to moderate liver fibrosis) and 2 (n = 13; F3 and F4, advanced course of liver fibrosis/cirrhosis) received in both phases fexofenadine (10 mg) and rosuvastatin (2 mg). OATP1B1 & BCRP activity (rosuvastatin area under the plasma concentration-time curve of rosuvastatin from time zero to infinity (AUC0-∞ )) was reduced in Groups 1 and 2, respectively, by 25% (ratio 0.75 (0.53-0.82), P < 0.01) and 31% (ratio 0.69 (0.46-0.85), P < 0.05) in Phase 1 compared with Phase 2. OATP1B1 & BCRP activity was reduced in Phases 1 and 2, respectively, by 49% (median ratio 1.51 (1.17-2.20), P < 0.05) and 61% (ratio 1.39 (1.16-2.02), P < 0.01) in Group 2 compared with Group 1. P-gp activity (fexofenadine AUC0-∞ ) was also reduced in Phase 1 compared with Phase 2 (ratio Phase2/Phase1 0.79 (0.66-0.96) in Group 1 and 0.81 (0.69-0.96) in Group 2) as well as in Group 2 compared with Group 1 in both Phases (ratio Group2/Group1 1.47 (1.08-2.01) in Phase 1 and 1.51 (1.10-2.07) in Phase 2). Thus, clinicians administering OATP1B1 & BCRP and P-gp substrates with low therapeutic indexes should consider the evolution of the treatment and the stage of HCV infection.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear feature: clinical, pathological, and molecular update 5 years after the nomenclature revision.

The term non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was proposed in 2016 and incorporated as a new entity in the World Health Organization (WHO) classification of tumours of endocrine organs in 2017. Since then, there has been debate regarding the histological criteria for the diagnosis, the need for molecular studies or the risk of lymph node metastasis or recurrence associated with this entity. Over the years, the concept of NIFTP evolved, now including both small (<1 cm) and large (>4 cm) tumours and oncocytic lesions. On the other hand, recent data on NIFTP in the setting of thyroid follicular nodular disease or frequent coexistence of malignant tumours raised concerns regarding the follow-up of these patients. Today, both pathologists and clinicians still face several challenges in the diagnosis, treatment, and follow-up of patients with NIFTP.

Survey on selenium clinical supplementation in autoimmune thyroid disease.

Objective: Previous trials show that selenium could be a very useful tool in the control and treatment of autoimmune thyroid diseases. In this cross-sectional study, through a survey, we aim to evaluate Portuguese endocrinologists' perception and pattern of prescription of selenium supplements in these diseases and verify its agreement with current guidelines. Methods: The endocrinologists registered in the Portuguese Medical Association were sent an email with a web-based questionnaire, regarding their knowledge and use of selenium supplements in thyroid autoimmune pathology. Results: A total of 105 physicians (33% of the total) submitted the survey. The selenium serum concentration in the general population was unknown to 80% of respondents. Over a third of respondents have never prescribed selenium for autoimmune thyroid disease. However, 89% are not afraid of recommending it, and 61% indicate Graves' orbitopathy as the pathology they would supplement. In Hashimoto's thyroiditis, 36% of respondents use selenium occasionally or frequently, and this percentage rises to 60% in Graves' disease. Conclusions: Although recommendations only encompass mild Graves' orbitopathy, selenium is prescribed across the spectrum of autoimmune thyroid diseases, probably due to recent studies that consistently show improvement of biochemical hallmarks in these patients. Further investigation is required on the impact of selenium supplements on primarily clinical outcomes and to identify disorders and/or patients who will benefit the most. Also, there is still insufficient knowledge of this field in the medical community, and evidence-based practice should continue to be promoted by endocrinology societies.

P-Glycoprotein and Organic Anion Transporter Polypeptide 1B/Breast Cancer Resistance Protein Drug Transporter Activity in Pregnant Women Living With HIV.

This study evaluates the influence of pregnancy and HIV infection in conjunction with the use of raltegravir, lamivudine, and tenofovir disoproxil fumarate (combined antiretroviral therapy [cART]) on intestinal P-glycoprotein (P-gp) and hepatic organic anion transporter polypeptide (OATP) 1B1/1B3 and/or breast cancer resistance protein (BCRP) drug transporter activity using rosuvastatin (OATP1B/BCRP) and fexofenadine (P-gp) probes. Single oral doses of 5-mg rosuvastatin and 60-mg fexofenadine were administered to women living with HIV under cART in the third trimester of gestation (n = 15) and postpartum period (n = 10). A control group of 12 healthy nonpregnant women also was investigated. Pharmacokinetic parameters were estimated by using a noncompartmental method and evaluated by t test (P < .05). The rosuvastatin area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC0-last ) value was higher in the third trimester of pregnancy (19.5 [95%CI, 16.8-22.3] ng • h/mL] when compared to postpartum (13.3 [95%CI, 9.3-17.5] ng • h/mL), while the fexofenadine AUC0-last values did not differ between the third trimester of pregnancy (738.0 [95%CI, 611.4-864.6] ng • h/mL) and postpartum period (874.9 [95%CI, 408.2-1342.0] ng• h/mL). The rosuvastatin AUC0-last values did not differ between healthy nonpregnant women (13.8 [95%CI, 10.0-17.6] ng • h/mL) and women living with HIV in the postpartum period (13.3 [95%CI, 9.3-17.5] ng • h/mL), and the fexofenadine AUC0-last values did not differ between the 2 investigated groups (603.6 [95%CI, 467.5-739.7] ng • h/mL vs 874.9 [95%CI, 408.2-1342.0] ng • h/mL). It is suggested that gestation inhibits the hepatic OATP1B1/1B3 and/or BCRP activity but does not alter intestinal P-gp activity. The influence of HIV infection in conjunction with use of cART on OATP1B/BCRP and intestinal P-gp activity was not observed.

Oropharyngeal colostrum administration in neonates with gastroschisis: a randomized clinical trial / Administração orofaríngea de colostro em recém-nascidos com gastrosquise: ensaio clínico randomizado

ABSTRACT Objective: To evaluate the effect of colostrum therapy on days to start a suckling diet in newborns diagnosed with simple gastroschisis. Methods: Randomized clinical trial with newborns diagnosed with simple gastroschisis at a federal hospital in Rio de Janeiro who were randomized to receive oropharyngeal administration of 0.2mL of colostrum or a "sham procedure" during the first 3 days of life. The analysis included clinical outcomes such as days without food, days with parenteral feeding, days until the start of enteral feeding, days to reach complete enteral feeding, sepsis and length of hospital stay. Results: The onset of oral feeding (suction) in patients with simple gastroschisis in both groups occurred at a median of 15 days. Conclusion: The present study showed that there were no significant differences in the use of colostrum therapy and the number of days to the start of enteral feeding and suction diet between groups of newborns with simple gastroschisis.

RESUMO Objetivo: Avaliar o efeito da colostroterapia em dias para iniciar a dieta por sucção em recém-nascidos com diagnóstico de gastrosquise simples. Métodos: Ensaio clínico randomizado com recém-nascidos diagnosticados com gastrosquise simples em um hospital federal no Rio de Janeiro que foram randomizados para receber administração orofaríngea de 0,2mL de colostro ou "procedimento simulado", nos primeiros 3 dias de vida. A análise incluiu desfechos clínicos, como dias sem alimentação, dias com alimentação parenteral, dias para iniciar a alimentação enteral, dias para atingir a alimentação completa, sepse e tempo de internação. Resultados: O início da alimentação por via oral (sucção) na gastrosquise simples, em ambos os grupos, ocorreu com mediana de 15 dias. Conclusão: O presente estudo mostrou que não há diferenças significativas no uso de colostroterapia em dias para início de alimentação enteral e dieta por sucção entre grupos de recém-nascidos com gastrosquise simples.

Internação e alta hospitalar do recém-nascido na unidade de cuidado neonatal: identificação das dúvidas dos pais / Hospitalization and discharge of the neonate in the neonatal care unit: identification of parents' doubts / Hospitalización y alta del recién nacido en la unidad de cuidado neonatal: identificación de las dudas de los padres

Objetivo:Identificar as dúvidas dos pais frente aos cuidados dos seus filhos na UTIN no processo de internação e alta hospitalar. Metodologia: estudo de natureza descritiva e abordagem qualitativa. O cenário da pesquisa foi uma unidade neonatal de um hospital terciário, localizado no Estado do Rio de Janeiro. Foram selecionadas, por conveniência, como participantes do estudo as mães e pais dos recém-nascidos internados na UTIN, com internação mínima de 2 semanas, e que estivessem presentes na unidade. A coleta de dados foi realizada através de dados obtidos no prontuário do recém-nascido e um questionário. Foram realizadas também entrevistas abertas com os pais na primeira semana de internação do RN na UTIN e nas semanas subsequentes, até a semana da alta. Nesta pesquisa, a análise de dados foi feita por meio da análise de conteúdo de Bardin. Resultados: Participaram desta pesquisa 10 mães e 02 pais de RNinternados na UTIN. Com a transcrição das entrevistas, emergiram setecategorias que se tratavam das dúvidas que as mães e os pais apresentavam durante o processo de internação, descritas a seguir: Cuidados Básicos; Amamentação/Alimentação; Tratamento; Exames/Cirurgias; Impeditivos para alta; Cuidados pós-cirúrgicos; Tempo de internação. A categoria com o maior número de dúvidas apresentada durante a pesquisa foi sobre Tratamento (25.5%). Conclusão:Foi possível constatarque a internação na UTIN gera nos pais diversas dúvidas. Dúvidas essas relacionadas aos cuidados prestados aos seus filhos, sobre amamentação e alimentação, sobre o tratamento, entre outras.

Objective: To identify the doubts of parents regarding the care of their babies in the NICU in the process of hospitalization and hospital discharge. Methodology: descriptive study and qualitative approach. The research scenario was a neonatal unit of a tertiary hospital, located in the Rio de Janeiro, Brazil. The mothers and fathers of newborns admitted to the NICU, with a minimum stay of 2 weeks, and who were present in the unit, were selected, for convenience, as study participants. Data collection was performed using data obtained from the newborn's medical record and a questionnaire. Open interviews were also carried out with the parents in the first week of the newborn's hospitalization in the NICU and in the subsequent weeks, until the week of discharge. In this research, data analysis was performed using Bardin's content analysis. Results: 10 mothers and 02 fathers of NBadmitted to the NICU participated in this research. With the transcription of the interviews, seven categories emerged that dealt with the doubts that mothers and fathers had during the hospitalization process, described below: Basic Care; Breastfeeding/Feeding; Treatment; Exams/Surgeries; Disadvantages for discharge; Post-surgical care; Hospitalization time. The category with the highest number of doubts presented during the survey was Treatment (25.5%). Conclusion: It was possible to verify that the hospitalization in the NICU generates several doubts in the parents. Doubts related to the care provided to their children, about breastfeeding and feeding, about treatment, among others.

Objetivo: Identificar las dudas de los padres sobre el cuidado de sus hijos en la UCIN en proceso de hospitalización y alta hospitalaria. Metodología: estudio descriptivo y enfoque cualitativo. El escenario de la investigación fue una unidad neonatal de un hospital de tercer nivel, ubicado en el Estado de Río de Janeiro. Las madres y padres de recién nacidos ingresados en la UCIN, con estancia mínima de 2 semanas, y que estuvieran presentes en la unidad, fueron seleccionados, por conveniencia, como participantes del estudio. La recolección de datos se realizó a partir de los datos obtenidos de la historia clínica del recién nacido y de un cuestionario. También se realizaron entrevistas abiertas con los padres en la primera semana de internación del RN en la UCIN y en las semanas posteriores, hasta la semana del alta. En esta investigación, el análisis de datos se realizó mediante el análisis de contenido de Bardin. Resultados: Participaron de esta investigación 10 madres y 02 padres de RN ingresados en la UCIN. Con la transcripción de las entrevistas, surgieron siete categorías que abordaban las dudas que las madres y los padres tenían durante el proceso de hospitalización, descritas a continuación: Atención Básica; Lactancia materna/Alimentación; Tratamiento; Exámenes/Cirugías; Desventajas para la descarga; Atención posquirúrgica; Tiempo de hospitalización. La categoría con mayor número de dudas presentadas durante la encuesta fue Tratamiento (25,5%). Conclusión: Se pudo verificar que la internación en la UCIN genera varias dudas en los padres. Dudas relacionadas con la atención brindada a sus hijos, sobre la lactancia y alimentación, sobre el tratamiento, entre otros.

Incidence and Risk Factors for Concurrent Syndromic Diagnosis in Presumed Idiopathic Developmental Dysplasia of the Hip.

BACKGROUND: Infants referred for developmental dysplasia of the hip (DDH) may have a previously unidentified concomitant diagnosis of syndromic pathology. Our purpose was to examine the incidence of syndromic pathology in infants referred to a tertiary center with presumed idiopathic DDH and identify risk factors and difference in treatment courses between idiopathic and nonidiopathic cohorts. METHODS: A retrospective analysis of a prospective cohort of infants younger than 3 years who were evaluated for DDH between 2008 and 2013 with a minimum 2-year follow-up. The clinical history and treatment were noted to determine the incidence and nature of concomitant syndromic diagnoses, after a confirmed diagnosis of DDH. RESULTS: There were 202 patients: 177 were females (87.6%). Thirteen patients (6.4%) were later diagnosed with a neurologic/syndromic diagnosis. The workup leading to additional diagnosis was initiated by the orthopaedic surgeon in 8 of 13 patients (61.5%). Half of the referrals (4 of 8) made to other specialists were because of an abnormal treatment course (three-failure of typical DDH treatment and one-relapsed clubfeet). 7 of the 8 referrals were made because of developmental delays and decreased tone. 5 of the 13 nonidiopathic patients had other orthopaedic problems. The syndromic diagnoses included three cerebral palsy, two Kabuki syndrome, one Down syndrome, one myopathy, and one neuropathy. The diagnosis was made at an average of 2.3 years (0.04 to 4.7). No notable difference was observed in the incidence of the four known risk factors for DDH in syndromic patients compared with the idiopathic group. The syndromic patients required more open reductions (P = 0.002). DISCUSSION: By the age of 3 years, 6% of the patients treated for DDH were found to have a syndrome or neurologic abnormality, and the referral for workup was made by the treating surgeon greater than 60% of the time.

Bem-vindo ao lar: dificuldades dos cuidadores de bebês nascidos prematuramente após a alta hospitalar / Welcome home: difficulties of caregivers of premature infants after hospital discharge / Bienvenido a casa: dificultades de los cuidadores de bebés prematuros después del alta del hospital

Objetivo: Identificar as dificuldades dos cuidadores após a alta hospitalar da UTI Neonatal. Metodologia: Pesquisa de abordagem quantitativa, tipo transversal de caráter descritivo e exploratório. Desenvolvido no ambulatório de seguimento/ Follow-up de um hospital terciário no Rio de Janeiro.Os voluntáriosda pesquisa foram os pais ou cuidadores de recém-nascidos com idade gestacional menor que 37 semanas e que tiveram o tempo mínimo de quinze dias de internação do filho na UTIN. Os dados foram coletados através de uma entrevista na primeira consulta do RN no follow-up, realizada após uma semana de alta. A análise dos dados foi feita por meio deestatística descritiva. Resultados: Foram incluídos no estudo 15 cuidadores. Dentre as orientações que não foram recebidas destaca-se os sinais de alerta (70,6%), Limpeza da mamadeira (52,9%) e uso da chupeta (52,9%). Ao relacionar o tempo de permanência na UTIN com as orientações recebidas vemos que os cuidadores em que o RN permanece por menor tempo na UTIN são os que acabam tendo menos orientações sobre os cuidados com atemperatura, cuidados com higiene e sinais de alerta. Conclusão: Os resultados aqui apresentados mostraram que a chegada da família ao domicílio com o bebê, representa orompimento com o mundo da internação e gera experiências próprias do contexto domiciliar.

Objective: To identify the difficulties of caregivers after hospital discharge from the Neonatal ICU. Methodology: Research with a quantitative approach, transversal type of descriptive and exploratory character. Developed in the follow-up/Follow-up clinic of a tertiary hospital in Rio de Janeiro. The research volunteers were parents or caregivers of preterm infants with a gestational age of less than 37 weeks and who had at least fifteen days of hospitalization. Data were collected through an interview during first follow-up appointment, carried out after one week of discharge. Data analysis was performed using descriptive statistics. Results: 15 caregivers were included in the study. Among the guidelines that were not received, warning signs (70.6%), bottle cleaning (52.9%) and pacifier use (52.9%) stand out. When relating the length of stay in the NICU with the guidelines received, we see that caregivers whose newborns spend less time in the NICU end up having less guidance on temperature care, hygiene care and warning signs. Conclusion: The results presented here showed that the arrival of the family at home with the baby represents a break with the world of hospitalization and generates experiences specific to the home context.

Objetivo: Identificar las dificultades de los cuidadores después del alta hospitalaria de la UTI Neonatal.Metodología: Investigación con enfoque cuantitativo, de tipo transversal de carácter descriptivo y exploratorio. Desarrollado en el ambulatorio de seguimiento/seguimiento de un hospital de tercer nivel en Río de Janeiro. Los voluntarios de la investigación fueron los padres o cuidadores de recién nacidos con edad gestacional menor de 37 semanas y que tuvieran un tiempo mínimo de quince días de internación del niño en la UCIN. Los datos fueron recolectados a través de una entrevista en la primera visita de seguimiento del RN, realizada después de una semana del alta. El análisis de los datos se realizó mediante estadística descriptiva. Resultados: Quince cuidadores fueron incluidos en el estudio. Entre las orientaciones que no fueron recibidas, se destacan las señales de advertencia (70,6%), limpieza del biberón (52,9%) y uso del chupete (52,9%). Al relacionar el tiempo de permanencia en la UCIN con las orientaciones recibidas, vemos que los cuidadores en los que el RN permanece menos tiempo en la UCIN son los que terminan teniendo menos orientaciones sobre cuidados de temperatura, cuidados de higiene y signos de alarma.Conclusión: Los resultados aquí presentados mostraron que la llegada de la familia a casa con el bebé representa una ruptura con el mundo de la hospitalización y genera vivencias del contexto domiciliario.

Estresse, qualidade de vida e copingem enfermeiros atuantes em uma unidade neonatal / Stress, quality of life and coping in nurses working in a neonatal unit / Estrés, calidad de vida y mecanismo de supervivenciaen enfermeros que trabajan en una unidad neonatal

Objetivo: Avaliar o estresse, qualidade de vida e relacionar com estratégias de enfrentamento em enfermeiros atuantes na unidade neonatal. Metodologia: estudo transversal do tipo descritivo, com abordagem quantitativa, no período de junho a novembro de 2020 na UTI Neonatal de uma instituiçãode Saúde no estado do Rio de Janeiro. Os participantes do estudo foram 17 enfermeiros plantonistas possuindo vínculo de trabalho que responderam três (3) questionários: Escala Bianchi de Stress ­EBS, World Health Organization Quality of Life -WHOQOL-bref e Inventário de Estratégias de Coping de Folkman e Lazarus. Resultados: De acordo com a classificação do estresse, todos os domínios apresentaram maior frequência de enfermeiros com nível de estresse médio. Os domínios C (atividades relacionadas à administração de pessoal), E (coordenação das atividades da unidade) e F (condições de trabalho para desempenho das atividades) também apresentaram enfermeiros com nível alto de estresse. O domínio F apresentou um percentual de 100% de respondentes classificando como estressor ­Entre os itens deste domínio, predominou o nível de ruído na unidade (29,8%) seguido de realizar tarefas com tempo mínimo disponível (29,6%) e o ambiente físico da unidade (27,9%). Quando perguntadas sobre como avaliariam a sua qualidade de vida, 52,9% das respondentes classificaram como boa. Somente 5,9% responderam como ruim.Conclusão: Os profissionais enfermeiros do estudo apresentam níveis médios e altos de estresse, entretanto, nãoafetaa qualidade de vida dos mesmos. Provavelmente porque diante do estresse a estratégia mais utilizada é a de fuga/esquiva.

Objective: To evaluate stress, quality of life and relate it to coping strategies in nurses working in the neonatal unit. Methodology: cross-sectional descriptive study, with a quantitative approach, from June to November 2020 in the neonatalICU of a Health institution in the state of Rio de Janeiro. The study participants were 17 nurses on duty with employment contract who answered three (3) questionnaires: Bianchi Stress Scale -EBS, World Health Organization Quality of Life -WHOQOL-bref and Folkman and Lazarus Coping Strategies Inventory. Results: According to the stress classification, all domains had a higher frequency of nurses with medium stress level. Domains C (activities related to personnel administration), E (coordination of unit activities) and F (working conditions to perform activities) also presented nurses with a high level of stress. Domain F had a percentage of 100% of respondents classifying it as a stressor -Among the items in this domain, the noise level in the unit predominated (29.8%), followed by performing tasks with minimum available time (29.6%) and physical environment of the unit (27.9%). When asked how they would assess their quality of life, 52.9% of respondents rated it as good. Only 5.9% responded as bad. Conclusion: The study nurses have medium and high levels of stress, however, not affect their quality of life. Probably due to in the face of stress, the most used strategy is escape/avoidance.

Objetivo: Evaluar el estrés, la calidad de vida y relacionarlo con las estrategias de afrontamiento en enfermeros que actúan en la unidad neonatal. Metodología: estudio descriptivo transversal, con abordaje cuantitativo, de junio a noviembre de 2020 en la UTI Neonatal de una institución de salud del estado de Río de Janeiro. Los participantes del estudio fueron 17 enfermeros en turno que respondieron tres cuestionarios: Bianchi Stress Scale, World Health Organization Quality of Life y Folkman and Lazarus Coping Strategies Inventory. Resultados: De acuerdo con la clasificación del estrés, todos los dominios presentaron mayor frecuencia de enfermeros con nivel de estrés medio. Los dominios C (actividades relacionadas con la administración del personal), E (coordinación de las actividades de la unidad) y F (condiciones de trabajo para el desempeño de las actividades) también presentaron a los enfermeros con alto nivel de estrés. El dominio F presentó un porcentaje del 100% de los encuestados clasificándolo como estresor -Entre los ítems de este dominio, predominó el nivel de ruido en la unidad (29,8%), seguido de la realización de tareas con mínimo tiempo disponible (29,6%) y el ambiente físico de la unidad (27,9%). Cuando se les preguntó cómo calificarían su calidad de vida, el 52,9% de los encuestados la clasificó como buena. Solo el 5,9% respondió como malo. Conclusión: Los profesionales de enfermería del estudio presentan niveles medios y altos de estrés, sin embargo, no afecta su calidad de vida. Probablemente porque ante el estrés la estrategia más utilizada es la de escape/evitación.

No implication of HIV coinfection on the plasma exposure to rifampicin, pyrazinamide, and ethambutol in tuberculosis patients.

There are contrasting findings regarding the effect of HIV on the pharmacokinetics of first-line anti-tubercular drugs (FLATDs) due to a lack of prospective controlled clinical studies, including patients with tuberculosis (TB) and patients with TB living with HIV. This study aims to assess the effect of HIV coinfection and antiviral therapy on the plasma exposure to FLATDs in patients with TB. HIV negative (TB-HIV- group; n = 15) and HIV positive (TB-HIV+ group; n = 18) adult patients with TB were enrolled during the second month of FLATDs treatment. All TB-HIV+ patients were on treatment with lamivudine, tenofovir (or zidovudine), and raltegravir (or efavirenz). Serial blood sampling was collected over 24 h and FLATDs pharmacokinetic parameters were evaluated using noncompartmental methods. In the TB-HIV+ patients, dose-normalized plasma exposure area under the curve from zero to 24 h (nAUC0-24 ; geometric mean and 95% confidence interval [CI]) values at steady-state to rifampicin, pyrazinamide, and ethambutol were 18.38 (95% CI 13.74-24.59), 238.21 (95% CI 191.09-296.95), and 18.33 (95% CI 14.56-23.09) µg∙h/ml, respectively. Similar plasma exposure was found in the TB-HIV- patients. The geometric mean and 90% CI of the ratios between TB-HIV- and TB-HIV+ groups suggest no significant pharmacokinetic interaction between the selected antivirals and FLATDs. Likewise, HIV coinfection itself does not appear to have any effect on the plasma exposure to FLATDs.

Suppression of multiple anti-apoptotic BCL2 family proteins recapitulates the effects of JAK2 inhibitors in JAK2V617F driven myeloproliferative neoplasms.

Several lines of research suggest that Bcl-xL-mediated anti-apoptotic effects may contribute to the pathogenesis of myeloproliferative neoplasms driven by JAK2V617F and serve as therapeutic target. Here, we used a knock-in JAK2V617F mouse model and confirmed that Bcl-xL was overexpressed in erythroid progenitors. The myeloproliferative neoplasm (MPN)-induced phenotype in the peripheral blood by conditional knock-in of JAK2V617F was abrogated by conditional knockout of Bcl2l1, which presented anemia and thrombocytopenia independently of JAK2 mutation status. Mx1-Cre Jak2V617W/VF /Bcl2l1f/f mice presented persistent splenomegaly as a result of extramedullary hematopoiesis and pro-apoptotic stimuli in terminally differentiated erythroid progenitors. The pan-BH3 mimetic inhibitor obatoclax showed superior cytotoxicity in JAK2V617F cell models, and reduced clonogenic capacity in ex vivo assay using Vav-Cre Jak2V617F bone marrow cells. Both ruxolitinib and obatoclax significantly reduced spleen weights in a murine Jak2V617F MPN model but did not show additive effect. The tumor burden reduction was observed with either ruxolitinib or obatoclax in terminal differentiation stage neoplastic cells but not in myeloid-erythroid precursors. Therefore, disrupting the BCL2 balance is not sufficient to treat MPN at the stem cell level, but it is certainly an additional option for controlling the critical myeloid expansion of the disease.

New insights on the relation between zooplankton and humic substances in tropical freshwater ecosystems.

Aquatic humic substances (HS) represent about 60-95% of the dissolved organic carbon (DOC) present in coastal environments of northern Rio de Janeiro state, Brazil. Although they are important regulators of processes involving aquatic communities, the response of the zooplankton community to their presence remains poorly understood, especially in natural tropical environments. Therefore, our objective was to elucidate zooplankton community responses along a natural gradient of HS. Such natural humic gradient was obtained in coastal freshwater environments with distinct DOC concentrations (20-200 mg L-1). Results show a decrease in zooplankton density and biomass along the HS gradient. However, microphages organisms (e.g. non-predatory rotifers and smaller testate amoeba, such as Difflugia) were most present in environments with higher concentration of HS, probably due to a stronger importance of the microbial-loop in these environments. Some species - such as Scapholeberis armata (Cladocera) and Lecane boettgeri (Rotifera) were only accounted for environments with high HS concentration, illustrating their potential as bioindicators for HS presence. Nevertheless, we were able to observe the effects of HS on the structure and composition of primary consumers and how these substances might indirectly affect species dynamics. We point out to new findings in highly humic tropical environments, which are still poorly studied and understood.

Clinical treatment for hepatitis C reverses CYP2C19 inhibition.

AIMS: Infection by the hepatitis C virus (HCV) generates inflammatory response selectively modulating cytochrome P450 protein (CYP) activities. This study assessed the effect of chronic hepatitis C on CYP2C19 activity in patients with HCV. METHODS: Patients with HCV infection (n = 23) at different fibrosis stages were allocated into groups 1 (F0/F1 and F2, mild to moderate fibrosis) and 2 (F3 and F4, advanced fibrosis stages). Phase 1 was conducted before the treatment with direct-acting antivirals (DAAs) and phase 2 after the sustained virological response. Participants were administered 2 mg of a single oral dose of omeprazole (OME) as probe drug in both phases. Metabolic ratios (MRs) (plasma samples collected at 4 h after OME administration) were calculated by dividing plasma concentrations of 5-hydroxyomeprazole by OME. RESULTS: The MRs for group 1 were 0.45 (0.34-0.60, 90% confidence interval) and 0.69 (0.50-0.96) for phases 1 and 2, respectively, while the MRs for group 2 were 0.25 (0.21-0.31) and 0.41 (0.30-0.56) for phases 1 and 2, respectively. MRs were different (P < .05) between phases 1 and 2 for both groups, as well as between groups 1 and 2 in phase 1, but not in phase 2 (P > .05). CONCLUSIONS: Both groups presented different MRs before and after treatment with DAAs, evidencing that CYP2C19 inhibition during inflammation was at least partially reversed after DAA treatment. Groups 1 and 2 were also found to be different in phase 1 but not phase 2, showing that CYP2C19 metabolic activity does not differ between groups after DAA treatment.

Nifedipine Does Not Alter the Pharmacokinetics of Venlafaxine Enantiomers in Healthy Subjects Phenotyped for CYP2D6, CYP2C19, and CYP3A.

Venlafaxine (VEN) is a P-glycoprotein (P-gp) substrate, and nifedipine has been described by in vitro and experimental studies as a P-gp inhibitor. The present study aimed to investigate whether nifedipine alters the kinetic disposition of VEN enantiomers and their metabolites in healthy subjects. A crossover study was conducted in 10 healthy subjects phenotyped as extensive metabolizers for cytochrome P450 (CYP) 2D6, CYP2C19, and CYP3A. In phase 1, the subjects received a single oral dose of 150 mg racemic VEN, and in phase 2, a single oral dose of 40 mg nifedipine was administered with the VEN treatment. Plasma concentrations of VEN enantiomers and their metabolites O-desmethylvenlafaxine and N, O- didesmethylvenlafaxine (ODV and DDV, respectively) were evaluated by liquid chromatography with tandem mass spectrometry up to 72 hours after drug administration. Phase 2 was compared with phase 1 using the 90% confidence interval (CI) of the ratio of geometric means for Cmax and area under the curve (AUC). AUC enantiomeric ratios S-(+)/R-(-) were evaluated within each and between phases using the Wilcoxon test (P ≤ .05). The kinetic disposition of VEN was enantioselective (phase 1) with VEN S-(+)/R-(-) AUC ratio median of 2.83 (AUC0-∞ , 526 vs 195 ng·h/mL). However, AUC median did not differ between enantiomers for the metabolites ODV (1971 vs 2226 ng·h/mL) and DDV (199 vs 151 ng·h/mL). The 90%CI of the ratio of geometric means showed that the phases are bioequivalent. A single oral dose of 40 mg nifedipine did not alter VEN enantiomer pharmacokinetics in healthy subjects.

Macronutrients of mothers milk of very low birth weight infants: analysis according to gestational age and maternal variables / Macronutrientes do leite materno de recém-nascidos de muito baixo peso: análise segundo idade gestacional e variáveis maternas

ABSTRACT Objective: To analyze the composition of macronutrients present in the milk of mothers of preterm newborn infants (PTNB) - protein, fat, carbohydrate, and calories - by gestational age (GA), chronological age (CA) and maternal variables. Methods: Longitudinal study that analyzed 215 milk samples from the 51 mothers of PTNB admitted in three Neonatal Intensive Care Units of Rio de Janeiro from May/2013-January/2014. Milk collection was performed by pickup pump, on a fixed day of each week until discharge. The spectrophotometric technique with Infrared Analysis (MilkoScan Minor 104) was used for the quantitative analysis. A sample of 7 mL of human milk was taken from the total volume of milk extracted by the mother. The data was grouped by GA (25-27, 28-31, 32-36, 37-40 weeks) and by CA (zero to 4, 5-8, 9-12, 13-16 weeks). Results: Protein, carbohydrate, fat and calories did not show any pattern of change, with no difference among groups of GA. When the macronutrients were analyzed by groups of CA, protein decreased, with significant difference between the first two groups of CA. Carbohydrates, fat and calories presented increasing values in all groups, without significant differences. Weight gain during pregnancy, maternal hypertension and maternal age were associated with changes in fat and calories in the first moment of the analysis of milk. Conclusions: There was a significant decrease in the levels of protein during the first eight weeks after birth. CA may be an important factor in the composition of human milk.

RESUMO Objetivo: Analisar a composição dos macronutrientes presentes no leite de mães de recém-nascidos pré-termo (RNPT) - gorduras, carboidratos e calorias - por idade gestacional (IG), idade cronológica (IC) e variáveis maternos. Métodos: Estudo longitudinal para analisar 215 amostras de leite de 51 mães de RNPT admitidos em três unidades neonatais do Rio de Janeiro de maio/2013 a janeiro/2014. A coleta de leite foi realizada por bomba coletora, em dia fixo a cada semana até a alta. Utilizou-se a técnica espectrofotométrica com análise de infravermelho (MilkoScan Minor 104) para a análise quantitativa. Uma amostra de 7 mL de leite humano foi retirada do volume total de leite extraído pela mãe. Os dados foram agrupados por IG (25-27, 28-31, 32-36 e 37-40 semanas) e por IC (0-4, 5-8, 9-12 e 13-16 semanas). Resultados: Proteínas, carboidratos, gorduras e calorias não apresentaram nenhum padrão de mudança, não havendo diferença entre os grupos de IG. Quando os macronutrientes foram analisados por grupos de IC, a proteína diminuiu, com diferença significante entre os dois primeiros grupos de IC. Carboidratos, gorduras e calorias apresentaram valores crescentes em todos os grupos, sem diferença estatística. O ganho de peso durante a gestação, a presença de hipertensão arterial e a idade materna foram associados a alterações de gordura e calorias no primeiro momento da análise do leite. Conclusões: Observou-se redução estatisticamente significante nos níveis de proteína durante as primeiras oito semanas após o nascimento. A IC pode ser um fator importante na composição do leite humano.