How Do Adolescent Smoking Prevention Interventions Work in Different Contextual Settings? A Qualitative Comparative Study Between the UK and Colombia.

BACKGROUND: Adolescent smoking is associated with significant health and social risks. Previous research has demonstrated the effectiveness of interventions based on behavior change theories in preventing adolescent smoking uptake. However, evidence from the theory-based perspective of evaluation is limited, especially for how such complex interventions work, and how they work when implemented in different contextual settings. METHOD: A comparative qualitative analysis was conducted to explore various influences on behavior change among participants taking part in two smoking prevention interventions in Northern Ireland and Bogotá. Twenty-seven focus groups were conducted in 12 schools (6 in Northern Ireland and 6 in Bogota, n = 195 pupils participated; aged 11-15 years). The Theoretical Domains Framework guided a content analysis of the data. RESULTS: We found similarities across settings in terms of knowledge, skills, and beliefs related to smoking or vaping behavior change, as well as differences in contextual resources and social influence. Different environmental resources included availability to purchase tobacco products in the neighborhoods and previous information about tobacco risk. Participants in both interventions perceived behavioral change outcomes related to personal skills and intention to not smoke or vape. CONCLUSION: These findings have highlighted how both individual factors and contextual resources influence behavior change for smoking prevention in practice. Local contextual factors and social influences affecting pupils should be taken into account in the implementation and evaluation of health behavior change interventions. In particular, this study supports using social and contextual influence strategies in interventions to reduce the onset of adolescent smoking and vaping.

Survivin inhibition with YM155 ameliorates experimental pulmonary arterial hypertension.

Background: Imbalance between cell proliferation and apoptosis underlies the development of pulmonary arterial hypertension (PAH). Current vasodilator treatment of PAH does not target the uncontrolled proliferative process in pulmonary arteries. Proteins involved in the apoptosis pathway may play a role in PAH and their inhibition might represent a potential therapeutic target. Survivin is a member of the apoptosis inhibitor protein family involved in cell proliferation. Objectives: This study aimed to explore the potential role of survivin in the pathogenesis of PAH and the effects of its inhibition. Methods: In SU5416/hypoxia-induced PAH mice we assessed the expression of survivin by immunohistochemistry, western-blot analysis, and RT-PCR; the expression of proliferation-related genes (Bcl2 and Mki67); and the effects of the survivin inhibitor YM155. In explanted lungs from patients with PAH we assessed the expression of survivin, BCL2 and MKI67. Results: SU5416/hypoxia mice showed increased expression of survivin in pulmonary arteries and lung tissue extract, and upregulation of survivin, Bcl2 and Mki67 genes. Treatment with YM155 reduced right ventricle (RV) systolic pressure, RV thickness, pulmonary vascular remodeling, and the expression of survivin, Bcl2, and Mki67 to values similar to those in control animals. Lungs of patients with PAH also showed increased expression of survivin in pulmonary arteries and lung extract, and also that of BCL2 and MKI67 genes, compared with control lungs. Conclusion: We conclude that survivin might be involved in the pathogenesis of PAH and that its inhibition with YM155 might represent a novel therapeutic approach that warrants further evaluation.

Menopausal Voice-Related Work Limitation Scale (MenoVWL): Development and Validation.

OBJECTIVES: Menopause has been reported to affect the voice of female professional voice users (FPVUs). The present study aims at the development and validation of a scale to measure self-perceived menopausal voice-related limitation to work in FPVUs, henceforth the Menopausal Voice-Related Work Limitation Scale (MenoVWL). METHODS: Items were drawn from previous studies on impacts of sex steroid hormones on voice, available validated scales, and in-depth interviews with post-menopausal FPVUs. A preliminary version with 16 items was evaluated by a panel of 15 voice experts. The resulting revised version was filled in online, together with questions on current endocrinological reproductive status and related symptoms, history of amenorrhea, professional occupation, and demographic information. Responses concerning only professional voice users were selected and inclusive and exclusive criteria were applied for correct allocation of participants into pre- and post-menopausal stages within a restrict age range;192 responses were subject to factorial analysis for MenoVWL validation. Cronbach's alpha measured internal reliability. The scale was tested by comparing MenoVWL scores between pre- and post-menopausal FPVUs (98 and 94, respectively). RESULTS: Thirteen items were retained from the expert panel evaluation. Items presented a high Content Validity Index (.94 out of 1) and high Item Acceptance Ratio (86.25 %). Both exploratory and confirmatory factorial analysis rendered one dimension scale with an excellent internal consistency (Cronbach's alpha = .9). The results of a Mann-Whitney test showed a higher MenoVWL score for post- as compared to pre-menopausal FPVUs (Z = - 2.818; P = .005). CONCLUSIONS: MenoVWL is a comprehensive and validated scale with a known factor structure. It constitutes a health care and safety outcome self-perceived measure of value to the early detection of voice-related limitations to work in FPVUs during menopause.

The role of retinal fluid location in atrophy and fibrosis evolution of patients with neovascular age-related macular degeneration long-term treated in real world.

PURPOSE: To assess the effect of clinical factors on the development and progression of atrophy and fibrosis in patients with neovascular age-related macular degeneration (nAMD) receiving long-term treatment in the real world. METHODS: An ambispective 36-month multicentre study, involving 359 nAMD patients from 17 Spanish hospitals treated according to the Spanish Vitreoretinal Society guidelines, was designed. The influence of demographic and clinical factors, including the presence and location of retinal fluid, on best-corrected visual acuity (BCVA) and progression to atrophy and/or fibrosis were analysed. RESULTS: After 36 months of follow-up and an average of 13.8 anti-VEGF intravitreal injections, the average BCVA gain was +1.5 letters, and atrophy and/or fibrosis were present in 54.8% of nAMD patients (OR = 8.54, 95% CI = 5.85-12.47, compared to baseline). Atrophy was associated with basal intraretinal fluid (IRF) (OR = 1.87, 95% CI = 1.09-3.20), whereas basal subretinal fluid (SRF) was associated with a lower rate of atrophy (OR = 0.40, 95% CI = 0.23-0.71) and its progression (OR = 0.44, 95% CI = 0.26-0.75), leading to a slow progression rate (OR = 0.34, 95% CI = 0.14-0.83). Fibrosis development and progression were related to IRF at any visit (p < 0.001). In contrast, 36-month SRF was related to a lower rate of fibrosis (OR = 0.49, 95% CI = 0.29-0.81) and its progression (OR = 0.50, 95% CI = 0.31-0.81). CONCLUSION: Atrophy and/or fibrosis were present in 1 of 2 nAMD patients treated for 3 years. Both, especially fibrosis, lead to vision loss. Subretinal fluid (SRF) was associated with good visual outcomes and lower rates of atrophy and fibrosis, whereas IRF yields worse visual results and a higher risk of atrophy and especially fibrosis in routine clinical practice.

Coordinated Intervention of Microglial and Müller Cells in Light-Induced Retinal Degeneration.

Purpose: To analyze the role of microglial and Müller cells in the formation of rings of photoreceptor degeneration caused by phototoxicity. Methods: Two-month-old Sprague-Dawley rats were exposed to light and processed 1, 2, or 3 months later. Retinas were dissected as whole-mounts, immunodetected for microglial cells, Müller cells, and S- and L/M-cones and analyzed using fluorescence, thunder imaging, and confocal microscopy. Cone populations were automatically counted and isodensity maps constructed to document cone topography. Results: Phototoxicity causes a significant progressive loss of S- and L/M-cones of up to 68% and 44%, respectively, at 3 months after light exposure (ALE). One month ALE, we observed rings of cone degeneration in the photosensitive area of the superior retina. Two and 3 months ALE, these rings had extended to the central and inferior retina. Within the rings of cone degeneration, there were degenerating cones, often activated microglial cells, and numerous radially oriented processes of Müller cells that showed increased expression of intermediate filaments. Between 1 and 3 months ALE, the rings coalesced, and at the same time the microglial cells resumed a mosaic-like distribution, and there was a decrease of Müller cell gliosis at the areas devoid of cones. Conclusions: Light-induced photoreceptor degeneration proceeds with rings of cone degeneration, as observed in inherited retinal degenerations in which cone death is secondary to rod degeneration. The spatiotemporal relationship of cone death microglial cell activation and Müller cell gliosis within the rings of cone degeneration suggests that, although both glial cells are involved in the formation of the rings, they may have coordinated actions and, while microglial cells may be more involved in photoreceptor phagocytosis, Müller cells may be more involved in cone and microglial cell migration, retinal remodeling and glial seal formation.

Stool Short-Chain Fatty Acids in Critically Ill Patients with Sepsis.

Objective: To determine the concentration of stool short-chain fatty acids (SCFAs) in critically ill patients with sepsis and to compare the results between the critically ill patient and the control group.Methods: This descriptive, multicenter, observational study was conducted in five health institutions. Over a 6-month study period, critically ill patients with sepsis who were admitted to the intensive care unit (ICU) and met the inclusion criteria were enrolled, and a control, paired by age and sex, was recruited for each patient. A spontaneous stool sample was collected from each participant and a gas chromatograph coupled to a mass spectrometer (Agilent 7890/MSD 5975 C) was used to measure the concentrations SCFAs.Results: The final sample included 44 patients and 45 controls. There were no differences in the age and sex distributions between the groups (p > 0.05). According to body mass index (BMI), undernutrition was more prevalent among critically ill patients, and BMI in control subjects was most frequently classified as overweight (p = 0.024). Propionic acid, acetic acid, butyric acid, and isobutyric acid concentrations were significantly lower in the critically ill patient group than in the control group (p = 0.000). No association with outcome variables (complications, ICU stay, and discharge condition) was found in the patients, and patients diagnosed with infection on ICU admission showed significant decreases in butyric and isobutyric acid concentrations with respect to other diagnostic criteria (p < 0.05).Conclusions: The results confirm significantly lower concentrations of stool SCFAs in critically ill patients with sepsis than in control subjects. Due to its role in intestinal integrity, barrier function, and anti-inflammatory effect, maintaining the concentration of SCFAs may be important in the ICU care protocols of the critical patient.

Gut microbiota profiles in critically ill patients, potential biomarkers and risk variables for sepsis.

Critically ill patients are physiologically unstable and recent studies indicate that the intestinal microbiota could be involved in the health decline of such patients during ICU stays. This study aims to assess the intestinal microbiota in critically ill patients with and without sepsis and to determine its impact on outcome variables, such as medical complications, ICU stay time, and mortality. A multi-center study was conducted with a total of 250 peri-rectal swabs obtained from 155 patients upon admission and during ICU stays. Intestinal microbiota was assessed by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Linear mixed models were used to integrate microbiota data with more than 40 clinical and demographic variables to detect covariates and minimize the effect of confounding factors. We found that the microbiota of ICU patients with sepsis has an increased abundance of microbes tightly associated with inflammation, such as Parabacteroides, Fusobacterium and Bilophila species. Female sex and aging would represent an increased risk for sepsis possibly because of some of their microbiota features. We also evidenced a remarkable loss of microbial diversity, during the ICU stay. Concomitantly, we detected that the abundance of pathogenic species, such as Enterococcus spp., was differentially increased in sepsis patients who died, indicating these species as potential biomarkers for monitoring during ICU stay. We concluded that particular intestinal microbiota signatures could predict sepsis development in ICU patients. We propose potential biomarkers for evaluation in the clinical management of ICU patients.

Chemometric classification of Garcinia madruno raw material: Impact of the regional origin and ripeness stage of a neotropical exotic species.

Garcinia madruno is a neotropical tree characterized by its exotic fruit and its functional compounds. The aim of this study was to evaluate the expression and variability of the chemical markers of G. madruno according to the part of the plant used, the origin and the ripeness stage by applying chemometric tools. A total of 167 samples were evaluated, and 27 compounds were quantified per sample. The expression of amentoflavone, morelloflavone-type biflavonoids and polyisoprenylated benzophenones (PIBs) promoted intergroup differentiation, whereas the expression of GB-2a-type biflavonoids promoted intragroup cluster generation. Epicarp was the main source of biflavonoids and the secondary source of PIBs, with values up to 25% in some individuals. The origin of the fruit significantly impacted the expression of metabolites, whereas the ripeness stage did not. The results indicate that epicarp is a good source of functional compounds and, with appropriately agronomic development, could be improved even more.

Realized niche and microhabitat selection of the eastern green lizard (Lacerta viridis) at the core and periphery of its distribution range.

The available range of habitats and suitable abiotic conditions like temperature and radiation tends to be narrower toward the periphery of the distribution range of species. Peripheral populations of generalist species could then be more specialized and have a smaller and differentiated realized niche (habitat niche in our study) compared to populations at the core. Likewise, patterns of microhabitat selection can differ between periphery and core. In our study, we compared niche size and microhabitat selection among core (Bulgaria) and northern peripheral (Germany, Czech Republic) populations of Lacerta viridis and estimated niche differentiation among regions. We collected data on vegetation structure and abiotic parameters at the microhabitat scale in each region. In order to compare niche size among regions and estimate niche differentiation, we built multidimensional niche hypervolumes. We applied generalized linear mixed models and model averaging, accounting for spatial autocorrelation when necessary, to analyze microhabitat differences among regions and microhabitat selection in each region. Peripheral populations were more specialized, having a smaller niche than core ones, and their niche differed from that in the core (Sørensen overlap in all comparisons <0.3). Microhabitats at the periphery had lower radiation and soil compaction and less structured vegetation. Microhabitat selection at the core depended solely on abiotic parameters, while at the periphery it was defined by only vegetation structure (Czech Republic) or a combination of both, vegetation structure, and abiotic factors (Germany). Thus, peripheral populations seem to compensate for overall harsher climatic conditions by responding to different parameters of the microhabitat compared to core populations. We suggest specific conservation measures for L. virids in each studied region and point out the general implications of a higher specialization degree of peripheral populations in relation to climate change and habitat fragmentation.

Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina / Juvenile form of Sandhoff disease: first case reported in Argentina

La enfermedad de Sandhoff es una patología neurodegenerativa, de almacenamiento lisosomal, causada por mutaciones en el gen HEXB. Existen tres formas clínicas: infantil, juvenil y adulta. Previamente, fue identificada una población endogámica en la provincia de Córdoba, Argentina, que presentaba una alta incidencia de la enfermedad; todos los casos correspondieron a la forma infantil. En este trabajo, se presenta por primera vez el caso de un paciente argentino con la variante juvenil de la enfermedad de Sandhoff. El paciente es un niño de 7 años que, a partir de los 2, presentó ataxia, trastorno del habla y retraso global en el desarrollo. El diagnóstico se confirmó con la detección de valores residuales de enzima hexosaminidasa y con la identificación de dos mutaciones ya descritas en estado de heterocigosis: c.796T>G (p.Y266D) y c.1615C>T (p.R539C).

Sandhoff disease is a neurodegenerative, lysosomal and autosomal recessive disease caused by mutations in the HEXB gene. Three forms are recognized: infantile, juvenile and adult. Previously, an endogamous population in Córdoba, Argentina, was identified with a high incidence of Sandhoff disease, all reported cases were of the infantile type. In this work, we describe a child with the juvenile form of Sandhoff disease, the first case reported in Argentina. The patient is a 7-year-old boy presenting with ataxia, speech disturbances and global developmental delay, symptoms starting at the age of 2 years. Diagnosis was based on the hexosaminidase deficiency. Sequencing of genomic DNA revealed compound heterozygosity for two HEXB gene mutations: c.796T>G (p.Y266D) and c.1615C>T (p.R539C), both already reported.

[Juvenile form of Sandhoff disease: first case reported in Argentina]. / Variante juvenil de la enfermedad de Sandhoff: presentación del primer caso descrito en Argentina.

Sandhoff disease is a neurodegenerative, lysosomal and autosomal recessive disease caused by mutations in the HEXB gene. Three forms are recognized: infantile, juvenile and adult. Previously, an endogamous population in Córdoba, Argentina, was identified with a high incidence of Sandhoff disease, all reported cases were of the infantile type. In this work, we describe a child with the juvenile form of Sandhoff disease, the first case reported in Argentina. The patient is a 7-year-old boy presenting with ataxia, speech disturbances and global developmental delay, symptoms starting at the age of 2 years. Diagnosis was based on the hexosaminidase deficiency. Sequencing of genomic DNA revealed compound heterozygosity for two HEXB gene mutations: c.796T>G (p.Y266D) and c.1615C>T (p.R539C), both already reported.

La enfermedad de Sandhoff es una patología neurodegenerativa, de almacenamiento lisosomal, causada por mutaciones en el gen HEXB. Existen tres formas clínicas: infantil, juvenil y adulta. Previamente, fue identificada una población endogámica en la provincia de Córdoba, Argentina, que presentaba una alta incidencia de la enfermedad; todos los casos correspondieron a la forma infantil. En este trabajo, se presenta por primera vez el caso de un paciente argentino con la variante juvenil de la enfermedad de Sandhoff. El paciente es un niño de 7 años que, a partir de los 2, presentó ataxia, trastorno del habla y retraso global en el desarrollo. El diagnóstico se confirmó con la detección de valores residuales de enzima hexosaminidasa y con la identificación de dos mutaciones ya descritas en estado de heterocigosis: c.796T>G (p.Y266D) y c.1615C>T (p.R539C).

Patient-reported outcomes in Spanish patients diagnosed with bilateral age-related macular degeneration.

PURPOSE: To evaluate the patient-reported outcomes (PRO) in age-related macular degeneration (AMD) patients by using instruments for eliciting health status and vision specific issues. METHODS: PRO were assessed using the 25-item National Eye Institute Visual Function Questionnaire (NEIVFQ-25) and the Short-Form General Health Survey (SF-12). RESULTS: The mean age and corrected distance visual acuity (CDVA) in the better eye of the AMD patients were 82.53 ± 5.17 years and 0.82 ± 0.43 logMAR, respectively. The overall NEIVFQ-25 composite score was 57.89. SF-12 physical and mental component summary scores were 37.28 and 57.25, respectively. There were significant correlations (p ≤ 0.05) between CDVA and the following NEIVFQ-25 subscales: general (r = -0.73), near (r = -0.40) and distance vision (r = -0.60), role limitations (r = -0.40), social function (r = -0.48) and mental health (r = -0.38). CONCLUSIONS: Visual function is severely affected in AMD patients. It hampers their daily living without, however, deeply disturbing their social function. This may help them retain adequate mental health despite their poor physical status.

Extrinsic bronchial obstruction caused by scoliosis.

STUDY DESIGN: A case report. OBJECTIVE: To emphasize the importance of monitoring the breathing capacity in patients with moderate to severe scoliosis, even in adulthood. SUMMARY OF BACKGROUND DATA: Diseases that disturb the structure of the chest wall affect the function of the respiratory pump. Restrictive respiratory pattern is caused by severe scoliosis. However, scoliosis may provoke obstructive changes due to compression of the airways. It can be a direct compression because of imprinting of vertebral bodies, or an indirect one, due to rotation forces. METHODS.: We have collected data from the patients' clinical history and have reviewed similar published cases. CASE PRESENTATION: a white female, with frequent respiratory tract infections during her childhood. She was diagnosed as having 55° right T5-T11 scoliosis. At age of 26, an increase of her pulmonary symptoms appeared with difficulty to expel mucus and medium efforts dyspnea. A computed axial tomographic scan showed T8 vertebral body pushing against the right intermediate bronchus. A bronchoscopy found a decrease in the bronchial area, with near contact between the walls. Lung function test: 41% forced vital capacity (FVC), 43% forced expiratory volume in 1 second (FEV1), and 91 FEV1/FVC1. The patient underwent surgical correction using rods and pedicle screws; she had improvement of symptoms, image tests, and pulmonary function (70% FVC, 71% FEV1, and 101 FEV1/FVC). CONCLUSION: Increased frequency and severity of respiratory tract infections, difficulty in expelling mucus and dyspnea are warning signs of compromised airways. Spirometry tests and image tests such as computed axial tomography and bronchoscopy are essential for diagnosis. Surgical approach may be the treatment of choice.

Genetic polymorphisms of serotonin transporter and receptor 1A could influence success during embryo implantation and maintenance of pregnancy.

OBJECTIVE: To explore whether serotonin-related gene polymorphisms influence clinical outcomes of IVF treatment in recipients using donated oocytes. DESIGN: Nested case-control study. SETTING: University-affiliated infertility clinic. PATIENT(S): Two hundred forty-five women undergoing IVF treatment with donated oocytes. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Genotype and haplotype analysis of the serotonin transporter-linked polymorphic region (5-HTTLPR), rs1800532, rs6295, rs6313, and rs3813929, between recipients grouped according to the results of the oocyte donation for IVF treatment. RESULT(S): No differences were found between genotype distribution of the tryptophan hydroxylase 1, serotonin receptor 2A, and serotonin receptor 2C polymorphisms. Recipients carrying the LL genotype for 5-HTTLPR had lower clinical pregnancy rates (PR) and higher biochemical pregnancy loss (BPL) events. Lower implantation rates were found in CC carriers for 5-HT1A.rs6295 who also presented higher BPL rates. A lower incidence of clinical pregnancy was observed for LC haplotypes, corresponding to an increase in BPL rates. CONCLUSION(S): A strong association was found between early pregnancy loss and recipients carrying the 5-HTTLPR and rs6295 genetic variants. Identifying biological processes involving serotonin and embryo implantation may help to understand the dynamics of the maternal-embryo dialogue.

[Molecular diagnosis of cystic fibrosis in 93 Argentinean patients and detection of heterozygotes in affected families. Impact on health services and therapeutic advances]. / Fibrosis quística: diagnóstico molecular en 93 pacientes argentinos y detección familiar de portadores. Impacto asistencial y proyección a nuevos avances terapéuticos.

INTRODUCTION: The cystic fibrosis is an autosomal recessive disease caused by more than 1500 mutations and variants in the cystic fibrosis transmembrane conductance regulator gene. OBJECTIVES: To establish the spectrum and frequency of mutations on this gene in Argentinean patients.To detect heterozygotes in affected families. PATIENTS AND METHODS: We investigated 91 clinical and biochemically confirmed patients with 2 elevated sweat tests and 2 sterile adults. We worked with 165 relatives. The molecular diagnosis was accomplished in 3 serial stages: a) determination of 29 frequent mutations; b) haplotypes for microsatellites; c) an extensive screening of gene through single strand conformation analysis and multiplex denaturing gradient gel electrophoresis with sequencing of abnormal patterns. Once patient's genotype was confirmed, we investigated the heterozygotes' state in the relatives. RESULTS: 1ST OBJECTIVE: Fourteen mutations were identified. Three more mutations were detected and other 11 mutations were characterized, 3 of them novel (p.G27R, c.622-2A>G, p.W277R). In total, we have identified 28 mutations responsible for 90.3% of the mutated alleles, 14 with a higher frequency than 1%. 2ND OBJECTIVE: From 165 investigated people, 143 were confirmed as heterozygotes and with normal genotype 22. CONCLUSIONS: This work contributed to the molecular characterization of patients with classic and atypical phenotypes and to the detection of great numbers of carriers. New pharmacological therapeutic investigations are based on the mutation type. Therefore, knowledge of patients, mutations (genotype) has significant importance for the future application of specific therapies.

Fibrosis quística: diagnóstico molecular en 93 pacientes argentinos y detección familiar de portadores. Impacto asistencial y proyección a nuevos avances terapéuticos / Molecular diagnosis of cystic fobrosis in 93 argentinean patients and detection of heterozygotes in affected families. Impact on health services and therapeutic advances

Introducción. La fibrosis quística es una enfermedad autosómica recesiva causada por más de 1.500mutaciones y variantes en el gen regulador de la conductancia transmembrana.Objetivos. Establecer el espectro y frecuencia demutaciones en este gen en pacientes argentinos.Detectar portadores en las familias involucradas.Material y métodos. Se investigó en 91 pacientes, clínica y bioquímicamente confirmados con 2 pruebas de sudor positivas y en 2 adultos estériles. Setrabajó con 165 familiares. El diagnóstico molecularcomprendió 3 etapas consecutivas: a) determinaciónde 29 mutaciones frecuentes; b) haplotipos por microsatélites; c) pesquisa completa del gen poranálisis conformacional de hebra simple y electroforesisen gel de gradiente desnaturalizante consecuenciamiento de los patrones anormales. Determinado el genotipo de los pacientes, se investigó elestado de portador en los familiares.Resultados. 1er Objetivo: Se identificaron 14 mutaciones, se detectaron otras 3 mutaciones y se caracterizaron otras 11 mutaciones, tres de ellas nuevas(p.G27R, c.622-2A>G, p.W277R). En total, se identificaron28 mutaciones responsables del 90,3 por ciento de losalelos mutados, 14 con una frecuencia superior al 1 por ciento2º Objetivo: De 165 personas investigadas, 143 fueronportadores y 22 con genotipo normal.Conclusiones. Este trabajo contribuyó a la caracterización molecular de pacientes con fenotipos clásicosy atípicos y a la detección de numerosos portadores.Las investigaciones fármaco-terapéuticas recientesse basan en el tipo de mutación. Por lo tanto,conocer las mutaciones de los pacientes (genotipo) tiene significativa importancia para la futura aplicaciónde terapias específicas.