Practices developed by nurses in primary health care in southern Brazil.

OBJECTIVE: To understand the practices developed by nurses in primary care in southern Brazil. METHOD: Qualitative study, with data collection via online interviews, conducted between October 2020 and May 2021, and recorded. 174 nurses from 24 municipalities in southern Brazil participated. Data analysis used inductive thematic analysis. RESULTS: The activity that stood out among nurses was the nurse consultation, for all age groups and health conditions, especially when dealing with chronic disease, prenatal care, attention to women and children, mental health, home visits, and the management of the nursing team and the health unit. FINAL CONSIDERATIONS: This study demonstrated that an excess of responsibilities associated to care and management, added to a lack of balance in the activities common to the team make it difficult for nurses to develop clinical practices.

Teaching-Learning Programs to Prevent and Control Infections Related to Long-Term Central Venous Access Device in Cancer Patients: A Systematic Review.

OBJECTIVES: To evaluate the effectiveness of teaching-learning programs for cancer patients and/or their caregivers or family in preventing and controlling infections associated with long-term central venous access devices. DATA SOURCES: This systematic review used the CINAHL, Cochrane Library, EMBASE, LILACS, and MEDLINE via PubMed portal, Scopus, and Web of Science. Google Scholar was used for the gray literature search. The included studies were analyzed, and the obtained data were qualitatively synthesized. The risk of bias was assessed using Cochrane tools: RoB 2 and ROBINS-I. The certainty of the evidence was evaluated using the GRADE. The review protocol was registered in PROSPERO (CRD42021267530). CONCLUSION: The teaching-learning programs were implemented through theoretical-practical and theoretical dimensions in five and two studies, respectively. The risk of bias in the studies was low, moderate, severe, and high in one, three, two, and one of them, respectively. The certainty was very low. Teaching-learning programs on central venous access devices care for cancer patients and/or their caregivers or families could be effective in reducing infection rates. IMPLICATIONS FOR NURSING PRACTICE: This systematic review addressed the teaching-learning programs for preventing and controlling infections associated with long-term central venous access devices. We identified that the most programs were effective in reducing the infection rates. The results may influence the clinical practice of oncology nurses, and consequently, the educational strategies and methods provided not only to these patients but for caregivers and families.

Cardiac Uptake of the Adrenergic Imaging Agent meta-Iodobenzylguanidine (mIBG) Is Mediated by Organic Cation Transporter 3 (Oct3).

Heart failure (HF) is a chronic disease affecting 1%-2% of the global population.123I-labeled meta-iodobenzylguanidine (mIBG) is US Food and Drug Administration-approved for cardiac imaging and prognosis risk assessment in patients with HF. As a norepinephrine analog, mIBG is believed to be transported into adrenergic nerve terminals by the neuronal norepinephrine transporter (NET) and hence image sympathetic innervation of the myocardium. We previously showed that mIBG is an excellent substrate of organic cation transporter 3 (OCT3), an extraneuronal transporter expressed in cardiomyocytes. Here, we evaluated the in vivo impact of Oct3 on mIBG disposition and tissue distribution using Oct3 knockout mice. Oct3 +/+ and Oct3 -/- mice were administered with mIBG intravenously, and mIBG plasma pharmacokinetics and tissue exposures were determined. In Oct3 +/+ mice, mIBG exhibited extensive accumulation in multiple tissues (heart, salivary gland, liver, and adrenal gland). No difference was observed in overall plasma exposure between Oct3 +/+ and Oct3 -/- mice. Strikingly, cardiac mIBG was depleted in Oct3 -/- mice, resulting in 83% reduction in overall cardiac exposure (AUC0-24 h: 12.7 vs. 2.1 µg × h/g). mIBG tissue exposure (AUC0-24 h) was also reduced by 66%, 36%, and 31% in skeletal muscle, salivary gland, and lung, respectively, in Oct3 -/- mice. Our data demonstrated that Oct3 is the primary transporter responsible for cardiac mIBG uptake in vivo and suggested that cardiac mIBG imaging mainly measures OCT3 activity in cardiomyocytes but not NET-mediated uptake in adrenergic nerve endings. Our findings challenge the current paradigm in interpreting cardiac mIBG imaging results and suggest OCT3 as a potential genetic risk marker for HF prognosis. SIGNIFICANCE STATEMENT: 123I-labeled meta-iodobenzylguanidine is used for cardiac imaging and risk assessment in heart failure patients. Contrary to the current belief that meta-iodobenzylguanidine (mIBG) tracks cardiac sympathetic innervation due to its uptake by the neuronal norepinephrine transporter, the authors demonstrated that cardiac mIBG uptake is mediated by the extraneuronal transporter Oct3. Their findings warrant a re-evaluation of the scientific rationale behind cardiac mIBG scan and further suggest organic cation transporter 3 as a risk factor for disease progression in heart failure patients.

Práticas de enfermeiros na prevenção e rastreio do câncer de mama e de colo uterino / Practices performed by nurses in the prevention and screening of breast and cervical cancer / Prácticas de enfermería en la prevención y detección del cáncer de mama y cervicouterino

Objetivo: Identificar como ocorrem as práticas de prevenção e de rastreio do câncer de mama e de colo uterino realizadas por enfermeiros que atuam na Atenção Primária à Saúde do Rio Grande do Sul. Métodos: Trata-se de um estudo de abordagem qualitativa e de natureza analítica e compreensiva. Realizou-se entrevistas semiestruturadas. Os dados foram submetidos à análise de conteúdo do tipo temática proposta por Minayo. Os colaboradores foram 58 enfermeiros atuantes na Atenção Primária à Saúde. Resultados: Os resultados apontam que as práticas se desenvolvem em um contexto de crescente autonomia profissional e de protagonismo da Enfermagem. Aspectos como proximidade e vínculo com a comunidade, outros procedimentos e ações ofertadas nos atendimentos, incluindo a condução clínica/terapêutica, na vigência de sinais e sintomas de infecção, condizem com uma atenção mais ampla às necessidades de saúde e de cuidado às mulheres. Conclusão: O estudo evidencia a importância do respaldo de protocolos para a atuação segura das práticas dos enfermeiros da Atenção Básica, visando a prevenção e rastreio do câncer de mama e de colo uterino. Esses instrumentos devem ser de fácil acesso e constantemente atualizados a fim de garantir a padronização preconizada pelo Ministério da Saúde. (AU)

Objective: To identify how the breast and cervical cancer prevention and screening practices performed by nurses working in Primary Health Care in the state of Rio Grande do Sul occurs. Methods: This is a qualitative study with an analytical and comprehensive nature. The collaborators were 58 nurses working in Primary Health Care. Results: The results indicate that the practices are developed in a context of increasing professional autonomy and the role of Nursing. Aspects such as proximity and bonding with the community, other procedures and actions offered in the consultations, including clinical/therapeutic management in cases of signs and symptoms of infection, are consistent with a broader attention to women's health and care needs. Conclusion: The study highlights the importance of supporting protocols for the safe performance of Primary Care nurses' practices, aiming at the prevention and screening of breast and cervical cancer. These documents must be easily accessible and constantly updated in order to guarantee the standardization recommended by the Ministry of Health. (AU)

Objetivo: Identificar cómo las prácticas de prevención y detección del cáncer de mama y cervicouterino son realizadas por enfermeros que actúan en la Atención Primaria de Salud en Rio Grande do Sul. Métodos: Se trata de un estudio cualitativo de carácter analítico y comprensivo. Los colaboradores fueron 58 enfermeros que actuaban en la Atención Primaria de Salud. Resultados: Los resultados indican que las prácticas se desarrollan en un contexto de aumento de la autonomía profesional y del papel de la Enfermería. Aspectos como la proximidad y el vínculo con la comunidad, otros procedimientos y acciones que se ofrecen en las consultas, incluido el manejo clínico/terapéutico en casos de signos y síntomas de infección, son consistentes con una atención más amplia a las necesidades de salud y cuidado de las mujeres. Conclusión: El estudio destaca la importancia de protocolos para la actuación segura de las prácticas de los enfermeros de Atención Primaria, con el objetivo de la prevención y el tamizaje del cáncer de mama y de cuello uterino. Estos instrumentos deben ser de fácil acceso y constantemente actualizados para garantizar la estandarización recomendada por el Ministerio de Salud. (AU)

Use of a Double-Transfected System to Predict hOCT2/hMATE1-Mediated Renal Drug-Drug Interactions.

Accurate predictions of renal drug-drug interactions (DDIs) mediated by the human organic cation transporter 2 (hOCT2) and multidrug and toxin extrusion proteins (hMATEs) remain challenging. Current DDI evaluation using plasma maximal unbound inhibitor concentrations (Imax,u) and IC50 values determined in single transporter-transfected cells frequently leads to false or overprediction especially for hMATE1. Emerging evidence suggests intracellular unbound inhibitor concentration may be more relevant for hMATE1 inhibition in vivo. However, determination of intrarenal inhibitor concentrations is impractical. Here, we explored the use of hOCT2/hMATE1 double-transfected Madin-Darby canine kidney (MDCK) cells as a new in vitro tool for DDI risk assessment. Our results showed that potent in vitro hMATE1 inhibitors (hydroxychloroquine, brigatinib, and famotidine) failed to inhibit metformin B-to-A flux in the double-transfected system. On the other side, the classic hOCT2/hMATE1 inhibitors, pyrimethamine and cimetidine, dose-dependently inhibited metformin apparent B-to-A permeability (Papp). The different behaviors of these hMATE1 inhibitors in the double-transfected system can be explained by their different ability to gain intracellular access either via passive diffusion or transporter-mediated uptake. A new parameter (IC50,flux) was proposed reflecting the inhibitor's potency on overall hOCT2/hMATE1-mediated tubular secretion. The IC50,flux values significantly differ from the IC50 values determined in single transporter-transfected cells. Importantly, the IC50,flux accurately predicted in vivo DDIs (within 2-fold) when used in a static model. Our data demonstrated that the IC50,flux approach circumvents the need to measure intracellular inhibitor concentrations and more accurately predicted hOCT2/hMATE1-mediated renal DDIs. This system represents a new approach that could be used for improved DDI assessment during drug development. SIGNIFICANCE STATEMENT: This study demonstrated that flux studies in double-transfected MDCK cells and the IC50,flux represents a better approach to assess in vivo DDI potential for the renal organic cation secretion system. This study highlights the importance of inhibitor intracellular accessibility for accurate prediction of hMATE1-mediated renal DDIs. This approach has the potential to identify in vitro hMATE1 inhibitors that are unlikely to result in in vivo DDIs, thus reducing the burden of unnecessary and costly clinical DDI investigations.

Interaction and Transport of Benzalkonium Chlorides by the Organic Cation and Multidrug and Toxin Extrusion Transporters.

Humans are chronically exposed to benzalkonium chlorides (BACs) from environmental sources. The U.S. Food and Drug Administration (FDA) has recently called for additional BAC safety data, as these compounds are cytotoxic and have great potential for biochemical interactions. Biodistribution studies revealed that BACs extensively distribute to many tissues and accumulate at high levels, especially in the kidneys, but the underlying mechanisms are unclear. In this study, we characterized the interactions of BACs of varying alkyl chain length (C8 to C14) with the human organic cation transporters (hOCT1-3) and multidrug and toxin extrusion proteins (hMATE1/2K) with the goal to identify transporters that could be involved in BAC disposition. Using transporter-expressing cell lines, we showed that all BACs are inhibitors of hOCT1-3 and hMATE1/2K (IC50 ranging 0.83-25.8 µM). Further, the short-chain BACs (C8 and C10) were identified as substrates of these transporters. Interestingly, although BAC C8 displayed typical Michaelis-Menten kinetics, C10 demonstrated a more complex substrate-inhibition profile. Transwell studies with transfected Madin-Darby canine kidney cells revealed that intracellular accumulation of basally applied BAC C8 and C10 was substantially higher (8.2- and 3.7-fold, respectively) in hOCT2/hMATE1 double-transfected cells in comparison with vector-transfected cells, supporting a role of these transporters in mediating renal accumulation of these compounds in vivo. Together, our results suggest that BACs interact with hOCT1-3 and hMATE1/2K as both inhibitors and substrates and that these transporters may play important roles in tissue-specific accumulation and potential toxicity of short-chain BACs. Our findings have important implications for understanding human exposure and susceptibility to BACs due to environmental exposure. SIGNIFICANCE STATEMENT: Humans are systemically exposed to benzalkonium chlorides (BACs). These compounds broadly distribute through tissues, and their safety has been questioned by the FDA. Our results demonstrate that hOCT2 and hMATE1 contribute to the renal accumulation of BAC C8 and C10 and that hOCT1 and hOCT3 may be involved in the tissue distribution of these compounds. These findings can improve our understanding of BAC disposition and toxicology in humans, as their accumulation could lead to biochemical interactions and deleterious effects.

A minimal interventive protocol using antimicrobial photodynamic therapy on teeth with molar incisor hypomineralization: A case report.

Molar incisor hypomineralization (MIH) is a qualitative developmental defect of enamel that occurs during the mineralization phase. Patients with MIH have increased risk of caries, hypersensitivity, and restoration failures. The present case report describes the treatment of a 10-year-old patient exhibiting two teeth with atypical carious lesions. A minimal interventive protocol was instituted combining antimicrobial photodynamic therapy and the selective chemical-mechanical removal of the carious tissue using the product Papacárie Duo®. This protocol is promising for the decontamination and control of hypersensitivity in teeth with MIH.

Prevalence of adverse events in pronated intubated adult COVID-19 patients: A systematic review with meta-analysis.

AIM: To present the pooled estimated prevalence of adverse events in pronated intubated adult COVID-19 patients. DESIGN: A systematic review and meta-analysis. DATA SOURCES: This study used the Cochrane Library, CINAHL, Embase, LILACS, Livivo, PubMed, Scopus, and Web of Science databases as data sources. METHODS: The studies were meta-analysed using JAMOVI 1.6.15 software. A random-effects model was used to identify the global prevalence of adverse events, confidence intervals and the heterogeneity data. Risk of bias was assessed using the Joanna Briggs Institute tool, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: Of the 7904 studies identified, 169 were included for full reading, and 10 were included in the review. The most prevalent adverse events were pressure injuries (59%), haemodynamic instability (23%), death (17%) and device loss or traction (9%). CONCLUSION: The most prevalent adverse events in mechanically ventilated pronated patients with COVID-19 are pressure injuries, presence of haemodynamic instability, death and device loss or traction. IMPLICATIONS FOR THE PATIENT CARE: The evidence identified in this review can help improve the quality and safety of patient care by helping to design care protocols to avoid the development of adverse events that can cause permanent sequelae in these patients. IMPACT: This systematic review addressed the adverse events related to prone position in intubated adult COVID-19 patients. We identified that the most prevalent adverse events in these patients were pressure injuries, haemodynamic instability, device loss or traction and death. The results of this review may influence the clinical practice of nurses who work in intensive care units and, consequently, the nursing care provided not only to COVID-19 patients but for all intubated patients due to other reasons in intensive care units. REPORTING METHOD: This systematic review adhered to the PRISMA reporting guideline. PATIENT OR PUBLIC CONTRIBUTION: As this is a systematic review, we analysed data from primary studies conducted by many researchers. Thus, there was no patient or public contribution in this review.

Influence of Quaternary climate change on the potential distribution of Atlantic Forest dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae)

ABSTRACT Influence of Quaternary climate change on the potencial distribution of Atlantic Forest dung beetles (Coleoptera: Scarabaeidae: Scarabaeinae). The role of Cenozoic paleoclimatic changes in the distribution of dung beetles species from the Atlantic Forest (AF) remains poorly understood. We used ecological niche modeling under different scenarios (present, 6 ka, 21 ka, and 120 ka) to investigate how climatic oscillations during the Quaternary might have influenced the distribution of species endemic to this region. Models were built for five of the nine dung beetle species of the Dichotomius sericeus group: D. iannuzziae, D. irinus, D. laevicollis, D. schiffleri, and D. sericeus. The models of climatic suitability for D. irinus and D. laevicollis show a similar historical pattern in response to climate change but were divergent from D. iannuzziae, D. schiffleri, and D. sericeus. Dichotomius schiffleri is the species with the smallest area of ​​potencial occurrence. Over time, the species probably remained limited to lowland AF areas on the Brazilian coast and, it is currently found preferentially in Restinga ecosystems along the coast. Regarding the potential distribution models at the present, D. iannuzziae, D. schiffleri, and D. sericeus have potential distributions similar to their realized distribution. This study shows that the historical distribution of the D. sericeus species group has been influenced by paleoclimatic changes that occurred in the AF over the last 120 ka.

Practices developed by nurses in primary health care in southern Brazil / Practicas desarrolladas por los enfermeros en atención primaria de salud en el sur de Brasil / Práticas desenvolvidas pelo enfermeiro na atenção primária na região sul do Brasil

ABSTRACT Objective: To understand the practices developed by nurses in primary care in southern Brazil. Method: Qualitative study, with data collection via online interviews, conducted between October 2020 and May 2021, and recorded. 174 nurses from 24 municipalities in southern Brazil participated. Data analysis used inductive thematic analysis. Results: The activity that stood out among nurses was the nurse consultation, for all age groups and health conditions, especially when dealing with chronic disease, prenatal care, attention to women and children, mental health, home visits, and the management of the nursing team and the health unit. Final considerations: This study demonstrated that an excess of responsibilities associated to care and management, added to a lack of balance in the activities common to the team make it difficult for nurses to develop clinical practices.

RESUMEN Objetivo: Comprender las prácticas desarrolladas por las enfermeras en la atención primaria en el sur de Brasil. Método: Estudio cualitativo, con recolección de datos a través de entrevistas en línea, realizadas entre octubre de 2020 y mayo de 2021 y grabadas. Participaron 174 enfermeras de 24 municipios en el sur de Brasil. El análisis de los datos fue temático inductivo. Resultados: La consulta de enfermería se destaca como actividad de los enfermerosen todas las edades y condiciones de salud, especialmente situaciones crónicas, atención prenatal, atención a mujeres y niños, salud mental, visitas domiciliarias y gestión del equipo de enfermería y la unidad de salud. Consideraciones finales: El estudio ha demostrado que el exceso de responsabilidades asistenciales y de gestión y la falta de equilibrio entre las actividades comunes del equipo dificultan a las enfermeras el desarrollo de las prácticas clínicas.

RESUMO Objetivo: Compreender as práticas desenvolvidas pelo enfermeiro na atenção primária, na região Sul do Brasil. Método: Estudo qualitativo, cuja coleta de dados foi com entrevistas online gravadas, entre outubro de 2020 e maio de 2021. Participaram 174 enfermeiros, de 24 municípios da região sul do Brasil. Análise temática indutiva dos dados. Resultados: A consulta do enfermeiro é a atividade que se destaca, para todas as faixas etárias e condições de saúde, especialmente nas situações crônicas, pré-natal, atenção a mulher e a criança, saúde mental, visitas domiciliares, além do gerenciamento da equipe de enfermagem e da unidade de saúde. Considerações finais: Demonstrou-se que o excesso de responsabilidades assistenciais e gerenciais e a falta de equilíbrio entre as atividades comuns à equipe, dificultam o desenvolvimento de práticas clínicas do enfermeiro.

Enabling genome editing in tropical maize lines through an improved, morphogenic regulator-assisted transformation protocol.

The recalcitrance exhibited by many maize (Zea mays) genotypes to traditional genetic transformation protocols poses a significant challenge to the large-scale application of genome editing (GE) in this major crop species. Although a few maize genotypes are widely used for genetic transformation, they prove unsuitable for agronomic tests in field trials or commercial applications. This challenge is exacerbated by the predominance of transformable maize lines adapted to temperate geographies, despite a considerable proportion of maize production occurring in the tropics. Ectopic expression of morphogenic regulators (MRs) stands out as a promising approach to overcome low efficiency and genotype dependency, aiming to achieve 'universal' transformation and GE capabilities in maize. Here, we report the successful GE of agronomically relevant tropical maize lines using a MR-based, Agrobacterium-mediated transformation protocol previously optimized for the B104 temperate inbred line. To this end, we used a CRISPR/Cas9-based construct aiming at the knockout of the VIRESCENT YELLOW-LIKE (VYL) gene, which results in an easily recognizable phenotype. Mutations at VYL were verified in protoplasts prepared from B104 and three tropical lines, regardless of the presence of a single nucleotide polymorphism (SNP) at the seed region of the VYL target site in two of the tropical lines. Three out of five tropical lines were amenable to transformation, with efficiencies reaching up to 6.63%. Remarkably, 97% of the recovered events presented indels at the target site, which were inherited by the next generation. We observed off-target activity of the CRISPR/Cas9-based construct towards the VYL paralog VYL-MODIFIER, which could be partly due to the expression of the WUSCHEL (WUS) MR. Our results demonstrate efficient GE of relevant tropical maize lines, expanding the current availability of GE-amenable genotypes of this major crop.

Prevalence of risk factors for primary postpartum hemorrhage in a university hospital.

OBJECTIVES: to identify the risk factors associated with primary postpartum hemorrhage in a university hospital. METHODS: a cross-sectional study was conducted with 277 postpartum women who received care during childbirth or cesarean section between June and August 2020. Data were collected using a pre-structured questionnaire administered 24 hours after delivery. Poisson Regression was employed to analyze the factors associated with postpartum hemorrhage. RESULTS: postpartum hemorrhage was observed in 30% of the study sample. Shock Index and uterine distension were found to be statistically associated with postpartum hemorrhage. Postpartum women with a Shock Index ≥ 0.9 had a 61% higher prevalence of postpartum hemorrhage (PR=1.61, 95% CI: 1.07 - 2.43), while those with uterine distension had a 134% higher prevalence (PR=2.34, 95% CI: 1.63 - 3.36). CONCLUSIONS: recognizing these factors contributes to improvements in clinical practice, as they enable the prediction of their occurrence and call for appropriate management, thereby preventing unfavorable outcomes.

Vulnerabilities of Venezuelan refugee women: violence and intersectional social relations.

OBJECTIVE: To analyze the vulnerabilities of Venezuelan women considering their experiences of violence in refugee situations. METHOD: Qualitative study, developed with ten (10) Venezuelan refugee women in the southern region of Brazil, through individual in-depth interviews. The theoretical framework of analysis was Vulnerability, Human Rights, and Intersectionality. RESULTS: The greater the intensity of the intersection of social markers present, such as sex, racial, nationality, generation, cultural, bodily, territorial and other relations, the greater the range of vulnerable experiences in the social relations of these women, producing exclusions and violation of rights. CONCLUSION: The situations of vulnerabilities of refugee women are enhanced as more or less social markers intersect in their life experiences and established social relationships, causing impacts that allow the transition from 'vulnerable to violated subjects'. Thus, intersectional relationships were formed, either promoting oppression or producing resilience and resistance.

Efficacy of BREATHOX® Device Inhalation on Acute Symptoms Associated with COVID-19 (BREATH Study): A Randomized Pilot Clinical Trial.

(1) Background: A high concentration of sodium chloride on in vitro cell culture leads to reduced SARS-CoV-2 replication. Therefore, our aim was to evaluate the effects of inhaling hypertonic NaCl particles (BREATHOX®) on the duration of COVID-19-induced acute symptoms. (2) Methods: A prospective, open label, randomized, standard of care-controlled group (SOC) pilot trial compared inhaled oral and nasal administered BREATHOX® (2.0 mg NaCl, particles size between 1-10 µm), with five or ten inhalations per day for ten days. The primary endpoint was the time to resolve COVID-19-related symptoms. Safety outcomes included adverse clinical and laboratory events. (3) Results: A total of 101 individuals were screened and 98 were randomly assigned to BREATHOX® ten sessions per day (Group 1; 33 patients), BREATHOX® five sessions per day (Group 2; 32 patients), or SOC (33 patients), and followed up for 28 days. There was an association with cough frequency after 10 days BREATHOX® compared to SOC [Group 1: hazard ratio (HR) 2.01, 95% confidence interval (CI) 1.06-3.81; Group 2: HR 2.17, 95% CI 1.17-4.04]. No differences between the groups for the reported symptoms' resolution time were seen after 28 days. After combining both BREATHOX® groups, the period to cough resolution 10 days after randomization was significantly lower than in SOC (HR 2.10, 95% CI 1.20-3.67). An adverse event occurred in 30% of Group 1, 36% of Group 2, and 9% in SOC individuals. One patient from SOC had a serious adverse event. Nasal burning, sore or itchy nose, and dry mouth were considered related to BREATHOX® use and resolved after stopping inhalations. (4) Conclusion: BREATHOX® inhalation is safe and may be effective in reducing the duration of COVID-19-induced coughing.

Interaction of ALK Inhibitors with Polyspecific Organic Cation Transporters and the Impact of Substrate-Dependent Inhibition on the Prediction of Drug-Drug Interactions.

Small molecules targeting aberrant anaplastic lymphoma kinase (ALK) are active against ALK-positive non-small-cell lung cancers and neuroblastoma. Several targeted tyrosine kinase inhibitors (TKIs) have been shown to interact with polyspecific organic cation transporters (pOCTs), raising concerns about potential drug-drug interactions (DDIs). The purpose of this study was to assess the interaction of ALK inhibitors with pOCTs and the impact of substrate-dependent inhibition on the prediction of DDIs. Inhibition assays were conducted in transporter-overexpressing cells using meta-iodobenzylguanidine (mIBG), metformin, or 1-methyl-4-phenylpyridinium (MPP+) as the substrate. The half-maximal inhibitory concentrations (IC50) of brigatinib and crizotinib for the substrates tested were used to predict their potential for in vivo transporter mediated DDIs. Here, we show that the inhibition potencies of brigatinib and crizotinib on pOCTs are isoform- and substrate-dependent. Human OCT3 (hOCT3) and multidrug and toxin extrusion protein 1 (hMATE1) were highly sensitive to inhibition by brigatinib and crizotinib for all three tested substrates. Apart from hMATE1, substrate-dependent inhibition was observed for all other transporters with varying degrees of dependency; hOCT1 inhibition showed the greatest substrate dependency, with differences in IC50 values of up to 22-fold across the tested substrates, followed by hOCT2 and hMATE2-K, with differences in IC50 values of up to 16- and 12-fold, respectively. Conversely, hOCT3 inhibition only showed a moderate substrate dependency (IC50 variance < 4.8). Among the substrates used, metformin was consistently shown to be the most sensitive substrate, followed by mIBG and MPP+. Pre-incubation of ALK inhibitors had little impact on their potencies toward hOCT2 and hMATE1. Our results underscore the complexity of the interactions between substrates and the inhibitors of pOCTs and have important implications for the clinical use of ALK inhibitors and their DDI predictions.

Impactos da pandemia de COVID-19 nas especialidades cirúrgicas em um hospital universitário da Bahia: um estudo transversal retrospectivo / Impacts of the COVID-19 pandemic on surgical specialties at a university hospital in Bahia: a retrospective cross-sectional study

Introdução: Desde o início da pandemia de COVID-19, as especialidades médicas adaptaram sua rotina, postergando procedimentos não essenciais, o que resultou em redução no número de atendimentos cirúrgicos, impactando diretamente nos hospitais de ensino. O objetivo desse trabalho é avaliar o impacto da pandemia de COVID-19 nas atividades das especialidades cirúrgicas do Hospital Universitário Professor Edgard Santos (C-HUPES), localizado em Salvador-BA. Método: Estudo observacional, transversal, retrospectivo, que compara o ano de 2020 ao ano de 2019, em que são analisados os impactos da pandemia nas atividades cirúrgicas (especialmente na cirurgia plástica) do hospital, através do número total de procedimentos, internações e de consultas ambulatoriais das especialidades cirúrgicas. Resultados: Redução de 45,45% no número total de procedimentos cirúrgicos foi observada, havendo um total de 220 cirurgias em 2019 e 120 cirurgias em 2020. Redução de 37,29% no número total de internamentos, total de 236 em 2019 e 148 em 2020. Observou-se diminuição de 40,90% nas consultas ambulatoriais, realizadas 2941 consultas em 2019 e 1738 consultas em 2020. Percebe-se que os piores períodos de redução em 2020 foram de março a junho, além de nova queda em novembro e dezembro. Conclusão: A pandemia impactou as atividades das especialidades cirúrgicas do C-HUPES, devido à redução total da quantidade de cirurgias, consultas e internamentos em 2020, prejudicando a assistência aos pacientes da cirurgia plástica em números absolutos. Infere-se que a pandemia de COVID-19 prejudicou a formação dos residentes de cirurgia plástica.

Introduction: Since the beginning of the COVID-19 pandemic, medical specialties have adapted their routine, postponing non-essential procedures, which resulted in a reduction in the number of surgical visits, directly impacting teaching hospitals. This work aims to evaluate the impact of the COVID-19 pandemic on the activities of the surgical specialties at the University Hospital Professor Edgard Santos (C-HUPES), located in Salvador-BA. Method: Observational, cross-sectional, retrospective study, which compares the year 2020 to the year 2019, in which the impacts of the pandemic on the surgical activities (especially plastic surgery) of the hospital are analyzed through the total number of procedures, hospitalizations, and outpatient consultations of surgical specialties. Results: A reduction of 45,45% of the total number of surgical procedures was observed, with 220 surgeries in 2019 and 120 surgeries in 2020. Reduction of 37.29% in hospitalizations, totaling 236 in 2019 and 148 in 2020. There was a decrease of 40.90% in outpatient consultations, with 2941 consultations performed in 2019 and 1738 consultations in 2020. It is noticed that the worst periods of reduction in 2020 were from March to June, in addition to a new drop in November and December. Conclusion: The pandemic impacted the activities of the surgical specialties at C-HUPES due to the total reduction in the number of surgeries, consultations, and hospitalizations in 2020, impairing the care of plastic surgery patients in absolute numbers. It is inferred that the COVID-19 pandemic hampered the training of plastic surgery residents.

The Plasma Membrane Monoamine Transporter is Highly Expressed in Neuroblastoma and Functions as an mIBG Transporter.

Neuroblastoma (NB) is a pediatric cancer with low survival rates in high-risk patients. 131I-mIBG has emerged as a promising therapy for high-risk NB and kills tumor cells by radiation. Consequently, 131I-mIBG tumor uptake and retention are major determinants for its therapeutic efficacy. mIBG enters NB cells through the norepinephrine transporter (NET), and accumulates in mitochondria through unknown mechanisms. Here we evaluated the expression of monoamine and organic cation transporters in high-risk NB tumors and explored their relationship with MYCN amplification and patient survival. We found that NB mainly expresses NET, the plasma membrane monoamine transporter (PMAT), and the vesicular membrane monoamine transporter 1/2 (VMAT1/2), and that the expression of these transporters is significantly reduced in MYCN-amplified tumor samples. PMAT expression is the highest and correlates with overall survival in high-risk NB patients without MYCN amplification. Immunostaining showed that PMAT resides intracellularly in NB cells and co-localizes with mitochondria. Using cells expressing PMAT, mIBG was identified as a PMAT substrate. In mitochondria isolated from NB cell lines, mIBG uptake was reduced by ∼50% by a PMAT inhibitor. Together, our data suggest that PMAT is a previously unrecognized transporter highly expressed in NB and could impact intracellular transport and therapeutic response to 131I-mIBG. SIGNIFICANCE STATEMENT: This study identified that plasma membrane monoamine transporter (PMAT) is a novel transporter highly expressed in neuroblastoma and its expression level is associated with overall survival rate in high-risk patients without MYCN amplification. PMAT is expressed intracellularly in neuroblastoma cells, transports meta-iodobenzylguanidine (mIBG) and thus could impact tumor retention and response to 131I-mIBG therapy. These findings have important clinical implications as PMAT could represent a novel molecular marker to help inform disease prognosis and predict response to 131I-mIBG therapy.

Textiles impregnated with antimicrobial substances in healthcare services: systematic review.

Background: Antimicrobial textiles have proved to be a promising biosafety strategy. Thus, the current study was focused on identifying which antimicrobial substances impregnated in textiles used in healthcare services confer efficacy in reducing the microbial load present in these textiles and/or the Healthcare-Associated Infection (HAI) rates, when compared to conventional textiles. Methods: A systematic review of intervention studies using MEDLINE via the PubMed portal, EMBASE, CINAHL, Web of Science, Scopus, Google Scholar and medRxiv. The studies identified were selected according to eligibility criteria and submitted to data extraction and methodological quality evaluation through Joanna Briggs Institute specific tools. The outcomes were synthesized qualitatively. Results: 23 studies were selected to comprise the final sample, in which antimicrobial textiles were used by hospitalized patients, by health professionals during work shifts and in inanimate healthcare environments. Conclusions: Copper, silver, zinc oxide, titanium and silver-doped titanium impregnated in textiles used by patients confer efficacy in reducing the microbial load of these textiles and/or the HAI rates. Quaternary ammonium, chlorhexidine, silver and copper together, quaternary ammonium, alcohols and isothiazolone derivatives together, chitosan and dimethylol dimethyl hydantoin together, all impregnated in textiles used by health professionals confer efficacy in reducing the microbial load of these textiles. Quaternary ammonium impregnated in textiles used in inanimate healthcare environments confers efficacy in reducing the microbial load of these textiles.

O vínculo na atenção primária à saúde: práticas dos enfermeiros da região Sul do Brasil / The bond in primary health care: practices of nurses in the southern region of Brazil / El vínculo en la atención primaria de salud: prátcticas de enfermeros en la región Sur de Brasil

Analisar as percepções dos enfermeiros sobre o vínculo nas práticas de enfermagem na Atenção Primária à Saúde. Trata-se de uma pesquisa qualitativa e de natureza analítica e compreensiva,com 174 enfermeiros que atuavam na atenção primária, nos três estados da Região Sul (Paraná, Rio Grande do Sul e Santa Catarina).Para a coleta de dados, foram utilizadas entrevistas semiestruturadas, realizadas no segundo semestre de 2020. Análise dos dados de Conteúdo do tipo temática. Identificou-se como núcleos relevantes: Vínculo como dispositivo relacional/atitudinal nas práticas de cuidado dos enfermeiros e A inter-relação entre o vínculo e demais atributos essenciais da atenção primária.A construção do vínculo entre os usuários e enfermeiro constitui-se em um importante dispositivo relacional para o desenvolvimento de práticas de cuidado acolhedoras e resolutivas.Aprimorar a utilização deste dispositivo relacional/atitudinal permitirá ampliar o espectro de sucesso nas ações de prevenção, promoção, diagnóstico, tratamento, reabilitação, redução de danos e manutenção da saúde, permitindo inclusive anteceder as demandas e viabilizar a corresponsabilização. (AU)

To analyze nurses' perceptions about the bond in nursing practices in Primary Health Care. This is a qualitative, analytical and comprehensive research, with 174 nurses who worked in primary care, in the three states of the South Region (Paraná, Rio Grande do Sul and Santa Catarina). For data collection, semi-structured interviews were used, carried out in the second half of 2020. Analysis of thematic content data. The following were identified as relevant cores: Bonding as a relational/attitudinal device in nurses' care practices and the interrelation between the bond and other essential attributes of primary care. The construction of the bond between users and nurses constitutes an important relational device for the development of welcoming and resolute care practices. Improving the use of this relational/attitudinal device will allow to expand the spectrum of success in prevention, promotion, diagnosis, treatment, rehabilitation, harm reduction and health maintenance, even allowing to precede demands and enable co-responsibility. (AU)

Analizar las percepciones de los enfermeros sobre el vínculo en las prácticas de enfermería en la Atención Primaria de Salud. Se trata de una investigación cualitativa, analítica e integral, con 174 enfermeros que actuaban en la atención primaria, en los tres estados de la Región Sur (Paraná, Rio Grande do Sul y Santa Catarina). Para la recolección de datos se utilizaron entrevistas semiestructuradas, realizadas en el segundo semestre de 2020. Análisis de datos de contenido temático. Se identificaron como núcleos relevantes: El vínculo como dispositivo relacional/actitudinal en las prácticas de cuidado del enfermero y la interrelación entre el vínculo y otros atributos esenciales de la atención primaria. La construcción del vínculo entre usuarios y enfermeros constituye un dispositivo relacional importante para el desarrollo de prácticas de cuidado acogedoras y resolutivas. Mejorar el uso de este dispositivo relacional/actitudinal permitirá ampliar el espectro de éxito en la prevención, promoción, diagnóstico, tratamiento, rehabilitación, reducción de daños y mantenimiento de la salud, permitiendo incluso anteponer demandas y posibilitar la corresponsabilidad. (AU)

Perfil e práticas dos enfermeiros da atenção primária à saúde: relatos da região Sul, Brasil / Profile and practices of primary health care nurses: reports from the Southern region, Brazil / Perfil y prácticas de las enfermeras de atención primaria de salud: informes de la región Sur, Brasil

Esse relato de experiência apresenta a caracterização do perfil dos enfermeiros e um breve recorte das práticas dos enfermeiros que atuam na Atenção Primária Saúde (APS), a partir da condução da pesquisa na região Sul do Brasil. Para este relato foi utilizado a base de dados do projeto multicêntrico intitulado "Práticas de Enfermagem no Contexto da Atenção Primária à Saúde: Estudo Nacional de Métodos Mistos". A equipe da pesquisa na região sul foi conduzida por pesquisadores e estudantes de graduação e pós-graduação vinculados às instituições públicas de ensino e pesquisa e os Conselhos Regionais de Enfermagem. Na etapa qualitativa, na região Sul, participaram do estudo 174 enfermeiros. Destes, 74 (42,5%) eram do estado do Paraná, 59 (33,9%) do Rio Grande do Sul e 41 (23,5%) de Santa Catarina. Na etapa quantitativa, participaram desta etapa 1.323 enfermeiros que atuam na APS há mais de 3 anos nos estados da região sul. Foram identificadas aspectos socioeconômicos, formação profissional e condições de emprego, trabalho e renda. As vivências entre estudantes e pesquisadores na condução da pesquisa em período de pandemia foi desafiadora pela inovação nas formas de coletar de dados e pela relação de fragilidade emocional e física de todos os envolvidos. Contudo, permitiu compreender o perfil das práticas dos enfermeiros e alertou para o caráter essencial do processo de trabalho preconizado neste ponto de atenção, em especial das ações e da responsabilidade sanitária que o profissional enfermeiro assume com protagonismo na APS. (AU)

This experience report presents the characterization of the profile of nurses and a brief outline of the practices of nurses who work in Primary Health Care (PHC), based on conducting research in the southern region of Brazil. For this report, the database of the multicenter project entitled "Nursing Practices in the Context of Primary Health Care: National Study of Mixed Methods" was used. The research team in the southern region was conducted by researchers and undergraduate and graduate students linked to public teaching and research institutions and the Regional Nursing Councils. In the qualitative stage, in the South region, 174 nurses participated in the study. Of these, 74 (42.5%) were from the state of Paraná, 59 (33.9%) from Rio Grande do Sul and 41 (23.5%) from Santa Catarina. In the quantitative stage, 1,323 nurses who have been working in PHC for more than 3 years in the states of the southern region participated in this stage. Socioeconomic aspects, professional training and conditions of employment, work and income were identified. The experiences between students and researchers in conducting research during a pandemic period was challenging due to the innovation in the ways of collecting data and due to the emotional and physical fragility of all those involved. However, it allowed understanding the profile of nurses' practices and alerted to the essential character of the work process recommended in this point of care, especially the actions and health responsibility that the professional nurse assumes with protagonism in PHC. (AU)

Este relato de experiencia presenta la caracterización del perfil de los enfermeros y un breve esbozo de las prácticas de los enfermeros que actúan en la Atención Primaria de Salud (APS), a partir de la realización de investigaciones en la región sur de Brasil. Para este informe se utilizó la base de datos del proyecto multicéntrico "Prácticas de Enfermería en el Contexto de la Atención Primaria de Salud: Estudio Nacional de Métodos Mixtos". El equipo de investigación en la región sur fue conducido por investigadores y estudiantes de grado y posgrado vinculados a las instituciones públicas de enseñanza e investigación ya los Consejos Regionales de Enfermería. En la etapa cualitativa, en la región Sur, participaron del estudio 174 enfermeros. De ellos, 74 (42,5%) eran del estado de Paraná, 59 (33,9%) de Rio Grande do Sul y 41 (23,5%) de Santa Catarina. En la etapa cuantitativa participaron de esta etapa 1.323 enfermeros que actúan en la APS hace más de 3 años en los estados de la región sur. Se identificaron aspectos socioeconómicos, formación profesional y condiciones de empleo, trabajo e ingresos. Las experiencias entre estudiantes e investigadores en la realización de investigaciones durante un período de pandemia fueron desafiantes debido a la innovación en las formas de recolección de datos y por la fragilidad emocional y física de todos los involucrados. Sin embargo, permitió comprender el perfil de las prácticas de los enfermeros y alertó sobre el carácter esencial del proceso de trabajo recomendado en este punto del cuidado, especialmente las acciones y la responsabilidad en salud que el profesional enfermero asume con protagonismo en la APS. (AU)