In Situ versus Systemic Immune Response in the Pathogenesis of Cutaneous Leishmaniasis.

The role of the immune response in the pathogenesis of cutaneous leishmaniasis (CL) due to Leishmania (Viannia) braziliensis is predominantly carried out via blood cells. Here, we evaluate whether cytokine production by peripheral blood mononuclear cells (PBMCs) reflects what has been documented at the lesion site. The participants included 22 CL patients diagnosed with a positive PCR. PBMCs were stimulated for 72 h with a soluble leishmania antigen (SLA). Biopsies obtained from the edge of the ulcers were incubated for the same period. Cytokines in supernatants were assessed via ELISA. TNF, IL-1ß, IL-6, IL-17, and granzyme B (GzmB) were higher in the supernatants of biopsies than in PBMCs, but IFN-γ was higher in the supernatants of PBMCs than in biopsies. There was a positive correlation between IFN-γ and TNF in PBMCs, and an inverse correlation between TNF and IL-10 in the cells from the lesion site. A strong correlation between IL-1ß, IL-17, and GzmB was observed in the biopsies, and a positive correlation was detected between these cytokines and the lesion size. Our results indicate that the immune response in L. braziliensis lesions is different from that observed in peripheral blood, and our data suggest that in addition to IL-1ß and GzmB, IL-17 participates in the pathology of CL.

Assessment of Immune and Clinical Response in Patients with Mucosal Leishmaniasis Treated with Pentavalent Antimony and Pentoxifylline.

Mucosal leishmaniasis (ML) is a severe form of tegumentary leishmaniasis associated with a persistent inflammatory response. High levels of TNF, IFN-γ, CXCL9 and CXCL10 are found in ML patients, and the association of pentoxifylline with antimony is more effective in decreasing the healing time in ML patients when compared to antimony alone. The present study aimed to investigate the existence of a correlation between cytokine and chemokine production and ML severity and evaluate the potential value of cytokine and chemokine production as marker of therapeutic response in ML patients. This prospective study included 86 subjects in an area of endemic Leishmania braziliensis transmission. Patients diagnosed with ML were classified into clinical stages ranging from I to V according to disease severity. TNF, IFN-γ, CXCL9 and CXCL10 levels were quantified in the supernatant of the mononuclear cell cultures by ELISA before and after treatment with antimony alone or antimony plus pentoxifylline. The median TNF level in the group with mild disease (Stages I-II) was 1064 pg/mL (142-3738 pg/mL), while, in the group with moderate or severe disease (Stages III-V), it was 1941 pg/mL (529-5294 pg/mL) (p = 0.008). A direct correlation was observed between ML clinical severity and levels of TNF production (r = 0.44, p = 0.007). Patients who were treated with antimony and pentoxifylline healed significantly faster than those treated with antimony alone (52 vs. 77 days, hazard ratio = 0.60; 95% confidence interval = 0.38-0.95, p = 0.013). Therapeutic failure was higher in the group that received antimony alone (25% vs. 7%; p = 0.041). There was a significant decrease in CXCL9 after therapy of ML in both groups (p = 0.013; p = 0.043). TNF levels are associated with the severity of mucosal diseases, and pentoxifylline associated with antimony should be the recommended therapy for ML in countries where liposomal amphotericin B is not available.

Influência do Estado Mental Cognitivo no Equilíbrio Postural de Idosos / Influence of Cognitive Mental State on Postural Balance of Older People

O estado cognitivo tem um papel importante na independência e na funcionalidade do idoso, assim é importante identificar sua influência no contexto do equilíbrio postural. O objetivo deste estudo foi analisar se o estado mental influência no desempenho de equilíbrio postural de idosos. Duzentos e sete idosos, fisicamente independentes de ambos os sexos, com idade média 67 anos foram divididos em três grupos de acordo com resultados obtidos pelo questionário do mini exame de estado mental (grupo 1, Funções cognitivas preservadas ­ FCP, n=57; grupo 2, Déficit cognitivo não sugestivo ­ DCNS, n=72; grupo 3, Sugestivo de déficit cognitivo ­ SDC, n=78). O equilíbrio postural foi avaliado em duas condições (bipodal e unipodal) por meio de uma plataforma de força. Três tentativas foram realizadas em cada condição e a média das tentativas foi utilizada para analisar a oscilação dos parâmetros do centro pressão (COP). Os resultados encontrados mostraram diferenças significativas entre todos grupos no questionário de mini mental (FCP > DCNS > SDC, P= <0,001). Por outro lado, nenhuma diferença estatisticamente significativa (P= >0,05) foi encontrada entre os grupos para todos os parâmetros do COP nas duas condições de equilíbrio avaliadas. Os achados do presente estudo sugerem que, a diferença encontrada no estado cognitivo não influenciou significativamente no equilíbrio postural de idosos fisicamente independentes. (AU).

Cognitive status have an important role in the independence and functionality of the older people, so it is important to identify their influence in the context of postural balance. The aim of this study was to analyze whether the mental state influences the postural balance performance of the older people. Two hundred and seven physically independent older people of both sexes, mean age 67 ± 4 years were divided into three groups according to results obtained by the mini mental state examination. (group 1, Preserved cognitive functions - PCF, n = 57; group 2, Non suggestive cognitive deficit - NSCD, n = 72; group 3, Suggestive cognitive deficit - SCD, n = 78). The postural balance was evaluated in two conditions (two- and one-legged stand) by means of a force platform. Three trials were performed in each condition and the mean number of trials was used to analyze the oscillation of the center pressure (COP). The results showed significant differences between all groups in the mini mental questionnaire (PCF> NSCD> SCD, P = <0.001) On the other hand, no statistically significant difference (P = >0.05) was found between the groups for all COP parameters in the two balance conditions evaluated. The findings of the present study suggest that the differences found in cognitive status do not significantly influence in the postural balance of physically independent elderly. (AU)

Relación entre las tasas de desempleo y los indicadores de absentismo por incapacidad temporal durante periodos de crisis económica / The relationship between unemployement rates adn lost work tiem due to sickness absence in an economic recession

Introducción: Estudios realizados en varios países presentan una relación inversa entre las tasas de desempleo (TD) y los indicadores de absentismo por incapacidad temporal (IT) durante periodos de crisis económica. Objetivo: Evaluar la relación entre indicadores de absentismo y el desempleo en España (2009-2015). Métodos: Se obtuvieron tasas de incidencia (TI) y absentismo (TA) por IT de origen común (ITcc) a partir de datos de la Seguridad Social, así como las TD según datos del Instituto Nacional de Estadística. Se describió gráficamente la evolución temporal de los indicadores de ITcc y el desempleo en el periodo 2009-2015. Para explorar dicha relación también se realizaron gráficos de dispersión de los indicadores frente a las TD. Posteriormente, se ajustaron modelos de regresión lineal simple. Resultados: Las TI y TA descienden en 2009-2013 (TI 2009=28,07%, TI 2013=20,41%, TA 2009=2,53%, TA 2013=1,86%) momento en que cambia su tendencia, iniciando una fase ascendente hasta 2015 (TI 2015=22,52%, TA 2015=2,12%). La TD asciende en 2009-2013 (TD 2009=17,86%, TD 2013=26,10%), pasando a descender hasta 2015 (TD 2015=22,06%). Las TD y los indicadores de absentismo presentan una relación lineal inversa. Conclusiones: Se observó una relación inversa entre el desempleo y los indicadores de absentismo en España. Son necesarios estudios específicos para poder evaluar hipótesis explicativas como las asociadas a los efectos de disciplina, selección y/o cambios en la fuerza de trabajo

Introduction: Different countries have shown an inverse relationship between unemployment rates (UR) and indicators of sickness absence during periods of economic recession. Objective: To evaluate the relationship between indicators of sickness absence and unemployment in Spain during 2009-2015. Methods: We obtained incidence and absenteeism rates of non-work related sickness absence (NWSA) from Social Security data, and UR from the National Institute of Statistics. The relationship between indicators of NWSA and UR in the period 2009 to 2015 was graphically described using time trend plots. Scatter plots of NWSA indicators were also made against UR. Finally, we fitted linear regression models. Results: Incidence (IR) and absenteeism rates (AR) of NWSA showed downward trends in 2009-2013 (IR 2009=28.07%, IR 2013=20.41%; AR 2009=2.53% and AR 2013=1.86%), changing to an upward trend up to 2015 (IR 2015=22.52%, AR 2015=2.12%). Unemployment rates trended upward in 2009-2013 (UR 2009=17.86%, UR 2013=26.10%), and then changed to a downward trend through 2015 (UR 2015=22.06%). There was an inverse relationship between UR and NWSA indicators. Conclusions: As in previous international studies, we found an inverse relationship between unemployment rates and indicators of sickness absence in Spain. More detailed studies are needed to evaluate explanatory hypotheses, such as those associated with the effects of discipline, selection and/or changes in the workforce

[The relationship between unemployment rates and lost work time due to sickness absence in an economic recession]. / Relación entre las tasas de desempleo y los indicadores de absentismo por incapacidad temporal durante periodos de crisis económica.

INTRODUCTION: Different countries have shown an inverse relationship between unemployment rates (UR) and indicators of sickness absence during periods of economic recession. OBJECTIVE: To evaluate the relationship between indicators of sickness absence and unemployment in Spain during 2009-2015. METHODS: We obtained incidence and absenteeism rates of non-work related sickness absence (NWSA) from Social Security data, and UR from the National Institute of Statistics. The relationship between indicators of NWSA and UR in the period 2009 to 2015 was graphically described using time trend plots. Scatter plots of NWSA indicators were also made against UR. Finally, we fitted linear regression models. RESULTS: Incidence (IR) and absenteeism rates (AR) of NWSA showed downward trends in 2009-2013 (IR 2009=28.07%, IR 2013=20.41%; AR 2009=2.53% and AR 2013=1.86%), changing to an upward trend up to 2015 (IR 2015=22.52%, AR 2015=2.12%). Unemployment rates trended upward in 2009-2013 (UR 2009=17.86%, UR 2013=26.10%), and then changed to a downward trend through 2015 (UR 2015=22.06%). There was an inverse relationship between UR and NWSA indicators. CONCLUSIONS: As in previous international studies, we found an inverse relationship between unemployment rates and indicators of sickness absence in Spain. More detailed studies are needed to evaluate explanatory hypotheses, such as those associated with the effects of discipline, selection and/or changes in the workforce.

INTRODUCCIÓN: Estudios realizados en varios países presentan una relación inversa entre las tasas de desempleo (TD) y los indicadores de absentismo por incapacidad temporal (IT) durante periodos de crisis económica. OBJETIVO: Evaluar la relación entre indicadores de absentismo y el desempleo en España (2009-2015). MÉTODOS: Se obtuvieron tasas de incidencia (TI) y absentismo (TA) por IT de origen común (ITcc) a partir de datos de la Seguridad Social, así como las TD según datos del Instituto Nacional de Estadística. Se describió gráficamente la evolución temporal de los indicadores de ITcc y el desempleo en el periodo 2009-2015. Para explorar dicha relación también se realizaron gráficos de dispersión de los indicadores frente a las TD. Posteriormente, se ajustaron modelos de regresión lineal simple. RESULTADOS: Las TI y TA descienden en 2009-2013 (TI 2009=28,07%, TI 2013=20,41%, TA 2009=2,53%, TA 2013=1,86%) momento en que cambia su tendencia, iniciando una fase ascendente hasta 2015 (TI 2015=22,52%, TA 2015=2,12%). La TD asciende en 2009-2013 (TD 2009=17,86%, TD 2013=26,10%), pasando a descender hasta 2015 (TD 2015=22,06%). Las TD y los indicadores de absentismo presentan una relación lineal inversa. CONCLUSIONES: Se observó una relación inversa entre el desempleo y los indicadores de absentismo en España. Son necesarios estudios específicos para poder evaluar hipótesis explicativas como las asociadas a los efectos de disciplina, selección y/o cambios en la fuerza de trabajo.

Early Cutaneous Leishmaniasis Patients Infected With Leishmania braziliensis Express Increased Inflammatory Responses After Antimony Therapy.

Background: Early cutaneous leishmaniasis (ECL) is characterized by a nonulcerated papular lesion and illness duration less than 30 days. Approximately 4 weeks later, the cutaneous leishmaniasis (CL) ulcers appear. We were surprised to find that failure after antimony therapy (Sb5) is higher in ECL than CL. We hypothesize that the inflammatory response in ECL patients may increase during Sb5 therapy, which leads to treatment failure. Methods: A cohort of 44 ECL patients infected by Leishmania braziliensis was established to evaluate the response to Sb5 and to compare immunologic responses in ECL patients with CL and healthy subjects. Results: A hierarchical clustering based on cytokine levels showed a weak positive correlation between proinflammatory cytokine levels and those patients that failed Sb5 treatment. Although Sb5 therapy decreased interferon-γ and tumor necrosis factor levels in CL patients, we were surprised to find that an increase in these cytokines was observed in ECL patients. Moreover, interleukin (IL)-10 was less able to down-modulate immune responses in ECL. Conclusions: The enhanced production of proinflammatory cytokines, due in part to the decreased ability of IL-10 to down-modulate immune response during therapy in ECL, promotes the development and persistence of leishmania ulcer despite antimony therapy.

Intermediate monocytes contribute to pathologic immune response in Leishmania braziliensis infections.

Ulcer development in patients with cutaneous leishmaniasis (CL) caused by Leishmania braziliensis is associated with high levels of tumor necrosis factor (TNF). We found that early after infection, before ulcer development, the frequency of CD16(+) (both intermediate [CD14(+)CD16(+)] and nonclassical [CD14(dim)CD16(+)]) monocytes was increased in the peripheral blood of patients with L. braziliensis, compared with uninfected controls. These results suggest that CD16(+) monocytes might promote disease. Also, we found that intermediate monocytes expressed CCR2 and that increased levels of CCL2 protein were present in lesions from patients, suggesting that intermediate monocytes are more likely than nonclassical monocytes to migrate to the lesion site. Finally, we found that the intermediate monocytes produced TNF. Our results show that intermediate monocytes are increased in frequency soon after infection; express CCR2, which would promote their migration into the lesions; and, owing to their production of TNF, can enhance the inflammatory response.

Matrix metalloproteinase 9 production by monocytes is enhanced by TNF and participates in the pathology of human cutaneous Leishmaniasis.

INTRODUCTION: Cutaneous leishmaniasis (CL) due to L.braziliensis infection is characterized by a strong inflammatory response with high levels of TNF and ulcer development. Less attention has been given to the role of mononuclear phagocytes to this process. Monocytes constitute a heterogeneous population subdivided into classical, intermediate and non-classical, and are known to migrate to inflammatory sites and secrete inflammatory mediators. TNF participates in the induction of matrix metalloproteinases (MMPs). MMP-9 is an enzyme that degrades basal membrane and its activity is controlled by the tissue inhibitor of metalloproteinase. METHODS: Mononuclear cells were obtained from ex-vivo labeling sub-populations of monocytes and MMP-9, and the frequency was determined by flow cytometry. Culture was performed during 72 hours, stimulating the cells with SLA, levels of MMP-9 and TIMP-1 in the supernatants were determined by ELISA. RESULTS: We observed that cells from CL lesions secrete high amounts of MMP-9 when compared to healthy subjects. Although MMP-9 was produced by monocytes, non-classical ones were the main source of this enzyme. We also observed that TNF produced in high level during CL contributes to MMP-9 production. CONCLUSIONS: These observations emphasize the role of monocytes, TNF and MMP-9 in the pathogenesis of L. braziliensis infection.

Epidemiological study of hepatitis A, B and C in the largest Afro-Brazilian isolated community.

This study was conducted to estimate the prevalence and molecular epidemiological features of viral hepatitis A, B and C in the Kalunga population, which represents the largest Afro-Brazilian isolated community. Among 878 individuals studied, the overall prevalence of anti-hepatitis A virus antibodies was 80.9%, with a significant rise from 44.8% to near 100% between the first and fourth decade of life. Rates for hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) of 1.8% and 35.4%, respectively, were found. Increasing age, male gender, illiteracy and history of multiple sexual partners were associated with hepatitis B virus (HBV) infection. An occult HBV infection rate of 1.7% (5/295) was found among anti-HBc-positive individuals. HBV genotype A (subtype Aa) was dominant in this community. Only 5/878 individuals (0.6%) were positive for anti-hepatitis C virus (HCV). HCV RNA was detected in three of them, who were infected with genotype 1 (subtype 1a). These findings point out high, intermediate and low endemicity for hepatitis A, B and C, respectively, in the Kalunga community in Brazil. Circulation of HBV genotype A (subtype Aa) in this Afro-Brazilian isolated community indicates the introduction of this virus during the slave trade from Africa to Brazil.

Consensus Statement on the Management of Paediatric Asthma. Update 2007

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Seasons and other factors affecting the quality of life of asthmatic children.

OBJECTIVE: To study the effect of seasons on the health-related quality of life (HRQL) of asthmatic children. METHODS: Four groups of asthmatic children 7 to 14 years old were recruited by pediatricians during each season of the year. Their HRQL was assessed by means of the Paediatric Asthma Quality of Life Questionnaire (PAQLQ). Other factors surveyed were asthma severity, atopy, medical treatment, immunotherapy, obesity, parental smoking, and anti-allergic measures. RESULTS: The mean (SD) overall PAQLQ score was highest in summer at 6.2 (1.0) and lowest in autumn at 5.5 (1.2). The same trend was found for domains in summer and autumn, respectively: symptoms, 6.2 (1.0) vs 5.4 (1.4); emotions, 6.5 (0.8) vs 6.0 (1.0); and activities, 5.9 (1.4) vs. 5.0 (1.5). Factors such as male gender (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.41-0.87), being on immunotherapy (OR, 0.59; 95% CI, 0.38-0.92), living in an urban environment (OR, 0.56; 0.33-0.93), and residing on the northern coast of Spain along the Bay of Biscay (OR, 0.56; 0.36-0.89) were independent protective factors against having a total PAQLQ score in the lower tertile. Conversely, being recruited in a primary care setting (OR, 1.55; 1.01-2.38) and having more severe asthma were risks for being in the lower tertile. CONCLUSIONS: Irrespective of the severity of the disease, season has a significant influence on the HRQL of asthmatic children.

Predicción de talla en deportistas / Height prediction in sportsmen

El médico de medicina del deporte debe familiarizarse con los métodos de predicción de la talla definitiva. Con frecuencia, nos encontramos ante niños que pretenden implicarse de una forma más intensa en la práctica de un deporte, al destacar en edades precoces en el mismo. Pero existe la duda razonable, si una constitución física y un desarrollo corporal aparentemente adecuado para la realización de dicho deporte durante el crecimiento, se mantendrán en un futuro, cuando éste niño haya concluido su desarrollo. La predicción de la talla definitiva puede ser un parámetro de excepcional importancia que responder a esta incógnita ayudándonos a evitar que el niño sufra un cúmulo de desilusiones y frustraciones cuando termine su crecimiento por no ser adecuado para alcanzar sus metas deportivas al haberse creado falsas expectativas durante el crecimiento.En éste artículo estudiamos los distintos métodos de predicción de talla más utilizados. Estos métodos presentan ciertas controversias cuando se aplican a situaciones variantes de la normalidad -retraso constitucional del crecimiento y retraso familiar del crecimiento, que son las más complicadas de discernir (AU)

[The behavior of FEV1 and PEFR in the free running test for the detection of exercise-induced asthma in childhood]. / Comportamiento del FEV1 y del PEFR en la prueba de carrera libre para la detección del asma inducida por ejercicio en la infancia.

OBJECTIVE: Our aim was to study the behavior and validity of PEFR and FEV1 in the free-running exercise test in order to diagnose exercise-induced asthma during childhood. PATIENTS AND METHODS: We studied 30 asthmatic children and 30 healthy children as controls. A provocation test was performed by means of free-running exercise in an indoor sports center. Environmental temperature and humidity were equal in both groups. Forced breathing spirometry and the "Mini-Wright peak flow meter" test were recorded before and two, five, fifteen and twenty minutes after the exercise challenge. The spirometric values representing two standard deviations below the mean for each variable studied in the control group were considered as reference values (FEV1 > or = 83.5% and PEFR > or = 81.5%). RESULTS: There was a decrease in FEV1 in 17 asthmatic children (56.7%) and a decrease in PEFR occurred in 14 children (46.7%). No statistically significant differences were found in either test. Specificity was 100% for FEV1 and 96.7% for PEFR. The greatest decrease in both spirometric parameters occurred at five minutes. CONCLUSIONS: According to our results, in a free-running provocation test if we maintain previously controlled environmental conditions and exercise intensity "forced breathing spirometry" and "Mini-Wright peak flow" can be used interchangeably in order to diagnose exercise-induced asthma.

Exercise-induced asthma in children: a comparative study of free and treadmill running.

BACKGROUND: Exercise is one of the most common precipitating factors of acute asthmatic crises in childhood. Although it has been described as more frequent among children, this is probably due to their more abundant physical activity. Nevertheless, it also occurs at other ages. OBJECTIVE: The aim of this study is to assess possible differences in postexercise spirometry after treadmill and free running provocation tests. METHODS: We compared the results obtained in a treadmill test performed by 30 asthmatic children and 30 healthy children with the results obtained with these same children in a free running test, keeping similar environmental conditions (temperature and humidity), exercise intensity (assessed by heart rate), and airway status at the time of the test. RESULTS: Seventy-three percent of the patients had positive treadmill tests and 63.3% had positive free running tests. For the spirometric parameters studied, there were no significant differences in the percent decrease in postexercise performance after either of the provocation tests. For FEV1, which is the most sensitive diagnostic parameter, the sensitivity was 53.3% in treadmill running and 56.7% in free running, with a specificity of 100% in both tests. CONCLUSIONS: If environmental conditions, exercise intensity, and airway status are controlled at the time of the test, treadmill and free running can be used indistinctly as asthma-inducing exercises.