Nicorandil antiallodynic activity in a model of neuropathic pain is associated with the activation of ATP-dependent potassium channels and opioidergic pathways, and reduced production of cytokines and neutrophils recruitment in paw, sciatic nerve, and dorsal root ganglia.

BACKGROUND: Recently, we demonstrated that nicorandil inhibits mechanical allodynia induced by paclitaxel. In the present study, we evaluated the effect induced by nicorandil in a model of neuropathic pain induced by chronic constriction injury (CCI) in mice. We also investigated putative mechanisms underlying such an effect. METHODS: CCI was induced by three ligatures of the left sciatic nerve. Mechanical allodynia was evaluated by measuring the paw withdrawal threshold with an electronic von Frey apparatus. Concentrations of cytokines and myeloperoxidase activity were determined in the paw tissue, sciatic nerve, and dorsal root ganglia (DRG). RESULTS: Oral administration of two doses of nicorandil (150 mg/kg po), but not equimolar doses of nicotinamide or nicotinic acid, attenuated mechanical allodynia induced by CCI. Nicorandil activity was reduced by previous administration of glibenclamide (40 mg/kg) or naltrexone (5 mg/kg or 10 mg/kg). Two doses of nicorandil (150 mg/kg, po) reduced tumor necrosis factor-α, interleukin-1ß and interleukin-6, but not CXCL-1, concentrations in the paw tissue of CCI mice. Two doses of nicorandil (150 mg/kg, po) reduced concentrations of all these mediators in the sciatic nerve and DRG. Two doses of nicorandil (150 mg/kg, po) also reduced the myeloperoxidase activity in the paw tissue, sciatic nerve, and DRG. CONCLUSIONS: Nicorandil exhibits antiallodynic activity in a model of neuropathic pain induced by CCI. Inhibition of cytokines production and reduction of neutrophils recruitment in paw tissue, sciatic nerve, and DRG as well as activation of ATP-dependent potassium channels and opioidergic pathways, underlie nicorandil antiallodynic activity.

Technology Readiness Level Roadmap for Developing Innovative Herbal Medicinal Products.

Despite the vast global botanical diversity, the pharmaceutical development of herbal medicinal products (HMPs) remains underexploited. Of over 370,000 described plant species, only a few hundred are utilized in HMPs. Most of these have originated from traditional use, and only a minority come from megadiverse countries. Exploiting the pharmacological synergies of the hundreds of compounds found in poorly studied plant species may unlock new therapeutic possibilities, enhance megadiverse countries' scientific and socio-economic development, and help conserve biodiversity. However, extensive constraints in the development process of HMPs pose significant barriers to transforming this unsatisfactory socio-economic landscape. This paper proposes a roadmap to overcome these challenges, based on the technology readiness levels (TRLs) introduced by NASA to assess the maturity of technologies. It aims to assist research entities, manufacturers, and funding agencies from megadiverse countries in the discovery, development, and global market authorization of innovative HMPs that comply with regulatory standards from ANVISA, EMA, and FDA, as well as WHO and ICH guidelines.

Nile Tilapia Skin Xenograft Versus Silver-Based Dressings in the Management of Partial-Thickness Burn Wounds: A Systematic Review and Meta-Analysis.

Background: Burns are a serious public health problem worldwide, causing high morbidity and mortality. This study aimed to compare two forms of treatment for partial skin burns and to determine whether one is superior to the other in terms of efficacy and benefits through a meta-analysis of randomized controlled trials. This article highlights the efficacy of tilapia skin in the treatment of burns. We performed a meta-analysis of 199 patients and highlighted the promising results that indicate the clinical relevance of this resource when we compared the cost of dressings with the daily need for dressing changes, healing potential, and reduction in pain level according to the VAS scale and reduced frequency of dressing changes. Methods: A search of PubMed, Cochrane Central, and LILACS was performed to identify randomized controlled trials comparing tilapia skin and silver-based dressings for treating burns. Studies involving overlapping populations and animals were excluded. The outcomes of interest were complete re-epithelialization, decreased pain level, and dressing change. Results: Summarize the article's main findings. Conclusions: Four randomized trials were included with a total of 199 patients with partial-thickness burns between the ages of 2 and 70 years. A total of 99 (49.74%) patients were treated with tilapia skin, and conventional treatment was used on 100 (50.25%) of the patients. Differences were found between the tilapia and silver-based treatments concerning re-epithelialization (MD -0.48; CI 95% -0.71 to -0.24; p < 0.01; I2 = 0%), decreased pain level (MD -0.79; CI 95% -1.10 to -0.47; p < 0.01; I2 = 0%), and dressing change outcome (MD -3.54; 95% CI -5.81 to -1.26; p = 0.02; I2 = 97%).

The Use of Honey for Cicatrization and Pain Control of Obstetric Wounds: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: Several studies point to antibacterial properties and beneficial effects of honey on scar tissue formation, which is a low-cost and easy-to-use option. This study aimed to compare honey versus a placebo for cicatrization and pain control of obstetric wounds, and determine if one is superior to the other, in terms of efficacy, through a meta-analysis. METHODS: We searched PubMed, Scopus, Cochrane Central Register of Controlled Trials, and Web of Science. Two independent investigators identified randomized controlled trials (RCTs) comparing honey and a placebo for obstetric wounds. The primary outcomes were wound healing and pain control. RESULTS: Five randomized controlled trials and 353 patients were included, of whom, 177 (50.1%) were treated with honey. Differences were not found in the final wound healing between the honey and placebo groups (MD -0.34; 95% CI -1.13, 0.44; p = 0.39); however, there was a decrease in pain levels in the middle of the treatment (SMD -0.54; 95% CI 0.83 to 0.25, p = 0.03), reduction in the use of pain medication (ORR 0.26; 95% CI 0.08, 0.86; p = 0.03), increase in personal satisfaction in women who underwent the intervention (ORR 0.81; 95% CI 0.65, 0.98), and reduction in complications. CONCLUSION: According to the study results, honey treatments showed greater efficiency and provided benefits to the patients by accelerating wound healing and decreasing reported pain.

Metformin inhibits paclitaxel-induced mechanical allodynia by activating opioidergic pathways and reducing cytokines production in the dorsal root ganglia and thalamus.

It has been shown that AMP-activated protein kinase (AMPK) is involved in the nociceptive processing. This observation has prompted us to investigate the effects of the AMPK activator metformin on the paclitaxel-induced mechanical allodynia, a well-established model of neuropathic pain. Mechanical allodynia was induced by four intraperitoneal (i.p) injections of paclitaxel (2 mg/kg.day) in mice. Metformin was administered per os (p.o.). Naltrexoneandglibenclamide were used to investigate mechanisms mediating metformin activity. Concentrations of cytokines in the dorsal root ganglia (DRG) and thalamus were determined. After a single p.o. administration, the two highest doses of metformin (500 and 1000 mg/kg) attenuated the mechanical allodynia. This response was attenuated by all doses of metformin (250, 500 and 1000 mg/kg) when two administrations, 2 h apart, were carried out. Naltrexone (5 and 10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, p.o.), attenuated metformin activity. Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and CXCL-1 in the DRG were increased after administration of paclitaxel. Metformin (1000 mg/kg) reduced concentrations of TNF-α, IL-1ß and CXCL-1 in the DRG. Concentration of IL-6, but not TNF-α, in the thalamus was increased after administration of paclitaxel. Metformin (1000 mg/kg) reduced concentration of IL-6 in the thalamus. In summary, metformin exhibits activity in the model of neuropathic pain induced by paclitaxel. This activity may be mediated by activation of opioidergic pathways and reduced production of TNF-α, IL-1ß and CXCL-1 in the DRG and IL-6 in the thalamus.

Awareness of stroke among patients with chronic kidney disease on hemodialysis: a cross-sectional study

ABSTRACT BACKGROUND: Stroke is a major cause of mortality worldwide. Renal dysfunction is an important risk factor for stroke. Brazilian studies on stroke knowledge are generally population based. Studies stratifying stroke knowledge according to comorbidities are rare. Scientific data are essential to guide the awareness of stroke. OBJECTIVE: To assess stroke knowledge in patients with chronic kidney disease (CKD) on hemodialysis. DESIGN AND SETTING: Cross-sectional analytical study of patients with CKD on hemodialysis in north-eastern Brazil. METHODS: A self-administered questionnaire survey on stroke awareness was administered to patients with CKD on hemodialysis between April and November 2022. The chi-square test and other descriptive statistics were used. Univariate and multivariate analyses were performed using logistic regression. RESULTS: A total of 197 patients were included in the analysis. The Brazilian acronym for stroke was used by 53.5% of the participants. Less than 10.0% of the sample showed optimal decision-making ability regarding stroke. Of the participants, 29.9% knew at least one risk factor and one symptom; however, this was considered as having below the minimum capacity because they did not know the emergency service call number. In the analysis adjusted for income and education, females (odds ratio [OR], 0.40%; 95% confidence interval [CI], 0.20-0.82), older patients (OR, 0.24%; 95% CI, 0.09-0.63) and having at most one comorbidity (OR, 0.48%; 95% CI, 0.23-0.98) were factors for lower levels of knowledge or ideal decision-making capacity against stroke. CONCLUSIONS: Patients on hemodialysis, especially women and older people, have little knowledge about stroke.

Efficacy and Safety of Setmelanotide, a Melanocortin-4 Receptor Agonist, for Obese Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: A malfunction in the melanocortin-4 receptor (MC4R) is associated with obesity in rare genetic syndromes; setmelanotide is a new drug that activates this receptor and is being used to treat severe obesity. This meta-analysis evaluated the efficacy and safety of setmelanotide for weight loss in severe obesity linked to human MC4R deficiency. METHODS: We searched PubMed, Embase, and Cochrane for randomized and nonrandomized clinical trials using setmelanotide. We considered a p-value ≤ 0.05 statistically significant. RESULTS: We included 376 patients, of whom 328 (87.2%) received setmelanotide for a mean follow-up of 52 weeks. The mean age was 32.8 (14.67) years. Weight loss was significant (MD -3.52; 95% CI -3.98, -3.05; p = 0.01; I2 = 92%), with an average proportion of -6.91% weight loss during treatment. Changes in BMI showed an MD of -10.55 kg/m2 in patients > 18 years and -0.61 kg/m2 in patients < 18 years (BMI score). However, the drug was associated with a higher risk of skin hyperpigmentation (OR 0.69; 95% CI 0.55, 0.80; p = 0.08). CONCLUSIONS: Our results support the use of setmelanotide in treating severe obesity.

Awareness of stroke among patients with chronic kidney disease on hemodialysis: a cross-sectional study.

BACKGROUND: Stroke is a major cause of mortality worldwide. Renal dysfunction is an important risk factor for stroke. Brazilian studies on stroke knowledge are generally population based. Studies stratifying stroke knowledge according to comorbidities are rare. Scientific data are essential to guide the awareness of stroke. OBJECTIVE: To assess stroke knowledge in patients with chronic kidney disease (CKD) on hemodialysis. DESIGN AND SETTING: Cross-sectional analytical study of patients with CKD on hemodialysis in north-eastern Brazil. METHODS: A self-administered questionnaire survey on stroke awareness was administered to patients with CKD on hemodialysis between April and November 2022. The chi-square test and other descriptive statistics were used. Univariate and multivariate analyses were performed using logistic regression. RESULTS: A total of 197 patients were included in the analysis. The Brazilian acronym for stroke was used by 53.5% of the participants. Less than 10.0% of the sample showed optimal decision-making ability regarding stroke. Of the participants, 29.9% knew at least one risk factor and one symptom; however, this was considered as having below the minimum capacity because they did not know the emergency service call number. In the analysis adjusted for income and education, females (odds ratio [OR], 0.40%; 95% confidence interval [CI], 0.20-0.82), older patients (OR, 0.24%; 95% CI, 0.09-0.63) and having at most one comorbidity (OR, 0.48%; 95% CI, 0.23-0.98) were factors for lower levels of knowledge or ideal decision-making capacity against stroke. CONCLUSIONS: Patients on hemodialysis, especially women and older people, have little knowledge about stroke.

A clindamycin acetylated derivative with reduced antibacterial activity inhibits articular hyperalgesia and edema by attenuating neutrophil recruitment, NF-κB activation and tumor necrosis factor-α production.

We recently demonstrated that clindamycin exhibits activities in acute and chronic models of pain and inflammation. In the present study, we investigated the effects of clindamycin and a clindamycin acetylated derivative (CAD) in models of acute joint inflammation and in a microbiological assay. Joint inflammation was induced in mice by intraarticular (i.a.) injection of zymosan or lipopolysaccharide (LPS). Clindamycin or CAD were administered via the intraperitoneal route 1 h before zymosan or LPS. Paw withdrawal threshold, joint diameter, histological changes, neutrophil recruitment, tumor necrosis factor-α (TNF-α) production and phosphorylation of the IκBα and NF-κB/p65 were evaluated. In vitro assays were used to measure the antibacterial activity of clindamycin and CAD and also their effects on zymosan-induced TNF-α production by RAW264.7 macrophages. Clindamycin exhibited activity against Staphylococcus aureus and Salmonella Typhimurium ATCC® strains at much lower concentrations than CAD. Intraarticular injection of zymosan or LPS induced articular hyperalgesia, edema and neutrophil infiltration in the joints. Zymosan also induced histological changes, NF-κB activation and TNF-α production. Responses induced by zymosan and LPS were inhibited by clindamycin (200 and 400 mg/kg) or CAD (436 mg/kg). Both clindamycin and CAD inhibited in vitro TNF-α production by macrophages. In summary, we provided additional insights of the clindamycin immunomodulatory effects, whose mechanism was associated with NF-κB inhibition and reduced TNF-α production. Such effects were extended to a clindamycin derivative with reduced antibacterial activity, indicating that clindamycin derivatives should be investigated as candidates to drugs that could be useful in the management of inflammatory and painful conditions.

Synthesis of 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione, a novel hydrogen sulfide-releasing phthalimide hybrid, and evaluation of its activity in models of inflammatory pain.

Hydrogen sulfide (H2S) is a gaseous mediator that modulates several physiological and pathological processes. Phthalimide analogues, substances that have the phthalimide ring in the structure, belong to the group of thalidomide analogues. Both H2S donors and phthalimide analogues exhibit activities in models of inflammation and pain. As molecular hybridization is an important strategy aiming to develop drugs with a better pharmacological profile, in the present study we synthesized a novel H2S-releasing phthalimide hybrid, 2-(2-(4-thioxo-3H-1,2-dithiole-5-yl) phenoxy)ethyl)isoindole-1,3-thione (PTD-H2S), and evaluated its activity in models of inflammatory pain in mice. Per os (p.o.) administration of PTD-H2S (125 or 250 mg/kg) reduced mechanical allodynia induced by carrageenan and lipopolysaccharide. Intraperitoneal (i.p.) administration of PTD-H2S (25 mg/kg), but not equimolar doses of its precursors 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (14.2 mg/kg) and 2-phthalimidethanol (12 mg/kg), reduced mechanical allodynia induced by lipopolysaccharide. The antiallodynic effect induced by PTD-H2S (25 mg/kg, i.p.) was more sustained than that induced by the H2S donor NaHS (8 mg/kg, i.p.). Previous administration of hydroxocobalamin (300 mg/kg, i.p.) or glibenclamide (40 mg/kg, p.o.) attenuated PTD-H2S antiallodynic activity. In conclusion, we synthesized a novel H2S-releasing phthalimide hybrid and demonstrated its activity in models of inflammatory pain. PTD-H2S activity may be due to H2S release and activation of ATP-sensitive potassium channels. The demonstration of PTD-H2S activity in models of pain stimulates further studies aiming to evaluate H2S-releasing phthalimide hybrids as candidates for analgesic drugs.

New mescaline-related N-acylhydrazone and its unsubstituted benzoyl derivative: Promising metallophores for copper-associated deleterious effects relief in Alzheimer's disease.

Alzheimer's disease (AD) is related to the presence of extracellular aggregated amyloid-ß peptide (Aß), which binds copper(II) with high affinity in its N-terminal region. In this sense, two new 1-methylimidazole-containing N-acylhydrazonic metallophores, namely, X1TMP and X1Benz, were synthesized as hydrochlorides and characterized. The compound X1TMP contains the 3,4,5-trimethoxybenzoyl moiety present in the structure of mescaline, a natural hallucinogenic protoalkaloid that occurs in some species of cacti. Single crystals of X1Benz, the unsubstituted derivative of X1TMP, were obtained. The experimental partition coefficients of both compounds were determined, as well as their apparent affinity for Cu2+ in aqueous solution. Ascorbate consumption assays showed that these N-acylhydrazones are able to lessen the production of ROS by the Cu(Aß)-system, and a short-time scale aggregation study, measured through turbidity and confirmed by TEM images, revealed their capacity in preventing Aß fibrillation at equimolar conditions in the presence and absence of copper. 1H15N HSQC NMR experiments demonstrated a direct interaction between Aß and X1Benz, the most soluble of the compounds. The Cu2+ sequestering potential of this hydrazone towards Aß was explored by 1H NMR. Although increasing amounts of X1Benz were unexpectedly not efficient at removing the metal-induced perturbations in Aß backbone amides, the broadening effects observed on the compound's signals indicate the formation of a ternary Aß­copper-X1Benz species, which can be responsible for the observed ROS-lessening and aggregation-preventing activities. Overall, the N-acylhydrazones X1TMP and X1Benz have shown promising prospects as agents for the treatment of AD.

Desafios do enfermeiro no tratamento aos pacientes com tuberculose pulmonar nos espaços de assistência à saúde / Nurse challenges in treating pulmonary tuberculosis patients in healthcare spaces / Desafíos de enfermería en el tratamiento de pacientes con tuberculosis de pulmón en espacios de asistencia sanitaria

Introdução: A tuberculose é causada pelo bacilo de Koch que atinge principalmente os pulmões. Contudo, uma pequena parcela, cerca de 15%, se desenvolve em outras estruturas corporais, como na laringe, gânglios, pleura, pele, intestinos, ossos e meninge, sendo denominada, tuberculose extrapulmonar. Sua transmissão ocorre por meio de aerossóis provenientes do sistema respiratório que após eliminadas, ficam suspensas no ar e/ou permanecem viáveis por um período no ambiente. No Brasil, no ano de 2020 estima-se que o número de óbitos foi de 4.543 pessoas, o coeficiente de mortalidade manteve-se de 2,3 por 100.000 habitantes e ao todo 36.000 foram infectadas. Objetivo: Evidenciar os principais desafios do enfermeiro no tratamento aos pacientes com tuberculose pulmonar nos espaços de assistência à saúde. Material e métodos: O estudo constitui-se de uma revisão de literatura, do tipo narrativa e de natureza descritiva, tendo como base teórica artigos científico acadêmicos. Para conduzir a revisão foram selecionadas as bases de dados Scielo e Biblioteca Virtual em Saúde: LILACS. Nisso, foram pautados artigos completos para levantamento de pesquisa em um período de até 5 anos. Resultados/Discussão: O modelo final desta revisão foi composto por nove artigos publicados entre os anos de 2019 e 2022. O presente estudo torna notório o importante papel da enfermagem no diagnóstico precoce na assistência primária, assim como na atuação de atividades para educação dos civis sobre promoção de saúde e prevenção de doenças. Entretanto, a falta de profissionais capacitados e a necessidade de maior participação da equipe multiprofissional representam as maiores problemáticas que cercam este estudo. A partir da leitura dos artigos tornou-se relevante segregar quatro tópicos que nortearam a discussão desta análise, são eles: Acessibilidade, incompletude de prontuários, renda familiar/estigma social e fortalecimento das estratégias de atendimento. Em relação a incompletude dos prontuários, notou-se que os enfermeiros que participaram da pesquisa delimitavam-se aos sinais e sintomas físicos dos pacientes e negligenciaram outros fatores, sendo uma influência do histórico do modelo biomédico, o que prejudica a integralidade da assistência à saúde. Esses indícios devem ser corrigidos, visto que outros métodos devem ser incluídos como fonte de informação para a assistência integral ao paciente. Identificou-se a necessidade de otimizar os registros no prontuário e reiterar a importância dessa prática para evitar que a real situação a respeito da TB seja disfarçada e haja tomada de decisões não condizentes e errôneas. Ademais, o fortalecimento das estratégias de enfrentamento da atenção primária é de tamanha importância, já que sua falta compromete a detecção precoce da doença, o tratamento adequado e a prevenção da disseminação da doença. Por fim, o enfermeiro tem o papel de orientar a população sobre meios de contaminação, buscar casos de TB e educar sobre os benefícios e malefícios do tratamento e da não adesão dele. Considerações finais: Conclui-se ser necessário uma padronização da conduta do enfermeiro, que deve incluir acesso integral aos doentes, acompanhamento do uso da medicação, teste rápidos, além de incentivar uma abordagem individualizada para os pacientes com tuberculose.

Introduction: Tuberculosis is caused by Koch's bacillus that mainly affects the lungs. However, a small portion, about 15%, develops in other body structures, such as the larynx, ganglia, pleura, skin, intestines, bones, and meninges, and is termed extrapulmonary tuberculosis. Its transmission occurs by means of aerosols coming from the respiratory system that, after being eliminated, remain suspended in the air and/or remain viable for a period in the environment. In Brazil, in the year 2020 it is estimated that the number of deaths was 4,543 people, the mortality coefficient remained 2.3 per 100,000 inhabitants and in all 36,000 were infected. Objective: To highlight the main challenges of the nurse in the treatment of patients with pulmonary tuberculosis in the health care spaces. Material and methods: The study consists of a review of literature, narrative type and descriptive nature, based on theoretical academic scientific articles. To conduct the review, the Scielo and Virtual Health Library databases were selected: LILACS. In this respect, full papers for the survey of research in a period of up to 5 years were drawn up. Results/Discussion: The final model of this review was composed of nine articles published between 2019 and 2022. The present study makes well known the important role of nursing in early diagnosis in primary care, as well as in the performance of activities for educating civilians about health promotion and disease prevention. However, the lack of skilled professionals and the need for greater participation of the multiprofessional team represent the biggest problems surrounding this study. From the reading of the articles, it became relevant to segregate four topics that guided the discussion of this analysis, are: Accessibility, incompleteness of medical records, family income/social stigma and strengthening of care strategies. Regarding the incompleteness of the medical records, it was noted that the nurses who participated in the research were limited to the physical signs and symptoms of the patients and neglected other factors, being an influence of the history of the biomedical model, which impairs the completeness of the health care. These indications should be corrected, as other methods should be included as a source of information for comprehensive patient care. The need to optimize the records in the medical record was identified and the importance of this practice was reiterated, to avoid the real situation with regard to TB being disguised and inconsistent and erroneous decisions being taken. Furthermore, the strengthening of strategies for coping with primary care is of such importance, since its lack compromises the early detection of the disease, the adequate treatment and the prevention of the dissemination of the disease. Finally, the nurse has the role of giving guidance to the population about means of contamination, of looking for cases of TB, and of educating about the benefits and harms of the treatment and of not adhering to it. Conclusion: It is concluded that a standardization of the nurse's conduct is necessary, which should include full access to patients, follow-up of the use of medication, rapid tests, besides encouraging an individualized approach for patients with tuberculosis.

Introducción: La tuberculosis es causada por el bacilo de Koch que afecta principalmente a los pulmones. Sin embargo, una pequeña porción, cercana al 15%, se desarrolla en otras estructuras corporales, como la laringe, ganglia, pleura, piel, intestinos, huesos y meninges, siendo llamada tuberculosis extrapulmonar. Su transmisión se realiza por medio de aerosoles procedentes del sistema respiratorio que, después de ser eliminados, se suspenden en el aire y/o permanecen viables durante un período en el medio ambiente. En el Brasil, en el año 2020, se estima que el número de fallecimientos fue de 4.543 personas, que el coeficiente de mortalidad se mantuvo en 2,3 por 100.000 habitantes y que en total 36.000 resultaron infectados. Objetivo: poner de relieve los principales retos del tratamiento de enfermería para pacientes con tuberculosis pulmonar en las áreas de atención de la salud. Material y métodos: El estudio es una revisión de la literatura, del tipo narrativo y de naturaleza descriptiva, basada en artículos teóricos académicos científicos. Para llevar a cabo el examen, se seleccionaron las bases de datos de Scielo y Virtual Library on Health: LILACS. A este respecto, se elaboraron artículos completos para un estudio de investigación en un período de hasta cinco años. Resultados/Debate: El modelo final de esta revisión se compone de nueve artículos publicados entre 2019 y 2022. En este estudio se destaca el importante papel de la enfermería en el diagnóstico precoz en la atención primaria, así como en las actividades de educación de los civiles sobre la promoción de la salud y la prevención de enfermedades. Sin embargo, la falta de profesionales cualificados y la necesidad de una mayor participación del equipo multiprofesional son los mayores problemas que rodean este estudio. A partir de la lectura de los artículos, se hizo relevante separar cuatro temas que guiaron el debate de este análisis, a saber: accesibilidad, registros incompletos, ingresos familiares/estigma social y el fortalecimiento de las estrategias de asistencia. En relación con la inexhaustividad de los registros médicos, se observó que las enfermeras que participaron en la investigación se limitaban a los signos y síntomas físicos de los pacientes y descuidaban otros factores, siendo una influencia de la historia del modelo biomédico, lo que daña la integridad de la atención sanitaria. Estas indicaciones deben corregirse, ya que se deben incluir otros métodos como fuente de información para la atención completa del paciente. Se ha identificado la necesidad de optimizar los registros médicos digitales y de reiterar la importancia de esta práctica para evitar que la situación real de la tuberculosis sea disfrazada, indigna y errónea. Además, el fortalecimiento de las estrategias de atención primaria es de tal importancia, ya que su ausencia pone en peligro la detección precoz de la enfermedad, el tratamiento adecuado y la prevención de la diseminación de la enfermedad. Finalmente, la enfermera tiene el papel de guiar a la población sobre los medios de contaminación, buscando casos de tuberculosis y educándolos sobre los beneficios y daños del tratamiento y de su falta de cumplimiento. Consideraciones finales: Se concluye que es necesaria la estandarización de la conducta de la enfermera, que debe incluir el pleno acceso a los pacientes, el seguimiento del uso de medicamentos, las pruebas rápidas y el fomento de un enfoque individualizado para los pacientes de tuberculosis.

A prática da episiotomia no Brasil / The practice of episiotomy in Brazil / La práctica de la episiotomía en Brasil

O parto é um processo fisiológico e natural que pode ser vivenciado sem complexidades pelas parturientes e bebês. A violência obstétrica atinge mulheres em seu processo reprodutivo e ocorre entre os períodos de gestação, parto e puerpério. Ocorre pelo desrespeito a sua autonomia, seu corpo e seus processos reprodutivos, utilizando procedimentos cientificamente desnecessários, podendo ser praticada de forma física, verbal, psicológica, sexual e negligência da assistência. Objetivo: Identificar a ocorrência de episiotomias realizadas, suas principais indicações e quando essa prática se torna uma violência. Materiais e métodos: Trata-se de uma revisão integrativa da literatura, considerando a questão norteadora: a episiotomia se torna um evento necessário ou uma violência? Para tanto, a busca de artigos ocorreu por meio da biblioteca virtual de saúde (BVS), utilizando as bases de dados LILACS, MEDLINE e BDENF. Os critérios para inclusão dos artigos foram: publicações entre os anos 2018 e 2023, no idioma português e inglês. Foram excluídos desta pesquisa os artigos sem relação direta com o tema, dissertações/teses. Resultados/Discussão: Após analisar os 312 artigos encontrados e aplicar os filtros, constatou-se que 200 deles não possuíam relação com o tema em questão, restando assim, 112 artigos para leitura de título e resumo. Em seguida, foram excluídos mais 91 artigos por não abrangerem o escopo desta pesquisa, por estarem em duplicidade ou por se tratar de dissertações/teses, resultando em um total de 21 artigos selecionados para o estudo que destacaram: mulheres que passaram por procedimentos de intervenção como a episiotomia relataram sequelas, como dores e dificuldades em retomar as atividades sexuais. A prática adotada, deve ser realizada apenas em casos de distocia ou 4866Arquivos de Ciências da Saúde da UNIPAR, Umuarama, v.27, n.9, p.4865-4892, 2023. ISSN 1982-114Xsofrimento fetal, com a autorização da parturiente. Mulheres submetidas à episiotomia, relatam dificuldades para realizar atividades diárias e habituais, comprometendo suas necessidades fisiológicas. Parturientes que tiveram acompanhamento adequado realizado pelo enfermeiro obstetra apresentaram menores taxas de realização de episiotomia, recuperação com maior índice de satisfação, ressaltando à importância da humanização do parto e redução de práticas desnecessárias para que o nascimento ocorra. As evidências apresentadas nesta revisão apoiam a necessidade de uma reavaliação crítica das práticas de episiotomia. Orientações adequadas, treinamento e maior conscientização dos profissionais de saúde são essenciais para garantir que a episiotomia seja realizada de forma criteriosa, respeitando a fisiologia e a integridade do corpo da mulher. Além disso, a implementação de abordagens de atendimento humanizado e consentimento informado é crucial para reduzir a prevalência de episiotomias desnecessárias e minimizar potenciais efeitos negativos na qualidade de vida das mulheres. Cada vez mais a episiotomia é realizada sem levar em conta nenhum critério de indicação, não respeitando limites da fisiologia, do corpo da mulher e do processo do nascer, causando inúmeros malefícios. Considerações finais: Em síntese, as evidências apresentadas apoiam a necessidade de uma reavaliação crítica na adoção da prática da episiotomia, que perpassa pela formação, capacitação e educação permanente dos profissionais que assistem a mulher durante o parto. Orientações adequadas, treinamento e maior conscientização dos profissionais de saúde são essenciais para garantir que a episiotomia seja realizada de forma criteriosa, respeitando a fisiologia e a integridade do corpo da mulher.

Childbirth is a physiological and natural process that can be experienced without complexities by parturients and babies. Obstetric violence affects women in their reproductive process and occurs between the periods of pregnancy, childbirth and puerperium. It occurs by disrespecting their autonomy, their body and their reproductive processes, using scientifically unnecessary procedures, and can be practiced physically, verbally, psychologically, sexually and negligence of care. Objective: To identify the occurrence of episiotomies performed, their main indications and when this practice becomes violence. Materials and methods: This is an integrative literature review, considering the guiding question: does episiotomy become a necessary event or a violence? To this end, the search for articles occurred through the virtual health library (VHL), using the LILACS, MEDLINE and BDENF databases. The criteria for inclusion of the articles were: publications between the years 2018 and 2023, in Portuguese and English. Articles with no direct relation to the theme, dissertations/theses were excluded from this research. Results/Discussion: After analyzing the 312 articles found and applying the filters, it was found that 200 of them were not related to the topic in question, thus leaving 112 articles for reading the title and abstract. Then, 91 more articles were excluded because they did not cover the scope of this research, because they were in duplicate or because they were dissertations/theses, resulting in a total of 21 articles selected for the study that highlighted: women who underwent intervention procedures such as episiotomy reported sequelae, such as pain and difficulties in resuming sexual activities. The practice adopted should be performed only in cases of dystocia or fetal distress, with the authorization of the parturient. Women undergoing episiotomy report difficulties in performing daily and usual activities, compromising their physiological needs. Parturients who had adequate follow-up performed by the obstetric nurse had lower rates of episiotomy, recovery with a higher satisfaction rate, highlighting the importance of humanizing childbirth and reducing unnecessary practices for birth to occur. The evidence presented in this review support the need for a critical reassessment of episiotomy practices. Appropriate guidance, training and increased awareness of health care providers are essential to ensure that episiotomy is performed judiciously, respecting the physiology and integrity of the woman's body. In addition, the implementation of humanized care approaches and informed consent is crucial to reduce the prevalence of unnecessary episiotomies and minimize potential negative effects on women's quality of life. Episiotomy is increasingly performed without taking into account any indication criteria, not respecting the limits of physiology, the woman's body and the birth process, causing numerous harms. Final considerations: In summary, the evidence presented supports the need for a critical reassessment in the adoption of the practice of episiotomy, which includes the training, qualification and permanent education of professionals who assist women during childbirth. Adequate guidance, training and greater awareness of health professionals are essential to ensure that episiotomy is performed carefully, respecting the physiology and integrity of the woman's body.

El parto es un proceso fisiológico y natural que puede ser vivido sin complejidades por parturientas y bebés. La violencia obstétrica afecta a las mujeres en su proceso reproductivo y ocurre entre los periodos de embarazo, parto y puerperio. Ocurre por la falta de respeto a su autonomía, a su cuerpo y a sus procesos reproductivos, utilizando procedimientos científicamente innecesarios, y puede ser practicada física, verbal, psicológica, sexual y negligencia de cuidados. Objetivo: Identificar la ocurrencia de episiotomías realizadas, sus principales indicaciones y cuando esa práctica se torna violencia. Materiales y métodos: Se trata de una revisión bibliográfica integradora, considerando la pregunta orientadora: ¿la episiotomía se convierte en un hecho necesario o en violencia? Para ello, la búsqueda de artículos se realizó a través de la biblioteca virtual de salud (BVS), utilizando las bases de datos LILACS, MEDLINE y BDENF. Los criterios de inclusión de los artículos fueron: publicaciones entre 2018 y 2023, en portugués e inglés. Fueron excluidos de esta investigación artículos sin relación directa con el tema, disertaciones/tesis. Resultados/Discusión: Después de analizar los 312 artículos encontrados y aplicar los filtros, se constató que 200 de ellos no estaban relacionados con el tema en cuestión, quedando así 112 artículos para la lectura del título y resumen. Luego, 91 artículos más fueron excluidos por no abarcar el alcance de esta investigación, por estar duplicados o por tratarse de disertaciones/tesis, resultando en un total de 21 artículos seleccionados para el estudio que destacaron: las mujeres sometidas a procedimientos de intervención como la episiotomía relataron secuelas, como dolor y dificultades para retomar las actividades sexuales. La práctica adoptada sólo debería realizarse en casos de distocia o sufrimiento fetal, con la autorización de la parturienta. Las mujeres sometidas a episiotomía relatan dificultades en la realización de las actividades cotidianas y habituales, comprometiendo sus necesidades fisiológicas. Las parturientas que tuvieron un seguimiento adecuado realizado por la enfermera obstétrica presentaron menores tasas de episiotomía, recuperación con una mayor tasa de satisfacción, destacando la importancia de humanizar el parto y reducir las prácticas innecesarias para que ocurra. Las pruebas presentadas en esta revisión apoyan la necesidad de una reevaluación crítica de las prácticas de episiotomía. La orientación adecuada, la formación y una mayor concienciación de los profesionales sanitarios son esenciales para garantizar que la episiotomía se realice con criterio, respetando la fisiología y la integridad del cuerpo de la mujer. Además, la aplicación de enfoques asistenciales humanizados y el consentimiento informado son cruciales para reducir la prevalencia de episiotomías innecesarias y minimizar los posibles efectos negativos en la calidad de vida de las mujeres. La episiotomía se realiza cada vez más sin tener en cuenta ningún criterio de indicación, sin respetar los límites de la fisiología, el cuerpo de la mujer y el proceso del parto, causando numerosos daños. Consideraciones finales: En resumen, las pruebas presentadas apoyan la necesidad de una reevaluación crítica de la adopción de la episiotomía, que incluya la formación, cualificación y educación permanente de los profesionales que asisten a las mujeres durante el parto. La orientación adecuada, la formación y una mayor concienciación de los profesionales de la salud son esenciales para garantizar que la episiotomía se realice con cuidado, respetando la fisiología y la integridad del cuerpo de la mujer.

Gestação de alto risco: perfil epidemiológico e fatores associados com o encaminhamento para serviço especializado / Embarazo de alto riesgo: perfil epidemiológico y factores asociados a la referencia a servicio especializado / High risk pregnancy: epidemiological profile and factors associated with referral to specialized servisse

Objetivo: Verificar o perfil epidemiológico das gestantes e os fatores associados com o encaminhamento de gestantes para um serviço especializado. Método: Estudo transversal retrospectivo, realizado nos prontuários de gestantes classificadas em alto risco, período de janeiro a dezembro de 2019. Realizou-se análise descritiva, bivariada e multivariada. Resultados: Dos 405 prontuários, a média de idade foi 29 anos, 19% eram hipertensas crônicas,14,2% desenvolveram diabetes gestacional. A diferença média entre a data da primeira consulta e a data do encaminhamento pela atenção primária foi de 4 semanas. A regressão logística mostrou que: gestantes de outros municípios, com baixa renda econômica e diferença no tempo de encaminhamento possuem interferência no início do pré-natal. Conclusão: As análises realizadas poderão contribuir para a elaboração de políticas intersetoriais em busca da promoção da saúdede gestantes.

Objective: To verify the epidemiological profile of pregnant women and the factors associated with referring pregnant women to a specialized service. Method: Retrospective cross-sectional study, carried out on the medical records of pregnant women classified as high risk, from January to December 2019. A descriptive, bivariate and multivariate analysis was performed. Results: Of the 405 medical records, mean age was 29 years, 19% were chronic hypertensive patients, 14.2% developed gestational diabetes. The average difference between the date of the first consultation and the date of referral by primary care was 4 weeks. The logistic regression showed that: pregnant women from other cities, withlow economic income and difference in referral time have interference in the beginning of prenatal care. Conclusion: The analyzes carried out may contribute to the development of intersectoral policies in search of health promotion for pregnant women.

Objetivo: Verificar el perfil epidemiológico de la gestante y los factores asociados a la derivación de gestantes a un servicio especializado. Método: Estudio retrospectivo, transversal, realizado sobre las historias clínicas de gestantes clasificadas como de alto riesgo, de enero a diciembre de 2019. Se realizó un análisis descriptivo, bivariado y multivariado. Resultados: De las 405 historias clínicas, la edad promedio fue de 29 años, el 19% eran hipertensos crónicos, el 14,2% desarrolló diabetes gestacional. La diferencia media entre la fecha de la primera consulta y la fecha de derivación por atención primaria fue de 4 semanas. La regresión logística mostró que: mujeres embarazadas de otras ciudades, con bajos ingresos económicos e diferencia en el tiempo de derivación tienen interferencia en el inicio de la atención prenatal. Conclusión: Los análisis realizados pueden contribuir a la elaboración de políticas intersectoriales en busca de promoción de la salud de la gestante.

miR-197, miR-26a and miR-27a analysis in chronic lymphocytic leukemia.

Aims: Chronic lymphocytic leukemia (CLL) involves the proliferation and increase of B-lymphocytes in the peripheral blood, bone marrow and lymphoid organs. This study evaluated the microRNAs miR-197, miR-26a and miR-27a as potential biomarkers for CLL. Patients & Methods: Eighty-two patients with CLL and 62 control subjects (CT) were investigated for these targets, using quantitative PCR (qPCR). Results: A significant reduction of all microRNAs was observed in CLL compared to the controls (p < 0.001). Significant negative correlations were observed for the clinical staging groups. After adjusting for multiple logistic regression analysis, miR-197 and miR-26a remained as possible independent risk factors related to the CLL. Conclusions: Our data indicated good performance of this microRNAs as potential biomarkers in CLL.

RI75, a curcumin analogue, inhibits tumor necrosis factor-α and interleukin-6 production and exhibits antiallodynic and antiedematogenic activities in mice.

Curcumin and its analogues exhibited anti-inflammatory activity in different experimental models. Recently, we synthesized (2E,3E)-3-buten-2-one-4-(4-hydroxy-3-methoxyphenyl)-2-(4-(4-methoxyphenyl)-2-thiazolyl)hydrazone (RI75), a curcumin analogue with a thiazolyl hydrazone moiety. In the present study, we investigated the effects induced by RI75 in different models of inflammation and pain in mice, as well as some underlying mechanisms. Pre-treatment with RI75 (40 mg/kg, intraperitoneal; i.p.) or curcumin (40 mg/kg, i.p.) reduced the mechanical allodynia and paw edema induced by intraplantar (i.pl) injection of carrageenan. RI75 antiallodynic activity was reduced by pre-treatment with naltrexone (5 and 10 mg/kg, i.p.) and cyproheptadine (10 mg/kg, i.p.), but not glibenclamide (20 and 40 mg/kg, i.p.). In a model of neuropathic pain, a single i.p. administration of RI75 (40 mg/kg) or curcumin (40 mg/kg) attenuated the ongoing mechanical allodynia induced by repeated administrations of paclitaxel. Pre-treatment with RI75 (40 mg/kg, i.p.) or curcumin (40 mg/kg, i.p.) also reduced tumor necrosis factor-α and interleukin-6 production and myeloperoxidase activity induced by carrageenan. The results of the present study demonstrate that RI75, a synthetic curcumin analogue, exhibits antiallodynic and antiedematogenic activities. Activation of opioidergic and serotonergic mechanisms and reduced production of inflammatory mediators and neutrophil recruitment may underlie RI75 activities.