Lower Urinary Tract Symptoms (LUTS) as a New Clinical Presentation of Histamine Intolerance: A Prevalence Study of Genetic Diamine Oxidase Deficiency.

Lower urinary tract symptoms (LUTS) are highly prevalent, and their treatment is mainly focused on the control of symptoms. Histamine intolerance (HIT) has been related to a variety of systemic symptoms. DAO deficiency has been identified as a significant factor contributing to histamine intolerance (HIT). Preclinical evidence indicates the involvement of histamine in the lower urinary tract. This study aimed to assess the prevalence of diamine oxidase deficiency (DAO) in a prospective cohort of 100 patients with at least moderate LUTS. A genetic study of four single nucleotide polymorphisms (SNPs) (c.-691G>T, c.47C>T, c.995C>T, and c.1990C>G) was performed. HIT was found in 85.9% of patients. The prevalence of at least one minor allele in the SNPs analyzed was 88%, without gender differences. Storage symptoms were more intense in the presence of HIT as well as asthenia and neurological and musculoskeletal symptoms. The presence of minor alleles of the AOC1 gene was associated with a higher intensity of symptoms. Minor alleles from c.-691G>T and c.47C>T SNPs were also associated with a greater severity of obstructive symptoms. Thirty-one percent of patients presented the four SNPS with at least one associated minor allele. The relationship between HIT and LUTS in a mixed population of men and women found in this study supports further investigations to define the pathophysiology of histamine in LUTS.

Assessment of an optimized manufacturing process for inactivated quadrivalent influenza vaccine: a phase III, randomized, double-blind, safety and immunogenicity study in children and adults.

BACKGROUND: GSK has modified the licensed monovalent bulk manufacturing process for its split-virion inactivated quadrivalent influenza vaccine (IIV4) to harmonize the process among different strains, resulting in an increased number of finished vaccine doses, while compensating for the change from inactivated trivalent influenza vaccine (IIV3) to IIV4. To confirm the manufacturing changes do not alter the profile of the vaccine, a clinical trial was conducted to compare IIV4 made by the currently licensed process with a vaccine made by the new (investigational) process (IIV4-I). The main objectives were to compare the reactogenicity and safety of IIV4-I versus IIV4 in all age groups, and to demonstrate the non-inferiority of the hemagglutination-inhibition (HI) antibody responses based on the geometric mean titer ratio of IIV4-I versus IIV4 in children. METHODS: The Phase III, randomized, double-blind, multinational study included three cohorts: adults (18-49 years; N = 120), children (3-17 years; N = 821), and infants (6-35 months; N = 940). Eligible subjects in each cohort were randomized 1:1 to receive IIV4-I or IIV4. Both vaccines contained 15 µg of hemagglutinin antigen for each of the four seasonal virus strains. Adults and vaccine-primed children received one dose of vaccine, and vaccine-unprimed children received two doses of vaccine 28 days apart. All children aged ≥9 years were considered to be vaccine-primed and received one dose of vaccine. RESULTS: The primary immunogenicity objective of the study was met in demonstrating immunogenic non-inferiority of IIV4-I versus IIV4 in children. The IIV4-I was immunogenic against all four vaccine strains in each age cohort. The reactogenicity and safety profile of IIV4-I was similar to IIV4 in each age cohort, and there was no increase in the relative risk of fever (≥38 °C) with IIV4-I versus IIV4 within the 7-day post-vaccination period in infants (1.06; 95% Confidence Interval: 0.75, 1.50; p = 0.786). CONCLUSIONS: The study demonstrated that in adults, children, and infants, the IIV4-I made using an investigational manufacturing process was immunogenic with a reactogenicity and safety profile that was similar to licensed IIV4. These results support that the investigational process used to manufacture IIV4-I is suitable to replace the current licensed process. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02207413 ; trial registration date: August 4, 2014.

AhR-dependent 2,3,7,8-tetrachlorodibenzo-p-dioxin toxicity in human neuronal cell line SHSY5Y.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a xenobiotic agent with high persistency that induces neurotoxic effects altering neurodevelopment and behavior. The molecular mechanisms and the signaling pathways involved in TCDD-mediated neurotoxicity, together with the search of its molecular targets in neurons are under intense study. We have previously shown that high nanomolar concentrations of TCDD for incubation times of minutes induce apoptosis in SHSY5Y human neuroblastoma cells by the disruption of calcium homeostasis, affecting membrane structural integrity. In this work, we have analyzed the effect of low nanomolar concentrations of TCDD for incubation times of hours to define the role of aryl hydrocarbon receptor which can be activated at those concentrations. TCDD induces toxicity in SHSY5Y human neuroblastoma cells under these experimental conditions with an EC50 value of approximately 3nM at 24h of incubation time. Transient transfection of a hairpin RNA for AhR protects against TCDD neurotoxicity, suggesting that AhR is mediating the dioxin effect. Altogether, these results support the hypothesis that TCDD toxicity in SHSY5Y neuroblastoma cells depends on dioxin concentration and time of incubation, with a main role of aryl hydrocarbon receptor at low nanomolar TCDD concentrations.

Safety and persistence of the humoral and cellular immune responses induced by 2 doses of an AS03-adjuvanted A(H1N1)pdm09 pandemic influenza vaccine administered to infants, children and adolescents: Two open, uncontrolled studies.

In children, 2 AS03-adjuvanted A(H1N1)pdm09 vaccine doses given 21 days apart were previously shown to induce a high humoral immune response and to have an acceptable safety profile up to 42 days following the first vaccination. Here, we analyzed the persistence data from 2 open-label studies, which assessed the safety, and humoral and cell-mediated immune responses induced by 2 doses of this vaccine. The first study was a phase II, randomized trial conducted in 104 children aged 6-35 months vaccinated with the A(H1N1)pdm09 vaccine containing 1.9 µg haemagglutinin antigen (HA) and AS03B (5.93 mg tocopherol) and the second study, a phase III, non-randomized trial conducted in 210 children and adolescents aged 3-17 years vaccinated with the A(H1N1)pdm09 vaccine containing 3.75 µg HA and AS03A (11.86 mg tocopherol). Approximately one year after the first dose, all children with available data were seropositive for haemagglutinin inhibition and neutralising antibody titres, but a decline in geometric mean antibody titres was noted. The vaccine induced a cell-mediated immune response in terms of antigen-specific CD4(+) T-cells, which persisted up to one year post-vaccination. The vaccine did not raise any safety concern, though these trials were not designed to detect rare events. In conclusion, 2 doses of the AS03-adjuvanted A(H1N1)pdm09 vaccine at 2 different dosages had a clinically acceptable safety profile, and induced high and persistent humoral and cell-mediated immune responses in children aged 6-35 months and 3-17 years. These studies have been registered at www.clinicaltrials.gov NCT00971321 and NCT00964158.

Trypan Blue staining method for quenching the autofluorescence of RPE cells for improving protein expression analysis.

Retinal pigment epithelial (RPE) cells are currently in the "spotlight" of cell therapy approaches to some retinal diseases. The analysis of the expressed proteins of RPE primary cells is an essential step for many of these approaches. But the emission of autofluorescence by RPE cells produces higher background noise interference thereby creating an impediment to this analysis. Trypan Blue (TB), a routinely used counterstain, has the capacity to quench this autofluorescence, if it is used in optimized concentration. The results from the method developed in our study indicate that incubation of the cultured RPE cells with 20 µg/ml of TB after immunolabelling (post-treatment) as well as incubation of the retinal tissue specimens with same concentration before paraffin embedding, sectioning and immunolabelling (pre-treatment) can be applied to effectively quench the autofluorescence of RPE cells. Thus it can facilitate the evaluation of expressed cellular proteins in experimental as well as in pathological conditions, fulfilling the current requirement for developing a method which can serve to eliminate the autofluorescence of the cells, not only in cell cultures but also in tissues samples. This method should significantly increase the quality and value of RPE cell protein analysis, as well as other cell protein analysis performed by Flow cytometry (FC) and Immunohistochemistry (IHC) techniques.

Immunogenicity and safety of AS03-adjuvanted 2009 influenza A H1N1 vaccine in children 6-35 months.

We report on the evaluation of the immunogenicity and reactogenicity/safety of AS03-adjuvanted vaccine against pandemic influenza A/H1N1/2009 in young children. In this open-label, randomized study, 157 healthy children aged 6-35 months received two doses (21 days apart) of split-virion inactivated A/California/7/2009 H1N1 vaccine containing either (i) 1.9microg hemagglutinin (HA) and AS03(B) (5.93mg tocopherol) (N=104) or (ii) 3.75mug HA and AS03(A) (11.86mg tocopherol) (N=53). At 21 days following the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the percentage of children with hemagglutination-inhibition titers of >or=40 against the vaccine strain rose from 3.0% before vaccination to 100%. The seroconversion rate was 99% and the geometric mean titer (GMT) increased from 6 to 313. After the second dose the GMT increased further to 2008. The higher dose AS03(A)-adjuvanted 3.75microg HA vaccine did not further increase the immune response. Solicited symptoms reported within 7 days following vaccination were mainly mild to moderate. After the first dose of AS03(B)-adjuvanted vaccine (1.9microg HA) the most common solicited symptoms were pain at the injection site (35.6%) and irritability (31.7%). Fever (axillary >or=37.5 degrees C) was reported with an incidence of 20.2%. After the second dose reactogenicity tended to increase (injection site pain: 41.3%; irritability: 46.2%; fever >or=37.5 degrees C: 67.3%). Spontaneously reported adverse events with an intensity that prevented normal activities were documented for 2.9-6.7% of doses with only one event (vomiting) considered related to vaccination. There was one serious adverse event reported in the AS03(A)-adjuvanted 3.75microg HA vaccine group (traumatic brain injury) which was not considered as related to vaccination. In conclusion, these data suggest that a first dose of AS03(B)-adjuvanted A/H1N1/2009 vaccine containing 1.9microg HA in children 6-35 months old is highly immunogenic and that the overall reactogenicity profile is acceptable although reactions including fever tend to increase after a second dose.

Factores predictores de conductas promotoras de salud en mujeres peri- post-menopáusicas de Cali, Colombia / Predictive factors acting on health promotion behavior of menopausic women at Cali, Colombia

Introducción: La mujer ha elevado su esperanza de vida en las últimas décadas, esto coincide con su ciclo vital de aparición de la peri- post-menopausia, este período presenta complejos cambios en su dimensión biopsicosociocultural que implica una transición del papel de la mujer y repercusiones negativas en su calidad de vida. Propósito: Determinar los factores predictores que influyen las conductas promotoras de salud (CPS), según el modelo Pender, en la mujer peri- post-menopáusica de Cali, Colombia. Material y métodos: Diseño descriptivo, no observacional, transversal y correlacional cuya muestra fue de 650 mujeres peri- post-menopáusicas de 45 a 60 años de Cali, muestra bietápica por conglomerados (manzanas y viviendas), con base en la estratificación del municipio. Las variables estudiadas fueron las CPS y los factores biopsicosocioculturales. Se aplicaron los siguientes instrumentos: escala de estilo de vida promotor de salud (EVPS) para medir la variable dependiente, percepción de auto-eficacia, percepción del estado de salud y conocimientos en peri- post-menopausia. Resultados: Un 54% de las mujeres mostraron unas CPS, superiores a la media. Las CPS más fuertes fueron: Crecimiento espiritual (64.3%), relaciones interpersonales (60.7%), manejo del estrés (57.9%), nutrición (57.3%), responsabilidad en salud (54.9%) y la más baja fue actividad física (49%). El modelo de regresión múltiple, mostró 7 factores que predijeron 37.1% de la variabilidad en las CPS: percepción del estado de salud (R2=21%, p<0.0001); auto-eficacia (R2=20.5%, p<0.0001); educación formal (R2=8.3%, p<0.0001); autonomía en el uso de terapia hormonal (R2=3.9%, p<0.0003); conocimientos peri- post-menopáusicos (R2=2.1%, p<0.001); dieta (R2=1.6%, p<0.006); situación peri- post-menopáusica (R2=0.9%, p<0.03). Conclusión: El comportamiento de las CPS en la mujer caleña se puede valorar como suficiente y los factores predictores se recomiendan como claves en el cuidado de enfermería.

Introduction: Women have raised life hope in last decades; this coincides with their vital cycle of peri- post-menopausal apparition. This period present complex changes in it’s by a psycho, sociocultural dimension that implies a position of the women role and negative repercussions in their life quality. Aim: To determine the predictive factors influencing the health promoter behaviors (HPB) in peri- post-menopausal women of Cali, Colombia, according to Pender’s model.Material and methods: A descriptive design, non observational, transversal and correlational, of a bietapic conglomerate sample of 650 peri- post-menopausal women between 45 and 60 years old was applied. HPB and biopsychosociocultural factors were studied. The following instruments were applied: scale of health promoter life style, perception of self-efficiency scale, and health state and peri- post-menopausal knowledge scale. Results: Of the women 54% obtained a HPB higher than the average. The strongest HPB in the peri- post-menopausal women were: spiritual growth (64.3%), interpersonal relationships (60.7%), stress management (57.9%), nutrition (57.3%), health responsibility (54.9%) and a deficient physical activity (49%). According to the multiple regression model, the factors suffering more variability, 37.1%, were: health state perception (R2=21%, p<0.0001); self-efficacy perception (R2=20.5%, p<0.0001), formal education (R2=8.3%, p<0.0001); autonomy in hormonal therapy use (R=3.9%, p<0.003); peri- post-menopausal knowledge (R2=2.1%, p<0.001); diet (R2=1.6%, p<0.006); peri-post-menopausal situation (R2=0.9%, p<0.03). Conclusions: HPB were evaluated with sufficiency and these factors are very important in nursing care.

Conocimientos peri-postmenopausicos en mujeres colombianas, una validacian psicometrica / Knowledge of peri- postmenopause in colombian women, a psychometric validation study

Objetivo: Validar una escala de conocimientos peri-postmenopáusicos en mujeres colombianas de 45 a 60 años. Material y métodos: Es un diseño no experimental de tipo transversal, que se realizó en una muestra por cuotas compuesta por 101 mujeres en etapa peri-postmenopáusica de Cali, Colombia, seleccionadas de sectores representativos de los estratos socioeconómicos bajo, medio y alto, entre junio-agosto del 2006. La escala se construyó con 22 reactivos, que incluyeron conocimientos, creencias, signos y síntomas y cuidado; en preguntas de formato dicotómico. Resultados: El puntaje total de la escala de conocimiento presentó una distribución normal, con una media de 15,8, y una desviación estándar de 4,3; su confiabilidad mediante Alpha de Cronbach resultó de 0,83, mostrando una estructura unidimensional, a través de la matriz y análisis factorial de componentes principales, que explicó el 36 por ciento de la varianza. La validez de apariencia fue obtenida mediante evaluación por un comité de expertos. Conclusiones: La escala de conocimientos es fiable y válida en mujeres peri y postmenopáusicas. Mediante análisis de componentes principales se determinó la unidimensionalidad de la escala.

Aim: To validate knowledge scale of peri-postmenopause in Colombian women, from 45 to 60 years. Material and Methods: It is a nonexperimental design of observational type, which was realized in a quota sample comprised by 101 women of peri-postmenopause stage at Cali, Colombia, selected from representative sectors of low, middle and high socioeconomic strata, between June-August, 2006. The knowledge scale was constructed by 22 items, which included knowledges, beliefs, signs and symptoms and care; using questions of dichotomous format. Results: The total scale score, presented a relatively normal distribution, with an average of 15.8, and a standard deviation of 4.3, reliability was measured by means of Cronbach's Alpha, which was 0.83. Principal component analysis showed an unidimensional structure, which explained 36 percent of the variance. Face validity was obtained by using an expert's committee. Conclusions: The scale of knowledge is reliable and valid in an application on Colombian peri-and postmenopause women. By means of principal components analysis scale unidimensionality was established.