Herramientas de la medicina genómica para la práctica clínica: el ejemplo de la psiquiatría / Tools of genomic medicine for clinical practice: The example of psychiatry

La mayoría de los trastornos psiquiátricos tienen una heredabilidad de moderada a alta, con diferentes arquitecturas genéticas. Aunque la investigación genética en psiquiatría ha tenido un avance progresivo, sus hallazgos, interpretación e impacto en la psiquiatría clínica resultan desconocidos para la mayoría de los profesionales de salud mental. En este artículo se abordan conceptos clave sobre genética para el entendimiento de algunas entidades clínicas, con énfasis en la nomenclatura genética y los tipos de mutaciones. Particularmente, se plantea el rol de la herencia en los inicios de la investigación genética en psiquiatría, los diseños de estudio más utilizados y sus principales objetivos. Por otro lado, se revisan algunas bases de datos genéticas y genómicas que pueden ser de utilidad para la práctica clínica. Entre ellas destacan , ClinVar, Ensembl y . Finalmente, se plantea una viñeta clínica en donde es posible aplicar algunas de las herramientas de la medicina genómica. Debido a que la evidencia en genética psiquiátrica se basa en estudios realizados en poblaciones con origen ancestral europeo o norteamericano, es de suma relevancia desarrollar estudios locales para incrementar el conocimiento y la aplicación de la medicina genómica sobre poblaciones subrepresentadas.

Most psychiatric disorders are moderate to highly heritable, often with different genetic architectures. Although genetic research in psychiatry has progressed, its findings, interpretation, and impact on clinical psychiatry are unknown to most mental healthcare professionals. This article addresses key genetic concepts to understand some clinical entities, emphasizing genetic terminology and types of mutations. Particularly, we describe the role of heritability in the early days of psychiatry genetic research, the most used study designs, and their main objectives. On the other hand, we review some genetic and genomic databases useful for clinical practice. These include Online Mendelian Inheritance in Man, ClinVar, Ensembl, and The Single Nucleotide Polymorphism Database. Finally, a clinical vignette is presented in which we can apply genomic medicine tools. Since the evidence in psychiatric genetics is based on studies carried out in European or North American ancestral populations, we must develop local studies to increase the knowledge and application of genomic medicine on underrepresented populations.

Posibles mecanismos de acción de la terapia electroconvulsiva en trastornos afectivos: revisión de la evidencia disponible en investigación con seres humanos

The mechanisms of action (MA) of electroconvulsive therapy (ECT) in affective disorders are poorly understood. We synthesized and discussed the evidence provided by primary studies and systematic reviews in humans. There are differences in the methylation of candidate genes involved in the response to ECT. Functioning of the hippocampal serotonin receptor 5-HT1B is associated with the response in patients with major depressive disorder (PMDD), while the striatal dopamine transporter would participate in the response of PMDD and in patients with bipolar disorders (BD). The only neurotrophic factor associated with ECT response was vascular endothelial growth factor. In BD, some oxidative stress metabolites had a clinical correlation, while tryptophan metabolism showed a clinical association in BD and PMDD. Furthermore, in PMDD, some neurodegeneration markers were implicated in the MA of ECT. There were no other biological dimensions associated with BD. In PMDD, multiple inflammatory mediators were associated with the clinical response (natural killer cells, tumor necrosis and growth factors, and interleukins 1, 4, 6, 10,1β). Likewise, some structures and circuits consistently involved at the morphological and functional level are the default mode network, cognitive control networks, frontal, temporal, cingulate, occipital and temporal cortices, frontal, temporal, precentral, fusiform and left angular gyri, hippocampus, thalamus and amygdala. Investigations are mostly focused on PMDD, are observational, and their samples limited, but they show relatively consistent results with clinical significance.

Estudio prospectivo descriptivo de las trayectorias de respuesta terapéutica en una cohorte de pacientes con trastorno depresivo mayor

Introducción: El trastorno depresivo mayor (TDM) constituye un problema de salud pública por su alta prevalencia y consecuencias biopsicosociales. Es un desorden clínicamente heterogéneo, complejo y de curso fluctuante. En Chile, no existen estudios sobre trayectorias terapéuticas en TDM. Objetivo: Describir las trayectorias de respuesta clínica en pacientes con TDM en tratamiento en centros de Atención Primaria de Salud (APS) en Chile. Método: Estudio de cohorte prospectiva de cinco meses de seguimiento. Se incluyeron pacientes ingresados en el Programa de Garantías Explícitas en Salud de Depresión de siete centros de APS de la Región de Valparaíso, Chile. Se realizaron cuatro evaluaciones (semanas 0, 4, 12 y 20) para describir variables clínicas y sociodemográficas relacionadas con la evolución. Se elaboraron trayectorias de respuesta en relación con el curso de los síntomas depresivos. Resultados: Se incluyeron 159 participantes (93% fueron mujeres), con un promedio de 43 años de edad. Las condiciones de riesgo para TDM más frecuentemente reportadas fueron el aislamiento social o la escasa red de apoyo y haber presenciado violencia intrafamiliar durante la infancia. Se obtuvo 12 trayectorias de respuesta de un total de 16 patrones posibles. Se observan diferencias al analizar las respuestas terapéuticas entre las semanas 0 y 12 y 0 y 20. Las trayectorias más frecuentes fueron el mantenimiento o empeoramiento de la sintomatología depresiva (37,7%). Conclusiones: Los resultados muestran una variabilidad sintomática durante el transcurso de un TDM. En este seguimiento de cinco meses, más de un tercio de las participantes no mejoraron sus síntomas depresivos.

Introduction: Major depressive disorder (MDD) is a public health problem due to its high prevalence and biopsychosocial consequences. It is a clinically heterogeneous and complex disorder with a fluctuating course. In Chile, there are no studies on clinical trajectories in MDD. Objective: To describe the clinical response trajectories in patients with MDD under treatment in primary care centers (PCC) in Chile. Method: We conducted a prospective cohort study with a five-month follow-up, including patients treated in the Explicit Guarantees in Healthcare program for depression at seven PCC in the Valparaíso Region, Chile. We carried out four evaluations (weeks 0, 4, 12 and 20) to describe various clinical and sociodemographic variables related to the therapeutic evolution. We elaborated response trajectories in relation to the course of depressive symptoms. Results: 159 participants were included (93% women), with an average age of 43 years old. The most frequently reported risk conditions for MDD were social isolation or poor support network and having witnessed domestic violence during childhood. Twelve response trajectories were obtained from a total of 16 possible patterns. Differences were observed when analyzing the therapeutic responses between weeks 0 and 12 and 0 and 20. The most frequent trajectories were the maintenance or worsening of depressive symptoms (37.7%). Conclusions: The results show a symptomatic variability during the course of MDD. In this five-month follow-up, more than a third of the participants did not improve their depressive symptoms.

Posibles mecanismos de acción de la terapia electroconvulsiva en esquizofrenia: revisión de la evidencia disponible en investigación con seres humanos / A review about the putative mechanisms of action of electroconvulsive therapy in schizophrenia in human research

Electroconvulsive therapy (ECT) has multiple uses in psychiatry, but its mechanisms of action (MA) in patients with schizophrenia (PS) are poorly understood. We synthesize and discuss the available evidence in this regard. We conducted a search for primary human studies and systematic reviews searching MA of ECT in PS published in PubMed/Medline, SciELO, PsycInfo, and the Cochrane Library, including 24 articles. Genetic findings are scarce and inconsistent. At the molecular level, the dopaminergic and GABAergic role stands out. The increase in brain derived neurotrophic factor (BDNF) after ECT, is a predictor of positive clinical outcomes, while the change in N-acetyl aspartate levels would demonstrate a neuroprotective role for ECT. This intervention would improve inflammatory and oxidative parameters, thereby resulting in a symptomatic improvement. ECT is associated with an increase in functional connectivity in the thalamus, right putamen, prefrontal cortex and left precuneus, structures that play a role in the neural default mode network. A decrease in connectivity between the thalamus and the sensory cortex and an enhanced functional connectivity of the right thalamus to right putamen along with a clinical improvement have been reported after ECT. Moreover a volumetric increase in hippocampus and insula has been reported after ECT. These changes could be associated with the biochemical pathophysiology of schizophrenia. Most of the included studies are observational or quasi-experimental, with small sample sizes. However, they show simultaneous changes at different neurobiological levels, with a pathophysiological and clinical correlation. We propose that the research on ECT should be carried out from neurobiological dimensions, but with a clinical perspective.

Aspectos neurobiológicos en la toma de decisiones afectivas y sociales e influencia del estrés: posibles implicancias en la toma de decisiones clínicas / Neurobiological aspects in affective and social decision-making: possible implications on clinical decision-making

RESUMEN: La toma de decisiones está influenciada por múltiples factores muchas veces no conscientes. En este artículo se sintetizan algunos correlatos neurobiológicos del componente afectivo y social sobre la toma de decisiones, incluyendo el impacto del estrés agudo y crónico y la perspectiva cognitiva de las heurísticas y los sesgos en la práctica clínica. A nivel afectivo, la hipótesis del marcador somático ha asociado la respuesta corporal periférica con estructuras nerviosas centrales en la configuración de las decisiones; intervienen estructuras como la corteza orbitofrontal y el hipocampo. En la toma de decisiones sociales se involucran las dimensiones recompensa y motivación. En este tipo de decisiones es crucial la capacidad de mentalizar a otro e integrar su perspectiva en la toma de decisiones. Esta función se ha relacionado con el surco temporal posterosuperior, la unión temporoparietal, la corteza cingulada anterior y la corteza prefrontal medial. No obstante, en la toma de decisiones sociales también se integra el cumplimiento de normas socialmente establecidas. El estrés agudo o crónico puede afectar la toma de decisiones, positiva o negativamente. En estos procesos se han involucrado al eje hipotálamo-hipófiso-adrenal junto con circuitos corticoestriados, prefrontales, amigdalinos e hipocampales. En la toma de decisiones clínicas se conjugan factores "prerreflexivos" emocionales, sociales y cognitivos que influyen directamente en las conductas adoptadas con los pacientes. Recomendamos enfatizar la investigación en esta área y fortalecer su enseñanza para reconocerlos adecuadamente.

ABSTRACT Decision-making is influenced by multiple unaware factors. We synthesize some neurobiological correlates of the affective and social components on decision-making, including the impact of acute and chronic stress. We also address the impact of heuristics and biases on clinical practice from the cognitive perspective. At an affective level, the hypothesis of the somatic marker has associated the peripheral body response with central nervous structures in the configuration of decisions; structures such as the orbitofrontal cortex and the hippocampus intervene. The reward and motivation dimensions are involved in social decision-making. In these types of decisions, the ability to mentally engage others and integrate their perspective into decision making is crucial. This function has been related to the posterior superior temporal sulcus, the temporoparietal junction, the anterior cingulate cortex, and the medial prefrontal cortex. However, compliance with socially established norms is also integrated into social decision-making. Acute or chronic stress may affect decision-making, positively or negatively. The hypothalamic-pituitary-adrenal axis has been involved in these processes together with corticostriatal, prefrontal, amygdala and hippocampal circuits. In clinical decision-making, "pre-reflective" emotional, social and cognitive factors are combined, influencing the decisions towards patients. We recommend emphasizing research in this field and strengthening education in this area to recognize these aspects adequately.

Diet and depressive disorders

ABSTRACT Background: The importance of foods or food constituents in mental health is increasingly recognized, and "nutritional psychiatry" is a growing discipline. Objective: This narrative review aims to present work supporting associations between food or food constituents and mental health, specifically depressive disorders. Methods: The data presented is derived from preclinical and clinical work, including in vitro and in vivo assays, as well as observational studies and randomized clinical trials of dietary interventions. The focus of the review is the mediation of inflammatory processes and oxidative stress by dietary constituents that are an integral part of a healthy diet, such as the Mediterranean diet and similar. Results and Discussion: We present evidence for the role of the diet in prevention and management of depressive disorders, beyond the effect of individual nutrients. The findings indicate that among the dietary components with higher degree of evidence to influence depressive disorders are long chain n-3 polyunsaturated fatty acids (EPA and DHA), and various dietary bioactive compounds, especially plant-derived secondary metabolites represented by polyphenols such as flavonoids and resveratrol. Conclusion: Diet exerts an important role on mental health, and evidence indicates that some dietary constituents contribute to the prevention of depressive disorders.

Dosis de células madre en el tratamiento de osteoartritis de rodilla / Stem cell doses in knee osteoarthritis

Resumen La osteoartritis (OA) es una enfermedad degenerativa, cuyo tratamiento convencional incluye medicamentos, fisioterapia o prótesis. Las células madre con Plasma Rico en Plaquetas y factores de crecimiento son una opción que promete controlar los síntomas, mejorar la función y regenerar el cartílago; sin embargo, no se han especificado muchos detalles del tratamiento, como el tipo y la cantidad de células madre que se deben aplicar para obtener mejores resultados. En este estudio buscamos comparar la efectividad, la seguridad y los costos de dos dosis (1X107vs 3X107) de células madre derivadas de tejido adiposo (ADSC), aplicadas por vía intraarticular. Diez pacientes, con OA de rodilla grados II y III, fueron aleatorizados para recibir 10 (n = 5) o 30 millones (n = 5) de ADSC autólogos. Al inicio y 6 a 10 meses después de la inyección, se evaluaron de acuerdo con los criterios clínicos (evaluación médica, escala WOMAC, calidad de vida) y paraclínicos (artroscopia, resonancia, biopsia). En términos de efectividad y seguridad no se observaron diferencias entre los dos grupos de dosificación, ya que todos los pacientes tuvieron una mejoría de acuerdo con los criterios médicos y la escala WOMAC (P = 0,001); en el control artroscópico, 7 pacientes tuvieron una respuesta "buena / muy buena", 1 "neutral" y 2 abandonaron el control; Las biopsias confirman la regeneración articular, aunque no hubo diferencias en las resonancias magnéticas anteriores y posteriores. En la osteoartritis de rodilla, la aplicación de 10 o 30 millones de ADSC fue igualmente efectiva y segura; sin embargo, el protocolo con 10 millones de células no requiere expansión in vitro, requiere menos tiempo, es más simple y tiene un costo menor. Este estudio muestra una buena razón para realizar ensayos clínicos aleatorios para obtener evidencia de mayor calidad.

Abstract Osteoarthritis (OA) is a degenerative disease where conventional treatment includes drugs, physiotherapy, or prostheses. Stem cells and growth factors are a promising option in controlling symptoms, functional improvement and cartilage regeneration; however, many treatment details have not been specified, such as type and number of stem cells that should be applied to obtain optimal results. In this study we sought to compare effectiveness, safety and costs of two doses (1X107vs 3X107) of adipose tissue derived stem cells (ADSC), applied intra-articularly. Ten patients, with knee OA grades II and III, were randomized to receive 10 (n=5) or 30 million (n=5) of autologous ADSCs. At baseline and 6 to 10 months after injection, they were evaluated according to clinical (medical evaluation, WOMAC scale, quality of life) and paraclinical criteria (arthroscopy, resonance, biopsy). In terms of effectiveness and safety there were no differences observed among the two dosage groups since all patients had improvement according to medical criteria and the WOMAC scale (P=0,001); in the arthroscopic control, 7 patients had "good/very good" response, 1 "neutral" and 2 forwent control; biopsies confirm joint regeneration, although there were no differences in the before and after magnetic resonances. In knee osteoarthritis, the application of 10 or 30 million ADSCs was equally effective and safe; however, the protocol with 10 million cells does not require in vitro expansion, requires less time, is simpler and has a lower cost. This study shows good reason to undertake randomized clinical trials to gain higher quality evidence.

Cerebral palsy: association between nutritional status and occurrence of oropharyngeal dysphagia / Paralisia cerebral: associação entre estado nutricional e ocorrência de disfagia orofaríngea

ABSTRACT Objective: to verify the association between nutritional status and the occurrence of oropharyngeal dysphagia in individuals with cerebral palsy. Methods: a cross-sectional, quantitative study with people aged between two and 20 years. Neuromotor impairment, occurrence and degree of dysphagia, anthropometry, food consumption, feeding route, diet fractionation and consistency were evaluated. Swallowing evaluation was performed by a skilled speech-language-hearing therapist, through the Clinical Evaluation Protocol of Pediatric Dysphagia (PAD-PED, Portuguese acronym).The statistical analysis was performed adopting p<0.05%. Results: 40 subjects with a median of 8.7 (5.45-14.5) years, 65% of whom were males. Concerning neuromotor impairment, 72.5% were classified at levels IV and V. The prevalence of dysphagia was 70%, the feeding route being predominantly oral (77.5%) with a normal diet consistency (55%). In the growth curves, all of them were classified within an adequate height for their age. As for weight, body mass index and skinfolds, 82.5%, 85% and 62.5% were eutrophic, respectively. Statistically significant association was found between dysphagia and body mass index (p=0.018). The mean daily caloric and proteic intake was 1427.29±338.62 kcal and 56.86±17.57 grams, respectively. Statistically significant association was found between the feeding route and the amount of protein ingested daily (p=0.041). Conclusion: most subjects presented oropharyngeal dysphagia and more severe motor impairment; they were fed orally with a normal diet consistency. It was observed that the greater the difficulty in swallowing, the greater the impairment of nutritional status.

RESUMO Objetivo: verificar a associação entre estado nutricional e ocorrência de disfagia orofaríngea em indivíduos com paralisia cerebral. Métodos: estudo transversal, quantitativo, realizado com indivíduos entre dois e 20 anos. Foi avaliado comprometimento neuromotor, ocorrência e grau de disfagia, antropometria, consumo alimentar, via alimentar, fracionamento e consistência da dieta. A avaliação da deglutição foi realizada por fonoaudióloga capacitada, por meio do Protocolo para Avaliação Clínica da Disfagia Pediátrica. Foi realizada análise estatística pertinente, adotando p<0,05%. Resultados: participaram 40 indivíduos com mediana de 8,7 (5,45-14,5) anos, sendo 65% do sexo masculino. Quanto ao comprometimento neuromotor, 72,5% foram classificados no nível IV e V. A prevalência de disfagia foi de 70%, via alimentar predominantemente oral (77,5%) e consistência da dieta normal (55%). Nas curvas de crescimento, todos foram classificados com estatura adequada para idade. Para peso, índice de massa corporal e dobras cutâneas houve, respectivamente, 82,5%, 85% e 62,5% em eutrofia. Foi encontrada associação estatisticamente significante entre disfagia e índice de massa corporal (p=0,018). A média diária de ingestão calórica e proteica foi de 1427,29±338,62 kcal e 56,86±17,57 gramas, respectivamente. Foi encontrada associação estatisticamente significante entre via alimentar e quantidade de proteína ingerida diariamente (p=0,041). Conclusão: a maioria dos indivíduos apresentou disfagia orofaríngea e comprometimento motor mais grave, alimentavam-se por via oral com consistência de dieta normal. Observou-se que quanto maior a dificuldade de deglutição, maior o comprometimento do estado nutricional.

Relação entre prontidão para início da alimentação oral e desempenho alimentar em recém-nascidos pré-termo / Association between readiness for oral feeding and feeding performance in preterm neonates

RESUMO Objetivo Verificar se a presença de prontidão para iniciar a alimentação oral, obtida por meio do Preterm Oral Feeding Readiness Scale (POFRAS) se relaciona com o desempenho alimentar na primeira oferta oral de leite, com o tempo de transição da sonda para a via oral plena e o tempo de internação hospitalar. Métodos Estudo longitudinal, que envolveu 65 recém-nascidos pré-termo. Foi realizada a avaliação da prontidão para início da alimentação oral, por meio do POFRAS, constituindo-se dois grupos: com e sem prontidão para iniciar a alimentação por via oral, em dois estratos de idade gestacional ao nascer: de 28 a 33 semanas e de 34 a 36 semanas. Em cada estrato, os grupos foram comparados entre si, quanto ao desempenho alimentar na primeira oferta oral de leite (por meio das variáveis proficiência, taxa de transferência e desempenho alimentar oral) e quanto ao tempo de transição da sonda para a via oral plena e o tempo de internação hospitalar. O teste t-Student ou o teste de Wilcoxon foram utilizados para comparar as variáveis contínuas e o teste exato de Fisher, para as variáveis categóricas. Resultados A prontidão para iniciar a alimentação por via oral se relacionou com melhores resultados de proficiência e taxa de transferência na primeira alimentação, contribuindo para a transição mais rápida da sonda para a via oral plena, nas crianças nascidas com idade gestacional entre 28 a 33 semanas. Conclusão a avaliação por meio do POFRAS permite estabelecer um prognóstico da alimentação oral em recém-nascidos pré-termo, menores de 34 semanas. No entanto, não exclui a necessidade de avaliação da biomecânica da deglutição.

ABSTRACT Purpose To verify whether readiness for oral feeding as evaluated by the Preterm Oral Feeding Readiness Scale (POFRAS) is associated with performance on the first oral feeding; length of transition from tube to full oral feeding, and duration of hospitalization. Methods This was a longitudinal study involving 65 preterm infants. Participants were divided into groups according to readiness for oral feeding as determined by the POFRAS, and gestational age (29-33 weeks and 34-36 weeks). Performance on the first oral feeding (proficiency, transfer rate and overall transfer), number of days from introduction to full independent oral feeding, and length of hospital stay were compared between groups. Continuous variables were compared using Student's t-test or Wilcoxon's signed-rank test. Categorical variables were compared using Fisher's exact test. Results Readiness for oral feeding was associated with higher proficiency and transfer rates on the first oral feeding, resulting in a shorter transition from tube to independent oral feeding in preterm infants with 29 to 33 weeks of gestational age at birth. Conclusion The POFRAS contributed to the prognosis of oral feeding outcomes in preterm neonates with less than 34 weeks of gestational age at birth. However, its use does not eliminate the need for an assessment of swallowing mechanisms.

Premature: growth and its relation to oral skills / Prematuros: crescimento e sua relação com as habilidades orais

OBJECTIVE: To evaluate the influence of oral motor skills of premature infants on their oral feeding performance and growth, during neonatal hospitalization.METHODS: Fifty-one newborns hospitalized in the neonatal intensive care unit of a hospital in Southern Brazil, between July 2012 and March 2013, were evaluated. The evaluation of oral feeding skills, according to Lau and Smith, was applied after prescription for starting oral feeding. The oral feeding performance was analyzed using the following variables: days taken to start independent oral feeding and hospital discharge. Growth was measured by weight, length, and head circumference, using the curves of Fenton, at birth, first and independent oral feeding, and hospital discharge.RESULTS: At birth, 71% preterm infants were proper for gestational age, most of them were males (53%), with average of 33.6 (±1.5) weeks of gestational age. The gestational age in the assessment did not influence the oral feeding performance of the premature infant and did not differ between levels. Time of transition from tube feeding to oral feeding and hospital stay was shorter when the oral skills were higher. At birth, there was a tendency of low weight and low oral feeding performance. Level IV premature infants in the release of oral feeding presented higher weights.CONCLUSION: The level of oral skills of the premature infant interfered positively on time of feeding transition from tube to independent oral feeding and hospital stay. Growth, represented by weight gain, was not affected by the level of oral skill.

OBJETIVO: Avaliar a influência da habilidade motora oral do prematuro sobre seu desempenho alimentar oral e crescimento, durante o período de internação neonatal.MÉTODOS: Foram avaliados 51 recém-nascidos (RNs) internados na Unidade de Tratamento Intensivo (UTI) Neonatal de um hospital do Sul do Brasil, entre julho 2012 e março 2013. A avaliação da habilidade de alimentação oral, segundo Lau e Smith, foi realizada após prescrição para início da alimentação por via oral (VO). O desempenho alimentar oral foi avaliado por meio das variáveis dias de transição da sonda para VO plena e tempo de internação. O crescimento foi avaliado por peso, comprimento e perímetro cefálico (PC), utilizando as curvas de Fenton, no nascimento, liberação VO, VO plena e alta hospitalar.RESULTADOS: Ao nascer, 71% dos prematuros eram adequados para idade gestacional, a maioria era do sexo masculino (53%), tendo média de 33,6 (±1,5) semanas de idade gestacional. A idade gestacional nos momentos avaliados não influenciou na habilidade oral do pré-termo, não diferindo entre os níveis. O tempo de transição da sonda para VO plena e o período de internação hospitalar foram menores quanto maior o nível de habilidade oral. Ao nascer, houve uma tendência a baixo peso e baixa habilidade oral. Na liberação da VO, as crianças do nível IV apresentaram maior peso.CONCLUSÃO: O nível de habilidade oral do prematuro interferiu positivamente no tempo de transição alimentar da sonda para VO plena e permanência hospitalar. O crescimento, representado pelo ganho de peso, não sofreu influência do nível de habilidade oral.

Therapeutic Options in Idiopathic Burning Mouth Syndrome: Literature Review

Introduction Burning mouth syndrome (BMS) is characterized by a burning sensation in the tongue, palate, lips, or gums of no well-defined etiology. The diagnosis and treatment for primary BMS are controversial. No specific laboratory tests or diagnostic criteria are well established, and the diagnosis is made by excluding all other possible disorders. Objective To review the literature on the main treatment options in idiopathic BMS and compare the best results of the main studies in 15 years. Data Synthesis We conducted a literature review on PubMed/MEDLINE, SciELO, and Cochrane-BIREME of work in the past 15 years, and only selected studies comparing different therapeutic options in idiopathic BMS, with preference for randomized and double-blind controlled studies. Final Comments Topical clonazepam showed good short-term results for the relief of pain, although this was not presented as a definitive cure. Similarly, α-lipoic acid showed good results, but there are few randomized controlled studies that showed the longterm results and complete remission of symptoms. On the other hand, cognitive therapy is reported as a good and lasting therapeutic option with the advantage of not having side effects, and it can be combined with pharmacologic therapy. .

Influência do uso do copo ou mamadeira durante a transição alimentar de recém-nascidos pré-termo sobre o sistema estomatognático e as taxas de aleitamento materno / Cup or bottle influence on pre-term newborn stomatognathic system during feed transition and breastfeeding rates / Influencia del uso de vaso o mamadera durante la transición alimentar de recién nacidos pretérmino sobre el sistema eatomatognático y las tasas de lactancia materna

Introdução: as vantagens do aleitamento materno para prematuros são: as propriedades nutritivas e imunológicas do leite humano, seu papel na maturação gastrointestinal, formação do vínculo mãe-filho, aumento do desempenho neurocomportamental, menor incidência de infecção, melhor desenvolvimento cognitivo e psicomotor e menor incidência de re-hospitalização. Objetivo: verificar por meio de revisão bibliográfica se o uso do copo ou mamadeira influência a prevalência do aleitamento. Resultados: estudos demonstram que o uso do copo é sugerido como um mecanismo de alimentação alternativo que não invade a cavidade oral, evitando a confusão de bicos e diminuindo o índice de desmame precoce. Na mamadeira, a língua apresenta postura mais retraída, o que dificulta o exercício do seu papel de guia sensorial. Desta forma, como resposta, muitos de seus reflexos estarão anulados. A alimentação por copo, por sua vez, estimula os reflexos necessários para amamentação por meio dos receptores sensórios orais e olfatórios, aumentando a produção de saliva e enzimas digestivas. O uso do copo é recomendado pela OMS (Organização Mundial da Saúde) nos casos de recém-nascidos que serão amamentados. Conclusão: pode-se perceber que apesar das vantagens e desvantagens sobre o uso do copo e da mamadeira como métodos alternativos de alimentação, a associação entre o uso desses métodos e a duração do aleitamento materno não está bem estabelecida.

Banckground: breastfeeding benefits for preterm infants are: nutritional and immunological properties from human milk, its role in gastrointestinal maturation, element of mother-infant bonding, neurobehavioral performance increasing, lower infection incidences, better psychomotor and cognitive development and lower re/hospitalization incidence. Aim: to verify through a literature review if using the cup or the bottle has an influence on breastfeeding. Results: studies show that the use of a cup is suggested as an alternative feed mechanism which does not invade the oral cavity, preventing nipple confusion and reducing the rate of early weaning. While the use of the bottle presents more retracted tongue position, making it difficult to exercise their role as a sensory guide. Thus, in response, many of its reflexes will be canceled. Besides, the cup feed, stimulates the reflexes required for feeding through the oral and olfactory sensory receptors, increasing the production of saliva and digestive enzymes. The use of cup is recommended by WHO (World Health Organization) in cases of infants who are breastfed. Conclusion: we can notice that, despite the advantages and disadvantages of using cup and bottle feeding as alternative methods, the association between the use of these methods and duration of breastfeeding is not well established.

INTRODUCCIÓN: las ventajas de la lactancia materna para bebes prematuros son: las propiedades nutritivas e inmunológicas de la leche humana, su papel en la maturación gastrointestinal, formación de vinculo madre-hijo, aumento del desarrollo neurocomportamental, menor incidencia de infección, mejor desarrollo cognitivo y psicomotor y menor incidencia de re-hospitalización. OBJETIVO: averiguar a través de una revisión bibliográfica si el uso de vaso o mamadera influye la prevalencia de lactancia. RESULTADOS: estudios demuestran que el uso del vaso se sugiere como un mecanismo de alimentación alternativo que no invade la cavidad oral, evitando confusión entre pezón y tete de la mamadera disminuyendo el índice de desmame precoz. En la mamadera, la lengua presenta una postura mas retraída, lo que dificulta el ejercicio de su papel de guía sensorial. De esta manera, como respuesta, muchos de sus reflejos estarán anulados. La alimentación a través del vaso, a su vez, estimula los reflejos necesarios para lactancia por medio de receptores sensorios orales y olfativos, aumentando la producción de saliva y enzimas digestivas. El uso del vaso es recomendado por la OMS (Organización Mundial de la Salud) en el caso de recién nacidos que serán amamantados. CONCLUSIÓN: se nota que a pesar de las ventajas y desventajas sobre el uso del vaso y de la mamadera como métodos alternativos de alimentación, la asociación entre el uso de esos métodos y la duración de lactancia materna no está bien establecida.

Hábitos alimentares e conhecimento de mulheres sobre os dez passos da alimentação saudável propostos pelo Ministério da Saúde / Feeding habits and women’s knowledge of the ten steps to healthy feeding proposed by the Ministry of Health

Introdução: Segundo dados do Ministério da Saúde, anualmente cerca de 260 mil brasileiros perdem a vida em decorrência de doenças relacionadas a uma alimentação inadequada. O objetivo deste estudo foi verificar hábitos alimentares e conhecimento de mulheres sobre os dez passos da alimentação saudável propostos pelo Ministério da Saúde. Métodos: A mostra foi constituída de 140 mulheres do município de Santa Maria, RS. Foram aplicados dois questionários: um sobre o hábito alimentar e outro sobre o conhecimento sobre os dez passos da alimentação saudável. A análise estatística dos resultados foi realizada através do programa SPSS versão 15.0, com teste qui-quadrado. Os dados foram considerados significativos para p<0,05. Resultados: Em relação à orientação nutricional, 87 mulheres entrevistadas não tiveram orientação nos últimos dois anos. Apenas 50 mulheres responderam realizar quatro refeições por dia, 44 mulheres referiram consumir 3 ou mais unidades de frutas por dia, o que é proposto pelo Ministério da Saúde. A prática de atividade física não é realizada pela maioria das pesquisadas e sobre a retirada de gorduras aparente das carnes os resultados foram satisfatórios, visto que a maioria das mulheres retira. Conclusão: As mulheres que apresentam hábitos de vida saudáveis têm maior conhecimento sobre os dez passos da alimentação saudável, contudo observamos que a maioria das mulheres se enquadra em baixo nível de conhecimento, independente do nível sócio-econômico. A promoção de hábitos saudáveis deveria ser incluída em ações socioeducativas a fim de desestimular hábitos inadequados e prevenir o surgimento doenças crônicas metabólicas.

Introduction: According to data of the Ministry of Health, about 260 thousand Brazilians die annually as a result of diseases related to inadequate feeding. The aim of this work was to determine women’s feeding habits and knowledge of the ten steps to healthy feeding proposed by the Ministry of Health. Methods: The sample was composed of 140 women living in Santa Maria, RS. Two questionnaires were responded: one about feeding habits and one about knowledge of the 10 steps to healthy feeding. The statistical analysis of the results was performed through the software SPSS, version 15.0, with the chi-square test. Data were considered significant when p<0.05. Results: Regarding nutritional guidance, 87 interviewees did not have any guidance for the last two years. Only 50 women reported they ate 4 meals a day, 44 women said they ate 3 or more fruits daily, as proposed by the Ministry of Health. Physical activity is not practiced by most of the respondents. Concerning removal of apparent fat from meats, the results were satisfactory, as most women do it. Conclusion: Women who have healthy living habits are more familiar with the ten steps to healthy feeding; however, we noted that most women have little knowledge, whatever their socioeconomic status. The promotion of healthy feeding habits should be included in socio-educational actions in order to discourage unhealthy habits and prevent the emergence of chronic metabolic diseases.

Composição corporal em mulheres com câncer da mama / Body compositiom in women with breast cancer

O câncer de mama é o tipo de câncer mais prevalente nas mulheres, sendo a principal causa de mortalidade por câncer na população feminina. Alguns estilos de vida têm sido associados a uma redução do risco de câncer da mama, como o controle do peso corporal. O objetivo do presente trabalho foi verificar a influência da composição corporal em pacientes com câncer da mama. Foram entrevistadas 48 mulheres com diagnóstico de câncer de mama, nos meses de setembro e outubro de 2006, no Hospital Universitário de Santa Maria, RS, e em uma clínica particular da cidade de Santa Maria, RS. Os dados obtidos foram analisados por intermédio de estatística descritiva e correlação de Spearman. A idade média ao diagnóstico foi de 52 anos. A maioria das mulheres possuía de dois a três filhos (52,1%). Em relação ao peso corporal, houve prevalência de eutrofia (37,5%), e o índice de obesos mostrou-se significativo (33,4% dos diferentes níveis de obesidade). O ganho de peso depois do tratamento foi verificado em grande parte da amostra. O conhecimento científico acumulado indica que apenas alguns casos de câncer da mama podem ser explicados pelos principais fatores de risco descritos neste estudo.

Breast cancer is the most prevalent in women, representing the main mortality cause by cancer in the female population. Some kinds of life style have been linked to the breast cancer reduction, as body weight control. The aim of the present work was to verify the body composition influence in breast cancer patients. Forty eight women presenting a breast cancer diagnosis have been interviewed, between September and October 2006, at the University Hospital and at Oncocentro Clinic, in Santa Maria, RS. The obtained data were analysed through the descriptive statistic and Spearman correlation. The average age at the diagnosis was 52. Most women had from two to three children (52%). Related to the body weight, there was prevalence of eutrophy (37,5%) and, even though the obese rates have not been prevalent, the latter was significant (33,4% of the different kinds of obesity). The weight earnings after the treatment was verified in a large part of the sample. The accumulated scientific knowledge indicates that just some cases of breast cancer can be explained by the main risk factors described in this study.

Transferrin uptake may occur through detergent-resistant membrane domains at the cytopharynx of Trypanosoma cruzi epimastigote forms

Uptake of transferrin by epimastigote forms of the protozoan Trypanosoma cruzi occurs mainly through a cytostome/ cytopharynx, via uncoated endocytic vesicles that bud off from the bottom of the cytopharynx. We have here examined whether detergent-resistant membrane (DRM) domains might be involved in this process. Purified whole cell membrane fractions were assayed for cholesterol levels and used in dot blot analyses. Detergent-resistant membrane markers (cholera B toxin and anti-flotillin-1 antibody) presented positive reaction by dot blots in cholesterol-rich/ protein-poor membrane sub-fractions. The positive dot blot fraction was submitted to lipid composition analysis, showing composition similar to that of raft fractions described for other eukaryotic cells. Immunofluorescence assays allowed the localization of punctual positive signal for flotillin-1, matching the precise cytostome/ cytopharynx location. These data were confirmed by immunofluorescence assays with the co-localization of flotillin-1 and the transferrin uptake site. Our data suggest that DRM domains occur and are integrated at the cytostome/ cytopharynx of T. cruzi epimastigotes, being the main route for transferrin uptake.