Paricalcitol prevents MAPK pathway activation and inflammation in adriamycin-induced kidney injury in rats.

BACKGROUND: Activation of the mitogen-activated protein kinase (MAPK) pathway induces uncontrolled cell proliferation in response to inflammatory stimuli. Adriamycin (ADR)-induced nephropathy (ADRN) in rats triggers MAPK activation and pro-inflammatory mechanisms by increasing cytokine secretion, similar to chronic kidney disease (CKD). Activation of the vitamin D receptor (VDR) plays a crucial role in suppressing the expression of inflammatory markers in the kidney and may contribute to reducing cellular proliferation. This study evaluated the effect of pre-treatment with paricalcitol on ADRN in renal inflammation mechanisms. METHODS: Male Sprague-Dawley rats were implanted with an osmotic minipump containing activated vitamin D (paricalcitol, Zemplar, 6 ng/day) or vehicle (NaCl 0.9%). Two days after implantation, ADR (Fauldoxo, 3.5 mg/kg) or vehicle (NaCl 0.9%) was injected. The rats were divided into four experimental groups: control, n = 6; paricalcitol, n = 6; ADR, n = 7 and, ADR + paricalcitol, n = 7. RESULTS: VDR activation was demonstrated by increased CYP24A1 in renal tissue. Paricalcitol prevented macrophage infiltration in the glomeruli, cortex, and outer medulla, prevented secretion of tumor necrosis factor-α, and interleukin-1ß, increased arginase I and decreased arginase II tissue expressions, effects associated with attenuation of MAPK pathways, increased zonula occludens-1, and reduced cell proliferation associated with proliferating cell nuclear antigen expression. Paricalcitol treatment decreased the stromal cell-derived factor 1α/chemokine C-X-C receptor type 4/ß-catenin pathway. CONCLUSIONS: Paricalcitol plays a renoprotective role by modulating renal inflammation and cell proliferation. These results highlight potential targets for treating CKD.

Case report: VEXAS syndrome: an atypical indolent presentation as sacroiliitis with molecular response to azacitidine.

VEXAS syndrome is a recently described autoinflammatory syndrome caused by the somatic acquisition of UBA1 mutations in myeloid precursors and is frequently associated with hematologic malignancies, chiefly myelodysplastic syndromes. Disease presentation can mimic several rheumatologic disorders, delaying the diagnosis. We describe a case of atypical presentation resembling late-onset axial spondylarthritis, later progressing to a systemic inflammatory syndrome with chondritis, cutaneous vasculitis, and transfusion-dependent anemia, requiring high doses of steroids. Ruxolitinib was used as the first steroid-sparing strategy without response. However, azacitidine showed activity in controlling both inflammation and the mutant clone. This case raises the question of whether azacitidine's anti-inflammatory effects are dependent on or independent of clonal control. We discuss the potential relevance of molecular remission in VEXAS syndrome and highlight the importance of a multidisciplinary team for the care of such complex patients.

Fatores Associados aos Custos do Tratamento no Primeiro Ano após Implantes Iniciais ou Trocas de Geradores de Pulsos de Marca-passos Cardíacos / Factors Associated with the Treatment Costs within the First Year after Pacemaker Implantation or Pulse Generator Replacement

Resumo Fundamento O uso de marca-passos cardíacos artificiais tem crescido constantemente, acompanhando o envelhecimento populacional. Objetivos Determinar as taxas de readmissões hospitalares e complicações após implante de marca-passo ou troca de gerador de pulsos e avaliar o impacto desses eventos nos custos anuais do tratamento sob a perspectiva do Sistema Único de Saúde (SUS). Métodos Registro prospectivo, com dados derivados da prática clínica assistencial, coletados na hospitalização índice e durante os primeiros 12 meses após o procedimento cirúrgico. O custo da hospitalização índice, do procedimento e do seguimento clínico foram estimados de acordo com os valores reembolsados pelo SUS e analisados ao nível do paciente. Modelos lineares generalizados foram utilizados para estudar fatores associados ao custo total anual do tratamento, adotando-se um nível de significância de 5%. Resultados No total, 1.223 pacientes consecutivos foram submetidos a implante inicial (n= 634) ou troca do gerador de pulsos (n= 589). Foram observados 70 episódios de complicação em 63 pacientes (5,1%). A incidência de readmissões hospitalares em um ano foi de 16,4% (IC 95% 13,7% - 19,6%) após implantes iniciais e 10,6% (IC 95% 8,3% - 13,4%) após trocas de geradores. Doença renal crônica, histórico de acidente vascular encefálico, tempo de permanência hospitalar, necessidade de cuidados intensivos pós-operatórios, complicações e readmissões hospitalares mostraram um impacto significativo sobre o custo anual total do tratamento. Conclusões Os resultados confirmam a influência da idade, comorbidades, complicações pós-operatórias e readmissões hospitalares como fatores associados ao incremento do custo total anual do tratamento de pacientes com marca-passo.

Abstract Background The use of artificial cardiac pacemakers has grown steadily in line with the aging population. Objectives To determine the rates of hospital readmissions and complications after pacemaker implantation or pulse generator replacement and to assess the impact of these events on annual treatment costs from the perspective of the Unified Health System (SUS). Methods A prospective registry, with data derived from clinical practice, collected during index hospitalization and during the first 12 months after the surgical procedure. The cost of index hospitalization, the procedure, and clinical follow-up were estimated according to the values reimbursed by SUS and analyzed at the patient level. Generalized linear models were used to study factors associated with the total annual treatment cost, adopting a significance level of 5%. Results A total of 1,223 consecutive patients underwent initial implantation (n=634) or pulse generator replacement (n=589). Seventy episodes of complication were observed in 63 patients (5.1%). The incidence of hospital readmissions within one year was 16.4% (95% CI 13.7% - 19.6%) after initial implants and 10.6% (95% CI 8.3% - 13.4%) after generator replacements. Chronic kidney disease, history of stroke, length of hospital stays, need for postoperative intensive care, complications, and hospital readmissions showed a significant impact on the total annual treatment cost. Conclusions The results confirm the influence of age, comorbidities, postoperative complications, and hospital readmissions as factors associated with increased total annual treatment cost for patients with pacemakers.

Preditores de Qualidade de Vida, Ansiedade e Aceitação em Pacientes com Cardioversor-Desfibrilador Implantável / Predictors of Quality of Life, Anxiety and Acceptance in Patients with Implantable Cardioverter-Defibrillator

Resumo Fundamento O cardioversor-desfibrilador implantável (CDI) pode causar níveis elevados de ansiedade e depressão, resultando em efeitos negativos na qualidade de vida. Objetivos Avaliar a qualidade de vida, a ansiedade e a aceitação do CDI por meio de instrumentos de medida padronizados e identificar preditores de melhores respostas para cada um dos desfechos estudados. Método Coorte prospectiva com pacientes submetidos a implante inicial de CDI ou reoperação para a manutenção do dispositivo. Os desfechos do estudo incluíram: qualidade de vida, ansiedade e aceitação do CDI. A mudança nos escores (30 e 180 dias) foi avaliada por meio da diferença mínima importante (DMI). Foi utilizada a análise univariada e o modelo de regressão logística multivariada para a identificação de preditores de melhores respostas, adotando-se o nível de significância de 5%. Resultados De janeiro/2020 a junho/2021 foram incluídos 147 pacientes, com idade média de 55,3 ± 13,4 anos e predomínio do sexo masculino (72,1%). A DMI para qualidade de vida, a ansiedade e a aceitação do CDI foram observadas em 33 (22,4%), 36 (24,5%) e 43 (29,3%) pacientes, respectivamente. Idade igual ou maior que 60 anos (OR=2,5; IC 95%=1,14-5,53; p=0,022), ausência de fibrilação atrial (OR=3,8; IC 95%=1,26-11,63; p=0,017) e sexo feminino (OR=2,2; IC 95%=1,02-4,97; p=0,045) foram preditores independentes de melhores respostas para qualidade de vida, ansiedade e aceitação do CDI, respectivamente. Conclusão A identificação de preditores para melhores escores de qualidade de vida, ansiedade e aceitação do dispositivo pode subsidiar a implementação de cuidados específicos para os pacientes com maiores chances de apresentar resultados desfavoráveis.

Abstract Background An implantable cardioverter-defibrillator (ICD) can cause high levels of anxiety and depression, resulting in negative effects on quality of life. Objectives To evaluate the quality of life, anxiety, and acceptance of the ICD using standardized measurement instruments and identify predictors of better responses for each of the outcomes studied. Method This is a prospective cohort study with patients undergoing initial ICD implantation or reoperation to maintain the device. The study outcomes included quality of life, anxiety, and acceptance of the ICD. The change in scores (30 and 180 days) was assessed using the minimal important difference (MID). Univariate analysis and the multivariate logistic regression model were used to identify predictors of better responses, adopting a significance level of 5%. Results A total of 147 patients were included between January/2020 to June/2021, with a mean age of 55.3 ± 13.4 years and a predominance of males (72.1%). The MID for quality of life, anxiety, and ICD acceptance were observed in 33 (22.4%), 36 (24.5%) and 43 (29.3%) patients, respectively. Age equal to or greater than 60 years (OR=2.5; 95%CI=1.14-5.53; p=0.022), absence of atrial fibrillation (OR=3.8; 95%CI=1.26-11.63; p=0.017) and female gender (OR=2.2; 95%CI=1.02-4.97; p=0.045) were independent predictors of better responses to quality of life, anxiety and acceptance of the ICD, respectively. Conclusion The identification of predictors for better quality of life scores, anxiety, and acceptance of the device can support the implementation of specific care for patients with a greater chance of presenting unfavorable results.

Cycling versus swapping strategies in psoriatic arthritis: results from the rheumatic diseases Portuguese register.

OBJECTIVE: To compare the 2-year retention rate between a second tumor necrosis factor alpha inhibitor (TNFi) and secukinumab (SEK) or ustekinumab (UST), in Psoriatic Arthritis (PsA) patients with previous inadequate response to their first TNFi. METHODS: Prospective longitudinal cohort study with a follow-up period of 2 years using the Nationwide Portuguese Reuma.pt database. Patients with a clinical diagnosis of PsA who also fulfill the CASPAR classification criteria, with previous treatment failure to a first-line TNFi and having started a second biotechnological drug (TNFi, SEK or UST) were included. The Cycling group was defined as switching from a first TNFi to a second TNFi, and the Swapping group as switching from a first TNFi to SEK or UST. Sociodemographic data, disease characteristics, disease activity scores and physical function at baseline and after 6, 12 and 24 months were recorded. Cox-proportional hazards regression was used to compare retention rates between Cycling and Swapping groups. To obtain a predictor model of 2-year discontinuation, a multivariable Cox regression model was performed. RESULTS: In total, 439 patients were included, 58% were female, with a mean age (standard deviation) of 49 (12) years. Globally, 75.6% initiated a second TNFi (Cycling group), and 24.4% started SEK/UST (Swapping group). The retention rates after 6, 12 and 24 months were 72%/66%/59% in the Cycling group; and 77%/66%/59% in the Swapping group. There were no significant differences in retention rates between both strategies (HR: 1.06, 95% CI 0.72-1.16). After 2 years of follow-up, 34.4% of patients discontinued their second biologic, mainly due to inefficacy (72.8%), with no differences found between groups. Baseline treatment with glucocorticoids was the only predictor of discontinuation after 2 years of follow-up (HR:1.668, 95% CI 1.154-2.409). CONCLUSIONS: After failure of a first TNF inhibitor, Cycling and Swapping strategies result in similar retention rates suggesting that both are acceptable in the management of patients with psoriatic arthritis.

Geographical Health District and Distance Traveled Influence on Clinical Status at Admission of Patients with Gestational Trophoblastic Disease.

OBJECTIVE: To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). METHODS: This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I-XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. RESULTS: This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (ß = 2.38 [0.87-3.88], p = 0.002) and XVI (ß = 0.78 [0.02-1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (ß = 3.32, 95% CI = 0.78-5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). CONCLUSION: Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

OBJETIVO: Avaliar a possível relação entre estado clínico na apresentação e distância percorrida a partir do distrito de saúde em mulheres com doença trofoblástica gestacional. MéTODOS: Estudo transversal incluindo mulheres com doença trofoblástica gestacional dos 17 distritos de saúde do estado de São Paulo (I­XVII), Brasil, encaminhadas ao Centro de Doenças Trofoblásticas de Botucatu (distrito VI), entre 1990 e 2018. Na admissão, avaliaram-se mola hidatiforme pelo sistema de pontuação de risco de Berkowitz et al. e neoplasia trofoblástica gestacional pelo escore de risco/estadiamento Federação Internacional de Ginecologia e Obstetrícia / Organização Mundial da Saúde (FIGO/OMS). Coletaram-se dados demográficos, clínicos e distância percorrida e análises de regressão múltipla foram realizadas. RESULTADOS: Este estudo incluiu 366 mulheres (335 mola hidatiforme, 31 neoplasia trofoblástica gestacional). O estado clínico na apresentação e distância percorrida diferiram significativamente entre o centro especializado e demais distritos. Nas pacientes encaminhadas pelos distritos IX (ß = 2,38 [0,87­3,88], p = 0,002) e XVI (ß = 0,78 [0,02­1,55], p = 0,045), os escores de mola hidatiforme foram maiores que no centro especializado. As pacientes com neoplasia trofoblástica gestacional do distrito XVI apresentaram escores FIGO 3,32 vezes maior que no centro especializado (ß = 3,32, 95% CI = 0,78­5,87, p = 0,010). A distância percorrida pelas pacientes dos distritos IX (200km) e XVI (203,5km) foi significativamente maior do que a percorrida pelas pacientes do centro especializado (76km). CONCLUSãO: Pacientes de distritos de saúde fora da cobertura do centro especializado apresentaram escores de risco mais alto para mola hidatiforme e para neoplasia trofoblástica gestacional na admissão. Longas distâncias (>80 km) pareceram influenciar negativamente o estado clínico da doença trofoblástica gestacional na apresentação, indicando barreiras no acesso a centros especializados.

Geographical Health District and Distance Traveled Influence on Clinical Status at Admission of Patients with Gestational Trophoblastic Disease / A influência do distrito de saúde e da distância viajada sobre o estado clínico na apresentação de pacientes com doença trofoblástica gestacional

Abstract Objective To assess the potential relationship of clinical status upon admission and distance traveled from geographical health district in women with gestational trophoblastic disease (GTD). Methods This is a cross-sectional study including women with GTD from the 17 health districts from the São Paulo state (I-XVII), Brazil, referred to the Botucatu Trophoblastic Disease Center (specialized center, district VI), between 1990 and 2018. At admission, hydatidiform mole was assessed according to the risk score system of Berkowitz et al. Gestational trophoblastic neoplasia was evaluated using the International Federation of Gynecology and Obstetrics / World Health Organization (FIGO/WHO) staging/risk score. Data on demographics, clinical status and distance traveled were collected. Multiple regression analyses were performed. Results This study included 366 women (335 hydatidiform mole, 31 gestational trophoblastic neoplasia). The clinical status at admission and distance traveled significantly differed between the specialized center district and other districts. Patients referred from health districts IX (β = 2.38 [0.87-3.88], p = 0.002) and XVI (β = 0.78 [0.02-1.55], p = 0.045) had higher hydatidiform mole scores than those from the specialized center district. Gestational trophoblastic neoplasia patients from district XVI showed a 3.32 increase in FIGO risk scores compared with those from the specialized center area (β = 3.32, 95% CI = 0.78-5.87, p = 0.010). Distance traveled by patients from districts IX (200km) and XVI (203.5km) was significantly longer than that traveled by patients from the specialized center district (76km). Conclusion Patients from health districts outside the specialized center area had higher risk scores for both hydatidiform mole and gestational trophoblastic neoplasia at admission. Long distances (>80 km) seemed to adversely influence gestational trophoblastic disease clinical status at admission, indicating barriers to accessing specialized centers.

Resumo Objetivo Avaliar a possível relação entre estado clínico na apresentação e distância percorrida a partir do distrito de saúde em mulheres com doença trofoblástica gestacional. Métodos Estudo transversal incluindo mulheres com doença trofoblástica gestacional dos 17 distritos de saúde do estado de São Paulo (I-XVII), Brasil, encaminhadas ao Centro de Doenças Trofoblásticas de Botucatu (distrito VI), entre 1990 e 2018. Na admissão, avaliaram-se mola hidatiforme pelo sistema de pontuação de risco de Berkowitz et al. e neoplasia trofoblástica gestacional pelo escore de risco/estadiamento Federação Internacional de Ginecologia e Obstetrícia / Organização Mundial da Saúde (FIGO/OMS). Coletaram-se dados demográficos, clínicos e distância percorrida e análises de regressão múltipla foram realizadas. Resultados Este estudo incluiu 366 mulheres (335 mola hidatiforme, 31 neoplasia trofoblástica gestacional). O estado clínico na apresentação e distância percorrida diferiram significativamente entre o centro especializado e demais distritos. Nas pacientes encaminhadas pelos distritos IX (β = 2,38 [0,87-3,88], p = 0,002) e XVI (β = 0,78 [0,02-1,55], p = 0,045), os escores de mola hidatiforme foram maiores que no centro especializado. As pacientes com neoplasia trofoblástica gestacional do distrito XVI apresentaram escores FIGO 3,32 vezes maior que no centro especializado (β = 3,32, 95% CI = 0,78-5,87, p = 0,010). A distância percorrida pelas pacientes dos distritos IX (200km) e XVI (203,5km) foi significativamente maior do que a percorrida pelas pacientes do centro especializado (76km). Conclusão Pacientes de distritos de saúde fora da cobertura do centro especializado apresentaram escores de risco mais alto para mola hidatiforme e para neoplasia trofoblástica gestacional na admissão. Longas distâncias (>80 km) pareceram influenciar negativamente o estado clínico da doença trofoblástica gestacional na apresentação, indicando barreiras no acesso a centros especializados.

Isolated massive histiocytes renal interstitial infiltration: a case report of an unexpected cause of acute kidney injury in a kidney transplant recipient.

BACKGROUND: Acute kidney injury is a frequent cause of hospital readmission in kidney transplant recipients (KTR), usually associated with infections and graft rejection. Herein, we report a case of an unusual cause of acute kidney injury in a KTR (massive histiocytes renal interstitial infiltration). CASE PRESENTATION: A 40-year-old woman was submitted to a second kidney transplant. One year after surgery, she presented asthenia, myalgia, and fever, haemoglobin 6.1 g/dL; neutrophils: 1.3 × 109/µL; platelets: 143 × 109/µL; blood creatinine 11.8 mg/dL, requiring dialysis. A kidney biopsy revealed diffuse histiocytic infiltration, which was assumed due to dysregulated immunological activation triggered by infections. The patient had multiple infections, including cytomegalovirus infection (CMV), aspergillosis, bacteraemia, and urinary tract infections, which could trigger the immune response. Haemophagocytic lymphohistiocytosis (HLH) was ruled out. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies. CONCLUSIONS: Renal histiocyte activation and infiltration may have been initiated by an immunological mechanism similar to what occurs in HLH and infectious processes. The present case highlights the occurrence of isolated massive renal interstitial infiltration of histiocytes that does not meet the criteria for HLH or other related pathologies.

Prevalence of psychoactive substance use by adolescents in public schools in a municipality in the São Paulo Metropolitan Area, Brazil.

This study aimed to estimate the prevalence of psychoactive substance use by adolescents from public schools. This is a cross-sectional study that used a random sample of adolescents from five public schools located in a municipality in the central-west region of the São Paulo Metropolitan Area, Brazil. Information on demographic, socioeconomic, and drug use was collected using self-report questionnaires. The sample consisted of 1,460 students, 716 (49%) males, aged 10-19 years (13.19±2.04 years). The prevalence of psychoactive substance use in the last month was 51% for analgesics; 48.8% for alcohol; 37.3% for tobacco; 30.8% for tranquilizers; 23.1% for marijuana; 22.6% for anabolic steroids; 21.6% for ecstasy; 15.3% for amphetamines/stimulants; 13.4% for phencyclidine; 12.9% for cocaine/crack; 12.6% for inhalants/solvents; 11.5% for opiates; 11.4% for hallucinogens; and 16.2% for other unclassified drugs. Elementary and middle school students were more likely to consume tobacco (OR = 2.306; 95%CI: 1.733-3.068; p < 0.001), and male students were more likely to consume any type of substance. We identified a high use of psychoactive substances among this study participants, with a higher prevalence among male students.

Pinch size can affect the skinfold thickness measurement and interfere in the estimation and classification of body adiposity / O tamanho da pinça pode afetar a medida de espessura das dobras cutâneas e interferir na estimativa e classificação da adiposidade corporal

Abstract The aim of this study was to verify the effect of pinch size on skinfold thickness measurement and the consequent interference in the estimation and classification of body adiposity components. Cross-sectional and quantitative study carried out with a sample of 29 subjects recruited from a university in the city of Fortaleza, Ceará, Brazil. Four measurement steps were performed at each site of the eight chosen skinfolds. The first step was performed with a subjective-landmark and the three subsequent steps with fixed-landmarks defined with an expanding secondary line at 2 cm intervals. Body adiposity components were determined from the skinfold thickness measured at each landmark. Repeated measures ANOVA and Bland-Altman agreement analysis were applied. The subjective-landmark was chosen as the dependent variable. The 6 cm-landmark showed similarity and statistical agreement with the subjective-landmark for all skinfolds except the thigh, and with the sums of five and eight skinfolds. All fixed-landmarks showed agreement below the cut-off point for the percentile classification of subcutaneous adiposity and normative relative body fat. Variation in pinch size is an important source of TEM that can affect the reproducibility of skinfold thickness measurements and interfere in the estimation and classification of the molecular and tissue component of body adiposity.

Resumo O objetivo deste estudo foi verificar o efeito do tamanho da pinça na medida de espessura das dobras cutâneas e a consequente interferência na estimativa e classificação dos componentes da adiposidade corporal. Estudo transversal e quantitativo realizado com amostra de 29 sujeitos recrutados em uma universidade da cidade de Fortaleza, Ceará, Brasil. Quatro etapas de medição foram realizadas em cada sítio das oito dobras cutâneas escolhidas. A primeira etapa foi realizada com um marco subjetivo e as três etapas subsequentes com marcos fixos definidos com uma linha secundária expansiva em intervalos de 2 cm. Os componentes da adiposidade corporal foram determinados a partir da espessura de dobras cutâneas mensuradas em cada marco. ANOVA de medidas repetidas e análise de concordância de Bland-Altman foram aplicadas. O marco subjetivo foi escolhido como variável dependente. O marco de 6 cm apresentou semelhança e concordância estatística com o marco subjetivo para todas as dobras cutâneas, exceto a coxa, e com as somas de cinco e oito espessuras de dobras cutâneas. Todos os marcos fixos mostraram concordância abaixo do ponto de corte para a classificação percentílica de adiposidade subcutânea e gordura corporal relativa normativa. A variação no tamanho da pinça é uma importante fonte de ETM que pode afetar a reprodutibilidade de medida de espessura das dobras cutâneas e interferir na confiabilidade da estimativa e classificação do componente molecular e tecidual da adiposidade corporal.

Prevalence of psychoactive substance use by adolescents in public schools in a municipality in the São Paulo Metropolitan Area, Brazil / Prevalência do uso de substâncias psicoativas por adolescentes em escolas públicas de um município da Região Metropolitana de São Paulo, Brasil / Prevalencia de consumo de sustancias psicoactivas en adolescentes en escuelas públicas de un municipio de la Región Metropolitana de São Paulo, Brasil

This study aimed to estimate the prevalence of psychoactive substance use by adolescents from public schools. This is a cross-sectional study that used a random sample of adolescents from five public schools located in a municipality in the central-west region of the São Paulo Metropolitan Area, Brazil. Information on demographic, socioeconomic, and drug use was collected using self-report questionnaires. The sample consisted of 1,460 students, 716 (49%) males, aged 10-19 years (13.19±2.04 years). The prevalence of psychoactive substance use in the last month was 51% for analgesics; 48.8% for alcohol; 37.3% for tobacco; 30.8% for tranquilizers; 23.1% for marijuana; 22.6% for anabolic steroids; 21.6% for ecstasy; 15.3% for amphetamines/stimulants; 13.4% for phencyclidine; 12.9% for cocaine/crack; 12.6% for inhalants/solvents; 11.5% for opiates; 11.4% for hallucinogens; and 16.2% for other unclassified drugs. Elementary and middle school students were more likely to consume tobacco (OR = 2.306; 95%CI: 1.733-3.068; p < 0.001), and male students were more likely to consume any type of substance. We identified a high use of psychoactive substances among this study participants, with a higher prevalence among male students.

O objetivo foi estimar a prevalência de uso de substâncias psicoativas por adolescentes de escolas públicas. Trata-se de um estudo transversal com uma amostra aleatória de adolescentes de cinco escolas públicas localizadas em um município da zona centro-oeste da Região Metropolitada de São Paulo, Brasil. Informações sobre as características demográficas, socioeconômicas e de uso de drogas foram coletadas por meio de questionários autorreferidos. A amostra foi composta por 1.460 estudantes, sendo 716 (49%) meninos, com idade entre 10 e 19 anos (13,19±2,04 anos). A prevalência de uso de substâncias psicoativas no último mês foi de 51,0% para analgésicos; álcool 48,8%; tabaco 37,3%; tranquilizantes 30,8%; maconha 23,1%; esteroides anabolizantes 22,6%; ecstasy 21,6%; anfetaminas/estimulantes 15,3%; fenciclidina 13,4%; cocaína/crack 12,9%; inalantes/solventes 12,6%; opiáceos 11,5%; alucinógenos 11,4%; e outras drogas não classificadas 16,2%. Alunos do Ensino Fundamental foram mais propensos a consumir tabaco (OR = 2,306; IC95%: 1,733-3,068; p < 0,001), e os estudantes do sexo masculino foram mais propensos a consumir qualquer tipo de substância. Identificou-se um alto uso de substâncias psicoativas entre os participantes deste estudo, com maior prevalência entre os estudantes do sexo masculino.

El objetivo de este estudio fue estimar la prevalencia de consumo de sustancias psicoactivas por adolescentes de escuelas públicas brasileñas. Se trata de un estudio transversal, realizado con una muestra aleatoria de adolescentes de cinco escuelas públicas, ubicadas en una ciudad de la región centro-oeste de la Región Metropolitana de São Paulo, Brasil. La información sobre las características demográficas, socioeconómicas y de consumo de drogas se recabó de cuestionarios autoinformados. La muestra estuvo compuesta por 1.460 estudiantes; 716 (49%) de los cuales eran varones, con edades entre 10 y 19 años (13,19±2,04 años). La prevalencia de consumo de sustancias psicoactivas en el último mes fue: para analgésicos 51%; alcohol 48,8%; tabaco 37,3%; tranquilizantes 30,8%; marihuana 23,1%; esteroides anabólicos 22,6%; éxtasis 21,6%; anfetaminas/estimulantes 15,3%; fenciclidina 13,4%; cocaína/crack 12,9%; inhalantes/disolventes 12,6%; opiáceos 11,5%; alucinógenos 11,4%; y otras drogas no clasificadas 16,2%. Los estudiantes de primaria fueron los más propensos a consumir tabaco (OR = 2,306; IC95%: 1,733-3,068; p < 0,001), y los varones los más propensos a consumir cualquier tipo de sustancia. Se identificó un alto consumo de sustancias psicoactivas entre los participantes, con mayor prevalencia entre los estudiantes del sexo masculino.

Paricalcitol Improves the Angiopoietin/Tie-2 and VEGF/VEGFR2 Signaling Pathways in Adriamycin-Induced Nephropathy.

Renal endothelial cell (EC) injury and microvascular dysfunction contribute to chronic kidney disease (CKD). In recent years, increasing evidence has suggested that EC undergoes an endothelial-to-mesenchymal transition (EndoMT), which might promote fibrosis. Adriamycin (ADR) induces glomerular endothelial dysfunction, which leads to progressive proteinuria in rodents. The activation of the vitamin D receptor (VDR) plays a crucial role in endothelial function modulation, cell differentiation, and suppression of the expression of fibrotic markers by regulating the production of nitric oxide (NO) by activating the endothelial NO synthase (eNOS) in the kidneys. This study aimed to evaluate the effect of paricalcitol treatment on renal endothelial toxicity in a model of CKD induced by ADR in rats and explore mechanisms involved in EC maintenance by eNOS/NO, angiopoietins (Angs)/endothelium cell-specific receptor tyrosine kinase (Tie-2, also known as TEK) and vascular endothelial growth factor (VEGF)-VEGF receptor 2 (VEGFR2) axis. The results show that paricalcitol attenuated the renal damage ADR-induced with antiproteinuric effects, glomerular and tubular structure, and function protection. Furthermore, activation of the VDR promoted the maintenance of the function and structure of glomerular, cortical, and external medullary endothelial cells by regulating NO production. In addition, it suppressed the expression of the mesenchymal markers in renal tissue through attenuation of (transforming growth factor-beta) TGF-ß1/Smad2/3-dependent and downregulated of Ang-2/Tie-2 axis. It regulated the VEGF/VEGFR2 pathway, which was ADR-deregulated. These effects were associated with lower AT1 expression and VDR recovery to renal tissue after paricalcitol treatment. Our results showed a protective role of paricalcitol in the renal microvasculature that could be used as a target for treating the beginning of CKD.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

Effect of Microencapsulation on Chemical Composition and Antimicrobial, Antioxidant and Cytotoxic Properties of Lemongrass (Cymbopogon flexuosus) Essential Oil.

Research background: Lemongrass (Cymbopogon flexuosus) essential oil exhibits antimicrobial and antioxidant properties due to the presence of α-citral and ß-citral. Essential oils are susceptible to volatilization and oxidation when applied to food matrices. Therefore, a barrier is needed to protect this material. The present study aims to produce microparticles containing lemongrass essential oil, with gum arabic and maltodextrin using spray drying technology. Experimental approach: Lemongrass essential oil was extracted by the hydrodistillation method and later microencapsulated with different wall materials. Free and microencapsulated lemongrass essential oil was evaluated for the cytotoxic activity (using Artemia salina as test sample), chemical composition (GC-MS), encapsulation efficiency, antioxidant activity (DPPH, ABTS and FRAP), antimicrobial activity and minimum inhibitory concentration. Results and conclusions: The lethal concentration (LC50) of lemongrass essential oil in the cytotoxic test was 8.43 µg/mL against Artemia salina; a high activity that can be associated with the presence of α-citral (~33%) and ß-citral (~21%) in the samples, since these were the main compounds with bioactive properties. The highest value of microencapsulation efficiency (88.11%) was obtained when only gum arabic was used as wall material. In general, the microparticles showed satisfactory antioxidant activity (expressed as Trolox equivalents, between 348.66 and 2042.30 µmol/100 g) and bactericidal effect in vitro against Gram-positive and Gram-negative microorganisms. In conclusion, the microencapsulated lemongrass essential oil is a promising functional additive in the food and pharmaceutical industries. Novelty and scientific contribution: This study shows that microparticles containing lemongrass essential oil can be prepared using gum arabic and maltodextrin as wall materials by spray drying, resulting in high microencapsulation efficiency. The drying process maintained the antimicrobial and antioxidant properties of the essential oil. Therefore, the microencapsulated lemongrass essential oil is considered a natural, functional and promising additive in the food industry. Its antimicrobial action can increase the shelf life of fresh and semi-fresh products such as cheese, yogurts and meat products. In addition, its antioxidant action can delay the lipid and protein oxidation in food products.

Artificial intelligence and its impact on the domains of universal health coverage, health emergencies and health promotion: An overview of systematic reviews.

BACKGROUND: Artificial intelligence is fueling a new revolution in medicine and in the healthcare sector. Despite the growing evidence on the benefits of artificial intelligence there are several aspects that limit the measure of its impact in people's health. It is necessary to assess the current status on the application of AI towards the improvement of people's health in the domains defined by WHO's Thirteenth General Programme of Work (GPW13) and the European Programme of Work (EPW), to inform about trends, gaps, opportunities, and challenges. OBJECTIVE: To perform a systematic overview of systematic reviews on the application of artificial intelligence in the people's health domains as defined in the GPW13 and provide a comprehensive and updated map on the application specialties of artificial intelligence in terms of methodologies, algorithms, data sources, outcomes, predictors, performance, and methodological quality. METHODS: A systematic search in MEDLINE, EMBASE, Cochrane and IEEEXplore was conducted between January 2015 and June 2021 to collect systematic reviews using a combination of keywords related to the domains of universal health coverage, health emergencies protection, and better health and wellbeing as defined by the WHO's PGW13 and EPW. Eligibility criteria was based on methodological quality and the inclusion of practical implementation of artificial intelligence. Records were classified and labeled using ICD-11 categories into the domains of the GPW13. Descriptors related to the area of implementation, type of modeling, data entities, outcomes and implementation on care delivery were extracted using a structured form and methodological aspects of the included reviews studies was assessed using the AMSTAR checklist. RESULTS: The search strategy resulted in the screening of 815 systematic reviews from which 203 were assessed for eligibility and 129 were included in the review. The most predominant domain for artificial intelligence applications was Universal Health Coverage (N = 98) followed by Health Emergencies (N = 16) and Better Health and Wellbeing (N = 15). Neoplasms area on Universal Health Coverage was the disease area featuring most of the applications (21.7 %, N = 28). The reviews featured analytics primarily over both public and private data sources (67.44 %, N = 87). The most used type of data was medical imaging (31.8 %, N = 41) and predictors based on regions of interest and clinical data. The most prominent subdomain of Artificial Intelligence was Machine Learning (43.4 %, N = 56), in which Support Vector Machine method was predominant (20.9 %, N = 27). Regarding the purpose, the application of Artificial Intelligence I is focused on the prediction of the diseases (36.4 %, N = 47). With respect to the validation, more than a half of the reviews (54.3 %, N = 70) did not report a validation procedure and, whenever available, the main performance indicator was the accuracy (28.7 %, N = 37). According to the methodological quality assessment, a third of the reviews (34.9 %, N = 45) implemented methods for analysis the risk of bias and the overall AMSTAR score below was 5 (4.01 ± 1.93) on all the included systematic reviews. CONCLUSION: Artificial intelligence is being used for disease modelling, diagnose, classification and prediction in the three domains of GPW13. However, the evidence is often limited to laboratory and the level of adoption is largely unbalanced between ICD-11 categoriesand diseases. Data availability is a determinant factor on the developmental stage of artificial intelligence applications. Most of the reviewed studies show a poor methodological quality and are at high risk of bias, which limits the reproducibility of the results and the reliability of translating these applications to real clinical scenarios. The analyzed papers show results only in laboratory and testing scenarios and not in clinical trials nor case studies, limiting the supporting evidence to transfer artificial intelligence to actual care delivery.

Pâncreas ectópico: provocando gastrite e baixo peso / Ectopic pancreas: producing gastritis and low weight

O pâncreas ectópico é uma anomalia congênita rara representada por um aglomerado de tecido pancreático aberrante fora de seu lugar anatômico natural, visto em qualquer época da vida. A localização mais frequente é o duodeno ou tecido gástrico. Suas manifestações clínicas são inespecíficas e podem dificultar o diagnóstico. A ectopia pancreática pode ser vista também em outros órgãos ou regiões extra-abdominais como, por exemplo, no pulmão, mediastino e no umbigo. A incidência do pâncreas ectópico em achados de necropsias varia entre 0,6 a 5,6%. O autor relata um caso de um paciente com pâncreas ectópico localizado no antro gástrico que provocava sintomatologia gastrointestinal associado a baixo peso e faz uma breve revisão da literatura. [au]

Ectopic pancreas is a rare congenital anomaly represented by a cluster of aberrant pancreatic tissue outside its natural anatomical place seen at any time in life. The most frequent location is the duodenum or gastric tissue. Its clinical manifestations are nonspecific and can make diagnosis difficult. Pancreatic ectopy can also be seen in other organs or extra-abdominal regions, for example, in the lung, mediastinum and umbilicus. The incidence of ectopic pancreas in necropsy findings ranges from 0.6 to 5.6%. The author reports the case of a patient with ectopic pancreas located in the gastric antrum and reviews the literature. [au]

Modulatory effect of two regimens of magnesium sulfate on the systemic inflammatory response in pregnant women with imminent eclampsia.

OBJECTIVE: This study compared the modulatory effect of two intravenous magnesium sulfate (MgSO4) regimens on the systemic inflammatory response in pregnant women diagnosed with imminent eclampsia. STUDY DESIGN: In a single-blind cross-sectional study, 33 women were allocated according to the Zuspan (n = 16) and Sibai (n = 17) MgSO4 regimens, and treated for 24 h. Blood samples were collected pre-administration of the loading dose, at 24 h of the maintenance dose of MgSO4, and at 48 h, when patients were without treatment. Plasma was used to determine interleukin (IL)-1 beta (IL-1ß), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), heat shock protein (Hsp70), and heme oxygenase-1 (HO-1) by ELISA. RESULTS: The treatment with the Zuspan's regimen didn't change plasma concentrations of TNF-α, IL-10, and Hsp70 in the three-time points studied. However, it decreased IL-1ß at 24 h and 48 h and IL-6 at 48 h, and increased HO-1 concentration at 48 h. On the other hand, compared to the pre-treatment period, Sibai's regimen induced a significant decrease in TNF-α, IL-1ß, IL-6, and Hsp70, while increased HO-1 levels both at 24 h and 48 h and, IL-10 concentration at 48 h. CONCLUSIONS: Sibai's regimen determined an early and efficient immunoregulatory effect on systemic inflammatory response in preeclampsia, suggesting that the maintenance dose of two grams of MgSO4 was better than one gram in the treatment of imminent eclampsia.

Characteristics and outcomes of autologous hematopoietic stem cell transplant recipients admitted to intensive care units: A multicenter study.

PURPOSE: Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission. METHODS: This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders. RESULTS: We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82-17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77-2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63-2.66) were not. CONCLUSIONS: In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

Fatores determinantes para a excelência no vôlei de praia: o caso de uma dupla de elite / Determining factors for excellence in beach volleyball: the case of an elite pai / Factores determinantes de laexcelenciaenel voleibol de playa: el caso de una pareja de élite

O objetivo deste estudo foi conhecer os fatores determinantes na aquisição, desenvolvimento e manutenção da excelência no Vôlei de Praia (VP) a partir da percepção de uma dupla de atletas de elite e seu técnico. Trata-se de um estudo de caso com abordagem qualitativa dos resultados que se utilizou da entrevista e análise documental para recolha dos dados. Sobre os fatores determinantes da excelência no VP destacaram-se nos fatores primários, o aspecto psicológico, verificado nos elementos disciplina, força de vontade, motivação e foco, seguido pelo tempo de parceria e da preparação física iniciada (prática deliberada). Enquanto nos fatores secundários, o apoio, técnico, infraestrutura, qualidade de material esportivo e financeiro. Conclui-se que a junção dos fatores primários e secundários descritos acima foi essencial para aquisição, desenvolvimento emanutenção da excelência no VP.

The objective of this study was to know the determining factors in the acquisition, development and maintenance of excellence in Beach Volleyball (VP) from the perception of a pair of elite athletes and theircoach. This is a case study with a qualitative approach to the results that used the interview and document analysis for data collection. Regarding the determining factors of excellence in the VP, the psychological aspect stood out in the primary factors,verified in the elements discipline, willpower, motivation and focus, followed by the partnership time and the physical preparation started (deliberate practice). While in secondary factors, support, technical, infrastructure, quality of sports and financial equipment. It is concluded that the combination of the primary and secondary factors described above was essential for the acquisition, development and maintenance of excellence in PV.

El propósito de este estudio fue conocer los factores determinantes en la adquisición, desarrollo y mantenimiento de la excelencia en el Voleibol de Playa (VP) a partir de la percepción de una pareja de deportistas de élite y su entrenador. Este es un estudio de caso con enfoque cualitativo de los resultados que utilizó la entrevista y el análisis de documentos para la recolección de datos. En cuanto a los determinantes de la excelencia en la PV, el aspecto psicológico se destacó en los factores primarios, verificado en los elementos disciplina, fuerza de voluntad, motivación y enfoque, seguido del tiempo de compañerismo y la preparación física iniciada (práctica deliberada). Mientras que en factores secundarios, soporte, técnico, infraestructura, calidad del equipamiento deportivo y financiero. Se concluye que la combinación de los factores primarios y secundarios descritos anteriormente fue fundamental para la adquisición, desarrollo y mantenimiento de la excelencia en el VP.