Differential Impact of Adolescent or Adult Stress on Behavior and Cortical Parvalbumin Interneurons and Perineuronal Nets in Male and Female Mice.

BACKGROUND: Stress has become a common public health concern, contributing to the rising prevalence of psychiatric disorders. Understanding the impact of stress considering critical variables, such as age, sex, and individual differences, is of the utmost importance for developing effective intervention strategies. METHODS: Stress effects (daily footshocks for 10 days) during adolescence (postnatal day [PND] 31-40) and adulthood (PND 65-74) were investigated on behavioral outcomes and parvalbumin (PV)-expressing GABAergic interneurons and their associated perineuronal nets (PNNs) in the prefrontal cortex of male and female mice 5 weeks post stress. RESULTS: In adulthood, adolescent stress induced behavioral alterations in male mice, including anxiety-like behaviors, social deficits, cognitive impairments, and altered dopamine system responsivity. Applying integrated behavioral z-score analysis, we identified sex-specific differences in response to adolescent stress, with males displaying greater vulnerability than females. Furthermore, adolescent-stressed male mice showed decreased PV+ and PNN+ cell numbers and PV+/PNN+ colocalization, while in females, adolescent stress reduced prefrontal PV+/PNN+ colocalization in the prefrontal cortex. Further analysis identified distinct behavioral clusters, with certain females demonstrating resilience to adolescent stress-induced deficits in sociability and PV+ cell number. Adult stress in male and female mice did not cause long-lasting changes in behavior and PV+ and PNN+ cell number. CONCLUSION: Our findings indicate that the timing of stress, sex, and individual variabilities seem to be determinants for the development of behavioral changes associated with psychiatric disorders, particularly in male mice during adolescence.

Carvacrol prevents D-( +)-galactose-induced aging-associated erectile dysfunction by improving endothelial dysfunction and oxidative stress in rats.

Aging is one of the risk factors involved in the development of erectile dysfunction (ED). Growing evidence suggests that oxidative stress is the critical mediator of changes in endothelial function and penile vascular tone in the aging process. Thus, reducing reactive oxygen species (ROS) levels may preserve the bioactivity of the penile vasculature. Antioxidant compounds, such as carvacrol, limit the damage caused by ROS and, therefore, benefit the treatment of ED. Thus, this study aims to evaluate the effects of carvacrol on ED using the D-( +)-galactose aging model. The animals were divided into five groups: control, D-( +)-galactose 150 mg/kg, carvacrol 50 mg/kg or 100 mg/kg, and sildenafil 1.5 mg/kg treated daily for 8 weeks. The physiological, functional, and morphological characteristics of aging-associated ED were evaluated after treatment with carvacrol. Carvacrol prevented ED in a D-( +)-galactose-induced aging model by reducing hypercontractility, enhancing endothelial dysfunction in the rat corpus cavernosum, and improving endothelial health of rat cavernous endothelial cells. In addition, carvacrol prevented the destruction of erectile components essential for penile erection and promoted a reduction of penile tissue senescence, probably through mechanisms that involve the harmful modulation of oxidative stress. Carvacrol significantly improved the erectile function of rats in a D-( +)-galactose-induced aging model and has excellent potential as a new therapeutic alternative in treating erectile dysfunction.

A mimetic peptide of ACE2 protects against SARS-CoV-2 infection and decreases pulmonary inflammation related to COVID-19.

Since human angiotensin-converting enzyme 2 (ACE2) serves as a primary receptor for SARS-CoV-2, characterizing ACE2 regions that allow SARS-CoV-2 to enter human cells is essential for designing peptide-based antiviral blockers and elucidating the pathogenesis of the virus. We identified and synthesized a 25-mer mimetic peptide (encompassing positions 22-46 of the ACE2 alpha-helix α1) implicated in the S1 receptor-binding domain (RBD)-ACE2 interface. The mimetic (wild-type, WT) ACE2 peptide significantly inhibited SARS-CoV-2 infection of human pulmonary Calu-3 cells in vitro. In silico protein modeling predicted that residues F28, K31, F32, F40, and Y41 of the ACE2 alpha-helix α1 are critical for the original, Delta, and Omicron strains of SARS-CoV-2 to establish the Spike RBD-ACE2 interface. Substituting these residues with alanine (A) or aspartic acid (D) abrogated the antiviral protective effect of the peptides, indicating that these positions are critical for viral entry into pulmonary cells. WT ACE2 peptide, but not the A or D mutated peptides, exhibited significant interaction with the SARS-CoV-2 S1 RBD, as shown through molecular dynamics simulations. Through identifying the critical amino acid residues of the ACE2 alpha-helix α1, which is necessary for the Spike RBD-ACE2 interface and mobilized during the in vitro viral infection of cells, we demonstrated that the WT ACE2 peptide protects susceptible K18-hACE2 mice against in vivo SARS-CoV-2 infection and is effective for the treatment of COVID-19.

Tuning Biocompatibility and Bactericidal Efficacy as a Function of Doping of Gold in ZnO Nanocrystals.

Doping nanoparticles represents a strategy for modulating the energy levels and surface states of nanocrystals (NCs), thereby enhancing their efficiency and mitigating toxicity. Thus, we herein focus on the successful synthesis of pure and gold (Au)-doped zinc oxide (ZnO) nanocrystals (NCs), investigating their physical-chemical properties and evaluating their applicability and toxicity through in vitro and in vivo assessments. The optical, structural, and photocatalytic characteristics of these NCs were scrutinized by using optical absorption (OA), X-ray diffraction (XRD), and methylene blue degradation, respectively. The formation and doping of the NCs were corroborated by the XRD and OA results. While the introduction of Au as a dopant did induce changes in the phase and size of ZnO, a high concentration of Au ions in ZnO led to a reduction in their photocatalytic activity. This demonstrated a restricted antibacterial efficacy against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. Remarkably, Au-doped counterparts exhibited enhanced biocompatibility in comparison to ZnO, as evidenced in both in vitro (murine macrophage cells) and in vivo (Drosophila melanogaster) studies. Furthermore, confocal microscopy images showed a high luminescence of Au-doped ZnO NCs in vivo. Thus, this study underscores the potential of Au doping of ZnO NCs as a promising technique to enhance material properties and increase biocompatibility.

Perineuronal nets as regulators of parvalbumin interneuron function: Factors implicated in their formation and degradation.

The brain extracellular matrix (ECM) has garnered increasing attention as a fundamental component of brain function in a predominantly "neuron-centric" paradigm. Particularly, the perineuronal nets (PNNs), a specialized net-like structure formed by ECM aggregates, play significant roles in brain development and physiology. PNNs enwrap synaptic junctions in various brain regions, precisely balancing new synaptic formation and long-term stabilization, and are highly dynamic entities that change in response to environmental stimuli, especially during the neurodevelopmental period. They are found mainly surrounding parvalbumin (PV)-expressing GABAergic interneurons, being proposed to promote PV interneuron maturation and protect them against oxidative stress and neurotoxic agents. This structural and functional proximity underscores the crucial role of PNNs in modulating PV interneuron function, which is critical for the excitatory/inhibitory balance and, consequently, higher-level behaviours. This review delves into the molecular underpinnings governing PNNs formation and degradation, elucidating their functional interactions with PV interneurons. In the broader physiological context and brain-related disorders, we also explore their intricate relationship with other molecules, such as reactive oxygen species and metalloproteinases, as well as glial cells. Additionally, we discuss potential therapeutic strategies for modulating PNNs in brain disorders.

Cardiovascular risk in women with nonclassical congenital adrenal hyperplasia.

CONTEXT: The outcomes related to cardiovascular risk (CVR) in patients with nonclassical form of congenital adrenal hyperplasia (NCAH) are unknown, especially those related to therapeutic options, including low doses of glucocorticoids (GCs) or oral contraceptive pills. OBJECTIVES: to analyze CVR by markers of atherosclerosis in females with nonclassical form according to therapeutic options. DESIGN AND SETTING: a cross-sectional study at a tertiary center. PATIENTS AND METHODS: Forty-seven females with NCAH (33.4 ± 10 years) were subdivided into: G1 (n = 28) treated with dexamethasone (0.14 ± 0.05 mg/m2/day); G2 (n = 19) with oral contraceptive pills; and G3 (30 matched controls). CVR was analyzed through serum lipids, HOMA-IR, inflammatory cytokines levels and quantitative image evaluations (pulse wave velocity-PWV, endothelial function by flow mediated dilatation-FMD, carotid intima media thickness-CIMT and visceral fat-VAT by abdominal tomography. RESULTS: There were no statistically significant differences in BMI, HOMA-IR, HDL-cholesterol, or triglyceride levels among groups (p > 0.05). Serum interleukin-6 levels ​​were higher in G1 than in G2 (p = 0.048), and interleukin-8 levels were higher in G1 than in G2/3 (p = 0.008). There were no statistically significant differences in VAT, PWV, FMD or CIMT among groups (p > 0.05). In multivariable regression analysis, there was no statistically significant association between glucocorticoid dose and evaluated outcomes. CONCLUSION: Adult females with NCAH did not show increased CVR using methodologies for detection of precocious atherosclerosis. Although patients receiving dexamethasone therapy had increased IL-6 and 8 levels, these data were not associated with radiological markers of atherosclerosis. Our cohort was composed of young adults and should be reevaluated in a long-term follow-up.

Gerenciamento clínico da hemorragia pós-parto pelo enfermeiro obstetra: um protocolo de revisão de escopo / Clinical management of postpartum hemorrhage by obstetric nurses: a scoping review protocol

OBJETIVO: Mapear as evidências científicas sobre as ações dos enfermeiros obstétricos no gerenciamento clínico da hemorragia pós-parto. MÉTODO: Trata-se de uma revisão de escopo elaborada segundo as recomendações do JBI Institute Manual do Revisor para Scoping Review. As buscas serão realizadas nas bases de dados eletrônicas CINAHL, Cochrane Library, EMBASE, Literatura Latino-americana e do Caribe em Ciências da Saúde, MEDLINE/PubMed, SciELO, ScienceDirect, SCOPUS, Web of Science e na literatura cinzenta. Os estudos que serão incluídos precisarão responder ao objetivo desta pesquisa e estar nos idiomas Português, Espanhol ou Inglês. Além disso, é necessário ter disponibilidade dos estudos na íntegra através de acesso remoto pelo acesso da CAFe. Os estudos que não serão incluídos serão os em formato de editorial e carta ao editor. Haverá a seleção por meio da leitura do título e resumo dos materiais encontrados nas buscas, sendo assim avaliados de maneira independente por dois revisores e nos casos de divergências por um terceiro avaliador. Os dados coletados estarão organizados e relacionados segundo a análise descritiva. Os resultados poderão estar dispostos em tabelas ou quadros, e serão discutidos com suporte de literatura acerca da temática, retratando a quinta etapa do método escolhido.

OBJECTIVE: To map the scientific evidence regarding the actions of obstetric nurses in the clinical management of postpartum hemorrhage. METHOD: This scoping review was developed according to the JBI Institute Reviewer's Manual for Scoping Reviews. The electronic databases CINAHL, Cochrane Library, EMBASE, Latin American and Caribbean Health Sciences Literature, MEDLINE/PubMed, SciELO, ScienceDirect, SCOPUS, Web of Science, and gray literature were searched. Included studies must address the research objective in Portuguese, Spanish, or English. In addition, full remote access to the studies via CAFe is required. Studies in editorial or letter format will be excluded. Selection will be based on the title and abstract of the materials found in the searches, independently assessed by two reviewers, with disagreements resolved by a third reviewer. Collected data will be organized and related through descriptive analysis. Results may be presented in tables or figures and discussed with support from literature, reflecting the fifth step of the selected methodology.

Tonsils are major sites of persistence of SARS-CoV-2 in children.

In the present study, we show that SARS-CoV-2 can infect palatine tonsils, adenoids, and secretions in children without symptoms of COVID-19, with no history of recent upper airway infection. We studied 48 children undergoing tonsillectomy due to snoring/OSA or recurrent tonsillitis between October 2020 and September 2021. Nasal cytobrushes, nasal washes, and tonsillar tissue fragments obtained at surgery were tested by RT-qPCR, immunohistochemistry (IHC), flow cytometry, and neutralization assay. We detected the presence of SARS-CoV-2 in at least one specimen tested in 27% of patients. IHC revealed the presence of the viral nucleoprotein in epithelial surface and in lymphoid cells in both extrafollicular and follicular regions, in adenoids and palatine tonsils. Also, IHC for the SARS-CoV-2 non-structural protein NSP-16 indicated the presence of viral replication in 53.8% of the SARS-CoV-2-infected tissues. Flow cytometry showed that CD20+ B lymphocytes were the most infected phenotypes, followed by CD4+ lymphocytes and CD123 dendritic cells, CD8+ T lymphocytes, and CD14+ macrophages. Additionally, IF indicated that infected tonsillar tissues had increased expression of ACE2 and TMPRSS2. NGS sequencing demonstrated the presence of different SARS-CoV-2 variants in tonsils from different tissues. SARS-CoV-2 antigen detection was not restricted to tonsils but was also detected in nasal cells from the olfactory region. Palatine tonsils and adenoids are sites of prolonged RNA presence by SARS-CoV-2 in children, even without COVID-19 symptoms. IMPORTANCE This study shows that SRS-CoV-2 of different lineages can infect tonsils and adenoids in one quarter of children undergoing tonsillectomy. These findings bring advancement to the area of SARS-CoV-2 pathogenesis, by showing that tonsils may be sites of prolonged infection, even without evidence of recent COVID-19 symptoms. SARS-CoV-2 infection of B and T lymphocytes, macrophages, and dendritic cells may interfere with the mounting of immune responses in these secondary lymphoid organs. Moreover, the shedding of SARS-CoV-2 RNA in respiratory secretions from silently infected children raises concern about possible diagnostic confusion in the presence of symptoms of acute respiratory infections caused by other etiologies.

Carvacrol Improves Vascular Function in Hypertensive Animals by Modulating Endothelial Progenitor Cells.

Carvacrol, a phenolic monoterpene, has diverse biological activities, highlighting its antioxidant and antihypertensive capacity. However, there is little evidence demonstrating its influence on vascular regeneration. Therefore, we evaluated the modulation of carvacrol on endothelial repair induced by endothelial progenitor cells (EPC) in hypertension. Twelve-week-old spontaneously hypertensive rats (SHR) were treated with a vehicle, carvacrol (50 or 100 mg/kg/day), or resveratrol (10 mg/kg/day) orally for four weeks. Wistar Kyoto (WKY) rats were used as the normotensive controls. Their systolic blood pressure (SBP) was measured weekly through the tail cuff. The EPCs were isolated from the bone marrow and peripherical circulation and were quantified by flow cytometry. The functionality of the EPC was evaluated after cultivation through the quantification of colony-forming units (CFU), evaluation of eNOS, intracellular detection of reactive oxygen species (ROS), and evaluation of senescence. The superior mesenteric artery was isolated to evaluate the quantification of ROS, CD34, and CD31. Treatment with carvacrol induced EPC migration, increased CFU formation and eNOS expression and activity, and reduced ROS and senescence. In addition, carvacrol reduced vascular ROS and increased CD31 and CD34 expression. This study showed that treatment with carvacrol improved the functionality of EPC, contributing to the reduction of endothelial dysfunction.

COVID-19-related hyperglycemia is associated with infection of hepatocytes and stimulation of gluconeogenesis.

Occurrence of hyperglycemia upon infection is associated with worse clinical outcome in COVID-19 patients. However, it is still unknown whether SARS-CoV-2 directly triggers hyperglycemia. Herein, we interrogated whether and how SARS-CoV-2 causes hyperglycemia by infecting hepatocytes and increasing glucose production. We performed a retrospective cohort study including patients that were admitted at a hospital with suspicion of COVID-19. Clinical and laboratory data were collected from the chart records and daily blood glucose values were analyzed to test the hypothesis on whether COVID-19 was independently associated with hyperglycemia. Blood glucose was collected from a subgroup of nondiabetic patients to assess pancreatic hormones. Postmortem liver biopsies were collected to assess the presence of SARS-CoV-2 and its transporters in hepatocytes. In human hepatocytes, we studied the mechanistic bases of SARS-CoV-2 entrance and its gluconeogenic effect. SARS-CoV-2 infection was independently associated with hyperglycemia, regardless of diabetic history and beta cell function. We detected replicating viruses in human hepatocytes from postmortem liver biopsies and in primary hepatocytes. We found that SARS-CoV-2 variants infected human hepatocytes in vitro with different susceptibility. SARS-CoV-2 infection in hepatocytes yields the release of new infectious viral particles, though not causing cell damage. We showed that infected hepatocytes increase glucose production and this is associated with induction of PEPCK activity. Furthermore, our results demonstrate that SARS-CoV-2 entry in hepatocytes occurs partially through ACE2- and GRP78-dependent mechanisms. SARS-CoV-2 infects and replicates in hepatocytes and exerts a PEPCK-dependent gluconeogenic effect in these cells that potentially is a key cause of hyperglycemia in infected patients.

The Effects of Titanium Dioxide Nanoparticles on Osteoblasts Mineralization: A Comparison between 2D and 3D Cell Culture Models.

Although several studies assess the biological effects of micro and titanium dioxide nanoparticles (TiO2 NPs), the literature shows controversial results regarding their effect on bone cell behavior. Studies on the effects of nanoparticles on mammalian cells on two-dimensional (2D) cell cultures display several disadvantages, such as changes in cell morphology, function, and metabolism and fewer cell-cell contacts. This highlights the need to explore the effects of TiO2 NPs in more complex 3D environments, to better mimic the bone microenvironment. This study aims to compare the differentiation and mineralized matrix production of human osteoblasts SAOS-2 in a monolayer or 3D models after exposure to different concentrations of TiO2 NPs. Nanoparticles were characterized, and their internalization and effects on the SAOS-2 monolayer and 3D spheroid cells were evaluated with morphological analysis. The mineralization of human osteoblasts upon exposure to TiO2 NPs was evaluated by alizarin red staining, demonstrating a dose-dependent increase in mineralized matrix in human primary osteoblasts and SAOS-2 both in the monolayer and 3D models. Furthermore, our results reveal that, after high exposure to TiO2 NPs, the dose-dependent increase in the bone mineralized matrix in the 3D cells model is higher than in the 2D culture, showing a promising model to test the effect on bone osteointegration.

Coronary computed tomography plaque-based scores predict long-term cardiovascular events.

OBJECTIVES: Coronary computed tomography angiography (coronary CTA) scores based on luminal obstruction, plaque burden, and characteristics are used for prognostication in coronary artery disease (CAD), such as segmental stenosis and plaque extent involvement and Gensini and Leaman scores. The use of coronary CTA scores for the long-term prognosis remains not completely defined. We sought to evaluate the long-term prognosis of CTA scores for cardiovascular events in symptomatic patients with suspected CAD. METHODS: The presence and extent of CAD were evaluated by coronary CTA in patients from two multicenter prospective studies, which were classified according to several coronary CTA scores. The primary endpoint was major adverse cardiac events (MACE). Two hundred and twenty-two patients were followed up for a median of 6.8 (6.3-9.1) years, and 73 patients met the composite endpoints of MACE. RESULTS: Compared to the clinical prediction model, the highest model improvement was observed when added obstructive CAD. After adjustment for the presence of obstructive CAD, the segment involvement score for non-calcified plaque (SISNoncalc) was independently associated with MACE, presenting incremental prognostic value over clinical data and CAD severity (χ2 39.5 vs 21.2, p < 0.001 for comparison with a clinical model; and χ2 39.5 vs 35.6, p = 0.04 for comparison with clinical + CAD severity). Patients with obstructive CAD and SISNoncalc > 3 were likely to experience events (HR 4.27, 95% CI 2.17-4.40, p < 0.001). CONCLUSIONS: Coronary CTA plaque-based scores provide incremental long-term prognostic value for up to 7 years. Among patients with obstructive CAD, the presence of extensive non-calcified disease (> 3 coronary segments) is associated with increased cardiovascular risk for late events independently of the presence of obstructive CAD. KEY POINTS: • Coronary CTA plaque-based scores are long-term prognostic markers in patients with stable CAD. • Besides obstructive CAD, the segment involvement score of non-calcified disease of 3 or more independently increased the risk of cardiovascular events.

Síndrome de arlequim idiopática: sucesso terapêutico com toxina botulínica / Idiopathic harlequin syndrome: successful therapy with botulium toxin

A síndrome de arlequim é uma rara desordem autonômica que se caracteriza por anidrose e falta de rubor unilateral da face, podendo acometer as regiões cervical e torácica. De forma paradoxal, há rubor e sudorese compensatórios no lado contralateral à alteração. É idiopática na maioria dos casos, mas pode ser congênita, secundária a lesões estruturais e à iatrogenia pós-cirúrgica. O tratamento é direcionado ao fator causal. Descreve-se caso de paciente com diagnóstico de síndrome de arlequim idiopática, sendo realizada aplicação de toxina botulínica na hemiface acometida pelos sintomas compensatórios com boa resposta terapêutica

Harlequin syndrome is a rare autonomic disorder characterized by anhidrosis and lack of unilateral flushing of the face, which may affect the cervical and thoracic regions. Paradoxically, there is compensatory flushing and sweating on the contralateral side to the alteration. It is idiopathic in most cases, but it can be congenital or secondary to structural or post-surgical iatrogenic lesions. Treatment is directed at the causative factor. We describe the case of a patient with a diagnosis of idiopathic Harlequin Syndrome with botulinum toxin application in the hemiface affected by compensatory symptoms with good therapeutic response.

Citopatológico do colo uterino e adequabilidade da amostra: ensaio clínico randomizado controlado / Cervical cytopathology and sample suitability: a randomized controlled clinical trial

Resumo Objetivo Avaliar duas técnicas de coleta cervicovaginal à adequabilidade da amostra e aos demais achados do laudo colpocitopatológico. Métodos O estudo foi realizado no período de setembro de 2018 a julho de 2019, em um centro de saúde-escola, localizado no município de Fortaleza - Ceará. A amostra foi composta por 365 mulheres divididas aleatoriamente, sendo 184 participantes no Grupo Controle (técnica na qual o esfregaço da ectocérvice foi disposto na lâmina antes da coleta do material da endocérvice) e 181 no Grupo Comparação (no qual o esfregaço da ectocérvice vaginal foi disposto na lâmina apenas após a coleta do material da endocérvice). Utilizou-se um instrumento contendo variáveis sociodemográficas, clínicas, sexuais, reprodutivas e referentes aos achados no laudo citopatológico. Incluíram-se mulheres na faixa etária de 18 a 64 anos, que já tinham iniciado vida sexual e que realizaram o exame de prevenção do câncer de colo uterino no período da coleta de dados. Os testes do qui-quadrado, Fisher e Kruskal-Wallis foram utilizados. Resultados Não houve associação estatística entre a adequabilidade da amostra citopatológica às duas técnicas de coleta cervicovaginal empregadas e às demais variáveis clínicas, sexuais, reprodutivas e referentes aos demais achados no laudo citopatológico, obtendo-se valor de p>5% em todas as associações realizadas. Conclusão As duas técnicas de coleta de células cervicais descritas em manuais oficiais não diferiram para a obtenção de uma amostra celular adequada, sendo igualmente eficazes e propiciando a garantia de um laudo colpocitopatológico preciso e oportuno. Registro Brasileiro de Ensaios Clínicos (ReBEC): RBR-2H4MPN.

Resumen Objetivo Evaluar dos técnicas de toma de muestra cervicovaginal con la adecuación de la muestra y con los demás resultados del informe colpocitológico. Métodos El estudio fue realizado durante el período de septiembre de 2018 a julio de 2019, en un centro de salud-escuela, ubicado en el municipio de Fortaleza, estado de Ceará. La muestra estaba compuesta por 365 mujeres divididas aleatoriamente, de las cuales 184 participantes estaban en el Grupo Control (técnica por la que el frotis del ectocérvix fue colocado en la lámina antes de la toma del material del endocérvix) y 181 en el Grupo Comparación (en el que el frotis del ectocérvix vaginal fue colocado sobre la lámina únicamente después de la toma del material del endocérvix). Se utilizó un instrumento con variables sociodemográficas, clínicas, sexuales, reproductivas y relativas a los resultados del informe citológico. Fueron incluidas mujeres del grupo de edad de 18 a 64 años, que ya habían empezado su vida sexual y que realizaron la prueba de prevención de cáncer de cuello uterino durante el período de la recopilación de datos. Se utilizaron las pruebas χ2 de Pearson, Fisher y Kruskal-Wallis. Resultados No hubo asociación estadística entre la adecuación de la muestra citológica con las dos técnicas de toma cervicovaginal utilizadas y con las demás variables clínicas, sexuales, reproductivas y referentes a los demás resultados del informe citológico, y se obtuvo un valor de p>5 % en todas las asociaciones realizadas. Conclusión Las dos técnicas de toma de células cervicales que se describen en manuales oficiales no difirieron en la obtención de una muestra celular adecuada y son igualmente eficaces y favorecen la garantía de un informe colpocitológico preciso y oportuno.

Abstract Objective To assess two cervicovaginal collection techniques to sample suitability and the other findings of Pap smear. Methods The study was conducted from September 2018 to July 2019, in a school health center located in the city of Fortaleza - Ceará. The sample consisted of 365 women randomly divided, with 184 participants in the Control Group (technique in which the ectocervix smear was placed on the slide before endocervical material was collected) and 181 in the Comparison Group (in which the vaginal ectocervix smear was placed on the slide only after collecting the material from the endocervix). An instrument containing sociodemographic, clinical, sexual, reproductive and findings in cytopathological report was used. Women aged between 18 and 64 years, who had already started their sexual life and who underwent the cervical cancer prevention test during the data collection period, were included. Chi-square, Fisher and Kruskal-Wallis tests were used. Results There was no statistical association between cytopathological sample suitability for the two cervicovaginal collection techniques used and for the other clinical, sexual, reproductive and other variables related to the other findings in cytopathological report, obtaining a value of p>5% in all associations performed. Conclusion The two techniques for collecting cervical cells described in official manuals did not differ for obtaining an adequate cell sample, being equally effective and providing the guarantee of an accurate and timely Pap smear. Brazilian Clinical Trial Registry (ReBEC): RBR-2H4MPN.

Desenvolvimento de cartilha como tecnologia educacional para alívio da dor do parto / Elaboración de cartilla como tecnología educativa para el alivio del dolor de parto / Development of a booklet as an educational technology for birth pain relief

Resumo Objetivo Descrever os processos de construção e validação de cartilha educativa sobre métodos não farmacológicos para alívio da dor no trabalho de parto e parto. Métodos Estudo metodológico, realizado em três etapas. Na primeira, foi realizado levantamento bibliográfico para seleção dos conteúdos referentes à temática. Na segunda etapa, realizou-se validação com 24 juízes de conteúdo e três juízes técnicos. Na terceira etapa, ocorreu validação pelo público-alvo, com 30 gestantes. O período do estudo foi de setembro a novembro de 2018. Foi utilizado o editor de planilhas do Office para análise dos dados. Resultados O nível de concordância atribuído pelos juízes de conteúdo e técnicos esteve entre 97,2% e 98,9% e entre 83,3% e 100%, respectivamente; o Índice de Validade de Conteúdo global foi de 0,92 e 0,97, respectivamente. Na avaliação realizada com o Suitability Assesment of Materials, os juízes de conteúdo classificaram a cartilha como "superior", com média de 85,2% e os técnicos com média de 77,5%. O público-alvo validou a cartilha com Índice de Validade de Conteúdo global de 0,98 e nível de concordância de 99,7%. Conclusão A cartilha educativa mostrou-se válida para ser utilizada junto às gestantes, sendo considerada tecnologia educativa inovadora e relevante na utilização em consulta pré-natal.

Resumen Objetivo Describir el proceso de elaboración y validación de cartilla educativa sobre métodos no farmacológicos para aliviar el dolor en el trabajo de parto y en el parto. Métodos Estudio metodológico, realizado en tres etapas. En la primera, se realizó el análisis bibliográfico para seleccionar contenidos relacionados con la temática. En la segunda etapa, se realizó la validación con 24 jueces de contenido y tres jueces técnicos. En la tercera etapa, se llevó a cabo la validación por parte del público destinatario, con 30 mujeres embarazadas. El período de estudio fue de septiembre a noviembre de 2018. Se utilizó el editor de planillas de Office para el análisis de datos. Resultados El nivel de concordancia atribuido por los jueces de contenido fue entre 97,2 % y 98,9 % y de los técnicos entre 83,3 % y 100 %. El Índice de Validez de Contenido global fue de 0,92 y 0,97, respectivamente. En la evaluación realizada con Suitability Assesment of Materials, los jueces de contenido clasificaron la cartilla como "superior", con promedio de 85,2 % y los técnicos con promedio de 77,5 %. El público destinatario validó la cartilla con Índice de Validez de Contenido global de 0,98 y nivel de concordancia de 99,7 %. Conclusión La cartilla educativa demostró ser válida para ser utilizada con mujeres embarazadas y fue considerada una tecnología educativa innovadora y relevante para utilizar en consultas de control prenatal.

Abstract Objective To describe the construction and validity of an educational booklet on non-pharmacological methods for labor and birth pain relief. Methods This is a methodological study, carried out in three stages. In the first, a bibliographic survey was carried out to select the contents related to the theme. In the second stage, validity was carried out with 24 content judges and three technical judges. In the third stage, there was validity by the target audience, with 30 pregnant women. The study took place from September to November 2018. The Office spreadsheet editor was used for data analysis. Results The level of agreement attributed by the content and technical judges was between 97.2% and 98.9% and between 83.3% and 100%, respectively. The overall Content Validity Index was 0.92 and 0.97, respectively. In the assessment carried out with the Suitability Assessment of Materials, the content judges classified the booklet as "superior", with an average of 85.2%, and the technicians, with an average of 77.5%. The target audience validated the booklet with an overall Content Validity Index of 0.98 and an agreement level of 99.7%. Conclusion The educational booklet proved to be valid for use with pregnant women, being considered innovative and relevant educational technology for use in prenatal consultation.

Effect of educational intervention for compliance of school adolescents with the human papillomavirus vaccine.

OBJECTIVE: to assess the effects of "Piss off, HPV!", an educational intervention to increase adolescents' knowledge, attitude and compliance with human papillomavirus vaccination. METHOD: a randomized clinical trial by cluster, carried out in six schools in two municipalities in Ceará, with 238 girls. The control group (n = 120) received routine instructions, and the intervention group (n = 118), printed message cards about the quadrivalent HPV vaccine. A pre- and post-intervention knowledge, attitude and practice survey was applied to both groups. The McNemar test, to analyze knowledge, attitude and pre- and post-intervention practice, the chi-square test, to compare compliance in relation to knowledge and attitude, and a logistic regression model, to assess vaccine compliance, were carried out. A significance level of 5% was adopted. RESULTS: pre-intervention, knowledge was inadequate and attitude was adequate in both groups. Post-intervention, adequate knowledge and practices became greater in the intervention group. Adequate post-intervention knowledge and attitude, in addition to being 12 years of age or older, increase the chance for vaccination, explaining 70% of the practice. CONCLUSION: the educational intervention was effective for adolescents' knowledge and compliance with the quadrivalent HPV vaccine. UTN: U1111-1254-5546; ReBEC: RBR-107hzdqt.

In vivo schistosomicidal activity of (±)-licarin A-loaded poly(ε-caprolactone) nanoparticles.

Schistosomiasis mansoni is an infectious parasitic disease caused by worms of the genus Schistosoma, and praziquantel (PZQ) is the medication available for the treatment of schistosomiasis. However, the existence of resistant strains reinforces the need to develop new schistosomicidal drugs safely and effectively. Thus, the (±)-licarin A neolignan incorporated into poly-Ɛ-caprolactone (PCL) nanoparticles and not incorporated were evaluated for their in vivo schistosomicidal activity. The (±)-licarin A -loaded poly(ε-caprolactone) nanoparticles and the pure (±)-licarin A showed a reduction in the number of worm eggs present in spleens of mice infected with Schistosoma mansoni. In addition, the (±)-licarin A incorporated in the concentration of 20 mg/kg and 200 mg/kg reduced the number of worms, presenting percentages of 56.3% and 41.7%, respectively.

Celastrol: A lead compound that inhibits SARS-CoV-2 replication, the activity of viral and human cysteine proteases, and virus-induced IL-6 secretion.

The global emergence of coronavirus disease 2019 (COVID-19) has caused substantial human casualties. Clinical manifestations of this disease vary from asymptomatic to lethal, and the symptomatic form can be associated with cytokine storm and hyperinflammation. In face of the urgent demand for effective drugs to treat COVID-19, we have searched for candidate compounds using in silico approach followed by experimental validation. Here we identified celastrol, a pentacyclic triterpene isolated from Tripterygium wilfordii Hook F, as one of the best compounds out of 39 drug candidates. Celastrol reverted the gene expression signature from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells and irreversibly inhibited the recombinant forms of the viral and human cysteine proteases involved in virus invasion, such as Mpro (main protease), PLpro (papain-like protease), and recombinant human cathepsin L. Celastrol suppressed SARS-CoV-2 replication in human and monkey cell lines and decreased interleukin-6 (IL-6) secretion in the SARS-CoV-2-infected human cell line. Celastrol acted in a concentration-dependent manner, with undetectable signs of cytotoxicity, and inhibited in vitro replication of the parental and SARS-CoV-2 variant. Therefore, celastrol is a promising lead compound to develop new drug candidates to face COVID-19 due to its ability to suppress SARS-CoV-2 replication and IL-6 production in infected cells.

Crotoxin modulates inflammation and macrophages' functions in a murine sepsis model.

Sepsis is a syndrome of physiological and biochemical abnormalities induced by an infection that represents a major public health concern. It involves the early activation of inflammatory responses. Crotoxin (CTX), the major toxin of the South American rattlesnake Crotalus durissus terrificus venom, presents longstanding anti-inflammatory properties. Since immune system modulation may be a strategic target in sepsis management, and macrophages' functional and secretory activities are related to the disease's progression, we evaluated the effects of CTX on macrophages from septic animals. Balb/c male mice submitted to cecal ligation and puncture (CLP) were treated with CTX (0.9 µg/animal, subcutaneously) 1 h after the procedure and euthanized after 6 h. We used plasma samples to quantify circulating cytokines and eicosanoids. Bone marrow differentiated macrophages (BMDM) were used to evaluate the CTX effect on macrophages' functions. Our data show that CTX administration increased the survival rate of the animals from 40% to 80%. Septic mice presented lower plasma concentrations of IL-6 and TNF-α after CTX treatment, and higher concentrations of LXA4, PGE2, and IL-1ß. No effect was observed in IL-10, IFN-γ, and RD1 concentrations. BMDM from septic mice treated with CTX presented decreased capacity of E. coli phagocytosis, but sustained NO and H2O2 production. We also observed higher IL-6 concentration in the culture medium of BMDM from septic mice, and CTX induced a significant reduction. CTX treatment increased IL-10 production by macrophages as well. Our data show that the protective effect of CTX in sepsis mortality involves modulation of macrophage functions and inflammatory mediators' production.

Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells.

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.