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ß3-Adrenergic receptor (ß3AR) agonists have been shown to protect against ischemia-reperfusion injury (IRI). Since ß3ARs are present both in cardiomyocytes and in endothelial cells, the cellular compartment responsible for this protection has remained unknown. Using transgenic mice constitutively expressing the human ß3AR (hß3AR) in cardiomyocytes or in the endothelium on a genetic background of null endogenous ß3AR expression, we show that only cardiomyocyte expression protects against IRI (45 min ischemia followed by reperfusion over 24 h). Infarct size was also limited after ischemia-reperfusion in mice with cardiomyocyte hß3AR overexpression on top of endogenous ß3AR expression. hß3AR overexpression in these mice reduced IRI-induced cardiac fibrosis and improved long-term left ventricular systolic function. Cardiomyocyte-specific ß3AR overexpression resulted in a baseline remodeling of the mitochondrial network, characterized by upregulated mitochondrial biogenesis and a downregulation of mitochondrial quality control (mitophagy), resulting in elevated numbers of small mitochondria with a depressed capacity for the generation of reactive oxygen species but improved capacity for ATP generation. These processes precondition cardiomyocyte mitochondria to be more resistant to IRI. Upon reperfusion, hearts with hß3AR overexpression display a restoration in the mitochondrial quality control and a rapid activation of antioxidant responses. Strong protection against IRI was also observed in mice infected with an adeno-associated virus (AAV) encoding hß3AR under a cardiomyocyte-specific promoter. These results confirm the translational potential of increased cardiomyocyte ß3AR expression, achieved either naturally through exercise or artificially through gene therapy approaches, to precondition the cardiomyocyte mitochondrial network to withstand future insults.
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AIMS: This work aims to evaluate the efficacy of nutritional supplementation with a glutamine-enriched oligomeric diet (GEOD) compared to a standard polymeric diet (SPD) in terms of oncology treatment-related diarrhea (OTRD) (frequency and consistency of stools), gastrointestinal toxicity, and functional and nutritional progress. METHODS: This prospective cohort study compared two groups of patients with rectal cancer in treatment with neoadjuvant chemotherapy and radiotherapy who were at risk of malnutrition. Patients were randomized to receive either 400 ml of GEOD or of SPD from the start of radiotherapy to 30 days after its completion. RESULTS: Eighty patients were recruited, 40 per arm. The GEOD arm had improved stool consistency and a greater reduction in the number of stools compared to the SPD arm (p < 0.001). The relative risk (RR) of developing diarrhea in the GEOD arm was 0.059 (95% CI 0.015-0.229). There was a reduced risk of developing intestinal mucositis in the GEOD arm compared to the SPD arm [RR 0.202 (95% CI 0.102 - 0.399)]. The GEOD arm had greater improvements in functional and nutritional status (p < 0.001). CONCLUSIONS: GEOD had a protective effect in terms of the development of gastrointestinal toxicity associated with chemotherapy and radiotherapy treatment in patients with rectal cancer.
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Glutamina , Neoplasias Retais , Humanos , Estudos Prospectivos , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Dieta , Diarreia/etiologiaRESUMO
PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.
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Braquiterapia , Neoplasias da Próstata , Masculino , Humanos , Próstata/patologia , Estudos Prospectivos , Braquiterapia/métodos , Dosagem Radioterapêutica , Recidiva Local de Neoplasia/radioterapiaRESUMO
OBJECTIVES: We aimed to investigate the rate of non-adherence to antimalarials and glucocorticoids (GCs) and to analyze their potential relationships with sociodemographic characteristics, disease activity and accumulate damage in a cohort of Systemic lupus erythematosus (SLE) patients. METHODS: A cross-sectional study was conducted among 670 patients. The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) and the Lupus Damage Index Questionnaire (LDIQ) were used to assess disease activity and accumulated damage. RESULTS: The prevalence of non-adherence to antimalarials and GCs were 10.67% and 39.61%. 86.9% of participants indicated that the reason for stopping therapy was the presence of side effects. SLE patients with non-adherence to antimalarials and GCs had significantly higher scores in disease severity (SLAQ) compared to adherence patients (5.03 (2.12) vs 4.39 (2.61); p = .004 and (4.75 (2.29) vs 4.05 (2.78); p ≤ .001). CONCLUSION: Adherence to the treatment indicated in SLE differs from drug to drug. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.
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Antimaláricos , Lúpus Eritematoso Sistêmico , Humanos , Lúpus Eritematoso Sistêmico/complicações , Glucocorticoides/uso terapêutico , Antimaláricos/uso terapêutico , Autorrelato , Estudos Transversais , Índice de Gravidade de DoençaRESUMO
Aortic stenosis (AS) is associated with left ventricular (LV) hypertrophy and heart failure (HF). There is a lack of therapies able to prevent/revert AS-induced HF. Beta3 adrenergic receptor (ß3AR) signaling is beneficial in several forms of HF. Here, we studied the potential beneficial effect of ß3AR overexpression on AS-induced HF. Selective ß3AR stimulation had a positive inotropic effect. Transgenic mice constitutively overexpressing human ß3AR in the heart (c-hß3tg) were protected from the development of HF in response to induced AS, and against cardiomyocyte mitochondrial dysfunction (fragmented mitochondria with remodeled cristae and metabolic reprogramming featuring altered substrate use). Similar beneficial effects were observed in wild-type mice inoculated with adeno-associated virus (AAV9) inducing cardiac-specific overexpression of human ß3AR before AS induction. Moreover, AAV9-hß3AR injection into wild-type mice at late disease stages, when cardiac hypertrophy and metabolic reprogramming are already advanced, reversed the HF phenotype and restored balanced mitochondrial dynamics, demonstrating the potential of gene-therapy-mediated ß3AR overexpression in AS. Mice with cardiac specific ablation of Yme1l (cYKO), characterized by fragmented mitochondria, showed an increased mortality upon AS challenge. AAV9-hß3AR injection in these mice before AS induction reverted the fragmented mitochondria phenotype and rescued them from death. In conclusion, our results step out that ß3AR overexpression might have translational potential as a therapeutic strategy in AS-induced HF.
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Estenose da Valva Aórtica , Insuficiência Cardíaca , Humanos , Camundongos , Animais , Receptores Adrenérgicos beta 3 , Dinâmica Mitocondrial , Hipertrofia Ventricular Esquerda , Miócitos Cardíacos , Camundongos Transgênicos , MetaloendopeptidasesRESUMO
AIMS: Clinical guidelines recommend early intravenous ß-blockers during ongoing myocardial infarction; however, it is unknown whether all ß-blockers exert a similar cardioprotective effect. We experimentally compared three clinically approved intravenous ß-blockers. METHODS AND RESULTS: Mice undergoing 45 min/24 h ischaemia-reperfusion (I/R) received vehicle, metoprolol, atenolol, or propranolol at min 35. The effect on neutrophil infiltration was tested in three models of exacerbated inflammation. Neutrophil migration was evaluated in vitro and in vivo by intravital microscopy. The effect of ß-blockers on the conformation of the ß1 adrenergic receptor was studied in silico. Of the tested ß-blockers, only metoprolol ameliorated I/R injury [infarct size (IS) = 18.0% ± 0.03% for metoprolol vs. 35.9% ± 0.03% for vehicle; P < 0.01]. Atenolol and propranolol had no effect on IS. In the three exacerbated inflammation models, neutrophil infiltration was significantly attenuated only in the presence of metoprolol (60%, 50%, and 70% reductions vs. vehicle in myocardial I/R injury, thioglycolate-induced peritonitis, and lipopolysaccharide-induced acute lung injury, respectively). Migration studies confirmed the particular ability of metoprolol to disrupt neutrophil dynamics. In silico analysis indicated different intracellular ß1 adrenergic receptor conformational changes when bound to metoprolol than to the other two ß-blockers. CONCLUSIONS: Metoprolol exerts a disruptive action on neutrophil dynamics during exacerbated inflammation, resulting in an infarct-limiting effect not observed with atenolol or propranolol. The differential effect of ß-blockers may be related to distinct conformational changes in the ß1 adrenergic receptor upon metoprolol binding. If these data are confirmed in a clinical trial, metoprolol should become the intravenous ß-blocker of choice for patients with ongoing infarction.
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Metoprolol , Infarto do Miocárdio , Antagonistas Adrenérgicos beta/farmacologia , Animais , Atenolol/farmacologia , Humanos , Inflamação , Metoprolol/farmacologia , CamundongosRESUMO
The aquaculture industry's rapid growth to meet commercial demand can trigger an outbreak of infectious diseases due to high-density farming. Antibiotic overuse and misuse in fish farming and its global health consequences have led to searching for more natural alternatives such as medicinal plants. In this sense, garlic (Allium sativum) has different bioactive compounds with biological properties for animal health. Among them are the ajoene, alliin, and allicin, which confer biological properties such as growth promotion, antimicrobial, antiviral, antioxidant, and antiparasitic. Ways to use garlic in aquaculture include oil, fresh mash, aqueous extract, and garlic powder. The powder presentation is the most used in aquaculture; it is generally applied by oral administration, adding to the feed, and the dose used ranges from 0.05 to 40 g/kg of feed. Garlic has been used in the aquaculture of different species such as rainbow trout (Oncorhynchus mykiss), spotted grouper (Epinephelus coioides), catfish (Clarias gariepinus), tilapia (Oreochromis niloticus), guppy fish (Poecilia reticulata), goldfish (Carassius auratus), and barramundi (Lates calcarifer). In addition to its properties, garlic's usage became popular, thanks to its low cost, easy incorporation into food, and little environmental impact. Therefore, its application can be an effective solution to combat diseases, improve organisms' health using natural supplies, and as an alternative to antibiotics. This review reports and discusses plant-derived products' beneficial properties, emphasizing garlic and its usages in fish aquaculture.
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Aquicultura , Alho , Adjuvantes Imunológicos/farmacologia , Animais , Anti-Infecciosos/farmacologia , Antioxidantes/farmacologia , Peixes/crescimento & desenvolvimento , Peixes/imunologia , Peixes/metabolismo , Peixes/microbiologiaRESUMO
Nonrevascularizable coronary artery disease is a frequent cause of hibernating myocardium leading to heart failure (HF). Currently, there is a paucity of therapeutic options for patients with this condition. There is a lack of animal models resembling clinical features of hibernating myocardium. Here we present a large animal model of hibernating myocardium characterized by serial multimodality imaging. Yucatan minipigs underwent a surgical casein ameroid implant around the proximal left anterior descending coronary artery (LAD), resulting in a progressive obstruction of the vessel. Pigs underwent serial multimodality imaging including invasive coronary angiography, cardiac magnetic resonance (CMR), and hybrid 18F-Fluorodeoxyglucose positron emission tomography-computed tomography (FDG-PET/CT). A total of 43 pigs were operated on and were followed for 120 ± 37 days with monthly multimodality imaging. 24 pigs (56%) died during the follow-up. Severe LAD luminal stenosis was documented in all survivors. In the group of 19 long-term survivors, 17 (90%) developed left ventricular systolic dysfunction [median LVEF of 35% (IQR 32.5-40.5%)]. In 17/17, at-risk territory was viable on CMR and 14 showed an increased glucose uptake in the at-risk myocardium on 18FDG-PET/CT. The present pig model resembles most of the human hibernated myocardium characteristics and associated heart failure (systolic dysfunction, viable myocardium, and metabolic switch to glucose). This human-like model might be used to test novel interventions for nonrevascularizable coronary artery disease and ischemia heart failure as a previous stage to clinical trials.
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Modelos Animais de Doenças , Miocárdio Atordoado/patologia , Animais , Angiografia Coronária/métodos , Insuficiência Cardíaca/patologia , Imagem Multimodal/métodos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Suínos , Porco Miniatura , Pesquisa Translacional BiomédicaRESUMO
Whipple's disease is a rare bacterial, chronic and multisystemic disease, produced by the gram-positive bacillus Tropheryma whipplei. The clinical manifestations are varied and diagnosis is often delayed. The four cardinal symptoms are arthralgias, weight loss, diarrhea and abdominal pain. The classic symptoms could be preceded up to three quarters by different joint manifestations that evolve intermittently. The average time to diagnosis is 6 years. We present the case of a young patient with recurrent febrile episodes and associated joint disease, in whom the absence of digestive symptoms led to a diagnostic laparoscopy since this entity was not suspected before.
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Endoscopia por Cápsula , Doença de Whipple , Antibacterianos , Diarreia , Humanos , TropherymaRESUMO
A complex network of chemokines can influence cancer progression with the recruitment and activation of hematopoietic cells, including macrophages to the supporting tumor stroma promoting carcinogenesis and metastasis. The aim of this study was to investigate the relation between tissue and plasma chemokine levels involved in macrophage recruitment with tumor-associated macrophage profile markers and clinicopathological features such as tumor-node-metastases stage, desmoplasia, tumor necrosis factor-α, and vascular endothelial growth factor plasma content. Plasma and tumor/healthy mucosa were obtained from Chilean patients undergoing colon cancer surgery. Chemokines were evaluated from tissue lysates (CCL2, CCL3, CCL4, CCL5, and CX3CL1) by Luminex. Statistical analysis was performed using Wilcoxon match-paired test ( p < 0.05). Macrophage markers (CD68, CD163, and iNOS) were evaluated by immunohistochemistry samples derived from colorectal cancer patients. Correlation analysis between chemokines and macrophage markers and clinicopathological features were performed using Spearman's test. Plasmatic levels of chemokines and inflammatory mediators' vascular endothelial growth factor and tumor necrosis factor-α were evaluated by Luminex. Tumor levels of CCL2 (mean ± standard deviation = 530.1 ± 613.9 pg/mg), CCL3 (102.7 ± 106.0 pg/mg), and CCL4 (64.98 ± 48.09 pg/mg) were higher than those found in healthy tissue (182.1 ± 116.5, 26.79 ± 22.40, and 27.06 ± 23.69 pg/mg, respectively p < 0.05). The tumor characterization allowed us to identify a positive correlation between CCL4 and the pro-tumor macrophages marker CD163 ( p = 0.0443), and a negative correlation of iNOS with desmoplastic reaction ( p = 0.0467). Moreover, we identified that tumors with immature desmoplasia have a higher CD163 density compared to those with a mature/intermediated stromal tissue ( p = 0.0288). Plasmatic CCL4 has shown a positive correlation with inflammatory mediators (tumor necrosis factor-α and vascular endothelial growth factor) that have previously been associated with poor prognosis in patients. In conclusion High expression of CCL4 in colon cancer could induce the infiltration of tumor-associated macrophages and specifically a pro-tumor macrophage profile (CD163+ cells). Moreover, plasmatic chemokines could be considered inflammatory mediators associated to CRC progression as well as tumor necrosis factor-α and vascular endothelial growth factor. These data reinforce the idea of chemokines as potential therapeutic targets or biomarker in CRC.
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Biomarcadores Tumorais/metabolismo , Quimiocina CCL2/metabolismo , Quimiocina CCL3/metabolismo , Quimiocina CCL4/metabolismo , Neoplasias Colorretais/patologia , Macrófagos/patologia , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Neoplasias Colorretais/metabolismo , Feminino , Seguimentos , Humanos , Macrófagos/metabolismo , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND: Different strains of invasive Escherichia coli (E. coli), isolated from intestinal mucosa of patients, are related to the pathogenesis of inflammatory bowel diseases (IBD). AIM: To evaluate an association between intracellular E. coli and IBD; its clinical characteristics and use of steroids. MATERIAL AND METHODS: Sixty one patients with Crohn's disease and 83 with ulcerative colitis were studied. To determine the intracellular E. coli content, colonoscopy biopsies of these patients and 29 control subjects were processed using the gentamicin protection assay. Differences in the bacterial content between patient groups were evaluated using Mann-Whitney test, while the association between presence of E. coli with endoscopic activity, location/extension and use of corticosteroid as anti-inflammatory treatment were evaluated with Fisher's exact test or Chi-square test. RESULTS: E. coli strains were detected in 36.1, 39.3 and 10.3% of patients with ulcerative colitis, Crohn's disease and controls, respectively. The number of bacteria per biopsy in Crohn's disease and ulcerative colitis was significantly higher than in controls (p < 0.01 between patients and controls). In ulcerative colitis, significant associations were found between the presence of bacteria and disease location and use of corticosteroids. In Crohn's disease, no association was found. CONCLUSIONS: IBD are associated with the presence of intracellular E. coli strains in the intestinal mucosa, suggesting an alteration in the microbiota or loss of integrity of the epithelial barrier. The association of intracellular E. coli with clinical features and the use of corticosteroids in ulcerative colitis suggests that different factors could promote colonization or proliferation of these bacteria.
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Colite Ulcerativa/microbiologia , Doença de Crohn/microbiologia , Escherichia coli/isolamento & purificação , Mucosa Intestinal/microbiologia , Adolescente , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Estudos de Casos e Controles , Colite Ulcerativa/tratamento farmacológico , Contagem de Colônia Microbiana , Doença de Crohn/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Valores de Referência , Estatísticas não Paramétricas , Adulto JovemRESUMO
OBJECTIVE: Recurrent tracheoesophageal fistula (RTEF) is a serious complication after primary repair of esophageal atresia and tracheoesophageal fistula (EA/TEF). Treatment of RTEF involved an open surgery by thoracotomy. Technically it is a challenge with a high morbidity and mortality. Congenital tracheoesophageal fistula (CTEF) traditionally involved an open surgery by thoracotomy or cervicotomy. Many endoscopic techniques have been developed since the past decades: thoracoscopic or bronchoscopic approach for the treatment of RTEF and CTEF; nevertheless, optimal treatment is not still determined because of few numbers of patients, short-term follow-up, and different procedures. We report our experience and evaluated the efficacy in the chemocauterization of CTEF and RTEF, with the use of 50% trichloroacetic acid (TCA) as a technique minimally invasive. MATERIALS AND METHODS: From 2010 to 2014, fourteen patients with TEF (twelve RTEF and two CTEF) were selected for endoscopic management in two centers. Twelve patients had RTEF after primary repair of EA/TEF by thoracotomy approach, and two patients had CTEF in the upper pouch, diagnosed after EA/TEF (Type B) long gap, treated by thoracotomy and thoracoscopy, respectively. In all cases the diagnosis was confirmed by esophagram, bronchoscopy, and clinical evaluation. Under general anesthesia, a rigid pediatric bronchoscope with a 0° rod lens telescope and tele-monitoring was used to localize the TEF. Cotton soaked with 50% TCA was applied on the TEF during 30 s, and the procedure was repeated 3 times. The endoscopic treatment was performed monthly until TEF closure was achieved. RESULTS: RTEF and CTEF were closed in all patients. The mean number of procedure in each patient was 1.8. Closure of TEF was confirmed by esophagram, bronchoscopy, and clinical evaluation. There were a bacterial pneumonia and bronchospasm as postoperative complications. Median follow-up was 41 months (8-72). All of these TEF remain completely obliterated, and all patients are asymptomatic. CONCLUSION: Endoscopic management of congenital and recurrent TEF with the use of 50% TCA is as a minimally invasive, effective, simple and safe technique in these patients and avoids the morbidity of open surgery.
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Cauterização/métodos , Atresia Esofágica/cirurgia , Fístula Traqueoesofágica/cirurgia , Ácido Tricloroacético/uso terapêutico , Adolescente , Broncoscopia/métodos , Cauterização/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/cirurgia , Estudos Retrospectivos , Toracoscopia/métodos , Toracotomia , Resultado do Tratamento , Ácido Tricloroacético/efeitos adversosRESUMO
The aim of this study was to estimate the prevalence of metabolic syndrome (MetS) in a Spanish rural population and assess differences in prevalence according to loneliness level, social isolation, and social support. This is a cross-sectional study of 310 patients. MetS was defined by National Cholesterol Education Program-Third Adult Treatment Panel. The UCLA (University of California, Los Angeles) Loneliness Scale, Multidimensional Scale of Social Support, and Lubben Social Network Scale were used to assess loneliness, perceived social support, and social isolation. Almost half of the participants fulfilled MetS diagnosis criteria. Subjects with MetS showed significantly higher levels of loneliness, less social support, and greater social isolation. Systolic blood pressure was significantly higher in socially isolated rural adults. Environmental factors may play a key role in the prevalence of MetS, so specific screening and prevention programs could help health professionals prevent the increasing rates of MetS in rural populations under these socially specific conditions of vulnerability.
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Síndrome Metabólica , População Rural , Adulto , Humanos , Fatores de Risco , Estudos Transversais , Síndrome Metabólica/epidemiologia , SolidãoRESUMO
BACKGROUND AND AIMS: Metabolic syndrome (MetS) is a chronic proinflammatory and prothrombotic condition that exacerbates insulin resistance, oxidative damage, and cardiovascular risk, being more prevalent in patients with systemic lupus erythematosus (SLE), a chronic multisystemic autoimmune disorder. This study aim was to determine the prevalence of MetS and associations with SLE clinical characteristics, cardiovascular risk and dietary pattern in a population of Spanish SLE patients. DESIGN AND METHODS: Cross-sectional study of 293 patients was conducted (90.4% females; mean age 46.8 (12.94)). The diagnosis of MetS was established based on the criteria of the National Cholesterol Education Program Adult Treatment Panel III. SLE Disease Activity Index (SLEDAI-2K) and SDI Damage Index were used to assess disease activity and disease-related damage, respectively. Med Diet adherence was assessed through a 14 items questionnaire on food consumption frequency and habits. RESULTS: MetS was present in 15% SLE patients. Triglycerides, high-density lipoprotein cholesterol, systolic blood pressure and waist circumference were significantly increased (p<0.001) in the group of MetS patients. Patients with MetS showed significantly increased SDI damage index (1.70 (1.69) vs 0.88 (1.12), p<0.001) and complement C3 level (118.70 (32.67) vs 107.55 (26.82), p=0.011). No significant differences were observed according to Med Diet adherence level. CONCLUSION: We observed a lower prevalence of MetS in SLE than that reported in previous studies, which may be a result of the good level of adherence to the MedDiet in our study sample. Additionally, MetS was associated with higher SDI and complement C3 levels but no with medication use.
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Dieta Mediterrânea , Lúpus Eritematoso Sistêmico , Síndrome Metabólica , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Masculino , Síndrome Metabólica/etiologia , Síndrome Metabólica/complicações , Complemento C3/uso terapêutico , Estudos Transversais , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/tratamento farmacológico , ColesterolRESUMO
Background: Anthracycline-induced cardiotoxicity (AIC) debilitates quality of life in cancer survivors. Serial characterizations are lacking of the molecular processes occurring with AIC. Objectives: The aim of this study was to characterize AIC progression in a mouse model from early (subclinical) to advanced heart failure stages, with an emphasis on cardiac metabolism and mitochondrial structure and function. Methods: CD1 mice received 5 weekly intraperitoneal doxorubicin injections (5 mg/kg) and were followed by serial echocardiography for 15 weeks. At 1, 9, and 15 weeks after the doxorubicin injections, mice underwent fluorodeoxyglucose positron emission tomography, and hearts were extracted for microscopy and molecular analysis. Results: Cardiac atrophy was evident at 1 week post-doxorubicin (left ventricular [LV] mass 117 ± 26 mg vs 97 ± 25 mg at baseline and 1 week, respectively; P < 0.001). Cardiac mass nadir was observed at week 3 post-doxorubicin (79 ± 16 mg; P = 0.002 vs baseline), remaining unchanged thereafter. Histology confirmed significantly reduced cardiomyocyte area (167 ± 19 µm2 in doxorubicin-treated mice vs 211 ± 26 µm2 in controls; P = 0.004). LV ejection fraction declined from week 6 post-doxorubicin (49% ± 9% vs 61% ± 9% at baseline; P < 0.001) until the end of follow-up at 15 weeks (43% ± 8%; P < 0.001 vs baseline). At 1 week post-doxorubicin, when LV ejection fraction remained normal, reduced cardiac metabolism was evident from down-regulated markers of fatty acid oxidation and glycolysis. Metabolic impairment continued to the end of follow-up in parallel with reduced mitochondrial adenosine triphosphate production. A transient early up-regulation of nutrient-sensing and mitophagy markers were observed, which was associated with mitochondrial enlargement. Later stages, when mitophagy was exhausted, were characterized by overt mitochondrial fragmentation. Conclusions: Cardiac atrophy, global hypometabolism, early transient-enhanced mitophagy, biogenesis, and nutrient sensing constitute candidate targets for AIC prevention.
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We aimed to investigate the impact of COVID-19 infection on maternal characteristics and obstetric and neonatal outcomes in a cohort of women in labor previously vaccinated who tested positive for SARS-CoV-2 infection, compared to aged-matched healthy controls. A retrospective case-control study was conducted among 66 women in labor. Clinical data were obtained from medical records. The attendance rates at childbirth and parenting classes, as well as the implementation of a birth plan, were significantly lower in the COVID-19 infection group (6.1% vs. 48.5%, <0.001; 6.1% vs. 33.3%, p = .005, respectively). Women with COVID-19 had a higher prevalence of prolonged postpartum hospital stay (33.3% vs. 9.1%, p = .016), and significantly higher prevalence of spontaneous preterm birth (27.3% vs. 1.09%, p = .006). Breastfeeding within the first 24 hr was also lower in women with COVID-19 (72.7% vs. 97.0%, p = .006). Maternal characteristics and neonatal outcomes are influenced by COVID-19 infection in vaccinated women. Complications include spontaneous preterm birth, prolonged postpartum hospital stay, and lack of breastfeeding within the first 24 hr. Childbirth education, parenting classes and implementing a birth plan may be associated with a decreased risk of COVID-19 infection.
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COVID-19 , SARS-CoV-2 , Humanos , Feminino , COVID-19/prevenção & controle , COVID-19/epidemiologia , Gravidez , Adulto , Projetos Piloto , Estudos Retrospectivos , Recém-Nascido , Estudos de Casos e Controles , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Vacinas contra COVID-19 , Estudos de Coortes , Vacinação/estatística & dados numéricos , Aleitamento Materno/estatística & dados numéricosRESUMO
Objectives: To compare complications associated with percutaneous gastrostomies performed using PUSH and PULL techniques, whether endoscopic (PEG) or radiological (PRG), in a tertiary-level hospital. Methods: This was a prospective observational study. Adult patients who underwent percutaneous PULL or PUSH gastrostomy using PEG or PRG techniques at the Virgen del Rocio University Hospital and subsequently followed up in the Nutrition Unit between 2009-2020 were included. X2 tests or Fisher's test were used for the comparison of proportions when necessary. Univariate analysis was conducted to study risk factors for PRG-associated complications. Results: n = 423 (PULL = 181; PUSH = 242). The PULL technique was associated with a higher percentage of total complications (37.6% vs. 23.8%; p = 0.005), exudate (18.2% vs. 11.2%; p = 0.039), and irritation (3.3% vs. 0%; p = 0.006). In the total sample, there were 5 (1.1%) cases of peritonitis, 3 (0.7%) gastrocolic fistulas, and 1 (0.2%) death due to complications associated with gastrostomy. Gender, age, and different indications were not risk factors for a higher number of complications. The most common indications were neurological diseases (35.9%), head and neck cancer (29%), and amyotrophic lateral sclerosis (17.2%). Conclusions: The PULL technique was associated with more total complications than the PUSH technique, but both were shown to be safe techniques, as the majority of complications were minor.
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AIM: We aimed to compare the debriefing experience, simulation assessment, reflection, anxiety and simulation satisfaction of using oral debriefing versus video-assisted debriefing after a simulated clinical session in an interdisciplinary cohort of health sciences students. BACKGROUND: Debriefing is a reflective process that takes place after a clinical simulation and that can be performed either in a traditional way (oral) or using video-assisted debriefing. DESIGN: A randomized controlled trial was conducted in 143 health sciences students (35.7% male, 61.5% female). METHODS: The simulation scenario was designed to evaluate the procedure for donning and doffing personal protective equipment. Differences in debriefing experience, simulation assessment, reflection, anxiety and satisfaction were assessed. RESULTS: Regarding debriefing experience, significant differences were observed for the category "learning" (34.9 (6.13) vs. 36.7 (3.89); p = 0.039). For simulation assessment, significantly higher scores for all categories were identified in video-assisted debriefing compared with oral debriefing (p<0.001). There were also significant differences between the oral debriefing versus video-assisted debriefing for the overall score of reflection ability (86.97 (10.55) vs. 90.74 (9.67); p=0.028) as well as for the category "reflective communication" (24.72 (3.77) vs 26.04 (4.07); p=0.047). Perceived satisfaction was significantly higher in the video-assisted debriefing group compared with oral debriefing group (p <0.001). For anxiety, no significant differences were observed between debriefing groups. CONCLUSION: Video-assisted debriefing after a simulated clinical session improves debriefing experience, simulation assessment, reflection and simulation satisfaction, but does not increase anxiety compared with oral debriefing among health sciences students.
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Comunicação , Aprendizagem , Humanos , Masculino , Feminino , Ocupações em Saúde , Competência ClínicaRESUMO
Introduction: Conservative management of primary obstructive megaureter (POM) appears as the best option in patients with adequate ureteral drainage. Nevertheless, surgical intervention is indicated in cases of recurrent urinary tract Infections (UTIs), deterioration of split renal function, and significant obstruction. The gold standard includes: Ureteral reimplantation with or without tapering by open approach. Our objective is to report our results in the treatment of POM by Laparoscopic-Assisted Extracorporeal Ureteral Tapering Repair (EUTR) and Laparoscopic Ureteral Extravesical Reimplantation (LUER) and to evaluate the efficacy and security of this procedure. Materials and Methods: From January 2011 to January 2018 a retrospective study was carried out by reviewing the clinical records of 26 patients diagnosed with POM. All patients underwent laparoscopic ureteral reimplantation following Lich Gregoir technique. In cases of ureteral tapering, an EUTR was performed with Hendren technique. Results: In all patients LUER and EUTR were performed without conversion. No ureteral tapering was necessary in six patients. There were no intraoperative complications. At 3 months in postoperative, 1 patient presented a febrile UTI, and subsequently, a vesicoureteral reflux (VUR) grade III was diagnosed by voiding cystourethrogram. In this case, a redo laparoscopic surgery was performed. After long-term follow-up, all patients were asymptomatic without recurrence of POM or VUR. Conclusion: Laparoscopic-assisted EUTR and LUER following Lich Gregoir technique for POM constitutes a safe and effective option, with a success rate similar to that of open procedure. Nevertheless, larger randomized prospective trials and long-term follow-up are required to validate this technique.
Assuntos
Laparoscopia , Ureter , Refluxo Vesicoureteral , Humanos , Criança , Estudos Retrospectivos , Estudos Prospectivos , Resultado do Tratamento , Procedimentos Cirúrgicos Urológicos/métodos , Ureter/cirurgia , Refluxo Vesicoureteral/cirurgia , Refluxo Vesicoureteral/etiologia , Laparoscopia/métodos , Reimplante/métodosRESUMO
Pest control is a main concern in agriculture. Indiscriminate application of synthetic pesticides has caused negative impacts leading to the rapid development of resistance in arthropod pests. Plant secondary metabolites have been proposed as a safer alternative to conventional pesticides. Monoterpenoids have reported bioactivities against important pests; however, due to their high volatility, low water solubility and chemical instability, the application of these compounds has been limited. Nanosystems represent a potential vehicle for the broad application of monoterpenoids. In this study, an 1,8-cineole nanoemulsion was prepared by the low energy method of phase inversion, characterization of droplet size distribution and polydispersity index (PDI) was carried out by dynamic light scattering and stability was evaluated by centrifugation and Turbiscan analysis. Fumigant bioactivity was evaluated against Tetranychus urticae, Rhopalosiphum maidis and Bemisia tabaci. A nanoemulsion with oil:surfactant:water ratio of 0.5:1:8.5 had a droplet size of 14.7 nm and PDI of 0.178. Formulation was stable after centrifugation and the Turbiscan analysis showed no particle migration and a delta backscattering of ±1%. Nanoemulsion exhibited around 50% more bioactivity as a fumigant on arthropods when compared to free monoterpenoid. These results suggest that nanoformulations can provide volatile compounds of protection against volatilization, improving their bioactivity.