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The Omicron variant of the severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infected a substantial proportion of Chinese population, and understanding the factors underlying the severity of the disease and fatality is valuable for future prevention and clinical treatment. We recruited 64 patients with invasive ventilation for COVID-19 and performed metatranscriptomic sequencing to profile host transcriptomic profiles, plus viral, bacterial, and fungal content, as well as virulence factors and examined their relationships to 28-day mortality were examined. In addition, the bronchoalveolar lavage fluid (BALF) samples from invasive ventilated hospital/community-acquired pneumonia patients (HAP/CAP) sampled in 2019 were included for comparison. Genomic analysis revealed that all Omicron strains belong to BA.5 and BF.7 sub-lineages, with no difference in 28-day mortality between them. Compared to HAP/CAP cohort, invasive ventilated COVID-19 patients have distinct host transcriptomic and microbial signatures in the lower respiratory tract; and in the COVID-19 non-survivors, we found significantly lower gene expressions in pathways related viral processes and positive regulation of protein localization to plasma membrane, higher abundance of opportunistic pathogens including bacterial Alloprevotella, Caulobacter, Escherichia-Shigella, Ralstonia and fungal Aspergillus sydowii and Penicillium rubens. Correlational analysis further revealed significant associations between host immune responses and microbial compositions, besides synergy within viral, bacterial, and fungal pathogens. Our study presents the relationships of lower respiratory tract microbiome and transcriptome in invasive ventilated COVID-19 patients, providing the basis for future clinical treatment and reduction of fatality.
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COVID-19 , Microbiota , Neumonía , Humanos , COVID-19/genética , COVID-19/metabolismo , SARS-CoV-2/genética , Respiración Artificial , Pulmón , Neumonía/metabolismo , BacteriasRESUMEN
Objective: To observe the present situation, efficacy and safety of immunotherapy in patients with malignant pleural mesothelioma (MPM). Methods: The data of 39 patients with MPM in two centers from 2016 to 2021 were collected and the efficacy and safety were evaluated. According to the application of immune checkpoint inhibitors (ICIs), these patients, whose median clinical follow-up amounting to 18.97 months, were divided into immunotherapy group (19 cases) and control group (20 cases). Kaplan-Meier method and Log-rank test were used for the survival analysis. Results: The objective response rate (ORR) and the disease control rate (DCR) in the immunotherapy group is 21.05% and 79.0% respectively, compared with 10.0% and 55.0% in the control group; and the difference was not statistically significant (P>0.05). The median overall survival (OS) in the immunotherapy group was significantly longer than that in the control group (14.53 months vs 7.07 months, P=0.015), but there was no significant difference in the median progression free survival (PFS) between two groups (4.80 months vs 2.03 months, P=0.062). Single factor survival analysis showed that the nature of pleural effusion, pathological subtype and the efficacy of immunotherapy were related to both PFS and OS of the patients with MPM (P<0.05). The incidence of adverse reactions in immunotherapy group was 89.5% (17 out of 19 cases), and the most common adverse event was hematological toxicity (9 cases), followed by nausea and vomiting (7 cases), fatigue (6 cases) and skin damage (6 cases). Five patients had immune checkpoint inhibitors (ICIs) related adverse reactions with grade 1-2. Conclusions: Patients with MPM have begun to receive immunotherapy in more than 2-line mainly combined chemotherapy in the real world, and the median treatment line is 2-line. Either combined with chemotherapy or anti-angiogenesis therapy, ICI inhibitors have significant efficacy, controllable adverse events and good clinical value.
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Humanos , Mesotelioma Maligno/tratamiento farmacológico , Mesotelioma/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/efectos adversosRESUMEN
PURPOSE: To compare the clinical effectiveness between transarterial embolization (TAE) with staged hepatectomy (SH) and emergency hepatectomy (EH) for ruptured hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Pubmed, Embase, and Cochrane Library databases were screened for eligible publications from the inception of the databases till February 2021. RESULTS: This meta-analysis included seven studies comprising 162 patients who underwent TAE with SH and 266 patients who underwent EH. The pooled intraoperative blood loss was less in the TAE with SH cohort, as compared to the EH cohort without significant difference (p = .20). The pooled blood transfer rate (p<.00001), blood transfer volume (p = .002), and 30-day patient death (p = .04) were all markedly reduced in the TAE with SH cohort versus the EH cohort. No significant differences in surgery duration (p = .27), hospital stay period (p = .81), complication rate (p = 0.92), disease-free survival (DFS) (p = .79), and overall survival (OS) (p = 0.28) were found between the two groups. CONCLUSIONS: Compared with EH for ruptured HCC, TAE with SH could effectively decrease intraoperative blood loss and 30-day mortality. However, the long-term DFS and OS might not be beneficial to preoperative TAE.
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Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Pérdida de Sangre Quirúrgica , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/cirugía , Hepatectomía , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Rotura Espontánea/complicaciones , Rotura Espontánea/cirugía , Resultado del TratamientoRESUMEN
INTRODUCTION: Transjugular intrahepatic portosystemic shunt (TIPS) is an approach that is used to alleviate portal hypertension-related symptoms. The optimal stent diameter for TIPS remains controversial. AIM: To assess outcomes in patients who underwent TIPS using 8 mm and 10 mm stents. MATERIAL AND METHODS: The PubMed, Embase, and Cochrane Library databases were queried for all pertinent studies. The meta-analysis was conducted using RevMan v5.3. This meta-analysis was registered at the PROSPERO website (Number: CRD42020212392). RESULTS: Eighty-two potentially relevant articles were initially detected, with seven of these ultimately being included in this meta-analysis. Patients in the 10 mm stent group exhibited a significantly higher Δportosystemic pressure gradient (ΔPPG) relative to the 8 mm group (p = 0.04), whereas no differences between groups were observed with respect to postoperative hepatic encephalopathy (HE, p = 0.25), re-bleeding (p = 0.82), liver transplantation (p = 0.45), or mortality (p = 0.43) rates. The TIPS dysfunction rate was significant lower in the 10 mm group (p = 0.01). In Asian studies, the postoperative HE rate was found to be significantly lower in the 8 mm group relative to the 10 mm group (p = 0.02), whereas all other endpoints were comparable between these groups. In Western studies, ΔPPG values were significantly greater in the 10 mm group (p < 0.0001), whereas all other endpoint data were comparable between these groups. CONCLUSIONS: TIPS with 10 mm stents provides a lower TIPS dysfunction rate. However, 8 mm stents may be recommended for Asian patients, as they can decrease the risk of postoperative HE.
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PURPOSE: The COVID-19 pandemic has led to the cancellation or deferment of many elective cancer surgeries. We performed a systematic review on the oncological effects of delayed surgery for patients with localised or metastatic renal cell carcinoma (RCC) in the targeted therapy (TT) era. METHOD: The protocol of this review is registered on PROSPERO(CRD42020190882). A comprehensive literature search was performed on Medline, Embase and Cochrane CENTRAL using MeSH terms and keywords for randomised controlled trials and observational studies on the topic. Risks of biases were assessed using the Cochrane RoB tool and the Newcastle-Ottawa Scale. For localised RCC, immediate surgery [including partial nephrectomy (PN) and radical nephrectomy (RN)] and delayed surgery [including active surveillance (AS) and delayed intervention (DI)] were compared. For metastatic RCC, upfront versus deferred cytoreductive nephrectomy (CN) were compared. RESULTS: Eleven studies were included for quantitative analysis. Delayed surgery was significantly associated with worse cancer-specific survival (HR 1.67, 95% CI 1.23-2.27, p < 0.01) in T1a RCC, but no significant difference was noted for overall survival. For localised ≥ T1b RCC, there were insufficient data for meta-analysis and the results from the individual reports were contradictory. For metastatic RCC, upfront TT followed by deferred CN was associated with better overall survival when compared to upfront CN followed by deferred TT (HR 0.61, 95% CI 0.43-0.86, p < 0.001). CONCLUSION: Noting potential selection bias, there is insufficient evidence to support the notion that delayed surgery is safe in localised RCC. For metastatic RCC, upfront TT followed by deferred CN should be considered.
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COVID-19/prevención & control , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Tiempo de Tratamiento , COVID-19/epidemiología , COVID-19/transmisión , Carcinoma de Células Renales/patología , Control de Enfermedades Transmisibles , Humanos , Neoplasias Renales/patología , Nefrectomía , Tasa de SupervivenciaRESUMEN
PURPOSE: This study was designed to assess the clinical efficacy of stent insertion with high intensity-focused ultrasound ablation (HIFUA) in patients with malignant biliary obstruction (MBO) as a consequence of pancreatic carcinoma (PC). MATERIALS AND METHODS: This was a single-center, open-label, prospective, randomized controlled trial. Consecutive patients with MBO caused by PC were randomly assigned to undergo stent insertion with or without HIFUA from June 2019 to February 2020. This study was registered at ClinicalTrials.gov (NCT03962478). RESULTS: In total, 92 patients were enrolled in this study and assigned to the stent-only (n=46) or combined (stent+HIFUA; n=46) treatment groups. Stent insertion was associated with a 100% technical success rate. For patients in the combination treatment group, 26, 18, and 2 patients underwent 2, 3, and 4 cycles of HIFUA, respectively. A positive clinical response to HIFUA treatment was noted in 38 patients (82.6%). Stent dysfunction was detected in 9 and 15 patients in the combination and stent-only groups, respectively (P=0.154), while median stent patency in these 2 groups was 188 and 120 days, respectively (P<0.001). All patients died over the course of the follow-up, with median survival periods of 218 and 140 days in the combination and stent-only treatment groups, respectively (P=0.001). The only detected predictor of prolonged survival was HIFUA treatment (P=0.004), and there were no significant differences in complication rates between these 2 treatment groups. CONCLUSION: A combination of stent insertion and HIFUA can improve stent patency and overall survival in patients suffering from MBO because of PC relative to stent insertion alone.
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Neoplasias de los Conductos Biliares , Colestasis , Neoplasias Pancreáticas , Colestasis/etiología , Colestasis/cirugía , Humanos , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/cirugía , Estudios Prospectivos , Stents , Resultado del Tratamiento , Neoplasias PancreáticasRESUMEN
OBJECTIVE: This study aimed to investigate the clinical manifestation and treatment effects of extrapulmonary complications in cases of novel coronavirus pneumonia. METHODS: The clinical data of patients with novel coronavirus pneumonia who were admitted to Hanchuan People's Hospital between January and March 2020 were retrospectively analyzed, and the clinical characteristics, laboratory test results, and treatment pathways of patients with extrapulmonary complications were analyzed and summarized. RESULTS: Of the 500 patients in this study, 97 patients with a history of chronic diseases were excluded, and 152 patients had extrapulmonary complications. Common extrapulmonary syndromes: 98 patients (64.47%) suffered from digestive system involvement; 43 patients (28.29%) suffered from cardiovascular system damage; 32 patients (21.05%) had urinary system damage; 25 patients (16.45%) had nervous system damage; and 30 patients (19.74%) had more than two kinds of system damage. In all cases, these patients were treated with comprehensive measures, and effective outcomes were achieved. CONCLUSION: According to the clinical characteristics and laboratory test results of this sample group, early evaluation of patients with extrapulmonary complications and timely symptomatic treatment can effectively improve outcomes of pneumonia treatment, accelerate the alleviation of symptoms, and improve patients' condition.
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CO2 capture, utilization, and storage are promising strategies to solving the problems of superfluous CO2 or energy shortage. Here, mechanochemical reduction of CO2 by a MgH2/CaH2 mixture was first performed, by which we achieve selective methanation of CO2 and acquire an effective CaO-based CO2 sorbent, simultaneously. The selectivity of methanation is near 100% and the yield of CH4 reaches 30%. Four MgO and carbon-doped CaO-based CO2 sorbents (MgO/CaO/C, MgO/2CaO/C, MgO/4CaO/C, and MgO/8CaO/C) were formed as solid products in these reactions. Among them, the MgO/4CaO/C sorbent shows high initial adsorption amount of 59.3 wt% and low average activity loss of 1.6% after 30 cycles. This work provides a novel, well-scalable, and sustainable approach to prepare an efficient inert additive-including CaO-based CO2 sorbent and selectively convert CO2 to CH4 at the same time.
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PURPOSE: To assess the safety and clinical effectiveness of catheter aspiration with recanalization in patients with Budd-Chiari syndrome (BCS) and inferior vena cava (IVC) thrombosis. MATERIALS AND METHODS: Between January 2010 and December 2017, 33 patients with BCS and IVC thrombosis were treated by catheter aspiration with IVC recanalization in our center. A 12 F angled-tip guiding catheter was used for the aspiration of thrombi in the IVC. Recanalization was conducted following thrombi aspiration. Rates of technical success, clinical success and long-term patency were calculated. RESULTS: Catheter aspiration with IVC recanalization was technically successful in all patients. After aspiration, no thrombi were detectable by IVC venography in 21 patients, while residual mural thrombi were found in 12 patients. IVC balloon dilation was performed in 18 patients, while stent insertion was performed in 15 patients. We also achieved clinical success in all patients. Symptomatic and asymptomatic pulmonary embolism were found in 1 patient each, respectively. The cumulative 1-, 3-, and 5-year patency rates were 93.6%, 93.6%, and 83.2%, respectively. All patients remained alive during the follow-up. CONCLUSIONS: Catheter aspiration with recanalization is a safe and efficacious approach to treating patients with BCS and IVC thrombosis.
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Síndrome de Budd-Chiari/epidemiología , Síndrome de Budd-Chiari/cirugía , Cateterismo/métodos , Trombosis de la Vena/epidemiología , Trombosis de la Vena/cirugía , Adulto , Síndrome de Budd-Chiari/diagnóstico por imagen , Estudios de Cohortes , Comorbilidad , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Flebografía/métodos , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Trombectomía/métodos , Resultado del Tratamiento , Grado de Desobstrucción Vascular/fisiología , Vena Cava Inferior/diagnóstico por imagen , Vena Cava Inferior/cirugía , Trombosis de la Vena/diagnóstico por imagenRESUMEN
OBJECTIVE: To evaluate the technical feasibility,safety,and clinical outcome of mechanical thrombectomy with Solitaire FR stent system for embolic occlusion of the superior mesenteric artery(SMA).METHODS: The clinical data of 6 patients with embolic occlusion of the SMA treated by mechanical thrombectomy with Solitaire FR stent system between January 2015 and June 2018 in Binzhou City People's Hospital were analyzed retrospectively.RESULTS: Superior mesenteric artery occlusion was initially diagnosed by computed tomography(CT)in all patients.A successful thrombus removal of superior mesenteric arterial by Solitaire FR stent system was observed in the 6 patients.Five patients had recovered well after operation and no complications such as artery dissection,perforation and hemorrhage or intestinal ischemia.One patient underwent bowel resection.CONCLUSION: The arterial mechanical thrombectomy with solitaire FR stent system are characterized with high rate of recanalization,fine security,minimal invasion and less complications in patients with acute superior mesentericvarterial embolism.
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Apresentam-se resultados de pesquisa realizada entre 2012-2014 em Santos, litoral de São Paulo, que buscou identificar perspectivas sobre a guarda familiar de pessoas em situação de rua, a partir de entrevistas semiabertas com dez trabalhadores e uma família. A proteção social a famílias envolve complexas tomadas de decisões, cabendo destacar as particularidades da guarda familiar de pessoas em situação de rua tendo por base as mais diferentes perspectivas: políticas públicas, modos de efetivação dessas políticas pelos trabalhadores e singularidades de crianças e famílias. Identificou-se a intenção da família de manter a guarda dos filhos e o esboço de projetos de futuro que demandam serviços de proteção social. Entre trabalhadores, verifica-se inclinação à generalização, institucionalização e culpabilização das famílias, somada ao sentimento de impotência dos trabalhadores diante da complexidade da situação de rua. Discute-se a relevância de produzir espaços em que ambos os grupos possam participar da proposição de caminhos a serem trilhados.
This paper presents results from a survey taken between 2012 and 2014 in Santos, São Paulo coast. The survey sought to identify perspectives regarding homeless people family custody with ten workers and one family by the means of semi-open interviews. The families social protection involves complex decision making. It is important to highlight the peculiarities of homeless people familiar custody from different perspectives: public policies, ways of execution of these policies by workers and children and families individuals. It was identified the family's intent to maintain the children's custody and the draft of future projects that demands services of social protection. Among workers there is a tendency towards generalization, institutionalization and blame of families, together with the feeling of powerlessness of the workers in the face of the complexity of the street situation. The relevance of producing spaces in which both groups can participate in the proposition of paths to be traced is discussed.
Este artículo presenta los resultados de una encuesta realizada entre 2012 y 2014 en Santos, costa de São Paulo. La encuesta buscó identificar perspectivas sobre la custodia familiar de las personas sin vivienda con diez trabajadores y una familia mediante entrevistas semiabiertas. La protección social de las familias implica una toma de decisiones compleja. Es importante resaltar las peculiaridades de la custodia familiar de las personas sin vivienda desde diferentes perspectivas: políticas públicas, formas de ejecución de estas políticas por parte de los trabajadores, niños y familias individuales. Se identificó la intención de la familia de mantener la custodia de los niños y el proyecto de futuros proyectos que exige servicios de protección social. Entre los trabajadores existe una tendencia hacia la generalización, la institucionalización y la culpa de las familias, junto con la sensación de impotencia de los trabajadores frente a la complejidad de la situación de la calle. Se discute la relevancia de producir espacios en los que ambos grupos puedan participar en la proposición de caminos a seguir.
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Políticas de Control Social , Custodia del Niño , Política Pública , Servicio Social , Personas con Mala Vivienda , Familia , Relaciones Comunidad-Institución , InstitucionalizaciónRESUMEN
Although recent works demonstrated that some potassium compounds that can be converted to KH during ball-milling or heat-treatment have obvious effects on enhancing the dehydrogenation properties of the Li-N-H system, the effect of KH on enhancing the dehydrogenation properties of the Li-N-H system and its catalytic mechanism remain unclear. In this study, the hydrogen desorption properties of the LiNH2-LiH system with alkali metal hydrides (LiH, NaH, or KH) were investigated and discussed. We find that the three types of hydrides are effective for enhancing the hydrogen desorption properties of the LiNH2-LiH system, among which, KH shows the best effect. In comparison with the broad shaped hydrogen desorption curve of the LiNH2-LiH composite without additive, the hydrogen desorption curve of the LiNH2-LiH-0.05KH composite becomes narrow. The dehydrogenation onset temperature of the LiNH2-LiH-0.05KH composite is decreased by approximately 20 °C, and the dehydrogenation peak temperature is lowered by approximately 30 °C. Moreover, the reversibility of the LiNH2-LiH system is enhanced drastically by the addition of KH. On the basis of previous reports and present experimental results, the mechanism for the enhancement of the dehydrogenation properties in the KH-added Li-N-H system is proposed. The reason for the improvement of the hydrogen desorption kinetics is that KH has superior reactivity with NH3 and plays the role of a catalyst to accelerate hydrogen release by cyclic reactions.
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BACKGROUND: Insulin resistance (IR) and progressive pancreatic ß-cell dysfunction have been identified as the two fundamental features in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. We aimed to investigate correlations between anthropometric indices of obesity and IR in non-diabetic obese individuals, and the cutoff value from receiver operating characteristic (ROC) curve analysis. DESIGN AND SETTING: Cross-sectional study conducted in a private clinic. METHODS: We included obese individuals (body mass index, BMI ≥ 30 kg/m2) with no diabetes mellitus (fasting glucose levels ≤ 126 mg/dl). The participants were evaluated for the presence of cardiovascular risk factors and through anthropometric measurements and biochemical tests. Furthermore, IR was assessed indirectly using the homeostatic model assessment (HOMA)-IR and HOMA-ß indexes. The area underthe curve (AUC) of the variables was compared.The sensitivity, specificity and cutoff of each variable for diagnosing IR were calculated. RESULTS: The most promising anthropometric parameters for indicating IR in non-diabetic obese individuals were waist-to-height ratio (WHtR), waist circumference (WC) and BMI. WHtR proved to be an independent predictor of IR, with risk increased by 0.53% in HOMA-IR, 5.3% in HOMA-ß and 1.14% in insulin. For HOMA-IR, WHtR had the highest AUC value (0.98), followed by WC (0.93) and BMI (0.81). For HOMA-ß, WHtR also had the highest AUC value (0.83), followed by WC (0.75) and BMI (0.73).The optimal WHtR cutoff was 0.65 for HOMA-IR and 0.67 for HOMA-ß. CONCLUSION: Among anthropometric obesity indicators, WHtR was most closely associated with occurrences of IR and predicted the onset of diabetes in obese individuals.
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Enfermedades Cardiovasculares/etiología , Resistencia a la Insulina/fisiología , Obesidad/complicaciones , Adulto , Estatura , Índice de Masa Corporal , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/fisiopatología , Valor Predictivo de las Pruebas , Curva ROC , Factores de Riesgo , Circunferencia de la Cintura , Relación Cintura-CaderaRESUMEN
ABSTRACT BACKGROUND: Insulin resistance (IR) and progressive pancreatic β-cell dysfunction have been identified as the two fundamental features in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. We aimed to investigate correlations between anthropometric indices of obesity and IR in non-diabetic obese individuals, and the cutoff value from receiver operating characteristic (ROC) curve analysis. DESIGN AND SETTING: Cross-sectional study conducted in a private clinic. METHODS: We included obese individuals (body mass index, BMI ≥ 30 kg/m2) with no diabetes mellitus (fasting glucose levels ≤ 126 mg/dl). The participants were evaluated for the presence of cardiovascular risk factors and through anthropometric measurements and biochemical tests. Furthermore, IR was assessed indirectly using the homeostatic model assessment (HOMA)-IR and HOMA-β indexes. The area underthe curve (AUC) of the variables was compared.The sensitivity, specificity and cutoff of each variable for diagnosing IR were calculated. RESULTS: The most promising anthropometric parameters for indicating IR in non-diabetic obese individuals were waist-to-height ratio (WHtR), waist circumference (WC) and BMI. WHtR proved to be an independent predictor of IR, with risk increased by 0.53% in HOMA-IR, 5.3% in HOMA-β and 1.14% in insulin. For HOMA-IR, WHtR had the highest AUC value (0.98), followed by WC (0.93) and BMI (0.81). For HOMA-β, WHtR also had the highest AUC value (0.83), followed by WC (0.75) and BMI (0.73).The optimal WHtR cutoff was 0.65 for HOMA-IR and 0.67 for HOMA-β. CONCLUSION: Among anthropometric obesity indicators, WHtR was most closely associated with occurrences of IR and predicted the onset of diabetes in obese individuals.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resistencia a la Insulina/fisiología , Enfermedades Cardiovasculares/etiología , Obesidad/complicaciones , Estatura , Enfermedades Cardiovasculares/fisiopatología , Índice de Masa Corporal , Estudios Transversales , Valor Predictivo de las Pruebas , Factores de Riesgo , Curva ROC , Relación Cintura-Cadera , Circunferencia de la Cintura , Obesidad/fisiopatologíaRESUMEN
Increased alcohol consumption and heightened aggression have been linked to social isolation. Furthermore, animals treated with alcohol following social separation showed higher aggression together with lower serotonin transmission. Although reduced serotonin transmission in the brain may be related to alcohol-induced heightened aggression and fluoxetine has been used to reduce alcohol intake and aggression, it remains unclear whether there are specific brain regions where changes in serotonin transmission are critical for animal aggression following the alcohol treatment. In the present study, we isolated mice for 4-6weeks and injected them with alcohol, fluoxetine and alcohol with fluoxetine. We studied their aggression by using two types of behavioral paradigms: isolation-induced attack behavior towards a naïve mouse in a neutral cage, or shock-induced target biting aggression. We observed that alcohol administered at 500mg/kg significantly increased animal attack behaviors towards naïve mice 30min after injections. This dose of alcohol co-administered with a low dose of fluoxetine (2mg/kg) further increased the attack behaviors, but with higher doses of fluoxetine, the attack behaviors were decreased. Alcohol administered at a dose of 1,000mg/kg significantly decreased the shock-induced target biting rates 24h after injections. Interestingly, 24h after injections, we observed a significant increase in target biting rates when alcohol was co-administered with fluoxetine at a dose of 16mg/kg. We also observed the same heightened target biting rates when animals were injected with fluoxetine alone. This heightened biting attack engendered by the fluoxetine (alone or in combination with the alcohol) occurred at a time when brain serotonin activity was reduced by these drugs in the frontal cortex and hypothalamus. These observations, in concordance with previous findings reported by others, indicate that heightened biting attack behavior may be associated with reduced serotonergic activity in brain regions regulating aggression.
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Agresión/efectos de los fármacos , Etanol/efectos adversos , Consumo de Bebidas Alcohólicas/psicología , Animales , Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Etanol/farmacología , Fluoxetina/efectos adversos , Fluoxetina/farmacología , Lóbulo Frontal/efectos de los fármacos , Hipotálamo/efectos de los fármacos , Masculino , Ratones , SerotoninaRESUMEN
Objective To develop a practical synthetic process of vonoprazan fumarate with high-yield and lower impurities to meet the quality requirements. Methods By using 5-(2-fluorophenyl)pyrrole-3-carboxaldehyde as the starting material,the qualified vonoprazan fumarate was synthesized via the following steps:①N-sulfonylation and the chloride impurity was removed by recrystalli-zation from MeOH;②the aldehyde was converted to amine by reductive amination,followed by forming the vonoprazan chloride to re-move the dimethylamino impurity;③vonoprazan free base was obtained by neutralization and then converted to fumarate at room tem-perature and finally recrystallized from MeOH/H2O(1:1). Results An impurity controllable synthetic process was developed with a 4%total yield improving. The final product was confirmed by ESI-MS and 1H NMR. Conclusion The synthetic process with single im-purity less than 0.1%and purity above 99.5%was obtained and suitable for scale production of vonoprazan fumarate.
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O estudo teve como objetivo investigar o cotidiano de gestantes em situação de rua e sua relação com as políticas públicas na cidade de Santos, litoral do Estado de São Paulo. A coleta de dados foi feita através do registro e estudo de narrativas de memórias de vida. A análise deu-se pelo agrupamento temático de trechos das narrativas, sendo identificadas quatro principais categorias: vida na rua; cuidado e gestação; projetos futuros; e rede pública de serviços. As narrativas revelam mulheres com capacidade criativa para desejar uma vida melhor a partir da possibilidade de ter um filho. Entretanto, a condição social em que vivem, envolvendo a luta diária pela sobrevivência e, em alguns casos, a dependência química dificultam o planejamento de estratégias que transformem o desejo em um projeto de vida. Dessa forma, na maioria das vezes perdem a guarda de seus filhos. Embora conheçam os serviços públicos, quase sempre os acessam apenas em casos de urgência. Não se identificaram na rede de serviços assistenciais - pública e do terceiro setor - programas focados na questão da gestante em situação de rua, ainda que o Brasil já viva, atualmente, histórias de famílias que têm a situação de rua como experiência intergeracional. Os resultados apontam para a necessidade de constituição de políticas intersetoriais, voltadas para gestantes em situação de rua.
The study aimed to investigate the daily routine of homeless pregnant women and their relation to public policies in the city of Santos, State of São Paulo. Data was collected through the record and study of narratives of life memories. The analysis was conducted through the thematic grouping of excerpts of narratives, and four main categories were identified: life on the street; care and pregnancy; future projects; and public services. The narratives reveal women with creative ability to desire a better life based on the possibility of having a child. However, the social condition in which they live, which involves the daily struggle for survival and, in some cases, drug addiction, hinders the planning of strategies to transform the desire into a life project. Thus, most of them lose custody of their children. Although they know the public services, they go to them only in emergencies, mostly. We have not identified, in the network of care services - public and third sector -, programs focusing on the issue of homeless pregnant women, even though Brazil already witnesses, today, stories of families who have the homeless situation as an intergenerational experience. The results point to the need of making intersectoral policies targeted at homeless pregnant women.
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Humanos , Femenino , Embarazo , Apoyo Social , Condiciones Sociales , Atención Prenatal , Mujeres Embarazadas , Personas con Mala Vivienda , Política Pública , Salud Materno-Infantil , Sistema Único de Salud , Estrategias de Salud , Planificación en SaludRESUMEN
Network analysis of human brain connectivity based on graph theory has consistently identified sets of regions that are critically important for enabling efficient information integration and communication, especially for the understanding of cognitive functions, the discoveries of aging effects and the network change due to brain diseases. Two major approaches, hub measurement (HM) and vulnerability measurement (VM), have been proposed to detect these `important nodes' within brain network organization. However, the relationship between the spatial localization and the number of these identified nodes found using HM and VM approaches respectively is still unknown. In this study, we aim to figure out the relationships between the identified critical nodes of brain network based on various HM and VM methods with DTI-based structural brain network. Two factors of parcellation atlases and level of scale are also considered to address the effects in the definition of these nodes. From the results, the great consistency is existed between the node identification using HM and VM approaches in the same atlases, but the divergence between different atlases and level of node scale.
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Encéfalo , Mapeo Encefálico , Cognición , HumanosRESUMEN
Rheumatoid arthritis is an autoimmune disease characterized as joint synovial inflammation. MicroRNA is a group of small noncoding RNA molecules discovered in recent years that can posttranscriptional regulate mRNA expression and involved in a variety processes of immune cell activation and differentiation. There is still lack of study about the role of miR-451 in rheumatoid arthritis. Synovial fibroblasts isolated from rheumatoid arthritis patients were cultured in vitro. Chemical synthesized miR-451 was lipo-transfected, real-time RT-PCR was applied to detect miR-451 expression level, and MTT method was used to detect the effect of miR-451 on synovial fibroblasts proliferation. Enzyme-linked immunosorbent assay was used to detect tumor necrosis factor TNF-α, IL-1ß, and IL-6 level in the supernatant. Western blot was applied to test target protein p38 MAPK expression level. Our study found that synovial fibroblasts expressed higher miR-451 mRNA level in miR-451 treatment group. MiR-451 treatment significantly decreased cell proliferation ability (P < 0.05). Compared with the control, p38 MAPK protein expression reduced obviously in the miR-451 treatment group (P < 0.05). MiR-451 transfected synovial fibroblasts secreted lower levels of TNF-α (198 ± 12 pg/ml vs 124 ± 13 pg/ml, P < 0.01), IL-1ß (352 ± 43 pg/ml vs 165 ± 87 pg/ml, P < 0.01), and IL-6 (487 ± 84 pg/ml vs 257 ± 92 pg/ml, P < 0.01). The results proved that miR-451 can down-regulate p38 MAPK protein expression, and reduce synovial fibroblasts proliferation and cytokine expression level.
Asunto(s)
Artritis Reumatoide/patología , Fibroblastos/metabolismo , Regulación de la Expresión Génica/genética , Sistema de Señalización de MAP Quinasas/fisiología , MicroARNs/genética , Artritis Reumatoide/genética , Western Blotting , Proliferación Celular/genética , Células Cultivadas , Citocinas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Inflamación/genética , Inflamación/metabolismo , MicroARNs/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Membrana Sinovial , TransfecciónRESUMEN
BACKGROUND: To investigate the association between the single nucleotide polymorphism (SNP) of hypoxia-inducible factor1 α (HIF-1α) and the susceptibility to cervical spondylotic myelopathy (CSM) and its outcome after surgical treatment. METHOD: A total of 230 CSM patients and 284 healthy controls were recruited. All patients received anterior cervical corpectomy and fusion (ACF) and were followed for 12 months. The genotypes for two HIF-1α variants (1772C>T and 1790G>A) were determined. RESULTS: In the present study, we found that the HIF-1α polymorphism at 1790G>A significantly affects the susceptibility to CSM and its clinical features, including severity and onset age. In addition, the 1790A>G polymorphism also determines the prognosis of CSM patients after ACF treatment. The GG genotype of 1790G>A polymorphism is associated with a higher risk to develop CSM, higher severity and earlier onset age. More importantly, we found that the 1790G>A polymorphism determines the clinical outcome in CSM patients who underwent ACF treatment. CONCLUSION: Our findings suggest that the HIF-1α 1790G>A polymorphism is associated with the susceptibility to CSM and can be used as predictor for the clinical outcome in CSM patients receiving ACF treatment.