BDNF and serum S100B levels according the spectrum of structural pathology in chronic pain patients.

Central sensitivity syndrome (CSS) consists of adaptive pathophysiological changes associated with neuroplasticity in some chronic pain disorders. It could be grouped in two main conceptual conditions: one includes those chronic pain patients without overt structural pathology such as fibromyalgia, and the other subgroup includes conditions with recognizable structural abnormalities, both somatic (osteoarthritis) and visceral (endometriosis). In order to understand the role of neuromodulators in CCS we aim to determine whether brain-derived neurotrophic factor (BDNF) and S100B are associated to specific chronic pain disorders. Serum BDNF and S100B were measured in chronic pain women with different diagnosis: 88 with osteoarthritis, 36 with endometriosis, 117 with fibromyalgia, 33 with chronic tension type headache and in 41 healthy controls. ANCOVA analysis followed by heteroscedasticity-consistent covariance matrix was performed to evaluate BDNF and S100B levels, adjusted for depression severity, pain levels and use of analgesics according different pathologies. Serum BDNF concentrations were higher and not different in patients with fibromyalgia and headache, the CSS group without structural pathology. In contrast, the concentrations of S100B were higher in patients with osteoarthritis and endometriosis, in comparison to controls, fibromyalgia and tensional headache patients. This study supports the hypothesis that BDNF and S100B neuromodulators present different serum levels according to the background disease associated to the chronic pain. These have the potential to be studied as markers of active disease or treatment evolution.

Contribution of FoxP3+ Tfr cells to overall human blood CXCR5+ T cells.

The identification that T follicular helper (Tfh) cells is critical for the emergence of germinal centre responses prompted the study of CXCR5-expressing CD4+ T cell subsets in autoimmunity. However, circulating CXCR5-expressing T cells are heterogeneous by containing Forkhead box protein 3 (FoxP3)+ T follicular regulatory (Tfr) cells in addition to bona fide Tfh cells. Such heterogeneity may hamper the analysis of the contribution of specific follicular T cell subsets for autoimmune pathogenesis. Therefore, separate assessment of Tfh and Tfr populations offer greater opportunities for stratification of autoimmune patients, such as Sjögren's syndrome patients.

Incisional hernia in hepatobiliary and pancreatic surgery: incidence and risk factors.

PURPOSE: The occurrence of incisional hernia (IH) is one of the main complications after open abdominal surgery. However, its incidence in hepatobiliary and pancreatic surgery is not known. Studies on hepatectomy and necrotizing pancreatitis show that the incidence can reach up to 42%. This study aims at evaluating the incidence of IH and its risk factors. METHODS: Patients submitted to open hepatobiliary and pancreatic surgery at our centre between 2010 and 2016 were selected. IH was defined as discontinuity in the abdominal fascia reported during physical examination or on computed tomography. Variables analysed range from individual characteristics and medical history to surgical and postoperative aspects. RESULTS: The cumulative incidence of IH was 21.6% at 72 months. In pancreatic surgery, this incidence was 11.6%, while hepatobiliary patients presented an incidence of 27.0%. Cox regression showed that height (p = 0.028), subcutaneous fat (p = 0.037), wound dehiscence (p = 0.001) and superficial surgical site infection (p = 0.001) correlate positively with IH in pancreatic surgery patients. BMI (p = 0.037) and perirenal fat (p = 0.043) associated independently with IH in hepatobiliary surgery. CONCLUSIONS: Height, obesity and wound complications are risk factors for IH in patients submitted to pancreatic surgery, whereas obesity presents as risk factor in hepatobiliary surgery patients. The incidence of IH goes up to 12% in patients submitted to pancreatic surgery, while this risk is higher in the hepatobiliary group (27%). It is suggested the adoption of strategies in the clinical practice prevents this high incidence, namely in high-risk patients.

Descending Control of Nociceptive Processing in Knee Osteoarthritis Is Associated With Intracortical Disinhibition: An Exploratory Study.

Based on the hypothesis that an imbalance in excitatory and inhibitory input is a central mechanism of knee osteoarthritis chronic pain (KOACP), this exploratory study had the following aims: to compare whether the function of the descending inhibitory pain pathway is associated with the state of inhibition in the corticospinal system indexed by the motor-evoked potential (MEP) and the cortical salient period (CSP) in patients with severe osteoarthritis (OA) and healthy controls; and to determine if there is correlation between the measures of intracortical inhibition (CSP, MEP) with changes on the numerical pain scale (NPS [0-10]) in KOACP during a conditioned pain modulation (CPM)-task considering the effect of self-reported function assessed by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and analgesic use.In a cross-sectional study, we included females (n = 21), with disability by pain or stiffness due to KOACP and healthy controls (n = 10), aged 19 to 75 years. The motor cortex excitability parameters (MEP and CSP) were assessed using the transcranial magnetic stimulation. We assessed the pain and disability by the WOMAC, and change on NPS (0-10) during CPM-task.A Multivariate analysis of covariance revealed that the adjusted mean (SD) on the MEP amplitude was 13.53% higher in the OA than in healthy subjects (1.33 [0.49] vs 1.15 [0.13]), respectively (P = 0.16). The adjusted mean (SD) on the CSP observed in OA patients was 23.43% lower than in healthy subjects (54.54 [16.10] vs 70.94 [22.87]), respectively (P = 0.01). The function of the descending pain modulatory system assessed by change on NPS (0-10) during a CPM-task was negatively correlated with the cortical excitability parameter indexed by the CSP (P = 0.001). Also, the CSP was negatively correlated with the pain and disability assessed by the WOMAC index.These findings support the hypothesis that the change in cortical plasticity in KOACP is associated with less intracortical inhibition, as measured by the CSP. These results show that the neural change in the motor cortex in KOACP is associated with pain and disability levels, and also with decreased activation of the endogenous pain-modulating system by a CPM-task.

What Makes Umbilical Cord Tissue-Derived Mesenchymal Stromal Cells Superior Immunomodulators When Compared to Bone Marrow Derived Mesenchymal Stromal Cells?

MSCs derived from the umbilical cord tissue, termed UCX, were investigated for their immunomodulatory properties and compared to bone marrow-derived MSCs (BM-MSCs), the gold-standard in immunotherapy. Immunogenicity and immunosuppression were assessed by mixed lymphocyte reactions, suppression of lymphocyte proliferation and induction of regulatory T cells. Results showed that UCX were less immunogenic and showed higher immunosuppression activity than BM-MSCs. Further, UCX did not need prior activation or priming to exert their immunomodulatory effects. This was further corroborated in vivo in a model of acute inflammation. To elucidate the potency differences observed between UCX and BM-MSCs, gene expression related to immune modulation was analysed in both cell types. Several gene expression profile differences were found between UCX and BM-MSCs, namely decreased expression of HLA-DRA, HO-1, IGFBP1, 4 and 6, ILR1, IL6R and PTGES and increased expression of CD200, CD273, CD274, IL1B, IL-8, LIF and TGFB2. The latter were confirmed at the protein expression level. Overall, these results show that UCX seem to be naturally more potent immunosuppressors and less immunogenic than BM-MSCs. We propose that these differences may be due to increased levels of immunomodulatory surface proteins such as CD200, CD273, CD274 and cytokines such as IL1ß, IL-8, LIF and TGFß2.

Employment conditions and health inequities: a case study of Brazil / Condições de emprego e iniquidades em saúde: um estudo de caso no Brasil

This paper was prepared for the Employment Conditions and Health Inequalities Knowledge Network (EMCONET), part of the WHO Commission on the Social Determinants of Health. We describe the Brazilian context of employment conditions, labor conditions and health, their characteristics and causal relationships. The social, political and economic factors that influence these relationships are also presented with an emphasis on social inequalities, and how they are reproduced within the labor market and thereby affect the health and wellbeing of workers. A literature review was conducted in SciELO, LILACS, Google and Google Scholar, MEDLINE and the CAPES Brazilian thesis database. We observed that there are more workers operating in the informal sector than in the formal sector and these former have no social insurance or any other social benefits. Work conditions and health are poor in both informal and formal enterprises since health and safety labor norms are not effective. The involvement of social movements and labor unions in the elaboration and management of workers' health polices and programs with universal coverage, is a promising initiative that is underway nationwide.

Este trabalho descreve aspectos das condições de trabalho e emprego e suas relações com a saúde, no contexto brasileiro, enfatizando as desigualdades sociais relacionadas com a inserção no mercado de trabalho, tendo sido desenvolvido como contribuição ao documento da rede "Employment Conditions and Health Inequalities Knowledge Network (EMCONET) - WHO Commission on Social Determinants of Health". A pesquisa bibliográfica foi realizada no SciELO, LILACS, Google, Google Scholar, MEDLINE e no banco de teses da CAPES. No Brasil, o número de trabalhadores inseridos no setor informal supera o daqueles no setor formal. As informações sobre adoecimento e morte relacionados ao trabalho não estão disponíveis para o conjunto da população economicamente ativa. As condições de trabalho e saúde são ruins em ambos os grupos e, apesar do complexo arcabouço legal referente à proteção dos trabalhadores e de avanços setoriais, as políticas públicas permanecem fragmentadas, apresentam baixa cobertura e pouca eficácia. O crescente envolvimento do movimento social e de sindicatos de trabalhadores na elaboração e gestão de políticas e programas de saúde sinaliza um processo promissor em curso no país.

Employment conditions and health inequities: a case study of Brazil.

This paper was prepared for the Employment Conditions and Health Inequalities Knowledge Network (EMCONET), part of the WHO Commission on the Social Determinants of Health. We describe the Brazilian context of employment conditions, labor conditions and health, their characteristics and causal relationships. The social, political and economic factors that influence these relationships are also presented with an emphasis on social inequalities, and how they are reproduced within the labor market and thereby affect the health and wellbeing of workers. A literature review was conducted in SciELO, LILACS, Google and Google Scholar, MEDLINE and the CAPES Brazilian thesis database. We observed that there are more workers operating in the informal sector than in the formal sector and these former have no social insurance or any other social benefits. Work conditions and health are poor in both informal and formal enterprises since health and safety labor norms are not effective. The involvement of social movements and labor unions in the elaboration and management of workers' health polices and programs with universal coverage, is a promising initiative that is underway nationwide.

Chronic arthritis directly induces quantitative and qualitative bone disturbances leading to compromised biomechanical properties.

OBJECTIVES: Rheumatoid arthritis (RA) is associated with an increased risk of fragility fractures. In RA patients, the direct effect of inflammation on bone is difficult to study because their skeleton is also affected by medication with corticosteroids and other drugs as well as aging and menopause, which contribute to bone fragility. This study used an animal model of chronic arthritis to evaluate the direct impact of chronic inflammation on biomechanical properties and structure of bone. METHODS: In the SKG mouse chronic arthritis model three point bending tests were performed on femoral bones and compression tests on vertebral bodies. Collagen structure was analysed using second-harmonic generation (SHG) imaging with a two-photon microscope, ultramorphology by scanning electron microscopy (SEM) coupled with energy dispersive x-ray spectroscopy (EDS) and bone density using water pycnometer. RESULTS: Arthritic bones had poor biomechanical quality compared to control bones. SHG, SEM and pycnometry disclosed variable signs of impaired collagen organization, poor trabecular architecture and low bone density. CONCLUSION: Present data demonstrate for the first time that chronic inflammation per se, without confounding influence of drugs and aging, leads to impairment of bone biomechanics in terms of stiffness, ductility and ultimate strength (fracture).

Percepção das mães sobre a importância das práticas alimentares no tratamento da constipação crônica funcional / Mothers' perception about the importance of feeding habits in the treatment of functional chronic constipation

OBJETIVO: Analisar o significado das práticas alimentares compreendendo as percepções, experiências e valores sobre a alimentação de mães de crianças e adolescentes com diagnóstico de constipação crônica funcional. MÉTODOS: 17 mães foram entrevistadas com base em um questionário semidirigido, que compreendia questões relacionadas à alimentação. Para análise, as falas foram agrupadas nos temas: "ambiente familiar durante as refeições", "dificuldades relacionadas à alimentação da criança e do adolescente", "atitudes das mães frente à recusa de alimentos" e "conhecimentos maternos sobre alimentação e sua relação com a constipação crônica funcional". RESULTADOS: A idade das mães variou de 20 a 35 anos. A maioria era casada, possuía ensino fundamental incompleto e renda familiar entre dois e três salários mínimos. Observou-se, no relato das mães, que: muitas não consideram o momento das refeições em família agradável; a limitação financeira é a maior dificuldade relacionada à alimentação dos filhos; a maioria delas, frente à recusa alimentar, adota estratégias para convencer a criança a aceitar a refeição; demonstram ter noção da importância da alimentação para melhora da constipação; creem que alguns alimentos têm efeito "obstipante". CONCLUSÕES: Mães de crianças com constipação intestinal crônica sabem que a alimentação é importante no tratamento dessa afecção e, no entanto, apenas uma parcela reconhece o papel das fibras alimentares. A refeição não é um momento prazeroso e o fator financeiro é limitante para definir os alimentos que compõem a dieta dessas crianças.

OBJECTIVE: Analyze the meaning of feeding habits according to the perceptions, experiences and values of mothers whose children and teenagers present functional chronic constipation. METHODS: 17 mothers were interviewed based on a semi-conducted questionnaire about feeding habits. The answers were gathered as following: family environment during meals, difficulties related to the eating habits of the teenager/child, the mothers' attitude regarding food rejection and mothers' knowledge about feeding and its relation to functional chronic constipation. RESULTS: The age of the mothers varied from 20 to 30 years, they had not finished high school and had an income of two to three minimum wages. The following problems aroused from their answers: most of them did not consider sharing meals with their families a pleasant time; financial constrains are the biggest obstacle to feed their children; when their children refuse to eat, most of them adopt strategies to convince them to eat; mothers do have some knowledge about the importance of the intake of different kinds of food to improve their children condition; they believe that certain kinds of food contribute to constipation. CONCLUSIONS: Despite knowing that the diet is important to the treatment of constipation, just a few mothers acknowledge the importance of dietary fiber. Meals are not a pleasant time for the families and financial problems limit the choice of proper food for these children.

Haemophilia care in children--benefits of early prophylaxis for inhibitor prevention.

Haemophilia therapy is aimed at treating and preventing bleeding episodes and related complications and clinical studies have shown that regular prophylaxis, started at an early age, is able to reduce physical impairment from haemophilic arthropathy. Today, the development of anti-Factor VIII (FVIII) inhibitors is the most serious treatment-related complication of haemophilia therapy and a number of genetic and environmental risk factors have been identified in the past years. Clinical data show that early start of prophylaxis and the avoidance of intensive treatment periods may protect patients from inhibitor development. The mechanisms are not completely understood; yet, recent experimental data suggest that pro-inflammatory or 'danger signals' may be involved in inducing tolerance vs. an effector immune response. So, exposure to a factor concentrate by itself may not be enough to trigger an immune response, while an intensive exposure to FVIII in the presence of such 'danger signals' can activate antigen-presenting cells, up-regulating co-stimulatory signals for T lymphocytes and ultimately enhancing antibody production. The 'optimal' regimen for primary prophylaxis is still not identified and barriers to prophylaxis implementation remain relevant. Key issues include the optimal age at prophylaxis onset, the optimal dosage/schedule, the proper clinical and laboratory monitoring and patients' compliance. Practical approaches to early prophylaxis as implemented in the haemophilia centres in Milan and Bremen are discussed in this respect.

Conhecimento de pediatras e nutricionistas sobre o tratamento da alergia ao leite de vaca no lactente / Pediatricians and nutritionists knowledge about treatment of cow milk allergy in infants

OBJETIVO: Avaliar o conhecimento de pediatras e nutricionistas sobre a dieta de exclusão do leite de vaca e seus derivados, com ênfase em questões relacionadas à nutrição da criança. MÉTODOS: Estudo transversal descritivo, do qual participaram pediatras (n=53) e nutricionistas (n=29), vinculados a hospitais públicos do Município de São Paulo, no ano de 2005. Os dados foram coletados por questionário auto-administrado. RESULTADOS: A idade dos profissionais variou de 21 a 50 anos. Quanto ao tempo de graduação, 41,2 por cento eram formados a menos de cinco anos e 91,6 por cento possuíam especialização, mestrado e/ou doutorado. A maioria (97,5 por cento) afirmou avaliar a dieta de crianças submetidas à exclusão do leite de vaca, entretanto, somente 48 por cento o faziam de forma mais detalhadas, incluindo o cálculo da ingestão alimentar. Apenas 38,7 por cento comparam a ingestão alimentar da criança com algum padrão de recomendação. A recomendação diária da ingestão de cálcio para crianças com até 36 meses foi corretamente assinalada por 22 por cento dos pediatras e 60,7 por cento dos nutricionistas (p=0,001). Produtos não adequados como substitutos do leite de vaca seriam recomendados por 66 por cento dos pediatras e 48,3 por cento dos nutricionistas. Com relação à leitura de rótulos de produtos industrializados, 81,6 por cento dos pediatras e 96,4 por cento dos nutricionistas orientam os pais a ler todos os termos que indicam a presença das proteínas do leite de vaca. CONCLUSÕES: Os pediatras e nutricionista demonstraram erro conceitual no que se refere às principais recomendações terapêuticas na alergia às proteínas do leite de vaca.

OBJECTIVE: Evaluate the knowledge of pediatricians and nutritionists regarding the exclusion diet of cow milk and derivates, with emphasis on questions related to the nutrition of children submitted to such diet. METHODS: Cross-sectional study that enrolled pediatricians (n=53) and nutritionists (n=29) from public hospitals in São Paulo, Brazil, during 2005. Data was collected through self-administered questionnaires. RESULTS: The age of the professionals varied from 21 to 50 years old. Regarding professional experience, 41.2 percent were graduated for less than five years and 91.6 percent had a specialization course, masters and/or PhD degree. The vast majority of professionals (97.5 percent) confirmed that they regularly evaluated the diet of children that needed exclusion of cow milk. However, only 48 percent of the professionals conducted a more detailed evaluation of the diet, including calculations of food ingestion. Only 38.7 percent of the professionals compared child's food ingestion with some recommended pattern. Recommendations for daily ingestion of calcium by children up to the age of 36 months were properly mentioned by 22 percent of the pediatricians and 60.7 percent of the nutritionists (p=0.001). Inadequate cow milk substitute products were recommended by 66 percent of the pediatricians and by 48.3 percent of the nutritionists. Regarding labels of industrialized products, 81.6 percent of the pediatricians and 96.4 percent of the nutritionists advised the parents to look for all terms that could indicate the presence of cow milk protein. CONCLUSIONS: Pediatricians and nutritionists made conceptual errors in their main recommendations regarding the treatment of cow milk protein allergy.

[B-Lynch suture in post partum hemorrhage]. / Suturas de B-Lynch em hemorragia pos-parto.

Post partum hemorrhage is a major cause of maternal morbidity and mortality. We describe a case of a woman with post partum hemorrhage due to uterine atony, successfully treated with B-Lynch suture. The authors review the causes and risk factors, and the range of medical and surgical options that may be considered for the management of post partum hemorrhage.

Regulatory T cells in transplantation tolerance.

Our ability to harness tolerance mechanisms will have a major impact in organ transplantation if it becomes possible to minimize drug maintenance, or even wean off immunosuppressive drugs. An improved understanding of the biology of regulatory T cells will make it possible to replace current induction regimens with those favouring the vaccination and selection of T cells that prevent graft rejection. Once tolerance is established, the continuous supply of graft antigens should sustain T cell mediated regulation as the dominant mechanism preventing graft rejection.

Directed differentiation of dendritic cells from mouse embryonic stem cells.

Dendritic cells (DCs) are uniquely capable of presenting antigen to naive T cells, either eliciting immunity [1] or ensuring self-tolerance [2]. This property identifies DCs as potential candidates for enhancing responses to foreign [3] and tumour antigens [4], and as targets for immune intervention in the treatment of autoimmunity and allograft rejection [1]. Realisation of their therapeutic potential would be greatly facilitated by a fuller understanding of the function of DC-specific genes, a goal that has frequently proven elusive because of the paucity of stable lines of DCs that retain their unique properties, and the inherent resistance of primary DCs to genetic modification. Protocols for the genetic manipulation of embryonic stem (ES) cells are, by contrast, well established [5], as is their capacity to differentiate into a wide variety of cell types in vitro, including many of hematopoietic origin [6]. Here, we report the establishment, from mouse ES cells, of long-term cultures of immature DCs that share many characteristics with macrophages, but acquire, upon maturation, the allostimulatory capacity and surface phenotype of classical DCs, including expression of CD11c, major histocompatibility complex (MHC) class II and co-stimulatory molecules. This novel source should prove valuable for the generation of primary, untransformed DCs in which candidate genes have been overexpressed or functionally ablated, while providing insights into the earliest stages of DC ontogeny.