Bioactive C-phycocyanin exerts immunomodulatory and antitumor activity in mice with induced melanoma.

Melanoma is the most aggressive and deadly skin cancer. The difficulty in its treatment arises from its ability to suppress the immune system, making it crucial to find a substance that increases anti-tumor immunity. C-phycocyanin (C-PC) appears as a promising bioactive, with multifaceted effects against several cancers, but its efficacy against melanoma has only been tested in vitro. Therefore, we investigated C-PC's the anti-tumor and immunomodulatory action in a murine melanoma model. The tumor was subcutaneously induced in C57BL/6 mice by injecting B16F10 cells. The animals were injected subcutaneously with C-PC for three consecutive days. After euthanasia, the tumor was weighed and measured. The inguinal lymph node was removed, and the cells were stained with antibodies and analyzed by flow cytometry. The heart, brain and lung were analyzed by histopathology. C-PC increased the B cell population of the inguinal lymph node in percentage and absolute number. The absolute number of T lymphocytes and myeloid cells were also increased in the groups treated with C-PC. Thus, C-PC showed a positive immunomodulatory effect both animals with and without tumor. However, this effect was more pronounced in the presence of the tumor. Positive immune system modulation may be associated with a reduction in tumor growth in animals treated with C-PC. Administration of C-PC subcutaneously did not cause organ damage. Our findings demonstrate C-PC's immunomodulatory and anti-melanoma action, paving the way for clinical research with this bioactive.

Environmental Health and Toxicology: Immunomodulation Promoted by Endocrine-Disrupting Chemical Tributyltin.

Tributyltin (TBT) is an environmental contaminant present on all continents, including Antarctica, with a potent biocidal action. Its use began to be intensified during the 1960s. It was effectively banned in 2003 but remains in the environment to this day due to several factors that increase its half-life and its misuse despite the bans. In addition to the endocrine-disrupting effect of TBT, which may lead to imposex induction in some invertebrate species, there are several studies that demonstrate that TBT also has an immunotoxic effect. The immunotoxic effects that have been observed experimentally in vertebrates using in vitro and in vivo models involve different mechanisms; mainly, there are alterations in the expression and/or secretion of cytokines. In this review, we summarize and update the literature on the impacts of TBT on the immune system, and we discuss issues that still need to be explored to fill the knowledge gaps regarding the impact of this endocrine-disrupting chemical on immune system homeostasis.

Is there correlation between perineometry and Modified Oxford Scale in women? Systematic review with meta-analysis and grade recommendations.

BACKGROUND: The International Continence Society (ICS) recommends the use of perineometry and digital palpation to assess the pelvic floor muscles (PFM). Exploring the degree of correlation between both assessment strategies will serve to improve safety for clinical practice. Therefore, we performed a systematic review and meta-analysis on the correlation between assessment strategies. METHODS: Observational studies were included. Bias risk assessment based on Downs and Black scale and the evidence's level were assessed using the GRADE. The random effect model measured the correlation values and were quantitatively analyzed through meta-analysis. Registration in PROSPERO database - CRD42021253775. RESULTS: Six studies were selected. There was a high positive correlation between perineometry and MOS (r = 0.74; 95%-IC 0.61-0.83; I2: 81%, p < 0.01). Subgroup analysis was performed with 3 studies with continent women, and revealed a high positive correlation (r = 0.80; 95%-IC 0.62-0.90; I2: 90%, p < 0.01), while 2 studies with incontinent women revealed a moderate positive correlation (r = 0.64; 95%-IC 0.48-0.75; I2: 0%, p = 0.40). GRADE analysis revealed a low strength of evidence. CONCLUSION: The high positive correlation between perineometry and MOS suggests that if the assessment strategies are applied in a standardized way, these tests can be used together or separately to assess the functionality of PFMs in clinical practice. However, the results should be interpreted with caution due to the low strength of GRADE evidence.

Potential Therapeutic Targets of Quercetin in the Cutaneous Melanoma Model and Its Cellular Regulation Pathways: A Systematic Review.

Melanoma is a skin cancer with a high mortality rate due to its invasive characteristics. Currently, immunotherapy and targeted therapy increase patient survival but are ineffective in the advanced stages of the tumor. Quercetin (Que) is a natural compound that has demonstrated chemopreventive effects against different types of tumors. This review provides evidence for the therapeutic potential of Que in melanoma and identifies its main targets. The Scopus, Web of Science, and PubMed databases were searched, and studies that used free or encapsulated Que in melanoma models were included, excluding associations, analogs, and extracts. As a result, 73 articles were retrieved and their data extracted. Que has multiple cellular targets in melanoma models, and the main regulated pathways are cell death, redox metabolism, metastasis, and melanization. Que was also able to regulate important targets of signaling pathways, such as PKC, RIG-I, STAT, and P53. In murine models, treatment with Que reduced tumor growth and weight, and decreased metastatic nodules and angiogenic vasculature. Several studies have incorporated Que into carriers, demonstrating improved efficacy and delivery to tumors. Thus, Que is a promising therapeutic agent for the treatment of melanoma; however, further studies are needed to evaluate its effectiveness in clinical trials.

Ouabain Effects on Human Anaplastic Thyroid Carcinoma 8505C Cells.

Anaplastic thyroid carcinoma (ATC) is a rare, but aggressive, carcinoma derived from follicular cells. While conventional treatments may improve patients' survival, the lethality remains high. Therefore, there is an urgent need for more effective ATC treatments. Cardiotonic steroids, such as ouabain, have been shown to have therapeutic potential in cancer treatment. Thus, we aimed to evaluate ouabain's effects in human anaplastic thyroid cells. For this, 8505C cells were cultured in the presence or absence of ouabain. Viability, cell death, cell cycle, colony formation and migratory ability were evaluated in ouabain-treated and control 8505C cells. The expression of differentiation and epithelial-to-mesenchymal transition (EMT) markers, as well as IL-6, TGFb1 and their respective receptors were also quantified in these same cells. Our results showed that ouabain in vitro decreased the number of viable 8505C cells, possibly due to an inhibition of proliferation. A reduction in migration was also observed in ouabain-treated 8505C cells. In contrast, decreased mRNA levels of PAX8 and TTF1 differentiation markers and increased levels of the N-cadherin EMT marker, as well as IL-6 and TGFb1, were found in ouabain-treated 8505C cells. In short, ouabain may have anti-proliferative and anti-migratory effect on 8505C cells, but maintains an aggressive and undifferentiated profile.

Efeito de um treinamento de músculos pélvicos em grupo para mulheres com incontinência urinária: um ensaio clínico randomizado / Effect of a training of pelvic muscles in group for women with urinary incontinence: arandomized clinical test

Introdução: A incontinência urinária (IU) é um problema muitas vezes subestimado, não recebendo a devida atenção. Dentre as possibilidades de tratamento conservador da IU, o treinamento dos músculos do assoalho pélvico (TMAP) supervisionado deve ser recomendado como primeira linha de tratamento para as mulheres. O TMAP pode ser desenvolvido em grupos, individualmente e em casa. Objetivos: Ainda há poucos estudos na literatura envolvendo TMAP em grupo com protocolos definidos que possam ser facilmente compreendidos e reproduzidos pelos pacientes. O objetivo deste estudo é demonstrar a eficácia de um protocolo de TMAP em grupo comparado a um protocolo de TMAP domiciliar para mulheres com IU. Métodos: Este foi um estudo experimental controlado randomizado cego que seguiu as recomendações do CONSORT. Os instrumentos de avaliação foram a escala PERFECT, ICIQ-SF e PISQ-12. O principal resultado foi a melhora da função dos músculos do assoalho pélvico (MAP) e os resultados secundários foram a melhora da qualidade de vida (QV) e da função sexual (FS). Resultados: Com doze semanas de tratamento o protocolo do grupo TMAP apresentou-se como uma forma de tratamento mais eficaz para IU, pois apresentou melhora nos itens potência e QV. Ao observar a efetividade dos protocolos, após vinte e quatro semanas, ambos foram efetivos apenas no que se refere aos desfechos secundários, QV e FS. Conclusão: Pode-se supor que a intervenção em grupo, utilizada nesta amostra específica, constitui uma estratégia de intervenção fisioterapêutica factível e viável, capaz de beneficiar muitas mulheres com IU, além de ser uma ferramenta de fácil compreensão e acompanhamento pelos pacientes.

Rac GTPases in acute myeloid leukemia cells: Expression profile and biological effects of pharmacological inhibition.

Acute myeloid leukemia (AML) is a highly heterogeneous hematological neoplasm with low survival rates. Thus, the investigation of new therapeutic targets is essential. The Rac subfamily of GTPase proteins has been shown to participate in the physiopathology of hematological malignancies. However, their expression and function in AML remain unclear. In this study, we evaluated Rac1, Rac2 and Rac3 gene expressions in AML and their impact on clinical outcomes. We further investigated the effects of the in vitro treatment with a Rac inhibitor (EHT-1864) on AML cell lines. Rac3 expression was increased in AML derived from myelodysplastic syndromes compared to healthy donors. Rac2 expression did not differ between AML patients and healthy donors, but de novo AML patients with higher Rac2 presented lower overall survival. Oncogenic pathway gene-sets related to AKT/mTOR were identified as associated with Rac1, Rac2 and Rac3 expressions. EHT-1864 treatment reduced the viability of OCI-AML3, KG1 and Kasumi-1 cells in a time and dose-dependent manner. In OCI-AML3 cells, treatment with EHT-1864 induced apoptosis, autophagy, and led to the accumulation of cells in the G1 phase of the cell cycle. These changes were concomitant with alterations in p53 and cyclins. Dowregulation of the PI3K/AKT/mTOR pathway was also observed. Interestingly, the combined treatment of EHT-1864 and low doses of daunorubicin enhanced OCI-AML3 cell apoptosis. In conclusion, Rac2 expression is a prognostic factor in AML and our preclinical results suggest that Rac inhibition may be an attractive mechanism to compose the antineoplastic strategy for this disease.

Can the inability to contract the pelvic floor muscles influence the severity of urinary incontinence symptoms in females?

INTRODUCTION AND HYPOTHESIS: The objective was to analyze if the inability to perform a maximal voluntary contraction (MVC) of the pelvic floor muscles (PFMs) in a first assessment can influence the severity of urinary incontinence symptoms in women. METHODS: A cross-sectional study was carried out using the medical records of women with UI who were referred for pelvic floor physiotherapy after undergoing a gynecological evaluation between May 2013 and December 2019. Records included data referring to age, body mass index (BMI), obstetric history, Modified Oxford Scale (MOS), and the final score of the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF) from a baseline assessment. Data were divided into women who were unable and those who were able to voluntarily perform an MVC of the PFMs. Statistical analysis was conducted using SPSS version 21. RESULTS: A total of 498 medical records were analyzed and 36.3% of those women were not able to perform a PFM MVC after verbal command and digital stimulus. Homogeneity was observed among groups and no significant difference was found regarding the severity of UI symptoms when the groups were compared. CONCLUSIONS: No association was found between the inability to contract the PFMs and the severity of UI symptoms. Other studies should be developed to better understand why some women are incapable of performing a voluntary PFM contraction. Also, it would be relevant to compare women with PFM dysfunction who are not able to contract the PFMs with healthy women with the same PFM condition to analyze whether this muscle condition could be related to dysfunctions such as UI or pelvic organ prolapse.

Implementation of a ventilator-associated pneumonia prevention bundle in a teaching hospital / Implementação de um bundle de prevenção de pneumonia associada à ventilação mecânica em um hospital universitário / Implementación de un paquete de prevención de neumonía asociada a ventilador en un hospital escuela

Background and objectives: the implementation of ventilator-associated pneumonia (VAP) prevention bundles in Intensive Care Units (ICU) has been recommended due to the considerable increase in hospital costs, length of stay, morbidity and mortality in affected hospitalized patients. However, the results of its effectiveness are still controversial. This study aimed to assess the impact of implementing a VAP prevention bundle in an Adult ICU of a university hospital. Methods: a quasi-experimental study, with implementation of a VAP prevention bundle in an Adult ICU and analysis of indicators. This study addressed secondary data from hospital records recommended in the routine of the Hospital Infection Control Commission team and from the medical records of patients undergoing mechanical ventilation, from June 2016 to July 2019, who developed VAP. Results: VAP incidence density before the intervention was 4.13 infections, and after the intervention, it was 7.15 infections per thousand patients on ventilation/day. When performing the linear regression test, we showed that VAP density decreased as sedation was reduced, extubation was increased, and when compliance with all bundle elements occurred. Conclusion: there was no reduction in VAP incidence after the adoption of preventive measures, perhaps due to an underreporting of cases in the period prior to the bundle and a low team compliance with the bundle components. However, we noticed a decrease in VAP notifications after the eighth month of implementation of bundle of measures.(AU)

Justificativa e objetivos: a implementação de bundles de prevenção de pneumonia associada à ventilação mecânica (PAV) em Unidades de Terapia Intensiva (UTI) tem sido recomendada devido ao aumento considerável dos custos hospitalares, tempo de internação, morbidade e mortalidade em pacientes hospitalizados acometidos. No entanto, os resultados de sua eficácia ainda são controversos. Este estudo teve como objetivo avaliar o impacto da implantação de um bundle de prevenção de PAV em uma UTI Adulto de um hospital universitário. Métodos: estudo quase experimental, com implantação de bundle de prevenção de PAV em UTI Adulto e análise de indicadores. Este estudo abordou dados secundários de prontuários hospitalares recomendados na rotina da equipe da Comissão de Controle de Infecção Hospitalar e dos prontuários de pacientes em ventilação mecânica, no período de junho de 2016 a julho de 2019, que desenvolveram PAV. Resultados: A densidade de incidência de PAV antes da intervenção foi de 4,13 infecções e após a intervenção foi de 7,15 infecções por mil pacientes em ventilação/dia. Ao realizar o teste de regressão linear, mostramos que a densidade da PAV diminuiu à medida que a sedação era reduzida, a extubação aumentava e quando ocorria complacência com todos os elementos do feixe. Conclusão: não houve redução da incidência de PAV após a adoção de medidas preventivas, talvez pela subnotificação de casos no período anterior ao bundle e baixa adesão da equipe aos componentes do bundle. No entanto, notamos diminuição das notificações de PAV após o oitavo mês de implantação do bundle de medidas.(AU)

Justificación y objetivos: la implementación de paquetes de prevención de neumonía asociada al ventilador (NAV) en las Unidades de Cuidados Intensivos (UCI) ha sido recomendada debido al aumento considerable de los costos hospitalarios, la estancia hospitalaria, la morbilidad y la mortalidad en los pacientes hospitalizados afectados. Sin embargo, los resultados de su eficacia aún son controvertidos. Este estudio tuvo como objetivo evaluar el impacto de la implementación de un paquete de prevención de NAVM en una UCI de adultos de un hospital universitario. Métodos: estudio cuasi-experimental, con implementación de un paquete de prevención de NAVM en una UCI de Adultos y análisis de indicadores. Este estudio abordó datos secundarios de registros hospitalarios recomendados en la rutina del equipo de la Comisión de Control de Infecciones Hospitalarias y de los registros médicos de pacientes en ventilación mecánica, de junio de 2016 a julio de 2019, que desarrollaron NAV. Resultados: La densidad de incidencia de NAVM antes de la intervención fue de 4,13 infecciones y después de la intervención fue de 7,15 infecciones por mil pacientes en ventilación/día. Al realizar la prueba de regresión lineal, mostramos que la densidad de VAP disminuyó a medida que se redujo la sedación, se incrementó la extubación y cuando se produjo el cumplimiento de todos los elementos del paquete. Conclusión: no hubo reducción en la incidencia de NAVM después de la adopción de las medidas preventivas, quizás debido a un subregistro de casos en el período anterior al paquete y al bajo cumplimiento del equipo con los componentes del paquete. Sin embargo, notamos una disminución en las notificaciones de VAP después del octavo mes de implementación del paquete de medidas.(Au)

Characterize the main adverse events with harm reported in a Teaching Hospital in Minas Gerais

Background and Objectives: adverse events are a major public health problem. The purpose of the study was to characterize the main adverse events with harm reported in a teaching hospital in Minas Gerais. Methods: this is a retrospective cross-sectional descriptive study with quantitative approach, which assessed the reports on adverse events, carried out between January 2015 and December 2018. Pearson's chi-square test was applied in order to verify the association between categorical variables. Cramer's measure V was calculated to assess the degree of association between the respective variables. In the observation of statistically significant results, the Z test was applied to compare proportions with adjustments by the Bonferroni method. Results: a total of 445 adverse events were reported, being the highest number in 2018 (61.8%) involving "Abrasion and friction" process (44.7%), which correspond to grades 3 and 4 pressure injuries. Most adverse events were reported by the Emergency Unit (29.2%), and serious harm (7.6%) and deaths (1.3%) were more prevalent in this place. There was a statistically significant association between types of harm and types of incidents (p<0.001), types of harm (p<0.001) and years of occurrence, and also between the harm and the hospital sectors (p=0.003). Conclusion: adverse event reports back institutional risk management by strengthening the patient safety culture.(AU)

In vitro antitumoral effects of the steroid ouabain on human thyroid papillary carcinoma cell lines.

Ouabain is a steroid described as a compound extracted from plants that is capable of binding to Na+ , K+ -ATPase, inhibiting ion transport and triggering cell signaling pathways. Due to its positive ionotropic effect, ouabain was used for more than 200 years for the treatment of cardiac dysfunctions. Numerous antitumor effects of ouabain have been described so far; however, its role on thyroid cancer is still poorly understood. Therefore, the aim of the present work was to evaluate the effect of ouabain on the biology of human papillary thyroid cancer cells. For this, three human thyroid cell lines were used: NTHY-ori, a non-tumor lineage, BCPAP and TPC-1, both derived from papillary carcinomas. Cells were cultured in the presence or absence of ouabain. Subsequently, we evaluated its effects on the viability, cell death, cell cycle, and migratory ability of these cell lines. We also investigated the impact of ouabain in IL-6/IL-6R and epithelial to mesenchymal transition markers expression. Our results indicate that ouabain (10-7 M), decreased the number of NTHY-ori, TPC-1 and BCPAP viable cells and induced cell cycle arrest after in vitro culture, but did not appear to promote cell death. In TPC-1 cells ouabain also inhibited cell migration; increased IL-6/IL-6R expression and IL-6 secretion; and diminished vimentin and SNAIL-1 expression. Collectively, our results indicate that ouabain has an antitumoral role on human papillary thyroid carcinomas in vitro. Even though additional studies are necessary, our work contributes to the discussion of the possibility of new clinical trials of ouabain.

Effects of RhoA and RhoC upon the sensitivity of prostate cancer cells to glutamine deprivation.

RhoA and RhoC contribute to the regulation of glutamine metabolism, which is a crucial determinant of cell growth in some types of cancer. Here we investigated the participation of RhoA and RhoC in the response of prostate cancer cells to glutamine deprivation. We found that RhoA and RhoC activities were up- or downregulated by glutamine reduction in PC3 and LNCaP cell lines, which was concomitant to a reduction in cell number and proliferation. Stable overexpression of wild type RhoA or RhoC did not alter the sensitivity to glutamine deprivation. However, PC3 cells expressing dominant negative RhoAN19 or RhoCN19 mutants were more resistant to glutamine deprivation. Our results indicate that RhoA and RhoC activities could affect cancer treatments targeting the glutamine pathway.

Ouabain pre-treatment modulates B and T lymphocytes and improves survival of melanoma-bearing animals.

Ouabain (OUA) is a glycoside shown to modulate B and T lymphocytes. Nevertheless, ouabain effects on B16F10 melanoma immune response, a mouse lineage that mimics human melanoma, are still unknown. Our aim was to study how OUA in vivo treatment modulates lymphocytes and if it improves the response against B16F10 cells. C57BL/6 mice were pre-treated with intraperitoneal (i.p) injection of OUA (0.56 mg/Kg) for three consecutive days. On the 4th day, 106 B16F10 cells or vehicle were i.p. injected. Animals were euthanized on days 4th and 21st for organs removal and subsequent lymphocyte analyses by flow cytometry. In vivo ouabain-treatment reduced regulatory T cells in the spleen in both melanoma and non-melanoma groups. Ouabain preserved the number and percentage of B lymphocytes in peripheral organs of melanoma-injected mice. Melanoma-injected mice pre-treated with OUA also survive longer. Our findings contribute to a better understanding of OUA immunological effects in a melanoma model.

Comparison of parasacral transcutaneous electrical stimulation and transcutaneous posterior tibial nerve stimulation in women with overactive bladder syndrome: A randomized clinical trial.

OBJECTIVE: To compare the effects of parasacral transcutaneous electrical stimulation with the effects of transcutaneous posterior tibial nerve stimulation in women with overactive bladder syndrome (OAB). STUDYDESIGN: A randomized clinical trial was performed with 50 women aged 40-76 years with symptoms of OAB, divided into two groups: the parasacral transcutaneous electrical stimulation (PS) group and the transcutaneous posterior tibial nerve stimulation (PTN) group. Both groups underwent the same protocol, at home, for 6 weeks, applying electrical stimulation three times per week. The tools used for evaluation were the King's Health Questionnaire (KHQ), the Overactive Bladder-Validated 8-question Awareness Tool (OAB-V8) and the Incontinence Severity Index (ISI). Statistical analysis was undertaken using independent t-test, Mann-Whitney test, Chi-squared test and generalized estimating equations. RESULTS: After 6 weeks of treatment, OAB-V8 showed a significant improvement in the PTN group compared with the PS group (Mann-Whitney test, p = 0.019). Post-intervention, no between-group differences were seen in terms of KHQ domains, average KHQ symptom scale and proportions of categories of ISI. All variables showed a significant effect of time after 6 weeks of treatment for both groups (p < 0.005). CONCLUSION: Both forms of transcutaneous electrical stimulation seem to be effective and safe for home treatment of women with OAB.

Effect of intravaginal vibratory versus electric stimulation on the pelvic floor muscles: A randomized clinical trial.

INTRODUCTION: According to the International Urogynecological Association and International Continence Society people with normal pelvic floor muscle function should have the ability to voluntarily and involuntarily contract and relax these muscles. However, many women are unaware of their pelvic floor, and it is estimated that about 30-50% do not know how to actively contract these muscles. Within this context, therapeutic strategies to improve pelvic floor muscle strength and function are particularly relevant. AIMS: To compare the use of an intravaginal vibratory stimulus (IVVS) versus intravaginal electrical stimulation (IVES) on pelvic floor muscle functionality in women with pelvic floor dysfunctions who cannot voluntarily contract these muscles. MATERIALS AND METHODS: Randomized clinical trial performed at a tertiary care hospital from June 2016 to September 2017. The sample comprised adult women with pelvic floor dysfunction who were unable to contract their pelvic floor muscles voluntarily. Women with latex allergy or other allergies in the pelvic region, vaginal or urinary tract infection, gynecological cancer, significant pain on palpation, or pelvic floor training over the preceding 6 months were excluded. After baseline assessment, women that met the inclusion criteria were randomized to receive once-weekly 20-minute sessions of IVVS or IVES for 6 weeks. RESULTS: Twenty-one women were randomly assigned to each group; 18 completed the IVVS and 17 completed the IVES protocols. The IVVS group presented a significant increase in PFM strength in relation to the IVES group (p = 0.026). There was a significant interaction between time and type of intervention for the same variable (p = 0.008) in the IVVS group. CONCLUSION: Both techniques were beneficial, but IVVS was significantly superior to IVES in improving pevic floor muscle strength. Additional studies are warranted to consolidate the utility of IVVS as a treatment modality for pelvic floor dysfunction.

Ouabain Decreases Regulatory T Cell Number in Mice by Reducing IL-2 Secretion.

BACKGROUND: Ouabain (OUA) is a cardiotonic glycoside originally extracted from African plants. It has also been described as an endogenous component in mammals, being released in stress situations mainly by the adrenal gland. OUA has been reported to be capable of inhibiting mitogen-induced lymphocyte proliferation and also affects B and T lymphocytes. OBJECTIVES: The aim of this work is to show the effects of OUA in peripheral T lymphocytes. METHODS: In the in vivo experiments, mice were injected intraperitoneally for 3 consecutive days with RPMI medium (control group) or 0.56 mg/kg of OUA diluted in RPMI medium (OUA group). On the fourth day, spleen or mesenteric lymph nodes were removed. RESULTS: OUA significantly reduced the number of CD4+ T lymphocytes in the spleen, especially regulatory T cells (Tregs). In vitro OUA did not inhibit the proliferation of CD4+T lymphocytes stimulated with anti-CD3 neither was able to induce the apoptosis of CD4+ nor Tregs. There was no increase in the number or percentage of T lymphocytes in the mesenteric lymph nodes, suggesting that there was no preferential accumulation of these cells in this organ. Secretion of IL-2 by activated T lymphocytes was decreased by the OUA, explaining at least in part the reduction of Tregs, since this cytokine is involved in the peripheral conversion and maintenance of Tregs. CONCLUSION: The impact of this reduction in autoimmune diseases, allergy and cancer as well as the potential use of OUA as a therapeutic approach in tumor treatment still needs more investigation.

Avian host composition, local speciation and dispersal drive the regional assembly of avian malaria parasites in South American birds.

Identifying the ecological factors that shape parasite distributions remains a central goal in disease ecology. These factors include dispersal capability, environmental filters and geographic distance. Using 520 haemosporidian parasite genetic lineages recovered from 7,534 birds sampled across tropical and temperate South America, we tested (a) the latitudinal diversity gradient hypothesis and (b) the distance-decay relationship (decreasing proportion of shared species between communities with increasing geographic distance) for this host-parasite system. We then inferred the biogeographic processes influencing the diversity and distributions of this cosmopolitan group of parasites across South America. We found support for a latitudinal gradient in diversity for avian haemosporidian parasites, potentially mediated through higher avian host diversity towards the equator. Parasite similarity was correlated with climate similarity, geographic distance and host composition. Local diversification in Amazonian lineages followed by dispersal was the most frequent biogeographic events reconstructed for haemosporidian parasites. Combining macroecological patterns and biogeographic processes, our study reveals that haemosporidian parasites are capable of circumventing geographic barriers and dispersing across biomes, although constrained by environmental filtering. The contemporary diversity and distributions of haemosporidian parasites are mainly driven by historical (speciation) and ecological (dispersal) processes, whereas the parasite community assembly is largely governed by host composition and to a lesser extent by environmental conditions.

BRD4 Inhibition Enhances Azacitidine Efficacy in Acute Myeloid Leukemia and Myelodysplastic Syndromes.

Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell-based disorders characterized by ineffective hematopoiesis, increased genomic instability and a tendency to progress toward acute myeloid leukemia (AML). MDS and AML cells present genetic and epigenetic abnormalities and, due to the heterogeneity of these molecular alterations, the current treatment options remain unsatisfactory. Hypomethylating agents (HMA), especially azacitidine, are the mainstay of treatment for high-risk MDS patients and HMA are used in treating elderly AML. The aim of this study was to investigate the potential role of the epigenetic reader bromodomain-containing protein-4 (BRD4) in MDS and AML patients. We identified the upregulation of the short variant BRD4 in MDS and AML patients, which was associated with a worse outcome of MDS. Furthermore, the inhibition of BRD4 in vitro with JQ1 or shRNA induced leukemia cell apoptosis, especially when combined to azacitidine, and triggered the activation of the DNA damage response pathway. JQ1 and AZD6738 (a specific ATR inhibitor) also synergized to induce apoptosis in leukemia cells. Our results indicate that the BRD4-dependent transcriptional program is a defective pathway in MDS and AML pathogenesis and its inhibition induces apoptosis of leukemia cells, which is enhanced in combination with HMA or an ATR inhibitor.

Depression, lower urinary tract symptoms and quality of life in women with multiple sclerosis: a descriptive and correlational study

Introduction: Among the most ordinary clinical manifestations of Multiple Sclerosis (MS) are depression and the presence of Lower Urinary Tract Symptoms (LUTS). Both can compromise a person's quality of life. The objective of this research was to identify the major urinary symptoms and correlate them with quality of life and with depressive symptoms in women with MS. Methods: This was an observatory, descriptive and correlational study, with nonprobabilistic sampling by convenience. This research included women over 18 years old who displayed LUT symptoms and who had been diagnosed with Relapsing-Remitting MS. Assessment consisted of an anamnesis card, the Kurtzke Expanded Disability Status Scale (EDSS), the Incontinence Impact Questionnaire-7 (IIQ-7-BR), the Urogenital Distress Inventory-6 (UDI-6-BR), the Beck Depression Inventory-2 (BDI-II) and the Multiple Sclerosis Quality of Life Questionnaire - Portuguese version (MSQOL-54). Results: 41 women participated in the study, with average age of 50.1 (± 9.45) and average of 4.11 in the EDSS. The most common urinary symptom was urinary urgency (78%). There was no correlation between the severity of the urinary symptom and quality of life. Moderate and significant negative correlation (r = -0.561 p < 0.001) was found between depression and the physical component of quality of life and strong negative correlation (r = -0.729 p < 0.001) was found between depression and the mental component. Conclusions: The most prevalent urinary symptom was urinary urgency. A strong correlation was found between symptoms of depression and quality of life and there was no correlation between urinary symptoms and quality of life.

Glucocorticoid susceptibility and in vivo ABCB1 activity differ in murine B cell subsets.

Glucocorticoids are produced and released by the adrenal gland and become elevated in response to stress. Although glucocorticoids are well known for their immunosuppressive effects, less is known about their effects on B cells. ABCB1 is an efflux pump expressed in both cancer and normal cells, modulating the gradient of various metabolites, including hydrocortisone. Our goal was to evaluate the effect of this glucocorticoid on murine B cell differentiation and whether sensitivity to hydrocortisone could be related to ABCB1 activity in vivo. C57BL/6 mice received one or three consecutive i.p. injections of hydrocortisone (70, 140 and 200 mg/kg/day). ABCB1 activity was evaluated via the rhodamine-123 transport and inhibited by cyclosporin A in hydrocortisone-treated and control mice. Cells from bone marrow, spleen and blood were counted, incubated with antibodies and analyzed by flow cytometry. A single hydrocortisone injection did not alter the number of bone marrow subsets. Conversely, three daily injections were able to reduce the cell number of most bone marrow subsets, excepting c-kit-sca-1+ and mature B cells. This treatment reduced marginal zone, follicular and transitional B cells, though splenic subsets were more resistant than bone marrow B cells. Recirculating follicular B cells in the blood were resistant to hydrocortisone. With the exception of follicular B cells, all subpopulations exhibited ABCB1 activity. However, hydrocortisone treatment did not affect ABCB1 activity in most subsets analyzed. Results suggest that hydrocortisone is able to regulate B cell lymphopoiesis although ABCB1 activity is not related to the susceptibility to that glucocorticoid in B cell subsets.