Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: A triple blinded, placebo controlled, randomized phase I/II safety and feasibility study.

BACKGROUND: Currently available treatments for secondary progressive multiple sclerosis(SPMS) have limited efficacy and/or safety concerns. Adipose-mesenchymal derived stem cells(AdMSCs) represent a promising option and can be readily obtained using minimally invasive procedures. PATIENTS AND METHODS: In this triple-blind, placebo-controlled study, cell samples were obtained from consenting patients by lipectomy and subsequently expanded. Patients were randomized to a single infusion of placebo, low-dose(1x106cells/kg) or high-dose(4x106cells/kg) autologous AdMSC product and followed for 12 months. Safety was monitored recording adverse events, laboratory parameters, vital signs and spirometry. Expanded disability status score (EDSS), magnetic-resonance-imaging, and other measures of possible treatment effects were also recorded. RESULTS: Thirty-four patients underwent lipectomy for AdMSCs collection, were randomized and thirty were infused (11 placebo, 10 low-dose and 9 high-dose); 4 randomized patients were not infused because of karyotype abnormalities in the cell product. Only one serious adverse event was observed in the treatment arms (urinary infection, considered not related to study treatment). No other safety parameters showed changes. Measures of treatment effect showed an inconclusive trend of efficacy. CONCLUSION: Infusion of autologous AdMSCs is safe and feasible in patients with SPMS. Larger studies and probably treatment at earlier phases would be needed to investigate the potential therapeutic benefit of this technique.

Biomarkers and polymorphisms in pancreatic neuroendocrine tumors treated with sunitinib.

Several circulating biomarkers and single nucleotide polymorphisms (SNPs) have been correlated with efficacy and tolerability to antiangiogenic agents. These associations remain unexplored in well-differentiated, metastatic pancreatic neuroendocrine tumors treated with the multitargeted tyrosine kinase inhibitor sunitinib. We have assessed the effect on tumor response at 6 months, overall survival, progression-free survival and safety of 14 SNPs, and 6 soluble proteins. Forty-three patients were recruited. Two SNPs in the vascular endothelial growth factor receptor 3 (VEGFR-3) gene predicted lower overall survival: rs307826 with hazard ratio (HR) 3.67 (confidence interval [CI] 95%, 1.35-10.00) and rs307821 with HR 3.84 (CI 95%, 1.47-10.0). Interleukin-6 was associated with increased mortality: HR 1.06 (CI 95%, 1.01-1.12), and osteopontin was associated with shorter PFS: HR 1.087 (1.01-1.16), independently of Ki-67. Furthermore, levels of osteopontin remained higher at the end of the study in patients considered non-responders: 38.5 ng/mL vs. responders: 18.7 ng/mL, p-value=0.039. Dynamic upward variations were also observed with respect to IL-8 levels in sunitinib-refractory individuals: 28.5 pg/mL at baseline vs. 38.3 pg/mL at 3 months, p-value=0.024. In conclusion, two VEGFR-3 SNPs as well as various serum biomarkers were associated with diverse clinical outcomes in patients with well-differentiated pancreatic neuroendocrine tumors treated with sunitinib.

Equity, barriers and cancer disparities: study of the Spanish Society of Medical Oncology on the access to oncologic drugs in the Spanish Regions.

PURPOSE: The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. METHODS: An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. RESULTS: 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. CONCLUSIONS: The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions.

Molecular Profiling of Circulating Tumour Cells Identifies Notch1 as a Principal Regulator in Advanced Non-Small Cell Lung Cancer.

Knowledge on the molecular mechanisms underlying metastasis colonization in Non-Small Cell Lung Cancer (NSCLC) remains incomplete. A complete overview integrating driver mutations, primary tumour heterogeneity and overt metastasis lacks the dynamic contribution of disseminating metastatic cells due to the inaccessibility to the molecular profiling of Circulating Tumour Cells (CTCs). By combining immunoisolation and whole genome amplification, we performed a global gene expression analysis of EpCAM positive CTCs from advanced NSCLC patients. We identified an EpCAM+ CTC-specific expression profile in NSCLC patients mostly associated with cellular movement, cell adhesion and cell-to-cell signalling mediated by PI3K/AKT, ERK1/2 and NF-kB pathways. NOTCH1 emerged as a driver connecting active signalling pathways, with a reduced number of related candidate genes (NOTCH1, PTP4A3, LGALS3 and ITGB3) being further validated by RT-qPCR on an independent cohort of NSCLC patients. In addition, these markers demonstrated high prognostic value for Progression-Free Survival (PFS). In conclusion, molecular characterization of EpCAM+ CTCs from advanced NSCLC patients provided with highly specific biomarkers with potential applicability as a "liquid biopsy" for monitoring of NSCLC patients and confirmed NOTCH1 as a potential therapeutic target to block lung cancer dissemination.

EGFR testing and clinical management of advanced NSCLC: a Galician Lung Cancer Group study (GGCP 048-10).

PURPOSE: This study aimed to assess the incidence of mutations in the epidermal growth factor receptor (EGFR) gene in non-small-cell lung cancer (NSCLC) patients in the Galician region of Spain and the clinical management and outcome of patients carrying EGFR mutations. PATIENTS AND METHODS: All newly diagnosed advanced or metastatic NSCLC patients were screened for EGFR mutations in matched tumor samples (tissue or cytology specimens) and serum samples. RESULTS: Of 198 patients screened for EGFR mutations in tumor samples, 184 had evaluable data and, of these, 25 (13.6%) had EGFR mutations (84% sensitizing mutations). EGFR mutation was found in serum in 14 (8.1%) patients (of 174 evaluable). Compared to matched tumor tissue, serum EGFR mutation testing specificity and sensitivity were 99% and 52%, respectively. All but two patients received gefitinib. Median progression-free survival and overall survival were 10 (95% confidence interval: 4.8-15.3) months and 17.8 (95% confidence interval: 13.9-21.6) months, respectively, in patients carrying sensitizing mutations. CONCLUSION: The incidence of EGFR mutations in Galicia is consistent with previous data in Spain. Our results also support the feasibility of EGFR testing to guide treatment decision making using tumor tissue or cytology samples, or serum samples if tumor specimens are unavailable. These findings also confirm that first-line gefitinib is an active treatment option in Caucasians with EGFR mutation-positive NSCLC.

Influencia de factores negativos del contexto de trabajo en desgaste psíquico de trabajadores en Colombia / Influence of negative factors in the context of work in psychological exhaustion of workers in Colombia / Influéncia de fatores negativos do contexto de trabalho i desgaste psíquico de trabalhadores i Colômbia

Objetivo: Identificar la influencia que la percepción sobre los factores de contexto de trabajo tiene sobre desgaste psíquico en trabajadores de Centro Oriente y Suroccidente en Colombia en 2013. Materiales y Métodos: Diseño no experimental, transversal, cuantitativo. Muestra no probabilística, seleccionada por conveniencia, 193 trabajadores de población laboral de diversos sectores empresariales. Instrumento: batería para estudio de condiciones de trabajo de carácter psicosocial "CTCPS-MAC" validada para población iberoamericana, evalúa cuatro dimensiones: contexto de trabajo, contenido de trabajo, factores individuales y desgaste psíquico e incluye 14 factores psicosociales. El tipo de investigación es descriptivo, comparativo y correlacional de tipo multivariante. El análisis de datos y los resultados de los instrumentos se hicieron en el programa IBM SPSS Statistics 21. Resultados: cultura organizacional [p = 0,000 Exp (B) = 9,300] y formación técnica o superior [p = 0,001 Exp (B) = 5,600] infieren mayor riesgo para provocar desgaste psíquico cognitivo-emocional. A nivel conductual el rol [p = 0,000 Exp (B) = 30,714] y las relaciones interpersonales en el trabajo [p = 0,001 Exp (B) = 16,381]. El trabajador con formación técnica o superior y percepción nociva de cultura de empresa tiene una probabilidad del 70,70% de desgaste psíquico cognitivo-emocional. Una mala percepción de rol y de las relaciones interpersonales una probabilidad del 35,10% de desgaste psíquico conductual. Conclusiones: El estudio permite profundizar en el conocimiento de factores psicosociales de contexto de trabajo y muestran la importancia que, una buena cultura de organización y gestión, adecuado papel o rol en la organización y buenas relaciones interpersonales en el trabajo, tienen en la consecución de una organización saludable, promotora de salud y bienestar en todos sus integrantes.

Objective: To identify the influence that the perception on the factors of work context have on the psychological exhaustion of workers in Central East and South-Western Colombia in 2013. Materials and Methods: Non-experimental, cross-sectional and quantitative design. Non-probabilistic sample, selected for convenience, 193 workers from the working population of various business sectors. Instruments: battery for the study of working conditions of psychosocial character "CTCPS-MAC" validated for Iberoamerican population. It evaluates four dimensions: work context, work content, individual factors and psychological exhaustion, and includes 14 psychosocial factors. The research is descriptive, comparative and co-relational of multivariate type. Data analysis and results of the instruments were analyzed through IBM SPSS Statistics 21. Results: The organizational culture [p = 0.000 Exp (B) = 9.300] and technical training or higher education [p = 0.001 Exp (B) = 5.600] cause higher risk to end up in psychological cognitive-emotional exhaustion. At the behavioral level, the role [p = 0.000 Exp (B) = 30.714] and the interpersonal relationships at work [p = 0.001 Exp (B) = 16.381] are the exhaustion cause. The workers with technical training or higher education and a harmful perception of the company culture has a 70.70% chance of psychological cognitive-emotional exhaustion. A bad perception of the role and of interpersonal relationships represent a 35.10% possibility of psychological behavioral exhaustion. Conclusions: This study allows deeper understanding of psychosocial factors of work context and shows the importance that a good organizational culture and management, an appropriate role in the organization and good interpersonal relationships at work, have in achieving a healthy organization that promotes health and wellness in all its members.

Objetivo: Identificar a influencia que a percepção sobre os fatores de contexto de trabalho tem sobre desgaste psíquico em trabalhadores de Centro Oriente e Sul ocidente em Colômbia em 2013. Materiais e Métodos: Desenho no experimental, transversal, qualitativo. Mostra no probabilístico, selecionada por conveniência, 193 trabalhadores de povoação laboral de diversos setores empresariais. Instrumento: bateria para estudo de condições de trabalho de caráter psicossocial "CTCPS-MAC" validada para povoação ibero-americana, avalia quatro dimensões: contexto de trabalho, conteúdo de trabalho, fatores individuais e desgastes psíquico e inclui 14 fatores psicossociais. O tipo de pesquisa é descritiva, comparativa e correlacional de tipo multivariante. O analise de dados e os resultados dos instrumentos se fizeram no programa IBM SPSS Statistics 21. Resultados: cultura organizacional [p = 0,000 Exp (B) = 9,300] e formação técnica ou superior [p = 0,001 Exp (B) = 5,600] inferem maior risco para provocar desgaste psíquico cognitivo-emocional. A nível conductual o rol [p = 0,000 Exp (B) = 30,714] e as relaciones interpessoais no trabalho [p = 0,001 Exp (B) = 16,381]. O trabalhador com formação técnica ou superior e percepção nociva de cultura tem uma probabilidade do 70,70% de desgaste psíquico cognitivo-emocional. Uma má percepção de rol e das relações interpessoais uma probabilidade do 35,10% de desgaste psíquico conductual. Conclusões: O estudo permite aprofundar no conhecimento de fatores psicossociais de contexto de trabalho e mostram a importância que, uma boa cultura de organização e gestão, adequada papel o rol na organização e boas relaciones interpessoais no trabalho, tem na consecução de uma organização saudável, promotora de saúde e bem estar em todos seus integrantes.

Condiciones de trabajo psicosociales y desgaste psíquico en trabajadores de diversos sectores empresariales de Centro-Oriente, Suroccidente y región Caribe en Colombia / Psychosocial working conditions and psychological exhaustion in workers of various business sectors in Center Orient, South Occidental and Caribbean Region in Colombia

Objetivo:Determinar la percepción de trabajadores de distintos sectores empresariales de Colombia sobre los factores psicosociales presentes en su entorno laboral y la relación entre los factores psicosociales nocivos y los síntomas subjetivos y alteraciones de la salud. Materiales y métodos: Estudio no experimental, transversal y cuantitativo. Participaron 370 trabajadores, de diferentes sectores empresariales de Colombia (Centro-Oriente, Suroc-cidente y región Caribe). Instrumento: batería para el estudio de las condiciones de trabajo de carácter psicosocial(CTCPS-MAC), validada para población iberoamericana, permite evaluar cuatro dimensiones: Contexto de trabajo, Contenido de trabajo, Factores individuales y Desgaste psíquico e incluye catorce factores psicosociales. Los datos se analizaron con IBM SPSS statistics 21. Se realizó análisis bivariado y regresión logística multivariante de factores psicosociales nocivos y desgaste psíquico. Resultados:Los factores formación, baja médica, contexto de trabajo, contenido de trabajo y factores individuales están asociados en este estudio con desgaste psíquico. El contexto de trabajo es la variable que infiere mayor riesgo (p=0.000; Exp (B)= 5.355) para provocar desgaste psíquico, seguida de la formación técnica o superior y del contenido del trabajo. Conclusiones: Si bien aquellos trabajadores cuya percepción nociva del contexto de trabajo (interrelación trabajo-vida familiar/personal, cultura de la organización, gestión de la empresa, etc.), del contenido de trabajo (concepción tareas, carga y ritmo de trabajo, etc.) y los que tienen formación técnica o superior tienen mayor probabilidad de padecer desgaste psíquico, se observan aspectos positivos de las condiciones de trabajo psicosocial y su influencia en los trabajadores y en las organizaciones.

Objective: Determine the perception of workers in different business sectors in Colombia, on psychosocial factors that are present in their work environment and the relationship between negative psychosocial factors and subjective symptoms and health disorders. Materials and methods: Non-experimental, cross-sectional and quantitative study. 370 employees participated from different business sectors in Colombia (Central East, Southwestern, and Caribbean Region). Instruments: battery for the study of working conditions of psychosocial character (CTCPS-MAC) validated in Latin American population, which allows evaluating four dimensions: work context, work content, individual factors and psychological exhaustion and includes fourteen psychosocial factors. Data was analyzed with IBM SPSS statistics 21. It was performed a bivariate analysis and multivariate logistic regression of adverse psychosocial factors and psychological exhaustion. Results: Factors formation, sick leave, work context, work content and individual factors are associated in this study with psychological exhaustion. The work context is the variable that infers increased risk (p = 0.000, Exp (B) = 5.355) to cause psychological exhaustion, followed by technical or higher education and work content. Conclusions: Although those workers with a noxious perception of work context (interrelation between work and family and personal life, organizational culture, company management, etc.), content of work (tasks content, load and work rate, etc.), and those with technical or higher education, have more probability to suffer psychological exhaustion, positive aspects of psychosocial work conditions and their impact on workers and organizations are observed.

Representaciones sociales sobre la práctica odontológica en un grupo de profesionistas de la salud en Guadalajara (México) / Social Representations about Dental Practice in a Group Health Professionals in Guadalajara (México)

Objetivo: Reconocer las representaciones sociales que un grupo de profesionistas tiene sobre la práctica profesional del odontólogo. Material y métodos: La metodología empleada fue de tipo cualitativa, con apoyo de técnicas etnográficas; se realizaron entrevistas en profundidad a 29 profesionistas de la salud, de ambos sexos, durante el periodo 2010-2011. El análisis de la información obtenida se realizó mediante codificación abierta, axial y selectiva. Resultados: Se identificó las categorías de miedo al dolor y mala relación entre paciente-dentista como parte de la representación social de la práctica dental. Conclusiones: Los resultados muestran que el dolor y los miedos a la asistencia odontológica afectan negativamente a la viabilidad del tratamiento y, por ende, repercute de forma desfavorable en la salud dental de los entrevistados.

Objective: To recognize the social representations that a group of professionals have over the professional practice of dentistry. Material and methods: The methodology employed was of qualitative and ethnographic, through In-depth interviews to 29 health professionals of both sexes during the period 20102011. The analysis of data obtained was performed using open, axial and selective coding. Results: The results show social representation linked to fear to pain and a bad relationship patient-dentist during dental practice. Conclusions: The results show that the pain and fears of dental treatment adversely affect the viability of treatment and therefore an adverse impact on dental health of respondents.

Evaluation of Circulating Tumor Cells and Related Events as Prognostic Factors and Surrogate Biomarkers in Advanced NSCLC Patients Receiving First-Line Systemic Treatment.

In the present study we investigated the prognostic value of Circulating Tumour Cells (CTC) and their utility for therapy monitoring in non-small cell lung cancer (NSCLC). A total of 43 patients newly diagnosed with NSCLC were prospectively enrolled. Blood samples were obtained before the 1st, 2nd and 5th cycles of chemotherapy and analyzed using CellSearch technology. Both CTC and CTC-related objects (not morphological standard or broken epithelial cells) were counted. At baseline 18 (41.9%) patients were positive for intact CTC count and 10 (23.2%) of them had ≥5 CTC, while CK positive events were found in 79.1% of patients. The group of patients with CTC ³5 at baseline presented worse PFS and OS than those with <5 CTC (p = 0.034 and p = 0.008, respectively). Additionally, high levels of total CK positive events were associated with poor prognosis in the group of patients with <5 CTC. Regarding therapy monitoring, patients presenting increased levels of CTC during the treatment demonstrated lower OS and PFS rates. All these data supported the value of CTC as a prognostic biomarker and as a surrogate indicator of chemotherapy effectiveness in advanced NSCLC patients, with the additional value of analyzing other "objects" such as apoptotic CTC or CK fragments to guide the clinical management of these patients.

Tiempo libre y trabajo doméstico en su relación con daños psicosociales en docentes de una universidad pública mexicana / Leisure time and household work and their relationship to psychosocial health effects in teachers at a Mexican Public University

Estudio de la salud en el trabajo en docentes de la Universidad Autónoma Metropolitana-Xochimilco, considerando ciertas condiciones relacionadas con el uso del tiempo libre y el trabajo doméstico que pueden asociarse tanto positiva como negativamente con el bienestar y la salud. Material y métodos: Estudio observacional, transversal y analítico en una población académica. Se aplicó una encuesta individual a una población académica seleccionada aleatoriamente, participando 199 docentes universitarios, se exploraron las exigencias laborales, actividades domésticas y el uso del tiempo libre, así como daños en la salud. Resultados: Hay mayores exigencias laborales, tareas domésticas y trastornos en la mujer. Los daños a la salud muestran las siguientes tasas de prevalencia para mujeres y hombres: músculo-esqueléticos 51 vs 29; distrés 50 vs 35; Disfonía 48 vs 31 y trastorno del sueño 41 vs 25, respectivamente, asociadas estadísticamente. Se identificaron mediante análisis de cluster efectos positivos a través de la cercanía estrecha de conglomerados que dieron cuenta del desarrollo de manera sostenida de actividades durante el tiempo libre y la ausencia de trastornos en la salud. Conclusiones: Se recomienda una mayor organización de las actividades laborales que permitan un uso más activo del tiempo libre, debiendo enfatizar la realización del ejercicio físico, que resultó ser el principal elemento protector contra trastornos en la salud física y mental.

Objectives: To conduct an occupational health study of teaching staff at the Universidad Autónoma Metropolitana-Xochimilco. The study considers conditions relating to use of leisure time and house-hold work which can be associated both positively and negatively with well-being and health. Materials and methods: Observational, cross-sectional, analytical study of an academic population. A survey was applied to a single randomly selected academic population. The participants were 199 university teaching staff. The survey asked about work demands, household activities and the use of leisure time, and adverse health effects. Results: More household tasks and work demands, and more adverse health effects, were found in women. Prevalence rates for statistically associated adverse health effects in women and men respectively were: musculoskeletal disorders 51 vs 29; stress 50 vs 35; dysphonia 48 vs 31; and sleep disorders 41 vs 25. Positive effects were identified by means of cluster analysis by the close proximity of clusters showing sustained activities carried out during leisure time and the absence of adverse health effects. Conclusions: Better organization of work activities to enable more active usage of leisure time is recommended, with an emphasis on physical activity, which is the main protective measure against harm to physical and mental health.

Methylphenidate in the management of asthenia in breast cancer patients treated with docetaxel: results of a pilot study.

BACKGROUND: The objectives of this pilot study were to evaluate the safety and efficacy of the central nervous system stimulant methylphenidate in the management of asthenia in breast cancer patients treated with docetaxel. PATIENTS AND METHODS: Patients with early breast cancer who presented asthenia >3 on the Visual Analogue Scale (VAS) after the first cycle of docetaxel-based chemotherapy were included. Patients received two additional cycles of chemotherapy, one with methylphenidate (10 mg bid) and the other without methylphenidate. Asthenia was evaluated using VAS and the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) scale. Distress was assessed using the Hospital Anxiety and Depression Scale (HADS), and quality of life using FACT-F. RESULTS: Ten patients were included and evaluated for efficacy and safety. Overall, cycles with methylphenidate were better tolerated than those without methylphenidate in terms of asthenia (VAS, p = 0.004; FACT-F, p = 0.027) and quality of life (FACT-F, p = 0.047). No significant differences were observed in terms of distress (HADS, p = 0.297). Six (60%) patients continued with methylphenidate after study end. Main adverse events during study were palpitations and insomnia (30% of patients each). CONCLUSIONS: This pilot study suggests that methylphenidate may reduce asthenia and improve quality of life in breast cancer patients treated with docetaxel.

Conflicto, violencia y acoso psicológico en un grupo de profesionales de enfermería de un centro hospitalario universitario sito en Catalunya (España) / Conflicts, violence and psychological harassment in a group of nursing professionals of the university centre located in Catalonia (Spain)

Objetivos: Identificar el nivel de conflicto, violencia psicológica y acoso psicológico en el trabajo en profesionales de enfermería de un Centro Hospitalario Universitario en la Comunidad Autónoma de Catalunya (España). Material y métodos: Estudio no experimental, transversal y descriptivo en profesionales de enfermería. Se administró el “Inventario de violencia y acoso psicológico en el trabajo IVAPT-E-R”. Resultados: No apareció ningún caso de percepción de acoso psicológico en los niveles alto y medio (0 por ciento), resultando dos casos (11,1 por ciento) en el nivel bajo. Las situaciones de conflicto, violencia y acoso psicológico, además de darse entre el personal del hospital, también las produjeron personas externas como los propios pacientes, usuarios, familiares y amigos de pacientes. Conclusiones: Los profesionales de enfermería de este Hospital Universitario deben enfrentarse con más situaciones conflictivas y de violencia psicológica que de acoso psicológico en el trabajo.

Objectives: To identify the level of conflicts, psychological violence and psychological harassment at work among the nursing staff of a University Hospital in the Autonomous Community of Catalonia (Spain). Material and methods: A non-experimental, cross-sectional and descriptive design is used in this study with nurses and the “Inventory of Violence and Psychological Harassment at Work IVAPTE-R” was applied. Results: No case of perceived harassment was found in the high and medium levels (0 percent) and two cases were identified in the low level (11.1 percent). Conflict situations, violence and psychological harassment were found to be caused by the personnel of the hospital and also by external persons such as patients, users, relatives and friends of patients. Conclusions: The nursing professionals of this hospital center have to face more conflict situations and psychological violence than psychological harassment at work.

School teachers' vocal use, risk factors, and voice disorder prevalence: guidelines to detect teachers with current voice problems.

UNLABELLED: Teachers' voice problems are widely recognized as a consequence of their work. The measurement of vocal demands and risk factors is essential for adjusting occupational safety and health services to this population's needs. OBJECTIVES: To correlate vocal behavior and symptomatology with risk factors and voice disorders, and to further analyze gender influence on these variables. SUBJECTS AND METHODS: 282 kindergarten and elementary education teachers were surveyed in a cross-sectional study using a self-administered questionnaire. For the purpose of this study, voice disorder prevalence was estimated based on the presence of a vocal effort plus 2 frequent symptoms. RESULTS: 81.5% of teachers reported some degree of vocal effort; more than 60% of subjects evidenced frequent throat paresthesias or vocal fatigue at the end of a working day, and about 55% reported hoarseness. Voice disorder prevalence was 59%. Multivariate logistic regression analysis revealed that female gender, time required to alleviate vocal symptoms, perceived general state of health, prolonged use of the voice, and pupils' indiscipline significantly increased the odds of having vocal problems. CONCLUSIONS: Voice disorders affected most teachers and had a multifactorial nature. Vocal health care is particularly necessary for those subjects reporting vocal effort and more than 2 frequent symptoms.

Additive effects of LPL, APOA5 and APOE variant combinations on triglyceride levels and hypertriglyceridemia: results of the ICARIA genetic sub-study.

BACKGROUND: Hypertriglyceridemia (HTG) is a well-established independent risk factor for cardiovascular disease and the influence of several genetic variants in genes related with triglyceride (TG) metabolism has been described, including LPL, APOA5 and APOE. The combined analysis of these polymorphisms could produce clinically meaningful complementary information. METHODS: A subgroup of the ICARIA study comprising 1825 Spanish subjects (80% men, mean age 36 years) was genotyped for the LPL-HindIII (rs320), S447X (rs328), D9N (rs1801177) and N291S (rs268) polymorphisms, the APOA5-S19W (rs3135506) and -1131T/C (rs662799) variants, and the APOE polymorphism (rs429358; rs7412) using PCR and restriction analysis and TaqMan assays. We used regression analyses to examine their combined effects on TG levels (with the log-transformed variable) and the association of variant combinations with TG levels and hypertriglyceridemia (TG > or = 1.69 mmol/L), including the covariates: gender, age, waist circumference, blood glucose, blood pressure, smoking and alcohol consumption. RESULTS: We found a significant lowering effect of the LPL-HindIII and S447X polymorphisms (p < 0.0001). In addition, the D9N, N291S, S19W and -1131T/C variants and the APOE-epsilon4 allele were significantly associated with an independent additive TG-raising effect (p < 0.05, p < 0.01, p < 0.001, p < 0.0001 and p < 0.001, respectively). Grouping individuals according to the presence of TG-lowering or TG-raising polymorphisms showed significant differences in TG levels (p < 0.0001), with the lowest levels exhibited by carriers of two lowering variants (10.2% reduction in TG geometric mean with respect to individuals who were homozygous for the frequent alleles of all the variants), and the highest levels in carriers of raising combinations (25.1% mean TG increase). Thus, carrying two lowering variants was protective against HTG (OR = 0.62; 95% CI, 0.39-0.98; p = 0.042) and having one single raising polymorphism (OR = 1.20; 95% CI, 1.39-2.87; p < 0.001) or more (2 or 3 raising variants; OR = 2.90; 95% CI, 1.56-5.41; p < 0.001) were associated with HTG. CONCLUSION: Our results showed a significant independent additive effect on TG levels of the LPL polymorphisms HindIII, S447X, D9N and N291S; the S19W and -1131T/C variants of APOA5, and the epsilon4 allele of APOE in our study population. Moreover, some of the variant combinations studied were significantly associated with the absence or the presence of hypertriglyceridemia.