Obesity aggravates acute kidney injury resulting from ischemia and reperfusion in mice.

In critically ill patients, overweight and obesity are associated with acute respiratory distress syndrome and acute kidney injury (AKI). However, the effect of obesity on ischemia-reperfusion injury (IRI)-induced AKI is unknown. We hypothesized that obesity would aggravate renal IRI in mice. We fed mice a standard or high-fat diet for eight weeks. The mice were divided into four groups and submitted to sham surgery or IRI: obese, normal, normal + IRI, obese, and obese + IRI. All studies were performed 48 h after the procedures. Serum glucose, cholesterol, and creatinine clearance did not differ among the groups. Survival and urinary osmolality were lower in the obese + IRI group than in the normal + IRI group, whereas urinary neutrophil gelatinase-associated lipocalin levels, tubular injury scores, and caspase 3 expression were higher. Proliferating cell nuclear antigen expression was highest in the obese + IRI group, as were the levels of oxidative stress (urinary levels of thiobarbituric acid-reactive substances and renal heme oxygenase-1 protein expression), whereas renal Klotho protein expression was lowest in that group. Expression of glutathione peroxidase 4 and peroxiredoxin 6, proteins that induce lipid peroxidation, a hallmark of ferroptosis, was lower in the obese + IRI group. Notably, among the mice not induced to AKI, macrophage infiltration was greater in the obese group. In conclusion, greater oxidative stress and ferroptosis might aggravate IRI in obese individuals, and Klotho could be a therapeutic target in those with AKI.

Methylene blue as an adjuvant during cardiopulmonary resuscitation: an experimental study in rats.

INTRODUCTION: Methylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. METHOD: Thirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11/group) and treated with EPI 20 µg.kg-1 (EPI), EPI 20 µg.kg-1 + MB 2 mg.kg-1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. RESULTS: No differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI + MB: 43.7 [116.31] ng/mL, p < 0.05). CONCLUSION: The coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

Methylene blue as an adjuvant during cardiopulmonary resuscitation: an experimental study in rats

Abstract Introduction: Methylene Blue (MB) has been shown to attenuate oxidative, inflammatory, myocardial, and neurological lesions during ischemia-reperfusion and has great potential during cardiac arrest. This study aimed to determine the effects of MB combined with epinephrine during cardiac arrest on myocardial and cerebral lesions. Method: Thirty-eight male Wistar rats were randomly assigned to four groups: the sham group (SH, n = 5), and three groups subjected to cardiac arrest (n = 11 /group) and treated with EPI 20 μg.kg−1 (EPI), EPI 20 μg.kg−1 + MB 2 mg.kg−1 (EPI + MB), or saline 0.9% 0.2 ml (CTL). Ventricular fibrillation was induced by direct electrical stimulation in the right ventricle for 3 minutes, and anoxia was maintained for 5 minutes. Cardiopulmonary Resuscitation (CPR) consisted of medications, ventilation, chest compressions, and defibrillation. After returning to spontaneous circulation, animals were observed for four hours. Blood gas, troponin, oxidative stress, histology, and TUNEL staining measurements were analyzed. Groups were compared using generalized estimating equations. Results: No differences in the Returning of Spontaneous Circulation (ROSC) rate were observed among the groups (EPI: 63%, EPI + MB: 45%, CTL: 40%, p = 0.672). The mean arterial pressure immediately after ROSC was higher in the EPI+MB group than in the CTRL group (CTL: 30.5 [5.8], EPI: 63 [25.5], EPI+MB: 123 [31] mmHg, p = 0.007). Serum troponin levels were high in the CTL group (CTL: 130.1 [333.8], EPI: 3.70 [36.0], EPI +MB: 43.7 [116.31] ng/mL, p < 0.05). Conclusion: The coadministration of MB and epinephrine failed to yield enhancements in cardiac or brain lesions in a rodent model of cardiac arrest.

Up-regulation of TNF-alpha/NFkB/SIRT1 axis drives aggressiveness and cancer stem cells accumulation in chemoresistant oral squamous cell carcinoma.

Tumor resistance remains an obstacle to successfully treating oral squamous cell carcinoma (OSCC). Cisplatin is widely used as a cytotoxic drug to treat solid tumors, including advanced OSCC, but with low efficacy due to chemoresistance. Therefore, identifying the pathways that contribute to chemoresistance may show new possibilities for improving the treatment. This work explored the role of the tumor necrosis factor-alpha (TNF-alpha)/NFkB signaling in driving the cisplatin resistance of OSCC and its potential as a pharmacological target to overcome chemoresistance. Differential accessibility analysis demonstrated the enrichment of opened chromatin regions in members of the TNF-alpha/NFkB signaling pathway, and RNA-Seq confirmed the upregulation of TNF-alpha/NFkB signaling in cisplatin-resistant cell lines. NFkB was accumulated in cisplatin-resistant cell lines and in cancer stem cells (CSC), and the administration of TNF-alpha increased the CSC, suggesting that TNF-alpha/NFkB signaling is involved in the accumulation of CSC. TNF-alpha stimulation also increased the histone deacetylases HDAC1 and SIRT1. Cisplatin-resistant cell lines were sensitive to the pharmacological inhibition of NFkB, and low doses of the NFkB inhibitors, CBL0137, and emetine, efficiently reduced the CSC and the levels of SIRT1, increasing histone acetylation. The NFkB inhibitors decreased stemness potential, clonogenicity, migration, and invasion of cisplatin-resistant cell lines. The administration of the emetine significantly reduced the tumor growth of cisplatin-resistant xenograft models, decreasing NFkB and SIRT1, increasing histone acetylation, and decreasing CSC. TNF-alpha/NFkB/SIRT1 signaling regulates the epigenetic machinery by modulating histone acetylation, CSC, and aggressiveness of cisplatin-resistant OSCC and the NFkB inhibition is a potential strategy to treat chemoresistant OSCC.

Caracterización de pacientes con enfermedades cerebrovasculares en fase aguda según diagnóstico tradicional chino

Fundamento en la medicina china, los accidentes cerebrovasculares se relacionan con el síndrome de golpe de viento (Zhong Feng), lo cual se corresponde en la medicina occidental con los accidentes cerebrovasculares hemorrágicos e isquémicos. Objetivo caracterizar a los pacientes con accidentes cerebrovasculares en fase aguda según diagnóstico de la medicina china. Métodos estudio descriptivo, de serie de casos (n=40), que incluyó a pacientes atendidos en el periodo marzo-diciembre de 2018 en el Hospital Dr. Gustavo Aldereguía Lima, de Cienfuegos. Se analizaron las variables: edad, sexo, tipo de enfermedad cerebrovascular en fase aguda, gravedad del ataque del golpe de viento, síndrome según órganos y vísceras, y factor patógeno presente. Resultados predominaron los accidentes cerebrovasculares trombóticos, de los cuales 75,0 % se comportaron como golpe de viento graves tipo flácido; y el 81,3 % estuvo asociado al síndrome de insuficiencia de sangre de hígado. Los embólicos: ataques leves en el 33,3 %; y 18,8 % síndrome de insuficiencia de sangre de hígado. Las hemorragias cerebrales intraparenquimatosas: 62,5 % ataque grave tipo tenso; y 71,4 % fuego de hígado. Hemorragia subaracnoidea: 15 % como ataque grave tipo flácido; y 17,6 % síndrome de insuficiencia de Yin de hígado. El factor patógeno más frecuente resultó el viento interno, presente en 90,0 % de los casos. Conclusiones el análisis de los pacientes con accidente cerebrovascular en fase aguda según diagnóstico tradicional chino, mostró que existe relación clínica con el síndrome golpe de viento y de los Zhang fu de la medicina china.

Foundation In Chinese medicine, strokes are related to wind stroke syndrome (Zhong Feng), which corresponds in Western medicine to hemorrhagic and ischemic strokes. Objective to characterize patients with strokes in the acute stage according to Chinese medicine diagnosis. Methods descriptive case series study (n=40), which included patients treated from March to December 2018 at the Dr. Gustavo Aldereguía Lima Hospital, Cienfuegos. The analyzed variables were: age, sex, type of cerebrovascular disease in the acute stage, severity of the wind stroke attack, syndrome according to organs and viscera, and pathogenic factor present. Results thrombotic strokes predominated, of which 75.0% behaved as severe flaccid type wind stroke; and 81.3% were associated with liver blood failure syndrome. Embolics: mild attacks in 33.3%; and 18.8% liver blood failure syndrome. Intraparenchymal cerebral hemorrhages: 62.5% severe tense attack; and 71.4% liver fire. Subarachnoid hemorrhage: 15% as severe flaccid type attack; and 17.6% liver Yin deficiency syndrome. The most frequent pathogenic factor was internal wind, present in 90.0% of cases. Conclusions the analysis of patients with stroke in the acute phase according to traditional Chinese diagnosis showed that there is a clinical relationship with wind stroke syndrome and the Zhang fu of Chinese medicine.

Understanding the impact of varicocele on sperm capacitation.

OBJECTIVE: To study the relationship between the seminal sample quality of men with varicocele and sperm capacitation. DESIGN: Cross-sectional observational study. SETTING: Academic hospital. PATIENT(S): Seventy-six men (19 control and 57 with varicocele) were analyzed. INTERVENTION(S): Semen samples were submitted to a discontinuous density gradient for sperm selection. Sperm capacitation was induced using a human tubal fluid medium supplemented with bovine serum albumin. MAIN OUTCOME MEASURE(S): After capacitation induction, the sperm were assessed by capacitation state, computer-assisted sperm motility, mitochondrial activity, membrane integrity, acrosome reaction, and intracellular oxidative stress. RESULT(S): The capacitation period increased sperm motility, showing an increase in the average path velocity and a decrease in the straightness compared with sperm before capacitation (paired analysis). After capacitation, the rate of capacitated sperm, motility, and mitochondrial activity showed differences between groups (control and varicocele). The varicocele group showed lower mitochondrial activity and capacitation than the control group. On the other hand, no significant differences were observed in the other variables evaluated. CONCLUSION(S): Varicocele men showed less viable sperm and mitochondrial activity than control men after capacitation sperm. The induction of capacitation altered motility by increasing path velocity and decreasing straightness in all of the studied groups, evidencing the occurrence of hyperactivation.

Aplicación de ozono por vía rectal a pacientes con diabetes mellitus

Fundamento: los pacientes con diabetes mellitus cursan con un aumento importante en el estrés oxidativo, donde hay una disminución en la actividad de los sistemas antioxidantes y un incremento de los productos de oxidación. El ozono actúa induciendo estrés oxidativo moderado y estimulando una defensa antioxidante enzimática. Objetivo: caracterizar el control metabólico de los pacientes diabéticos al inicio y al culminar la terapia con ozono rectal. Métodos: se realizó un estudio cuasi experimental con pre y post terapia, donde el universo estuvo constituido por 121 pacientes diabéticos del consultorio médico de familia, número 15 del Policlínico Comunitario Docente José Luis Chaviano de Cienfuegos aplicándoles ozonoterapia por vía rectal previa evaluación médica, por 15 sesiones dos veces al año. Fueron recogidas como variables demográficas: edad y sexo; clínicas: parámetros hemoquímicos, tiempo de evolución de la enfermedad y estado nutricional; como complicaciones neurovasculares: pie diabético, polineuropatía diabética y retinopatía diabética; tratamientos: hipoglucemiantes; factores de riesgo modificables: hipertensión arterial, diabetes mellitus, tabaquismo, alcoholismo, realización de ejercicio físico; cálculo del índice de masa corporal. Los resultados hallados fueron expresados fundamentalmente mediante tablas y gráficos como principales recursos del lenguaje estadístico. Resultados: los pacientes con diabetes mellitus tipo 2 predominaron con un 95,0 %. Existió una disminución de 2, 769 mmol/L de las cifras de glucemia después del tratamiento con ozono rectal lo que muestra un control metabólico. Conclusiones: la ozonoterapia rectal puede ser utilizada como terapia complementaria al tratamiento convencional de pacientes con diabetes mellitus, pues mejora los parámetros de glucemia.

Background: patients with diabetes mellitus have a significant increase in oxidative stress, where there is a decrease in the activity of antioxidant systems and an increase in oxidation products. Ozone acts by inducing moderate oxidative stress and stimulating an enzymatic antioxidant defense. Objective: to characterize the metabolic control of diabetic patients at the beginning and at the end of rectal ozone therapy. Methods: a quasi-experimental study was carried out with pre and post therapy, where the universe consisted of 121 diabetic patients from the family doctor's office, number 15 of the José Luis Chaviano Community Teaching Polyclinic in Cienfuegos, applying rectal ozone therapy prior medical evaluation for 15 sessions twice a year. Demographic variables were collected: age and sex; clinics: hemochemical parameters, time of evolution of the disease and nutritional status; as neurovascular complications: diabetic foot, diabetic polyneuropathy and diabetic retinopathy; treatments: hypoglycemic; modifiable risk factors: arterial hypertension, diabetes mellitus, smoking, alcoholism, physical exercise; calculation of body mass index. The results found were expressed mainly through tables and graphs as the main resources of the statistical language. Results: patients with type 2 diabetes mellitus predominated with 95.0 %. There was a 2,769 mmol/L decrease in blood glucose levels after treatment with rectal ozone, which shows metabolic control. Conclusions: rectal ozone therapy can be used as a complementary therapy to the conventional treatment of patients with diabetes mellitus, since it improves glycemia parameters.

Seroprevalence study prior and post vaccination in cancer patients in principality of Andorra (COVONCO study).

BACKGROUND: COVID-19 serologic response in patients with cancer may be lower than in the general population and may be influenced by the type of tumor or anticancer treatment. This study aims to analyze serological response prior and after vaccination of COVID-19 within the oncological population in Andorra. We set out to identify risk factors for a higher or lower serological response. PATIENTS AND METHODS: Observational, unicentric, prospective cohort study of oncologic patients in Andorra. We calculated the seroprevalence of antibodies against SARS-CoV-2 (May 2020-June 2021) and analyzed the main demographic, oncologic features and factors associated with being seropositive. RESULTS: A total of 373 patients were analyzed, mainly with solid tumours (n = 334, 89.5%). At baseline, seroprevalence was 13%, increasing during follow-up to 19%; lower seroprevalence was observed in patients with hematologic malignancies (2.6% vs 14.2%; p = 0.041) and patients receiving biological therapies (0% vs 15%, p = 0.005). In the overall seroprevalence analysis, women (23% vs 11.9%; p = 0.006) and tumour-free patients (p = 0.034) showed higher seroprevalence. The multivariable analysis showed that odds of being seropositive were higher among women (OR: 2.44, 95% CI 1.28-4.64), and patients who underwent surgery (OR: 3.35, 95% CI 1.10-10.20). About 80% of the cohort received at least one dose of COVID-19 vaccination, showing a higher seroprevalence of patients who received ChAdOx1-S than those who received BNT162b2 (24.4% vs 6.4%: p = 0.001). CONCLUSION: The seroprevalence of antibodies against SARS-COV-2 in oncologic patients in Andorra was higher among females and patients who received hormonal therapy and surgery while patients with hematologic malignancies and biologic therapies showed lower seropositivity without finding differences in the type of tumour or anticancer treatment.

Adoption in the school context: Exploring perspectives / Adoção no Contexto Escolar: explorando olhares

Objective This article sought to analyze the perceptions of parents and teachers regarding the school trajectory of adopted children. For this, Elementary School (3rd to 7th grade) teachers and adoptive parents were interviewed, investigating how they perceive adopted children's possible successes and difficulties in school, and if there is a relationship between adoption and school performance. Method The theoretical-methodological perspective of the "Rede de Significações" [Network of Meanings] was employed, seeking to understand and investigate the perceptions of the interviewees in a contextualized and articulated way. It was understood that it is important to go beyond the analysis of the child's individual components (as a biological or adopted child), considering the interactional network and the context in which he/she is inserted. Results As results, teachers attributed a direct influence on learning to the "family structure", while parents focused their representations on individual issues of their children. Conclusion The children's school difficulties and successes, therefore, were not directly related to adoption, but to previous experiences and the current family context.

Objetivo Este artigo buscou analisar as percepções de pais e professores a respeito da trajetória escolar de crianças adotadas. Para isto, entrevistamos professores do Ensino Fundamental (3º ao 7º ano) e pais adotivos, investigando como compreendem a existência de possíveis sucessos e dificuldades escolares nas crianças adotadas, e se há relação entre adoção e atuação escolar. Método Utilizamos a perspectiva teórico-metodológica da Rede de Significações, buscando compreender e investigar as percepções dos entrevistados de forma contextualizada e articulada. Entendemos ser importante ir além da análise de componentes individuais da criança (como filho biológico ou adotivo), considerando a rede interacional e o contexto em que ela está inserida. Resultados Como resultados, os professores atribuíram à "estrutura familiar" influência direta na aprendizagem, enquanto os pais focalizaram suas representações em questões individuais dos filhos. Conclusão As dificuldades e os sucessos escolares das crianças, portanto, não foram diretamente relacionados à adoção, mas às vivências anteriores e ao contexto familiar atual.

Prática deliberada e prática deliberada em ciclos rápidos para suporte básico de vida: scoping review / Práctica deliberada y práctica deliberada en ciclos rápidos para soporte básico de vida: revisión de alcance / Deliberate practice and rapid cycle deliberate practice for basic life support: a scoping review

Resumo Objetivo mapear evidências sobre a prática deliberada (PD) e a prática deliberada em ciclos rápidos (PDCR) no ensino do Suporte Básico de Vida (SBV) de estudantes de ciências da saúde. Método scoping review, conforme JBI Reviewer's Manual for Scoping Reviews e PRISMA-ScR. Buscas e seleções foram realizadas nas bases de dados estabelecidas por intermédio de descritores e sinônimos, analisando a relevância dos estudos, selecionando os que responderam à pergunta de investigação, no período de abril a novembro de 2021. Em dezembro de 2022 realizou-se atualização da busca e seleção dos estudos. Resultados dos 4.155 estudos encontrados, 116 foram analisados na íntegra, com 9 incluídos neste estudo. 44,4% são americanos e 66,6% foram realizados em cursos de medicina. 11,1% apresentaram cenários simulados no contexto intra e extra-hospitalar, e 11,1%, em cenários intra-hospitalares. Conclusão e implicações para a prática a PD e a PDCR no ensino em saúde vêm sendo consolidadas nos últimos anos, evidenciando melhorias de aprendizado e retenção de conhecimento ao longo do tempo. Foi identificado que a maioria dos estudos abordam o contexto hospitalar, demonstrando a lacuna de produção de conhecimento pré-hospitalar. Ademais, a maioria dos estudos se concentrou entre Europa e América do Norte, confirmando a necessidade de realização de estudos para aplicabilidade da PD e PDCR em SBV em diferentes públicos e contextos.

Resumen Objetivo mapear evidencias sobre Práctica Deliberada (PD) y Práctica Deliberada em Ciclos Rápidos (PDCR) em la enseñanza del Soporte Básico de Vida (SBV) a estudiantes del área de la salud. Método una scoping review según JBI Reviewer's Manual for Scoping Reviews y PRISMA-ScR. Se realizaron búsquedas y selecciones en las bases de datos establecidas a través de descriptores y sinónimos, analizando la pertinencia de los estudios, seleccionando aquellos que respondían a la pregunta de investigación, de abril a noviembre de 2021. En diciembre de 2022 se realizó la actualización de la búsqueda y selección de estudios. Resultados de los 4.155 estudios encontrados, 116 fueron analizados en su totalidad, siendo 9 incluidos en este estudio. El 44,4% son estadounidenses y el 66,6% se realizaron en cursos de medicina. El 11,1% presentó escenarios simulados en el contexto intra y extrahospitalario y el 11,1% en escenarios intrahospitalarios. Conclusión e implicaciones para la práctica PD y PDCR en educación para la salud se han consolidado en los últimos años, mostrando mejoras en el aprendizaje y la retención de conocimientos a lo largo del tiempo. Se identificó que la mayoría de los estudios abordan el contexto hospitalario, demostrando la brecha de producción de conocimiento prehospitalario. Además, la mayoría de los estudios se concentraron en Europa y América del Norte, lo que confirma la necesidad de realizar estudios sobre la aplicabilidad de PD y PDCR en SBV en diferentes audiencias y contextos.

Abstract Objective to map evidence on deliberate practice (DP) and rapid cycle deliberate practice (RCDP) in teaching Basic Life Support (BLS) to health occupations students. Method a scoping review according to JBI Reviewer's Manual for Scoping Reviews and PRISMA-ScR. Searches and selections were carried out in the databases through descriptors and synonyms, and it was analyzed the relevance of the studies, selecting those that answered the research question, from April to November 2021. In December 2022, study search and selection were updated. Results of the 4,155 studies found, 116 were analyzed in full, with 9 included in this study. 44.4% are Americans and 66.6% were accomplished in medical courses. 11.1% presented simulated scenarios in the intra- and extra-hospital context, and 11.1%, in intra-hospital scenarios. Conclusion and implications for practice DP and RCDP in health education have been consolidated in recent years, showing improvements in learning and knowledge retention over time. This scope identified that most studies address the hospital context, which demonstrates the knowledge production gap in the pre-hospital area. Furthermore, most of the studies focused on Europe and North America, confirming the need to carry out studies for the applicability of DP and RCDP in BLS in different audiences and contexts.

Terlipressin combined with conservative fluid management attenuates hemorrhagic shock-induced acute kidney injury in rats.

Hemorrhagic shock (HS), a major cause of trauma-related mortality, is mainly treated by crystalloid fluid administration, typically with lactated Ringer's (LR). Despite beneficial hemodynamic effects, such as the restoration of mean arterial pressure (MAP), LR administration has major side effects, including organ damage due to edema. One strategy to avoid such effects is pre-hospitalization intravenous administration of the potent vasoconstrictor terlipressin, which can restore hemodynamic stability/homeostasis and has anti-inflammatory effects. Wistar rats were subjected to HS for 60 min, at a target MAP of 30-40 mmHg, thereafter being allocated to receive LR infusion at 3 times the volume of the blood withdrawn (liberal fluid management); at 2 times the volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight); and at an equal volume (conservative fluid management), plus terlipressin (10 µg/100 g body weight). A control group comprised rats not subjected to HS and receiving no fluid resuscitation or treatment. At 15 min after fluid resuscitation/treatment, the blood previously withdrawn was reinfused. At 24 h after HS, MAP was higher among the terlipressin-treated animals. Terlipressin also improved post-HS survival and provided significant improvements in glomerular/tubular function (creatinine clearance), neutrophil gelatinase-associated lipocalin expression, fractional excretion of sodium, aquaporin 2 expression, tubular injury, macrophage infiltration, interleukin 6 levels, interleukin 18 levels, and nuclear factor kappa B expression. In terlipressin-treated animals, there was also significantly higher angiotensin II type 1 receptor expression and normalization of arginine vasopressin 1a receptor expression. Terlipressin associated with conservative fluid management could be a viable therapy for HS-induced acute kidney injury, likely attenuating such injury by modulating the inflammatory response via the arginine vasopressin 1a receptor.

Evaluation of Blood Soluble CD26 as a Complementary Biomarker for Colorectal Cancer Screening Programs.

Fecal hemoglobin immunodetection (FIT) in combination with endoscopy has been implemented to reduce mortality from colorectal cancer (CRC), although there are issues that can be improved in relation to participation rates. We studied whether the blood biomarker soluble-CD26 (sCD26), related at least in part to the immune system and inflammation, and/or its dipeptidyl peptidase enzyme activity (DPP4), could help reduce false positives. In a cohort of 1703 individuals who underwent colonoscopy and had a serum sample, sCD26 and DPP4 activity showed statistically significant differences regarding sex and age. According to the colonoscopy findings, sCD26 and DPP4 activity progressively decreased in advanced adenomas and CRC, with statistically significant differences, even between both groups; 918 of them had a FIT result (n = 596 positive cases) with approximately 70% of these (n = 412) false positives. With cut-offs of 440 ng/mL for sCD26, 42 mU/mL for DPP4, and 11 ng/mU for their ratio, the combined information of the three biomarkers (at least positive for one biomarker) identified almost all advanced adenomas and CRC cases in the FIT cohort with approximately half of the false positives compared to FIT. A sequential testing strategy with FIT and our blood biomarker test is proposed.

Bullying According to Gender, and Immigration Background in Spanish Students.

BACKGROUND: Boys are more frequent aggressors than girls, but there are no conclusive findings on gender differences in victimization. There is a relationship between immigration background and bullying, but differences between generations are still debated. Therefore, the objectives of this study were: 1) to analyze victimization according to gender and immigration background (first and second generation); 2) to compare the attitudes of students against bullying based on these variables. METHOD: A multivariate analysis of covariance (MANCOVA) was carried out, considering gender and immigration background as independent variables, and types of offline bullying (physical, verbal and relational) as dependent variables. The sample was made up of 6,335 Spanish students (50.1% girls; 49.9% boys; average age: 15.83, DT: 0.29). RESULTS: Statistically significant differences were detected in types of bullying (considered together) and in attitudes against bullying according to gender and immigration background (p <.001). CONCLUSIONS: Being a first-generation immigrant stands out as the main risk factor. Findings are discussed as to the need to address cultural victimization in schools.

Role of Glycine and Glycine Receptors in Vascular Endothelium: A New Perspective for the Management of the Post-Ischemic Injury.

Glycine Receptors (GlyRs) are cell-surface transmembrane proteins that belong to the Cysloop ligand-gated ion channels superfamily (Cys-loop LGICs). Functional glycine receptors are conformed only by α-subunits (homomeric channels) or by α- and ß-subunits (heteromeric channels). The role of glycine as a cytoprotective is widely studied. New information about glycine modulation of vascular endothelial cells (ECs) function emerged last year. Glycine and its receptors are recognized to play a role as neurovascular protectors by a mechanism that involves α2GlyRs. Interestingly, the expression of α2GlyRs reduces after stroke injury. However, glycine reverses the inhibition of α2GlyRs by a mechanism involving the VEGF/pSTAT3 signaling. On the other hand, consistent evidence has demonstrated that ECs participate actively in the innate and adaptive immunological response. We recently reported that GlyRs are modulated by interleukin-1ß, suggesting new perspectives to explain the immune modulation of vascular function in pathological conditions such as cerebrovascular stroke. In this work, we distinguish the role of glycine and the allosteric modulation of glycine receptors as a new therapeutic target to confront post-ischemic injury.

Tratamiento multidisciplinario de condrosarcoma gigante de fémur proximal mediante hemipelvectomía externa y reconstrucción con colgajo pediculado tipo fillet flap: presentación de un caso clínico / Multidisciplinary treatment of giant chondrosarcoma of the proximal femur by external hemipelvectomy and reconstruction with a pedunculated fillet flap: presentation of a clinical case / Tratamento multidisciplinar do condrossarcoma gigante do fêmur proximal por hemipelvectomia externa e reconstrução com retalho fillet flap: apresentação de um caso clínico

El condrosarcoma forma parte de los tumores primarios malignos más frecuentes. Las localizaciones pélvicas y de raíz de muslo requerirán abordajes amplios con la consecuente dificultad de cobertura de partes blandas. La hemipelvectomía externa es habitualmente el procedimiento de elección para estas localizaciones. Implica la resección de la extremidad inferior en bloque asociada a la hemipelvis ipsilateral, dando como resultado un gran defecto de cobertura. En algunas circunstancias, la extensa resección de partes blandas hace imposible la utilización de colgajos rotacionales locales. La reconstrucción con colgajo tipo "Fillet flaps" ofrece a estos defectos de partes blandas la opción de lograr una adecuada cobertura. El objetivo del trabajo es mostrar la resolución de un caso poco convencional de condrosarcoma de fémur proximal y su reconstrucción de partes blandas con un método nunca antes utilizado en nuestro medio.

Chondrosarcoma is one of the most frequent malignant primary tumors. Pelvic and proximal femur locations require extensive approaches with the consequent difficulty of soft tissue reconstruction. External hemipelvectomy is usually the procedure for these locations. It involves total en bloc resection of the lower extremity associated with ipsilateral hemipelvis, resulting in a large coverage defect. In some cases, local rotational flaps are impossible. Reconstruction with fillet flaps offers an adequate coverage for soft tissue defects. The objective of this study is to show the resolution of an unconventional case of chondrosarcoma of the proximal femur and its soft tissue reconstruction with a method never before used in our country.

O condrossarcoma é um dos tumores primários malignos mais frequentes. As localizações das raízes pélvicas e da coxa exigirão amplas abordagens com a conseqüente dificuldade em cobrir os tecidos moles. A hemipelvectomia externa costuma ser o procedimento de escolha para esses locais. Envolve a ressecção do membro inferior em bloco associado à hemipelve ipsilateral, resultando em um grande defeito de cobertura. Em algumas circunstâncias, a ressecção extensa de partes moles impossibilita o uso de retalhos rotacionais locais. A reconstrução com retalhos de filé oferece a esses defeitos de tecidos moles a opção de obter uma cobertura adequada. O objetivo deste trabalho é mostrar a resolução de um caso não convencional de condrossarcoma do fêmur proximal e sua reconstrução de partes moles com método nunca antes utilizado em nosso meio.

Bullying According to Gender, and Immigration Background in Spanish Students / Acoso Escolar Según el Género y los Antecedentes de Inmigración en Estudiantes Españoles

Background: Boys are more frequent aggressors than girls, but there are no conclusive findings on gender differences in victimization. There is a relationship between immigration background and bullying, but differences between generations are still debated. Therefore, the objectives of this study were: 1) to analyze victimization according to gender and immigration background (first and second generation); 2) to compare the attitudes of students against bullying based on these variables. Method: a multivariate analysis of covariance (MANCOVA) was carried out, considering gender and immigration background as independent variables, and types of offline bullying (physical, verbal and relational) as dependent variables. The sample was made up of 6,335 Spanish students (50.1% girls; 49.9% boys; average age: 15.83, DT: 0.29). Results: Statistically significant differences were detected in types of bullying (considered together) and in attitudes against bullying according to gender and immigration background (p <.001). Conclusions: being a first-generation immigrant stands out as the main risk factor. Findings are discussed as to the need to address cultural victimization in schools.(AU)

Antecedentes: Los chicos son agresores más frecuentemente que ellas, pero no hay hallazgos concluyentes sobre diferencias de género en la victimización. Existe relación entre antecedentes de inmigración y acoso escolar, pero todavía se discuten las diferencias entre generaciones. Por ello, los objetivos de este estudio fueron: 1) analizar el acoso escolar en función del género y los antecedentes de inmigración (primera y segunda generación); 2) comparar las actitudes de los estudiantes contra el acoso escolar en función de dichas variables. Método: se llevó a cabo un análisis multivariado de covarianza (MANCOVA). Las variables independientes fueron el género y los antecedentes de inmigración. Las variables dependientes fueron los tipos de acoso escolar presencial (físico, verbal y relacional). La muestra fue constituida por 6335 estudiantes españoles (50.1% mujeres; 49.9% hombres; media de edad: 15.83, DT: 0.29). Resultados: se detectaron diferencias estadísticamente significativas en los tipos de acoso escolar considerados conjuntamente y en las actitudes contra el acoso en función del género y de los antecedentes de inmigración (p < .001). Conclusiones: el principal factor de riesgo encontrado fue ser inmigrante de primera generación. Los hallazgos se discuten en cuanto a la necesidad de abordar la victimización cultural en las escuelas.(AU)

Paternal effect does not affect in vitro embryo morphokinetics but modulates molecular profile.

The use of different sires influences in vitro embryo production (IVP) outcome. Paternal effects are observed from the first cleavages until after embryonic genome activation (EGA). Little is known about the mechanisms that promote in vitro fertility differences, even less about the consequences on embryo development. Therefore, this study aimed to evaluate the paternal effect at fertilization, embryo developmental kinetics, gene expression and quality from high and low in vitro fertility bulls. A retrospective analysis for bull selection was performed using the In vitro Brazil company database from 2012 to 2015. The dataset was edited employing cleavage and blastocyst rates ranking a total of 140 bulls. Subsequently, the dataset was restricted by embryo development rate (blastocyst/cleaved rate) and ten bulls were selected as high (HF; n = 5) and low (LF; n = 5) in vitro fertility groups. IVP embryos derived from high and low fertility bulls were classified according to their stage of development (2 cells, 3-4 cells, 6 cells, 8-16 cells), at 24, 36, 48, 60, 72 hpi, respectively, to evaluate embryo kinetics. Pronuclei formation (24 hpi), cleavage rate (Day 3), development rate, and blastocyst morphology (Grade I and II - Day 7) were also assessed, as well as the abundance of 96 transcripts at 8-16 cell stage and blastocysts. There was no difference in early embryo kinetics (P > 0.05), and cleavage rate (HF = 86.7%; LF = 84.9%; P = 0.25). Nevertheless, the fertilization rate was higher on HF (72%) than LF (62%) and the polyspermy rate was lower on HF compared to LF (HF:16.2% LF:29.2%). As expected, blastocyst rate (HF = 29.4%; LF = 16.0%; P < 0.0001) and development rate (HF = 33.9% LF = 18.9%; P < 0.0001) were higher in HF than LF. At the 8-16 cell stage, 22 transcripts were differentially represented (P ≤ 0.05) between the two groups. Only PGK1 and TFAM levels were higher in HF while transcripts related to stress (6/22, ∼27%), cell proliferation (6/22, ∼27%), lipid metabolism genes (5/22, ∼23%), and other cellular functions (5/22, ∼23%) were higher on LF embryos. Blastocysts had 9 differentially represented transcripts (P ≤ 0.05); being only ACSL3 and ELOV1 higher in the HF group. Lipid metabolism genes (3/9, 33%) and other cellular functions (6/9, 67%) were higher in the LF group. In conclusion, the timing of the first cleavages is not affected by in vitro bull fertility. However, low in vitro fertility bulls presented higher polyspermy rates and produced 8-16 cells embryos with higher levels of transcripts related to apoptosis and cell damage pathways compared to high in vitro fertility ones. Evidence such as polyspermy and increase in apoptotic and oxidative stress genes at the EGA stage suggest that embryo development is impaired in the LF group leading to the reduction of blastocyst rate.

Mixed Models in Nonlinear Regression for Description of the Growth of Nelore Cattle.

Body weight records were used to characterize the growth curve of Nelore cattle. Body weight was regressed as a function of age, for both sexes, by using nonlinear models through the functions of Brody, Gompertz, Logistic, Richards, Meloun 1, Von Bertalanffy, and Von Bertalanffy. The quality of the model arrangements was evaluated by employing Akaike and Bayesian Schwarz information criteria. The Brody function provided the best adaptations by the evaluators and, considering the asymptotic weight and the maturation rate as random, a reduction in residual variance of 79% for males and 83% for females was obtained in relation to the models under fixed contexts. In males, the absolute and relative growth rates ranged from 0.921 to 0.261 kg/day and 2.39 to 0.08%, respectively. For the same rates, under another approach, females ranged from 0.922 to 0.198 kg/day and 2.55 to 0.06%, respectively. Males showed greater growth acceleration at the beginning of the growth trajectory, being equal to females at 397 days of age and from that age onward they presented lower estimates. The nonlinear regression model approach under the mixed-models context allows reduction of residual variance, increasing model accuracy.

Acute kidney injury in a mouse model of meningococcal disease.

INTRODUCTION: Meningococcal disease is associated with high mortality. When acute kidney injury (AKI) occurs in patients with severe meningococcal disease, it is typically attributable to sepsis, although meningococcal disease and lipopolysaccharide release are rarely investigated. Therefore, we evaluated renal tissue in a mouse model of meningococcal disease. METHODS: Female BALB/c mice were induced to AKI by meningococcal challenge. Markers of renal function were evaluated in infected and control mice. RESULTS: In the infected mice, serum concentrations of tumor necrosis factor alpha, interferon gamma, interleukins (IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, and IL-12), and granulocyte-macrophage colony-stimulating factor were elevated, as was renal interstitial infiltration with lymphocytes and neutrophils (p < 0.01 for the latter). Histological analysis showed meningococcal microcolonies in the renal interstitium, without acute tubular necrosis. Infected mice also showed elevated renal expression of toll-like receptor 2, toll-like receptor 4, and Tamm-Horsfall protein. The expression of factors in the intrinsic pathway of apoptosis was equal to or lower than that observed in the control mice. Urinary sodium and potassium were also lower in infected mice, probably due to a tubular defect. CONCLUSION: Our findings corroborate those of other studies of AKI in sepsis. To our knowledge, this is the first time that meningococci have been identified in renal interstitium and that the resulting apoptosis and inflammation have been evaluated. However, additional studies are needed in order to elucidate the mechanisms involved.