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.

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.

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.

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.

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.

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.

Influence of pelvic floor muscle fatigue on stress urinary incontinence: a systematic review.

INTRODUCTION AND HYPOTHESIS: Stress urinary incontinence (SUI) is the most common urinary complaint among women and is defined by the International Continence Society as any involuntary loss of urine due to physical effort, sneezing or coughing. Many women with SUI state that the loss of urine occurs after performing repetitive movements, which may suggest that it is the result of fatigue of the pelvic floor muscles (PFM). Thus, we performed the systematic review of the literature on the influence of PFM fatigue on the development or worsening of the symptoms of SUI in women. METHODS: The PubMed, Scopus, EMBASE, PEDro, LILACS, SciELO, Cochrane Library, Google Scholar, CINAHL and Periódicos CAPES databases were searched for articles using the keywords "fatigue", "pelvic floor", "stress urinary incontinence" and "women", in Portuguese and in English. Methodological quality was assessed using the Downs and Black scale, and the data collected from the studies were analyzed descriptively. RESULTS: Of the 2,010 articles found, five met the inclusion criteria and were analyzed. They were published between 2004 and 2015, and included a total of 30,320 women with ages ranging from 24 to 53.6 years. Of the studies analyzed, three showed an association between fatigue and SUI, and two did not show such an association. CONCLUSIONS: This study confirmed that PFM fatigue can influence the development and/or worsening of SUI.

Vibratory perineal stimulation for the treatment of female stress urinary incontinence: a systematic review.

INTRODUCTION AND HYPOTHESIS: The pelvic floor muscles (PFM) play an important part in the urinary continence mechanism. Changes in their structure and functionality may lead to a predisposition to pelvic floor dysfunction such as urinary incontinence (UI), which is the involuntary loss of urine. Some techniques for conservative treatment of UI are already well documented. However, new approaches have been found that require scientific proof of their effectiveness, such as vibratory stimulation (VS). Thus, we performed a systematic review of studies that investigated the use of perineal VS (PVS) for the treatment of stress UI. MATERIALS AND METHODS: This study followed the recommendations of the Cochrane Collaboration for systematic reviews. Studies that used PVS for the treatment of female UI were eligible. RESULTS: A total of 56 studies were found, of which ten were duplicates and were excluded. Analysis of the titles and abstracts led to the exclusion of 30 studies, leaving 16 for detailed analysis. Of these, only three were included as they fulfilled all the eligibility criteria previously established for the present study. In spite of the heterogeneity of the protocols, all the studies had the goal of assessing the effects of vibration on the PFM, and the stimulation was found to be effective in reducing urinary leakage, improving muscle strength and consequently the patients' quality of life. CONCLUSIONS: Because of the heterogeneity and the small number of studies, it is not possible to draw a conclusion as to the effectiveness of PVS for the treatment of stress UI, and further studies are needed to provide scientific support for its use.

Prevalence of urinary incontinence in female athletes: a systematic review with meta-analysis.

Urinary incontinence (UI) is any involuntary loss of urine. In female athletes, physical exercise may be a risk factor for UI because of increased intra-abdominal pressure generated during high-impact exercises, which overloads the pelvic organs, predisposing them to UI. This is a systematic review of the prevalence of UI in female athletes in different sports. A search for articles was carried out in the PEDro, Scopus, Cinahl, PubMed, LILACS, SciELO, Science Direct, Web of Science, Embase, and Cochrane databases as well as a manual search of the references of studies already published on the subject with the keywords "athlete," "urinary incontinence," and "women" in Portuguese and English. Only articles published from 2000 to 2016 were included. Observational studies assessing the prevalence of UI in female athletes were selected. Methodological quality was assessed using the Downs and Black scale, and the data collected from the studies were analyzed through meta-analysis. Eight studies met the eligibility criteria. Meta-analysis showed a 36% prevalence of UI in female athletes in different sports, and compared with sedentary women, the athletes had a 177% higher risk of presenting with UI. There is a higher prevalence of UI in female athletes compared with sedentary women. There have been reports of UI in different sports.

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.

Pelvic floor muscle training in groups versus individual or home treatment of women with urinary incontinence: systematic review and meta-analysis.

INTRODUCTION AND HYPOTHESIS: Urinary Incontinence (UI) in women is a condition that becomes more common with age. Pelvic floor muscle training (PFMT) is recommended as a first option of treatment for women with symptoms of stress urinary incontinence (SUI), mixed urinary incontinence (MUI), and for some with symptoms of urge urinary incontinence (UUI). PFMT can be performed in groups, individually, and at home, and there is no consensus as to which of the approaches is more efficient for the conservative treatment of UI. The objective was to perform a systematic review comparing the effects of group PFMT vs individual or home training in the treatment of women with UI. METHODS: Cochrane's recommendations for systematic reviews were followed. The inclusion criteria were that the studies had been carried out in adult women who suffered from UI and who underwent PFMT in a group. RESULTS: Ten studies that fit the criteria previously mentioned were included in this systematic review. The meta-analysis showed that there was no difference when comparing PFMT in groups vs individual PFMT. However, when comparing PFMT in groups vs PFMT at home, the group intervention was more efficient in the treatment of UI. CONCLUSION: PFMT is an efficient technique for the improvement of the symptoms of female UI. When PFMT was supervised by a physiotherapist, no significant difference was noted when comparing group with individual approaches.

Enhanced renewal of regulatory T cells in relation to CD4(+) conventional T lymphocytes in the peripheral compartment.

CD4(+) Foxp3(+) regulatory T (Treg) cells are necessary for the maintenance of self-tolerance and T-cell homeostasis. This population is kept at stable frequencies in secondary lymphoid organs for the majority of the lifetime, despite permanent thymic emigration or in the face of thymic involution. Continuous competition is expected to occur between recently thymus-emigrated and resident Treg cells (either natural or post-thymically induced). In the present work, we analysed the renewal dynamics of Treg cells compared with CD4(+) Foxp3- conventional T cells (Tconv), using protocols of single or successive T-cell transfers into syngeneic euthymic or lymphopenic (nu/nu or RAG2(-/-)) mice, respectively. Our results show a higher turnover for Treg cells in the peripheral compartment, compared with Tconv cells, when B cell-sufficient euthymic or nude hosts are studied. This increased renewal within the Treg pool, shown by the greater replacement of resident Treg cells by donor counterparts, correlates with augmented rates of proliferation and is not modified following temporary environmental perturbations induced by inflammatory state or microbiota alterations. Notably, the preferential substitution of Treg lymphocytes was not observed in RAG2(-/-) hosts. We showed that limited B-cell replenishment in the RAG2(-/-) hosts decisively contributed to the altered peripheral T-cell homeostasis. Accordingly, weekly transfers of B cells to RAG2(-/-) hosts rescued the preferential substitution of Treg lymphocytes. Our study discloses a new aspect of T-cell homeostasis that depends on the presence of B lymphocytes to regulate the relative incorporation of recently arrived Treg and Tconv cells in the peripheral compartment.

Comparison of the functionality of pelvic floor muscles in women who practice the Pilates method and sedentary women: a pilot study.

INTRODUCTION AND HYPOTHESIS: The Pilates method is a form of physical exercise that improves the control of the core muscles, improving the conditioning of all the muscle groups that comprise the core, including the pelvic floor muscles (PFM). Thus, this study had the goal of verifying the existence of differences in the functioning of the PFM in women who practice the Pilates method and sedentary women. METHODS: This was an observational, cross-sectional pilot study. A sample size calculation was performed using preliminary data and it determined that the sample should have at least 24 individuals in each group. The participants were 60 women aged 20 to 40 years; 30 women practiced the Pilates method (PMG) and 30 were sedentary (SG). An anamnesis file was used to collect personal data and assess the knowledge and perception of the PFM. The Perina perineometer and vaginal palpation were used to determine the functionality of the PFM. RESULTS: There was no significant difference between the PMG and the SG in any of the variables analyzed. CONCLUSIONS: We concluded that the functionality of the PFM in younger women who practice the Pilates method is not different from that of sedentary women.

Triage in an adult emergency service: patient satisfaction.

OBJECTIVE: Assess the degree of patient satisfaction with triage in the adult emergency service of a public hospital. METHOD: Exploratory, descriptive, cross-sectional study with a quantitative approach. Three hundred patients were interviewed and the data were analyzed using descriptive statistics based on sociodemographic variables and those related to patient satisfaction. RESULTS: There was a predominance of women, with elementary education and a mean age of 41 years. Most of the interviewees reported being satisfied in regard to the following items: timely service, embracement, trust, environment (comfort, cleanliness and signage), humanization (courtesy, respect, and interest), timely referral/scheduling of appointments and care expectations. CONCLUSION: There was a high level of patient satisfaction, evidenced by the strong association of user satisfaction with the items investigated. OBJETIVO: Avaliar o grau de satisfação dos usuários no setor de Acolhimento com Classificação de Risco do Pronto-Socorro Adulto de um hospital público. MÉTODO: Pesquisa exploratória, descritiva e transversal com abordagem quantitativa. Foram entrevistados 300 usuários e os dados foram analisados por meio de estatística descritiva a partir de variáveis sociodemográficas e as relacionadas à satisfação do usuário. RESULTADOS: Houve predominância do sexo feminino, nível de escolaridade fundamental e idade média de 41 anos. A maioria dos entrevistados respondeu estar satisfeito em relação aos itens: agilidade no atendimento; acolhimento; confiança; ambiência (conforto, limpeza, sinalização), humanização (educação, respeito e interesse); agilidade no encaminhamento/agendamento de consulta e expectativa sobre o serviço. CONCLUSÃO: Verificou-se elevado grau de satisfação dos usuários, evidenciada pela forte associação da satisfação do usuário com os itens investigados.

[Content validation of the nursing diagnosis Nausea]. / Validação de conteúdo do diagnóstico de enfermagem Náusea.

This study aimed to evaluate the content validity of the nursing diagnosis of nausea in the immediate post-operative period, considering Fehring's model. Descriptive study with 52 nurses experts who responded an instrument containing identification and validation of nausea diagnosis data. Most experts considered the domain 12 (Comfort), Class 1 (Physical Comfort) and the statement (Nausea) adequate to the diagnosis. Modifications were suggested in the current definition of this nursing diagnosis. Four defining characteristics were considered primary (reported nausea, increased salivation, aversion to food and vomiting sensation) and eight secondary (increased swallowing, sour taste in the mouth, pallor, tachycardia, diaphoresis, sensation of hot and cold, changes in blood pressure and pupil dilation). The total score for the diagnosis of nausea was 0.79. Reports of nausea, vomiting sensation, increased salivation and aversion to food are strong predictors of nursing diagnosis of nausea.

Comparison of photobiomodulation with cryotherapy in the immediate postpartum period of parturients with grade I, grade II lacerations and/or episiotomy in reducing perineal and vulvar and edema: A randomized clinical trial.

INTRODUCTION: Vaginal delivery has several benefits for the parturient; however, during labor, some injuries, such as lacerations and/or episiotomy, can occur. Perineal pain may occur in the puerperium and can be aggravated in cases of perineal injury during childbirth, potentially impacting the physical and emotional aspects of the parturient. For this reason, it is necessary to use techniques that can relieve pain and edema in the immediate postpartum period, directly influencing recovery. OBJECTIVE: To compare the reduction of pain and improvement in healing using two techniques, namely photobiomodulation and cryotherapy, performed in the immediate postpartum period of up to 12 h, in parturients who suffered grade I and II lacerations and/or episiotomy. METHODS: Data collection was carried out through an evaluation questionnaire. Photobiomodulation was applied using the red and infrared laser from the DMC brand. The EVA and McGill scales were used for pain assessment, and the REEDA scale was used for the evaluation of edema and healing. RESULTS: The techniques were evaluated and applied to 56 patients, with 28 in each group (cryotherapy and LBI). Patients who received photobiomodulation showed superior improvement compared to cryotherapy. In the immediate postpartum period, there was a greater reduction in pain in favor of photobiomodulation (p = 0.008); and after 24 h, the difference was even more significant (p < 0.001).

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.

TLR4 promotes B cell maturation: independence and cooperation with B lymphocyte-activating factor.

We have previously shown that TLR4 triggering promotes the generation of CD23(+)CD93(+) transitional T2-like cells in vitro from mouse B cell precursors, suggesting a possible role for this receptor in B cell maturation. In this study, we perform an extensive study of cell surface markers and functional properties of B cells matured in vitro with LPS, comparatively with the well-known B cell maturation factor B lymphocyte-activating factor (BAFF). LPS increased generation of CD23(+) transitional B cells in a TLR4-dependent way, upregulating IgD and CD21 and downregulating CD93, without inducing cell proliferation, in a manner essentially equivalent to BAFF. For both BAFF and LPS, functional maturation of the IgM(+)CD23(+)CD93(+) cells was confirmed by their higher proliferative response to anti-CD40 plus IL-4 compared with IgM(+)CD23(neg)CD93(+) cells. BAFF-R-Fc-mediated neutralization experiments showed that TLR4-induced B cell maturation was independent of BAFF. Distinct from BAFF, maturation by LPS relied on the activation of canonical NF-kappaB pathway, and the two factors together had complementary effects, leading to higher numbers of IgM(+)CD23(+)CD93(+) cells with their simultaneous addition. Importantly, BCR cross-linking abrogated the generation of CD23(+) B cells by LPS or BAFF, indicating that signals mimicking central tolerance act on both systems. Addition of cyclosporin A reverted BCR-mediated inhibition, both for BAFF and LPS, suggesting similar regulation of signaling pathways by calcineurin. Finally, LPS-injected mice showed a rapid increase of mature B cells in the bone marrow, suggesting that TLR4 signaling may effectively stimulate B cell maturation in vivo, acting as an accessory stimulus in B cell development, complementary to the BAFF physiological pathway.