Episiotomia: resultados maternos e neonatais precoces do uso seletivo versus generalizado

Overview and aims: Episiotomy is one of the most common procedures in Obstetrics, despite actual scientific evidence does not support its routine practice.The aim of this study was to determine the impact of selective and routine practice of episiotomy in early maternal and neonatal outcomes. Study design:An observational, transversal, descriptive and analytic study was conducted in two public Hospitals in northern Portugal, with different policies for the practice of episiotomy: selective practice (Hospital A) and routine practice (Hospital B). Population: A non-random sampling of convenience of the whole puerperal women whose deliveries was performed in these hospitals during months of July and August 2011 was utilized. A total of 397 women was analyzed, 200 in selective group and 197 in routine group. Methods: Data was collected by consultation of medical records of the puerperal women. Comparison between hospitals was performed with the chi-square test. Results: The groups were similar for the obstetric history, demographic, biometric, pregnancy and labor characteristics. However, gestational age, weight and head circumference of newborns as well as instrumentation rate were significantly higher in selective group. Episiotomy was performed in 72.5% cases of selective group and in 88.8% of routine group (p≤0.001).There wasless perinealsuturing (p=0.001) and a greater number of intact perineum in selective group (p≤0.001), without differences in lacerations type or degree. The routine group presented more frequent early perineal complications and higher pain levels in the first postpartum day (p≤0.001). No differences were found between groups in Apgar scores, neonatal trauma and Neonatal Intensive Care Unit admissions number. Conclusions: The selective use of episiotomy was associated with better early maternal outcomes, with no differences in neonatal morbidity. Thus, the routine practice of episiotomy showed no benefit

Identification of clinical predictors of flare in systemic lupus erythematosus patients: a 24-month prospective cohort study

Objective. SLE has a relapsing-remitting course with disease activity flares over time. This study aims to identify clinical predictors of SLE flares.Methods. This prospective cohort study over 24 months included all SLE patients on follow-up at one academic lupus clinic. Flare was defined as an increase in SLEDAI-2K score ≥4 points. Baseline clinical and demographic parameters were compared using survival analysis for time-to-flare outcome with univariate log-rank tests. Variables with significant differences were further evaluated as predictors with multivariate Cox regression models adjusting for potential confounding or contributing factors and hazard ratio (HR) calculation.Results. A total of 202 SLE patients were included. Over the follow-up period, 1083 visits were documented and 16.8% of patients presented with flares. In multivariate analysis, the following parameters emerged as flare predictors: SLE diagnosis up to 25 years of age (HR = 2.14, P = 0.03), lupus nephritis previous to baseline visit (HR = 4.78, P < 0.0001) and immunosuppressor treatment for severe SLE (HR = 3.22, P < 0.001). Baseline disease activity, disease duration and treatment with prednisone or HCQ were not predictive factors.Conclusion. Patients with an SLE diagnosis before age 25 years, lupus nephritis or immunosuppressor treatment for severe SLE present greater HRs for flares, suggesting the need for tighter clinical monitoring. Current immunosuppressive strategies seem to be inefficient in providing flare prevention

Oncogenic Gain of Function in Glioblastoma Is Linked to Mutant p53 Amyloid Oligomers.

Tumor-associated p53 mutations endow cells with malignant phenotypes, including chemoresistance. Amyloid-like oligomers of mutant p53 transform this tumor suppressor into an oncogene. However, the composition and distribution of mutant p53 oligomers are unknown and the mechanism involved in the conversion is sparse. Here, we report accumulation of a p53 mutant within amyloid-like p53 oligomers in glioblastoma-derived cells presenting a chemoresistant gain-of-function phenotype. Statistical analysis from fluorescence fluctuation spectroscopy, pressure-induced measurements, and thioflavin T kinetics demonstrates the distribution of oligomers larger than the active tetrameric form of p53 in the nuclei of living cells and the destabilization of native-drifted p53 species that become amyloid. Collectively, these results provide insights into the role of amyloid-like mutant p53 oligomers in the chemoresistance phenotype of malignant and invasive brain tumors and shed light on therapeutic options to avert cancer

Geographical variation in antimicrobial use and multiresistant pathogens in Brazilian intensive care units: a nationwide study

Introduction: Geographical analyses of antibiotic use identify regions with the highest consumption and help design policies for strategic patient groups.Methodology: We conducted a cross-sectional study based on official data available in July 2022 from Brazilian Health Surveillance Agency (Anvisa). Antibiotics are reported as a defined daily dose (DDD) per 1,000 patient-days, and central line-associated bloodstream infection (CLABSI) is defined according to Anvisa criteria. We also considered multi-drug resistant (MDR) as the critical pathogens the World Health Organization listed. We measured antimicrobial use and CLABSI trends per ICU bed using the compound annual growth rate (CAGR). Results: we evaluated the regional variation in CLABSI by multidrug-resistant pathogens and the antimicrobial use in 1,836 hospital intensive care units (ICUs). In 2020, the leader in use in intensive care units (ICUs) in the North was piperacillin/tazobactam (DDD = 929.7) in the Northeast. Midwest and South were meropenem (DDD = 809.4 and DDD = 688.1, respectively), and Southeast was ceftriaxone (DDD = 751.1). The North has reduced polymyxin use (91.1%), and ciprofloxacin increased (439%) in the South. There was an increase in CLABSI by carbapenem-resistant Pseudomonas aeruginosa in the North region (CAGR = 120.5%). Otherwise, CLABSI by vancomycin-resistant Enterococcus faecium (VRE) increased in all regions except the North (CAGR =-62.2%), while that carbapenem-resistant Acinetobacter baumannii increased in the Midwest (CAGR = 27.3%). Conclusions: we found heterogeneity in antimicrobial use patterns and CLABSI etiology among Brazilian ICUs. Although Gram-negative bacilli were the primary responsible agent, we observed a notable increase trend of CLABSI by VRE

Ghrelin and obestatin: Different role in fetal lung development?

Ghrelin and obestatin are two proteins that originate from post-translational processing of the preproghrelin peptide. Various authors claim an opposed role of ghrelin and obestatin in several systems. Preproghrelin mRNA is significantly expressed in airway epithelium throughout lung development, predominantly during the earliest stages. The aim of this study was to evaluate the role of ghrelin and obestatin in fetal lung development in vitro. Immunohistochemistry studies were performed at different gestational ages in order to clarify the expression pattern of ghrelin, GHS-R1a, obestatin and GPR39 during fetal lung development. Fetal rat lung explants were harvested at 13.5 days post-conception (dpc) and cultured during 4 days with increasing doses of total ghrelin, acylated ghrelin, desacyl-ghrelin, ghrelin antagonist (D-Lys(3)-GHRP-6) or obestatin. Immunohistochemistry studies demonstrated that ghrelin, GHS-R1a, obestatin and GPR39 proteins were expressed in primitive rat lung epithelium throughout all studied gestational ages. Total and acylated ghrelin supplementation significantly increased the total number of peripheral airway buds, whereas desacyl-ghrelin induced no effect. Moreover, GHS-R1a antagonist significantly decreased lung branching. Finally, obestatin supplementation induced no significant effect in the measured parameters. The present study showed that ghrelin has a positive effect in fetal lung development through its GHS-R1a receptor, whereas obestatin has no effect on lung branching

A System for Accessible Artificial Intelligence

While artificial intelligence (AI) has become widespread, many commercial AI systems are not yet accessible to individual researchers nor the general public due to the deep knowledge of the systems required to use them. We believe that AI has matured to the point where it should be an accessible technology for everyone. We present an ongoing project whose ultimate goal is to deliver an open source, user-friendly AI system that is specialized for machine learning analysis of complex data in the biomedical and health care domains. We discuss how genetic programming can aid in this endeavor, and highlight specific examples where genetic programming has automated machine learning analyses in previous projects.Comment: 14 pages, 5 figures, submitted to Genetic Programming Theory and Practice 2017 worksho

Contextuality and Noncommutative Geometry in Quantum Mechanics

Observable properties of a classical physical system can be modelled deterministically as functions from the space of pure states to outcome values; dually, states can be modelled as functions from the algebra of observables to outcome values. The probabilistic predictions of quantum physics are contextual in that they preclude this classical assumption of reality: noncommuting observables, which are not assumed to be jointly measurable, cannot be consistently ascribed deterministic values even if one enriches the description of a quantum state. Here, we consider the geometrically dual objects of noncommutative operator algebras of observables as being generalisations of classical (deterministic) state spaces to the quantum setting and argue that these generalised state spaces represent the objects of study of noncommutative operator geometry. By adapting the spectral presheaf of Hamilton–Isham–Butterfield, a formulation of quantum state space that collates contextual data, we reconstruct tools of noncommutative geometry in an explicitly geometric fashion. In this way, we bridge the foundations of quantum mechanics with the foundations of noncommutative geometry à la Connes et al. To each unital C*- algebra A we associate a geometric object—a diagram of topological spaces collating quotient spaces of the noncommutative space underlying A —that performs the role of a generalised Gel'fand spectrum. We show how any functor F from compact Hausdorff spaces to a suitable target category C can be applied directly to these geometric objects to automatically yield an extension F~ acting on all unital C*-algebras. This procedure is used to give a novel formulation of the operator K0-functor via a finitary variant K~f of the extension K~ of the topological K-functor. We then delineate a C*-algebraic conjecture that the extension of the functor that assigns to a topological space its lattice of open sets assigns to a unital C*-algebra the Zariski topological lattice of its primitive ideal spectrum, i.e. its lattice of closed two-sided ideals. We prove the von Neumann algebraic analogue of this conjecture

The effects of nitric oxide on the immune system during Trypanosoma cruzi infection

Trypanosoma cruzi infection triggers substantial production of nitric oxide (NO), which has been shown to have protective and toxic effects on the host's immune system. Sensing of trypomastigotes by phagocytes activates the inducible NO-synthase (NOS2) pathway, which produces NO and is largely responsible for macrophage-mediated killing of T. cruzi. NO is also responsible for modulating virtually all steps of innate and adaptive immunity. However, NO can also cause oxidative stress, which is especially damaging to the host due to increased tissue damage. The cytokines IFN-³ and TNF-±, as well as chemokines, are strong inducers of NOS2 and are produced in large amounts during T. cruzi acute infection. Conversely, TGF-² and IL-10 negatively regulate NO production. Here we discuss the recent evidence describing the mechanisms by which NO is able to exert its antimicrobial and immune regulatory effects, the mechanisms involved in the oxidative stress response during infection and the implications of NO for the development of therapeutic strategies against T. cruzi.FAPESPFRSGTWPMPMMGThe Millennium Institute for Vaccine Development and TechnologyCNP

Successful management of bilateral orbital metastases from invasive lobular breast cancer with abemaciclib and letrozole: a case report and literature review

Breast cancer is a significant global health concern, contributing to substantial morbidity and mortality among women. Hormone receptor-positive (HR+)/HER2- negative (HER2-) breast cancer constitutes a considerable proportion of cases, and significant advancements have been made in its management. CDK4/6 inhibitors (CDK4/6is) are a new targeted therapy that has demonstrated efficacy in adjuvant, advanced and metastatic settings. The propensity of lobular breast carcinomas for estrogen-rich sites, such as periocular tissues and orbital fat, may explain their tendency for orbital metastases. Current treatment strategies for these cases are predominantly palliative, and the prognosis remains poor. This article presents a unique case of a 51-year-old female with progressive right periorbital edema, pain, and limited ocular motility. An imaging work-up showed bilateral intra and extraconal orbital infiltration, which was biopsied. The histopathologic analysis disclosed mild chronic inflammatory infiltrate with thickened fibrous tissue and moderately differentiated lobular carcinoma cells, positive for GATA3 and CK7 markers, with 100% of tumor nuclei expressing estrogen receptors (ER+). A systemic evaluation showed a multicentric nodular formation in both breasts. Further diagnostic assessments unveiled an HR+/HER2- bilateral lobular breast carcinoma with synchronous bilateral orbital metastases. Systemic treatment was initiated with abemaciclib 150mg twice daily and letrozole 2.5mg once a day. However, this regimen was interrupted due to toxicity. After two weeks, treatment was resumed with a reduced abemaciclib dose (100mg twice daily) alongside letrozole, with a reasonable tolerance. Nearly two years after the initial diagnosis of inoperable metastatic cancer, the patient remains on the same systemic treatment regimen with no signs of invasive disease. This case report is the first of a patientpresenting with bilateral orbital metastases from bilateral lobular breast cancer, showing an impressive and sustained response to a first-line treatment regimen combining abemaciclib and letrozole. A literature review on bilateral orbital metastases from breast cancer is also presented.info:eu-repo/semantics/publishedVersio

Tissue distribution of a plasmid DNA encoding Hsp65 gene is dependent on the dose administered through intramuscular delivery

In order to assess a new strategy of DNA vaccine for a more complete understanding of its action in immune response, it is important to determine the in vivo biodistribution fate and antigen expression. In previous studies, our group focused on the prophylactic and therapeutic use of a plasmid DNA encoding the Mycobacterium leprae 65-kDa heat shock protein (Hsp65) and achieved an efficient immune response induction as well as protection against virulent M. tuberculosis challenge. In the present study, we examined in vivo tissue distribution of naked DNA-Hsp65 vaccine, the Hsp65 message, genome integration and methylation status of plasmid DNA. The DNA-Hsp65 was detectable in several tissue types, indicating that DNA-Hsp65 disseminates widely throughout the body. The biodistribution was dose-dependent. In contrast, RT-PCR detected the Hsp65 message for at least 15 days in muscle or liver tissue from immunized mice. We also analyzed the methylation status and integration of the injected plasmid DNA into the host cellular genome. The bacterial methylation pattern persisted for at least 6 months, indicating that the plasmid DNA-Hsp65 does not replicate in mammalian tissue, and Southern blot analysis showed that plasmid DNA was not integrated. These results have important implications for the use of DNA-Hsp65 vaccine in a clinical setting and open new perspectives for DNA vaccines and new considerations about the inoculation site and delivery system