Emerging Challenges of Mpox Transmission: An In-depth Scoping Review and Evidence Mapping on Breastfeeding Practices in South America.

BACKGROUND: In 2022, a marked escalation in Monkeypox (Mpox) cases was observed in nonendemic regions, notably South America, despite the virus being traditionally endemic to Central and West Africa. This unexpected shift necessitated a deeper exploration of the novel transmission dynamics, including breastfeeding, given the emerging evidence of potential horizontal and vertical Mpox transmission during mother-infant interactions. RESEARCH AIM: The study aimed to critically evaluate existing evidence on potential horizontal and vertical Mpox transmission related to breastfeeding and to assess guidelines in South American countries regarding Mpox prevention during breastfeeding. METHODS: A scoping review and evidence mapping were conducted, adhering to the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guideline. Data extraction involved identifying primary studies evaluating breastfeeding as a transmission route. Additionally, official documents from South American Health Ministries detailing guidelines or policies on breastfeeding in the context of maternal Mpox infection were reviewed. RESULTS: Three of 215 studies were found relevant; 2 were case reports, and 1 was a laboratory study. Available evidence suggests that contamination could likely occur horizontally through skin-to-skin contact. Six South American countries had issued guidelines on breastfeeding during Mpox infection, but the guidance varied and was not consistent across the region. CONCLUSIONS: The study emphasizes the need for clear and consistent guidelines on breastfeeding during Mpox outbreaks, particularly in South America. Collaborative strategies and regular research updates will be essential in addressing the ongoing public health challenge.

Quality of life and metamemory in higher education students during the COVID-19 pandemic / Qualidade de vida e metamemória em estudantes do nível superior durante a pandemia da COVID-19

ABSTRACT Purpose: to analyze the quality of life and metamemory and verify their predictors in students during the COVID-19 pandemic. Methods: a cross-sectional survey carried out through online collection with the application of an initial questionnaire to characterize the sample, the WHOQOL-brief to investigate the quality of life, and the Metamemory Questionnaire in Adults (short version) - MIAr to evaluate metamemory in a group of undergraduate and postgraduate students. Data were analyzed using descriptive and inferential statistics. Multiple linear regression was performed to verify the predictor variables. A significance level of 5% (p ≤ 0.05) was considered. Results: 977 university students participated in the study, the majority (70.73%) of whom were females and with an income range below three minimum wages (63.56%). For quality of life, income range, being in the risk group for COVID-19, and age were predictors for both the undergraduate and postgraduate groups. In contrast, on an excellent metamemory, the predictors were male gender and age. Conclusion: for students, during the COVID-19 pandemic, the main predictor of quality of life was having a higher income bracket, and the main predictor of metamemory was being a male.

RESUMO Objetivo: analisar a qualidade de vida e a metamemória e verificar seus preditores em estudantes durante a pandemia da COVID-19. Métodos: trata-se de uma pesquisa transversal realizada por meio de coleta online com a aplicação de um questionário inicial para caracterizar a amostra, do WHOQOL-bref para investigar a qualidade de vida e do Questionário de Metamemória em Adultos (versão reduzida) - MIAr para avaliar a metamemória, em um grupo de estudantes de graduação e outro de pós-graduação. Os dados foram analisados por meio de estatística descritiva e inferencial. Realizou-se a regressão linear múltipla para verificar as variáveis preditoras. Foi considerado o nível de significância de 5% (p≤0,05). Resultados: participaram do estudo 977 universitários, sendo a maioria (70,73%) do gênero feminino e com faixa de renda menor que três salários-mínimos (63,56%). Para a qualidade de vida, tanto para o grupo de graduandos quanto de pós-graduandos, a faixa de renda, o grupo de risco para COVID-19 e a idade foram preditores, enquanto para uma boa metamemória os preditores foram o gênero masculino e a idade. Conclusão: para os estudantes, durante a pandemia da COVID-19, o principal preditor da qualidade de vida foi possuir maior faixa de renda e o da metamemória foi ser do gênero masculino.

The Cytoplasmic Region of SARAF Reduces Triple-Negative Breast Cancer Metastasis through the Regulation of Store-Operated Calcium Entry.

Triple-negative breast cancer has a poor prognosis and is non-responsive to first-line therapies; hence, new therapeutic strategies are needed. Enhanced store-operated Ca2+ entry (SOCE) has been widely described as a contributing factor to tumorigenic behavior in several tumor types, particularly in breast cancer cells. SOCE-associated regulatory factor (SARAF) acts as an inhibitor of the SOCE response and, therefore, can be a potential antitumor factor. Herein, we generated a C-terminal SARAF fragment to evaluate the effect of overexpression of this peptide on the malignancy of triple-negative breast cancer cell lines. Using both in vitro and in vivo approaches, we showed that overexpression of the C-terminal SARAF fragment reduced proliferation, cell migration, and the invasion of murine and human breast cancer cells by decreasing the SOCE response. Our data suggest that regulating the activity of the SOCE response via SARAF activity might constitute the basis for further alternative therapeutic strategies for triple-negative breast cancer.

Depressão em indivíduos transgêneros atendidos em um hospital universitário / Depression in transgender individuals assisted at a university hospital / Depresión en individuos transexuales atendidos en un hospital universitario

O objetivo deste estudo foi avaliar a presença e a gravidade de sintomas depressivos em indivíduos transexuais atendidos em um ambulatório de sexualidade. Caracteriza-se como descritivo, transversal e quantitativo, adotando amostra por conveniência (n=46). Foi realizado nas dependências do HUUFMA mediante aplicação do Inventário de Depressão de Beck (BDI-II) e formulário sociodemográfico. Os dados foram abordados no EpiInfo. Os resultados demostraram indivíduos na maioria jovens, de cor parda, solteiros, com ensino médio completo, estudantes, residiam com pais e/ou parentes, não religiosos, e metade com vínculo empregatício. A depressão moderada e grave esteve presente em 37% dos pacientes e a ideação suicida em 34,8%. Identificou- se relevância estatística na relação entre em depressão e vínculo empregatício (depressão moderada 39,2% e grave 21,7%). Então, observou-se relevantemente sintomas depressivos e, por vezes, a ideação suicida, todavia, o suporte social e o vínculo de trabalho foram importantes na redução de seu adoecimento.

The aim of this study was to assess the presence and severity of depressive symptoms in transsexual individuals treated at a sexuality outpatient clinic. It is characterized as descriptive, transversal and quantitative, adopting a convenience sample (n=46). It was carried out at the HUUFMA premises by applying the Beck Depression Inventory (BDI-II) and a sociodemographic form. The data were approached in EpiInfo. The results showed mostly young individuals, of brown race, single, with complete secondary education, students, living with parents and/or relatives, non-religious, and half with employment. Moderate and severe depression was present in 37% of patients and suicidal ideation in 34.8%. Statistical relevance was identified in the relationship between depression and employment (moderate depression 39.2% and severe depression 21.7%). So, depressive symptoms and, sometimes, suicidal ideation were observed relevantly, however, social support and the work bond were important in reducing his illness.

El objetivo de este estudio fue evaluar la presencia y la gravedad de los síntomas depresivos en individuos transexuales atendidos en un ambulatorio de sexualidad. Se caracteriza por ser descriptivo, transversal y cuantitativo, adoptando una muestra de conveniencia (n=46). Se realizó en las instalaciones del HUUFMA aplicando el Inventario de Depresión de Beck (BDI-II) y un formulario sociodemográfico. Los datos fueron abordados en EpiInfo. Los resultados mostraron individuos mayoritariamente jóvenes, de raza morena, solteros, con estudios secundarios completos, estudiantes, que vivían con sus padres y/o familiares, no religiosos, y la mitad con empleo. La depresión moderada y grave estaba presente en el 37% de los pacientes y la ideación suicida en el 34,8%. Se identificó relevancia estadística en la relación entre depresión y empleo (depresión moderada 39,2% y depresión grave 21,7%). Así, se observó relevancia de los síntomas depresivos y, en ocasiones, de la ideación suicida, sin embargo, el apoyo social y el vínculo laboral fueron importantes en la reducción de su enfermedad.

Ansiedade em transgêneros acompanhados em um ambulatório de sexualidade maranhense / Anxiety in transgenders accompanied in a maranhão sexuality outpatient clinic / Ansiedad en transgéneros acompañada de una ambulatoria de sexualidad maranhena

O objetivo deste estudo foi avaliar os sintomas ansiosos em indivíduos transexuais atendidos em um ambulatório de gênero e sexualidade. Caracteriza-se como um estudo descritivo, de corte transversal e abordagem quantitativa, adotando amostra por conveniência (n=46). Foi realizado nas dependências de um Hospital Universitário Nordestino mediante aplicação do Inventário de Ansiedade de Beck (BAI) e formulário sociodemográfico, os dados coletados foram trabalhados no EpiInfo. Os resultados revelaram trans em sua maioria jovens, de cor parda, solteiros, com ensino médio completo, estudantes, residiam com pais e/ou parentes, não religiosos, e metade com vínculo empregatício. A ansiedade leve esteve presente em 21,7% e mínima em 34,8% dos pacientes, enquanto, a moderada em 28,3% e a grave 15,2%. Identificou-se relevância estatística na associação entre ansiedade e idade (p= 0,0072), e de ansiedade com vínculo empregatício (p=0,0039). Portanto, demonstrou-se que a maioria dos entrevistados apresentaram com menor severidade sintomas ansiosos, podendo ter relação com seu maior grau de instrução, presença de suporte social e presença de vínculo de trabalho.

The objective of this study was to evaluate anxious symptoms in transgender individuals attended in an outpatient clinic of gender and sexuality. It is characterized as a descriptive, cross-sectional and quantitative study, adopting a sample for convenience (n=46). It was carried out in the premises of a Northeastern University Hospital by applying the Beck Anxiety Inventory (BAI) and sociodemographic form, the data collected were worked on at EpiInfo. The results revealed that the majority of them were young, of a brown color, single, with a full high school education, students, resided with parents and/or relatives, non-religious, and half with employment. Mild anxiety was present in 21.7% and minimal in 34.8% of the patients, while moderate in 28.3% and severe in 15.2%. Statistical relevance was identified in the association between anxiety and age (p= 0.0072), and anxiety with employment (p=0.0039). Therefore, it was demonstrated that the majority of the interviewees presented with less severity anxious symptoms, which may have a relationship with their higher degree of education, presence of social support and presence of a work bond.

El objetivo de este estudio fue evaluar los síntomas ansiosos en los individuos transgénero atendidos en una clínica ambulatoria de género y sexualidad. Se caracteriza por un enfoque descriptivo, transversal y cuantitativo, tomando una muestra para su conveniencia (n=46). Se realizó en las instalaciones de un Hospital Universitario del Noreste, aplicando el Inventario de Ansiedad Beck (BAI) y el formulario sociodemográfico, los datos recogidos se trabajaron en EpiInfo. Los resultados revelaron transexuales en la mayoría de los jóvenes, de color marrón, solteros, estudiantes de secundaria, que vivían con padres y/o parientes, no religiosos y la mitad con un vínculo laboral. La ansiedad leve fue del 21,7% y mínima del 34,8% de los pacientes, mientras que la moderada fue del 28,3% y la grave del 15,2%. Se identificó la relevancia estadística en la asociación entre ansiedad y edad (p= 0,0072) y ansiedad con relación al empleo (p=0,0039). Por lo tanto, se demostró que la mayoría de los entrevistados presentaban síntomas menos ansiosos, que podían tener relación con su nivel de educación superior, la presencia de apoyo social y la presencia de un vínculo de trabajo.

Aspectos audiológicos e cognitivos em adultos com Diabetes Mellitus tipo 2 / Auditory and cognitive aspects in adults with type 2 Diabetes Mellitus / Aspectos auditivos y cognitivos en adultos con Diabetes Mellitus tipo 2

Introdução: A Diabetes Mellitus (DM) é um distúrbio metabólico causado pela ausência ou diminuição da secreção de insulina ou por alterações do funcionamento deste hormônio no organismo, podendo envolver alterações físicas e cognitivas. Objetivo: Analisar os aspectos audiológicos e cognitivos de adultos com Diabetes Mellitus tipo 2. Método: Estudo transversal realizado em pessoas com idade entre 18 e 59 anos, de ambos os gêneros. Os participantes foram divididos em dois grupos: Grupo Estudo (GE) - pessoas com diagnóstico de Diabetes Mellitus e o Grupo Controle (GC) - pessoas sem Diabetes. Todos foram submetidos à avaliação glicêmica, cognitiva e audiológica. Para análise estatística foi utilizado o teste de Mann-Whitney, sendo estipulado o nível de significância de 0,05. Resultados: Participaram do estudo 32 indivíduos sendo 19 (59,4%) no GE e 13 (40,6%) no GC. A média de idade dos participantes foi de 46,8 ± 8,3 anos, com escolaridade média de 6,8 ± 6 anos, sendo 25 (78,1%) do gênero feminino e 7 (21,9%) do masculino. Foi observada diferença estatisticamente significativa entre os grupos para a pontuação referente à atenção e cálculo, recordação e escore total do MEEM, com pior desempenho no GE. Não foi observada diferença estatisticamente significante entre os grupos nos aspectos audiológicos avaliados. Conclusão: Indivíduos com Diabetes Mellitus tipo 2 não apresentaram riscos para alterações audiológicas com os instrumentos utilizados, entretanto apresentaram um alto risco para alterações cognitivas. Os achados demonstram que o acompanhamento fonoaudiológico constante é essencial para identificar as alterações precocemente.

Introduction: Diabetes Mellitus (DM) is a metabolic disorder caused by the absence or reduction of insulin secretion or by changes in the functioning of this hormone in the body, which may involve physical and cognitive changes. Objective: To analyze the audiological and cognitive aspects of type 2 Diabetes Mellitus in adults. Method: Cross-sectional study carried out in people aged between 18 and 59 years, of both genders. Participants were divided into two groups: Study Group (SG) - people diagnosed with Diabetes Mellitus and the Control Group (CG) - people without Diabetes. All underwent glycemic, cognitive and auditory assessment. Mann-Whitney's test was used for statistical analysis, with a significance level of 0.05. Results: 32 individuals participated in the study, 19 (59.4%) in the EG and 13 (40.6%) in the CG. The mean age of the participants was 46.8 ± 8.3 years, with a mean education of 6.8 ± 6 years, with 25 (78.1%) females and 7 (21.9%) males. A statistically significant difference was observed between the groups for the score related to attention and calculation, recall and total Mini-Mental State Examination (MMSE) score, with worse performance in the EG. There was no statistically significant difference between the groups regarding the audiological aspects evaluated. Conclusion: Individuals with type 2 Diabetes Mellitus did not present risks for audiological alterations, however they presented a high risk for cognitive alterations. the findings demonstrate that constant speech therapy monitoring is essential to identify changes early.

Introducción: La Diabetes Mellitus (DM) es un trastorno metabólico causado por la ausencia o reducción de la secreción de insulina o por alteraciones en el funcionamiento de esta hormona en el organismo que puede implicar alteraciones físicas y cognitivas. Objetivo: Analizar los aspectos audiológicos y cognitivos de adultos con Diabetes Mellitus tipo 2. Método: Estudio transversal realizado en personas de entre 18 y 59 años, de ambos sexos. Los participantes se dividieron en dos grupos: Grupo de Estudio (GE) - personas diagnosticadas con diabetes mellitus y Grupo Control (GC) - personas sin Diabetes. Todos se sometieron a evaluación glucémica, cognitiva y audiológica. Para el análisis estadístico se utilizó la prueba de Mann-Whitney, con un nivel de significancia de 0.05. Resultados:Treinta y dos individuos participaron en el estudio, 19 (59,4%) en el GE y 13 (40,6%) en el GC. La edad media de los participantes fue de 46,8 ± 8,3 años, con una educación media de 6,8 ± 6 años, con 25 (78,1%) mujeres y 7 (21,9%) hombres. Se observó diferencia estadísticamente significativa entre los grupos para la puntuación relacionada con atención y cálculo, recuerdo y puntuación total del MEEM, con peor desempeño en el GE. No hubo diferencia estadísticamente significativa entre los grupos en los aspectos audiológicos evaluados. Conclusión: Los individuos con Diabetes Mellitus tipo 2 no presentaban riesgo de alteraciones audiológicas, sin embargo presentaban un alto riesgo de alteraciones cognitivas. Los resultados demuestran que el monitoreo constante de la terapia del habla es esencial para identificar cambios temprano.

Função mastigatória nos diferentes ciclos de vida: análise eletromiográfica / Chewing function in different life cycles: analysis with electromyography / Función masticatoria en diferentes ciclos de vida: análisis con electromiografía

Introdução: A mastigação tem uma importância significativa para o desenvolvimento das estruturas do Sistema Estomatognático (SE), sendo esta aperfeiçoada no decorrer da vida. A eletromiografia de superfície destaca-se como uma importante ferramenta de avaliação capaz de quantificar a atividade elétrica dos músculos mastigatórios, sendo uma forma de caracterizar o comportamento dessa função estomatognática. Observando a complexidade e importância da mastigação, torna-se importante conhecer melhor as modificações desta função no decorrer dos ciclos de vida. Objetivo: O objetivo do estudo foi realizar análise eletromiográfica dos músculos da mastigação em indivíduos sem queixas orofaciais representantes dos ciclos da infância, adolescência, fase adulta e senescência. Método: A amostra foi composta por 120 voluntários de ambos os sexos, distribuídos em quatro grupos de acordo com a faixa de idade. Os voluntários foram submetidos à avaliação da mastigação por meio da eletromiografia de superfície durante o repouso, contração voluntária máxima, mastigações unilaterais direita e esquerda e mastigação habitual; bem como a verificação da força de mordida entre os dentes incisivos centrais, molares do lado direito e molares do lado esquerdo. Realizou-se, ainda, a tomada de medidas antropométricas faciais das hemifaces direta e esquerda dos voluntários. Resultados: Os resultados apontaram comportamentos morfológicos e funcionais distintos entre os grupos estudados, bem como a influência da variável sexo nas respostas eletrofisiológicas da função mastigatória. Conclusão: foi verificado que o comportamento mastigatório variou segundo a idade e o sexo, apontando uma tendência de correlação entre os componetes anatômicos e funcionais envolvidos nessa função estomatognática.

Introduction: Chewing is of significant importance for the development of the structures of the Stomatognathic System (SE), which is improved throughout life. Surface electromyography stands out as an important assessment tool capable of quantifying the electrical activity of the masticatory muscles, being a way to characterize the behavior of this stomatognathic function. Observing the complexity and importance of chewing, it is important to better understand the changes in this function during the life cycles. Objective: The objective of the study was to perform an electromyographic analysis of the muscles of mastication in individuals without orofacial complaints representing the cycles of childhood, adolescence, adulthood and senescence. Method: The sample consisted of 120 volunteers of both sexes, distributed in four groups according to the age group. The volunteers underwent chewing assessment by means of surface electromyography during rest, maximum voluntary contraction, unilateral right and left chewing and habitual chewing; as well as the verification of the bite force between the central incisor teeth, molars on the right side and molars on the left side. Facial anthropometric measurements of the direct and left hemifaces of the volunteers were also taken. Results: The results showed distinct morphological and functional behaviors between the groups studied, as well as the influence of the gender variable on the electrophysiological responses of the masticatory function. Conclusion: it was found that the masticatory behavior varied according to age and sex, pointing to a trend of correlation between the anatomical and functional components involved in this stomatognathic function.

Introducción: La masticación es de gran importancia para el desarrollo de las estructuras del Sistema Estomatognático (SE), que se mejora a lo largo de la vida. La electromiografía de superficie se destaca como una importante herramienta de evaluación capaz de cuantificar la actividad eléctrica de los músculos masticatorios, siendo una forma de caracterizar el comportamiento de esta función estomatognática. Observando la complejidad de esta función, es importante conocer mejor los cambios de esta función durante los ciclos de vida. Objetivo: El objetivo del estudio fue realizar un análisis electromiográfico de los músculos de la masticación en individuos sin quejas orofaciales representando los ciclos de niñez, adolescencia, adultez y senescencia. Método: La muestra estuvo formada por 120 voluntarios de ambos sexos, distribuidos en cuatro grupos según el grupo de edad. Los voluntarios fueron sometidos a valoración masticatoria mediante electromiografía de superficie en reposo, máxima contracción voluntaria, masticación unilateral derecha e izquierda y masticación habitual; así como la verificación de la fuerza de mordida entre los incisivos centrales, molares del lado derecho y molares del lado izquierdo. También se tomaron medidas antropométricas faciales de los hemifaces directo e izquierdo de los voluntarios. Resultados: Los resultados mostraron distintos comportamientos morfológicos y funcionales entre los grupos estudiados, así como la influencia de la variable género en las respuestas electrofisiológicas de la función masticatoria. Conclusión: se encontró que el comportamiento masticatorio varió según la edad y el sexo, apuntando a una tendencia de correlación entre los componentes anatómicos y funcionales involucrados en esta función estomatognática.

Artichoke extracts with potential application in chemoprevention and inflammatory processes

Abstract The aim of this work is to study three cultivars of artichoke (Cynara cardunculus var. scolymus): Gauchito, Guri and Oro Verde in terms of their in vitro chemoprevention and anti-inflammatory properties. These cultivars show good productive performance. The phenolic composition of their fresh leaves and edible bracts was analyzed by high performance liquid chromatography and high resolution mass spectrometry (HPLC-HRMS), showing mainly caffeoylquinic acids and flavonoids. Caffeoylquinic acids were quantified and the highest content was found in Gauchito cultivar. In this cultivar, the content of dicaffeoylquinic acids in fresh bracts was six times higher than that in fresh leaves (10064.5 ± 378.3 mg/kg versus 1451.0 ± 209.3 mg/kg respectively). Luteolin flavonoids were detected in leaves. The extracts from fresh bracts and leaves were assessed in their in vitro bioactivity against human neuroblastoma cells (SH-SY5Y). Inhibition of SH-SY5Y cells proliferation by Gauchito and Guri leaf extracts (8 µg/mL) was higher than 50 %. The leaf extracts of the same cultivars showed an inhibitory effect on human interferon IFN-I, decreasing its activity 50% at 40 µg/mL. Interestingly, the bract extracts did not show in vitro bioactivity at these concentrations, nor did the pure compounds chlorogenic acid, cynarin, apigenin and luteolin (at 2 µg/mL). These results suggest that Gauchito and Guri leaf extracts have potential for human neuroblastoma chemoprevention and treatment of inflammatory processes.

TRP Channels Interactome as a Novel Therapeutic Target in Breast Cancer.

Breast cancer is one of the most frequent cancer types worldwide and the first cause of cancer-related deaths in women. Although significant therapeutic advances have been achieved with drugs such as tamoxifen and trastuzumab, breast cancer still caused 627,000 deaths in 2018. Since cancer is a multifactorial disease, it has become necessary to develop new molecular therapies that can target several relevant cellular processes at once. Ion channels are versatile regulators of several physiological- and pathophysiological-related mechanisms, including cancer-relevant processes such as tumor progression, apoptosis inhibition, proliferation, migration, invasion, and chemoresistance. Ion channels are the main regulators of cellular functions, conducting ions selectively through a pore-forming structure located in the plasma membrane, protein-protein interactions one of their main regulatory mechanisms. Among the different ion channel families, the Transient Receptor Potential (TRP) family stands out in the context of breast cancer since several members have been proposed as prognostic markers in this pathology. However, only a few approaches exist to block their specific activity during tumoral progress. In this article, we describe several TRP channels that have been involved in breast cancer progress with a particular focus on their binding partners that have also been described as drivers of breast cancer progression. Here, we propose disrupting these interactions as attractive and potential new therapeutic targets for treating this neoplastic disease.

RBD-specific polyclonal F(ab´)2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial.

BACKGROUND: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2. METHODS: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984). FINDINGS: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65•1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5•28% [-3•95; 14•50]; p = 0•15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14•2 (± 0•7) days in the INM005 group and 16•3 (± 0•7) days in the placebo group, hazard ratio 1•31 (95% CI 1•0 to 1•74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6•9% the INM005 group and 11•4% in the placebo group (risk difference [95% IC]: 0•57 [0•24 to 1•37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported. INTERPRETATION: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.

Inhibition of InsP3R with Xestospongin B Reduces Mitochondrial Respiration and Induces Selective Cell Death in T Cell Acute Lymphoblastic Leukemia Cells.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy whose chemoresistance and relapse persist as a problem despite significant advances in its chemotherapeutic treatments. Mitochondrial metabolism has emerged as an interesting therapeutic target given its essential role in maintaining bioenergetic and metabolic homeostasis. T-ALL cells are characterized by high levels of mitochondrial respiration, making them suitable for this type of intervention. Mitochondrial function is sustained by a constitutive transfer of calcium from the endoplasmic reticulum to mitochondria through the inositol 1,4,5-trisphosphate receptor (InsP3R), making T-ALL cells vulnerable to its inhibition. Here, we determine the bioenergetic profile of the T-ALL cell lines CCRF-CEM and Jurkat and evaluate their sensitivity to InsP3R inhibition with the specific inhibitor, Xestospongin B (XeB). Our results show that T-ALL cell lines exhibit higher mitochondrial respiration than non-malignant cells, which is blunted by the inhibition of the InsP3R. Prolonged treatment with XeB causes T-ALL cell death without affecting the normal counterpart. Moreover, the combination of XeB and glucocorticoids significantly enhanced cell death in the CCRF-CEM cells. The inhibition of InsP3R with XeB rises as a potential therapeutic alternative for the treatment of T-ALL.

Corrección de mielomeningocele intrautero: Reporte del primer caso en Ecuador / Case report: First intrauterine myelomeningocele correction in Ecuador

This is the case of a 26 year old patient, at week 27 of gestational age and with a prenatal diagnosis of myelomeningocele. It was decided to enter the clinic to perform the first correction of the spina bifida defect in Ecuador, with the support of a multidisciplinary team of national and foreign professionals. This procedure was carried out within international parameters and standards for the management of this pathology, with the equipment, supplies and trained personnel to carry this surgery to a successful outcome, both for the fetus and its mother. It is demonstrated that our country has the capacity of both human resources and equipment to solve highly complex pathologies.

Se trata del caso de una paciente de 26 años, en la semana 27 de edad gestacional y con un diagnóstico prenatal de mielome- ningocele. Se decide ingresar a la clínica para realizar la primera corrección de defecto de espina bífida del Ecuador, con apoyo de un equipo multidisciplinario de profesionales nacionales y extranjeros. Este procedimiento se llevó a cabo dentro de parámetros y estándares internacionales de manejo de esta patología, contando con los equipos, insumos y el personal capacitado para llevar esta cirugía a un desenlace exitoso, tanto para el feto como su madre. Queda demostrado que en nuestro país se cuenta con la capacidad tanto de recursos humanos y equipos para resolver patologías de gran complejidad.

TRP Channels Regulation of Rho GTPases in Brain Context and Diseases.

Neurological and neuropsychiatric disorders are mediated by several pathophysiological mechanisms, including developmental and degenerative abnormalities caused primarily by disturbances in cell migration, structural plasticity of the synapse, and blood-vessel barrier function. In this context, critical pathways involved in the pathogenesis of these diseases are related to structural, scaffolding, and enzymatic activity-bearing proteins, which participate in Ca2+- and Ras Homologs (Rho) GTPases-mediated signaling. Rho GTPases are GDP/GTP binding proteins that regulate the cytoskeletal structure, cellular protrusion, and migration. These proteins cycle between GTP-bound (active) and GDP-bound (inactive) states due to their intrinsic GTPase activity and their dynamic regulation by GEFs, GAPs, and GDIs. One of the most important upstream inputs that modulate Rho GTPases activity is Ca2+ signaling, positioning ion channels as pivotal molecular entities for Rho GTPases regulation. Multiple non-selective cationic channels belonging to the Transient Receptor Potential (TRP) family participate in cytoskeletal-dependent processes through Ca2+-mediated modulation of Rho GTPases. Moreover, these ion channels have a role in several neuropathological events such as neuronal cell death, brain tumor progression and strokes. Although Rho GTPases-dependent pathways have been extensively studied, how they converge with TRP channels in the development or progression of neuropathologies is poorly understood. Herein, we review recent evidence and insights that link TRP channels activity to downstream Rho GTPase signaling or modulation. Moreover, using the TRIP database, we establish associations between possible mediators of Rho GTPase signaling with TRP ion channels. As such, we propose mechanisms that might explain the TRP-dependent modulation of Rho GTPases as possible pathways participating in the emergence or maintenance of neuropathological conditions.

K+ Channel Tetramerization Domain 5 (KCTD5) Protein Regulates Cell Migration, Focal Adhesion Dynamics and Spreading through Modulation of Ca2+ Signaling and Rac1 Activity.

Cell migration is critical for several physiological and pathophysiological processes. It depends on the coordinated action of kinases, phosphatases, Rho-GTPases proteins, and Ca2+ signaling. Interestingly, ubiquitination events have emerged as regulatory elements of migration. Thus, the role of proteins involved in ubiquitination processes could be relevant to a complete understanding of pro-migratory mechanisms. KCTD5 is a member of Potassium Channel Tetramerization Domain (KCTD) proteins that have been proposed as a putative adaptor for Cullin3-E3 ubiquitin ligase and a novel regulatory protein of TRPM4 channels. Here, we study whether KCTD5 participates in cell migration-associated mechanisms, such as focal adhesion dynamics and cellular spreading. Our results show that KCTD5 CRISPR/Cas9- and shRNA-based depletion in B16-F10 cells promoted an increase in cell migration and cell spreading, and a decrease in the focal adhesion area, consistent with an increased focal adhesion disassembly rate. The expression of a dominant-negative mutant of Rho-GTPases Rac1 precluded the KCTD5 depletion-induced increase in cell spreading. Additionally, KCTD5 silencing decreased the serum-induced Ca2+ response, and the reversion of this with ionomycin abolished the KCTD5 knockdown-induced decrease in focal adhesion size. Together, these data suggest that KCTD5 acts as a regulator of cell migration by modulating cell spreading and focal adhesion dynamics through Rac1 activity and Ca2+ signaling, respectively.

KCTD5, a novel TRPM4-regulatory protein required for cell migration as a new predictor for breast cancer prognosis.

Transient receptor potential melastatin 4 (TRPM4) is a Ca2+ -activated nonselective cationic channel that regulates cell migration and contractility. Increased TRPM4 expression has been related to pathologies, in which cytoskeletal rearrangement and cell migration are altered, such as metastatic cancer. Here, we identify the K+ channel tetramerization domain 5 (KCTD5) protein, a putative adaptor of cullin3 E3 ubiquitin ligase, as a novel TRPM4-interacting protein. We demonstrate that KCTD5 is a positive regulator of TRPM4 activity by enhancing its Ca2+ sensitivity. We show that through its effects on TRPM4 that KCTD5 promotes cell migration and contractility. Finally, we observed that both TRPM4 and KCTD5 expression are increased in distinct patterns in different classes of breast cancer tumor samples. Together, these data support that TRPM4 activity can be regulated through expression levels of either TRPM4 or KCTD5, not only contributing to increased understanding of the molecular mechanisms involved on the regulation of these important ion channels, but also providing information that could inform treatments based on targeting these distinct molecules that define TRPM4 activity.

Ferramentas e Protocolos Utilizados na Perícia Criminal Relacionados à Voz: Revisão de Literatura / Tools and Protocols Used in Criminal Skills Related to Voice: Literature Review / Herramientas y Protocolos Utilizados en la Experiencia Criminal Relacionados a la Voz: Revisión de Literatura

A perícia criminal tem como objetivo compor provas para esclarecer crimes, sendo que na Fonoaudiologia, dentre as possibilidades de ação, a perícia fonética relacionada à voz pode ser uma destas ferramentas. Objetivo: Verificar quais as ferramentas ou protocolos utilizados pelos profissionais brasileiros para a realização da perícia forense fonética relacionada aos parâmetros vocais. Método: Pesquisa de revisão bibliográfica integrativa a partir da consulta isolada e combinada dos descritores em ciências da saúde: medicina legal, voz, perícia criminal, crimes e fonoaudiologia nos bancos de dados Lilacs, Scielo, Google Scholar, Open Grey e Open Thesis. Resultados: De 457 acervos, oito foram selecionados para leitura na íntegra. A identificação de um criminoso através da voz tem sido realizada nas perícias forenses tendo em vista que a voz apresenta características possíveis de comparação, principalmente a frequência fundamental, os formantes das vogais, o voice onset time. Cuidados quanto ao registro devem ser efetivados para que as provas não sejam excluídas dos processos criminais, sendo analisadas de forma imparcial. É uma área recente na Fonoaudiologia que carece de publicações na área. Conclusão: Os recursos utilizados na perícia forense fonética relacionada aos parâmetros vocais vão desde o profissional capacitado, de diferentes áreas do conhecimento (Linguística, Fonoaudiologia, Engenharia, Direito etc.) até o uso de softwares que possam comparar a voz de diferentes falantes. Há escassez de literatura e o exercício de tal prática requer capacitação profissional interdisciplinar.

The criminal investigation aims to compose evidence to clarify crimes, and in Speech Therapy, among the possibilities of action, voice-related phonetic expertise may be one of these tools. Objective: To verify the tools or protocols used by Brazilian professionals to perform phonetic forensics related to vocal parameters. Method: Research of integrative bibliographic review from the isolated and combined consultation of the descriptors in health sciences: legal medicine, voice, criminal expertise, crimes and speech therapy in the Lilacs, Scielo, Google Scholar, Open Gray and Open Thesis databases. Results: Of 457 collections, eight were selected for reading in their entirety. The identification of a criminal through the voice has been carried out in forensic examinations since the voice presents possible characteristics of comparison, mainly the fundamental frequency, the vowels formants, the voice onset time. Registration care must be carried out so that the evidence is not excluded from criminal prosecution, being analyzed in an impartial manner. It is a recent area in Speech Therapy that lacks publications in the area. Conclusion: The resources used in phonetic forensic expertise related to vocal parameters range from the qualified professional, from different areas of knowledge (Linguistics, Speech Therapy, Engineering, Law, etc.) to the use of software that can compare the voice of different speakers. There is a shortage of literature and the practice of such practice requires interdisciplinary professional training.

La pericia criminal tiene como objetivo componer pruebas para aclarar crímenes, siendo que en la Fonoaudiología, entre las posibilidades de acción, la pericia fonética relacionada a la voz puede ser una de estas herramientas. Objetivo: Verificar cuáles son las herramientas o protocolos utilizados por los profesionales brasileños para la realización de la pericia forense fonética relacionada a los parámetros vocales. En el presente trabajo se analizaron los resultados obtenidos en el estudio de los resultados obtenidos en el estudio de los resultados obtenidos en el estudio. Resultados: De 457 acervos, ocho fueron seleccionados para lectura en su totalidad. La identificación de un criminal a través de la voz ha sido realizada en las pericias forenses teniendo en vista que la voz presenta características posibles de comparación, principalmente la frecuencia fundamental, los formantes de las vocales, el voice onset time. Los cuidados en cuanto al registro deben ser efectivos para que las pruebas no sean excluidas de los procesos criminales, siendo analizadas de forma imparcial. Es un área reciente en la Fonoaudiología que carece de publicaciones en el área. Conclusión: Los recursos utilizados en la pericia forense fonética relacionada a los parámetros vocales van desde el profesional capacitado, de diferentes áreas del conocimiento (Lingüística, Fonoaudiología, Ingeniería, Derecho, etc.) hasta el uso de softwares que puedan comparar la voz de diferentes hablantes. Hay escasez de literatura y el ejercicio de tal práctica requiere una capacitación profesional interdisciplinaria.

Complex I and II are required for normal mitochondrial Ca2+ homeostasis.

Cytosolic calcium (cCa2+) entry into mitochondria is facilitated by the mitochondrial membrane potential (ΔΨm), an electrochemical gradient generated by the electron transport chain (ETC). Is has been assumed that as long as mutations that affect the ETC do not affect the ΔΨm, the mitochondrial Ca2+ (mCa2+) homeostasis remains normal. We show that knockdown of NDUFAF3 and SDHB reduce ETC activity altering mCa2+ efflux and influx rates while ΔΨm remains intact. Shifting the equilibrium toward lower [Ca2+]m accumulation renders cells resistant to death. Our findings reveal an unexpected relationship between complex I and II with the mCa2+ homeostasis independent of ΔΨm.

FR58P1a; a new uncoupler of OXPHOS that inhibits migration in triple-negative breast cancer cells via Sirt1/AMPK/ß1-integrin pathway.

Highly malignant triple-negative breast cancer (TNBC) cells rely mostly on glycolysis to maintain cellular homeostasis; however, mitochondria are still required for migration and metastasis. Taking advantage of the metabolic flexibility of TNBC MDA-MB-231 cells to generate subpopulations with glycolytic or oxidative phenotypes, we screened phenolic compounds containing an ortho-carbonyl group with mitochondrial activity and identified a bromoalkyl-ester of hydroquinone named FR58P1a, as a mitochondrial metabolism-affecting compound that uncouples OXPHOS through a protonophoric mechanism. In contrast to well-known protonophore uncoupler FCCP, FR58P1a does not depolarize the plasma membrane and its effect on the mitochondrial membrane potential and bioenergetics is moderate suggesting a mild uncoupling of OXPHOS. FR58P1a activates AMPK in a Sirt1-dependent fashion. Although the activation of Sirt1/AMPK axis by FR58P1a has a cyto-protective role, selectively inhibits fibronectin-dependent adhesion and migration in TNBC cells but not in non-tumoral MCF10A cells by decreasing ß1-integrin at the cell surface. Prolonged exposure to FR58P1a triggers a metabolic reprograming in TNBC cells characterized by down-regulation of OXPHOS-related genes that promote cell survival but comprise their ability to migrate. Taken together, our results show that TNBC cell migration is susceptible to mitochondrial alterations induced by small molecules as FR58P1a, which may have therapeutic implications.

[Extracorporeal cytokine hemadsorption for the treatment of refractory septic shock. Report of two cases]. / Adsorción extracorpórea de citoquinas en el tratamiento del shock séptico refractario. Casos clínicos.

If Septic shock (SS) evolves to refractory SS, mortality could reach 90%, despite giving an optimal treatment. Nowadays, extracorporeal devices which adsorb inflammatory cytokines are available, reducing the systemic inflammatory response syndrome. These devices can be used with continuous renal replacement therapy or conventional hemodialysis. We report two diabetic females aged 50 and 58 years, who underwent a total colectomy and amputation of diabetic foot and who developed a SS with high requirements of vasoactive drugs (norepinephrine and adrenaline) to maintain a mean arterial pressure about 60 mmHg. Both were subjected to hemodialysis, connected to a cytokine hemadsorption device. The most important finding was the progressive reduction of vasopressor doses, effect that was observed nine hours after the beginning of the hemadsorption and lasted until its removal at 26 hours. Both patients survived.

Adsorción extracorpórea de citoquinas en el tratamiento del shock séptico refractario: casos clínicos / Extracorporeal cytokine hemadsorption for the treatment of refractory septic shock: report of two cases

If Septic shock (SS) evolves to refractory SS, mortality could reach 90%, despite giving an optimal treatment. Nowadays, extracorporeal devices which adsorb inflammatory cytokines are available, reducing the systemic inflammatory response syndrome. These devices can be used with continuous renal replacement therapy or conventional hemodialysis. We report two diabetic females aged 50 and 58 years, who underwent a total colectomy and amputation of diabetic foot and who developed a SS with high requirements of vasoactive drugs (norepinephrine and adrenaline) to maintain a mean arterial pressure about 60 mmHg. Both were subjected to hemodialysis, connected to a cytokine hemadsorption device. The most important finding was the progressive reduction of vasopressor doses, effect that was observed nine hours after the beginning of the hemadsorption and lasted until its removal at 26 hours. Both patients survived.