Bortezomib suppresses acute myelogenous leukaemia stem-like KG-1a cells via NF-κB inhibition and the induction of oxidative stress.

Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a cells, as observed by the reduction in CD34- and CD123-positive cells. A reduction in NF-κB p65 nuclear staining was observed in BTZ-treated KG-1a cells, in addition to upregulation of the NF-κB inhibitor gene NFΚBIB. BTZ-induced DNA fragmentation, nuclear condensation, cell shrinkage and loss of transmembrane mitochondrial potential along with an increase in active caspase-3 and cleaved PARP-(Asp 214) level in KG-1a cells. Furthermore, BTZ-induced cell death was partially prevented by pretreatment with the pancaspase inhibitor Z-VAD-(OMe)-FMK, indicating that BTZ induces caspase-mediated apoptosis. BTZ also increased mitochondrial superoxide levels in KG-1a cells, and BTZ-induced apoptosis was partially prevented by pretreatment with the antioxidant N-acetylcysteine, indicating that BTZ induces oxidative stress-mediated apoptosis in KG-1a cells. At a dosage of 0.1 mg/kg every other day for 2 weeks, BTZ significantly reduced the percentage of hCD45-positive cells in the bone marrow and peripheral blood of NSG mice engrafted with KG-1a cells with tolerable toxicity. Taken together, these data indicate that the anti-LSC potential of BTZ appears to be an important strategy for AML treatment.

Are women with endometriosis more likely to experience reduced physical performance compared to women without the condition?

Background: Endometriosis is a condition of the female reproductive system associated with pelvic pain. Chronic pain can affect physical performance by limiting the functional activities, thus, it is hypothesized that women with endometriosis may also present decreased functional capacity, decreased strength, and mobility. The objective of this study is to compare physical performance in women with and without endometriosis. Methods: This is a cross-sectional study composed of 115 women equally divided into two groups: the endometriosis group (EG), composed of women with a confirmed diagnosis of the disease by magnetic resonance imaging, and the comparator group (CG), consisting of women without suspicion of the disease. Physical performance (dependent variable) was assessed using hand dynamometry, the 6-min walk test (6MWT), gait speed, and the chair stands test. CG participants performed the tests during the luteal phase of the menstrual cycle. Descriptive statistics, unpaired t-tests, and chi-square tests were used to describe and compare the groups. Multiple linear regression tested the associations adjusted for covariates (age, income, education, age at menarche, and body mass index). Results: The EG had worse gait speed (mean difference: -0.11; 95% CI: [-0.18 to -0.04]), weaker grip strength (mean difference: -3.32; 95% CI: [-5.30 to -1.33]), shorter distance covered in the 6MWT (mean difference: -83.46; 95% CI: [-121.38 to -45.53]), and a lower number of repetitions in the chair stands test (mean difference: -8.44; 95% CI: [-10.64 to -6.25]) than the CG, even after adjusting for covariates. Conclusion: Grip strength, lower limb strength, mobility, and functional capacity were worse in women diagnosed with endometriosis. Women with endometriosis should be encouraged to engage in physical exercise, adopt healthy lifestyle habits, and participate in rehabilitation activities to control pain, with the aim of reducing functional impairments.

Emetine induces oxidative stress, cell differentiation and NF-κB inhibition, suppressing AML stem/progenitor cells.

Acute myeloid leukemia (AML) is a fatal malignancy of the blood and bone marrow. Leukemic stem cells (LSCs) are a rare subset of leukemic cells that promote the development and progression of AML, and eradication of LSCs is critical for effective control of this disease. Emetine is an FDA-approved antiparasitic drug with antitumor properties; however, little is known about its potential against LSCs. Herein, we explored the antileukemic potential of emetine, focusing on its effects on AML stem/progenitor cells. Emetine exhibited potent cytotoxic activity both in hematologic and solid cancer cells and induced AML cell differentiation. Emetine also inhibited AML stem/progenitor cells, as evidenced by decreased expression of CD34, CD97, CD99, and CD123 in KG-1a cells, indicating anti-AML stem/progenitor cell activities. The administration of emetine at a dosage of 10 mg/kg for two weeks showed no significant toxicity and significantly reduced xenograft leukemic growth in vivo. NF-κB activation was reduced in emetine-treated KG-1a cells, as shown by reduced phospho-NF-κB p65 (S529) and nuclear NF-κB p65. DNA fragmentation, YO-PRO-1 staining, mitochondrial depolarization and increased levels of active caspase-3 and cleaved PARP (Asp214) were detected in emetine-treated KG-1a cells. Moreover, treatment with the pancaspase inhibitor Z-VAD(OMe)-FMK partially prevented the apoptotic cell death induced by emetine. Emetine treatment also increased cellular and mitochondrial reactive oxygen species, and emetine-induced apoptosis in KG-1a cells was partially prevented by the antioxidant N-acetylcysteine, indicating that emetine induces apoptosis, at least in part, by inducing oxidative stress. Overall, these studies indicate that emetine is a novel potential anti-AML agent with promising activity against stem/progenitor cells, encouraging the development of further studies aimed at its clinical application.

Piplartine eliminates CD34 + AML stem/progenitor cells by inducing oxidative stress and suppressing NF-κB signalling.

Acute myeloid leukaemia (AML) is a haematological malignancy characterised by the accumulation of transformed myeloid progenitors in the bone marrow. Piplartine (PL), also known as piperlongumine, is a pro-oxidant small molecule extracted from peppers that has demonstrated antineoplastic potential in solid tumours and other haematological malignancies. In this work, we explored the potential of PL to treat AML through the use of a combination of cellular and molecular analyses of primary and cultured leukaemia cells in vitro and in vivo. We showed that PL exhibits in vitro cytotoxicity against AML cells, including CD34+ leukaemia-propagating cells, but not healthy haematopoietic progenitors, suggesting anti-leukaemia selectivity. Mechanistically, PL treatment increased reactive oxygen species (ROS) levels and induced ROS-mediated apoptosis in AML cells, which could be prevented by treatment with the antioxidant scavenger N-acetyl-cysteine and the pancaspase inhibitor Z-VAD(OMe)-FMK. PL treatment reduced NFKB1 gene transcription and the level of NF-κB p65 (pS536), which was depleted from the nucleus of AML cells, indicating suppression of NF-κB p65 signalling. Significantly, PL suppressed AML development in a mouse xenograft model, and its combination with current AML treatments (cytarabine, daunorubicin and azacytidine) had synergistic effects, indicating translational therapeutic potential. Taken together, these data position PL as a novel anti-AML candidate drug that can target leukaemia stem/progenitors and is amenable to combinatorial therapeutic strategies.

A Health App for Evidence-Based Postpartum Information: Development and Validation Study.

BACKGROUND: After childbirth, women undergo substantial physical and emotional changes. Therefore, it is important to provide them with information that helps them identify what is expected during this stage, as well as signs and symptoms that indicate complications after they have been discharged from the hospital. OBJECTIVE: This study aimed to develop a health app-Towards Motherhood-that provides evidence-based information about the postpartum period and evaluate the usability of the app with the target population. METHODS: This was a validation study involving 80 participants, including 24 professionals from the obstetric health field, 15 professionals from the technology field, and 41 postpartum women. The app was developed using React Native technology. Health professionals evaluated the app's content using the Content Validity Index, technology professionals completed a validated evaluation to assess the appearance of the app, and postpartum women completed the System Usability Scale (SUS) to measure the usability of the app. RESULTS: The measurement of content validity using a Likert scale obtained an approval score of 99%. Regarding the app's appearance, 92% of responses were positive, reflecting favorable approval. The SUS usability score was 86.2, which represents excellent acceptance. CONCLUSIONS: The Towards Motherhood mobile app is a valid tool for promoting self-care during the postpartum period. The app's evidence-based information, user-friendly design, and high usability make it an essential resource for women during this critical stage of their live.

Emerging drugs targeting cellular redox homeostasis to eliminate acute myeloid leukemia stem cells.

Acute myeloid leukemia (AML) is a very heterogeneous group of disorders with large differences in the percentage of immature blasts that presently are classified according to the specific mutations that trigger malignant proliferation among thousands of mutations reported thus far. It is an aggressive disease for which few targeted therapies are available and still has a high recurrence rate and low overall survival. The main reason for AML relapse is believed to be due to leukemic stem cells (LSCs) that have unlimited self-renewal capacity and long residence in a quiescent state, which promote greater resistance to traditional therapies for this cancer. AML LSCs have low oxidative stress levels, which appear to be caused by a combination of low mitochondrial activity and high activity of ROS-removing pathways. In this sense, oxidative stress has been thought to be an important new potential target for the treatment of AML patients, targeting the eradication of AML LSCs. The aim of this review is to discuss some drugs that induce oxidative stress to direct new goals for future research focusing on redox imbalance as an effective strategy to eliminate AML LSCs.

Genomic, biochemical, and phylogenetic evaluation of bacteria isolated from deep-sea sediment harboring methane hydrates.

Over half of the organic carbon on Earth's surface is trapped in marine sediment as methane hydrates. Ocean warming causes hydrate dissociation and methane leakage to the water column, rendering the characterization of microbes from hydrate depositions a pressing matter. Through genomic, phylogenetic, and biochemical assays, we characterize the first microorganisms isolated from the Rio Grande Cone (Brazil), reservoir responsible for massive methane releases to the water column. From sediment harboring rich benthic communities, we obtained 43 strains of Brevibacillus sp., Paenibacillus sp. and groups of Bacillus sp. Methane-enriched samples yielded strains of the Pseudomonas fluorescens complex, exhibiting fluorescent siderophore production and broad multi-carbon catabolism. Genomic characterization of a novel Pseudomonas sp. strain indicated 32 genes not identified in the closest related type-species, including proteins involved with mercury resistance. Our results provide phylogenetic and genomic insights on the first bacterial isolates retrieved from a poorly explored region of the South Atlantic Ocean.

Chemical composition of selected insect meals and their effect on apparent total tract digestibility, fecal metabolites, and microbiota of adult cats fed insect-based retorted diets.

Insect meals are novel and potentially sustainable protein sources. The objectives of this study were to determine the chemical composition and standardized amino acid digestibility using the cecectomized rooster model of three selected insect meals (i.e., speckled cockroach [SC], Madagascar hissing cockroach [MC], and superworm [SW]) and to determine the effects of these insect meals on food intake, apparent total tract digestibility (ATTD) of macronutrients, fecal scores, and metabolites of adult cats fed insect- or chicken-based retorted diets. This study consisted of a complete randomized design, with 28 adult cats randomly assigned to one of the four experimental retorted diets: Control (chicken-based diet), SC diet, MC diet, or SW diet. All animal procedures were approved by the University of Illinois Institutional Animal Care and Use Committee. All diets were formulated to be complete and balanced and meet or exceed the nutritional requirements of adult cats. The experimental period was 28 d, with the first 7 d allotted for diet adaptation. The total fecal collection was completed during the last 4 d of the experimental period. On day 21, a fresh fecal sample from each cat was collected for the determination of fecal metabolites and microbiota. Food was offered twice daily to maintain body weight and body condition score. Among the three selected insect meals evaluated, oleic acid, palmitic acid, linoleic acid, and stearic acid were the most prevalent fatty acids. Branched-chain amino acids and arginine were the most preponderant indispensable amino acids in these insect meals. ATTD of dry matter, organic matter, acid-hydrolyzed fat, and crude protein did not differ among treatments (P > 0.05), and all diets were well digested by the cats. Similarly, fecal scores did not differ among the treatments and were within ideal range. No differences (P > 0.05) in fecal metabolite concentrations or microbiota diversity were observed among cats fed different experimental diets; only a few genera from Firmicutes and Bacteroidota phyla differ (P < 0.05) in cats fed SW diet in contrast to other dietary treatments. In conclusion, the selected insect meals evaluated herein are rich in linoleic acid, an essential fatty acid for cats. Insect-based retorted diets led to comparable results to those achieved with a chicken-based retorted diet, suggesting that these novel protein sources might be adequate alternative ingredients in feline diets.

Insect meals are novel and potentially sustainable protein sources. The objectives of this study were to determine the nutrient composition of speckled cockroach, Madagascar hissing cockroach, and superworm (SW) and to determine the effects of these insect meals on food intake, digestibility of macronutrients, fecal scores, metabolites, and microbiota of adult cats fed insect- or chicken-based wet pet foods. Among the three selected insect meals evaluated, oleic acid, palmitic acid, linoleic acid, and stearic acid were the most prevalent fatty acids. Branched-chain amino acids and arginine were the most preponderant indispensable amino acids in these insect meals. All diets were well digested by the cats with no differences observed on macronutrient digestibility. Similarly, fecal scores did not differ among the treatments and were within the ideal range. No differences in fecal metabolite concentrations were observed. Only a few genera from Firmicutes and Bacteroidota phyla differ in cats fed SW diet in contrast to other dietary treatments. Overall, the selected insect meals evaluated herein are rich in linoleic acid, an essential fatty acid for cats. Insect-based retorted diets led to comparable results to those achieved with a chicken-based retorted diet, suggesting that these novel protein sources might be adequate alternative ingredients in feline diets.

Biochemical features and early adhesion of marine Candida parapsilosis strains on high-density polyethylene.

AIMS: Plastic debris are constantly released into oceans where, due to weathering processes, they suffer fragmentation into micro- and nanoplastics. Diverse microbes often colonize these persisting fragments, contributing to their degradation. However, there are scarce reports regarding the biofilm formation of eukaryotic decomposing microorganisms on plastics. Here, we evaluated five yeast isolates from deep-sea sediment for catabolic properties and early adhesion ability on high-density polyethylene (HDPE). METHODS AND RESULTS: We assessed yeast catabolic features and adhesion ability on HDPE fragments subjected to abiotic weathering. Adhered cells were evaluated through Crystal Violet Assay, Scanning Electron Microscopy, Atomic Force Microscopy and Infrared Spectroscopy. Isolates were identified as Candida parapsilosis and exhibited wide catabolic capacity. Two isolates showed high adhesion ability on HDPE, consistently higher than the reference C. parapsilosis strain, despite an increase in fragment roughness due to weathering. Isolate Y5 displayed the most efficient colonization, with production of polysaccharides and lipids after 48 h of incubation. CONCLUSION: This work provides insights on catabolic metabolism and initial yeast-HDPE interactions of marine C. parapsilosis strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings represent an essential contribution to the characterization of early interactions between deep-sea undescribed yeast strains and plastic pollutants found in oceans.

Pelvic floor muscle training program for women in the puerperal period: clinical progress after intervention.

OBJECTIVE: To evaluate the sexual function of women in the puerperal period after a postpartum pelvic floor musculature training program. We also sought to evaluate correlations between sexual dysfunction in the women and their delivery type and compare the frequency of sexual dysfunction and the quality of resumed sexual function following vaginal and cesarean deliveries. METHODS: This clinical study included an intervention, carried out between July and December 2019, in which data were collected about 28 rooming-in women at a Maternity School. Data were divided into vaginal delivery and cesarean delivery. Sexual function was evaluated by the Female Sexual Function Index and the International Consultation on Incontinence Questionnaire-Short Form to assess the Incontinence Urinary and qualifies urinary loss. The intervention consisted of a muscle training exercise program. ANOVA tests were used to establish differences between groups. RESULTS: There was an improvement in all outcomes, but there was no time versus group interaction. Improvement in sexual function was observed (p<0.001), the impact of urinary incontinence on quality of life (p<0.001), and pressure of the muscles of pelvic floor muscles (p<0.001) over time. There was no time versus group interaction for sexual function (p=0.87), the impact of urinary incontinence on quality of life (p=0.88), and pressure of the pelvic floor muscles (p=0.66). CONCLUSIONS: Pelvic floor muscle exercise programs seem to be a very promising strategy concerning improving sexual activity among puerperal patients.

Evaluation of satisfaction of pelvic floor muscle training isolated and associated with tibial nerve stimulation in women with mixed urinary incontinence: A randomized, single-blinded clinical trial.

OBJECTIVES: To compare the satisfaction degree and pelvic floor manometry after pelvic floor muscle training isolated and associated with tibial nerve stimulation in women with mixed urinary incontinence (MUI). STUDY DESIGN: A randomized, single-blinded clinical trial was conducted. 24 women diagnosed with MUI were equally divided into two groups: pelvic floor muscle training isolated and associated to transcutaneous tibial nerve stimulation (TTNS). The study occurred in four stages: 1) evaluation: general information, pelvic floor manometry, the International Consultation on Incontinence Questionnaire - Urinary Incontinence - Short Form (ICIQ-UI-SF) and International Consultation on Incontinence Questionnaire - Overactive Bladder (OAB) application; 2) intervention: carried out over 2 months twice a week; 3) post-intervention evaluation: vaginal manometry, reapplication of the questionnaires and the Patient Global Impression (PGI) application at the end of the 2-month intervention; and, 4) follow-up: evaluation after 1 month of the end of the intervention. The primary outcome was the ICIQ-UI-SF and the secondary outcomes were ICIQ-OAB, vaginal manometry, and PGI. The repeated measures ANOVA was used to assess the time-to-group interaction by assigning a significance level of 5%. RESULTS: There was no interaction between time and group for ICIQ-UI-SF (p = 0.17) and manometry (p = 0.56). There was interaction for ICIQ-OAB (p < 0.01). PGI was reported as "much better" with 41.67% in the PFMTG + TTNS and 16.67% in the PFMTG after the intervention (p = 0.04). CONCLUSIONS: The results showed weak evidence that TTNS, in combination with PFMT, may be an intervention that can be used to treat MUI. The satisfaction degree was better with associated intervention.

Transcranial direct current electrical stimulation for the treatment of interstitial cystitis: A study protocol.

BACKGROUND: Interstitial cystitis or painful bladder syndrome is a chronic disorder that presents an unknown etiology, with no generally accepted treatment. Although there is no gold standard treatment, transcranial direct current stimulation (tDCS) has shown efficacy in several chronic pain syndromes with decrease in pain, and improved functionality and mood. tDCS could be a safe, ease to use, and low-cost complementary intervention for patients with interstitial cystitis. AIM: This study will investigate the effects of a tDCS protocol on pain, functionality, and mood in patients with interstitial cystitis. METHODS: A randomized controlled clinical trial with two arms. Women will be randomized into two groups: active or sham. Anodal tDCS over the primary motor cortex will be performed for 5 consecutive days with an intensity of 2 mA for 20 min. Participants will be evaluated five times: 1 week before intervention; on the 5th day of tDCS; and 1, 6, and 12 months after the last day of tDCS. The outcomes will be assessed using the numeric rating scale, McGill pain questionnaire, positive and negative affect scale, international consultation on incontinence questionnaire for female lower urinary tract symptoms, Hamilton anxiety scale, six-minute walk test, patient global impression of change, and voiding diary. DISCUSSION: Only the active group will be expected to show decreased pain. The results of this trial will be the first step in the use of neuromodulation in interstitial cystitis and will provide additional data to support new studies with tDCS.

Pelvic floor muscle training program for women in the puerperal period: clinical progress after intervention

SUMMARY OBJECTIVE: To evaluate the sexual function of women in the puerperal period after a postpartum pelvic floor musculature training program. We also sought to evaluate correlations between sexual dysfunction in the women and their delivery type and compare the frequency of sexual dysfunction and the quality of resumed sexual function following vaginal and cesarean deliveries. METHODS: This clinical study included an intervention, carried out between July and December 2019, in which data were collected about 28 rooming-in women at a Maternity School. Data were divided into vaginal delivery and cesarean delivery. Sexual function was evaluated by the Female Sexual Function Index and the International Consultation on Incontinence Questionnaire-Short Form to assess the Incontinence Urinary and qualifies urinary loss. The intervention consisted of a muscle training exercise program. ANOVA tests were used to establish differences between groups. RESULTS: There was an improvement in all outcomes, but there was no time versus group interaction. Improvement in sexual function was observed (p<0.001), the impact of urinary incontinence on quality of life (p<0.001), and pressure of the muscles of pelvic floor muscles (p<0.001) over time. There was no time versus group interaction for sexual function (p=0.87), the impact of urinary incontinence on quality of life (p=0.88), and pressure of the pelvic floor muscles (p=0.66). CONCLUSIONS: Pelvic floor muscle exercise programs seem to be a very promising strategy concerning improving sexual activity among puerperal patients.

Biofilms of Pseudomonas and Lysinibacillus Marine Strains on High-Density Polyethylene.

Environmental pollution by plastic debris is estimated on a scale of 100 million metric tons, a portion of which is fragmented into micro- and nanoplastics. These fragments are often colonized by bacterial species in marine environments, possibly contributing to the biodegradation of such materials. However, further investigations are necessary to determine the impact of abiotic polymer weathering on biofilm adhesion, as well as the specific biofilm formation strategies employed by marine isolates. Here, we evaluate deep-sea sediment bacterial isolates for biofilm adhesion, extracellular matrix production, and polymer degradation ability. Our study focuses on high-density polyethylene (HDPE) fragments for their high durability and environmental persistence, subjecting fragments to abiotic weathering prior to bacterial colonization. Marine isolates identified as Pseudomonas sp. and Lysinibacillus sp. exhibited decreasing biofilm formation on weathered HDPE, especially over the first 24 h of incubation. This effect was countered by increased extracellular matrix production, likely improving cell adhesion to surfaces roughened by abiotic degradation. These adhesion strategies were contrasted with a reference Pseudomonas aeruginosa strain, which displayed high levels of biofilm formation on non-weathered HDPE and lower extracellular matrix production over the first 24 h of incubation. Furthermore, our results suggest that an increase in biofilm biomass correlated with changes to HDPE structure, indicating that these strains have a potential for biodegradation of plastic fragments. Therefore, this work provides a detailed account of biofilm formation strategies and bacteria-plastic interactions that represent crucial steps in the biodegradation of plastic fragments in marine environments.

Redes de atenção à saúde e implicações no cuidado pós-alta hospitalar: um estudo de caso / Health care networks and implications on post-discharge care: a case study / Redes de atención de salud e implicaciones en la atención posthospitalaria: un estudio de caso

Este estudo buscou compreender os caminhos percorridos por uma usuária do Sistema Único de Saúde (SUS) em busca do cuidado no pós-alta hospitalar, destacando as experiências relacionadas às Redes de Atenção à Saúde (RAS) e os entraves encontrados em seu percurso. Foi realizado um estudo de caso com abordagem qualitativa e as técnicas de produção de dados foram diário de campo e entrevista semiestruturada. Foram identificados fatores como: fragmentação do cuidado e ausência de integração das Redes de Atenção à Saúde. Constatou-se que é imprescindível a consolidação de estratégias para estruturação das Redes de Atenção à Saúde no estado da Bahia, visando ao acesso e à integralidade do cuidado.

This study sought to understand the paths taken by a user of the Brazilian Unified Health System (SUS) seeking care after hospital discharge, highlight her experiences related to the Health Care Networks (RAS) and the obstacles encountered along the way. A qualitative case study with qualitative was carried out using data collected by field diary and semi-structured interviews. Factors such as fragmentation of care and lack of integration between Health Care Networks were identified. In conclusion, it is essential to consolidate strategies for structuring the Health Care Networks in the state of Bahia, aiming at access and comprehensiveness of care.

Este estudio tuvo como objetivo comprender los caminos tomados por una usuaria del Sistema Único de Salud (SUS) en busca de atención después del alta hospitalaria, destacando las experiencias relacionadas con las redes de atención de salud (RAS) y los obstáculos durante el camino. Se realizó un estudio de caso, con enfoque cualitativo, y las técnicas de producción de datos fueron el diario de campo y la entrevista semiestructurada. Los factores identificados fueron: fragmentación de la atención y falta de integración de las redes de atención de salud. Se descubrió que es esencial consolidar estrategias para estructurar las redes de atención de salud en el estado de Bahía con el objetivo brindar acceso y atención integral a la población.

Game therapy a new approach to treat women facing mixed urinary incontinence: A study protocol.

AIMS: To describe a pelvic floor muscle training (PFMT) isolated and associated with game therapy (PFMT + GT) for women facing mixed urinary incontinence (MUI) during climacteric period. METHODS: To standardize a randomized controlled clinical trial intervention, a protocol was created, in an attempt to decrease women's symptomatology generated by MUI, through pelvic floor and abdomino-loin-pelvic muscles strength, and endurance. This study protocol will be composed of 32 volunteers, divided into two groups of 16. They will perform PFMT isolated or PFMT + GT, twice a week during 8 weeks. Interventions will last 40 minutes and will be divided into warming (5 minutes), training (30 minutes), and 5 minutes will be composed of resting time between exercises (1 minute each). Isolated PFMT sessions will be performed through four modalities of exercises: diaphragmatic, bridge, abdominal (plank), and pelvic mobility. PFMT + GT training will be carried out by using Wii Fit Plus games, such as Lotus Focus, Penguin Slide, Basic Step, and Hula Hoop from Wii equipment. Assessments will occur before, after, and 1 month after interventions. Vaginal manometry, 1-hour Pad Test, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), and Patient Global Intervention (PGI) will be used to evaluate the sample. CONCLUSIONS: It is expected greater increase on pelvic floor muscle (PFM) strength, endurance, vaginal pressure for PFMT + GG. Moreover, it is supposed that PFMT + GT volunteers present better treatment adherence due to games motivational inclusion.

Participação do pai no aleitamento materno exclusivo / Father's participation in exclusive breastfeeding

Objetivo: conhecer a influência da participação do pai no aleitamento materno exclusivo. Metodologia: pesquisa qualitativa descritiva e exploratória, realizada por meio de entrevista semiestruturada, com 10 mães, que fizeram acompanhamento em uma Unidade Básica de Saúde durante o pré-natal, puerpério e/ou puericultura nos anos 2017 e 2018, e que amamentaram de forma exclusiva, até os seis meses do bebê. A análise temática subsidiou a análise e discussão dos dados, emergindo as seguintes categorias: Amamentação e a participação do pai, e a importância de incentivar a participação do pai no processo de amamentar. Resultados: evidenciaram que o apoio do pai influenciou positivamente a conquista do aleitamento materno exclusivo, visto que muitas se sentiam amparadas e seguras com a presença do pai. Também foi possível identificar fragilidades no que tange o incentivo da participação do pai na amamentação. Conclusão: é necessário incorporar estratégias para incentivar a participação dos pais no processo do aleitamento materno, por meio de ações educativas voltadas ao casal.

Objective: to know the influence of the father's participation in breastfeeding. Methodology: it is a descriptive and exploratory qualitative research, carried out through semi-structured interviews, with 10 mothers, who were followed up in a basic health unit during prenatal, puerperium and/or childcare in 2017 and 2018, and who exclusively breastfed up to six months-old of the baby. The thematic analysis supported the analysis and the discussion of the data, when the following categories emerged: Breastfeeding and the father's participation, and the importance of encouraging the father's participation in the breastfeeding process. Results: they evidenced that the father's support have influenced the achievement of exclusive breastfeeding positively, since many of them felt supported and safe with the father's presence. It was also possible to identify weaknesses in terms of encouraging the father's participation in breastfeeding. Conclusion: it is necessary to incorporate an objective to encourage parental participation in the breastfeeding process, through educational actions aimed at the couple.

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells.

Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.

Oat beta-glucan as a dietary supplement for dogs.

The aim of this study was to evaluate the effects of oat beta-glucan supplementation on metabolic, physiological, immunological and nutritional variables in adult dogs. Fourteen dogs were fed a control diet or a diet supplemented with 1% beta-glucan during 71 days. Serum concentrations of glucose, total cholesterol and lipoprotein fractions, as well as plasma concentrations of peptide YY and ghrelin, were determined. In addition, coefficient of total tract apparent macronutrient digestibility (CTTAD), food intake and fecal output, score, and pH were evaluated. For evaluation of immunological variables, serum concentrations of interleukin-4 and interferon gamma were determined on days 0, 57 and 71, which corresponded to blood collection prior to beta-glucan supplementation, and at 7 and 14 days post first and second dose of vaccination (Pneumodog®, Merial, Campinas, Brazil), respectively. Animals fed the supplemented diet showed (P<0.05) lower serum concentrations of total cholesterol and low and very low density lipoproteins, lower coefficients of total tract apparent digestibility of dry matter, organic matter, mineral matter and ether extract, higher fecal output and lower fecal consistency, as well as a tendency (P = 0.07) of decreasing the coefficient of total tract apparent digestibility of crude protein. Moreover, the supplemented diet resulted in lower number of red blood cells, hematocrit percentage and hemoglobin concentration 21 days post-vaccination as well as lower serum concentration of interleukin-4 seven days post-vaccination (P<0.05). It is concluded that oat beta-glucan extract can be used as a dietary supplement for dogs at a dose of 10 g/kg of food, being effective in reducing blood concentrations of total cholesterol, LDL-c and VLDL-c as well as CTTAD of nutrients, demonstrating a potential to be used in the feeding of obese animals. In addition, by reducing the predominance of a Th2 response, oat beta-glucan can positively modulate the vaccine response of animals.

Ru(II)-Thymine Complex Causes Cell Growth Inhibition and Induction of Caspase-Mediated Apoptosis in Human Promyelocytic Leukemia HL-60 Cells.

Ruthenium-based compounds represent a class of potential antineoplastic drugs. Recently, we designed, synthesized, and identified the Ru(II)-thymine complex [Ru(PPh3)2(Thy)(bipy)]PF6 (where PPh = triphenylphosphine, Thy = thymine and bipy = 2,2'-bipyridine) as a potent cytotoxic agent with the ability to bind to DNA and human and bovine serum albumins. In this study, the underlying cytotoxic mechanism of the [Ru(PPh3)2(Thy)(bipy)]PF6 complex was assessed. This complex displayed potent cytotoxicity in different cancer cell lines; the morphology that is associated with apoptotic cell death, increased internucleosomal DNA fragmentation without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization, and caspase-3 activation were observed in human promyelocytic leukemia HL-60 cells that were treated with the complex. Moreover, pretreatment of HL-60 cells with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, partially reduced the apoptosis that was induced by the complex, indicating that the apoptotic cell death occurred through a caspase-mediated pathway. In conclusion, the [Ru(PPh3)2(Thy)(bipy)]PF6 complex displays potent cytotoxicity to different cancer cells and induces caspase-mediated apoptosis in HL-60 cells.