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BackgroundChagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ.MethodologyFemale BALB/c mice were infected with a bioluminescent T. cruzi H1 clone for approximately 70 days, then randomly divided into groups of 15 mice each. Mice were treated with a 25mg/kg BNZ, 25μg Tc24-C4 protein/ 5μg E6020-SE (Vaccine), 25mg/kg BNZ followed by vaccine, or 100mg/kg BNZ (curative dose). At study endpoints we evaluated hepatomegaly, parasite burden by quantitative PCR, cellular infiltration by histology, and expression of B-cell translocation gene 2(BTG2) and Peroxisome proliferator-activated receptor alpha (PPARα) by RT-PCR. Levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were quantified from serum.ResultsCurative BNZ treatment significantly reduced hepatomegaly, liver parasite burdens, and the quantity of cellular infiltrate, but significantly elevated serum levels of ALT, AST, and LDH. Low BNZ plus vaccine did not significantly affect hepatomegaly, parasite burdens or the quantity of cellular infiltrate, but only elevated ALT and AST. Low dose BNZ significantly decreased expression of both BTG2 and PPARα, and curative BNZ reduced expression of BTG2 while low BNZ plus vaccine had no impact.ConclusionsThese data confirm toxicity associated with curative doses of BNZ and suggest that while dose sparing low BNZ plus vaccine treatment does not reduce parasite burdens, it better preserves liver health.

Introducción y objetivos La fractura de escafoides es la más común dentro de las fracturas del carpo. El objetivo de nuestro trabajo es realizar un estudio analizando los resultados de las fracturas de escafoides en gente de edad avanzada.

Resumo A investigação doutoral em curso apresenta como principal objetivo identificar/classificar a natureza das práticas pedagógicas utilizadas e competências desenvolvidas por via do European Action Scheme for the Mobility of Students (Erasmus+) no ensino secundário. Metodologicamente, recorremos ao método qualitativo, focado na pesquisa exploratório-descritiva, por análise de conteúdo, de um corpus de 12 artigos, com recurso ao software NVIVO11. As conclusões prelimi-nares revelam que esse programa tem vindo a construir trajetos e práticas de inovação pedagógicos sustentados em pedagogias e metodologias ativas, com particular enfoque nas aprendizagens essenciais e na educação intercultural. A máxima é aprender uns com os outros e, em conjunto, aprender a viver juntos e a tornarem-se cidadãos para o mundo.

BackgroundPrimary care providers (PCPs) play an essential role in obesity care as they represent the first contact for patients seeking weight loss interventions.ObjectiveThis study explored the knowledge, experiences, and perceptions of PCPs in the Lazio Region of Italy in the management of obesity.Design and subjectsWe conducted an anonymous survey delivered from March to July 2022 via the newsletter of Rome Provincial Order of Physicians and Dentists and at the annual meeting of the regional section of the Italian Obesity Society.ApproachThe survey consisted of 24 closed-ended questions grouped into 5 sections: sociodemographic and work information; assessment of obesity; management of obesity; connections with regional Centres for Obesity Management; attitudes towards obesity.Key resultsA total of 92 PCPs accessed the survey. Of those, 2.2% were excluded because they did not see any patients with obesity. A total of 68 PCPs (75.6%) had complete questionnaires and were included in this analysis. All participants reported asking their patients about their eating habits, lifestyle, and clinical complications at the first assessment. Body weight and blood pressure were measured by 98.5% of participants and 82% calculate body mass index (BMI), while a small proportion of PCPs analysed body composition and fat distribution. Over 80% prescribed laboratory tests and ECG. Approximately 40% of PCPs did not refer patients for nutritional counselling, and most prescribed a low-calorie diet. Sixty-three percent referred patients to an endocrinologist, 48.5% to a psychotherapist, and a minority to specialists for obesity complications. Twenty-three percent prescribed anti-obesity medications and 46.5% referred patients for bariatric surgery only in severe cases. Ninety-one percent stated that obesity is “a complex and multifactorial disease” and 7.4% considered obesity to be secondary to other conditions.ConclusionsDespite most PCPs adopt a correct approach to manage patients with obesity, many aspects could be improved to ensure optimal and multidisciplinary management.

Reliable access to safe water is essential for health, wellbeing, and the livelihoods of people. However, water security innovations benefit when engineering and geoscience decisions consider systemic human, social, and organizational realities, needs, and goals. Indeed, true innovation that leads to water security requires intensively inclusive and iterative processes to occur at multiple scales of analysis across diverse sciences—for this, expertise and knowledge across the varied sciences is essential to facilitate such convergent, transdisciplinary research. Here, we articulate our perspective for identifying points of intersection and working across disciplinary boundaries to address water crises. Our perspective takes a multidimensional view of community, organization, family, and individual resilience in the face of natural and human hazards. It builds upon previous models of cumulative water related risk by nuancing the relationships amongst levels of analysis, and expanding the idea of cumulative impacts to include interactive impacts (e.g., buffering, enhancing, effects and other moderators), mediated effects (i.e., mechanisms of impact), as well as additive and suppressive linkages amongst risk and protective factors.

Tissue growth and morphogenesis are interrelated processes, whose tight coordination is essential for the production of different cell fates and the timely precise allocation of stem cell capacities. The zebrafish embryonic brainstem, the hindbrain, exemplifies such coupling between spatiotemporal cell diversity acquisition and tissue growth as the neurogenic commitment is differentially distributed over time. Here, we combined cell lineage and in vivo imaging approaches to reveal the emergence of specific cell population properties within the rhombomeres. We studied the molecular identity of hindbrain rhombomere centers and showed that they harbor different progenitor capacities that change over time. By clonal analysis, we revealed that cells within the center of rhombomeres decrease the proliferative capacity to remain mainly in the G1 phase. Proliferating progenitors give rise to neurons by asymmetric and symmetric neurogenic divisions while maintaining the pool of progenitors. The proliferative capacity of these cells differs from their neighbors, and they are delayed in the onset of Notch activity. Through functional studies, we demonstrated that they rely on Notch3 signaling to be maintained as non-committed progenitors. In this study, we show that cells in rhombomere centers, despite the neurogenic asynchrony, might share steps of a similar program with the rhombomere counterparts, to ensure proper tissue growth.

Introduction: Lesions in the oral mucosa constitute a heterogeneous group of disorders which prognosis and treatment depend on the early diagnosis. Objective: To characterize patients with lesions in the oral mucosa according to clinical, epidemiological, histological and pathological variables. Methods: A descriptive, longitudinal and prospective study of 23 patients with lesions in the oral mucosa was carried out. They belonged to the family doctor offices from Vista Alegre neighborhood and were assisted in the Stomatology Service of Dr. Juan Bruno Zayas Alfonso Teaching General Hospital in Santiago de Cuba from September, 2021 to June, 2022. Results: In the series there was a prevalence of the female sex, the 60 years and over age group, subprosthesis stomatitis as more frequent lesion (39.1%) and chronic traumatisms as risk factors (65.2%); also, in patients referred to the secondary care level there was coincidence between the clinical, histological and pathological diagnoses (76.9%). Conclusions: The final diagnosis will depend on the clinical, epidemiological, histological and pathological valuation of these lesions and on the preparation of the specialists on the topic.

BackgroundRoutine anticoagulation therapy in acute pancreatitis (AP) is not recommended by the guidelines in the field, although it is frequently used in clinical practice.ObjectivesWe aimed to analyze the efficacy and safety of adding anticoagulants therapy to AP management.MethodsThe systematic search was performed in three databases on the 14th of October 2022 without restrictions. Randomized controlled trials (RCTs) and observational studies that reported the differences in the outcomes of AP for patients receiving anticoagulants (intervention group) in addition to the standard of care (SOC), compared to patients managed by SOC alone (control group), were eligible. A random-effects model was used to calculate the pooled odds ratios (OR) and mean differences (MD) with the corresponding 95%-confidence intervals (CI). We performed subgroup analysis for study design and disease severity, among other criteria.ResultsOf the 8,223 screened records, we included eight in the meta-analysis. Except one, all studies reported on low-molecular-weight heparin (LMWH). Both RCTs and observational studies reported results in favor of the LMWH group. Subgroup RCTs’ analysis revealed significantly decreased odds of mortality [OR 0.24; 95%CI 0.17–0.34] and multiple organ failure [OR 0.32; 95%CI 0.17–0.62] in the intervention group. Moreover, the need for endoscopic or surgical interventions [OR 0.41; 95%CI 0.28–0.61] were significantly reduced by LMWH. The subgroup analyzes for moderate and severe cases, respectively, yielded similar results. Due to limited data, we could no perform subgroup analysis for mild cases.ConclusionLMWH therapy reduces major complication rates in moderate and severe AP. Across all identified RCTs, LMWH were initiated early after AP diagnosis and improved its prognosis.

ABSTRACT Purpose: Enterocutaneous fistula (ECF) is a condition in which there is an abnormal connection between the intestinal tract and the skin. It can lead to high morbidity and mortality rates despite the availability of therapeutic options. Stem cells have emerged as a potential strategy to treat ECF. This study aimed to evaluate the effect of adipose tissue-derived stem cells (ASC) on ECF in an experimental model. Methods: ECF was induced in 21 Wistar rats, and after one month, they were divided into three groups: control group (C), culture medium without ASC group (CM), and allogeneic ASC group (ASC). After 30 days, the animals underwent macroscopic analysis of ECF diameter and histopathological analysis of inflammatory cells, tissue fibrosis, and vascular density. Results: The study found a 55% decrease in the ECF diameter in the ASC group (4.5 ± 1.4 mm) compared to the control group (10.0 ± 2.1 mm, p = 0.001) and a 59.1% decrease in the CM group (11.0 ± 4.3 mm, p = 0.003). The fibrosis score in the ASC group was 20.9% lower than the control group (p = 0.03). There were no significant differences in inflammation scores among the three groups. Conclusions: This study suggests that ASC treatment can reduce ECF diameter, and reduction in tissue fibrosis may be a related mechanism. Further studies are needed to understand the underlying mechanisms fully.

ABSTRACT We aimed to describe the characteristics and outcomes of biliary source bloodstream infections (BSIs) in oncological patients. Secondarily, we analyzed risk factors for recurrent BSI episodes. All episodes of biliary source BSIs in oncological patients were prospectively collected (2008–2019) and retrospectively analyzed. Logistic regression analyses were performed. A rule to stratify patients into risk groups for recurrent biliary source BSI was conducted. Four hundred biliary source BSIs were documented in 291 oncological patients. The most frequent causative agents were Escherichia coli (42%) and Klebsiella spp. (27%), and 86 (21.5%) episodes were caused by multidrug-resistant Gram-negative bacilli (MDR-GNB). The rates of MDR-GNB increased over time. Overall, 73 patients developed 118 recurrent BSI episodes. Independent risk factors for recurrent BSI episodes were prior antibiotic therapy (OR 3.781, 95% CI 1.906–7.503), biliary prosthesis (OR 2.232, 95% CI 1.157–4.305), prior admission due to suspected biliary source infection (OR 4.409, 95% CI 2.338–8.311), and BSI episode caused by an MDR-GNB (OR 2.857, 95% CI 1.389–5.874). With these variables, a score was generated that predicted recurrent biliary source BSI with an area under the receiver operating characteristic (ROC) curve of 0.819. Inappropriate empirical antibiotic treatment (IEAT) was administered in 23.8% of patients, and 30-d mortality was 19.5%. As a conclusion, biliary source BSI in oncological patients is mainly caused by GNB, with high and increasing MDR rates, frequent IEAT, and high mortality. Recurrent BSI episodes are frequent. A simple score to identify recurrent episodes was developed to potentially establish prophylactic strategies. IMPORTANCE This study shows that biliary source bloodstream infections (BSIs) in oncological patients are mainly caused by Gram-negative bacilli (GNB), with high and increasing rates of multidrug resistance. Importantly, recurrent biliary source BSI episodes were very frequent and associated with delays in chemotherapy, high rates of inappropriate empirical antibiotic therapy, and high 30-d mortality (19.5%). Using the variable independently associated with recurrent BSI episodes, a score was generated that predicted recurrent biliary source BSI with high accuracy. This score could be used to establish prophylactic strategies and lower the risk of relapsing episodes and the associated morbidity and mortality.

IntroductionHookworms are parasitic helminths that secrete a variety of proteins that induce anti-inflammatory immune responses, stimulating increased CD4+Foxp3+ regulatory T cells and IL-10 production. Hookworm-derived recombinant proteins AIP-1 and AIP-2 have been shown to reduce inflammation in mouse models of inflammatory bowel disease and inflammatory airway disease by inducing CD4+Foxp3+ cells and IL-10 production. In contrast, chronic infection with the protozoal parasite Trypanosoma cruzi, the causative agent of Chagas disease, leads to chronic inflammation in tissues. Persistence of the parasites in tissues drives chronic low-grade inflammation, with increased infiltration of inflammatory cells into the heart, accompanied by increased production of inflammatory cytokines. There are no current antiparasitic drugs that effectively reduce or prevent chronic myocarditis caused by the onset of Chagas disease, thus new therapies are urgently needed. Therefore, the impact of AIP-1 and AIP-2 on myocarditis was investigated in a mouse model of chronic T. cruzi infection. MethodsFemale BALB/c mice infected with bioluminescent T. cruzi H1 strain trypomastigotes for 70 days were treated once daily for 7 days with 1mg/kg AIP-1 or AIP-2 protein by intraperitoneal injection. Control mice were left untreated or treated once daily for 14 days with 25mg/kg aspirin in drinking water. At 84 days of infection, splenocytes, cardiac tissue and serum were collected for evaluation. ResultsTreatment with both AIP-1 and AIP-2 proteins significantly reduced cardiac cellular infiltration, and reduced cardiac levels of IFNγ, IL-6 and IL-2. AIP-2 treatment reduced cardiac expression of COX-2. Further, while incubation with AIP-1 and AIP-2 proteins did not induce a significant upregulation of an immunoregulatory phenotype in dendritic cells (DC), there was a modest upregulation of CD11c+CD11b+MHCII+SIRPα+ expression, suggesting a regulatory phenotype. Ex-vivo stimulation of splenocytes from the treatment groups with AIP-1 loaded DC induced reduced levels of cytotoxic and pro-inflammatory T cells, stimulation with AIP-2 loaded DC specifically induced enhanced levels of CD4+CD25+Foxp3+ regulatory T cells among treatment groups. DiscussionAll in vivo and in vitro results demonstrate that hookworm-derived AIP-1 and AIP-2 proteins reduce T. cruzi induced cardiac inflammation, possibly through multiple anti-inflammatory mechanisms.

A Atenção Primária à Saúde (APS) atende às necessidades individuais e coletivas da sua população adstrita. Dessa forma, considera-se que a equipe de saúde acolhe as mulheres, que sofreram violência. Contudo, os estudos mostram a fragilidade nos atendimentos a esse grupo. Nesse sentido, questiona-se, especificamente, a atuação dos enfermeiros. Eles são capazes de reconhecer, de maneira precoce, as usuárias do serviço de saúde, que sofrem, ou que correm risco de sofrer violência? Denunciariam a violência contra mulheres atendidas, na unidade de saúde? Existe um ditado, muito forte no Brasil, que diz: “em briga de marido e mulher, não se mete a colher”. Será que esta crença interfere nas ações dos enfermeiros da Atenção Primária à Saúde (APS)? Diante deste contexto, a pergunta desta investigação é: “Como o enfermeiro atua perante a violência contra a mulher na APS?” Objetivo: Identificar e sistematizar a atuação do enfermeiro perante a violência contra a mulher na APS. Método: Utilizou-se da Revisão Integrativa, buscando nas bases de dados LILACS e BDENF, no período entre 2011 a 2021, e nos idiomas inglês e português, artigos que respondiam à pergunta de pesquisa. Resultados: Os encaminhamentos para serviços especializados, serviço social e de psicologia, construção do vínculo, acolhimento e empatia são atuações promovidas pelos enfermeiros na APS. Considerações Finais: Considera-se que a revisão integrativa alcançou os objetivos propostos, uma vez que foi possível identificar e sistematizar a atuação do enfermeiro. Este profissional possui o papel de coordenador e, por sua vez, integrador da equipe. É importante que o mesmo elabore atividades de capacitação, atue com uma visão holística e multiprofissional, devido à alta complexidade da violência doméstica contra a mulher.

Summary: Gout is an autoinflammatory disease triggered by a complex innate immune response to MSU crystals and inflammatory triggers. While hyperuricemia is an obligatory risk factor for the development of gout, the majority of individuals with hyperuricemia never develop gout but have an increased risk of developing cardiometabolic disorders. Current management of gout aims at MSU crystal dissolution by lowering serum urate. We apply a targeted proteomic analysis, using Olink inflammation panel, to a large group of individuals with gout, asymptomatic hyperuricemia, and normouricemic controls, and we show a urate-driven inflammatory signature. We add in vivo evidence of persistent immune activation linked to urate exposure and describe immune pathways involved in the pathogenesis of gout. Our results support a pro-inflammatory effect of asymptomatic hyperuricemia and pave the way for new research into targetable mechanisms in gout and cardiometabolic complications of asymptomatic hyperuricemia.

Referência do artigo comentado: Aguirre, Carlos Aguirre. El Infierno de Frantz Fanon. Trans/Form/Ação: Revista de filosofia da Unesp, v. 46, n. 4, p. 49-70, 2023.

6D pose recognition has been a crucial factor in the success of robotic grasping, and recent deep learning based approaches have achieved remarkable results on benchmarks. However, their generalization capabilities in real-world applications remain unclear. To overcome this gap, we introduce 6IMPOSE, a novel framework for sim-to-real data generation and 6D pose estimation. 6IMPOSE consists of four modules: First, a data generation pipeline that employs the 3D software suite Blender to create synthetic RGBD image datasets with 6D pose annotations. Second, an annotated RGBD dataset of five household objects was generated using the proposed pipeline. Third, a real-time two-stage 6D pose estimation approach that integrates the object detector YOLO-V4 and a streamlined, real-time version of the 6D pose estimation algorithm PVN3D optimized for time-sensitive robotics applications. Fourth, a codebase designed to facilitate the integration of the vision system into a robotic grasping experiment. Our approach demonstrates the efficient generation of large amounts of photo-realistic RGBD images and the successful transfer of the trained inference model to robotic grasping experiments, achieving an overall success rate of 87% in grasping five different household objects from cluttered backgrounds under varying lighting conditions. This is made possible by fine-tuning data generation and domain randomization techniques and optimizing the inference pipeline, overcoming the generalization and performance shortcomings of the original PVN3D algorithm. Finally, we make the code, synthetic dataset, and all the pre-trained models available on GitHub.

The pathogenesis of frontal fibrosing alopecia has been linked to specific genetic variants. CYP1B1 codes for a component of the cytochrome p450 machinery that is involved in the metabolism of xenobiotic oestrogens. The study of the prevalence of polymorphisms in this gene may help to understand their role in the development of frontal fibrosing alopecia. The aim of this study is to describe the frequency of genetic variations in the alleles HLA-B*07:02 and CYP1B1 in patients with frontal fibrosing alopecia. A cross-sectional study was designed to evaluate blood samples from patients with frontal fibrosing alopecia who attended the Dermatology Department at University Hospital Ramón y Cajal (Madrid, Spain), in search of the polymorphisms rs9258883 and rs1800440 in the alleles HLA-B*07:02 and CYP1B1, respectively. A total of 223 patients were included in the study. Among the 83.8% of patients who carried the rs9258883 polymorphism in HLA-B*07:02, 58.7% were heterozygous for this variant and it was not present in 14.8% of the cases. The majority of patients with frontal fibrosing alopecia lacked the protective rs1800440 polymorphism in CYP1B1 (75.2%). This suggests a relevant role of this variant in development of frontal fibrosing alopecia. The genetic approach to this condition might influence patient prognosis and therapy options.

Introduction: The study aimed to estimate the prevalence of vulnerability, and to identify the associated factors of vulnerability among rural community-dwelling older adults living in the municipality of Rio Grande, Rio Grande do Sul, Brazil. Methods: This was a cross-sectional, population-based study of a sample of individuals aged 60 years or older. Data from the first follow-up of the EpiRural Cohort Study (2018-2019) were used. Vulnerability was assessed using the Vulnerable Elders Survey (VES-13). The maximum score is 10 and older adults with scores of 3 or more are classified as vulnerable. Poisson regression with robust adjustment of variance was used for crude and adjusted analyses. For the analysis of the associated factors, a theoretical model was constructed with three hierarchical levels. The variables were adjusted in relation to each other within each level; those with a significance level of 0.20 or less were included in the regression model and adjusted to a higher level, with a subsequent level of significance of 5%. Results: The overall prevalence of vulnerability was 40.8% (95%CI 37.5-44.3). Vulnerability was more prevalent among women (PR=1.45; 95%CI 1.23-1.71), older adults who did not work (PR=1.70; 95%CI 1.17-2.45), those who lived without a partner (PR=1.26; 95%CI 1.07-1.47), those with diabetes (PR=1.23; 95%CI 1.03-1.48), those with depression (PR=1.21; 95%CI 1.02-1.42), those with osteoporosis (PR=1.38; 95%CI 1.15-1.66), and those with sarcopenia (PR=1.67; 95%CI 1.38-2.02). Conclusion: Vulnerability is common among rural community-dwelling older adults and is associated with sociodemographic and health characteristics.

IntroductionMultiple sclerosis (MS) is an inflammatory and demyelinating disorder of central nervous system that can be diagnosed in pediatric age (

When entering the job market, prospective translators face certain difficulties concerning professional know-how that they have to overcome in order to succeed in their career. For this reason, the aim of this article is to provide insights into the main concerns of future translators regarding professional competences. To understand these concerns, a corpus was created using the questions posted by future translators in a forum located on a very well-known translation site: Proz.com. A total of 125 posts were processed and thematically coded using the corpus manager Sketch Engine. The thematic codes were based on two multi-componential models of translator competence: PACTE’s and EMT Board’s models. Once the content was coded, qualitative content analysis was carried out in order to analyse the main concerns of translators-to-be in relation to professional competences. Results show that marketing, industry, and business knowledge are among the main causes of worry of prospective translators. Although the results are not generalisable, the conclusions drawn from this study provide translator trainers with a comprehensive view of what professional competences should be reinforced in the classroom.

IntroductionInfections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018.MethodsA national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0.ResultsA total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017–2018 compared to 2014–2016.DiscussionData from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.

This essay presents the reflections of four Education Doctorate (EdD) students on the pilot testing strategies used during an online research methods course. Rigorous questionnaire and interview development skills are challenging to acquire. Pilot testing is an under-researched stage of instrument design, yet it is crucial to ensure validity and reliability, reduce bias, and psychologically prepare researchers for data collection. A structured, multi-step pilot testing process led to the collective development of stronger scholar-practitioner identities, the use of innovative synchronous/asynchronous methods during COVID-19 and increased academic rigor. These reflections demonstrate how several types of pilot testing can support the development of rigorous data collection instruments and prepare post-graduate students for the psychological and technical challenges they may encounter in future research.

Summary: Fetal growth restriction (FGR) affects 5–10% of pregnancies, is the largest contributor to fetal death, and can have long-term consequences for the child. Implementation of a standard clinical classification system is hampered by the multiphenotypic spectrum of small fetuses with substantial differences in perinatal risks. Machine learning and multiomics data can potentially revolutionize clinical decision-making in FGR by identifying new phenotypes. Herein, we describe a cluster analysis of FGR based on an unbiased machine-learning method. Our results confirm the existence of two subtypes of human FGR with distinct molecular and clinical features based on multiomic analysis. In addition, we demonstrated that clusters generated by machine learning significantly outperform single data subtype analysis and biologically support the current clinical classification in predicting adverse maternal and neonatal outcomes. Our approach can aid in the refinement of clinical classification systems for FGR supported by molecular and clinical signatures.

Multiple myeloma (MM) is a hematologic cancer defined by an abnormal development of clonal plasma cells in the bone marrow, releasing vast quantities of immunoglobulins and different proteins. In the majority of patients, MM remains incurable despite decades of medical improvement and a number of treatment breakthroughs. Frontline standard-of-care has little long-term success, with the majority of patients eventually relapsing, although the overall progression-free survival (PFS) has improved significantly in the last ten years. Patients who are eligible for a transplant have the highest PFS rate at 5 years, depending on medication response and other various factors that are yet to be discovered. Therefore, the current study aimed to evaluate the response to VCD (bortezomib, cyclophosphamide, dexamethasone) and VTD (bortezomib, thalidomide, dexamethasone) used as pretransplant regimens, as well as to compare responses between thalidomide and lenalidomide used as maintenance therapy posttransplant. This retrospective study was performed on a group of 105 hospitalized patients in the Hematology Department of the Timisoara Municipal Emergency Clinical Hospital between January 2016 and December 2021. Data was collected from the paper records of patients with MM who were under-followed. The treatment regimens used as induction therapy were either VCD or VTD if cyclophosphamide was contraindicated. Of the 105 patients, 27 became eligible for bone marrow transplantation. Furthermore, they received maintenance therapy which was based on either lenalidomide with dexamethasone or thalidomide with dexamethasone. Of the 62 patients treated with VTD, 17.7% were in complete remission before stem cell transplantation. Of the 43 patients treated with VCD, 37.2% were in complete remission. The 5-year mean progression-free survival (PFS) in the entire cohort was better in the group treated with the VTD regimen (31.6 vs. 27.2 months). However, in the 27 patients undergoing maintenance after ASCT, the PFS with thalidomide was 35.5 months (95% CI = 27–42), while the PFS rate in those receiving maintenance treatment with lenalidomide was 46.1 months (95% CI = 20–73). VCD proved to be superior to VTD in inducing complete pretransplant responses. Regarding maintenance therapy, patients from the lenalidomide group had superior responses compared with those under thalidomide.

Abstract Acute myeloid leukaemia carrying the translocation t(7;12)(q36;p13) is an adverse-risk leukaemia uniquely observed in infants. Despite constituting up to 30% of cases in under 2-year-olds, it remains poorly understood. Known molecular features are ectopic overexpression of the MNX1 gene and generation of a fusion transcript in 50% of patients. Lack of research models has hindered understanding of t(7;12) biology, which has historically focused on MNX1 overexpression rather than the cytogenetic entity itself. Here, we employed CRISPR/Cas9 to generate t(7;12) in the human K562 cell line, and in healthy CD34+ haematopoietic progenitors where the translocation was not sustained in long-term cultures or through serial replating. In contrast, in K562 cells, t(7;12) was propagated in self-renewing clonogenic assays, with sustained myeloid bias in colony formation and baseline depletion of erythroid signatures. Nuclear localisation analysis revealed repositioning of the translocated MNX1 locus to the interior of t(7;12)-harbouring K562 nuclei — a known phenomenon in t(7;12) patients which associates with ectopic overexpression of MNX1. Crucially, the K562-t(7;12) model successfully recapitulated the transcriptional landscape of t(7;12) patient leukaemia. In summary, we engineered a clinically-relevant model of t(7;12) acute myeloid leukaemia with the potential to unravel targetable molecular mechanisms of disease.

Gliosarcoma (GS) is a primary malignant neoplasm of the central nervous system, treated with an unfavorable prognosis with surgery, radiotherapy, and chemotherapy. The treatment for GS consists of surgical resection, almost always accompanied by radiotherapy and/or chemotherapy, given the invasive behavior of the tumor. Photodynamic Therapy (PDT) is studied as an alternative method that combines light, a photosensitizer (PS), and molecular oxygen. This study aimed to compare the effects of PDT using the photosensitizers Fotoenticine (FTC) and Photodithazine (PDZ) at low concentrations and fluences. For this study, 9 L/lacZ cells, concentrations of 1.55 µg mL−1, 12.5 µg mL−1, and 50 µg mL−1 of chlorins and fluences of 1, 5, and 10 J/cm2 were used. A test was also carried out with Trypan Blue in L929 cells at the mentioned concentrations at 5 J/cm2. Both chlorins were internalized in the cytoplasm, with a significant reduction in viability (>95%) in almost all groups and altered cell adhesion and morphology after PDT. HSP70 expression decreased in both PS, while HSP27 increased only in PDT with FTC, and although there was a change in cell adhesion in the 9 L/LacZ lineage it was not observed in the L929 fibroblast lineage. Both chlorins were effective, highlighting the concentration of 50 µg mL−1 at the fluence of 5 J/cm2; according to the present study, the PDZ showed better results.

Multiple sclerosis (MS) represents the most common acquired demyelinating disorder of the central nervous system (CNS). Its pathogenesis, in parallel with the well-established role of mechanisms pertaining to autoimmunity, involves several key functions of immune, glial and nerve cells. The disease’s natural history is complex, heterogeneous and may evolve over a relapsing-remitting (RRMS) or progressive (PPMS/SPMS) course. Acute inflammation, driven by infiltration of peripheral cells in the CNS, is thought to be the most relevant process during the earliest phases and in RRMS, while disruption in glial and neural cells of pathways pertaining to energy metabolism, survival cascades, synaptic and ionic homeostasis are thought to be mostly relevant in long-standing disease, such as in progressive forms. In this complex scenario, many mechanisms originally thought to be distinctive of neurodegenerative disorders are being increasingly recognized as crucial from the beginning of the disease. The present review aims at highlighting mechanisms in common between MS, autoimmune diseases and biology of neurodegenerative disorders. In fact, there is an unmet need to explore new targets that might be involved as master regulators of autoimmunity, inflammation and survival of nerve cells.

Abstract Background Among commercially-available upper-limb prostheses, the two most often used solutions are simple hook-style grippers and poly-articulated hands, which present a higher number of articulations and show a closer resemblance to biological limbs. In their majority, the former type of prostheses is body-powered, while the second type is controlled by myoelectric signals. Body-powered grippers are easy to control and allow a simple form of force feedback, frequently appreciated by users. However, they present limited versatility. Poly-articulated hands afford a wide range of grasp and manipulation types, but require enough residual muscle activation for dexterous control. Several factors, e.g. level of limb loss, personal preferences, cost, current occupation, and hobbies can influence the preference for one option over the other, and is always a result of the trade-off between system performance and users’ needs. Methods The SoftHand Pro (SHP) is an artificial hand platform that has 19 independent joints (degrees-of-freedom), but is controlled by a single input. The design of this prosthesis is inspired by the concept of postural synergies in motor control and implemented with soft-robotic technologies. Their combination provides increased robustness, safe interaction and the execution of diverse grasps. The potential of the SHP is fully unleashed when users learn how to exploit its features and create an intimate relationship between the technical aspects of the prosthesis design and its control by the user. Results The great versatility of the SoftHand Pro (a reasearch protpotype) permitted its adaptation to the user requirements. This was experienced by the SoftHand Pro Team during the preparation for different CYBATHLON events (from 2016 to 2020). The mixed power and dexterous hand operations required by each task of the race is inspired by everyday tasks. Our prosthesis was driven by different pilots, with different habits and backgrounds. Consequently, the hand control modality was customized according to the user’s preferences. Furthermore, the CYBATHLON tasks had some variations in this period, promoting the continuous development of our technology with a user-centered approach. In this paper, we describe the participation and preparation of the SoftHand Pro Team from 2016 to 2020 with three pilots and two different activation modalities, hybrid body-controlled and myoelectric control. Conclusions We introduced our pilots, the implementation of the two control modalities, and describe the successful participation in all CYBATHLON events. This work proves the versatility of the system towards the user’s preferences and the changes in the race requirements. Finally, we discussed how the CYBATHLON experience and the training in the real-world scenario have driven the evolution of our system and gave us remarkable insights for future perspectives.

Antecedentes. La serie pedagógica De la universidad a la escuela compila actividades docentes innovadoras que incluyen formación y difusión científica en escuelas primarias y secundarias argentinas. Objetivo. Desarrollar una actividad docente innovadora que expanda las realizadas anteriormente e incluya clases y trabajos prácticos afines en laboratorios escolares. Enfoque y actividades. En un temario de infecciones, se relacionaron las áreas de biología y química con estudiantes que cursaban primero, segundo o cuarto año de una escuela municipal de Buenos Aires (Argentina). Se repasaron, seleccionaron y relacionaron conocimientos de la curricula escolar; luego se agregó información relacionada extraída de los programas universitarios de farmacología y microbiología, además de datos científicos recientes. Se expandió y profundizó el temario de infecciones comunes en adolescentes, particularmente las candidiasis. Se informó sobre Candida albicans resistente a medicamentos, su relevancia médica y la búsqueda de nuevos medicamentos para solucionar el problema sanitario. Como ejemplos de potenciales medicamentos antimicóticos de origen vegetal para combatir Candida albicans resistente a azoles, se tomó en forma comparativa la curcumina y el 8PP, en función de su similar actividad antimicrobiana, aspecto físico y conocimientos previos del alumnado. La primera está contenida en el condimento popular cúrcuma o azafrán de la India; se seleccionó este último por ser conocido por el alumnado. El 8PP, extraído de las raíces de la leguminosa Dalea elegans, continúa siendo investigado en estrategias farmacológicas en Argentina. En este trabajo docente se diseñaron y desarrollaron clases teóricas y prácticas interactivas, adecuadas a los temas tratados y al laboratorio escolar. Resultados. Se desarrolló una propuesta innovadora docente que integra y actualiza distintos conocimientos científicos relacionados con la búsqueda de nuevos medicamentos antimicóticos. Conclusiones.Esta experiencia amplía y enriquece la curricula docente del nivel secundario, tanto en criterios científicos como en datos provenientes de ámbitos argentinos y extranjeros, siguiendo recomendaciones derivadas de su reconocida y valorada originalidad.

Poly(butylene succinate) (PBS) is one of the contaminants in the Poly(ethylene terephthalate) (PET) recycling process. It is known that high contents of PBS in PET significantly reduce PET properties, but the effect of low contents on PET has yet to be studied. This work studied the influence of low contents of PBS on recycled PET. Five formulations of PBS in PET were prepared, and the properties of relative affinity, mechanical, thermal, and disintegration under composting conditions were assessed. The solubility parameter indicated that PET and PBS are miscible. However, FESEM images show slight marks of immiscibility, and the mechanical characterization results showed that PBS, even in low contents, reduced the mechanical properties of recycled PET, which proves that the materials are not miscible in the studied contents. The DSC results indicated that PBS could not be quickly detected in PET. However, its presence can be inferred by the reduction in PET crystallization degree. Finally, the presence of PBS up to 15 wt.% does neither affect the disintegration under composting conditions nor the thermal stability of recycled PET. The drop in mechanical properties shows that PBS must be removed from the PET waste stream to preserve the quality of the material.

Abstract This retrospective observational study (NEUF) included adult patients with B-cell acute lymphoblastic leukemia (B-cell ALL) who had received blinatumomab for the treatment of minimal residual disease-positive (MRD+) or relapsed/refractory (R/R) B-cell ALL via an expanded access program (EAP). Patients were eligible if blinatumomab was initiated via the EAP between January 2014 and June 2017. Patients were followed from blinatumomab initiation until death, entry into a clinical trial, the end of follow-up, or the end of the study period (December 31, 2017), whichever occurred first. Of the 249 adult patients included, 109 were MRD+ (83 Philadelphia chromosome-negative [Ph−] and 26 Philadelphia chromosome-positive [Ph+]) and 140 had a diagnosis of R/R B-cell ALL (106 Ph− and 34 Ph+). In the MRD+ group, within the first cycle of blinatumomab treatment, 93% (n = 49/53) of Ph− and 64% (n = 7/11) of Ph+ patients with evaluable MRD achieved an MRD response (MRD

Fungi mostly reproduce through spores that are adapted for airborne dispersal; hence, fungal spores (and fungi) are found virtually everywhere. Fungi can be "friends or foes." Our friends include fungi used in the food and biotech industries, fungi that contribute to the cycling of carbon and nutrients, and those involved in the decontamination of polluted soils and/or water, to mention just a few examples. Many species, however, are foes--they are detrimental to plants, animals, and/or humans. Annually, >1.5 million people die due to invasive fungal infections. With the aim of enhancing microbiology literacy and the understanding of microbial concepts, we set up a project for the collection of airborne spores (the principal agent through which human airways are exposed to fungi). Students from five high schools in the Oeiras municipality partnered with us as citizen scientists; they carried out sampling by collecting fungal spores on adhesive stickers. The fungal spores collected by the students were subsequently processed in the schools and our research laboratory. Results obtained by the students themselves revealed a large variety of fungal species capable of growing in a rich medium at 30°C. In the research laboratory, using selective isolation conditions, 40 thermotolerant fungi were isolated, 32 of which were taxonomically identified as aspergilla, mostly from within the Aspergillus fumigatus taxa, yet exhibiting high genetic heterogeneity. The protocols and results were presented to the students, who were made aware of the local dispersal of airborne fungal spores, including some from potentially pathogenic fungi. Through carrying out scientific activities, the students developed both the interest and the self-confidence needed to implement future environmental investigations.

Textile conservation has given rise to small and medium-sized museums, usually with scarce resources. In Sicily, the little evidence that remains of silk production and opulent imports by the rich and powerful local aristocracy is kept in museums, parishes, and other cultural institutions. The documentation, dissemination, and enhancement of such a fragile heritage is today possible by means of technological tools that provide novel means to preserve, analyze, and exploit digital information. In this paper, we present some outcomes of the SILKNOW project, a project that applies computing research to the needs of diverse users (museums, educational institutions, the tourism industry, creative industries, media, etc.) and preserves the tangible and intangible heritage associated with silk. We show the methodology followed to build end users’ needs into the Virtual Loom, a tool that deals with the 3D reconstruction of silk fabrics at the yarn level. We also provide a real example of how to integrate it at the museum level, specifically, at Piraino’s Collection. The results demonstrate how small and medium-sized museums can access tools that will help them to carry out their daily tasks.

Periodontitis patients are known to have increased circulating lipopolysaccharide activity and metabolic disturbances, which may be either the cause or effect of endotoxemia. This review approaches endotoxemia as a possible molecular mediator between periodontitis and increased risk of cardiometabolic disorders. Observations that bacteria disseminate into circulation after toothbrushing and periodontal procedures and assumptions that endotoxin may disseminate through inflamed periodontium and bleeding gums support the idea of endotoxemia in periodontitis. However, the evidence that periodontitis-associated dysbiosis contributes to endotoxemia is not as strong as in the case of gut microbiome dysbiosis. Although the causality is insufficiently demonstrated thus far, many studies have associated changes of the gut microbiome composition, function, and specific bacterial metabolites with cardiometabolic diseases, whereas research on the oral microbiome has severely fallen behind.

Periodontitis patients are known to have increased circulating lipopolysaccharide activity and metabolic disturbances, which may be either the cause or effect of endotoxemia. This review approaches endotoxemia as a possible molecular mediator between periodontitis and increased risk of cardiometabolic disorders. Observations that bacteria disseminate into circulation after toothbrushing and periodontal procedures and assumptions that endotoxin may disseminate through inflamed periodontium and bleeding gums support the idea of endotoxemia in periodontitis. However, the evidence that periodontitis-associated dysbiosis contributes to endotoxemia is not as strong as in the case of gut microbiome dysbiosis. We describe the structure-function relationship of lipopolysaccharide, the local and systemic inflammatory and immunological responses caused by lipopolysaccharide, current knowledge on endotoxemia in periodontitis, factors affecting the levels of endotoxemia, and its relation to cardiometabolic disorders. They are physically, microbiologically, and biochemically connected to each other, and only crumbs of information are known about this connection. Although the causality is insufficiently demonstrated thus far, many studies have associated changes of the gut microbiome composition, function, and specific bacterial metabolites with cardiometabolic diseases, whereas research on the oral microbiome has severely fallen behind.

Transplantul hepatic este un tratament important pentru insuficiență hepatică acută si boala hepatică in stadiu terminal. In 2002, modelul pentru boala hepatica in stadiu terminal (MELD) a fost incorporat pentru a acorda prioritate pacientilor care asteapta transplant hepatic. Deși există date despre modul în care scorul MELD afectează timpul de așteptare, există o lipsă de literatură cu privire la alte componente. Ne-am propus să evaluăm factorii care afectează timpul de așteptare pentru TH. Folosind baza de date din Republica Moldova au fost incluși pacienții cu vîrsta cuprinsă între 18-65 de ani listați pentru transplanți hepatic în perioada 2013-2022. Variabilele testate în model au inclus caracteristicile pacientului, analize biochimice, scorul MELD și grupa de sînge ABO. Scorul MELD este utilizat în prioritizarea alocării ficatului și era de așteptat să prezică timpul pe lista de așteptare. Ventilația mecanică și alți markeri ai severității bolii sunt asociați cu scoruri MELD mai mare, prin urmare, timpul de așteptare mai scurt. Sunt necesare cercetări suplimentare pentru a aborda motivele variației timpului de așteptare în încercarea de a reduce timpul pînă la TH, de a standardiza procesul de listare și de a îmbunătăți rezultatele pacienților.Obiective. Scopul lucrării științifice a fost de a analiza factorii de risc și timpul de așteptare a pacienților cu boli hepatice pe lista de așteptare pentru transplant hepatic. Materiale și metode. S-a efectuat un studiu retrospectiv 2013-2018 și prospectiv 2018-2022, în care fost incluși 265 de pacienți cu ciroză hepatică decompensată, pe lista de așteptare pentru transplant hepatic. Deasemenea ca sursă de literatură științifică au fost utilizate următoarele baze de date: Google Scholar, PubMed și eLibrary. Cuvintele cheie care au fost folosite în căutare: ,,transplant hepatic’’, ,,insuficiență hepatică acută și cronică’’. Rezultate. Rezultatele noastre arată că cei cu sodiu seric mai scăzut au avut un timp de așteptare mai scurt în comparație cu candidații cu sodiu mai mare. Astfel pacienți cu grupa de sînge A au fost cei mai multi pacienți, care deasemenea este un prognostic pentru aceasta grupă să fie mai expuși riscului de infectie virală.

Abstract Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with highly variable presentation, characteristics, and clinical course. Thrombocytopenia is a common complication of many viral infections, including SARS-CoV-2. In addition, both de novo ITP and exacerbation of ITP after vaccination against SARS-CoV-2 have been reported. Patients infected with SARS-CoV-2 develop a prothrombotic coagulopathy called COVID-19-associated coagulopathy (CAC). In addition, autoimmune hematological disorders secondary to SARS-CoV-2 infection, mainly ITP and autoimmune hemolytic anemia (AIHA), have been described. Furthermore, SARS-CoV-2 infection has been associated with exacerbation of autoimmune processes, including ITP. In fact, there is evidence of a high relapse rate in patients with preexisting ITP and COVID-19. As for vaccination against SARS-CoV-2, hematological adverse events (HAE) are practically anecdotal. The most common HAE is thrombocytopenia-associated thrombosis syndrome (TTS) linked to vectored virus vaccines. Other HAEs are very rare, but should be considered in patients with previous complement activation disease or autoimmunity. In patients with ITP who are vaccinated against SARS-CoV-2, the main complication is exacerbation of ITP and the bleeding that may result. In fact, this complication occurs in 12% of patients, with splenectomized and refractory patients with more than five lines of previous treatment and platelet counts below 50 × 109/L being the most vulnerable. We conclude that, in general, there is no greater risk of severe SARS-CoV-2 infection in ITP patients than in the general population. Furthermore, no changes are advised in patients with stable ITP, the use of immunosuppressants is discouraged unless there is no other therapeutic option, and patients with ITP are not contraindicated for vaccination against COVID-19.

Periodontal pathology and early clinical manifestations in the context of leukemia are influenced by the host organism, by immunological, microbiological and genetic factors, but also by environmental factors (physical agents (ionizing radiation, x-rays) and chemical agents (drugs such as cytostatics, exposure to organic solvents or to pesticides, herbicides, exposure to cigarette smoke). The purpose of this article is to emphasize both the importance of the health status of the marginal periodontium and the severity of gingival-periodontal manifestations in the context of haematological diseases. We also want to draw attention to the role of periodontal treatment: the elimination of periodontal inflammation, the reduction of periodontal pockets, the maintenance of rigorous oral hygiene and the periodic check-up in a dental practice in this category of patients. Clinical and radiological evidence-gathering is very important in the recognition and diagnosis of gingival-periodontal manifestations in haematological diseases, as when they are not treated in time, they become a source of infection of the oral cavity and in the entire body. Conclusions. It is essential to analyze this interaction in all aspects, from a clinical, microbiological, immunological and genetic point of view, in order to make a diagnosis and implement a correct and complete treatment plan.

The Oil and Gas industry is pursuing major changes in automation, with the aim of reducing the risk involved in operations and increasing efficiency, speeding up processes to reduce costs. Internationally and especially in the Offshore environment, deposits with high productive potential are targeted, which are put into operation through a small number of wells with a high flow rate, due to the complexity of marine drilling. The high costs in this sector of the industry make it necessary to optimize all operational times, thus we very often encounter automation elements in the marine drilling process. This work intends to present the advantages of using the Simulink program package in the simulation of the processes, respectively of the maneuver operation in a drilling installation, to predict their real behavior.