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Background Asthma and chronic obstructive pulmonary disease (COPD) are the most common respiratory diseases, presenting overlapping prevalence with age. Mepolizumab is a humanized monoclonal antibody targeting interleukin-5. In major randomized clinical trials, this antibody reportedly reduced the circulating eosinophil count, exacerbation rate, and oral corticosteroid (OCS) dosage in patients with severe eosinophilic asthma. However, data regarding the efficacy of mepolizumab in elderly patients with asthma and overlapping COPD are limited. Methods This was a single-center, retrospective, observational study. Elderly patients (age ≥65 years) administered mepolizumab between August 2016 and March 2019 were enrolled and the effects of mepolizumab on the eosinophil level, exacerbation numbers, OCS dosage, and lung functions were assessed. We compared treatment responses in patients with asthma and COPD overlap (ACO) with responses observed in patients with severe asthma alone. Adverse events were also evaluated. Results Twenty patients (10 men and 10 women), with a mean age of 77.5 ± 1.3 years, were included. Mepolizumab significantly reduced the blood eosinophil count, as well as significantly decreased clinically significant exacerbation, in both populations. The OCS dosage was significantly reduced in patients treated receiving maintenance OCS therapy. However, mepolizumab did not improve lung function in either population, and no significant difference was observed in treatment responses between patients with asthma alone and ACO. Conclusions Mepolizumab may be effective in elderly patients with eosinophilic asthma and ACO.

Rationale: Cancer phosphoproteomics can provide insights regarding kinases that can be targeted for therapeutic applications. Monitoring the phosphoproteomics in cancer is expected to play a key role in optimizing treatments with kinase inhibitors. Clinical phosphoproteomics in surgical tissues and patient-derived models has been studied intensively. However, the reported data may not accurately reflect the phosphosignaling status in patients due to the effect of ischemia occurring during surgery or changes in the characteristics of cancer cells when establishing the models. In contrast, endoscopic biopsies have an advantage for clinical phosphoproteomics because they can be rapidly cryo-preserved. We aimed to develop a highly sensitive method for phosphoproteomics in endoscopic biopsies of gastric cancer. Methods: Three tumor biopsies and three normal gastric biopsies were obtained by endoscopy at one time, and subjected to our optimized phosphoproteomics. Phosphopeptides were enriched with an immobilized metal affinity chromatography, and labeled with Tandem Mass Tag reagent. Quantified phosphosites were compared between the pairs of tumor/normal biopsies within same patient. Cancer-specific activated pathways and kinases were identified by pathway enrichment analysis and kinase-substrate enrichment analysis. Results: Our protocol enabled the identification of more than 10,000 class 1 phosphosites from endoscopic biopsies. A comparison between samples from cancer tissue and normal mucosa demonstrated differences in the phosphosignaling, including biomarkers of response to DNA damage. Finally, cancer-specific activation of DNA damage response signaling was validated by additional phosphoproteomics of other patients and western blotting of gastric cancer/normal cells. Conclusion: In summary, our pioneering approach will facilitate more accurate clinical phosphoproteomics in endoscopic biopsies, which can be applied to monitor the activities of therapeutic kinases and, ultimately, can be a useful tool to precision medicine.

Background Aggregation of solid-phase calcium–phosphate and fetuin-A form nanoparticles called calciprotein particles (CPP). Serum CPP levels are increased in CKD patients and correlated with vascular stiffness and calcification. In this study, we evaluated effects of lanthanum carbonate (LC) and calcium carbonate (CC) on serum CPP levels in hemodialysis (HD) patients. Methods Twenty-four (24) HD patients (50% men, age; 68 ± 12 years, dialysis period; 6.2 ± 4.8 years, Kt/v; 1.74 ± 0.34) were treated with CC during 0–8 weeks and then switched to LC during 9–16 weeks. Blood samples were obtained at 0, 8, 16 weeks. Serum CPP levels (TCPP) were measured by the gel-filtration method. Low-density CPP (LCPP) levels were determined by centrifuging the serum samples at 16,000 g for 2 h and measuring CPP levels in the supernatant. The difference between TCPP and LCPP was defined as the high-density CPP (HCPP) level. We evaluated association of TCPP, LCPP, and HCPP with serum calcium (Ca), phosphorus (P), intact PTH, FGF23, Klotho, fetuin-A, aortic calcification index (ACI), LDL cholesterol, and hs-CRP. Results TCPP and LCPP levels were significantly decreased after switching CC to LC, whereas Ca and P levels were not changed. HCPP levels were below the lower limit quantification in all patients. The changes in P, Ca × P, LDL cholesterol, but not ACI and the changes in hs-CRP, were correlated with the change in TCPP levels. Conclusion The TCPP levels were significantly decreased after switching CC to LC. Non-calcium-containing phosphate binders may be preferable for lowering CPP levels.

Tachycardia is common in intensive care units (ICUs). It is unknown whether tachycardia or prolonged tachycardia affects patient outcomes. We investigated the association between tachycardia and mortality in critically ill patients. This retrospective cohort study’s primary outcome was patient mortality in the ICU and the hospital. We stratified the patients (n=476) by heart rate (HR) as LowHR, MediumHR, and HighHR groups. We also stratified them by their durations of HR >100 (prolonged HR; tachycardia): MildT, ModerateT, and SevereT groups. We determined the six groups’ mortality. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; significantly higher in the HighHR vs. LowHR group. The in-hospital mortality rates of these groups were 1%, 4.5%, and 14.6%, respectively; significantly higher in the HighHR vs. LowHR group. The ICU mortality rates of the MildT, ModerateT, and SevereT groups were 0.9%, 5.6%, and 57.1%, respectively. The mortality of the HRT=0 (i.e., all HR ≤ 100) patients was 0%. The in-hospital mortality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT=0 patients was 0.5%. Both higher HR and prolonged tachycardia were associated with poor outcomes.

Atherosclerosis is a chronic inflammatory disease associated with macrophage aggregate and transformation into foam cells. In this study, we sought to investigate the impact of dietary intake of ω3 fatty acid on the development of atherosclerosis, and demonstrate the mechanism of action by identifying anti-inflammatory lipid metabolite. Mice were exposed to a high-fat diet (HFD) supplemented with either conventional soybean oil or α-linolenic acid-rich linseed oil. We found that as mice became obese they also showed increased pulsatility and resistive indexes in the common carotid artery. In sharp contrast, the addition of linseed oil to the HFD improved pulsatility and resistive indexes without affecting weight gain. Histological analysis revealed that dietary linseed oil inhibited foam cell formation in the aortic valve. Lipidomic analysis demonstrated a particularly marked increase in the eicosapentaenoic acid-derived metabolite 12-hydroxyeicosapentaenoic acid (12-HEPE) in the serum from mice fed with linseed oil. When we gave 12-HEPE to mice with HFD, the pulsatility and resistive indexes was improved. Indeed, 12-HEPE inhibited the foamy transformation of macrophages in a peroxisome proliferator-activated receptor (PPAR)γ-dependent manner. These results demonstrate that the 12-HEPE-PPARγ axis ameliorates the pathogenesis of atherosclerosis by inhibiting foam cell formation.

Background Breastfeeding and adequate complementary feeding in the first years of life provide short- and long-term benefits for child health. However, breastfeeding and adequate complementary feeding prevalence's are low. In Brazil, the Estratégia Amamenta e Alimenta Brasil (EAAB) aims to improve the quality of the assistance provided by primary healthcare teams to ultimately improving infant feeding practices in the Brazilian population. In primary healthcare units, continuing education in breastfeeding and complementary feeding is facilitated by EAAB tutors. A Manual to Support EAAB Tutor (the Manual) was developed following a problem-based learning methodology. This study aimed to evaluate the effectiveness of using the Manual by analyzing exclusive breastfeeding and complementary feeding indicators. Methods A before and after study was conducted at primary healthcare units in Embu das Artes, Brazil. The intervention consisted in the use of the Manual by EAAB tutors who performed some comprehensive training activities with healthcare teams, in a period of 8 months. Subjects consisted of mothers of infants under one year of age attended at primary healthcare units. 561 mothers before and 598 mothers after intervention were interviewed about breastfeeding and complementary feeding practices. Multivariate analysis was performed using Poisson multilevel regression to test the hypothesis. Results Lack of minimum food diversity (before 62.9%; after 50.3%) and lack of food adequacy (before 77.5%; after 63.3%) decreased significantly. Regression analysis confirmed that infants after the intervention had lower prevalence of inadequacy of complementary feeding. While the intervention did not show significant association with exclusive breastfeeding, it showed association with the improvement of complementary feeding practices. Conclusions The Manual is a continuing educational strategy that improved complementary feeding practices in primary health care. Key messages The use of a continuing education strategy grounded on a problem-based learning methodology was effective to produce improvements in complementary feeding practices in primary health care. The 'Manual to Support EAAB Tutor' consists of a tool that has the potential to be adapted for different contexts and easy to disclose to all EAAB tutors in the country.

Little is known about the role of a strong ions in humans with respiratory abnormalities. In this study, we investigated the associations between partial carbon dioxide pressure (pCO2) and each of sodium ion (Na+) concentrations, chloride ion (Cl−) concentrations and their difference (SIDNa-Cl). Blood gas data were obtained from patients in a teaching hospital intensive care unit between August 2013 and January 2017. The association between pCO2 and SIDNa-Cl was defined as the primary outcome. The associations between pCO2 and [Cl−], [Na+] and other strong ions were secondary outcomes. pCO2 was stratified into 10 mmHg-wide bands and treated as a categorical variable for comparison. As a result, we reviewed 115,936 blood gas data points from 3,840 different ICU stays. There were significant differences in SIDNa-Cl, [Cl−], and [Na+] among all categorized pCO2 bands. The respective pCO2 SIDNa-Cl, [Cl−], and [Na+] correlation coefficients were 0.48, −0.31, and 0.08. SIDNa-Cl increased and [Cl−] decreased with pCO2, with little relationship between pCO2 and [Na+] across subsets. In conclusion, we found relatively strong correlations between pCO2 and SIDNa-Cl in the multiple blood gas datasets examined. Correlations between pCO2 and chloride concentrations, but not sodium concentrations, were further found to be moderate in these ICU data.

Purpose: Taletrectinib (DS-6051b/AB-106) is an oral, tyrosine kinase inhibitor of ROS1 and NTRK with potent preclinical activity against ROS1 G2032R solvent-front mutation among others. We report the first-in-human U.S. phase I results of taletrectinib. Patients and Methods: Patients ≥18 years old with neuroendocrine tumors, with tumor-induced pain, or tumors harboring ROS1/NTRK rearrangements were eligible. Accelerated titration followed by modified continuous reassessment method and escalation with overdose control was used (50–1,200 mg once daily or 400 mg twice daily). Primary objectives were safety/tolerability, and MTD determination. Secondary objectives were food-effect pharmacokinetics and antitumor activity. Results: A total of 46 patients were enrolled. Steady-state peak concentration (Cmax) and exposure (AUC0-8) increased dose dependently from 50-mg to 800-mg once-daily doses. The ratio of the geometric mean of AUC0-24 between low-fat-diet-fed/fasted state was 123% (90% confidence interval, 104%–149%). Dose-limiting toxicities (grade 3 transaminases increase) occurred in two patients (1,200-mg once-daily dose). MTD was 800 mg once daily. Most common treatment-related adverse events were nausea (47.8%), diarrhea (43.5%), and vomiting (32.6%). Pain score reductions were observed in the 800-mg once-daily dose cohort. Confirmed objective response rate was 33.3% among the six patients with RECIST-evaluable crizotinib-refractory ROS1+ NSCLC. One patient with TPM3-NTRK1 differentiated thyroid cancer achieving a confirmed partial response of 27 months at data cutoff. We identified a cabozantinib-sensitive ROS1 L2086F as an acquired taletrectinib-resistance mutation. Conclusions: Taletrectinib has manageable toxicities at the MTD of 800 mg daily. Preliminary efficacy was observed in patients with crizotinib-refractory ROS1+ NSCLC.

BACKGROUND Overactive bladder (OAB) is a symptomatic syndrome defined by urinary urgency, usually accompanied by increased urination frequency and nocturia, with or without urinary incontinence. The prevalence of pediatric OAB in 5-13 year olds is as high as 16.6%, but the pathophysiology and epidemiology have not been sufficiently elucidated. METHODS We retrospectively reviewed medical records in 117 children with OAB aged between 5 and 15 years during the years 2012-2016. At initial presentation, abdominal ultrasound and uroflowmetry were performed, and behavioral modifications, such as timed voiding, and constipation therapy were initiated. If there was no response after 4 weeks, antimuscarinic treatment was added. We evaluated the clinical features of OAB and factors related to the recovery period, which was defined as the period from the start of behavioral modifications to cure. RESULTS The average recovery period was 11.9 ± 9.73 months. There was no significant difference in the recovery period according to age, gender, percentage of urination frequency, nocturnal enuresis, or constipation. The recovery period was significantly shorter in the group with bladder wall thickness ≥5 mm than with bladder wall thickness

To verify the type of milk consumed by children under one year of age and identify variables associated with non-maternal milk consumption (formula or cow milk).Cross-sectional study developed during the 2012 National Vaccination Campaign against Poliomyelitis. The companions of 935 children under one year of age answered a structured questionnaire on the child's diet in the last 24 hours. The estimates are presented by points, with 95%CI. F-statistics were used to check for differences in the proportion of the types of milk consumption according to the children's age range (6 months and 6-11 months) and the association between non-maternal milk consumption and the study variables.The consumption of maternal milk and child formula was higher for children under six months of age - corresponding to 82.8% (95%CI 78.5-86.3) and 70.4% (95%CI 61.4-78.0), respectively -, whereas the consumption of cow milk was higher among children between 6 and 11 months of age - 74.2% (95%CI 66.5-80.6) -, with differences in the consumption proportions (p0.0001). The variables associated with higher cow milk consumption were lower maternal education (p0.0001), the fact that the mother does not have a paid occupation (p=0.0015), child doctor's appointment in the public health network (p0.0001) and participation in the Child's Milk Program (p0.0001).The infants received cow's milk early (before the first year of life), especially children from families with lower socioeconomic levels and children who took part in a specific social program for milk distribuition.Verificar o tipo de leite consumido por crianças menores de um ano de idade e identificar variáveis associadas ao consumo de leite não materno (LNM) - fórmula infantil ou leite de vaca (LV).Estudo transversal realizado durante a Campanha Nacional de Vacinação contra Poliomielite 2012. Os acompanhantes de 935 crianças menores de um ano responderam a um questionário estruturado sobre a alimentação da criança nas últimas 24 horas. As estimativas são apresentadas por pontos e intervalo de confiança de 95% (IC95%). Adotou-se a estatística F para verificar diferenças na proporção de consumo dos tipos de leite segundo a faixa etária das crianças (6 meses e 6-11 meses) e a associação entre o consumo de leite não materno e as variáveis estudadas.O consumo de leite materno e fórmula infantil foi maior entre as crianças menores de 6 meses - sendo 82,8% (IC95% 78,5-86,3) e 70,4% (IC95% 61,4-78,0), respectivamente -, enquanto o de leite de vaca foi maior entre as crianças de 6 a 11 meses - 74,2% (IC95% 66,5-80,6) -, com diferenças nas proporções de consumo (p0,0001). As variáveis associadas ao maior consumo de leite de vaca foram: menor escolaridade materna (p0,0001), o fato de a mãe não trabalhar fora (p=0,0015), a criança consultar na rede pública de saúde (p0,0001) e participar do Programa Leite das Crianças - PLC (p0,0001).As crianças receberam leite de vaca precocemente (antes do primeiro ano de vida), em especial aquelas pertencentes às famílias de menor nível socioeconômico e inseridas em programa social específico para recebimento de leite.

Objective: To analyze the prevalence of ultra-processed food intake among children under one year of age and to identify associated factors. Methods: A cross-sectional design was employed. We interviewed 198 mothers of children aged between 6 and 12 months in primary healthcare units located in a city of the metropolitan region of São Paulo, Brazil. Specific foods consumed in the previous 24 h of the interview were considered to evaluate the consumption of ultra-processed foods. Variables related to mothers’ and children's characteristics as well as primary healthcare units were grouped into three blocks of increasingly proximal influence on the outcome. A Poisson regression analysis was performed following a statistical hierarchical modeling to determine factors associated with ultra-processed food intake. Results: The prevalence of ultra-processed food intake was 43.1%. Infants that were not being breastfed had a higher prevalence of ultra-processed food intake but no statistical significance was found. Lower maternal education (prevalence ratio 1.55 [1.08–2.24]) and the child's first appointment at the primary healthcare unit having happened after the first week of life (prevalence ratio 1.51 [1.01–2.27]) were factors associated with the consumption of ultra-processed foods. Conclusions: High consumption of ultra-processed foods among children under 1 year of age was found. Both maternal socioeconomic status and time until the child's first appointment at the primary healthcare unit were associated with the prevalence of ultra-processed food intake. Resumo: Objetivo: Analisar a prevalência do consumo de alimentos ultraprocessados entre crianças com menos de um ano e identificar os fatores associados. Métodos: Foi realizado um estudo transversal. Entrevistamos 198 mães de crianças com idades entre 6 e 12 meses em unidades de atenção primária à saúde localizadas em Embu das Artes, uma cidade da região metropolitana de São Paulo, Brasil. Alimentos específicos consumidos nas 24 horas anteriores à entrevista foram considerados para avaliar o consumo de alimentos ultraprocessados. As variáveis relacionadas às características das mães e crianças e as unidades de atenção primária à saúde foram agrupadas em três blocos de influência cada vez mais proximal com o resultado. Foi realizada uma análise de regressão de Poisson de acordo com um modelo estatístico hierárquico para determinar os fatores associados ao consumo de alimentos ultraprocessados. Resultados: A prevalência de consumo de alimentos ultraprocessados foi 43,1%. As crianças que não eram amamentadas apresentaram maior prevalência de consumo de alimentos ultraprocessados, porém não foi encontrada diferença estatística. Menor nível de escolaridade materna (RP 1,55 [1,08–2,24]) e o fato de a primeira consulta da criança na unidade de atenção primária à saúde acontecer na primeira semana de vida (RP 1,51 [1,01–2,27]) foram fatores associados ao consumo de alimentos ultraprocessados. Conclusões: Foi encontrado consumo elevado de alimentos ultraprocessados entre crianças com menos de um ano. A situação socioeconômica materna e o tempo da primeira consulta da criança na unidade de atenção primária à saúde foram associados à prevalência de consumo de alimentos ultraprocessados. Keywords: Complementary feeding, Infant feeding practices, Primary health care, Ultra-processed food, Palavras-chave: Alimentação complementar, Práticas de alimentação infantil, Atenção primária à saúde, Alimento ultraprocessado

A 56-year-old man was admitted to our hospital for management of acute epigastric abdominal pain and elevation of pancreatic enzymes. The CT scan revealed enlargement ofthe pancreatic body as well as the lung tumor ofthe right hilar and superior mediastinum. Therefore, bronchoscopy was performed and a diagnosis of small cell lung cancer with metastasisinduced acute pancreatitis(MIAP)was made. Prompt improvement in pancreatic findings was observed following chemotherapy. MIAP, which is a rare complication of lung cancer may affect the prognosis and quality of life of the patients; therefore, rapid diagnosis and appropriate treatment are important.

Sinusoidal obstructive syndrome prophylaxis with recombinant human soluble thrombomodulin is feasible in gemtuzumab ozogamicin-treated patients undergoing allogeneic hematopoietic cell transplantation

Renal ischemia-reperfusion (I/R) injury is closely associated with delayed graft function and poor long-term graft survival following transplantation. Various pathophysiologies can cause the deterioration of renal function; however, the immune system plays important roles in promoting and protecting renal tissues. Receptor activator of NFκB ligand (RANKL) is a member of the TNF superfamily and is produced by bone-forming osteoblasts; the receptor for RANKL is called RANK. In bone biology, RANKL-RANK signaling has been extensively studied, but its roles in the immune system are still obscure. We investigated the role of the RANK system in I/R injury of the kidney using an experimental mouse I/R model. The left renal pedicles of 10-week-old male mice were clamped for 60 min, and reperfusion and right nephrectomy were simultaneously performed. Separate groups were administered an anti-RANKL antibody and recombinant RANKL (rRANKL) 24 h prior to I/R. After reperfusion for a set period of time, the serum creatinine level was measured, and the left kidney was removed for histological examination and western blotting to evaluate the expression and localization of RANK-associated molecules and cytokines. The serum creatinine levels were significantly elevated after I/R injury. A time-dependent increase in RANKL was observed up to 24 h, whereas RANK was induced for 12 h after reperfusion. RANK was expressed in infiltrating inflammatory cells, which were positive for CD68, a marker of monocytes/macrophages. The pre-treatment with the anti-RANKL antibody significantly impaired renal function and increased the induction of inflammatory cytokines (TNFα and IL-6), Toll-like receptor (TLR4) and MyD88 (all p .05) compared to the levels in the I/R group. However, rRANKL significantly improved renal function and decreased the levels of inflammatory cytokines (TNFα and IL-6), TLR4 and MyD88 (p .05) compared to those in the I/R group. The present study is the first to evaluate the role of the RANK system in renal I/R injury. RANKL-RANK signaling affects macrophage function and results in the downregulation of TLR4 and reduction in TNFα and IL-6, leading to improved renal function following I/R injury.

Objective Hyperchloremia recently has been shown to have an association with the development of acute kidney injury (AKI) in critically ill patients. However, there is little information about the prevalence of an abnormal chloride concentration after pediatric cardiac surgery and its association with postoperative AKI. The aim of this study was to determine the prevalence of hyperchloremia and its association with AKI in pediatric patients after cardiac surgery. Design A retrospective single-center study. Setting Referral high-volume pediatric cardiac center in a tertiary teaching hospital. Participants Patients under 72 months of age with congenital heart disease who underwent cardiac surgery with the use of cardiopulmonary bypass. Interventions None. Measurements and main results The primary outcome was development of AKI diagnosed by Kidney Disease Improving Global Outcomes consensus criteria. The associations of outcomes with the highest serum chloride concentration ([Cl-]max) and time-weighted average chloride concentration ([Cl-]ave) within the first 48 hours after surgery were investigated. Of 521 patients included in the study, 463 patients (88.9%) had hyperchloremia at least 1 time within the first 48 hours after surgery. Postoperative AKI occurred in 205 patients (39.3%). [Cl-]ave and [Cl-]max in the AKI group were significantly higher than those in the non-AKI group (112 [110-114] mEq/L v 111 [109-113] mEq/L, p = 0.001 and 116 [113, 119] mEq/L v 114 [112-118] mEq/L, p = 0.002, respectively). After adjustment for other predictors of AKI by multivariable analyses, neither [Cl-]ave nor [Cl-]max was associated independently with the development of AKI (odds ratio [OR] = 1.040, 95% confidence interval [CI]: 0.885-1.220, p = 0.63; OR = 0.992, 95% CI: 0.874-1.130. p = 0.90). Conclusion Postoperative hyperchloremia was common and was associated with the development of AKI in pediatric patients after congenital cardiac surgery in univariate analysis. After adjustment for predictors of AKI by multivariate analyses, there was no significant relationship between postoperative chloride concentration and AKI.

The study aimed to assess factors associated with exclusive breastfeeding in low birthweight infants under six months of age in 64 Brazilian municipalities. This cross-sectional study included the 2,745 low birth weight infants under six months of age in the Survey on Prevalence of Breastfeeding (2008) in Brazilian municipalities. The outcome was exclusive breastfeeding. Individual determinants included socioeconomic characteristics (infants' age and sex), maternal characteristics (age bracket, work status, and parity), and characteristics of health services (birth in a Child-Friendly Hospital; place of outpatient follow-up; type of delivery). Two contextual determinants were also included: "number of Human Milk Banks per municipality per 10,000 live births" and "municipal human development index". The individualized effect of the study factor on the outcome was assessed by multilevel Poisson regression with level of significance under 5%. Exclusive Breastfeeding was more prevalent in low birth weight infants whose mothers were 20-35 years of age, who were not working away from home or were on maternity leave, who had given birth in a Child-Friendly Hospital, and who lived in municipalities with more human milk banks per 10,000 live births. The result of the positive and independent effect of strategies that were already part of the National Breastfeeding Policy (birth in a Child-Friendly Hospital, living in a municipality with more human milk banks, and adopting laws that guarantee maternity leave) on exclusive breastfeeding in low birth weight infants points to the need to expand the coverage of these measures in order to meet the breastfeeding targets proposed by the World Health Organization.Objetivou-se avaliar os fatores associados ao aleitamento materno exclusivo (AME) em lactentes com baixo peso ao nascer, menores de seis meses e residentes em 64 municípios brasileiros. Este estudo transversal incluiu os 2.745 lactentes com baixo peso ao nascer menores de seis meses da Pesquisa de Prevalência de Aleitamento Materno (2008) em municípios brasileiros. O desfecho foi “AME”. Os determinantes individuais corresponderam às características socioeconômicas dos lactentes (idade; sexo), das mães (faixa etária; situação de trabalho; paridade) e dos serviços de saúde (nascimento em Hospital Amigo da Criança; local de acompanhamento ambulatorial; tipo de parto). Dois determinantes contextuais foram incluídos: “número de bancos de leite humano por município por 10 mil nascidos vivos”, e “IDH do município”. O efeito individualizado do fator de estudo sobre o desfecho foi avaliado mediante regressão de Poisson com estrutura multinível, considerando-se associação significante quando p5%. O AME foi mais prevalente entre lactentes com baixo peso ao nascer cujas mães tinham de 20-35 anos, não trabalhavam fora ou estavam em licença maternidade; nos que nasceram em Hospital Amigo da Criança e que residiam em municípios com maior número de bancos de leite humano por 10 mil nascidos vivos. O resultado do efeito positivo e independente de estratégias que já integram a Política Nacional de Aleitamento Materno (nascer em Hospital Amigo da Criança, residir em município com maior disponibilidade de bancos de leite humano e adotar leis que garantam a licença maternidade) sobre o AME em lactentes com baixo peso ao nascer, aponta para a necessidade de expansão da cobertura dessas ações com vistas ao cumprimento das metas de aleitamento propostas pela Organização Mundial da Saúde.El objetivo fue evaluar los factores asociados a la lactancia materna exclusiva en lactantes con bajo peso al nacer menores de seis meses, residentes en 64 municipios brasileños. Este estudio transversal incluyó a los 2.745 lactantes con bajo peso al nacer, menores de seis meses, de la Encuesta de Prevalencia de Lactancia Materna (2008) en municipios Brasileños. El desenlace fue “lactancia materna exclusiva”. Los determinantes individuales correspondieron a las características socioeconómicas de los lactantes (edad; sexo), de las madres (franja etaria; situación laboral; igualdad) y de los servicios de salud (nacimiento en un Hospital Amigo da Criança; lugar de seguimiento ambulatorio; tipo de parto). Se incluyeron dos determinantes contextuales: “número de bancos de leche humana por municipio por 10 mil nacidos vivos”, e “IDH del municipio”. El efecto individualizado del factor de estudio sobre el desenlace fue evaluado mediante regresión de Poisson con estructura multinivel, considerándose una asociación significante cuando p5%. El lactancia materna exclusiva fue más prevalente entre lactantes con bajo peso al nacer, cuyas madres tenían de 20-35 años, no trabajaban fuera o estaban con licencia de maternidad; en quienes nacieron en un Hospital Amigo da Criança y que residían en municipios con mayor número de bancos de leche humana por 10 mil nacidos vivos. El resultado del efecto positivo e independiente de estrategias, que ya integran la Política Nacional de Lactancia Materna (nacer en Hospital Amigo da Criança, residir en municipio con mayor disponibilidad de bancos de leche humana y adoptar leyes que garanticen la baja por maternidad), sobre el lactancia materna exclusiva en lactantes con bajo peso al nacer, apunta la necesidad de expansión de la cobertura de esas acciones con vistas al cumplimiento de las metas de lactancia propuestas por la Organización Mundial de la Salud.

Background Identifying key interventions to increase exclusive breastfeeding duration has been a challenge. Pacifier use has been associated with exclusive breastfeeding discontinuation in Brazil. However, the proportion of the improvement in exclusive breastfeeding duration attributable to pacifier use remains unknown. Research aim Quantify the proportion of increases in exclusive breastfeeding prevalence that can be attributed to reduced pacifier use over time. Methods Secondary data analyses of two nationally representative cross-sectional surveys conducted in States' capitals in 1999 and in 2008 (N = 42,395 Brazilian infants under 6 months of age). We estimated the fraction of exclusive breastfeeding prevalence improvements that could be attributed to pacifier use based on multilevel regression analysis. Results From 1999 to 2008, there was an increase of 15.2 percentage points in exclusive breastfeeding prevalence and a decrease of approximately 17 percentage points in the prevalence of pacifier use among infants under 6 months. Reduction in pacifier use explained an increase in 5.5 percentage points' exclusive breastfeeding rates. If pacifier use were to decrease from 41.6% (prevalence in 2008) to 14% (as found in New Zealand), there would be an expected additional increase in exclusive breastfeeding of approximately 12 percentage points. Conclusions About one-third of the improvements in EBF prevalence observed in Brazil over a decade can be attributed to the corresponding decline in pacifier use.

Background: Exclusive breastfeeding (EBF) rates for infants younger than 6 months have increased in Brazil, although at the current pace of improvement it would take 6 years to reach an EBF rate of 50%. Thus, it is important to identify relevant modifiable key risk factors for the premature interruption of EBF. Objective: This study aimed to find out if pacifier use is an independent risk factor for the interruption of EBF among Brazilian infants. Methods: We conducted secondary cross-sectional data analyses of 2 waves of infant feeding surveys conducted in 1999 and in 2008 in the Brazilian state capitals and Federal District (N = 42 395 children < 6 months). Multivariate logistic regression was used to test the association between pacifier use and the risk of interruption of EBF in a pooled sample and within each survey wave, adjusting for socioeconomic, demographic, and biomedical confounders. Results: In the pooled sample, a third of the infants were exclusively breastfed (32.7%) and almost 50% had used a pacifier. Whereas EBF prevalence among infants increased from 25.1% in 1999 to 40.3% in 2008, pacifier use prevalence decreased from 58.5% to 41.6% in the same time period. Pacifier use was strongly associated with the risk of interruption of EBF in 1999 (adjusted odds ratio [AOR] = 2.65; 95% confidence interval [CI], 2.38-2.94), in 2008 (AOR = 3.18; 95% CI, 2.81-3.60), and in the pooled sample (AOR = 2.77; 95% CI, 2.63-2.91) after adjusting for key confounders. Conclusion: Pacifier use was the strongest risk factor for EBF interruption. Effective strategies to reduce pacifier use among infants younger than 6 months may further improve EBF rates in Brazil.

Objective: To estimate the association between the implementation of the Brazilian Breastfeeding Network and prevalence of breastfeeding in a medium-size city in southern Brazil. Methods: This was a cross-sectional study involving 405 children under 1 year who participated in the second phase of the multivaccination campaign in 2012. Children's consumption of food on the day before the interview was obtained through interviews with mothers or guardians. The manager and one health professional from every health facility that joined the Network were interviewed in order to investigate the process of implementation of this initiative. The association between prevalence of breastfeeding and exclusive breastfeeding and adherence to the Network implementation process was tested using Poisson regression with robust variance. Results: Multivariate analysis revealed that among the children assisted by health facilities who joined the Network and those attending services that did not adhere to this strategy, the prevalence of breastfeeding (74% and 70.4% among children under 1 year, respectively) and exclusive breastfeeding (43.3% and 38.1% among children under 6 months, respectively) did not differ significantly. Difficulties in implementing the Network, such as high turnover of professionals, not meeting the criteria for accreditation, and insufficient participation of tutors in the process were identified. Conclusion: Contrary to the hypothesis of this study, there was no significant association between the implementation of the Brazilian Breastfeeding Network and prevalence of breastfeeding and exclusive breastfeeding in the studied city. It is possible that the difficulties found in implementing the Network in this city have influenced this result. Resumo: Objetivo: Estimar a associação entre a implementação da Rede Amamenta Brasil e as prevalências de aleitamento materno (AM) em um município de médio porte do sul do Brasil. Métodos: Estudo transversal envolvendo 405 crianças menores de um ano que participaram da segunda fase da campanha de multivacinação de 2012. O consumo de alimentos pela criança no dia anterior à entrevista foi obtido mediante entrevistas com as mães ou responsáveis. Para investigar o processo de implementação da Rede foram entrevistados o gerente e um profissional de saúde de cada unidade que aderiu a esse processo. A associação entre as prevalências de AM e AM exclusivo (AME) e a adesão ao processo de implementação da Rede foi testada utilizando-se regressão de Poisson com variância robusta. Resultados: A análise multivariada revelou que, entre as crianças assistidas por unidades que aderiram ao processo de implementação da Rede e as que frequentavam serviços que não aderiram a essa estratégia, as prevalências de AM (74% e 70,4% em menores de um ano, respectivamente) e AME (43,3% e 38,1% em menores de seis meses, respectivamente) não diferiram significativamente. Foram identificadas dificuldades na implementação da Rede, tais como alta rotatividade dos profissionais, não cumprimento dos critérios para certificação e acompanhamento insuficiente das unidades pelos tutores da Rede. Conclusão: Contrariando a nossa hipótese, não houve associação significativa entre a implementação da Rede Amamenta Brasil e as prevalências de AM e AME no município estudado. É possível que as dificuldades encontradas na implementação da Rede nesse município tenham influenciado esse resultado. Keywords: Breastfeeding, Primary health care, Health promotion, Evaluation of health programs and projects, Palavras-chave: Aleitamento materno, Atenção primária à saúde, Promoção da saúde, Avaliação de programas e projetos de saúde

Hepatic SOS is a potentially life-threatening complication of conditioning for allogeneic HSCT. rTM is a new drug for treating DIC. We report our experience of the use of rTM as a prophylaxis against SOS in high-risk pediatric patients that underwent HSCT. We evaluated the cases of 19 pediatric hematology and oncology patients who underwent HSCT at our institution between 2007 and 2016. The patients who received HSCT after 2012 (n = 8) were treated with rTM as a prophylaxis against SOS together with UDCA and LMWH, whereas the others (n = 11) were only treated with UDCA and LMWH. Although SOS occurred by post-HSCT day 35 in 3 (27%) patients in the control group, SOS was not seen in the rTM group. Two of the former three patients suffered severe SOS, and one died of the condition. The mean peak level of PAI-1 (a marker of endothelial damage) was significantly lower in the rTM group. rTM appears to be a safe prophylaxis for SOS. The present findings suggest that prophylactic rTM after HSCT might help to prevent SOS.

Background The combination of fludarabine (Flu), high-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF; FLAG), with anthracyclines has become standard chemotherapy for refractory acute myeloid leukemia (AML) in European children and adults. To clarify the efficacy and the safety of FLAG-idarubicin (IDA) for children prospectively, we planned a multicenter phase II study (AML-R11) by the Japanese Pediatric Leukemia/Lymphoma Study Group. Methods Patients with AML aged between 2 and 20 years old, who had the first bone marrow (BM) relapse or induction failure, were enrolled. The FLAG-IDA regimen consisted of Flu 30 mg/m2 for 5 days, Ara-C 2 g/m2 for 5 days, G-CSF (lenograstim) 5 μg/kg for 6 days and IDA 10 mg/m2 for 3 days. The primary endpoint was remission rate after therapy. Results Due to drug supply issues, the trial was suspended after the inclusion of seven eligible patients. There were six cases of early relapse within 1 year of the first remission. All seven patients completed the therapy and no early death was observed. Hematological toxicity was common, and one patient developed grade 4 non-hematological toxicity of bacterial meningitis. Although only one patient with late relapse achieved complete remission, minimal residual disease was positive on both flow cytometry and Wilms' tumor 1 mRNA. Two patients were alive in remission following hematopoietic stem cell transplantation, whereas the other five patients died of either the disease or treatment-related causes. Conclusion FLAG-IDA might be tolerable for children with refractory AML although the efficacy should be further investigated.

Objectives To investigate renal concentrating ability after long-term fast-melting oral desmopressin lyophilisate treatment in children with monosymptomatic nocturnal enuresis. Methods The present retrospective study involved 58 children (43 boys, 15 girls; aged 6–12 years) with nocturnal enuresis receiving oral desmopressin lyophilisate. After treatment for 4 weeks with a complete response, patients were placed on a reduced dose of 120 μg on alternate days. Moring urine osmolality was measured using urine samples obtained after medication and non-medication dry nights. Patients who experienced ≥1 wet nights/month during alternate-day oral desmopressin lyophilisate treatment or within 6 months after its cessation were assigned to the relapse group, whereas those who experienced

Background and objectives Reduced muscle mass and strength are prevalent conditions in dialysis patients. However, muscle strength and muscle mass are not congruent; muscle strength can diminish even though muscle mass is maintained or increased. This study addresses phenotype and mortality associations of these muscle dysfunction entities alone or in combination ( i.e., concurrent loss of muscle mass and strength/mobility, here defined as sarcopenia). Design, setting, participants, & measurements This study included 330 incident dialysis patients (203 men, mean age 53±13 years, and mean GFR 7±2 ml/min per 1.73 m 2 ) recruited between 1994 and 2010 and followed prospectively for up to 5 years. Low muscle mass (by dual-energy x-ray absorptiometry appendicular mass index) and low muscle strength (by handgrip) were defined against young reference populations according to the European Working Group on Sarcopenia in Older People. Results Whereas 20% of patients had sarcopenia, low muscle mass and low muscle strength alone were observed in a further 24% and 15% of patients, respectively. Old age, comorbidities, protein-energy wasting, physical inactivity, low albumin, and inflammation associated with low muscle strength, but not with low muscle mass (multivariate ANOVA interactions). During follow-up, 95 patients (29%) died and both conditions associated with mortality as separate entities. When combined, individuals with low muscle mass alone were not at increased risk of mortality (adjusted hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 0.56 to 2.67). Individuals with low muscle strength were at increased risk, irrespective of their muscle stores being appropriate (HR, 1.98; 95% CI, 1.01 to 3.87) or low (HR, 1.93; 95% CI, 1.01 to 3.71). Conclusions Low muscle strength was more strongly associated with aging, protein-energy wasting, physical inactivity, inflammation, and mortality than low muscle mass. Assessment of muscle functionality may provide additional diagnostic and prognostic information to muscle-mass evaluation.

OBJECTIVE To analyze the factors associated with the use of pacifiers and/or bottle feeding in infants aged under one year.METHODS This is a cross-sectional study with 34,366 children and using data from the database of the 2nd Nationwide Survey of Breastfeeding Prevalence performed in the Brazilian capitals and Federal District in 2008. Cluster sampling was used. The questionnaire included questions about the use of artificial nipples in the last 24 hours. The analysis considered three outcomes: exclusive use of pacifier, exclusive use of bottle feeding, and use of artificial nipples (pacifier and bottle feeding). Prevalence ratios were obtained using Poisson regression with robust variance following a hierarchical model.RESULTS The following factors were associated with exclusive use of the pacifier: mother working outside the home, primiparity, child was not breastfed within the first hour, and child had consumed tea on the first day at home. The following factors were associated with exclusive use of bottle feeding: mother working outside the home, primiparity, low birth weight, child not breastfed within the first hour, and child had consumed milk formula and tea on the first day at home. The following factors were associated with use of artificial nipples (pacifier and bottle feeding): mother working outside the home, primiparity, cesarean delivery, the male gender, low birth weight, born in a hospital not accredited as “baby friendly”, required health baby monitoring in the Primary Health Care Unit (PR = 0.91), and child had consumed milk formula, water, or tea on the first day at home.CONCLUSIONS This study identified profiles of exclusive users of pacifiers, bottle feeding, and both. The provided information can guide preventive practices for child health. OBJETIVO Analisar os fatores associados ao uso de chupeta e/ou mamadeira em lactentes menores de um ano.MÉTODOS Estudo transversal realizado com dados de 34.366 crianças obtidos da II Pesquisa Nacional de Prevalência de Aleitamento Materno, realizada em 2008, nas capitais brasileiras e Distrito Federal. Foi utilizada amostragem por conglomerados e o questionário incluiu perguntas sobre o uso de bicos artificiais nas últimas 24h. Três desfechos foram considerados para a análise: uso exclusivo de chupeta, uso exclusivo de mamadeira e uso de bicos artificiais (chupeta e mamadeira). As razões de prevalência foram obtidas por regressão de Poisson com variância robusta seguindo modelo hierárquico.RESULTADOS Associaram-se ao uso exclusivo de chupeta: mãe trabalhar fora, primiparidade, não ter sido amamentado na primeira hora e uso do chá no primeiro dia em casa. Para uso exclusivo da mamadeira, foram identificados: mãe trabalhar fora, primiparidade, baixo peso ao nascer, não amamentado na primeira hora de vida, uso de fórmula e chá no primeiro dia em casa. O uso de bicos artificiais (chupeta e mamadeira) foi associado com trabalho materno fora do lar, primiparidade, parto cesárea, bebês do sexo masculino, baixo peso ao nascer, nascimento em um hospital não credenciado como “Amigo da Criança”, realizar o acompanhamento de saúde da criança em unidade básica de saúde (RP = 0,91), uso de fórmula, água e chá no primeiro dia em casa.CONCLUSÕES Este estudo encontrou perfis de usuários exclusivos de chupetas, mamadeiras e de ambos. Essas informações podem orientar as práticas preventivas para a saúde da criança.

Summary The Tokyo Children's Cancer Study Group conducted a randomized controlled study to evaluate the effect of experimental early intensification using high-dose cytarabine and L-asparaginase in paediatric intermediate-risk (IR) acute lymphoblastic leukaemia (ALL). A total of 310 IR ALL patients were randomized to receive either experimental early intensification (n = 156) or standard early intensification including standard-dose cytarabine arm (n = 154) after induction therapy. The experimental arm consisted of high-dose cytarabine and L-asparaginase, while the standard arm consisted of standard-dose cytarabine, oral 6-mercaptopurine and cyclophosphamide. The probabilities of event-free survival at 8 years in the experimental and standard arms were 72·3 ± 3·7% and 77·5 ± 3·5%, respectively (P = 0·32). The 8-year overall survival rates for these two arms were 85·0 ± 3·0% and 86·9 ± 2·8%, respectively (P = 0·72). The frequency of infectious events was significantly higher in the experimental arm (66·4%) than in the standard arm (24·6%) (P

Objective In order to characterize the significance of immune system function in patients with advanced renal cell carcinoma (RCC), we investigated the interactive relationships among the following parameters: metastatic characteristics, expression of Fas ligand (FasL) in nephrectomized specimens, immunological parameters, and patient's prognosis. Materials and methods Thirty-five patients with advanced RCC were stratified into 3 groups according to the characteristics of metastasis timing, at first presentation (mFP), within 5 years of nephrectomy (early-recurrence), after 5 years (late-recurrence). Immunological parameters [hemoglobin, lymphocyte count, neutrophil/lymphocyte ratio (NLR), serum albumin, Eastern Cooperative Oncology Group (ECOG) performance status (PS), and Charlson Comorbidity Index], FasL expression in RCC, and patient prognosis from occurrence of metastasis were compared among the groups. Thirty-five patients were also stratified into 2 groups according to FasL positivity and individual parameters. Patient's prognosis and the remaining immunological parameters were compared between groups. Results The NLRs of the late-recurrence group were significantly lower than those of the mFP (P = 0.0004) and early-recurrence (P = 0.013) groups. The FasL mRNA positivity of the late-recurrence group was significantly lower than those of the mFP (P = 0.001) and early-recurrence (P = 0.0277) groups. The prognosis of the late-recurrence group was significantly better than that of the early-recurrence group (P = 0.0255). NLRs were significantly lower in the FasL-negative group than in the -positive group (P = 0.0182). The cause-specific survival rates of the ECOG PS 0 group were significantly higher than that of the ECOG PS > 0 group (P Conclusions Our results suggest the associations of the prognosis in advanced RCC with peripheral blood NLR and FasL expression in nephrectomized tumor. The characteristics of lower values of NLR and FasL expression positivity in late-recurrence compared with other metastatic timings suggest strong host immune activity, and may imply relatively long survival. On the other hand, elucidation of the patient's general condition obtained not only by chemical data but also by ECOG PS is crucial in the management of patients with advanced RCC.

Infants (

OBJECTIVE To evaluate the association between the level of implementation of the Brazilian Breastfeeding Network and the prevalence of exclusive breastfeeding. METHODS Cross-sectional study of a representative sample of 916 infants < 6 months, in Ribeirao Preto, SP, Southeastern Brazil, in 2011. Data on breastfeeding, place of outpatient care and other characteristics were collected during the National Vaccination Campaign. The factor studied is where outpatient care took place: Private; Non-Network Public; Public with Network Workshop; and Public certified by Network. The individualized effect of the factor studied on the outcome was analyzed using Poisson regression with robust variance. RESULTS The comparison between private (reference category) and other outpatient care showed significant dose-response relationship with a progressive increase in the prevalence of exclusive breastfeeding in public non-Network, public with Network Workshop and public accredited by Network outpatient care (p = 0.047). As regards the Basic Health Units accredited by Network category, the Prevalence Ratio of exclusive breastfeeding was equal to 1.47 (95%CI 1.00;2.17), after adjustment for confounding variables. CONCLUSIONS The prevalence of exclusive breastfeeding for infants < 6 months was higher in places accredited by the Brazilian Breastfeeding Network, which evinces the importance of investing in accreditation of Basic Units of Health by this strategy.

Renal ischemia-reperfusion (I/R) injury is associated with delayed graft function and results in poor long-term graft survival. We previously showed that splenectomy (SPLN) protects the kidney from I/R injury and reduces serum TNF-α levels. Herein, we further investigated the effects of SPLN on inflammatory responses and tissue injury in renal I/R by examining the expression of major inflammatory cytokines and heat shock protein 70 (HSP70). Because it was shown previously that the anti-TNF-α agent infliximab (IFX) attenuated renal I/R injury, we also investigated whether IFX administration mimics the effects of SPLN.The left renal pedicles of adult male Wistar rats were clamped for 45 minutes and then reperfused for 24 hours; right nephrectomy and SPLN were performed immediately. A separate cohort was administered IFX 1 hour before surgery in lieu of SPLN.Serum creatinine and blood urea nitrogen levels were markedly elevated by I/R injury; these increases were significantly reversed by IFX. Furthermore, IFX inhibited the induction of inflammatory cytokines and HSP70 during renal I/R injury. Time-dependent profiles revealed that the expression of inflammatory cytokines was elevated immediately after I/R, whereas levels of HSP70, serum creatinine, and blood urea nitrogen began to rise 3 hours postreperfusion. Macrophages/monocytes were significantly increased in I/R-injured kidneys, but not in those administered IFX. The outcomes of SPLN mirrored those of IFX administration.Splenectomy and TNF-α inhibition both protect the kidney from I/R injury by reducing the accumulation of renal macrophages/monocytes and induction of major inflammatory cytokines.

In vivo electronic monitoring systems are promising technology to obtain biosignals with high spatiotemporal resolution and sensitivity. Here we demonstrate the fabrication of a biocompatible highly conductive gel composite comprising multi-walled carbon nanotube-dispersed sheet with an aqueous hydrogel. This gel composite exhibits admittance of 100 mS cm−2 and maintains high admittance even in a low-frequency range. On implantation into a living hypodermal tissue for 4 weeks, it showed a small foreign-body reaction compared with widely used metal electrodes. Capitalizing on the multi-functional gel composite, we fabricated an ultrathin and mechanically flexible organic active matrix amplifier on a 1.2-μm-thick polyethylene-naphthalate film to amplify (amplification factor: ∼200) weak biosignals. The composite was integrated to the amplifier to realize a direct lead epicardial electrocardiography that is easily spread over an uneven heart tissue., Flexible electronics promise the opportunity to monitor biological activity via implanted devices. Here, the authors develop a biocompatible conductive carbon nanotube/gel composite and couple it with an ultrathin flexible amplifier, enabling in vivo measurement of epicardial electrocardiogram signals.

Background The pro-inflammatory receptor of advanced glycation end-products (RAGE)-ligand S100A12 is thought to promote, whereas anti-inflammatory soluble RAGE (sRAGE) may protect against, vascular disease. We evaluated circulating S100A12 and sRAGE in relation to vascular disease, inflammation, nutritional status, and mortality risk in peritoneal dialysis (PD) patients. Methods Plasma S100A12 and sRAGE, biomarkers of inflammation, nutritional status, and comorbidities were analyzed in 82 prevalent PD patients (median age 65 years; 70% men; median vintage 12 months) and, for comparative analysis, also in 190 hemodialysis (HD) patients and 50 control subjects. Associations between mortality risk and concentrations of S100A12 and sRAGE were assessed in PD and HD patients after a mean follow-up period of 31 and 29 months respectively using a competing risk Cox regression model. Results In PD patients, median S100A12, sRAGE and S100A12/sRAGE were markedly higher than in controls, and S100A12 was 1.9 times higher and median sRAGE 14% lower compared with HD patients. In PD patients, S100A12 associated with C-reactive protein (ρ = 0.46; p < 0.001) and interleukin-6 (ρ = 0.38; p < 0.001), and, negatively, with s-albumin (ρ = -0.27; p < 0.05) whereas sRAGE associated negatively with body mass index (ρ = -0.37; p < 0.001), fat body mass index (ρ = -0.34; p < 0.001), and lean body mass index (ρ = -0.36; p < 0.001). Peripheral vascular disease or cerebrovascular disease (PCVD) was present in 28% of PD patients and, in multivariate analysis, associated mainly with high S100A12 (odds ratio [OR] 3.52, p = 0.04). In both PD and HD patients, the highest versus other tertiles of S100A12 associated with increased mortality. In contrast, sRAGE did not associate with PCVD or mortality in PD and HD patients. Conclusions Plasma S100A12 and sRAGE are markedly elevated in PD patients. Soluble RAGE was inversely related to body mass indices while S100A12 associated with increased inflammation, PCVD, and mortality, suggesting that S100A12 may identify PD patients at high risk for vascular disease and increased mortality.

Background Circulating advanced glycated end-products (AGEs) including pentosidine accumulating in chronic kidney disease (CKD) patients due to retention and increased formation are thought to contribute to cardiovascular disease (CVD). Here we evaluated factors linked to increased plasma pentosidine and its association with mortality in patients with different stages of CKD and undergoing different treatments. Methods Plasma pentosidine, biomarkers of inflammation, oxidative stress and nutritional status were investigated in CKD 1–2 (n = 37), CKD 3–4 (n = 54), CKD 5 non-dialyzed (CKD5-ND; n = 386), peritoneal dialysis (PD; n = 74) and hemodialysis (HD; n = 195) patients. Factors predicting plasma pentosidine were analysed by multivariate regression analysis and mortality risk was assessed by GENMOD procedure. Results Plasma pentosidine levels, which were higher in CKD5-ND, PD and HD groups than in CKD 1–2 group, were significantly lower in PD than in HD patients, and not different between PD patients and CKD5-ND patients. Pentosidine associated inversely with glomerular filtration rate (GFR), and additionally in PD with 8-hydroxy-2‘-deoxyguanosine (8-OHdG), and interleukin 6 (IL-6); in HD with age, IL-6 and body mass index (BMI); in CKD5-ND with age, 8-OHdG, IL-6, high-sensitive C-reactive protein (hsCRP), and soluble vascular cell adhesion protein-1 (sVCAM-1); in CKD 3–4 with 8-OHdG and sVCAM-1; and in CKD 1–2 with age and sVCAM-1. In multivariate analysis, age (one standard deviation, 1-SD higher), malnutrition (subjective global assessment, SGA), oxidative stress (8-OHdG, 1-SD higher), and belonging to CKD5-ND, HD and PD cohorts associated with 1-SD higher pentosidine. In GENMOD, 1-SD higher pentosidine independently predicted all-cause mortality (relative risk, RR = 1.04; 95% confidence interval, CI, 1.01–1.08, p = 0.01) and CVD mortality (RR = 1.03; 95% CI, 1.01–1.06, p = 0.03) after adjusting for all confounders. Conclusions Plasma pentosidine is markedly elevated in CKD and associates with low GFR, oxidative stress and inflammation, and is an independent predictor of mortality in CKD patients.

To evaluate the clinical significance of preoperative biomarkers such as laboratory data, Eastern Cooperative Oncology Group Performance Status (ECOG PS) and clinicopathological factors in patients undergoing radical nephroureterectomy for upper urinary tract urothelial carcinoma. Between 1995 and 2011, a total of 99 patients treated at our institution for upper urinary tract urothelial carcinoma were enrolled in this study. The prognostic significance of various preoperative data and clinicopathological factors were analyzed. Univariate and multivariate analyses were performed using the Kaplan–Meier method with the log-rank test and a Cox proportional hazards regression model. Median patient age was 73 years (range 44–86 years), and the median follow-up period after radical nephroureterectomy was 37.9 months (range 6.6–171.4 months). The 5-year intravesical recurrence-free survival and cancer-specific survival estimates were 47.1 and 70.0 %, respectively. On multivariate analysis, concomitant bladder carcinoma was an independent predictor of intravesical recurrence (hazard ratio 3.689; P = 0.002), and infiltration (hazard ratio 14.842; P = 0.002), preoperative serum creatinine level (hazard ratio 9.992; P = 0.005), preoperative serum hemoglobin level (hazard ratio 6.370; P = 0.018) and ECOG PS (hazard ratio 4.326; P = 0.037) were associated with worse cancer-specific survival. This study is limited by biases associated with its retrospective design. This study indicates that not only clinicopathological factors, but also preoperative biomarkers, such as serum creatinine and hemoglobin levels and ECOG PS, predict a poor survival in patients with upper urinary tract urothelial carcinoma.

The specific cell surface markers on mesenchymal stem/progenitor cells (MSCs) have been poorly defined in vivo, but in one recent study, an MSC subpopulation was directly isolated from a CD271-positive fraction of human bone marrow cells. The aim of this study was to identify circulating CD271+ MSCs in human peripheral blood and investigate whether the cells are mobilized after acute myocardial infarction (MI). A flow cytometric analysis identified CD45low/−CD34+CD271+ cells in adult human peripheral blood. The numbers of circulating CD45low/−CD34+CD133+ cells (hematopoietic linage progenitors) were significantly lower in elderly subjects without coronary artery disease than in healthy young subjects, whereas the numbers of CD45low/−CD34+CD271+ cells were comparable between elderly subjects and younger subjects. The CD45low/−CD34+CD271+ and CD133+ cell counts were both higher in patients with acute MI than in patients with stable coronary artery disease. In our investigation of the time course changes after acute MI, the CD45low/−CD34+CD133+ cell counts gradually increased up to day 7. Over the same period, the CD45low/−CD34+CD271+ cell counts peaked at day 3 and then declined up to day 7. Importantly, the CD271+ cell counts at day 3 were positively correlated with the peak concentrations of creatine kinase after acute MI. Results of the present study suggest that the CD271+ MSCs are mobilized differently from the CD133+ hematopoietic progenitors and may play a specific role in the tissue repair process during age-related changes and after acute myocardial infarction.

Objectives: To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). Patients and Methods: mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. Results: A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. Conclusions: The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis.

HDR syndrome is an autosomal dominant disorder characterized by hypoparathyroidism, sensorineural deafness, and renal anomaly caused by mutation of the GATA3 gene located at chromosome 10p15. We report the case of a neonate with HDR syndrome and a novel GATA3 mutation. We performed genetic and functional analysis of GATA3 in this patient and identified a novel heterozygous 1516G> C missense mutation in exon 5, resulting in a cysteine-to-serine substitution at codon 321 (Cys321Ser). Mutated and wild-type GATA3 proteins were expressed at a similar level in vitro, indicating that the mutated GATA3 protein was stable. Luciferase assay revealed that the Cys321Ser-mutated GATA3 lacked transactivation activity due to loss of DNA-binding activity as confirmed by gel shift assay. Moreover, mutated GATA3 exerted a dominant-negative effect over the transactivation activity of wild-type GATA3. These findings indicate that not only haploinsufficiency of GATA3 but also the dominant-negative effect of Cys321Ser-mutated GATA3 might have been responsible for the HDR syndrome phenotype of our patient.

FTY720 is known to not only accelerate lymphocyte homing to secondary lymphoid organs but also induce apoptosis in lymphocytes. To investigate the effect of FTY720 in rat thymocytes, rats were intramuscularly injected with 10 mg/kg/day of FTY720. Light microscopy revealed obvious reductions in the size of the cortical region of thymuses treated with FTY720. FTY720 significantly reduced the total number of thymocytes, particularly affecting the CD4 + 8 + TCRαβ negative/low population. TUNEL analysis showed that thymocyte apoptosis was induced in the cortical region and western blotting revealed activated caspase-3 and -6. Furthermore, caspase-9 was activated and the level of cytochrome c was increased. In contrast, the protein level of Bax did not increase following FTY720 treatment, suggesting that FTY720 may have perturbed mitochondrial function. Therefore, FTY720-induced apoptosis is initiated by the release of cytochrome c from mitochondria, resulting in the activation of caspases in rat thymocytes.

Objective Encapsulating peritoneal sclerosis (EPS) is a serious complication of continuous ambulatory peritoneal dialysis. Previous studies have created peritoneal sclerosis rat models using daily intraperitoneal injection of chlorhexidine gluconate (CG), but this technique is cumbersome and thickening of the peritoneum makes it difficult to evaluate the injection site. We therefore aimed to make a rat model using a continuous-infusion pump. Methods Various concentrations of CG (5%, 8%, 10%, 12%, and 14%) in ethanol were dissolved in saline within the infusion pumps, each of which was placed in the lower abdominal cavity of a male Wister rat. After a peritoneal equilibration test was performed, the rats were sacrificed and the lower anterior parietal and visceral peritoneum was removed. Each excised peritoneum was analyzed by macroscopic and microscopic examinations, including immunohistochemistry for the expression of transforming growth factor-beta 1 (TGF-β1), vascular endothelial growth factor (VEGF), and alpha-smooth muscle actin (αSMA). The results were compared with those of control rats injected with ethanol dissolved in saline within the infusion pump and with no-pump rats. Results Two of the 5 rats in the 12% CG group and 3 of the 5 rats in the 14% CG group died of ileus within 14 days. All the rats in the 5%, 8%, and 10% CG groups survived to 28 days. Macroscopic examination in the 10% CG group showed bowel dilatation, bowel adhesion, and bloody ascites, similar to those seen in human EPS patients. All rats in each CG group showed the same extent of thickening of the submesothelial compact zone, proliferation of collagen fibers, and presence of numerous cells and neovascularization. Within same CG groups, an equal degree of thickening was observed at all sites of the peritoneum. TGF-β1, VEGF, and αSMA were highly expressed in the peritoneum of the 10% CG group. Conclusion We developed a novel method of creating a peritoneal sclerosis rat model using a continuous-infusion pump. Our technique is simple and highly reproducible, and will be useful in the study of peritoneal sclerosis mechanisms.

We analysed 86 patients with CML who received unrelated cord blood transplantation (UCBT), identified through a registry of the Japan Cord Blood Bank Network. At transplantation, the median patient age was 39 years (range, 1-67 years); 38 patients were in chronic phase (CP), 13 in the accelerated phase (AP) and 35 in blast crisis (BC). Median duration from diagnosis to UCBT was 1.5 years (range, 0.2-14.6 years). A nucleated cell (NC) dose of more than 3.0 x 10(7) per kg was sufficient to achieve neutrophil (91%) and platelet recovery (86%), whereas the lower dose of NC achieved only 60 and 61%, respectively. The duration and type of pre-transplant treatment did not affect neutrophil or platelet recovery. Results of multivariate analysis indicated that older patients (50 years) had a higher incidence of transplant-related mortality. Advanced-disease stage and lower doses of NCs were significantly associated with lower leukaemia-free and event-free survival. At 2-year survival for patients in CP, AP and BC was 71, 59 and 32%, respectively (P=0.0004). A pre-transplant European Group for Blood and Marrow Transplantation scoring system was effective in predicting the outcome of UCBT. We conclude that UCBT is a reasonable alternative therapy for patients with CML.

Many reports about breastfeeding prevalence and factors associated with weaning have been published in the scientific literature. However, the influence of newborn feeding practices on the duration of exclusive breastfeeding has received less attention. This study provides information about the introduction of liquids, other than the mother's milk, to infants in the first 6 months and factors associated with this practice. J Hum Lact. 24(2):168-174.

ObjectiveTo evaluate the association between overweight and wheezing in pre-school children in 14 small Brazilian communities.MethodsCross-sectional epidemiological study, conducted between 2001 and 2002. A sample of 3453 children under 5 years of age was taken from nine communities in the state of Bahia and five in the state of São Paulo. Data on housing, family and children were obtained by applying structured questionnaires in loco. Weight and height for each child were also measured. The association between wheezing and overweight was assessed by unconditional logistic multivariate regression models.ResultsOverweight children had a greater frequency of wheezing and an odds ratio of 2.57 (95% confidence interval 1.51–4.37) was estimated after controlling for several potential confounding variables. The magnitude of the risk was not affected by several different model specifications.ConclusionExcess weight is associated with increased risk for wheezing in this population of children below 5 years of age.

We evaluated the efficacy of a treatment strategy in which infants with acute lymphoblastic leukemia (ALL) were stratified by their MLL gene status and then assigned to different risk-based therapies. A total of 102 patients were registered on two consecutive multicenter trials, designated MLL96 and MLL98, between 1995 and 2001. Those with a rearranged MLL gene (MLL-R, n=80) were assigned to receive intensive chemotherapy followed by hematopoietic stem cell transplantation (HSCT), while those with germline MLL (MLL-G, n=22) were treated with chemotherapy alone. The 5-year event-free survival (EFS) rate for all 102 infants was 50.9% (95% confidence interval, 41.0-60.8%). The most prominent late effect was growth impairment, observed in 58.9% of all evaluable patients in the MLL-R group. This plan of risk-based therapy appears to have improved the overall prognosis for infants with ALL, compared with previously reported results. However, over half the events in patients with MLL rearrangement occurred before the instigation of HSCT, and that HSCT-related toxic events comprised 36.3% (8/22) of post-transplantation events, suggesting that further stratification within the MLL-R group and the development of more effective early-phase intensification chemotherapy will be needed before the full potential of this strategy is realized.

Residual disease (RD) after induction chemotherapy may predict clinical outcome in acute myeloid leukemia (AML). In the present study, we investigated the prognostic significance of RD detected by multidimensional flow cytometry (MDF) among 34 children treated for AML in a clinical trial (JPLSG AML-05) in Japan. Bone marrow samples were analyzed at the points of the end of the first induction course (BMA-1) and second induction course (BMA-2) by MDF. RD was evaluated by detecting the immature cells showing abnormal antigen expression pattern; CD34(+), CD15(+), CD7(+). Thirteen (39.4 %) of 34 patients at BMA-1 and 8 (27.6 %) of 34 at BMA-2 had RD levels ≥0.1 %. There was no significant difference in 3y-EFS and 3y-OS between patients with RD levels ≥0.1 % and those with RD levels

This study compares complementary feeding World Health Organization (WHO) indicators with those built in accordance with Brazilian recommendations (Ten Steps to Healthy Feeding). A cross-sectional study was carried out during the National Immunization Campaign against Poliomyelitis in Guarapuava-Paraná, Brazil, in 2012. Feeding data from 1,355 children aged 6-23 months were obtained through the 24 h diet recall. Based on five indicators, the proportion of adequacy was evaluated: introduction of solid, semi-solid, or soft foods; minimum dietary diversity; meal frequency; acceptable diet; and consumption of iron-rich foods. Complementary feeding showed adequacy higher than 85% in most WHO indicators, while review by the Ten Steps assessment method showed a less favorable circumstance and a high intake of unhealthy foods. WHO indicators may not reflect the complementary feeding conditions of children in countries with low malnutrition rates and an increased prevalence of overweight/obesity. The use of indicators according to the Ten Steps can be useful to identify problems and redirect actions aimed at promoting complementary feeding.

This study aimed to evaluate the implementation of the Brazilian Breastfeeding Network and its impact on breastfeeding indicators. Implementation was analyzed according to type, including 56 primary healthcare units from three Brazilian municipalities. For evaluation of the degree of implementation, a score was created for each unit based on compliance with Ministry of Health certification criteria. Effects of implementation were analyzed according to exclusive and overall breastfeeding rates. Eighteen (32.1%) of the units met the four criteria for certification. The study sample included 1,052 children less than one year of age, of whom 563 were less than six months old. Units that met the four criteria for certification showed higher rates of exclusive breastfeeding (44%) when compared to the other units. Difficulties in implementing the Brazilian Breastfeeding Network were identified, and breastfeeding indicators varied according to the number of certification criteria met by the primary healthcare unit.

Hyaluronidase (HAase), a class of enzymes which degrade hyaluronic acid (HA), are involved in the spread of infections/toxins, ovum fertilization, and cancer progression. Thus, HAase inhibitors may have use in disease treatments. We evaluated 21 HAase inhibitors against HYAL-1, testicular, honeybee, and Streptomyces HAases. Among these inhibitors, polymers of poly (styrene-4-sulfonate) (PSS) (i.e., molecular weight 1400-990,000 or PSS 1400-PSS 990,000) and O-sulfated HA (sHA) derivatives (sHA2.0, 2.5, and 2.75) were the most effective. HYAL-1 and bee HAases were the most sensitive, followed by testicular HAase; Streptomyces HAase was resistant to all inhibitors, except PSS 990,000 and VERSA-TL 502 (i.e., PSS 10(6) dalton). The length of the PSS polymer determined their potency (e.g., IC50 for HYAL-1, PSS 990,000: 0.0096 microM; PSS 210 no inhibition; IC50 for testicular HAase, PSS 990,000: 0.042 microM; PSS 210 no inhibition). The presence, but not the number, of sulfate groups on the sHA molecule determined its potency (e.g., IC50 for HYAL-1: sHA2.0, 0.019 microM; sHA2.75, 0.0083 microM). Other known HAase inhibitors, such as gossypol, sodium-aurothiomalate, 1-tetradecane sulfonic acid, and glycerrhizic acid, were not effective. Both PSS and sHA inhibited HAases by a mixed inhibition mechanism (i.e., competitive + uncompetitive) and were 5- to 17-fold better as uncompetitive inhibitors than as competitive inhibitors. These results demonstrate that HAase inhibitors show selectivity toward the different types of HAases, which could be exploited to inhibit specific HAases involved in a variety of pathophysiologic conditions.

A high incidence of disseminated intravascular coagulation (DIC) in adult patients with acute lymphoblastic leukemia (ALL) is reported. However, studies comprising both childhood and adult patients are sparse and the clinical relevance of DIC in ALL patients has been a conflicting issue. Coagulation profiles at presentation and within seven days after starting remission-induction therapy of 44 childhood and 51 adult ALL patients were studied. At presentation, two childhood (5%) and 11 adult (22%) patients had DIC (p

The transradial approach for catheterization is becoming increasingly more popular. At present, the choice of the right or left radial artery depends on the operator's preference. We examined how the laterality influenced the effectiveness of the approach. Employing Judkins-type catheters, we performed coronary angiography in 232 patients with the left approach and in 205 patients with the right approach. Although access time did not differ between the two groups of patients, the duration of catheter manipulation was shorter in the left- than in the right-approach group (11.7 ± 5.9 vs. 9.8 ± 4.4 min; P < 0.001). Because of the shorter duration of catheter manipulation, the total procedural duration was shorter in the left-approach group (13.7 ± 6.4 vs. 11.4 ± 4.8 min; P < 0.001). The fluoroscopy time was shorter in the left- than in the right-approach group (3.7 ± 2.5 vs. 5.0 ± 3.3 min; P < 0.001). The amount of contrast material did not differ between the groups (79 ± 27 vs. 83 ± 25 ml). The rate of guidewire usage to engage the coronary ostium was higher in the right- than in the left-approach group because of the severe tortuosity of the right subclavian artery (20/205 vs. 0/232; P < 0.001). Thus, for operators with significant experience, the left radial approach may provide increased procedural efficacy for coronary angiography compared to the right radial approach. Catheter Cardiovasc Interv 2004;61:333–337. © 2004 Wiley-Liss, Inc.

To elucidate whether myocardial CD38/cyclic ADP-ribose (cADPR) signaling plays a physiological role, we investigated the heart of CD38 knockout mice (CD38KO). In CD38KO, the myocardial cADPR content was reduced by 85% compared with wild-type mice (WT). Cardiac hypertrophy developed only in males. At 36 degrees C, none of the parameters for Ca(2+) transients and forces of the papillary muscles differed between WT and CD38KO. In contrast, at 27 degrees C, at which cADPR does not work, the peak [Ca(2+)](i) was increased and the decline in [Ca(2+)](i) was accelerated in CD38KO compared with WT. In CD38KO, the protein expression of SR Ca(2+) ATPase type2 (SERCA2) and the SERCA2-to-phospholamban ratio were increased compared with WT. The ryanodine receptor protein was increased only in female CD38KO compared with WT. These data suggest that the CD38/cADPR signaling plays an important role in intracellular Ca(2+) homeostasis in cardiac myocytes in vivo. Its deficiency was compensated differentially according to gender.