Photoprotection habits, attitudes and knowledge among school communities in the Costa del sol (Spain).

BACKGROUND: Scholar photoprotection campaigns are among the most effective strategies for preventing skin cancer. Analysis of the target population constitutes a valuable starting point for the implementation of primary prevention strategies. Our aim is to study photoprotection habits, attitudes and knowledge among a Spanish school community. METHODS: Descriptive cross-sectional study targeting schoolchildren, parents and teachers at 20 schools in the area of the Costa del Sol Health Agency in southern Spain. Two population-specific, validated questionnaires were used: the CHRESI (for children aged 0-10 years) and CHACES Questionnaire(for adults and adolescents aged > 11 years). We collected demographic data, skin colour, skin phototype, sunburn episodes, sun exposure and photoprotection practices, attitudes and knowledge. RESULTS: 1728 questionnaires were analyzed (22% parents, 14.5% teachers, 44.8% adolescents and 18.6% children). The average ages were 8 years (children), 16 years (adolescents), 39 years (teachers) and 42 years (parents). Globally, the predominant features were: male sex (52%), Spanish nationality (92%) and phototypes II-III (61%). Children, followed by adolescents, reported the highest exposure to the sun, both in frequency and in duration. Adolescents had the higher rate of sunburn (75%), followed by parents/teachers (54.1%) and children (44.1%). Children and their parents were the most likely to adopt photoprotection measures, while adolescents presented more risky attitudes. Knowledge regarding photoprotection was acceptable (6.9/10). CONCLUSIONS: This study highlights the need to improve photoprotection knowledge, habits and attitudes among our target population. Scholars, parents and teachers in our area should be addressed in campaigns to promote healthy sun exposure habits, thus reducing skin cancer-related morbidity and mortality in this region.

Novel amide and imidazole compounds as potent hematopoietic prostaglandin D2 synthase inhibitors.

In seeking novel and potent small molecule hematopoietic prostaglandin D2 synthase (H-PGDS) inhibitors as potential therapies for PGD2-mediated diseases and conditions, we explored a series comprising multiple aryl/heteroaryl rings attached in a linear arrangement. Each compound incorporates an amide or imidazole "linker" between the pyrimidine or pyridine "core" ring and the "tail" ring system. We synthesized and screened twenty analogs by fluorescence polarization binding assay, thermal shift assay, glutathione S-transferase inhibition assay, and a cell-based assay measuring suppression of LPS-induced PGD2 stimulation. Amide analogs show ten-fold greater shift in the thermal shift assay in the presence of glutathione (GSH) versus the same assay run in the absence of GSH. The imidazole analogs did not produce a significant change in thermal shift between the two assay conditions, suggesting a possible stabilization effect of the amide linker in the synthase-GSH-inhibitor complex. Imidazole analog 23, (KMN-010034) demonstrates superior potency across the in vitro assays and good in vitro metabolic stability in both human and guinea pig liver microsomes.

Validation of a Questionnaire Designed to Study Knowledge, Attitudes, and Habits Related to Sun Exposure Among Young Adults: The CHACES Questionnaire. / Validación de un cuestionario para el estudio sobre hábitos, actitudes y conocimientos en fotoprotección en la población adultojuvenil: «cuestionario CHACES¼.

Skin cancer prevention campaigns in schools have been shown to be both effective and cost-effective. The success of such programs depends on the use of an appropriate design informed by a prior survey of the target population (pupils, teachers, and parents). There are, however, very few validated Spanish-language questionnaires designed to study the habits and knowledge of this population with respect to sun exposure in childhood and none designed for use with a young adult population. OBJECTIVES: To construct and validate a questionnaire designed to explore sun exposure behaviors in a young adult population. METHODOLOGY: Two questionnaires were developed, one for adults (18+) and the other for young adults (11-17); both included demographic information, skin color, Fitzpatrick skin type, and history of sunburn as well as questions on knowledge, attitudes and practices related to sun exposure. The content was then piloted and its validity analyzed. The subsequent validation study was divided into 2 phases as follows: 1) analysis of the validity and internal consistency of the items in a cross-sectional study of 1,482 adults and adolescents, using exploratory factor analysis to test construct validity and Cronbach α to measure internal consistency; and 2) evaluation of test-retest reliability in 39 individuals. RESULTS: The pilot study demonstrated the content validity of both questionnaires. Principal component analysis revealed that 2 components in each of the dimensions studied accounted for over 50% of the variance. A good correlation was found between the items studied. Validity was demonstrated in the first phase of the analysis with a Cronbach α of between 0.45 and 0.8 for all components except knowledge (0.335). In the second phase, test-retest reliability was demonstrated (absolute agreement>60%). CONCLUSIONS: The psychometric properties of the questionnaire make it a valid and reliable tool for the study of knowledge, attitudes, and habits with respect to sun exposure in the young adult school population.

Improved homology modeling of the human & rat EP4 prostanoid receptors.

BACKGROUND: The EP4 prostanoid receptor is one of four GPCRs that mediate the diverse actions of prostaglandin E2 (PGE2). Novel selective EP4 receptor agonists would assist to further elucidate receptor sub-type function and promote development of therapeutics for bone healing, heart failure, and other receptor associated conditions. The rat EP4 (rEP4) receptor has been used as a surrogate for the human EP4 (hEP4) receptor in multiple SAR studies. To better understand the validity of this traditional approach, homology models were generated by threading for both receptors using the RaptorX server. These models were fit to an implicit membrane using the PPM server and OPM database with refinement of intra and extracellular loops by Prime (Schrödinger). To understand the interaction between the receptors and known agonists, induced-fit docking experiments were performed using Glide and Prime (Schrödinger), with both endogenous agonists and receptor sub-type selective, small-molecule agonists. The docking scores and observed interactions were compared with radioligand displacement experiments and receptor (rat & human) activation assays monitoring cAMP. RESULTS: Rank-ordering of in silico compound docking scores aligned well with in vitro activity assay EC50 and radioligand binding Ki. We observed variations between rat and human EP4 binding pockets that have implications in future small-molecule receptor-modulator design and SAR, specifically a S103G mutation within the rEP4 receptor. Additionally, these models helped identify key interactions between the EP4 receptor and ligands including PGE2 and several known sub-type selective agonists while serving as a marked improvement over the previously reported models. CONCLUSIONS: This work has generated a set of novel homology models of the rEP4 and hEP4 receptors. The homology models provide an improvement upon the previously reported model, largely due to improved solvation. The hEP4 docking scores correlates best with the cAMP activation data, where both data sets rank order Rivenprost>CAY10684 > PGE1 ≈ PGE2 > 11-deoxy-PGE1 ≈ 11-dexoy-PGE2 > 8-aza-11-deoxy-PGE1. This rank-ordering matches closely with the rEP4 receptor as well. Species-specific differences were noted for the weak agonists Sulprostone and Misoprostol, which appear to dock more readily within human receptor versus rat receptor.

Lepra en Santa Fe: Características clínico-epidemiológicas / Leprosy in Santa Fe: Clinical-epidemiological characteristics

La lepra es una enfermedad infecto-contagiosa crónica, no hereditaria, curable y controlable, causada por el Mycobacterium leprae, que afecta principalmente la piel, mucosas y nervios periféricos. En Argentina es un problema regional y nacional, por la migración que abarca a las provincias de Formosa, Chaco, Corrientes, Entre Ríos, Misiones, Santa Fe y Buenos Aires. Objetivo General: determinar el comportamiento clínico-epidemiológico de la lepra en la Provincia de Santa Fe, desde el 1º de Enero del año 2012 al 31 de Agosto del año 2016. Métodos y Materiales: la información se obtuvo de la revisión de las fichas epidemiológicas, de pacientes con diagnóstico de lepra en el período abarcado. Las variables utilizadas fueron: edad y sexo del paciente, residencia, foco epidemiológico, condiciones ambientales y económicas, clínica, tipo de lepra, grado de discapacidad general y tratamiento. Resultados: se diagnosticaron 86 casos de lepra; 59,3% correspondieron al sexo masculino y 40, 7% al sexo femenino. El promedio de edad fue de 56 años. El 86% de los casos fueron multibacilares y la lepra lepromatosa, fue la forma clínica más frecuente. El 26,7% presentó discapacidad al momento del diagnóstico, 16,3% grado 1 y 10,5% grado 2. Conclusión: la detección de nuevos casos en la Provincia de Santa Fe, fue en promedio de 18 casos anuales, excluido el año 2016, en vigencia. Rosario fue el departamento con más casos registrados. El 60% de los casos se comunicó entre los 35 y 66 años; el sexo masculino fue el más afectado. Los casos multibacilares prevalecieron sobre los paucibacilares; la forma clínica más frecuente fue la lepra lepromatosa. Se estableció discapacidad en uno de cada cuatro pacientes.

Leprosy is a chronic disease which, despite having a variable clinic, is diagnosable and treatable when receiving a multidrug therapy (MDT) as the one proposed by the World Health Organization (WHO). In Argentina, it is characterized by moderate endemicity and focus on certain geographic areas (provinces of northeastern, northwest and center of Argentina). General Objective: determine the clinical and epidemiological behavior of leprosy in the province of Santa Fe. Methods and Materials: the cases reported since 1º January 2012 to 31 August 2016, were retrospectively collected from the review of the epidemiological records of the Ministry of Health, Environment and Social Action of the Province of Santa Fe. The variables were: age and sex of the patient, residence, epidemiological focus, environmental and economic conditions, kind of leprosy, degree of disability and finally the treatment. Results: 86 cases of leprosy were diagnosed: 59,3% were male and 40,7% sex, were female. The average age was 56 years. 86% of cases were multibacillary and lepromatous leprosy was the most frequent clinical form. The 26,7% had disability at the moment of diagnosis, 16,3% 10,5% grade 1 and grade 2. Conclusion: in the Province of Santa Fe, the detection of new leprosy cases have been stable in the last years, with a minimun of 17 and a maximum of 29 cases per year. Rosario was the city with more registered cases, followed by: La capital, General Obligado y Nueve de Julio. The most affected patients were male, and 60% of cases reported between 35 and 66 years. Multibacillary cases prevailed over paucibacillary; the most frequent clinical form was lepromatous leprosy. One in four patients had disability at the moment of diagnosis.

Exercise capacity impairment in COPD patients with comorbidities.

BACKGROUND: Comorbidities are common in COPD and have been associated with reduced health status, increased health care utilization, all-cause hospitalization, and mortality. There is a scarcity of data on the relationship between comorbidities and functional capacity. OBJECTIVE: to evaluate the impact of comorbidities on functional capacity of COPD patients. METHODS: a cross-sectional study was conducted at two teaching hospitals in Fortaleza, Brazil. The functional capacity was assessed by spirometry and the 6-min walking test (6MWT). The health status was assessed by the St. George's respiratory questionnaire (SGRQ) and the COPD assessment test (CAT). The sample was stratified as having "none", "one" and "two or three" comorbidities groups. One-way ANOVA was used to compare means of the three groups and a multiple linear regression was run to predict the impact of comorbidities on 6MWT. RESULTS: Comorbidities (hypertension, coronary disease and diabetes) were found in 54% of the studied patients. The mean age of the 79 patients was 67±8 years and 55% were male. CAT scores increased from "no comorbidity" (17.9±7.7) to "one comorbidity" (22.8±6.8) and "two or three comorbidities" groups (24.2±10.2). A post hoc test showed a significant difference in the "no comorbidity" compared to the "two or three comorbidities" groups (p=0.01). The distance walked by the patients decreased from "no comorbidity" (386.1±83.2m) to "one comorbidity" (350±98m) and "two or three comorbidities" groups (312.6±91m). A post hoc test showed significant difference in the "no comorbidity" compared to "two or three comorbidities" groups (p=0.007). Numbers of comorbidities were independently associated with the 6MWT adjusting for age, severity of COPD and CAT scores. CONCLUSION: in the studied sample, the presence of comorbidities contributed to impair exercise capacity in patients with COPD.

Local delivery of the Neuregulin1 receptor ecto-domain (ecto-ErbB4) has a positive effect on regenerated nerve fiber maturation.

The Neuregulin/ErbB system plays an important role in the peripheral nervous system, under both normal and pathological conditions. We previously demonstrated that expression of soluble ecto-ErbB4, the released extracellular fragment of the ErbB4 receptor, stimulated glial cell migration in vitro. In this study we examined the possibility of manipulating this system in vivo in order to improve injured peripheral nerve regeneration. Transected rat median nerves of adult female Wistar rats were repaired with a 10-mm-long graft made by muscle-in-vein combined nerve guide previously transduced with either the adeno-associated viral (AAV) vector AAV2-LacZ or AAV2-ecto-ErbB4. Autologous nerve grafts were used as control. Both stereological and functional analyses were performed to assess nerve regeneration. Data show that delivery of soluble ecto-ErbB4 by gene transfer in the muscle-in-vein combined nerve guide has a positive effect on fiber maturation, suggesting that it could represent a potential tool for improving peripheral nerve regeneration.

Sensibilización de contacto a alérgenos de la serie estándar en el Hospital Costa del Sol: Estudio retrospectivo (2005-2010) / Contact Sensitization to Allergens in the Spanish Standard Series at Hospital Costa del Sol in Marbella, Spain: a Retrospective Study (2005-2010)

La prevalencia de la alergia de contacto a los diferentes compuestos puede variar dependiendo de la población estudiada, de la técnica y del material empleado en las pruebas epicutáneas. En España el Grupo Español de Investigación en Dermatitis de Contacto y Alergia Cutánea (GEIDAC) ha propuesto una batería de 29 alérgenos para estudiar a los pacientes con sospecha de dermatitis de contacto alérgica. Material y métodos: Análisis retrospectivo de 839 pacientes con sospecha de dermatitis de contacto, realizado en el Hospital Costa del Sol desde el 1 de enero de 2005 hasta el 31 de diciembre de 2010. Para ello se utilizaron pruebas epicutáneas estándar de 34 alérgenos en las que estuvieron incluidos los 29 compuestos de la batería estándar española propuesta por el GEIDAC. Objetivo: Valorar la prevalencia de la sensibilización de contacto entre los pacientes estudiados y estudiar su asociación con factores sociodemográficos (sexo, edad, localización, ocupación) y clínicos (dermatitis atópica). Resultados: El 48% de los pacientes presentó sensibilización al menos a uno de los alérgenos testados. Las mujeres presentaron una frecuencia de sensibilización más elevada que los hombres (56,9 vs. 33,1%). La localización afectada con mayor frecuencia fue la mano (36,1%). Los alérgenos más frecuentes fueron sulfato de níquel (25,9%), dicromato potásico (7,6%), tiomersal (5,1%), cloruro de cobalto (4,5%) y mezcla de fragancias I (3,8%). Por el contrario, se detectó una baja frecuencia de sensibilización a conservantes como mezcla de parabenos (0,1%), imidazolidinil urea (0,1%), diazolidinil urea (0,2%) y mezcla de quinoleínas (0,2%). No se registraron sensibilizaciones para lactonas sesquiterpénicas y metildibromoglutaronitrilo (euxyl K400). Conclusiones: Nuestros resultados son similares a los previamente publicados a nivel nacional. La baja sensibilización a ciertos alérgenos, como la mayoría de conservantes y las lactonas sesquiterpénicas, podría hacer necesario reconsiderar su utilidad como alérgenos en futuras series estándar (AU)

Background: The prevalence of contact allergy to different compounds can vary according to the population studied, the technique used, and the materials employed in patch tests. The Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) has proposed a panel of 29 allergens for use in patients with suspected allergic contact dermatitis. Objective: To determine the prevalence of contact sensitization in a group of Spanish patients and to analyze potential associations with sociodemographic and clinical variables (sex, age, site of lesions, occupation, and diagnosis of atopic dermatitis). Material and methods: A retrospective study of patients with suspected contact dermatitis was undertaken at Hospital Costa del Sol in Marbella, Spain, for the period between January 1, 2005 and December 31, 2010; 839 patients were included in the analysis. Patch tests were carried out with 34 allergens, including the 29 compounds that comprise the Spanish standard panel proposed by the GEIDAC. Results: Sensitization to at least 1 allergen in the panel was observed in 48% of patients. Women had a higher frequency of sensitization than men (56.9% vs 33.1%). The hands were the most commonly affected site (36.1%). The most frequently involved allergens were nickel sulfate (25.9%), potassium dichromate (7.6%), thiomersal (5.1%), cobalt chloride (4.5%), and fragrance mix I (3.8%). In contrast, preservatives such as paraben mix (0.1%), imidazolidinyl urea (0.1%), diazolidinyl urea (0.2%), and quinoline mix (0.2%) had low rates of sensitization. Sensitization to sesquiterpene lactones and methyldibromo glutaronitrile (euxyl K 400) were not observed. Conclusions: Our results are similar to those previously reported for Spanish patients. The low level of sensitization to certain allergens such as most preservatives and sesquiterpene lactones may suggest that their use in standard patch test series should be reconsidered(AU)

[Contact sensitization to allergens in the Spanish standard series at Hospital Costa del Sol in Marbella, Spain: a retrospective study (2005-2010)]. / Sensibilización de contacto a alérgenos de la serie estándar en el Hospital Costa del Sol: Estudio retrospectivo (2005-2010).

BACKGROUND: The prevalence of contact allergy to different compounds can vary according to the population studied, the technique used, and the materials employed in patch tests. The Spanish Contact Dermatitis and Skin Allergy Research Group (GEIDAC) has proposed a panel of 29 allergens for use in patients with suspected allergic contact dermatitis. OBJECTIVE: To determine the prevalence of contact sensitization in a group of Spanish patients and to analyze potential associations with sociodemographic and clinical variables (sex, age, site of lesions, occupation, and diagnosis of atopic dermatitis). MATERIAL AND METHODS: A retrospective study of patients with suspected contact dermatitis was undertaken at Hospital Costa del Sol in Marbella, Spain, for the period between January 1, 2005 and December 31, 2010; 839 patients were included in the analysis. Patch tests were carried out with 34 allergens, including the 29 compounds that comprise the Spanish standard panel proposed by the GEIDAC. RESULTS: Sensitization to at least 1 allergen in the panel was observed in 48% of patients. Women had a higher frequency of sensitization than men (56.9% vs 33.1%). The hands were the most commonly affected site (36.1%). The most frequently involved allergens were nickel sulfate (25.9%), potassium dichromate (7.6%), thiomersal (5.1%), cobalt chloride (4.5%), and fragrance mix I (3.8%). In contrast, preservatives such as paraben mix (0.1%), imidazolidinyl urea (0.1%), diazolidinyl urea (0.2%), and quinoline mix (0.2%) had low rates of sensitization. Sensitization to sesquiterpene lactones and methyldibromo glutaronitrile (euxyl K 400) were not observed. CONCLUSIONS: Our results are similar to those previously reported for Spanish patients. The low level of sensitization to certain allergens such as most preservatives and sesquiterpene lactones may suggest that their use in standard patch test series should be reconsidered.

Physical self-perception and motor performance in normal-weight, overweight and obese children.

The aim of this study was to examine the relationships among physical self-perception, body image and motor performance in Italian middle school students. Two hundred and sixty children were categorized into normal-weight (n=103), overweight (n=86) or obese (n=71) groups. Perceived coordination, body fat and sports competence were assessed using the Physical Self-Description Questionnaire, while body image was measured using Collins' Child Figure Drawings. Individuals' perceptions of strength, speed and agility were assessed using the Perceived Physical Ability Scale. Tests involving the standing long jump, 2 kg medicine-ball throw, 10 × 5 m shuttle-run and 20 and 30 m sprints were also administered. Girls, when compared with boys, and overweight and obese participants, when compared with normal-weight peers, reported lower perceived and actual physical competence, higher perceived body fat and greater body dissatisfaction. Body dissatisfaction mediated all the associations between body mass index (BMI) and the different aspects of physical self-perception in boys, but not in girls. The same pattern of results was found for physical self-perception as a mediator of the relationship between BMI and body dissatisfaction. In conclusion, obesity proved to have adverse effects on both motor performance and physical self-perception.

Characterization of basal nitric oxide production in living cells.

Nitric oxide (NO) is an important modulator of immune, endocrine and neuronal functions; however, measuring physiological levels of NO in cell cultures is generally difficult because of the lack of suitable methodologies. We have selected three cell lines from different origins: the neuroblastoma-derived Neuro2A (N2A), the cholinergic SN56 and the non-neuronal COS-1. We first demonstrated the presence of NADPH-diaphoretic activity, a potential marker of the NO-synthesizing (NOS) enzyme. By immunocytochemistry, using specific antibodies for each NOS subtype, we observed that subtype I was present in all cell lines and that subtype II was present in COS-1 and N2A cell lines. The presence of these NOS subtypes was further verified by Western blot analysis. Control cells treated with DAF-2 DA exhibited significant fluorescent levels corresponding to basal NO production. The subcellular distribution of the synthesizing enzyme was consistent with the NO-fluorescence signal; whereas, fixation affected the subcellular pattern of NO fluorescence signal. Addition of NOS inhibitors or NO scavengers to the incubation medium reduced the intensity of the NO fluorescence signal in a concentration-dependent manner. Conversely, increasing concentrations of a NO donor, or incident light, increased the fluorescence intensity. Our observation of NO production and distribution using the DAF-2 method has a direct impact on studies using these cell lines.

Benign paroxysmal positional vertigo, incidence and treatment.

Benign paroxysmal positional vertigo is characterized by acute vertigo that is accentuated by movements of the head. It can be identified by the presence of nystagmus triggered by certain head positions. Over a 1-year period, among 1,902 cases of different types of equilibrium disorders, there were 98 cases of BPPV including 63 BPPV ofthe posterior canal, 21 of the lateral canal, 13 combined (HC + PC) and one case affecting the anterior canal. Most of the cases were idiopathic. Treatment was based on the Semont maneuver for BPPV-PC. BPPV-HC was treated with the Vannucchi maneuver and a personal method. The one case of BPPV-AC was treated with a modified Semont maneuver. Satisfactory therapeutic results were noted in all cases. Cases with a long-term follow-up showed a high percentage of elimination of relapse after 24 months.

Corticosteroid receptors: a dynamic interplay between protein folding and homeostatic control. Possible implications in psychiatric disorders.

Glucocorticoids are key elements in the maintenance of an organism's homeostasis, a dynamic balance that is constantly challenged by internal and external stressors. Chronic exposure to elevated glucocorticoids may induce profound effects on an individual's physical and mental well-being. Therefore, a complex neuroendocrine system, the limbic-hypothalamo-pituitary-adrenocortical (LHPA) axis, exists to regulate glucocorticoid homeostasis. Dysregulation of the LHPA axis has been linked to numerous psychiatric disorders, including eating disorders, anxiety, depression, posttraumatic stress disorder, memory impairment, neurodegenerative disorders, and even Alzheimer disease. At a molecular level, the actions of glucocorticoids are mediated by two different cytoplasmic receptors, the mineralocorticoid receptor and the glucocorticoid receptor. These corticosteroid receptors are heteromeric complexes found in dynamic association with a still growing number of chaperone proteins and other factors mediating their actions. Because this dynamic association is extremely sensitive to changes in cellular environment, energy, and metabolic state, we hypothesize that these corticosteroid receptors act as "sensor" signal transducers critical for homeostasis. In this review, we focus on the interplay among protein folding, transport, and function of the corticosteroid receptors at the cellular level, which provides a foundation for understanding the pathogenesis of glucocorticoid resistance or hypersensitivity, causing imbalances in the LHPA axis, and possibly triggering psychiatric disorders.

Direct evidence of nitric oxide presence within mitochondria.

Nitric oxide (NO) has been implicated in the modulation of mitochondrial respiration, membrane potential, and subsequently in apoptosis. Although the presence of a mitochondrial NO synthase (mtNOS) has been described, there is no direct evidence in vivo of the presence of NO within mitochondria. It was the aim of this study to demonstrate the in vivo production of NO within mitochondria. Using the novel fluorometric NO detection system, 4,5-diaminofluorescein diacetate (DAF-2/DA), we observed the presence of NO production in PC12 and COS-1 cells by conventional and confocal fluorescence microscopy. Part of the overall NO signal was colocalized within a subpopulation of mitochondria, labeled with the potential-dependent probe MitoTracker red. These findings demonstrate for the first time that the subcellular distribution of NO production is consistent with the presence of a mitochondrial NOS. Our results provide a new tool to directly study the modulatory role of NO in mitochondrial respiration and membrane potential, in vivo.