CRISPR/sgRNA-directed synergistic activation mediator (SAM) as a therapeutic tool for Parkinson´s disease.

Parkinson`s disease (PD) is the second most prevalent neurodegenerative disease, and different gene therapy strategies have been used as experimental treatments. As a proof-of-concept for the treatment of PD, we used SAM, a CRISPR gene activation system, to activate the endogenous tyrosine hydroxylase gene (th) of astrocytes to produce dopamine (DA) in the striatum of 6-OHDA-lesioned rats. Potential sgRNAs within the rat th promoter region were tested, and the expression of the Th protein was determined in the C6 glial cell line. Employing pseudo-lentivirus, the SAM complex and the selected sgRNA were transferred into cultures of rat astrocytes, and gene expression and Th protein synthesis were ascertained; furthermore, DA release into the culture medium was determined by HPLC. The DA-producing astrocytes were implanted into the striatum of 6-OHDA hemiparkinsonian rats. We observed motor behavior improvement in the lesioned rats that received DA-astrocytes compared to lesioned rats receiving astrocytes that did not produce DA. Our data indicate that the SAM-induced expression of the astrocyte´s endogenous th gene can generate DA-producing astrocytes that effectively reduce the motor asymmetry induced by the lesion.

Parents' Perception of Barriers to the Comprehensive Management of Children With Cleft Lip and Palate in Bogota, Colombia.

OBJECT: To identify the perception of barriers to the comprehensive management of cleft lip and palate (CLP) by parents/caregivers of Colombian children with this condition. SETTING AND SAMPLE POPULATION: Fifty parents/caregivers of children with CLP under 12 years attending a center specialized in the management of craniofacial congenital conditions in Bogota, Colombia. MATERIALS AND METHODS: This study consisted of 2 phases: a quantitative phase (descriptive cross-sectional) and a qualitative phase (focus group [FG]). Chi-square and Fisher exact tests were used to analyze the association variables. The barriers and alternative ways to overcome barriers were analyzed in the FG. RESULTS: Comprehensive management was mostly defined as access to multiple treatments (54%), and this concept was expanded in the FG toward understanding CLP at all levels. Monoparental families spend their income on treatments (29%) than nuclear families (0%) (P = .001). All parents with high education levels were familiar with healthcare centers specialized in CLP as opposed to 66.7% of parents with basic primary education (P < .05). Regarding the timeliness of appointments, 12.2% of parents earning between 1 and 2 minimum wages reported some kind of difficulty, whereas those earning less than one minimum wage reported difficulties in 66.7% of cases (P = .046). CONCLUSIONS: All participants reported barriers, which increased or decreased depending on their socioeconomic status. The FG allowed the discussion of alternatives to overcome barriers, such as structural, solidarity, and self-management actions.

Percepciones asociadas a conductas sexuales de riesgo / Perceptions associated with risky sexual behaviors

Resumen: Objetivo: Identificar en un grupo de jóvenes tabasqueños las percepciones asociadas con conductas sexuales de riesgo. Material y métodos: Se trata de un estudio mixto y transversal, realizado con un muestreo no probabilístico a conveniencia de 60 personas, quienes cumplían con los criterios de inclusión (18-25 años) pertenecientes al estado de Tabasco, 30 hombres y 30 mujeres. Se les aplicó la encuesta de salud y hábitos sexuales. Resultados: Las mujeres señalaron como sus mayores fuentes de educación sexual a los médicos (30%) y a sus madres (23%); mientras que, en el grupo de los hombres, fueron médicos, amistades, libros, etc. Para la percepción de riesgo de contraer VIH con el comportamiento sexual actual, los hombres percibieron mayor riesgo de contagio que las mujeres. Relacionado con las medidas que protegen del VIH, el uso del preservativo fue el método identificado como el más seguro, tanto en hombres (96.66%) como en mujeres (100%). En segundo lugar, se reconoció la opción "hacerse pruebas con frecuencia"; sin embargo, el 65% señaló nunca haberse realizado la prueba de VIH. Acerca del uso de los preservativos, en ambos grupos, predominaron respuestas, tales como, "son complicados de usar", "crean desconfianza en la pareja", entre otras. Sobre la percepción de los mecanismos a través de los cuales se podría adquirir el VIH, los 60 (100%) encuestados marcaron que el VIH se transmite a través de las relaciones sexuales; sin embargo, la opción "por picadura de mosquito" fue elegida por 3 (10%) hombres y una mujer (3.33%). Conclusiones: Las percepciones erróneas pueden ser determinantes para acceder a prácticas sexuales inseguras. Identificar las percepciones equivocadas, las fuentes, calidad y veracidad de la información en temas de sexualidad, así como los factores de riesgo y de protección, puede servir para diseñar intervenciones psicoeducativas eficientes, como estrategia de prevención para los adolescentes y los jóvenes.

Abstract: Objective: To identify youth perceptions associated to risky sexual behaviors in a group of teenagers from Tabasco. Material and methods: It is a mixed, cross-sectional study with a non-probabilistic sampling which was carried out at the convenience of 60 people who met the inclusion criteria (18-25 years old) belonging to the state of Tabasco, consisting of 30 women and 30 men. Health and sexual habits surveys were applied to them. Results: Women indicated doctors (30%) and their mothers (23%) as their main sources of sexual education; while, in the group of men, they referred to doctors, friends, books, etc. For the perception of risk of acquiring HIV with current sexual behavior, men perceived a higher risk of infection in comparison to women. In relation of measures that protect against HIV, the use of condoms was identified as the safest method, both in men (96.66%) and in women (100%). The second safest option they referred to was "to get tested frequently"; however, 65% reported never having an HIV test in the past. Regarding the use of condoms, in both groups, responses predominated, such as, "they are difficult to use", "they create mistrust in the partner", among others. Concerning about the perception of mechanisms through which HIV could be acquired, 60 participants (100%) indicated that HIV is transmitted through sexual intercourse; however, the option "by mosquito bite" was chosen by 3 men (10%) and one woman (3.33%). Conclusions: Wrongful perceptions can be decisive in the practice of unsafe sexual practices. Identifying misperceptions, sources, quality and veracity of information on sexuality issues, as well as risk and protective factors, can be useful to design efficient psychoeducational interventions as a prevention strategy for adolescents and the youth.

[Los niveles de mediadores prorresolutivos no corresponden con los de mediadores inflamatorios en enfermedades isquémicas coronarias].

BACKGROUND: Inflammation can be grouped into three phases: proinflammatory, anti-inflammatory, and resolution. The latter, mainly attributed to lipid mediators, is the most recently described, and has been studied little in coronary ischemic diseases. OBJECTIVE: To evaluate 1) if acute coronary syndromes (ACS) manifest different circulating levels of resolution mediators compared with stable angina (SA); 2) if their concentrations are related to those of pro and anti-inflammatory mediators; and 3) if such concentrations are associated with the severity of the disease and the damage produced. METHOD: LTB4, RvD1, LXA4, ET-1, MMP-2, MMP-9, TIMP-1, IL-1ß, IL-6, IL-8 and IL-10 were measured in serum. The GRACE score was established as parameter of gravity, and LVEF as a damage parameter. RESULTS: Thirty patients with SA, 37 with NEST-ACS, 38 with STEMI, and 10 individuals with non-cardiogenic chest pain were included. Patients with coronary artery disease showed elevated levels of inflammatory cytokines and low levels of resolution mediators. CONCLUSIONS: The low resolution response even in patients with acute coronary disease suggests an inability to repair damage. Testing this hypothesis would have the potential to suggest new therapies for the management of chronic cardiovascular inflammation.

ANTECEDENTES: La inflamación puede agruparse en tres fases: proinflamatoria, antiinflamatoria y de resolución. Esta última, principalmente atribuida a mediadores lipídicos, es la de más reciente descripción y se ha estudiado poco en las enfermedades isquémicas coronarias. OBJETIVOS: Evaluar 1) si los síndromes coronarios agudos (SICA) manifiestan niveles circulantes distintos de mediadores de resolución comparados con la angina estable (AE); 2) si sus concentraciones se relacionan con las de mediadores proinflamatorios y antiinflamatorios; y 3) si dichas concentraciones se asocian con la gravedad de la enfermedad y el daño producido. MÉTODO: Se midieron LTB4, RvD1, LXA4, ET-1, MMP-2, MMP-9, TIMP-1, IL-1ß, IL-6, IL-8 e IL-10 en suero. Se establecieron la puntuación GRACE como parámetro de gravedad y la fracción de eyección del ventrículo izquierdo (FEVI) como parámetro de daño. RESULTADOS: Se incluyeron 30 pacientes con AE, 37 con SICA sin elevación del segmento ST (SICA-SEST), 38 con Infarto agudo del miocardio con elevación del segmetno ST(IAM-CEST) y 10 con dolor torácico no cardiogénico. Los pacientes con enfermedad coronaria mostraron niveles elevados de citocinas inflamatorias y bajos de mediadores de resolución. CONCLUSIONES: La escasa respuesta de resolución aun en pacientes con enfermedad coronaria aguda sugiere una incapacidad para reparar daños. Probar esta hipótesis tendría el potencial de sugerir nuevas terapias para el manejo de la inflamación cardiovascular crónica.

Relationship between family-related social determinants and dental caries in preschoolers from Anapoima, Cundinamarca / Relación entre determinantes sociales del ámbito familiar y caries dental en niños preescolares de Anapoima, Cundinamarca

ABSTRACT. Objective: identify social determinants of health in families of preschoolers from Anapoima, Cundinamarca, and their relationship with prevalence of caries experience. Methods: in the framework of the Alliance for a Caries-Free Future - Colombia Chapter (Alianza por un Futuro Libre de Caries-Capítulo Colombia, AFLC-CC), the prevalence of caries experience in preschool children from Anapoima, Cundinamarca, was assessed using the International Caries Detection and Assessment System (ICDAS) and the dmft (decayed, missing, filled teeth) index, characterizing their families and homes. Descriptive analysis was done, using X2 to explore associations between dmft and ICDAS with socioeconomic and infrastructure conditions, as well as health practices in families. Results: 120 kindergarten children from the municipality of Anapoima were assessed and their homes were visited. The prevalence of caries experience (dmft) was 33.3% (average: 1.3 ± 2.5); when initial lesions were included, the prevalence reached 46.7% (4.3 ± 7.0). There was a relationship between the presence of caries and type of oral health problems referred to by parents, kin relationship with caregiver, visits to the oral health service, and availability of a space for the toothbrush (p < 0.05). Conclusions: the assessed children showed low caries experience compared to national benchmarks, which can be explained by the intermediate determinants identified in their family environments, with economic, infrastructure and family structure conditions favorable to health practices. It is necessary to better understand the relationship between social determinants and oral health from a structural point of view and to strengthen health strategies, in order to achieve caries-free populations.

RESUMEN Objetivo: identificar determinantes sociales de salud, en el ámbito familiar, en preescolares de Anapoima, Cundinamarca, y su relación con la prevalencia de experiencia de caries. Métodos: en el marco de la Alianza por un Futuro Libre de Caries-Capítulo Colombia (AFLC-CC), se valoró la prevalencia de experiencia de caries en niños preescolares de Anapoima, Cundinamarca, usando el Sistema Internacional de Detección y Valoración de Caries (ICDAS) y el índice ceod (cariados, extraídos y obturados, por diente), y se caracterizaron sus familias y viviendas. Se hizo análisis descriptivo y usando 2 se exploraron asociaciones entre ceod e ICDAS y condiciones socioeconómicas, de infraestructura y prácticas de salud en las familias. Resultados: se valoraron 120 niños de jardines infantiles del municipio de Anapoima y se visitaron sus hogares. La prevalencia de experiencia de caries (ceod) fue de 33,3% (promedio: 1,3 ± 2,5); al incluir lesiones iniciales, fue de 46,7% (4,3 ± 7,0). Se encontró relación entre presencia de caries y tipo de problemas de salud bucal referidos por los padres, relación filial con el cuidador, asistencia al servicio de salud bucal y disponibilidad de un espacio para el cepillo (p < 0,05). Conclusiones: los niños valorados presentaron baja experiencia de caries, en comparación con referentes nacionales, lo cual se explica por los determinantes intermedios identificados en su ámbito familiar, en los que se evidencian condiciones económicas, de infraestructura y de conformación familiar favorables para las prácticas de salud. Es necesario profundizar en la comprensión de la relación entre determinantes sociales y salud bucal desde la esfera estructural y fortalecer las estrategias en salud, con miras a lograr poblaciones libres de caries.

A PREDICTIVE MODEL FOR AXILLARY LYMPH NODE PATHOLOGIC COMPLETE RESPONSE IN PREMENOPAUSAL BREAST CANCER PATIENTS AFTER NEOADJUVANT CHEMOTHERAPY: A CROSS-SECTIONAL STUDY IN A L ATIN-AMERICAN POPULATION / Um modelo preditivo para a resposta patológica completa axilar em pacientes com câncer de mama premenopausal após quimioterapia adjuvante: estudo transversal em uma população latino-americana

Introduction: A large group of lymph node-positive breast cancer patients receive neoadjuvant chemotherapy and subsequently undergo axillary lymph node dissection. It has been previously proposed that axillary lymph node dissection may be avoided ­ and it's associated reduced morbidity ­ in patients showing pathologic complete response. Therefore, the purpose of this study was to develop a nomogram to predict axillary node pathologic response to neoadjuvant chemotherapy in breast cancer patients in order to guide the surgical treatment decision-making process for this group of patients. Methods: A cross-sectional, secondary data study was carried out between 2013-2016 on 222 lymph node-positive breast cancer patients who received neoadjuvant chemotherapy followed by locoregional management, including axillary lymph node dissection. Logistic regression analysis was performed to determine the association of the axillary pathologic complete response with the different clinical and pathological variables. Variables found to be statistically significantly associated with axillary pCR (pathologic complete response) were used to create the logistic regression model and the nomogram in pre-menopausal patients. Axillary pCR was defined as absence of residual disease in the breast and of micro-metastasis in axillary lymph nodes. Samples with isolated tumor cells were considered as positive for residual disease. Results: a total of 222 patients were included, of which 131 were premenopausal at the time of diagnosis. Axillary pathologic complete response was observed in 55.7% (73 of 131) of patients, and was significantly associated with estrogen receptor (ER) negative tumors (OR 2.59, 95%CI 1.21-5.53), progesterone receptor (PR) negative tumors (OR 2.63, 95%CI 1.28-5.38), and Her2 positive tumors (OR 0.40, 95%CI 0.19-0.84), for which a significant correlation with increased probability of achieving axillary pathologic complete response was evidenced. Conclusion: The performance of this model to predict axillary pCR in pre-menopausal patients was weak, and therefore the decision to avoid surgical axillary dissection should not be based solely on the developed nomogram. However, further studies may lead to validation of this model

Introdução: Um grande grupo de pacientes com câncer de mama linfonodo-positivo recebe quimioterapia neoadjuvante, que subsequentemente são submetidos a dissecção de linfonodos axilares. Foi proposto anteriormente que a dissecção de linfonodos axilares pode ser evitada ­ assim como a redução de sua morbidade - em pacientes que apresentam resposta patológica completa. Portanto, o objetivo deste estudo foi desenvolver um nomograma para prever a resposta patológica do linfonodo axilar à quimioterapia neoadjuvante em pacientes com câncer de mama, a fim de orientar o processo de decisão do tratamento cirúrgico para este grupo de pacientes. Metodologia: Foi realizado um estudo transversal, de dados secundários, entre os anos de 2013-2016 em 222 pacientes com câncer de mama linfonodo-positivo, que receberam quimioterapia neoadjuvante seguida de tratamento locorregional, incluindo dissecção de linfonodos axilares. A análise de regressão logística foi realizada para determinar a associação da resposta completa patológica axilar com as diferentes variáveis clínicas e patológicas. Variáveis estatisticamente associadas à pCR axilar (resposta completa patológica) foram usadas para criar o modelo de regressão logística e nomograma em pacientes na pré-menopausa. A pCR axilar foi definida como ausência de doença residual na mama e de micro-metástase nos linfonodos axilares. Amostras com células tumorais isoladas foram consideradas positivas para doença residual. Resultados: foram incluídos 222 pacientes, dos quais 131 estavam na prémenopausa no momento do diagnóstico. A resposta patológica axilar completa foi observada em 55,7% (73 de 131) dos pacientes, e foi significativamente associada a tumores negativos para receptores de estrogênio(RE) (OR 2,59; IC 95% 1,21-5,53) e negativos para receptores de progesterona (RP) (OR 2.63, IC 95% 1.28-5.38), e Her2 positivos (OR 0.40, IC 95% 0.19-0.84), para o qual foi evidenciada uma correlação significativa com o aumento da probabilidade de atingir resposta completa patológica axilar. Conclusão: O desempenho deste modelo para prever a pCR axilar em pacientes na pré-menopausa era fraco e, portanto, a decisão de evitar a dissecção axilar cirúrgica não deve ser baseada apenas no nomograma desenvolvido. No entanto, estudos posteriores podem levar à validação desse modelo

Risk factors for early childhood caries experience expressed by ICDAS criteria in Anapoima, Colombia: a cross-sectional study.

The aim of this study was to assess whether caries risk, nutritional status, access to dental care and socio-behavioral factors are associated to two caries experience outcome variables using the Epidemiologic International Caries Detection and Assessment System (ICDASepi), which includes initial enamel caries lesions: 1- The presence of ICDAS-epi caries experience (dmf-ICDASepi ≥ 1), and 2- Having an ICDAS-epi caries experience (dmft-ICDASepi) higher than national figures for the same age. The sample included 316 eight- to 71-month-old children from the municipality of Anapoima, Colombia. Assessments included: prevalence and mean of caries experience using the ICDASepi system without compressed air-drying of teeth surfaces (dmf-ICDASepi), caries risk and nutritional status. Caregivers completed an elevenitem questionnaire assessing oral health-related social determinants, practices and quality of life (OHRQoL), and children's access to dental care. Data were analysed using the Wilcoxon-rank-sum test, the test, the Fisher-exact test, and bivariate-linear and non-conditioned logistic-multivariate regression models. Prevalence and mean number of teeth with dmft-ICDASepi were 65. 2% and 3. 5±4. 13, respectively. Nutritional status outside the normal status, lower educational level of caregivers and age were significantly associated with dmf-ICDASepi≥ 1. OHRQoL, access barriers to miss and to attend dental care, operative-treatment or emergency being the reason to attend dental care, high caries risk, and age were significantly associated with a higher-than-national dmft-ICDASepi. The significant associations found between early childhood caries experience and other variables represent oral-health inequalities in early childhood in Anapoima, Colombia.

El objetivo de este estudio fue evaluar en la primera infancia la asociación entre el riesgo de caries, el estado nutricional, el acceso a la consulta odontológica y los factores socio-comportamentales y dos variables de desenlace de experiencia de caries usando el Sistema epidemiológico Internacional de Detección y Valoración de Caries (ICDASepi), que incluye lesiones de caries en el esmalte: 1-La presencia de experiencia de caries ICDAS-epi (ceod-ICDASepi ≥ 1) y, 2- Tener una experiencia de caries ICDASepi (ceod-ICDASepi) mayor que los datos nacionales correspondientes para la misma edad. La muestra fue de 316 niños del municipio de Anapoima, Colombia, de 8 a 71 meses de edad. Las valoraciones incluyeron: prevalencia y promedio de experiencia de caries usando el sistema ICDASepi sin secado de las superficies de los dientes con aire comprimido (dmf-ICDASepi); riesgo de caries y estado nutricional. Los cuidadores respondieron un cuestionario de once ítems que valoraba en relación con salud oral, determinantes sociales, prácticas y calidad de vida y, el acceso de los niños a la consulta odontológica. Los datos fueron analizados con la prueba de suma de rangos de Wilcoxon, la prueba de χ2, la prueba exacta de Fisher y, modelos de regresión logística multivariada tipos bivariantelineal y no condicionada. La prevalencia de experiencia de caries (ceod-ICDASepi) fue de 65. 18% y el promedio de dientes con ceod-ICDASepi de 3. 5 ± 4. 13. El estado nutricional por fuera de rangos de normalidad, el bajo nivel educativo de los cuidadores y la edad se asociaron significativamente con ceo-ICDASepi ≥ 1. Se encontró asociación estadísticamente significativa entre tener un ceod-ICDASepi mayor que el promedio nacional y, calidad de vida relacionada con salud oral, barreras de acceso para perder y asistir a consulta odontológica, tratamiento operatorio o urgencia como motivo de consulta odontológica, alto riesgo de caries y edad. Las asociaciones estadísticamente significativas encontradas en este estudio entre la experiencia de caries de infancia temprana y demás variables representan inequidades en salud oral en la primera infancia en Anapoima, Colombia.

Risk factors for early childhood caries experience expressed by ICDAS criteria in Anapoima, Colombia: a cross-sectional study / Factores de riesgo de experiencia de caries temprana expresada con criterios ICDAS en niños de Anapoima, Colombia. Estudio de corte transversal

The aim of this study was to assess whether caries risk, nutritional status, access to dental care and sociobehavioral factors are associated to two caries experience outcome variables using the Epidemiologic International Caries Detection and Assessment System (ICDASepi), which includes initial enamel caries lesions: 1The presence of ICDASepi caries experience (dmfICDASepi ≥ 1), and 2Having an ICDASepi caries experience (dmftICDASepi) higher than national figures for the same age. The sample included 316 eightto 71monthold children from the municipality of Anapoima, Colombia. Assessments included: prevalence and mean of caries experience using the ICDASepi system without compressed airdrying of teeth surfaces (dmfICDASepi), caries risk and nutritional status. Caregivers completed an elevenitem questionnaire assessing oral healthrelated social determinants, practices and quality of life (OHRQoL), and children's access to dental care. Data were analysed using the Wilcoxonranksum test, the test, the Fisherexact test, and bivariatelinear and nonconditioned logisticmultivariate regression models. Prevalence and mean number of teeth with dmftICDASepi were 65.2% and 3.5±4.13, respectively. Nutritional status outside the normal status, lower educational level of caregivers and age were significantly associated with dmfICDASepi≥ 1. OHRQoL, access barriers to miss and to attend dental care, operativetreatment or emergency being the reason to attend dental care, high caries risk, and age were significantly associated with a higherthannational dmftICDASepi. The significant associations found between early childhood caries experience and other variables represent oralhealth inequalities in early childhood in Anapoima, Colombia (AU)

El objetivo de este estudio fue evaluar en la primera infancia la asociación entre el riesgo de caries, el estado nutricional, el acceso a la consulta odontológica y los factores sociocomporta mentales y dos variables de desenlace de experiencia de caries usando el Sistema epidemiológico Internacional de Detección y Valoración de Caries (ICDASepi), que incluye lesiones de caries en el esmalte: 1La presencia de experiencia de caries ICDASepi (ceodICDASepi ≥ 1) y, 2Tener una experiencia de caries ICDASepi (ceodICDASepi) mayor que los datos nacionales correspondientes para la misma edad.La muestra fue de 316 niños del municipio de Anapoima, Colombia, de 8 a 71 meses de edad. Las valoraciones incluyeron: prevalencia y promedio de experiencia de caries usando el sistema ICDASepi sin secado de las superficies de los dientes con aire comprimido (dmfICDASepi) ; riesgo de caries y estado nutricional. Los cuidadores respondieron un cuestionario de once ítems que valoraba en relación con salud oral, determinantes sociales, prácticas y calidad de vida y, el acceso de los niños a la consulta odontológica. Los datos fueron analizados con la prueba de suma de rangos de Wilcoxon, la prueba de χ2, la prueba exacta de Fisher y, modelos de regresión logística multivariada tipos bivariantelineal y no condicionada. La prevalencia de experiencia de caries (ceodICDASepi) fue de 65.18% y el promedio de dientes con ceodICDASepi de 3.5 ± 4.13. El estado nutricional por fuera de rangos de normalidad, el bajo nivel educativo de los cuidadores y la edad se asociaron significativamente con ceoICDASepi ≥ 1. Se encontró asociación estadísticamente significativa entre tener un ceodICDASepi mayor que el promedio nacional y, calidad de vida relacionada con salud oral, barreras de acceso para perder y asistir a consulta odontológica, tratamiento operatorio o urgencia como motivo de consulta odontológica, alto riesgo de caries y edad. Las asociaciones estadísticamente significativas encontradas en este estudio entre la experiencia de caries de infancia temprana y demás variables representan inequidades en salud oral en la primera infancia en Anapoima, Colombia (AU)

Ambroxol for fibromyalgia: one group pretest-posttest open-label pilot study.

A consistent line of investigation proposes that fibromyalgia is a sympathetically maintained neuropathic pain syndrome. Dorsal root ganglia sodium channels may play a major role in fibromyalgia pain transmission. Ambroxol is a secretolytic agent used in the treatment of various airway disorders. Recently, it was discovered that this compound is also an efficient sodium channel blocker with potent anti-neuropathic pain properties. We evaluated the add-on effect of ambroxol to the treatment of fibromyalgia. We studied 25 patients with fibromyalgia. Ambroxol was prescribed at the usual clinical dose of 30 mg PO 3 times a day × 1 month. At the beginning and at the end of the study, all participants filled out the Revised Fibromyalgia Impact Questionnaire (FIQ-R) and the 2010 ACR diagnostic criteria including the widespread pain index (WPI). At the end of the study, FIQ-R decreased from a baseline value of 62 ± 15 to 51 ± 19 (p = 0.013). Pain visual analogue scale decreased from 77 ± 14 to 56 ± 30 (p = 0.018). WPI diminished from 14.6 ± 3.1 to 10.4 ± 5.3 (p = 0.001). Side effects were minor. In this pilot study, the use of ambroxol was associated to decreased fibromyalgia pain and improved fibromyalgia symptoms. The open nature of our study does not allow extracting the placebo effect from the positive results. The drug was well tolerated. Ambroxol newly recognized pharmacological properties could theoretically interfere with fibromyalgia pain pathways. Dose escalating-controlled studies seem warranted.

Serum Concentrations of IgG4 in the Spanish Adult Population: Relationship with Age, Gender, and Atopy.

BACKGROUND AND AIM: Serum IgG4 concentrations are commonly measured in clinical practice. The aim of this study was to investigate serum IgG4 concentrations in adults and their potential relationship with demographic, lifestyle, metabolic, and allergy-related factors. METHODS: Serum IgG4 concentrations were measured with a commercial assay in 413 individuals (median age 55 years, 45% males) who were randomly selected from a general adult population. RESULTS: Median IgG4 concentration was 26.8 mg/dL. Five out of the 413 individuals (1.2%) exhibited IgG4 concentrations >135 mg/dL, and 17 out of 411 (4.1%) exhibited an IgG4/total IgG ratio >8%. Serum IgG4 concentrations were significantly higher in males than in females and decreased with age. After adjusting for age and sex, serum IgG4 concentrations were not significantly influenced by alcohol consumption, smoking or common metabolic abnormalities (obesity and the related metabolic syndrome). Serum IgG4 concentrations were not significantly correlated with serum concentrations of proinflammatory cytokines and inflammation markers. Serum IgG4 concentrations were significantly correlated with IgE concentrations. Serum IgG4 concentrations tended to be higher in atopics (individuals with IgE-mediated sensitization to aeroallergens) than in non-atopics, particularly among atopics without respiratory symptoms. Serum IgG4 concentrations were not significantly correlated with total eosinophil blood count. Cases of IgG4-related disease were neither present at baseline nor detected after a median of 11 years of follow-up. CONCLUSIONS: Studies aimed at defining reference IgG4 values should consider partitioning by age and sex. Further studies are needed to confirm the potential influence of atopy status on serum IgG4 concentrations.

Ruptura traumática de la aorta: hallazgos radiológicos con TAC multidetector: serie de casos / Traumatic rupture of the aorta: multidetector CT radiologic findings: case series

La ruptura traumática de la aorta es la lesión vascular mayor que más frecuentemente se asocia a trauma cerrado de tórax luego de accidentes automovilísticos. Por lo general, es ocasionada por un mecanismo de desaceleración súbita, producida por la colisión. La tomografía computarizada con multidetectores y las reconstrucciones multiplanares mejoran la exactitud diagnóstica, al detectar lesiones de menor tamaño.

Gliosarcoma: presentación de caso / Gliosarcoma: case report

En este artículo se presenta el caso de un paciente con gliosarcoma, un tumor glial poco frecuente con gran componente vascular. Las características vasculares de estos tumores dificultan su diagnóstico imaginológico inicial, debido a la alta frecuencia de zonas de hemorragia dentro de la lesión. La resonancia magnética permite una mejor caracterización de estas lesiones, asociadas con un pobre pronóstico clínico.

Serum TNF-alpha levels in relation to alcohol consumption and common TNF gene polymorphisms.

Tumor necrosis factor-alpha (TNF-alpha) mediates alcohol-induced organ dysfunction, including alcoholic hepatitis. Variations in the TNF-alpha gene may underlie the individual predisposition to alcoholic liver disease. Measurement of serum TNF-alpha levels has become a routine in clinical practice. The study was aimed at investigating the level of serum TNF-alpha levels in adults and analyzing its relationship with different levels of alcohol consumption, as well as the potential interaction between alcohol consumption and common TNF-alpha gene polymorphisms in relation to TNF-alpha levels and liver disease. Serum TNF-alpha was measured in a random sample of 459 individuals from a general adult population and in 137 hospital-admitted alcoholics. Three common TNF-alpha gene polymorphisms (-238G> A, -308G> A, and -857C> T) were investigated in 419 of these individuals. In the general adult population, the TNF-alpha levels were similar in alcohol abstainers and alcohol drinkers. Alcoholics admitted to the hospital showed the highest TNF-alpha levels, which were correlated with liver dysfunction. We found no evidence of an interaction between alcohol consumption and TNF-alpha gene polymorphisms in relation to TNF-alpha levels. Carriers of the TNF -238A allele tended to have a higher prevalence of advanced liver disease than -238G homozygotes, confirming previous reports. In conclusion, light-to-moderate drinking had no significant effect on the levels of serum TNF-alpha levels. Serum TNF-alpha levels are elevated in alcoholics independently of common TNF gene polymorphisms.

Serum concentrations of interleukin-8 in relation to different levels of alcohol consumption.

Serum levels of interleukin-8 (IL-8) are increased in patients with alcoholic hepatitis and correlate with disease severity. The present study was aimed at investigating serum IL-8 levels in relation to different levels of alcohol consumption. Serum IL-8 was measured in (a) 459 individuals randomly selected from the general adult population, including 221 alcohol abstainers, 140 light drinkers (1-140 g/week), 53 moderate drinkers (141-280 g/week), and 45 heavy drinkers (>280 g/week), as well as (b) 137 alcoholics admitted to the hospital. The proportion of individuals with abnormally high (>10 pg/mL) IL-8 levels increased with alcohol use from 5.9% in abstainers to 10.7% in light, 13.2% in moderate, and 17.8% in heavy drinkers (P=0.004). This proportion was exceedingly high in alcoholics admitted to the hospital (70.1%, P<0.001 with respect to all other categories). Extremely high (>100 pg/mL) IL-8 levels were only observed among alcoholics, and were more frequent in females than in males (23.5% versus 9.7%, P=0.03) in spite of lower alcohol consumption among the former. These data indicate that the effect of alcohol on serum IL-8 levels begins with light-to-moderate drinking and is dose-dependent. Females may be more prone than males to develop extremely high IL-8 levels after heavy alcohol intake.

Serum levels of cytokeratin-18 (tissue polypeptide-specific antigen) in liver diseases.

OBJECTIVE: The tissue polypeptide-specific antigen (TPS, cytokeratin-18, a normal constituent of the hepatocyte cytoskeleton) is a standard tumour marker. This study aimed to evaluate serum TPS levels in patients with liver disease. METHODS: Serum TPS was measured with a commercial immunoassay in 884 individuals (753 outpatients from a liver disease clinic, 131 patients admitted to the hospital with acute liver disease). RESULTS: Abnormally high (> 80 U/l) TPS levels were found in 57.7% (95% CI 54.0-61.3%) of outpatients with liver disease. Elevated TPS levels were observed for all liver diseases, including fatty liver, alcoholic disease, chronic viral hepatitis, autoimmune hepatitis, cholestasis, transplantation, and hepatocarcinoma. TPS levels correlated with liver markers, particularly serum AST. In addition, TPS levels correlated with Knodell's score in patients with chronic hepatitis. TPS was increased in one-third of patients with normal liver enzyme values. Serum TPS levels decreased after specific therapy in patients with hepatitis C and autoimmune hepatitis. Abnormally high TPS levels were found in the vast majority of patients admitted to the hospital, with markedly high (> 800 U/l) values being observed in 47.5% (95% CI 36.1-55.7%) of patients with alcoholic liver disease and in 80.8% (95% CI 60.0-92.7%) of patients with acute hepatitis. CONCLUSIONS: Serum TPS (cytokeratin-18) is elevated in patients with non-malignant liver diseases, particularly in those with prominent cytolysis. Further studies are needed to evaluate the use of TPS as a marker of liver disease.

Increased urinary levels of tissue polypeptide specific antigen (TPS) in alcoholics.

BACKGROUND: Urinary levels of tissue polypeptide specific antigen (TPS, cytokeratin-18) have been proposed as a marker of urothelial malignancies. Previous studies have shown that serum TPS levels are elevated in alcoholics. This study was designed to determine whether alcoholics had elevated urinary TPS levels as well. PATIENTS AND METHODS: Serum and urinary TPS levels were determined in 24 alcoholics and 15 healthy controls by means of a commercial chemiluminiscent immunoassay. RESULTS: Serum TPS levels were higher in alcoholics than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range 15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5 U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated with serum TPS levels in alcoholics. CONCLUSION: Urinary TPS levels are elevated in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may be limited in alcoholics.

The -159C/T polymorphism in the promoter region of the CD14 gene is associated with advanced liver disease and higher serum levels of acute-phase proteins in heavy drinkers.

BACKGROUND: Innate inflammatory responses to endotoxin (lipopolysaccharide) contribute to the development of alcoholic liver disease (ALD). A single-nucleotide polymorphism (-159C/T) in the promoter region of the gene coding for CD14 (a lipopolysaccharide receptor) could be associated with the development of ALD. We sought too investigate the relationship between the CD14/-159C/T polymorphism and advanced ALD and acute-phase protein levels in heavy drinkers. METHODS: A total of 138 heavy drinkers consecutively admitted to an Internal Medicine department were genotyped for the CD14/-159C/T polymorphism. Serum samples were analyzed for lipopolysaccharide-binding protein (LBP), soluble CD14 (sCD14), C-reactive protein (CRP), and immunoglobulin (Ig) A, IgG, and IgM. Patients with ascites or liver encephalopathy (n = 35) were classified as having advanced ALD. RESULTS: After adjusting for potential confounding variables, the CD14/-159TT genotype was positively associated with advanced ALD (odds ratio, 2.99; 95% confidence interval, 1.09-8.24, p = 0.03) and serum LBP (p = 0.01) and sCD14 (p = 0.04) levels. The CD14/-159C/T polymorphism was not associated with serum levels of CRP, IgA, IgG, or IgM. CONCLUSIONS: Our results support the notion that CD14/-159TT homozygous heavy drinkers have higher levels of the LPS-binding acute-phase proteins (LBP and sCD14) than do carriers of the CD14/-159C allele. Also, the CD14/-159TT genotype may be a risk factor for advanced ALD.

[Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives]. / Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva.

Bacterial meningitis constitutes a significant global public health problem. In particular, Neisseria meningitidis continues to be a public health problem among human populations in both developed and developing countries. Meningococcal infection is present as an endemic and an epidemic disease. Meningococcal disease is manifested not only as meningitis, but also as meningococcemia. The latter is usually fulminant. The global persistence of N. meningitidis is due to the significant number of carriers and the dynamics of transmission and disease. Approximately 500 million people worldwide are carriers of the bacterium in their nasopharynx. Multiple factors have been identified that predispose to the transmissibility of N. meningitidis, including active or passive inhalation tobacco smoking, upper viral respiratory tract infections, drought seasons, and overcrowding. These factors explain the frequent occurrence of outbreaks in military barracks, schools, prisons, and dormitories. Some of the determinants of invasiveness of the bacteria include nasopharyngeal mucosal damage in colonized individuals, virulence of the strains, absence of bactericidal antibodies, and deficiencies of the complement system. During both endemic and epidemic scenarios of meningococcal disease, control measures should include treating the cases with appropriate antimicrobial therapy (penicillin, ceftriaxone, or chloramphenicol); providing chemoprophylactic drugs to contacts (rifampin or ciprofloxacin), and close observation of contacts. Nevertheless, the key to effective control and prevention of meningococcal disease is immunoprophylaxis. Available vaccines include the polysaccharide monovalent, bivalent (serogroups A, C), or tetravalent (A, C, Y, W-135 serogroups) vaccines; conjugate vaccine (serogroup C); and the combined vaccine with outer membrane proteins and polysaccharide (serogroups B, C). Due to a recent increase in case reporting of serogroup C N. meningitidis in Mexico, we have developed a national response strategy that includes availability of vaccines and medications for chemoprophylaxis. This review aims at providing health care workers with updated information regarding the epidemiological, clinical, and preventive aspects of meningococcal disease. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva / Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives

La meningitis bacteriana continúa siendo uno de los grandes problemas de la salud pública mundial. En particular, la infección por Neisseria meningitidis afecta tanto a países desarrollados como subdesarrollados, y se presenta en formas endémicas y epidémicas. La enfermedad meningocóccica se puede manifestar clínicamente no sólo como meningitis, sino con cuadros fulminantes de meningococcemia. La persistencia de N. meningitidis se debe al gran porcentaje de portadores y a la dinámica de transmisión de la bacteria. Aproximadamente 500 millones de personas en el mundo son portadoras de N. meningitidis en la nasofaringe. Los factores de transmisiblidad identificados han sido el tabaquismo activo o pasivo, la presencia de infecciones virales del tracto respiratorio superior, épocas de sequía, y el hacinamiento. Por lo anterior, se han descrito brotes de enfermedad meningocóccica en cuarteles militares, escuelas, cárceles y dormitorios. Algunos determinantes que permiten la invasión sistémica incluyen daños en la mucosa nasofaríngea de portadores, cepas virulentas con formación de cápsula, ausencia de anticuerpos bactericidas y deficiencias del sistema del complemento. El control de la enfermedad meningocóccica en circunstancias endémicas y epidémicas se logra por el tratamiento de casos con antibióticos adecuados (penicilina, ceftriaxona o cloranfenicol), la quimioprofilaxis de contactos cercanos (ciprofloxacina, rifampicina o ceftriaxona), y la vigilancia clínica de éstos. Sin embargo, es fundamental subrayar que la clave para el control efectivo de la enfermedad meningocóccica es la inmunoprofilaxis. Las vacunas disponibles incluyen las de polisacáridos monovalentes o bivalentes (serogrupos A y C), tetravalentes (A, C, Y, W-135), la conjugada (C) o la combinada de proteínas de membrana celular y polisacárido (B y C). Recientemente nos hemos visto forzados a establecer planes nacionales de respuesta que incluyen la disponibilidad de vacuna y de medicamentos para quimioprofilaxis, debido a que se ha documentado un incremento de casos de enfermedad por N. meningitidis, serogrupo C, en el país. Es por lo anterior que esta revisión está dirigida a proporcionar al personal de salud un recordatorio de los aspectos relevantes de la epidemiología, y de los clínicos y preventivos de la enfermedad meningocóccica.

Time-course changes of serum immunoglobulins (IgA, IgG, IgM) after liver transplantation for alcoholic cirrhosis.

BACKGROUND: Serum immunoglubulin increase is a hallmark of liver disease. Serum IgA is specifically increased in alcoholic liver disease, which has been considered an IgA-associated disorder. No previous studies have been focused on the time-course changes of serum immunoglobulins (IgG, IgA, IgM) after liver transplantation. AIM OF THE STUDY: To investigate the outcome of serum immunoglobulin levels in alcoholic cirrhosis after liver transplantation, with special focus on IgA values. PATIENTS AND METHODS: A total of 18 patients, liver transplanted in our center because of alcoholic cirrhosis were included in the study. Serum immunoglobulins were assayed by nephelometry before transplantation and at different intervals after the procedure from the intraoperative period to more than a year after transplantation. RESULTS: A rapid drop in IgA, IgG and IgM concentration was observed during the surgical procedure, particularly after donor liver reperfusion, and during the first days after transplantation. Mild transient hypogammaglobulinemia (IgG) was present. After a subsequent moderate re-increase, serum immunoglobulins (particularly IgA and IgG) remained stable within normal or near-normal limits during the following months after liver transplantation. CONCLUSIONS: Liver transplantation for alcoholic cirrhosis is followed by a decrease in serum IgA, IgG and IgM. In the short term, low IgG levels may be observed. In the long term, serum levels of IgA and IgG become normal or near-normal.