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Evidence suggests that maternal metabolome may be associated with child health outcomes. We analyzed the association between the maternal metabolome between 28-35 gestational weeks and child growth and development during the first year. A prospective cohort of 98 mother-child dyads was followed at birth, 1, 6, and 12 months. Maternal serum samples were collected for targeted LC-MS/MS analysis, which measured 132 metabolites. The child's growth and development were assessed at each time-point. Z-scores were calculated based on WHO growth standards, and the domains of development were assessed using the Ages and Stages Questionnaires (ASQ-3). Multiple linear mixed-effects models were performed and confounders were identified using a Diagram Acyclic Graph. The Benjamini-Hochberg correction was used for multiple comparison adjustments. We found a positive association between lysophosphatidylcholines (14:0; 16:0; 16:1; 17:0; 18:0; 18:1; 18:2; 20:4) with the z-score of weight-for-age, and lysophosphatidylcholines (14:0; 16:0; 16:1; 18:0) and taurine with the z-score of weight-for-length, and lysophosphatidylcholines (14:0; 16:0; 16:1; 17:0; 18:0; 18:1; 18:2; 20:4) and glycine with the z-score of BMI-for-age. The leucine, methionine, tryptophan, and valine were negatively associated with the fine motor skills domain. We observed an association between maternal metabolome and the growth and child's development throughout the first year.
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Desenvolvimento Infantil , Metaboloma , Terceiro Trimestre da Gravidez , Humanos , Feminino , Gravidez , Lactente , Terceiro Trimestre da Gravidez/sangue , Recém-Nascido , Masculino , Estudos Prospectivos , Adulto , MãesRESUMO
BACKGROUND: The COVID-19 pandemic added new challenges and stressors to the childbirth period, potentially increasing the risk of traumatic childbirth experiences. There is little known about posttraumatic growth (PTG) in a childbearing population. This study describes PTG in women after traumatic childbirth during the COVID-19 pandemic and its association with sociodemographic, birth-related characteristics, traumatic childbirth events, perceived stress, and core beliefs, as well as explores what factors predict PTG. METHODS: A cross-sectional study was conducted with 202 women who self-identified as having experienced traumatic childbirth. Measures included sociodemographic and birth-related characteristics, traumatic childbirth events, self-reported stress during childbirth, the PTG Inventory, and the Core Beliefs Inventory (CBI). RESULTS: Perceived stress at the time of birth was very high in 70% of the respondents. CBI showed moderate disruption of core beliefs. 41.6% of mothers indicated substantial PTG. Education and type of birth were related to perceived stress levels; higher disruption of core beliefs was observed in individuals who experienced perineal trauma and lack of partners' presence during childbirth, and higher disruption of core beliefs was positively associated with PTG. Predictive models showed that perceived stress had a minimal effect, while the disruption of core beliefs showed a significant positive association with PTG. CONCLUSION: Traumatic childbirth experiences during the COVID-19 pandemic were positively related to PTG. Health professionals should create an environment where women can explore their feelings and emotions. Changes in current practices are also necessary as cesareans have been shown to be highly associated with high levels of perceived stress.
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Progesterone (P4) is predicted to act as a negative regulatory hormone for oocyte maturation events; however, its local effects during follicular development remain poorly understood in bovine. The complex process of oocyte meiosis progression is dependent on cellular communication among follicular cells. Besides, the breakdown of this communication, mainly between cumulus cells (CC) and oocyte, through the retraction of cumulus projections connecting these cells can impact oocyte maturation. In our study, we observed that follicles from the ovary ipsilateral to the corpus luteum (CL) containing high intrafollicular P4 concentrations enhance the abundance of proteins detected in follicular-derived small extracellular vesicles (sEVs) predicted to be involved in the retraction of membrane projections based on actin filaments, such as transzonal projections (TZPs). Conversely, we found that follicles from the ovary contralateral to the CL, which contained low intrafollicular P4 concentrations, had a high detection of proteins predicted to regulate the maintenance of TZPs. We also performed RNAseq analysis which demonstrated that 177 genes were differentially expressed in CC under the different P4 environments. Bioinformatic analysis points to changes associated to cell metabolism in cells from follicles ipsilateral to the CL in comparison to genes involved in cell communication in CC from follicles contralateral to the CL. Our functional analysis experiment confirmed that supplementation of cumulus-oocyte complexes during in vitro maturation with P4 at concentration similar to ipsilateral follicles reduces the number of TZPs. In summary, our study underscores a direct association between P4 concentration and cumulus-oocyte interaction, with potential consequences for the acquisition of oocyte competence.
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Introduction: Preoperative anxiety, with its multifactorial origins, affects a wide range of surgical patients, leading to adverse physiological and psychological effects in the perioperative period. Customized, autonomous nursing interventions are needed to address individual person needs. The shift toward outpatient surgery emphasizes the need for restructured nursing approaches. Existing literature suggests that preoperative nursing consultations offer opportunities for assessing needs, providing information, and prescribing anxiety-reduction strategies. Psychoeducation, a specialized skill within mental health and psychiatric nursing, has proven effective in alleviating preoperative anxiety and reducing postoperative complications. The aim is to obtain and analyze the information reflecting nurses' understanding of the design, structure, and operationalization of a psychoeducation program to reduce preoperative anxiety in adults. Methods: A qualitative, exploratory, descriptive study was conducted. Data were collected through a 90-min focus group session held online via Zoom Meetings videoconferencing platform. Inclusion criteria for the participant's selection were established. The focus group was guided to deliberate on potential strategies for crafting effective psychoeducational interventions. Data collection ceased upon reaching theoretical saturation and gathered information was submitted for content analysis. Ethical procedures were ensured. Results: Of the participants, 10 were specialist nurses (7 working in mental health and psychiatric nursing and the remaining in medical-surgical nursing), with an average age of 41 and an average of 15 years working in surgical services. The nurses selected the target population, the structure and content of the psychoeducation sessions, and the resources and addressed the perceived importance, effectiveness, and feasibility of the designed psychoeducation program. Discussion: The study revealed the nurses' understanding of the design of a psychoeducation program potentially effective in reducing preoperative anxiety in adults, in an outpatient surgery context. This result will allow the transfer of the produced knowledge to nurses' professional practice reflecting lower levels of anxiety and promoting a better surgical recovery. This is an unprecedented study conducted in Portugal, adding substantial knowledge to the nursing discipline. However, further research into implementing psychoeducation in a surgical context is suggested aiming to consolidate the results of research already carried out internationally.
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Ansiedade , Grupos Focais , Pesquisa Qualitativa , Humanos , Ansiedade/prevenção & controle , Adulto , Feminino , Cuidados Pré-Operatórios , Masculino , Educação de Pacientes como Assunto/métodos , Pessoa de Meia-Idade , Enfermagem Psiquiátrica/educaçãoRESUMO
BACKGROUND: Ministerial Decrete 77 (DM 77) promotes dehospitalization for chronic patients and defines out-of-hospital health facilities at this purpose. It has never been investigated how much patients with cancer know and judge this decree law. MATERIAL AND METHODS: The Collegio italiano dei primari oncologi medici ospedalieri (Cipomo) carried out a survey with a dedicated questionnaire on oncological patients attending public hospital to investigate the liking of DM 77. RESULTS: Anonymous responses were obtained from 1.443 patients. Median age 64ys, 42% males, 21% live alone, 70% have a companion. 19% thinks that oral chemotherapy could be managed outside the hospital, 26.68% carried out follow-up (FU),19.15% parenteral therapy, 32.16% basic examinations. Home is preferred by 21.8%, a health facility close to home by 36.3%, hospital by 37.54%. 59.67% would like FU in hospital by their personal oncologist, 5.47% by GP, 35.41% by both together and 9.45% by oncologist outside the hospital. Asked what they might feel about being followed out of the hospital, 29.94% say of not being treated at its best, 12.68% of not being able to be visited in hospital anymore, 5.27% of being abandoned, 30.7% of being freer and 10.88% of feeling less sick. Regarding the use of new technical tools to favor dehospitalisation, 44.15% answered yes, 15.88% no and 30.07% did not know. About the distance or traveling time from home to the therapy administration side, 20.26% answered this should be no more than 15 km or 30 mins, 9.91% no more than 30 km or 45 mins, 5.47% no more than 50 km or 60 mins but 39.5% say that the distance does not matter to them but only the continuity of care. The question related to the inconveniences with going to hospital for therapy: 40.81% waiting time, 20.47% lack of parking, 17.02% rotation of doctors,12.76% travel time and 5.62% bureaucracy. CONCLUSIONS: The patients' answers suggest that dehospitalization could improve their quality of life, but at the condition of being able to maintain a close relationship with the personal oncologist.
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Neoplasias , Humanos , Itália , Neoplasias/tratamento farmacológico , Neoplasias/terapia , Inquéritos e Questionários , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Adulto , Idoso de 80 Anos ou mais , Hospitais Públicos , Hospitalização/estatística & dados numéricosRESUMO
INTRODUCTION: Gene identification for genetic diseases is critical for the development of new diagnostic approaches and personalized treatment options. Prioritization of gene translation is an important consideration in the molecular biology field, allowing researchers to focus on the most promising candidates for further investigation. AREAS COVERED: In this paper, we discussed different approaches to prioritize genes for translation, including the use of computational tools and machine learning algorithms, as well as experimental techniques such as knockdown and overexpression studies. We also explored the potential biases and limitations of these approaches and proposed strategies to improve the accuracy and reliability of gene prioritization methods. Although numerous computational methods have been developed for this purpose, there is a need for computational methods that incorporate tissue-specific information to enable more accurate prioritization of candidate genes. Such methods should provide tissue-specific predictions, insights into underlying disease mechanisms, and more accurate prioritization of genes. EXPERT OPINION: Using advanced computational tools and machine learning algorithms to prioritize genes, we can identify potential targets for therapeutic intervention of complex diseases. This represents an up-and-coming method for drug development and personalized medicine.
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Biologia Computacional , Aprendizado de Máquina , Humanos , Algoritmos , Biologia Computacional/métodos , Medicina de Precisão/métodos , Biossíntese de Proteínas/genéticaRESUMO
BACKGROUND: Klebsiella pneumoniae species complex (KpSC) is an important disseminator of carbapenemase-encoding genes, mainly blaKPC-2 and blaNDM-1, from hospitals to the environment. Consequently, carbapenem-resistant strains can be spread through the agrifood system, raising concerns about food safety. This study therefore aimed to isolate carbapenem-resistant KpSC strains from the agricultural and environmental sectors and characterize them using phenotypic, molecular, and genomic analyses. RESULTS: Klebsiella pneumoniae and Klebsiella quasipneumoniae strains isolated from soils used for lemon, guava, and fig cultivation, and from surface waters, displayed an extensive drug-resistance profile and carried blaKPC-2, blaNDM-1, or both. In addition to carbapenemase-encoding genes, KpSC strains harbor a broad resistome (antimicrobial resistance and metal tolerance) and present putative hypervirulence. Soil-derived K. pneumoniae strains were assigned as high-risk clones (ST11 and ST307) and harbored the blaKPC-2 gene associated with Tn4401b and Tn3-like elements on IncN-pST15 and IncX5 plasmids. In surface waters, the coexistence of blaKPC-2 and blaNDM-1 genes was identified in K. pneumoniae ST6326, a new carbapenem-resistant regional Brazilian clone. In this case, blaKPC-2 with Tn4401a isoform and blaNDM-1 associated with a Tn125-like transposon were located on different plasmids. Klebsiella quasipneumoniae ST526 also presented the blaNDM-1 gene associated with a Tn3000 transposon on an IncX3 plasmid. CONCLUSION: These findings provide a warning regarding the transmission of carbapenemase-positive KpSC across the agricultural and environmental sectors, raising critical food safety and environmental issues. © 2024 Society of Chemical Industry.
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Antibacterianos , Proteínas de Bactérias , Carbapenêmicos , Klebsiella pneumoniae , beta-Lactamases , beta-Lactamases/genética , beta-Lactamases/metabolismo , Klebsiella pneumoniae/genética , Klebsiella pneumoniae/efeitos dos fármacos , Klebsiella pneumoniae/isolamento & purificação , Klebsiella pneumoniae/enzimologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Antibacterianos/farmacologia , Microbiologia do Solo , Testes de Sensibilidade Microbiana , Infecções por Klebsiella/microbiologia , Klebsiella/genética , Klebsiella/efeitos dos fármacos , Klebsiella/isolamento & purificação , Klebsiella/enzimologia , HumanosRESUMO
Introduction: Many of the essential practices in palliative care (PC) had to be adapted to the COVID-19 pandemic. This global spread of the infectious respiratory disease, caused by SARS-CoV-2, created unprecedented obstacles. The aim of this research was to comprehensively assess the experiences and perceptions of healthcare professionals, individuals, and families in palliative and end-of-life situations during the COVID-19 pandemic. Methods: A scoping review was conducted using the databases CINAHL Complete, MEDLINE, Scopus, SciELO, Cochrane Central Register of Controlled Trials, Psychology and Behavioral Sciences, MEDIClatina, and Portugal's Open Access Scientific Repository. The review followed the JBI® methodological approach for scoping reviews. Results: Out of the initially identified 999 articles, 22 studies were included for analysis. The deprivation of relationships due to the safety protocols required to control the spread of COVID-19 was a universally perceived experience by healthcare professionals, individuals in PC, and their families. Social isolation, with significant psychological impact, including depersonalization and despair, was among the most frequently reported experiences by individuals in palliative situation. Despite healthcare professionals' efforts to mitigate the lack of relationships, the families of these individuals emphasized the irreplaceability of in-person bedside contact. Systematic review registration: https://osf.io/xmpf2/.
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COVID-19 , Pessoal de Saúde , Cuidados Paliativos , Humanos , COVID-19/epidemiologia , Pessoal de Saúde/psicologia , SARS-CoV-2 , Assistência Terminal , Pandemias , Isolamento Social/psicologiaRESUMO
Lower limb amputation affects several parameters of a patient's life. Family caregivers providing care for these patients experience multiple feelings and needs; knowing caregivers' needs is essential to prepare them for this new role, as well as the health planning of this type of care. This scoping review aimed to identify and map the needs of family caregivers of people with lower limb amputations. This scoping review was conducted in accordance with the JBI methodological framework and the PRISMA-ScR reporting guidelines. A bibliographical search was carried out on the needs of family caregivers of lower limb amputees in 15 databases. Two independent reviewers extracted data using a data extraction tool developed for this scoping review. Eight studies were included in the present review (n = 6 quantitative studies; n = 2 reviews). Results indicate that family caregivers of people with lower limb amputations may experience an extensive range of needs, as follows: (i) mental health and psychological support, (ii) physical health, (iii) health and well-being, (iv) supportive care, (v) social support, and (vi) educational/informational support. The needs identified in this review can help to develop interventions and programs that provide better support during the situational transition process.
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Non-small cell lung cancer (NSCLC) is a predominant form of lung cancer characterized by its aggressive nature and high mortality rate, primarily due to late-stage diagnosis and metastatic spread. Recent studies underscore the pivotal role of mitophagy, a selective form of autophagy targeting damaged or superfluous mitochondria, in cancer biology, including NSCLC. Mitophagy regulation may influence cancer cell survival, proliferation, and metastasis by modulating mitochondrial quality and cellular energy homeostasis. Herein, we present a comprehensive methodology developed in our laboratory for the evaluation of mitophagy in NSCLC tumor cells. Utilizing a combination of immunoblotting, immunocytochemistry, and fluorescent microscopy, we detail the steps to quantify early and late mitophagy markers and mitochondrial dynamics. Our findings highlight the potential of targeting mitophagy pathways as a novel therapeutic strategy in NSCLC, offering insights into the complex interplay between mitochondrial dysfunction and tumor progression. This study not only sheds light on the significance of mitophagy in NSCLC but also establishes a foundational approach for its investigation, paving way for future research in this critical area of cancer biology.
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PURPOSE: The aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. METHODS: The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). RESULTS: 1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27-85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1-17.9), median OS was 16.1 months (95% CI, 14.4-18.8) and PFS was 9.9 months (95% CI, 8.8-11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6-17.1). ORR was 43.4% (95% CI, 40.4-46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). CONCLUSIONS: First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.
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Anticorpos Monoclonais Humanizados , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Idoso , Neoplasias Pulmonares/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Pemetrexede , Platina/uso terapêutico , Antígeno B7-H1 , Estudos Prospectivos , Estudos Retrospectivos , Itália , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
Non-small cell lung cancer (NSCLC) is among the most malignant tumors with high propensity for metastasis and is the leading cause of cancer-related death globally. Most patients present with regional and distant metastasis, associated with poor prognosis. Lipids may play an essential role in either activating or inhibiting detachment-induced apoptosis (anoikis), where the latter is a crucial mechanism to prevent metastasis, and it may have a cross-talk with autophagy. Autophagy has been shown to be induced in various human cancer metastasis, modulating tumor cell motility and invasion, cancer cell differentiation, resistance to anoikis, and epithelial to mesenchymal transition. Hence, it may play a crucial role in the transition of benign to malignant phenotypes, the core of metastasis initiation. Here, we provide a method we have established in our laboratory for detecting lipids in attached and detached non-small lung cancer cells and show how to analyze lipidomics data to find its correlation with autophagy-related pathways.
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The absence of tumor-infiltrating lymphocytes negatively impacts the response to chemotherapy and prognosis in all subtypes of breast cancer. Therapies that stimulate a proinflammatory environment may help improve the response to standard treatments and also to immunotherapies such as checkpoint inhibitors. Newcastle disease virus (NDV) shows oncolytic activity, as well as immune modulating potential, in the treatment of breast cancer in vitro and in vivo; however, its potential to enhance tumor-infiltrating immune cells in breast cancer has yet to be evaluated. Since spontaneous canine mammary tumors represent a translational model of human breast cancer, we conducted this proof-of-concept study, which could provide a rationale for further investigating NDV-MLS as immunotherapy for mammary cancer. Six female companion dogs with spontaneous mammary cancer received a single intravenous and intratumoral injection of oncolytic NDV-MLS. Immune cell infiltrates were evaluated by histology and immunohistochemistry in the stromal, intratumoral, and peritumoral compartments on day 6 after viral administration. Increasing numbers of immune cells were documented post-viral treatment, mainly in the peritumoral compartment, where plasma cells and CD3+ and CD3-/CD79- lymphocytes predominated. Viral administration was well tolerated, with no significant adverse events. These findings support additional research on the use of NDV-MLS immunotherapy for mammary cancer.
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Neoplasias , Terapia Viral Oncolítica , Vírus Oncolíticos , Humanos , Animais , Feminino , Cães , Vírus da Doença de Newcastle/fisiologia , Animais de Estimação , Vírus Oncolíticos/fisiologia , Imunoterapia , Linhagem Celular Tumoral , Neoplasias/terapiaRESUMO
BACKGROUND: It is well described that circulating progesterone (P4) plays a key role in several reproductive events such as oocyte maturation. However, during diestrus, when circulating P4 is at the highest concentrations, little is known about its local impact on the follicular cells such as intrafollicular P4 concentration due to corpus luteum (CL) presence within the same ovary. Based on that, our hypothesis is that the CL presence in the ovary during diestrus alters intrafollicular P4 concentrations, oocyte competence acquisition, follicular cells gene expression, and small extracellular vesicles (sEVs) miRNAs contents. RESULTS: P4 hormonal analysis revealed that ipsilateral to the CL follicular fluid (iFF) presented higher P4 concentration compared to contralateral follicular fluid (cFF). Furthermore, oocyte maturation and miRNA biogenesis pathways transcripts (ADAMTS-1 and AGO2, respectively) were increased in cumulus and granulosa cells of iFF, respectively. Nevertheless, a RT-PCR screening of 382 miRNAs showed that three miRNAs were upregulated and two exclusively expressed in sEVs from iFF and are predicted to regulate cell communication pathways. Similarly, seven miRNAs were higher and two exclusively expressed from cFF sEVs and are predicted to modulate proliferation signaling pathways. CONCLUSION: In conclusion, intrafollicular P4 concentration is influenced by the presence of the CL and modulates biological processes related to follicular cell development and oocyte competence, which may influence the oocyte quality. Altogether, these results are crucial to improve our knowledge about the follicular microenvironment involved in oocyte competence acquisition.
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Vesículas Extracelulares , MicroRNAs , Feminino , Animais , Bovinos , Líquido Folicular/metabolismo , Progesterona/metabolismo , Folículo Ovariano/metabolismo , Ovário/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Oócitos/metabolismo , Corpo Lúteo/metabolismo , Vesículas Extracelulares/genética , Expressão GênicaRESUMO
OBJECTIVE: This study targets women who had a self-defined traumatic childbirth experience to (a) explore the differences between sociodemographic-, obstetric-, and trauma-related variables in relation to the rumination style; (b) determine differences between intrusive and deliberate rumination in relation to posttraumatic growth (PTG) dimensions, and (c) test whether intrusive rumination is associated with deliberate rumination, which in turn is associated with PTG dimensions. METHOD: A cross-sectional study design was employed using a web-based survey method for data collection. In total, 202 women who identified their childbirth experience as traumatic participated in this study. RESULTS: Intrusive rumination and deliberate rumination were positively associated with all dimensions of PTG in women following the traumatic childbirth event. Deliberate rumination fully explained the relationship between intrusive rumination and PTG aspects of relating to others, new opportunities, and personal strength, and partially explained the relationship between intrusive rumination and PTG aspects of spiritual changes and appreciation of life. CONCLUSIONS: The results suggest that deliberate rumination can contribute to explain the occurrence of PTG. These findings could help develop psychosocial interventions to maximize opportunities for deliberate rumination for women with traumatic childbirth experiences. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
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Alveolar rhabdomyosarcoma (ARMS), an invasive subtype of rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes, PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine transforming growth factor beta (TGF-ß). This overexpression of TGF-ß1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes epithelial to mesenchymal transition (EMT). Overexpression of TGF-ß also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-ß in this tumor type. We next highlight current chemotherapy strategies, including a combination of the FDA-approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC); cabozantinib; bortezomib; vinorelbine; AZD 1775; and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS, which include all-trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-ß1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.
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Rabdomiossarcoma Alveolar , Rabdomiossarcoma , Humanos , Rabdomiossarcoma Alveolar/genética , Rabdomiossarcoma Alveolar/metabolismo , Rabdomiossarcoma Alveolar/patologia , Fator de Crescimento Transformador beta , Fator de Crescimento Transformador beta1 , Fatores de Transcrição Box Pareados/genética , Transição Epitelial-Mesenquimal , Rabdomiossarcoma/genética , Proteínas de Fusão Oncogênica/genéticaRESUMO
BACKGROUND: Pregnant women with hypertensive disorders are at increased risk for inflammatory diseases and oxidative stress. The dilemma raised by the best dosage of calcium supplementation on these factors is evident. The aim of the current study was to examine the effects of calcium on biomarkers of the purinergic system, inflammation and oxidative stress, which are factors contributing to vascular damage in pregnant women at high risk of pre-eclampsia. METHODS: A prospective, double-blind and placebo-controlled study conducted with 101 women at risk of pre-eclampsia were randomized to take 500 mg calcium/day or 1,500 mg calcium/day or placebo for 6 weeks from the 20th gestational week until delivery. Fasting blood samples were collected at the beginning of the study and 6 weeks after the intervention. RESULTS: Taking calcium supplements (500 mg calcium/day) led to a significant increase in ATP hydrolysis (p < 0.05), NTPDase activity with increased hydrolysis of ADP and AMP nucleotides in platelets and lymphocytes. In the intragroup analysis IL-2, IL-6, IL-4 and interferon-É£ presented lower values in the calcium 1,500 mg/day group (p < 0.005). Oxidative stress was assessed by TBARS pro-oxidant marker, with an increase for the calcium groups when compared to the placebo group. The Vitamin C antioxidant marker presented a significant increase (p < 0.005) for the group that received high calcium doses. CONCLUSIONS: Calcium administration for 6 weeks had antioxidant action and positively modulated the purinergic system and inflammatory markers in pregnant women at risk of pre-eclampsia.
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Pré-Eclâmpsia , Feminino , Gravidez , Humanos , Pré-Eclâmpsia/prevenção & controle , Cálcio , Suplementos Nutricionais , Interleucina-10 , Interleucina-2 , Interleucina-4 , Interleucina-6 , Gestantes , Antioxidantes , Estudos Prospectivos , Cálcio da Dieta , Estresse OxidativoRESUMO
Glioblastoma (GBM) is the most common aggressive central nervous system cancer. GBM has a high mortality rate, with a median survival time of 12-15 months after diagnosis. A poor prognosis and a shorter life expectancy may result from resistance to standard treatments such as radiation and chemotherapy. Temozolomide has been the mainstay treatment for GBM, but unfortunately, there are high rates of resistance with GBM bypassing apoptosis. A proposed mechanism for bypassing apoptosis is decreased ceramide levels, and previous research has shown that within GBM cells, B cell lymphoma 2-like 13 (BCL2L13) can inhibit ceramide synthase. This review aims to discuss the causes of resistance in GBM cells, followed by a brief description of BCL2L13 and an explanation of its mechanism of action. Further, lipids, specifically ceramide, will be discussed concerning cancer and GBM cells, focusing on ceramide synthase and its role in developing GBM. By gathering all current information on BCL2L13 and ceramide synthase, this review seeks to enable an understanding of these pieces of GBM in the hope of finding an effective treatment for this disease.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Glioblastoma/tratamento farmacológico , Linhagem Celular Tumoral , Temozolomida/farmacologia , Apoptose , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/patologia , Ceramidas/uso terapêutico , Resistencia a Medicamentos AntineoplásicosRESUMO
Cutaneous leishmaniasis (CL) is a neglected disease widely distributed in Maranhão, Brazil and presents a significant public health problem. However, its transmission dynamics and determining factors are not clearly understood. In this context, geospatial technologies help interpret the process. This study, then, characterized the space-time dynamics and the influence of social vulnerability on CL in an endemic area in Northeast Brazil. This is an ecological study about new cases of CL in Maranhão, from 2007 to 2020, obtained directly from the Notifiable Diseases Information System. The incidence rate was smoothed using a spatial empirical Bayesian method. Subsequently, global and local Moran statistics and their association with social vulnerability indicators were determined. Disease distribution was not random but grouped in space and time. All Social Vulnerability Index domains were positively correlated with the CL incidence. A likely cluster was detected in western Maranhão (Pâ <â 0.001), which encompassed 18 municipalities, from January 2007 to December 2013, with a high relative risk (5.06). The research findings suggest that planning public health actions and allocating resources should be prioritized in these areas to help effectively reduce the incidence of the disease.