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Human papillomavirus (HPV) testing using self-collected vaginal samples and urine samples is convenient and effective for improving the screening rate. But, to serve as an alternative cervical cancer screening technique, such tests must offer sensitivity equivalent to the HPV testing of physician-collected cervical samples. To examine the effectiveness of HPV testing using self-collected samples and urine samples, we compared the results of HPV testing using these samples with those of HPV testing using physician-collected samples and cytological examinations.The study population included 300 women (age: 20-50 years) with abnormal cervical cytology. The results of HPV testing using self-collected samples and urine samples and physician-collected samples and cervical cytology were compared.For all HPV types, the κ-value was 0.773 for physician- and self-collected samples and 0.575 for physician-collected and urine samples. The κ-value for HPV type 16-positive samples was 0.988 for physician- and self-collected samples and 0.896 for physician-collected and urine samples. The κ-value for HPV type 18-positive samples was 0.856 for physician- and self-collected samples and 0.831 for physician-collected and urine samples. For other HPV types, the value was 0.809 for physician- and self-collected samples and 0.617 for physician-collected and urine samples.The obtained results were consistent between physician- and self-collected samples as well as between physician-collected and urine samples. Considering that the agreement rate was particularly high for the high-risk HPV types 16 and 18, HPV testing using physician-collected samples, self-collected samples, and urine samples was equally effective for the types with high carcinogenicity.

Objective: To develop a rapid review on effective actions for the promotion of breastfeeding and healthy complementary feeding in primary health care and to summarize a list of actions and their elements for implementation. Data source: The review included systematic reviews on the effectiveness of interventions to promote breastfeeding and/or healthy complementary feeding for mothers and other caregivers, and/or professionals who work with this population, in comparison with any usual approach or none. Data synthesis: A total of 32 systematic reviews were included in the evidence synthesis. Ten types of interventions were evaluated in systematic reviews on promotion of breastfeeding and four types of interventions on promotion of healthy complementary feeding. The synthesis allowed six aspects to be discussed, and these must be considered to increase the chances of interventions’ impact: type of intervention, target audience, timing of intervention, actors that can implement it, strategies and methods of intervention, and intensity of intervention. Conclusions: It was possible to assemble a list of actions whose effectiveness has already been demonstrated, providing elements for local adaptations. Evidence is expected to support and strengthen the implementation of programs aimed at promoting breastfeeding and complementary feeding in primary health care. Resumo Objetivo: Desenvolver uma revisão rápida sobre intervenções efetivas para a promoção do aleitamento materno e da alimentação complementar saudável na Atenção Primária à Saúde e sintetizar um cardápio de ações e seus elementos para implementação. Fontes de dados: Foram incluídas revisões sistemáticas que avaliaram a efetividade de intervenções para promoção do aleitamento materno e/ou alimentação complementar saudável com mães e outros cuidadores e/ou profissionais que atuam com essa população em comparação com qualquer abordagem usual ou nenhuma. Síntese dos dados: Na síntese das evidências, foram incluídas 32 revisões sistemáticas. Nas revisões sistemáticas, foram avaliados dez tipos de intervenções no tema “promoção do aleitamento materno” e quatro tipos de intervenções no tema “promoção da alimentação complementar saudável”. A síntese dos resultados permitiu discutir seis aspectos da implementação que devem ser considerados para aumentar as chances de impacto das intervenções: tipo de intervenção, público-alvo, momento da intervenção, atores que podem implementar, estratégias e métodos para conduzir a intervenção, e intensidade da intervenção. Conclusões: Os resultados permitiram apresentar um cardápio de ações cuja efetividade já foi demonstrada, fornecendo elementos para adaptações locais. Espera-se que as evidências apresentadas possam apoiar e fortalecer a implementação de programas de promoção do aleitamento materno e da alimentação complementar saudável na Atenção Primária à Saúde.

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.

Background: Optimal early child development (ECD) is fundamental for every child to achieve their developmental potential and thrive. Household food insecurity (HFI) is a risk factor for suboptimal development, but there is still a need to better understand the pathways that explain this relationship. Objective: To evaluate whether maternal mental health and infant’s diet mediate the association between HFI and ECD using structural equation modeling. Methods: Cross-sectional study with 474 mother–infant dyads. Mothers answered a questionnaire that evaluated variables through validated instruments. Structural equation modeling analyses were conducted to obtain standardized effects (β) and bias-corrected 95% CI, enabling comparisons between the magnitude of the effects. The following observed variables were included: HFI, ECD, consumption of a healthy and diverse diet, the presence of a partner in the household, wanted pregnancy, and current breastfeeding. Latent variables were included to evaluate mental health, poverty, and neonatal health. Results: Poor maternal mental health mediated the relationship between HFI and ECD (β = −.05), but a healthy and diverse diet was not a mediator in this relationship. Poverty was related to lower development scores directly (β = .21) and indirectly (β = .02). Not having a partner (β = .05) and having an unwanted pregnancy (β = .02) predicted indirectly lower development scores. Conclusions: Poor maternal mental health mediates the relationship between HFI and ECD, and ECD is influenced by poverty, single motherhood, and unwanted pregnancy through different pathways. Therefore, public policies and interventions that aim to promote an optimal ECD should also approach these aspects.

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.

Objectives: Breastfeeding support rooms are low-cost interventions that may prolong breastfeeding and improve work performance. Thus, we sought to understand the experiences and perceptions of working women who use breastfeeding support rooms and the potential contribution to sustainable development goals.Methods: Descriptive and exploratory research was conducted through convenience sampling of women working in companies with breastfeeding support rooms in the state of Paraná, Brazil. A semi-structured questionnaire was applied through interviews and online self-completion.Results: Fifty-three women between 28 and 41 years old participated in the study. In addition, 88.7% had graduated from college, and 96% were married. From the women's experiences and perceptions, we identified that breastfeeding support rooms contribute to prolonged breastfeeding, improve physical and emotional well-being, allow women to exercise their professional activities comfortably, contribute to women's professional appreciation for the excellent relationship between employees and employers.Conclusion: In this novel study, we demonstrate how, from a female point of view, breastfeeding support rooms can contribute to 8 of the 17 sustainable development goals and should therefore be encouraged and promoted.

BackgroundImmune checkpoint blockade (ICB) induces durable clinical responses in patients with various types of cancer. However, its limited clinical efficacy requires the development of better approaches. In addition to immune checkpoint molecules, tumor-infiltrating immunosuppressive cells including regulatory T cells (Tregs) play crucial roles in the immune suppressive tumor microenvironment. While phosphatidylinositol 3-kinase (PI3K) inhibition as a Treg-targeted treatment has been implicated in animal models, its effects on human Tregs and on the potential impairment of effector T cells are required to be clarified for successful cancer immunotherapy.MethodsThe impact of a selective-PI3K inhibitor ZSTK474 with or without anti-programmed cell death 1 (PD-1) monoclonal antibody on Tregs and CD8+T cells were examined with in vivo animal models and in vitro experiments with antigen specific and non-specific fashions using peripheral blood from healthy individuals and cancer patients. Phenotypes and functions of Tregs and effector T cells were examined with comprehensive gene and protein expression assays.ResultsImproved antitumor effects by the PI3K inhibitor in combination with ICB, particularly PD-1 blockade, were observed in mice and humans. Although administration of the PI3K inhibitor at higher doses impaired activation of CD8+T cells as well as Tregs, the optimization (doses and timing) of this combination treatment selectively decreased intratumoral Tregs, resulting in increased tumor antigen-specific CD8+T cells in the treated mice. Moreover, on the administration of the PI3K inhibitor with the optimal dose for selectively deleting Tregs, PI3K signaling was inhibited not only in Tregs but also in activated CD8+T cells, leading to the enhanced generation of tumor antigen-specific memory CD8+T cells which contributed to durable antitumor immunity. These opposing outcomes between Tregs and CD8+T cells were attributed to the high degree of dependence on T cell signaling in the former but not in the latter.ConclusionsPI3K inhibitor in the combination with ICB with the optimized protocol fine-tuned T cell activation signaling for antitumor immunity via decreasing Tregs and optimizing memory CD8+T cell responses, illustrating a promising combination therapy.

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.

ω3 fatty acids show potent bioactivities via conversion into lipid mediators; therefore, metabolism of dietary lipids is a critical determinant in the properties of ω3 fatty acids in the control of allergic inflammatory diseases. However, metabolic progression of ω3 fatty acids in the skin and their roles in the regulation of skin inflammation remains to be clarified. In this study, we found that 12-hydroxyeicosapentaenoic acid (12-HEPE), which is a 12-lipoxygenase metabolite of eicosapentaenoic acid, was the prominent metabolite accumulated in the skin of mice fed ω3 fatty acid-rich linseed oil. Consistently, the gene expression levels of Alox12 and Alox12b, which encode proteins involved in the generation of 12-HEPE, were much higher in the skin than in the other tissues (eg, gut). We also found that the topical application of 12-HEPE inhibited the inflammation associated with contact hypersensitivity by inhibiting neutrophil infiltration into the skin. In human keratinocytes in vitro, 12-HEPE inhibited the expression of two genes encoding neutrophil chemoattractants, CXCL1 and CXCL2, via retinoid X receptor α. Together, the present results demonstrate that the metabolic progression of dietary ω3 fatty acids differs in different organs, and identify 12-HEPE as the dominant ω3 fatty acid metabolite in the skin.

Background: The Brazilian Breastfeeding and Complementary Feeding Strategy—Estratégia Amamenta e Alimenta Brasil (EAAB) aims to promote optimal breastfeeding (BF) and complementary feeding (CF) practices through the training of primary health professionals. Competition among health priorities and programs is one of the organizational contextual barriers to consolidating the implementation of the EAAB. Methods: This case study included six Primary Health Units (PHU) certified in the EAAB. Documentary analysis, interviews, and surveys were conducted, which informed a conceptual logical model. Organizational context indicators (positive and negative) were identified across the logical model based on the Matus Triangle, and they were used to analyze the degree of implementation of the EAAB in the PHUs. Results: The logic model elucidated six stages of EAAB implementation, but none on post-certification monitoring. Ten indicators positively influenced the implementation, including having legislation that prioritizes BF and CF. Seven indicators exerted negative influence, especially the lack of specific funding resources for the EAAB. Only one PHU had a consolidated degree of implementation. Conclusions: Lack of specific funding, monitoring of BF and CF practices, and compliance with certification criteria are the main challenges for the EAAB’s sustainability.

The study aimed to evaluate care for women with high-risk pregnancies from the healthcare team's perspective in primary healthcare (PHC) services in the city of São Paulo, Brazil. This is an evaluative study with a qualitative approach that used the open interview technique for data collection from PHC personnel. The data were explored through thematic categories built from the content emerging spontaneously from the interviews, discussed according to Health Work Process Theory. The results evidenced three domains: a "normal work routine", organized from the perspective of exclusively biological practices and in which the management model sometimes fails to allow compliance with the recommended practices; a "referral and counter-referral" system, which sometimes allows more timely interventions, more unique to the pregnant women's needs, but still disconnected from the referral services; and "shared responsibility of the PHC team for the pregnant woman", characterized by flexibilization of the work routine that extends beyond application of clinical protocols, encouraging the building of a bond and favoring qualification of care. The study revealed the need for flexibilization of use of patient care protocols in the work process, which can promote the shared responsibility of PHC teams for care, to adjust it to each pregnant woman's unique needs, beyond the limits of services' organization based on the logic of exclusively biological practices.O presente estudo objetivou avaliar a atenção às mulheres durante a gestação de alto risco, sob a ótica de quem atua nos serviços de atenção primária à saúde (APS) do Município de São Paulo, Brasil. Trata-se de uma pesquisa avaliativa de abordagem qualitativa, que utilizou a técnica da entrevista aberta para a coleta dos dados com profissionais da APS. Os dados foram explorados por meio de categorias temáticas construídas a partir do conteúdo que emergiu, de modo espontâneo, dos depoimentos, discutidos a partir da Teoria do Processo de Trabalho em Saúde. Os resultados evidenciaram três categorias: uma “rotina de trabalho protocolar”, organizada na perspectiva de práticas biologicistas e cujo modelo de gestão, algumas vezes, não permite o cumprimento das práticas preconizadas; um sistema de “referência e contrarreferência” que, por vezes, permite intervenções mais oportunas e singulares às necessidades das gestantes, mas, ainda, desarticulado dos serviços de referência; e a “corresponsabilização da equipe de APS pelo cuidado com a gestante”, caracterizado pela flexibilização da rotina de trabalho que transcende a aplicação de protocolos clínicos, incentivando a construção de vínculo e favorecendo a qualificação do cuidado. Desvelou-se a necessidade de flexibilização do uso de protocolos assistenciais no processo de trabalho, o que pode impulsionar a corresponsabilização das equipes de APS pelo cuidado, a fim de adequá-la às singularidades e necessidades de cada gestante, para além dos limites da organização dos serviços baseada na lógica de práticas biologicistas.El presente estudio tuvo como objetivo evaluar la atención a las mujeres durante la gestación de alto riesgo bajo la óptica de quien actúa en los servicios de atención primaria en salud (APS) del municipio de São Paulo. Se trata de una investigación evaluativa de abordaje cualitativo, que utilizó la técnica de la entrevista abierta para la recogida de datos con profesionales de la APS. Los datos se investigaron mediante categorías temáticas, construidas a partir del contenido que emergió, de modo espontáneo, de las declaraciones discutidas a partir de la Teoría del Proceso de Trabajo en Salud. Los resultados evidenciaron tres categorías: una “rutina de trabajo protocolaria”, organizada desde la perspectiva de prácticas biologicistas y cuyo modelo de gestión, algunas veces, no permite el cumplimiento de las prácticas preconizadas; un sistema de “referencia y contrarreferencia” que a veces permite intervenciones más oportunas y singulares para las necesidades de las gestantes, sin embargo, todavía está desarticulado respecto a los servicios de referencia; y la “corresponsabilización del equipo de APS del cuidado con la gestante”, caracterizado por la flexibilización de la rutina de trabajo, que transciende la aplicación de protocolos clínicos, incentivando la construcción de un vínculo y favoreciendo la cualificación del cuidado. Se desveló la necesidad de flexibilización del uso de protocolos asistenciales en el proceso de trabajo, lo que puede impulsar la corresponsabilización de los equipos de APS por el cuidado, a fin de adecuarlo a las singularidades y necesidades de cada gestante, yendo más allá de los límites de la organización, en cuanto a servicios basados en la lógica de prácticas biologicistas.

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

Objectives: To describe the profile of women with children aged under 4 months living in the Brazilian state capitals and in the Federal District according to their working status and to analyze the influence of maternity leave on exclusive breastfeeding (EBF) among working women. Methods: This was a cross-sectional study with data extracted from the II National Maternal Breastfeeding Prevalence Survey carried out in 2008. Initially, a descriptive analysis of the profile of 12,794 women was performed, according to their working status and maternity leave and the frequency of maternity leave in the Brazilian regions and capitals. The study used a multiple model to identify the influence of maternity leave on EBF interruption, including 3766 women who declared they were working and were on maternity leave at the time of the interview. The outcome assessed in the study was the interruption of the EBF, classified by the WHO. Results: Regarding the working status of the mothers, 63.4% did not work outside of their homes and among those who worked, 69.8% were on maternity leave. The largest prevalence among workers was of women older than 35 years of age, with more than 12 years of schooling, primiparous and from the Southeast and South regions. The lack of maternity leave increased by 23% the chance of EBF interruption. Conclusion: Maternity leave contributed to increase the prevalence of EBF in the Brazilian states capitals, supporting the importance of increasing the maternity leave period from four to six months. Resumo: Objetivos: Descrever perfil das mulheres com filhos menores de 4 meses residentes nas capitais brasileiras e no Distrito Federal segundo situação de trabalho e analisar a influência da licença-maternidade sobre o aleitamento materno exclusivo entre as mulheres trabalhadoras. Métodos: Trata-se de um estudo transversal com dados extraídos da II Pesquisa Nacional de Prevalência do Aleitamento Materno realizada em 2008. Inicialmente foi realizada análise descritiva do perfil das 10.995 mulheres participantes do estudo segundo situação de trabalho e de licença-maternidade, bem como a frequência de licença-maternidade nas regiões brasileiras e capitais. Em seguida, para identificar a influência da licença-maternidade na interrupção do aleitamento materno exclusivo, realizou-se modelo múltiplo, onde foram incluídas 3.766 mulheres que declararam trabalhar e estar em licença-maternidade no momento da entrevista. O desfecho adotado no estudo foi a interrupção do aleitamento materno exclusivo, classificado de acordo com a definição da Organização Mundial da Saúde. Resultados: Em relação à situação de trabalho, 63,4% das mães entrevistadas no Brasil não trabalhavam fora do lar e dentre as que trabalhavam fora, 69,8% usufruíam da licença-maternidade. Verificou-se maior concentração de mulheres que trabalhavam fora entre aquelas com mais de 35 anos, mais de 12 anos de escolaridade, primíparas, das regiões Sudeste e Sul. Para as mulheres que não estavam em licença-maternidade, após ajuste para todas as co-variáveis, houve um aumento da prevalência de interrupção do aleitamento materno exclusivo (RP [IC95%] ajustada 1,23 [1,11 – 1,37]). Conclusão: Verificou-se que as mulheres que não estavam em licença-maternidade de 120 dias apresentaram maior prevalência de interrupção do aleitamento materno exclusivo nas capitais brasileiras e Distrito Federal, no ano de 2008, reforçando a importância da ampliação da licença-maternidade para 6 meses. Keywords: Exclusive breastfeeding, Maternity leave, Women and work, Palavras-chave: Aleitamento materno exclusivo, Licença-maternidade, Mulher e trabalho

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

We examined the association between household food insecurity and early child development and whether or not maternal depression and anxiety modifies this association. The cross‐sectional study included 468 mother–infant pairs recruited at primary health centers of the Federal District, Brazil. Mothers answered a questionnaire that evaluated early child development (outcome), household food insecurity (independent variable), maternal depression and trait anxiety (effect modifiers). Variables were collected with validated questionnaires for the Brazilian population. Pearson's χ 2 test and logistic regression analyses were conducted. Infants who lived in a moderate or severe food insecure household had 2.52 times (95% confidence interval [CI] [1.13, 5.65]) the odds of having early child development delays compared with infants in secure households. Maternal depression and anxiety modified the strength of association between household food insecurity and early child development, which is an innovative finding. Among infants with depressed mothers, those experiencing mild (adjusted odds ratio [aOR] 3.33, 95% CI [1.17, 9.46]) and moderate/severe household food insecurity (aOR 10.13, 95% CI [2.18, 47.10]) had higher odds of having early child development delays, compared with infants in food secure households. Among infants with both anxious and depressed mothers, these associations were even stronger for mild (aOR 4.69, 95% CI [1.41, 15.59]) and moderate/severe household food insecurity (aOR 16.07, 95% CI [2.70, 95.66]). In conclusion, household food insecurity is a risk factor for early child development delays, and this association is modified by maternal depression and anxiety. Future studies should evaluate the impact of intervention packages that address maternal depression and anxiety and household food insecurity on preventing early child development delays.

The study assessed care for high-risk pregnancy, including access, functioning, and use of health services, ranging from primary healthcare (PHC) to specialized care. This was an evaluative study anchored in an analytical model that used triangulation of different information sources and comparative analysis of care for high-risk pregnancy in four Brazilian metropolises. The selected analytical categories were: access to consultations and tests, linkage between components of the healthcare networks and between users and healthcare professionals, and the care provided. Contexts of care for high-risk pregnancy were characterized by health system information indicators and a qualitative descriptive study produced by key informants, in addition to a questionnaire applied to 1,886 pregnant women seen at specialized services, having been referred by PHC. Triangulation of data obtained from secondary sources, contextualization of healthcare networks, and a survey with high-risk pregnant women allowed encompassing the complexity of the organizational arrangements in the healthcare network among the municipalities. Significant differences were identified in access, linkage, and care provided for high-risk pregnancy in the four metropolises. Campinas (São Paulo State, Brazil) was the municipality with the best performance in the indicators related to linkage and access by pregnant women to PHC. São Paulo and Porto Alegre (Rio Grande do Sul State) showed fair performance on the set of indicators as a whole, while Fortaleza (Ceará State) revealed the need for improvement in the three categories analyzed.

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

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.

Background: Since the 1980s, Brazil has implemented several initiatives to support breastfeeding. Maternity leave, paid in full for 16 weeks, has been available since 1988. However, few studies in Brazil have analyzed the impacts of maternity leave on breastfeeding using population-based indicators. Research aim: The aim was to analyze the association between maternity leave and exclusive breastfeeding interruption in children younger than 4 months residing in the Federal District of Brazil, in 2008 and 2014. Methods: Data from two surveys were used: the 2008 Second National Survey on Prevalence of Breastfeeding and the 2014 Monitoring of Infant Feeding Practices. The sample included 1,742 mothers with children younger than 4 months residing in the Federal District and using the Public Unified Health System. The main independent variable was the mother being on maternity leave and the outcome was interruption of exclusive breastfeeding. Multiple analyses were performed to test the association between maternity leave and the risk of interrupting exclusive breastfeeding, adjusting for socioeconomic, demographic, and biomedical characteristics. Results: In 2008 and 2014, the prevalence of exclusive breastfeeding was 60% and 71.4% and prevalence of maternity leave was 27% and 41%, respectively. The lack of maternity leave was strongly associated with interruption of exclusive breastfeeding in 2008 (prevalence ratio [PR] = 1.78, 95% confidence interval [CI] [1.12, 2.82]) and in 2014 (PR = 3.95, 95% CI [1.88, 8.31]) after adjusting for confounding variables. Conclusion: Not being on maternity leave was strongly associated with the interruption of exclusive breastfeeding among employed women residing in the Federal District.

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.

Coconut oil is used as a dietary oil worldwide, and its healthy effects are recognized by the fact that coconut oil is easy to digest, helps in weight management, increases healthy cholesterol, and provides instant energy. Although topical application of coconut oil is known to reduce skin infection and inflammation, whether dietary coconut oil has any role in decreasing skin inflammation is unknown. In this study, we showed the impact of dietary coconut oil in allergic skin inflammation by using a mouse model of contact hypersensitivity (CHS). Mice maintained on coconut oil showed amelioration of skin inflammation and increased levels of cis-5, 8, 11-eicosatrienoic acid (mead acid) in serum. Intraperitoneal injection of mead acid inhibited CHS and reduced the number of neutrophils infiltrating to the skin. Detailed mechanistic studies unveiled that mead acid inhibited the directional migration of neutrophils by inhibiting the filamentous actin polymerization and leukotriene B4 production required for secondary recruitment of neutrophils. Our findings provide valuable insights into the preventive roles of coconut oil and mead acid against skin inflammation, thereby offering attractive therapeutic possibilities.

This study assessed prenatal care in high-risk pregnancies and associated factors in the city of São Paulo, Brazil. This was an evaluative study of 689 pregnant women referred from primary care (PHC) to specialized care in 2016. The type of PHC model was used as the main independent variable: family health units (USF), basic health units (UBS), and UBS/mixed. Multiple logistic regression models with forward selection were used for the outcomes "early initiation of prenatal care" and "shared follow-up between specialized care and PHC". Referral by a USF was associated with higher odds of "early initiation of prenatal care" and "shared follow-up between specialized care and PHC". Independently of the type of PHC, there were associations between "early initiation of prenatal care" and white skin color, and between "shared follow-up between specialized care and PHC" and having received a home visit. The results demonstrate the importance of services organized according to the USF model, which conducts home visits and is attuned to the implicit vulnerabilities in pregnant women's individual characteristics.Avaliou-se a atenção ao pré-natal de gestantes de alto risco e a identificação de fatores associados, no Município de São Paulo, Brasil. Pesquisa avaliativa com 689 gestantes encaminhadas pela atenção primária à saúde (APS) para a atenção especializada (AE) em 2016. Considerou-se o modelo de APS como variável independente principal: unidade de saúde da família (USF), unidade básica de saúde (UBS) e UBS mista. Utilizou-se modelos de regressão logística múltipla (forward selection) para os desfechos “início precoce do pré-natal” e “acompanhamento compartilhado entre AE e APS”. Evidenciou-se maior chance de “início precoce do pré-natal” e “acompanhamento compartilhado entre AE e APS” ser encaminhada por USF. Independentemente da APS, apresentou associação para “início precoce do pré-natal” ter a pele branca, e para “acompanhamento compartilhado entre AE e APS” ter recebido visita domiciliar. Os resultados evidenciam a importância de serviços organizados segundo o modelo USF, que realizam visita domiciliar e são atentos às vulnerabilidades implícitas nas características individuais das gestantes.Se evaluó la atención prenatal en gestantes de alto riesgo y la identificación de factores asociados, en el municipio de São Paulo, Brasil. Se realizó una encuesta evaluativa a 689 gestantes que fueron dirigidas desde la atención primaria a la salud (APS) a la atención especializada (AE) en 2016. Se consideró el modelo de APS como variable independiente principal: unidad de salud familiar (USF), unidad básica de salud (UBS) y UBS/mixta. Se utilizaron modelos de regresión logística múltiple (forward selection) para los resultados “inicio precoz de prenatal” y “seguimiento compartido entre AE y APS”. Se evidenció una mayor oportunidad de “inicio precoz de la atención prenatal” y “seguimiento compartido entre AE y APS” siempre que fuera dirigido por USF. Independientemente de la APS, se presentó asociación en “inicio precoz de la atención prenatal”, tener la piel blanca y, en “acompañamiento compartido entre AE y APS”, haber recibido una visita domiciliaria. Los resultados muestran la importancia de los servicios organizados según el modelo USF, que realizan una visita domiciliaria y están atentos a las vulnerabilidades implícitas en las características individuales de las gestantes.

A 9-year-old girl was referred to our hospital because of facial palsy. Both physical and blood examination revealed hepatosplenomegaly and leukocytosis, respectively. A bone marrow examination demonstrated marked hypercellularity involving myeloblasts and lymphoblasts. Based on these results, we suspected mixed phenotype acute leukemia. However, her leukemic blasts expressed B-cell antigens, and a chromosomal analysis of her bone marrow cells revealed the following karyotype: 46, XX, t (9;22) (q34;q11.2). All her neutrophils were positive for the breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion protein. Based on these findings, she was diagnosed with a lymphoblastic crisis of chronic myelogenous leukemia (CML). Combined chemotherapy, involving imatinib, resulted in complete molecular remission. She received cord blood transplant (CBT) during the first complete remission; she is alive and has not suffered a relapse since two years after the CBT. The sudden onset of a blastic crisis in pediatric CML is rare, and it may be difficult to distinguish such cases from de novo Ph-positive leukemia. For diagnostic purposes, it is essential to consider a patient's clinical course and blood test results.

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.

It has been suggested that pain control during intracavitary brachytherapy for cervical cancer is insufficient in most hospitals in Japan. Our hospital began using caudal epidural anesthesia during high-dose-rate (HDR) intracavitary brachytherapy in 2011. The purpose of the present study was to retrospectively investigate the effects of caudal epidural anesthesia during HDR intracavitary brachytherapy for cervical cancer patients. Caudal epidural anesthesia for 34 cervical cancer patients was performed during HDR intracavitary brachytherapy between October 2011 and August 2013. We used the patients' self-reported Numeric Rating Scale (NRS) score at the first session of HDR intracavitary brachytherapy as a subjective evaluation of pain. We compared NRS scores of the patients with anesthesia with those of 30 patients who underwent HDR intracavitary brachytherapy without sacral epidural anesthesia at our hospital between May 2010 and August 2011. Caudal epidural anesthesia succeeded in 33 patients (97%), and the NRS score was recorded in 30 patients. The mean NRS score of the anesthesia group was 5.17 ± 2.97, significantly lower than that of the control group's 6.80 ± 2.59 (P = 0.035). The caudal epidural block resulted in no side-effects. Caudal epidural anesthesia is an effective and safe anesthesia option during HDR intracavitary brachytherapy for cervical cancer.

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

Drug resistance often critically limits the efficacy of molecular targeted drugs. Although pharmacological inhibition of phosphatidylinositol 3-kinase (PI3K) is an attractive therapeutic strategy for cancer therapy, molecular determinants for efficacy of PI3K inhibitors (PI3Kis) remain unclear. We previously identified that overexpression of insulin-like growth factor 1 receptor (IGF1R) contributed to the development of drug resistance after long-term exposure to PI3Kis. In this study, we examined the involvement of basal IGF1R expression in intrinsic resistance of drug-naïve cancer cells to PI3Kis and whether inhibition of IGF1R overcomes the resistance. We found that cancer cells highly expressing IGF1R showed resistance to dephosphorylation of Akt and subsequent antitumor effect by ZSTK474 treatment. Knockdown of IGF1R by siRNAs facilitated the dephosphorylation and enhanced the drug efficacy. These cells expressed tyrosine-phosphorylated insulin receptor substrate 1 at high levels, which was dependent on basal IGF1R expression. In these cells, the efficacy of ZSTK474 in vitro and in vivo was improved by its combination with the IGF1R inhibitor OSI-906. Finally, we found a significant correlation between the basal expression level of IGF1R and the inefficacy of ZSTK474 in an in vivo human cancer panel, as well as in vitro. These results suggest that basal IGF1R expression affects intrinsic resistance of cancer cells to ZSTK474, and IGF1R is a promising target to improve the therapeutic efficacy. The current results provide evidence of combination therapy of PI3Kis with IGF1R inhibitors for treating IGF1R-positive human cancers.

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.

OBJECTIVE: Update breastfeeding indicators trend in Brazil for the last three decades, incorporating more up-to-date information from the National Health Survey. METHODS: We used secondary data from national surveys with information on breastfeeding (1986, 1996, 2006, and 2013) to construct the time series of prevalence for the following indicators: exclusive breastfeeding in children under six months of age (EBF6m), breastfeeding in toddlers under 2 years of age (BF), continued breastfeeding at one year of age (BF1year), and continued breastfeeding at two years of age (BF2years). RESULTS: The prevalence of EBF6m, BF, and BF1year increased until 2006 (rising from 4.7%, 37.4%, and 25.5% in 1986 to 37.1%, 56.3%, and 47.2% in 2006, respectively). For these three indicators, there was relative stabilization between 2006 and 2013 (36.6%, 52.1%, and 45.4%, respectively). The BF2years indicator had a distinct behavior – relatively stable prevalence, around 25% between 1986 and 2006, and a subsequent increase, reaching 31.8% in 2013. CONCLUSIONS: The time series of breastfeeding indicators in Brazil shows an upward trend until 2006, stabilizing from that date onwards on three of the four indicators evaluated. This result, which can be considered as a warning sign, requires evaluation and revision of policies and programs to promote, protect and support breastfeeding, strengthening existing ones and proposing new strategies so that the prevalence of breastfeeding indicators returns to an upwards trend.

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.

Patients with an ultra-short uterine cervix as a result of large conization, repeated conization or radical trachelectomy (RT), are at high risk of preterm premature rupture of the membrane, which leads to preterm birth. We have commenced performing transabdominal cerclage (TAC) of the uterine cervix for these patients. In this study, we examined the safety of TAC and its impact on pregnancy.We have performed TAC in 11 patients before pregnancy: in six after large cervical operations, such as repeated conization; and in five for difficulties with cervical cerclage after RT. After laparotomy, a Teflon thread was placed in the avascular space between the uterine vessels and the uterine muscle, and tied. The clinical course of the patients after TAC and their pregnancy course were retrospectively reviewed.TAC was performed safely without any complications. The mean operative duration was 53 ± 10 min, and the mean blood loss during the operation was 49 ± 64 mL. Seven women conceived within 2 years after TAC. Their pregnancy courses were favorable. Five of the women underwent scheduled cesarean sections, while two pregnancies are ongoing.Although there are risks of various complications as a result of the use of non-absorbable thread and the need for two extra laparotomies, TAC can be a safe and useful option for patients who show cervical incompetence after large uterine cervical operations, such as RT or large conization.

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.

The total artificial heart (TAH) requires physiological control to respond to the metabolic demand of the body. To date, 1/R control is a single physiological control method that can control venous pressure. To realize an implantable 1/R control system, we are developing a new pressure measuring method using absolute pressure sensor. To find a method for absolute pressure sensor, which went well without calibration, concept of left atrial pressure (LAP) estimation using its pulsatile amplitude was proposed. Its possibility was investigated with two long-term survived goats whose hearts were replaced with the helical flow TAHs. In manual control condition, there existed a positive relation between mean LAP (mLAP) and normalized pulsatile amplitude (NPA). Percent systole revealed not to affect the relationship between mLAP and NPA. Dispersion was observed between different pulse rates. As for cardiac output difference (QLD) that is the difference of flow rate between systolic and diastolic phases, similar results were obtained except in low QLDs. In the 1/R control condition, relatively high correlation between mLAP and NPA could be obtained. In estimation of mLAP using the correlating function of individual goat, fairly good correlation was obtained between measured mLAP and estimated mLAP. Despite that further studies are necessary, it was demonstrated that the concept of the LAP estimation could be possible.

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.

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

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 effectiveness of acupuncture and moxibustion as an adjuvant treatment in women undergoing in vitro fertilisation (IVF) when embryo implantation has failed. Methods A prospective, randomised controlled clinical trial was conducted with 84 infertile patients who had had at least two unsuccessful attempts of IVF. The patients were randomised in three groups: control (n=28), sham (n=28) and acupuncture (n=28). The sample size was calculated by assuming a pregnancy rate of 10% when embryo implantation had failed. The pregnancy rates of the current IVF cycle were evaluated by measurement of blood β human chorionic gonadotrophin (βhCG) and subsequent transvaginal ultrasound. Acupuncture was performed on the first and seventh day of ovulation induction, on the day before ovarian puncture and on the day after embryo transfer. In the acupuncture group, patients were treated with moxibustion at nine acupuncture points (BL18, BL22, BL23, BL52, CV3, CV4, CV5, CV7, GV4) and needling at 12 points. In the sham group needles were inserted in eight areas that did not correspond to known acupuncture points. Results The clinical pregnancy rate in the acupuncture group was significantly higher than that in the control and sham groups (35.7% vs 7.1% vs 10.7%; p=0.0169). Conclusions In this study, acupuncture and moxibustion increased pregnancy rates when used as an adjuvant treatment in women undergoing IVF, when embryo implantation had failed.

The effects of repeated mild stress on DNA and lipid metabolic damages in multiple organs of dyslipidemic mice, and the preventive role of metallothionein (MT) were investigated. Female adult wild-type and MT-null mice fed high-fat diet (HFD) or standard diet (STD) were repeatedly subjected to fasting or restraint for three weeks. The liver, pancreas, spleen, bone marrow and serum samples were taken for evaluating DNA damage, MT, glutathione (GSH), corticosterone, carnitine and adiponectin. Body weights of restraint groups were reduced with the intensity of stress increased, even if the energy intakes were higher than those of STD group. Hepatic GSH levels were reduced in HFD control group and were further reduced in stress groups, especially in restraint groups, while the hepatic MT and serum corticosterone levels were increased in concert with the intensity of stress. Cellular DNA damages were generally increased by the restraint stress, especially in MT-null mice. Hepatic carnitine levels of MT-null mice were markedly lower than those of wild-type mice. The data suggest that MT plays a preventive role by acting as an antioxidant in corporation with GSH decreased by repeated stress and that MT may be an essential factor for inducing carnitine under the stress.

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.