Exploring protein-protein interactions for the development of new analgesics.

The development of new analgesics has been challenging. Candidate drugs often have limited clinical utility due to side effects that arise because many drug targets are involved in signaling pathways other than pain transduction. Here, we explored the potential of targeting protein-protein interactions (PPIs) that mediate pain signaling as an approach to developing drugs to treat chronic pain. We reviewed the approaches used to identify small molecules and peptide modulators of PPIs and their ability to decrease pain-like behaviors in rodent animal models. We analyzed data from rodent and human sensory nerve tissues to build associated signaling networks and assessed both validated and potential interactions and the structures of the interacting domains that could inform the design of synthetic peptides and small molecules. This resource identifies PPIs that could be explored for the development of new analgesics, particularly between scaffolding proteins and receptors for various growth factors and neurotransmitters, as well as ion channels and other enzymes. Targeting the adaptor function of CBL by blocking interactions between its proline-rich carboxyl-terminal domain and its SH3-domain-containing protein partners, such as GRB2, could disrupt endosomal signaling induced by pain-associated growth factors. This approach would leave intact its E3-ligase functions, which are mediated by other domains and are critical for other cellular functions. This potential of PPI modulators to be more selective may mitigate side effects and improve the clinical management of pain.

Blunted inflammatory response is associated with a lower response to a weight loss dietary intervention in liver recipients.

BACKGROUND & AIMS: Obesity is associated with chronic low-grade inflammation, and adipose tissue inflammation is required for fatty tissue remodeling. Interestingly, immunosuppressed patients, as liver transplant recipients, often experience excessive weight gain. We investigated how liver recipients' inflammatory response affects body weight loss induced by dietary treatment. METHODS: Overweight liver recipients were paired with non-transplanted subjects to compare their peripheral immune profiles. RESULTS: Transplanted patients had similar profiles of peripheral blood mononuclear cells compared to controls but lower CD8lowCD56+CD16+NK cells and higher B lymphocytes. Patients showed lower serum concentrations of IFN-γ, TNF, IL-4, IL-2, and IL-10 and lower inflammatory responsiveness of peripheral blood mononuclear cells under inflammatory stimuli. Liver recipients paired with non-transplanted subjects followed a weight loss dietary plan for 6 months to verify body composition changes. After 3 and 6 months of nutritional follow-up, the control group lost more body weight than the liver recipient group. The control group decreased fat mass and waist circumference, which was not observed in transplanted patients. CONCLUSION: Therefore, liver recipients under immunosuppressant treatment responded less to different inflammatory stimuli. This impaired inflammatory milieu might be implicated in the lack of response to weight loss dietary intervention. Inflammation may be essential to trigger the weight loss induced by dietary prescription. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov identification number: NCT03103984.

Identification of a novel alternative splicing isoform of the Hippo kinase STK3/MST2 with impaired kinase and cell growth suppressing activities.

Mammalian Ste-20-like Kinases 1 and 2 (MST1/2) are core serine-threonine kinases of the Hippo pathway regulating several cellular processes, including cell cycle arrest and cell death. Here, we discovered a novel alternative splicing variant of the MST2 encoding gene, STK3, in malignant cells and tumor datasets. This variant, named STK3∆7 or MST2∆7 (for mRNA or protein, respectively), resulted from the skipping of exon 7. MST2∆7 exhibited increased ubiquitylation and interaction with the E3 ubiquitin-protein ligase CHIP compared to the full-length protein (MST2FL). Exon 7 in STK3 encodes a segment within the kinase domain, and its exclusion compromised MST2 interaction with and phosphorylation of MOB, a major MST1/2 substrate. Nevertheless, MST2∆7 was capable of interacting with MST1 and MST2FL. Unlike MST2FL, overexpression of MST2∆7 did not lead to increased cell death and growth arrest. Strikingly, we observed the exclusion of STK3 exon 7 in 3.2-15% of tumor samples from patients of several types of cancer, while STK3∆7 was seldomly found in healthy tissues. Our study identified a novel STK3 splicing variant with loss of function and the potential to disturb tissue homeostasis by impacting on MST2 activities in the regulation of cell death and quiescence.

High resting energy expenditure in women with episodic migraine: exploring the use of predictive formulas.

Introduction: Migraine is a common and disabling primary headache, and its pathophysiology is not fully understood. Previous studies have suggested that pain can increase humans' Resting Energy Expenditure (REE). However, no previous study has investigated whether the REE of individuals with migraine differs from the general population. Therefore, this study aims to assess whether the REE of women with migraine differs from that of women without headaches. We also tested the accuracy of REE predictive formulas in the migraine patients. Methods: This cross-sectional study involves 131 adult women aged between 18 and 65 years, 83 with migraine and 48 without (controls). We collected clinical, demographic, and anthropometric data. Migraine severity was measured using the Migraine Disability Test and Headache Impact Test, version 6. The REE was measured by indirect calorimetry, and it was compared with the predicted REE calculated by formulas. Results: Patients with migraine had higher REE when compared to controls (p < 0.01). There was a positive correlation between REE and the patient-reported number of migraine attacks per month (Rho = 0.226; p = 0.044). Mifflin-St Jeor and Henry and Rees were the predictive formulas that have more accuracy in predicting REE in women with migraine. Discussion: Considering the benefits of nutritional interventions on treating migraines, accurately measuring REE can positively impact migraine patient care. This study enhances our understanding of the relationship between pain and energy expenditure. Our results also provide valuable insights for healthcare professionals in selecting the most effective predictive formula to calculate energy expenditure in patients with migraine.

A molecular landscape of quiescence and proliferation highlights the role of Pten in mammary gland acinogenesis.

Cell context is key for cell state. Using physiologically relevant models of laminin-rich extracellular matrix (lrECM) induction of mammary epithelial cell quiescence and differentiation, we provide a landscape of the key molecules for the proliferation-quiescence decision, identifying multiple layers of regulation at the mRNA and protein levels. Quiescence occurred despite activity of Fak (also known as PTK2), Src and phosphoinositide 3-kinases (PI3Ks), suggesting the existence of a disconnecting node between upstream and downstream proliferative signalling. Pten, a lipid and protein phosphatase, fulfils this role, because its inhibition increased proliferation and restored signalling via the Akt, mTORC1, mTORC2 and mitogen-activated protein kinase (MAPK) pathways. Pten and laminin levels were positively correlated in developing murine mammary epithelia, and Pten localized apicolaterally in luminal cells in ducts and near the nascent lumen in terminal end buds. Consistently, in three-dimensional acinogenesis models, Pten was required for triggering and sustaining quiescence, polarity and architecture. The multilayered regulatory circuitry that we uncovered provides an explanation for the robustness of quiescence within a growth-suppressive microenvironment, which could nonetheless be disrupted by perturbations in master regulators such as Pten.

Association of physical activity and sitting with metabolic syndrome and hyperglycemic clamp parameters in adolescents - BRAMS pediatric study.

Introduction: Obesity and metabolic syndrome (MetS) have immediate and long-term consequences on adolescent health and well-being. Among the available treatments for MetS in adolescents, behavioral interventions such as increasing physical activity (PA) are preferred. This study aimed to investigate the association of PA and sitting time with MetS and a complete set of metabolic health parameters. Methods: Data from the Pediatric Brazilian Metabolic Syndrome Study (BRAMS-P), a cross-sectional multicenter study conducted using a convenience sample of 448 Brazilian adolescents (10y-19y), were used. Sociodemographic and lifestyle information were collected using a standardized questionnaire. Daily PA and sitting time were estimated from the International PA Questionnaire. Anthropometric parameters, body composition, and blood pressure were measured by trained researchers. Blood lipids, uric acid, hepatic enzymes, creatinine, glycated hemoglobin, glucose, and insulin were measured in fasting blood samples, and the Homeostasis Model Assessment for Insulin Resistance was calculated. A subsample of 57 adolescents underwent the hyperglycemic clamp protocol. Results: The odds for metabolic syndrome were higher among adolescents who spent >8h sitting (OR (95%CI)=2.11 (1.02 - 4.38)), but not in those classified as active (OR (95%CI)=0.98 (0.42 - 2.26)). Adolescents who spent more time sitting had higher BMI, waist circumference, sagittal abdominal diameter, neck circumference, percentage of body fat, and worse blood lipid profile. The insulin sensitivity index was moderately and positively correlated with moderate-to-high PA in minutes per day (rho=0.29; p=0.047). Conclusion: Time spent sitting was associated with worse metabolic parameters and must be restricted in favor of adolescent health. Regular PA is associated with improved insulin sensitivity and may be encouraged not only in adolescents with obesity or metabolic disorders but also to prevent adverse metabolic outcomes in normal-weight adolescents.

Mapa de evidências sobre a efetividade clínica da medicina antroposófica: informe executivo / Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

O mapa apresenta uma visão geral das evidências sobre os efeitos da Medicina Antroposófica, referida na PNPIC como Antroposofia Aplicada à Saúde, em função de sua natureza multiprofissional. A partir de uma ampla busca bibliográfica foram incluídos no mapa 33 estudos de revisão que analisaram o efeito de intervenções com medicamentos antroposóficos, terapias antroposóficas e terapias multimodais para desfechos clínicos. No mapa estão representadas 63 associações entre 5 tipos de intervenções e 19 desfechos clínicos, com indicação do efeito reportado e nível de confiança da evidência reportada nos estudos. Principais Achados: • As intervenções foram organizadas em três grupos: Medicamentos Antroposóficos (Viscum album ­ 22 revisões e Outros medicamentos ­ 4 revisões), Terapias Antroposóficas (Euritmia ­ 2 revisões e Outras terapias ­ 1 revisão) e Terapias Multimodais (Em Geral ­ 4 revisões). • As intervenções foram associadas a 19 desfechos ordenados em cinco grupos: Bem-estar e Qualidade de Vida, Câncer, Atenção à Saúde, Indicadores Fisiológicos e Metabólicos e Outras Condições Patológicas. • A maioria das associações foi para o grupo de desfecho Câncer, seguido pelo grupo Bem-estar e Qualidade de Vida. Dentre os desfechos, destaque para: Qualidade de Vida (12 revisões), Sobrevida (9 revisões), Segurança do Paciente (8 revisões) e Sintomas de Quimioterapia e Radioterapia (7 revisões). • Dentre as intervenções, a maioria das associações foi para Viscum album (48 associações). • As intervenções multimodais, outros medicamentos, Euritmia e outras terapias foram associadas aos desfechos: Resultado do tratamento (5 associações), Satisfação e Segurança do paciente (2 associações cada), Infecções respiratórias (3 associações), Coordenação cardiorrespiratória, Transtornos gastrointestinais e Edema (1 associação cada). Implicações para a prática e pesquisa: • Considerando os efeitos positivos reportados (em 27 associações), destaque para o uso de medicamento antroposófico Viscum album (19 associações) para os desfechos Qualidade de Vida, Segurança do Paciente e Sintomas de Quimioterapia e Radioterapia. • Quanto aos efeitos potencialmente positivos (em 21 associações), a maioria foi associado ao Viscum album (18 associações) para os desfechos: Sobrevida ao câncer, Sintomas de Quimioterapia e Radioterapia e Qualidade de Vida. • Identificaram-se efeitos inconclusivos em 15 associações para 11 diferentes desfechos, o que sugere uma necessidade de novos estudos primários sobre intervenções com medicamentos e terapias antroposóficas. • Não foram identificados estudos com ausência de efeito ou efeitos negativos.

Evidence map on the clinical effectiveness of anthroposophic medicine: executive report

The map provides an overview of the evidence on the effects of Anthroposophic Medicine, referred to in the National Policy on Integrative and Complementary Practices (PNPIC) as applied Anthroposophy in Health, due to its multiprofessional nature. Based on an extensive literature search, the map includes 33 review studies that analyzed the effects of interventions with anthroposophic medicines, anthroposophic therapies, and multimodal therapies on clinical outcomes. The map represents 63 associations between 5 types of interventions and 19 clinical outcomes, indicating the reported effect and level of confidence in the evidence reported in the studies. Key Findings: • The interventions were organized into three groups: Anthroposophic Medicines (Viscum album - 22 reviews and Other medicines - 4 reviews), Anthroposophic Therapies (Eurythmy - 2 reviews and Other therapies - 1 review), and Multimodal Therapies (Overall - 4 reviews). • The interventions were associated with 19 outcomes grouped into five categories: Well-being and Quality of Life, Cancer, Healthcare, Physiological and Metabolic Indicators, and other Pathological Conditions. • The majority of associations were found in the Cancer outcome group, followed by the Well-being and Quality of Life group. Notable outcomes included Quality of Life (12 reviews), Survival (9 reviews), Patient Safety (8 reviews), and Chemotherapy and Radiotherapy Symptoms (7 reviews). • Among the interventions, the majority of associations were related to Viscum album (48 associations). • Multimodal interventions, other medicines, eurythmy, and other therapies were associated with outcomes such as Treatment Outcome (5 associations), Patient Satisfaction and Safety (2 associations each), Respiratory Infections (3 associations), Cardiorespiratory Coordination, Gastrointestinal Disorders, and Edema (1 association each). Implications for Practice and Research: • Considering the reported positive effects (in 27 associations), the use of anthroposophic medicines Viscum album (19 associations) stands out for Quality of Life, Patient Safety, and Chemotherapy and Radiotherapy Symptoms outcomes. • Regarding potentially positive effects (in 21 associations), the majority were associated with Viscum album (18 associations) for Cancer Survival, Chemotherapy and Radiotherapy Symptoms, and Quality of Life outcomes. • Inconclusive effects were identified in 15 associations for 11 different outcomes, suggesting a need for further primary studies on interventions with anthroposophic medicines and therapies. • No studies were identified with no effect or negative effects.

Decreased plasma levels and dietary intake of minerals in women with migraine.

It has been suggested that an imbalance in mineral levels is involved in the pathophysiology of migraine. However, only a few studies have investigated the circulating levels of mineral in patients with migraine during the pain-free period (i.e. interictal). This study aimed to investigate whether the interictal plasma levels of minerals of women with migraine differ from those of women without migraine (controls). This is a cross-sectional study involving 67 women, of which 38 were diagnosed with migraine and 29 were controls. The groups were similar in age and body mass index. Plasma levels of magnesium (Mg), copper (Cu), calcium (Ca), zinc (Zn), iron (Fe), and selenium (Se) were measured. Dietary intake was assessed using a 24-hour food recall, and migraine impact was evaluated using the Headache Impact Test, version 6 (HIT-6). The association between migraine disability, and plasma levels and dietary intake of minerals was assessed through correlation and logistic regression analyses. Women with migraine had significantly lower plasma levels of Mg, Ca, Cu, and Zn than controls. In parallel, dietary intake of Mg, Cu, and Fe was significantly lower in patients with migraine. Migraine impact was not associated with plasma levels or dietary intake of minerals. The results suggest that patients with migraine have lower plasma levels of minerals, and dietary intervention to ensure adequate mineral intake should be considered as a therapeutic strategy for migraine.

Organ Preservation Solutions in Transplantation: A Literature Review.

OBJECTIVES: Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABOincompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant. MATERIALS AND METHODS: This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update. RESULTS: We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year. CONCLUSIONS: The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABOincompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

Effects of Holder Pasteurization on Immune Composition of Human Milk.

Background: Human milk (HM) is the ideal food for newborn (NB) nutrition, it provides all macro and micronutrients for human growth and development and also contains bioactive compounds, which influence the development of the neonatal digestive and immune systems. The holder pasteurization process is essential to prevent NB infection from donated milk. Therefore, the aim of this study was to check whether or not holder pasteurization could impact the concentration of immune components in HM and the capacity to induce epithelial cell growth. Materials and Methods: The study was performed on raw and holder pasteurized (62.5°C/30 minutes) paired milk samples after submission to the freezing process in both phases. For cytokine and adipokine measurements, ELISA was performed on 40 individual samples of HM from single donors. For analyzes of epithelial cell growth, HuTu-80 cells were cultivated in Minimum Essential Eagle medium with 15% of raw or pasteurized milk, eight pairs of milk were used. Results: The results showed that no alteration was observed in the concentration of cytokine after milk holder pasteurization, and leptin concentration was reduced in holder pasteurized milk. The heat treatment also did not impact the capacity of breast milk to promote intestinal epithelial cell growth. Conclusions: The results showed that donated breast milk pasteurization has a small impact on the HM bioactive concentration compounds. This technique is important to avoid NB infection.

Study and Development of an Anthroposophical Formula Based on Phosphorus and Formica rufa for Onychomycosis´s Treatment.

Onychomycosis is a fungal infection of the nail plate or nail bed that leads to the gradual destruction of the nail. The main difficulties in the treatment of onychomycosis refer to the duration of treatments and their side effects. Thus, it becomes relevant to look for new therapeutic alternatives in the treatment of such common diseases that are efficient without causing the undesirable side effects on the patient's body. In this way, the objective of this study was to develop an anthroposophical formula for the treatment of onychomycosis, based on Phosphorus and Formica rufa, from an extensive bibliographic survey on the functions of these components, evaluating within the principles of Anthroposophy. Considering the set of knowledge and practices on the use of these components, it was possible to arrive at a proposal therapy that can be effective for the treatment of onychomycosis. After an extensive review of several existing patents, it was observed that formulations containing Phosphorus and Formica rufa together have not been described in other studies. Subsequently, our research group published a patent of the anthroposophical formula using these two components, with the number BR1020180750755, which will be efficient to help the recovery of nails, and facilitate normal growth.

Prognostic Significance of Chronic Kidney Disease (CKD-EPI Equation) and Anemia in Patients with Chronic Heart Failure Secondary to Chagas Cardiomyopathy.

BACKGROUND: Few studies regarding chronic kidney disease (CKD) and anemia have been conducted in patients with Chagas cardiomyopathy (CC). We evaluated the risk prediction performance of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation and anemia in CC patients. METHODS: From 2000 to 2010, a total of 232 patients were studied in a single-center retrospective study. CKD was defined as creatinine clearance <60 mL/min/1.73 m2 according to CKD-EPI equation. Anemia was defined as hemoglobin <12 g/dL (women) and <13 g/dL (men). Cox proportional hazards models were used to establish predictors for death. RESULTS: At baseline, 98 individuals (42.2%) had criteria for CKD and 41 (17.7%) for anemia. During follow-up, 136 patients (58.6%) died. Independently, CKD and anemia were not associated with all-cause mortality. However, when they coexisted, an additional risk was attributed for these patients. Cox proportional hazard models analysis identified systolic blood pressure (hazard ratio, 0.99; 95% confidence interval (CI), 0.98 to 1.00; P=0.015), implantable cardioverter-defibrillator (hazard ratio, 0.48; 95% CI, 0.27 to 0.85; P=0.012), left anterior fascicular block (hazard ratio, 1.52; 95% CI, 1.08 to 2.13; P=0.017), left ventricular end-diastolic diameter (hazard ratio, 1.04; 95% CI, 1.02 to 1.06; P < 0.001), and serum sodium (hazard ratio, 0.95; 95% CI, 0.92 to 0.99; P=0.020) as independent predictors for death. CONCLUSIONS: CKD and anemia are not independent predictors for long-term mortality in CC patients. However, the prognosis is poorer in individuals with both comorbidities.

Double-blind placebo-controlled randomized clinical trial of ginger (Zingiber officinale Rosc.) in the prophylactic treatment of migraine.

BACKGROUND: Previous studies have shown an analgesic effect of ginger in the acute treatment of migraine, and there is anecdotal evidence of its efficacy in migraine prophylaxis. OBJECTIVE: This study aimed to evaluate the potential of ginger to prevent migraine attacks. METHODS: This double-blind, placebo-controlled randomized clinical trial took place at the Headache Clinic, Universidade Federal de Minas Gerais (Belo Horizonte, Minas Gerais, Brazil), involving 107 patients. Only subjects diagnosed with episodic migraine, aged between 18 and 60 years old, and who were not taking any prophylactic medication, were enrolled in the study. After one month of observation, subjects selected for the study were randomized 1:1 into placebo and treatment groups. Patients received capsules three times per day of 200 mg of dry extract of ginger (5% active ingredient) or placebo (cellulose) for three months. Visits were performed monthly and the patients were asked to fill in a migraine diary. The adherence to treatment was evaluated by counting capsules. RESULTS: The percentage of patients who responded to treatment (i.e. a reduction of 50% in the number of migraine attacks at the end of treatment) did not differ between the groups. There was a decrease in the number of days with severe pain, analgesic use for acute migraine and duration of migraine attacks in both groups, without significant difference between ginger and placebo groups. CONCLUSIONS: Ginger provides no greater benefit in the prophylactic treatment of migraine when compared to placebo. This trial is registered at ClinicalTrials.gov (NCT02570633).

Nutritional intervention may improve migraine severity: a pilot study.

OBJECTIVE: Although some studies have investigated the role of nutritional intervention on migraine, they had focused on triggers or on weight change and, to the best of our knowledge, none studied diet quality. OBJECTIVE: To investigate whether nutritional intervention focused on improving diet quality and healthy weight can promote improvement in clinical parameters of women with migraine. METHODS: Non-controlled and non-randomized intervention study conducted for 90 days. Women received an individualized diet meal plan and nutritional orientation according to their nutritional diagnosis. Anthropometric, clinical and nutritional data were measured once a month. Diet energy content and macronutrients were evaluated using 24-hour dietary recall. Diet quality was assessed through the Brazilian Healthy Eating Index-Revised (BHEI-R). The Migraine Disability Assessment and Headache Impact Test version 6 were used to assess the severity of migraine, and the Beck Depression Inventory evaluated depressive symptoms. RESULTS: Fifty-two women aged 44.0 ± 13.0 years were enrolled. Anthropometric characteristics, energy, macronutrients and fiber intake did not change after intervention. However, the BHEI-R scores improved after 60 and 90 days of intervention. Concurrent to this, the Beck Depression Inventory scores and Headache Impact Test scores decreased after 60 and 90 days, respectively. The change in the BHEI-R score was negatively correlated with the migraine severity as assessed by the Headache Impact Test at the end of the intervention. CONCLUSIONS: We concluded that the management of diet quality may be a good strategy for improving migraine severity, regardless of the nutritional status and weight change.

Nutritional intervention may improve migraine severity: a pilot study / Intervenção nutricional melhora a gravidade da migrânea: estudo piloto

ABSTRACT Although some studies have investigated the role of nutritional intervention on migraine, they had focused on triggers or on weight change and, to the best of our knowledge, none studied diet quality. Objective To investigate whether nutritional intervention focused on improving diet quality and healthy weight can promote improvement in clinical parameters of women with migraine. Methods Non-controlled and non-randomized intervention study conducted for 90 days. Women received an individualized diet meal plan and nutritional orientation according to their nutritional diagnosis. Anthropometric, clinical and nutritional data were measured once a month. Diet energy content and macronutrients were evaluated using 24-hour dietary recall. Diet quality was assessed through the Brazilian Healthy Eating Index-Revised (BHEI-R). The Migraine Disability Assessment and Headache Impact Test version 6 were used to assess the severity of migraine, and the Beck Depression Inventory evaluated depressive symptoms. Results Fifty-two women aged 44.0 ± 13.0 years were enrolled. Anthropometric characteristics, energy, macronutrients and fiber intake did not change after intervention. However, the BHEI-R scores improved after 60 and 90 days of intervention. Concurrent to this, the Beck Depression Inventory scores and Headache Impact Test scores decreased after 60 and 90 days, respectively. The change in the BHEI-R score was negatively correlated with the migraine severity as assessed by the Headache Impact Test at the end of the intervention. Conclusions We concluded that the management of diet quality may be a good strategy for improving migraine severity, regardless of the nutritional status and weight change.

RESUMO Estudos investigaram o papel da intervenção nutricional, focada no consumo de alimentos "gatilhos" ou na alteração de peso, na melhora da migrânea. Porém, mudanças na qualidade da dieta ainda não foram abordadas. Objetivo Investigar se intervenção nutricional focada na qualidade da dieta e peso saudável pode melhorar parâmetros clínicos em mulheres com migrânea. Métodos Estudo de intervenção, não controlado e não randomizado. As mulheres receberam plano alimentar individualizado e orientações nutricionais, conforme o diagnóstico nutricional. Dados antropométricos, clínicos e alimentares foram medidos uma vez por mês durante três meses. Recordatório alimentar de 24 horas forneceu informações sobre o consumo alimentar. Qualidade da dieta foi avaliada pelo Índice Brasileiro de Alimentação Saudável (IQD-R). Os questionários Migraine Disability Test (MIDAS) e Headache Impact Test, versão 6 (HIT-6) avaliaram a incapacidade gerada pela enxaqueca e o Inventário de Depressão de Beck (BDI) investigou sintomas depressivos. Resultados Cinquenta e duas mulheres com 44,0 ± 13,0 anos participaram da amostra. Características antropométricas e consumo de energia, macronutrientes e fibras não se alteraram depois da intervenção. No entanto, os escores do IQD-R melhoraram após 60 e 90 dias de intervenção. Os escores do BDI e do HIT-6 diminuíram após 60 e 90 dias, respectivamente. A mudança no escore do IQD-R correlacionou de maneira negativa com a gravidade da enxaqueca avaliada pelo HIT-6 ao final da intervenção. Conclusões O manejo da qualidade da dieta pode ser estratégia para melhorar a gravidade da migrânea, independente do estado nutricional e da mudança de peso dos pacientes.

Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance.

BACKGROUND: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. OBJECTIVES: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. METHODS: This was a cross-sectional study of 56 adolescents (aged 10-18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. RESULTS: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. CONCLUSIONS: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.

Double-blind placebo-controlled randomized clinical trial of ginger ( Zingiber officinale Rosc.) addition in migraine acute treatment.

BACKGROUND: Previous studies have demonstrated the analgesic effects of ginger in different conditions, but evidence about its efficacy in migraine treatment is scarce. OBJECTIVE: This study aimed to evaluate the potential of ginger to improve acute migraine as an add-on strategy to standard treatment. METHODS: A double-blind placebo-controlled randomized clinical trial in the emergency room of a general hospital was conducted. Patients who sought medical care at the time of migraine attack were enrolled in this study. Only adults with episodic migraine (one to six migraine attacks per month) with or without aura were included. Sixty participants were randomized into two groups in which they received 400 mg of ginger extract (5% active ingredient) or placebo (cellulose), in addition to an intravenous drug (100 mg of ketoprofen) to treat the migraine attack. Patients filled a headache diary before, 0.5 h, 1 h, 1.5 h and 2 h after the medication. Pain severity, functional status, migraine symptoms and treatment satisfaction were also recorded. RESULTS: Patients treated with ginger showed significantly better clinical response after 1 h ( p = 0.04), 1.5 h ( p = 0.01) and 2 h ( p = 0.04). Furthermore, ginger treatment promoted reduction in pain and improvement on functional status at all times assessed. CONCLUSIONS: The addition of ginger to non-steroidal anti-inflammatory drugs may contribute to the treatment of migraine attack. This trial is registered at ClinicalTrials.gov (NCT02568644).

Sagittal abdominal diameter resembles waist circumference as a surrogate marker of insulin resistance in adolescents-Brazilian Metabolic Syndrome Study.

OBJECTIVE: To evaluate the association of the sagittal abdominal diameter (SAD) with insulin resistance (IR) and metabolic syndrome (MetS) components, and to compare SAD with waist circumference (WC). SUBJECTS/METHODS: This was a multicenter, cross-sectional study of 520 adolescents (10- to 18-years old). IR was assessed using the homeostasis model assessment of IR (HOMA-IR) and the hyperglycaemic clamp (n = 76). RESULTS: SAD and WC were positively correlated with HOMA-IR (r = 0.637 and r = 0.653) and inversely correlated with the clamp-derived insulin sensitivity index (ISI) (r = -0.734 and r = -0.731); P < .001. In the multivariable linear regression analysis, SAD was positively associated with HOMA-IR (B = 0.046 ± 0.003) and inversely associated with the clamp-derived ISI (B = -0.084 ± 0.009) after adjusting for sex, age, and Tanner's stages (P < .001). When WC replaced the SAD, it was positively associated with HOMA-IR (B = 0.011 ± 0.001) and inversely associated with the clamp-derived ISI (B = -0.018 ± 0.002); P < .001. The values of the areas under the curves (AUC) were 0.823 and 0.813 for SAD and WC, respectively. In Bland-Altman analysis, there were agreement between both, SAD and WC, with the clamp-derived ISI (mean = 0.00; P > .05). The SAD and WC were positively associated with blood pressure, triglycerides, and uric acid, and inversely associated with high-density lipoprotein (HDL)-cholesterol after adjusting for sex, age, and Tanner's stages. CONCLUSION: The SAD was associated with IR and MetS components, with a good discriminatory power for detecting IR. When compared to WC, SAD showed equivalent results.

Estratégias de Intervenção para Adesão ao Tratamento do Câncer Infantojuvenil: Relato de Caso / Intervention Strategies for Adherence to the Treatment of Childhood Cancer: Case Report / Estrategias de Intervención para la Adhesión al Tratamiento del Cancer Infanto Juvenil: Relato de Caso

Introdução: o câncer infantil é considerado um problema de saúde pública em razão do seu impacto na mortalidade. o abandono de tratamento é apontado como uma das principais causas de insucesso da terapêutica; dessa forma, estratégias para evitar o abandono são fundamentais para a melhora dos resultados de tratamento em países de baixa e média rendas. Relato do caso: Paciente com 4 anos e 11 meses de idade, admitido na instituição com massa abdominal à direita de crescimento rápido. a biópsia da tumoração confirmou se tratar de neoplasia maligna. o plano de tratamento incluiu quimioterapia e radioterapia. o paciente teve acompanhamento irregular com múltiplas faltas às consultas, aos exames agendados e ao tratamento devido ao contexto socioeconômico em que estava inserido. a equipe multiprofissional orientou à família sobre a importância do tratamento, buscando salvaguardar a saúde da criança, assim como garantir a continuidade do tratamento. as estratégias implementadas foram: institucionais, articulação com a rede e suporte social. Conclusão: após diversas intervenções da equipe multiprofissional do inca, foi possível contribuir para aderência da criança ao tratamento proposto.

Introduction: childhood cancer is considered as public health problem because of the impact on mortality. The abandonment of treatment is indicated as one of the main causes of failure in therapy; because of this, strategies to avoid abandonment are fundamental for the improvement of treatment outcomes in low-and middle-income countries. Case report:Patient 4 years 11 months, admitted in the institution with abdominal mass on the right of rapid growth. Biopsy confirmed malignant disease. The treatment included chemotherapy and radiation therapy. The patient had irregular follow-up with multiple faults in appointments, scheduled exams and treatment due to the socioeconomic context in which he was inserted. The multiprofessional team advised the family about the importance of treatment, seeking to safeguard the child's health, as well as ensuring continuity of treatment. The implemented strategies were: institutional, articulation with the network and social support. Conclusion: after several interventions by inca's multiprofessional team, it was possible to contribute to the child's adherence to the proposed treatment

ntroducción: e l cancer infantil es considerado un problema de salud pública, devido a su impacto en la mortalidad. el abandono del tratamiento es apuntado como una de las principales causas del fracaso de la terapeutica; de esta forma, estratégias para evitar el abandono son fundamentales para la mejoría de los resultados del tratamiento en países de baja y média renta. Relato del caso: Paciente con 4 anos y 11 meses de edad, admitido en la institución con masa abdominal a la derecha con crescimento rápido. la biopsia de la tumoración confirmó tratarse de neoplasia maligna. el plano de tratamiento incluye quimioterapia y radioterapia. el paciente tuvo acompañamiento irregular con múltiplas faltas a las consultas, a los exámenes agendados y al tratamento, debido al contexto socioeconómico en el que estaba insertado. el equipo multiprofissional orientó a la familia sobre la importancia del tratamiento, buscando salvaguardar la salud del niño, así como garantizar la continuidad del tratamiento. las estrategias implementadas fueron: institucionales, articulación con la red de la salud y soporte social. Conclusión: después de diversas intervenciones del equipo multiprofisional del inca, fue posible contribuir para la adherencia del niño al tratamiento propuesto.