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1.
Breast Cancer Res Treat ; 205(3): 567-577, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38520597

RESUMEN

PURPOSE: Recruit and sequence breast cancer subjects in Guatemalan and US Hispanic populations. Identify optimum strategies to recruit Latin American and Hispanic women into genetic studies of breast cancer. METHODS: We used targeted gene sequencing to identify pathogenic variants in 19 familial breast cancer susceptibility genes in DNA from unselected Hispanic breast cancer cases in the US and Guatemala. Recruitment across the US was achieved through community-based strategies. In addition, we obtained patients receiving cancer treatment at major hospitals in Texas and Guatemala. RESULTS: We recruited 287 Hispanic US women, 38 (13%) from community-based and 249 (87%) from hospital-based strategies. In addition, we ascertained 801 Guatemalan women using hospital-based recruitment. In our experience, a hospital-based approach was more efficient than community-based recruitment. In this study, we sequenced 103 US and 137 Guatemalan women and found 11 and 10 pathogenic variants, respectively. The most frequently mutated genes were BRCA1, BRCA2, CHEK2, and ATM. In addition, an analysis of 287 US Hispanic patients with pathology reports showed a significantly higher percentage of triple-negative disease in patients with pathogenic variants (41% vs. 15%). Finally, an analysis of mammography usage in 801 Guatemalan patients found reduced screening in women with a lower socioeconomic status (p < 0.001). CONCLUSION: Guatemalan and US Hispanic women have rates of hereditary breast cancer pathogenic variants similar to other populations and are more likely to have early age at diagnosis, a family history, and a more aggressive disease. Patient recruitment was higher using hospital-based versus community enrollment. This data supports genetic testing in breast cancer patients to reduce breast cancer mortality in Hispanic women.


Asunto(s)
Predisposición Genética a la Enfermedad , Mutación de Línea Germinal , Hispánicos o Latinos , Neoplasias de la Mama Triple Negativas , Humanos , Femenino , Neoplasias de la Mama Triple Negativas/genética , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/etnología , Neoplasias de la Mama Triple Negativas/epidemiología , Hispánicos o Latinos/genética , Hispánicos o Latinos/estadística & datos numéricos , Guatemala/epidemiología , Persona de Mediana Edad , Adulto , Anciano , Estados Unidos/epidemiología , Selección de Paciente
2.
Exp Eye Res ; 241: 109850, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38423204

RESUMEN

This study aims to determine the risk associated with early age-related macular degeneration (AMD) due to refractive errors (RE) using an analysis of genome-wide association study (GWAS) data through the two-sample Mendelian randomization approach. Single-nucleotide polymorphisms (SNPs) linked to refractive errors (RE) were obtained from numerous GWAS studies involving individuals of European descent. The data for early AMD was obtained from a diverse, multiethnic GWAS meta-analysis that included 105,248 participants (14,034 cases and 91,214 controls). The primary outcome measure focused on the rise in early AMD risk corresponding to a 1-diopter alteration in spherical power and cylindrical power. In the main Mendelian randomization analysis, inverse-variance weighting (IVW) methods were applied for the evaluation. Mendelian Randomization (MR) study revealed a substantial impact of refractive error (RE) on early AMD risk, with a 1-diopter increase in hypermetropia being related to a 1.16 odds ratio (OR) for a greater risk of early AMD (95% CI, 1.10-1.23; P < 0.01). This conclusion was further supported by four supplementary approaches, namely, Weighted mode, Weighted-median, Simple mode, and MR-Egger. The results suggest a heightened risk of early AMD correlated with hyperopia, necessitating further research to thoroughly elucidate this potential causal relationship.


Asunto(s)
Hiperopía , Degeneración Macular , Errores de Refracción , Humanos , Estudio de Asociación del Genoma Completo , Degeneración Macular/genética , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Errores de Refracción/genética , Metaanálisis como Asunto
3.
Colorectal Dis ; 26(6): 1166-1174, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38745343

RESUMEN

AIM: Early-onset colorectal cancer (EOCRC) patients are more likely to have advanced disease and undergo more aggressive treatment modalities. However, current literature investigating the health-related quality of life (HRQoL) of EOCRC patients is scarce. This study aimed to determine the HRQoL of an Australian cohort of EOCRC patients including a subset who underwent pelvic exenteration (PE) or cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHOD: A cross-sectional study of EOCRC patients treated at the Royal Prince Alfred Hospital, Sydney Australia was performed. Patients were divided into groups based on the time interval from their index operation: ≤2 years and >2 years. HRQoL was evaluated using the SF-36v2 questionnaire. RESULTS: A total of 50 patients were included. For patients ≤2 years from surgery, the median physical component summary (PCS) and mental health component summary (MCS) scores were 53.3 (36.4-58.9) and 47.3 (37.5-55.7). In the >2 years group, the median PCS and MCS scores were 50.6 (43.3-57.7) and 50.2 (39.04-56.2), respectively. Stage I (vs. stage II) disease and emergency (vs. elective) surgery conferred poorer PCS scores in patients ≤2 years from surgery. No other variables impacted PCS or MCS scores in EOCRC patients in either group. CONCLUSIONS: HRQoL of EOCRC patients was equivocal to the Australian population. Having an earlier stage of diagnosis and emergency index operation was associated with poorer levels of physical functioning in patients ≤2 years from surgery. However, because of the limitations of this study, these findings require validation in future large-scale prospective research.


Asunto(s)
Neoplasias Colorrectales , Calidad de Vida , Humanos , Estudios Transversales , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/psicología , Neoplasias Colorrectales/terapia , Masculino , Femenino , Adulto , Persona de Mediana Edad , Australia , Encuestas y Cuestionarios , Edad de Inicio , Procedimientos Quirúrgicos de Citorreducción , Exenteración Pélvica , Factores de Tiempo
4.
Eur Spine J ; 32(7): 2533-2540, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37160441

RESUMEN

PURPOSE: To report and analyze development trends in the surgical treatment of congenital scoliosis (CS) in a large CS cohort over a 10-year period. METHODS: We retrospectively searched and extracted medical records of CS inpatients receiving posterior instrumented fusion surgery at our institute from January 2010 to December 2019. We analyzed information on demographics and surgical information, including the surgical approach, number of fused segments, use of osteotomy and titanium cage implantation, length of stay, intraoperative blood loss, and rates of complications and readmission. RESULTS: 1207 CS inpatients were included. In the past decade, the proportion of patients younger than 5 years increased from 15.5 to 26.9%. The average number of fused segments decreased from 9.24 to 7.48, and the proportion of patients treated with short-segment fusion increased from 13.4 to 30.3%. The proportion of patients treated with osteotomy and titanium cage implantation increased from 55.65% and 12.03% to 76.5% and 40.22%. The average length of stay and blood loss decreased from 16.5 days and 816.1 ml to 13.5 days and 501.7 ml. The complication and readmission rates also decreased during these ten years. CONCLUSION: During this ten-year period, the surgical treatment of CS at our institute showed trends toward a younger age at fusion, lower number of fused segments, higher rate of osteotomy and titanium cage implantation, reduced blood loss, shorter length of stay and lower rate complications and readmission. These results suggest performing osteotomy combined with titanium cage implantation at an earlier age can achieve fewer fused segments and complications.


Asunto(s)
Escoliosis , Fusión Vertebral , Humanos , Escoliosis/etiología , Resultado del Tratamiento , Estudios Retrospectivos , Titanio , Prótesis e Implantes , Fusión Vertebral/métodos
5.
Sensors (Basel) ; 23(14)2023 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-37514943

RESUMEN

This paper proposes a physics-informed neural network (PINN) for predicting the early-age time-dependent behaviors of prestressed concrete beams. The PINN utilizes deep neural networks to learn the time-dependent coupling among the effective prestress force and the several factors that affect the time-dependent behavior of the beam, such as concrete creep and shrinkage, tendon relaxation, and changes in concrete elastic modulus. Unlike traditional numerical algorithms such as the finite difference method, the PINN directly solves the integro-differential equation without the need for discretization, offering an efficient and accurate solution. Considering the trade-off between solution accuracy and the computing cost, optimal hyperparameter combinations are determined for the PINN. The proposed PINN is verified through the comparison to the numerical results from the finite difference method for two representative cross sections of PSC beams.

6.
Prev Med ; 155: 106923, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34929223

RESUMEN

The United States Preventive Services Task Force (USPSTF) recently issued an updated recommendation for population-based colorectal cancer (CRC) screening starting at age 45, due to a sustained increase in the incidence of early-age-at-onset CRC (eoCRC). A similar increase in the incidence of eoCRC has been observed in Canada since the early 2000s. However, the inherent differences between the US and Canadian health care systems with many different reimbursement and capacity considerations limit the applicability of the recommendations to the Canadian context. In order to facilitate further discussion around Canadian guidelines and recommendations, several research gaps need to be addressed: 1) a detailed understanding of trends in histology, topography, initial stage at diagnosis, and mortality among eoCRC; 2) a detailed analysis of cost-effectiveness outlining the impacts to the current screening programs with potential harms and benefits; 3) a comprehensive understanding of risk factor profiles that may lead to meaningful recommendations for screening decisions within the 40-49 age group in the absence of wide-spread screening programs; and 4) an evaluation of the effectiveness of current and novel screening tests or biomarkers specifically in the 40-49 age group. In the meantime, we suggest that physicians and patients begin discussions about screening at age 45 by reviewing family history and alerting patients to symptoms of CRC, which may increase screening adherence at age 50. This issue will remain an active area of debate with Canada as a careful laggard in changing recommendations, while attempting to balance system considerations with eoCRC trends and patient outcomes.


Asunto(s)
Neoplasias Colorrectales , Detección Precoz del Cáncer , Edad de Inicio , Canadá/epidemiología , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/prevención & control , Humanos , Tamizaje Masivo , Persona de Mediana Edad , Estados Unidos
7.
Mater Struct ; 55(3): 94, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36852297

RESUMEN

Early-age carbonation curing of concrete is receiving more interest in terms of performance improvement and emission reduction. However, the volume change of cement-based products subject to carbonation curing may become a concern because of the potential carbonation shrinkage and its related shrinkage cracking. The purpose of this study was to investigate the dimensional stability of cement paste and concrete subject to the early-age carbonation curing. It was found that the carbonation curing introduced first an initial shrinkage due to water evaporation upon gas injection and then generated an expansion due to CO2 uptake and carbonate precipitation. As carbonation proceeded, the deformation was switched to a secondary shrinkage after expansion. The residual deformation due to carbonation curing was shrinkage in cement paste samples and expansion in concrete samples. This was because the relative expansion due to carbonate precipitation in paste was not large enough to compensate for the shrinkage caused by water loss. However, for concrete samples, the introduction of aggregates reduced the pore spaces in concrete, leading to an expansion owing to the limited precipitation. The results of carbon dioxide uptake, XRD, and SEM analysis confirmed that calcium carbonate formation played a critical role in the relative expansion. The study also showed that cement-based products were more resistant to weathering carbonation after the early-age carbonation curing. After 61-day weathering carbonation exposure, both paste and concrete samples exhibited carbonation shrinkage as a result of carbonation of hydration products. However, the magnitude of shrinkage was much smaller in carbonation curing than in weathering carbonation because of the short period of exposure. Both carbonations did not significantly affect the compressive strength of carbonated products. Carbonation curing likely makes concrete products more dimensionally stable in the long-term service.

8.
Vestn Otorinolaringol ; 87(4): 19-22, 2022.
Artículo en Ruso | MEDLINE | ID: mdl-36107175

RESUMEN

Mucopolysaccharidoses are a group of rare lysosomal accumulation diseases caused by a deficiency of the lysosomal enzyme and the accumulation of mucopolysaccharides in various organs and tissues. Children with mucopolysaccharidosis type II (Hunter syndrome) develop multisystem dysfunction, including severe airway obstruction. At the same time, 34% of patients already at an early age (2-3 years) undergo surgical manipulations related to ENT organs (tonsillectomy, adenotomy). The article describes a clinical case of diagnosis of type II mucopolysaccharidosis by a pediatric otorhinolaryngologist. The main manifestations of the disease are discussed in detail, including the presence of indications for adenotomy at the age of 2 years, episodes of otitis media, which served as diagnostic markers for suspected orphan disease mucopolysaccharidosis type II. The leading role of the pediatric otorhinolaryngologist in the early diagnosis of the rare disease mucopolysaccharidosis type II is substantiated.


Asunto(s)
Mucopolisacaridosis II , Otitis Media , Niño , Preescolar , Glicosaminoglicanos , Humanos , Mucopolisacaridosis II/diagnóstico , Mucopolisacaridosis II/cirugía
9.
Gastroenterology ; 158(2): 341-353, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31394082

RESUMEN

In contrast to the decreasing incidence of colorectal cancer (CRC) in older populations, the incidence has nearly doubled in younger adults since the early 1990s. Approximately 1 in 10 new diagnoses of CRC are now made in individuals 50 years or younger. Patients' risk of CRC has been calculated largely by age and family history, yet 3 of 4 patients with early-onset CRC have no family history of the disease. Rapidly increasing incidence rates in younger people could result from generational differences in diet, environmental exposures, and lifestyle factors. We review epidemiologic trends in CRC, data on genetic and nongenetic risk factors, and new approaches for determining CRC risk. These may identify individuals likely to benefit from early screening and specialized surveillance.


Asunto(s)
Neoplasias del Colon/epidemiología , Detección Precoz del Cáncer/normas , Estilo de Vida , Tamizaje Masivo/normas , Neoplasias del Recto/epidemiología , Factores de Edad , Edad de Inicio , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/prevención & control , Humanos , Incidencia , Selección de Paciente , Guías de Práctica Clínica como Asunto , Neoplasias del Recto/diagnóstico , Neoplasias del Recto/prevención & control , Medición de Riesgo , Factores de Riesgo , Análisis de Supervivencia , Tasa de Supervivencia , Estados Unidos/epidemiología , Adulto Joven
10.
Mol Biol Rep ; 48(1): 371-379, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33300088

RESUMEN

Mutations in Lysine-Specific Histone Methyltransferase 2B gene (KMT2B) have been reported to be associated with isolated and complex early-onset generalized dystonia. We describe clinico-genetic features on a Greek patient with a novel de novo variant and demonstrate the phenotypic spectrum of KMT2B variants. We performed whole exome sequencing (WES), in a Greek patient with sporadic generalized dystonia. Additionally, we performed a systematic review of all published cases with KMT2B variants. The patient presented with isolated and mild generalized dystonia. We identified a novel splice site variant that was confirmed by Sanger sequencing and was not found in parents. This is the first reported KMT2B variant, in the Greek population. This case report further highlights the growing trend of identifying genetic diseases previously restricted to few cases in many different ethnic groups worldwide via exome sequencing. In the systematic review, we evaluated the mutation pathogenicity in all previously reported cases to investigate possible phenotype-genotype correlations. Greater mutation numbers in different populations will be important and mutation-specific functional studies will be essential to identify the pathogenicity of the various KMT2B variants.


Asunto(s)
Distonía/genética , N-Metiltransferasa de Histona-Lisina/genética , Isoformas de Proteínas/genética , Adulto , Edad de Inicio , Distonía/patología , Exoma/genética , Femenino , Estudios de Asociación Genética , Grecia , Histonas/genética , Humanos , Masculino , Chaperonas Moleculares/genética , Mutación/genética , Linaje , Fenotipo , Secuenciación del Exoma
11.
Graefes Arch Clin Exp Ophthalmol ; 259(9): 2545-2557, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33738626

RESUMEN

PURPOSE: This study aims to analyze the retinal layers and choroidal thickness in a large set of eyes with early age-related macular degeneration (AMD), in order to detect differences by stage suggestive of early neurodegeneration, and to explore biomarkers of different phenotypes. METHODS: This study is a population-based, cross-sectional study. Patients from the incidence AMD study (NCT02748824) with early AMD (Rotterdam 2a, 2b, 3) were included. All performed spectral-domain optical coherence tomography (SD-OCT) (Spectralis, Heidelberg Engineering, Germany) and automatic segmentation of all retinal layers was obtained with built-in software. Manual correction was performed whenever necessary. The mean thicknesses (ETDRS grid) and volume of each layer were recorded. Subfoveal choroidal thickness was manually measured. Estimates for each layer thickness were calculated with linear mixed models and tested for pairwise differences between stages. Associations between layer thickness and microstructural findings were assessed by multivariate regression analysis. RESULTS: The final cohort comprised 346 eyes (233 patients): 82.66% (n = 286) in stage 2a, 5.49% (n = 19) in stage 2b, and 11.85% (n = 41) in stage 3. A global tendency for lower/inferior thickness of the neuroretinal layers was found comparing stage 3 to 2a: retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), and inner plexiform layer (IPL) were inferior in the inner/outer ETDRS circles and the outer nuclear layer (ONL) and photoreceptors' segments layer in the central circle (p ≤ 0.002). The retinal pigment epithelium-Bruch's membrane (RPE/BrM) layer was thicker in stage 3 (p ≤ 0.001). Subretinal drusenoid deposits (SDD) were associated with thinner neuroretinal layers and choroid (p < 0.05). CONCLUSIONS: Our results showed in a large population-based dataset that several inner and outer neuroretinal layers were thinner with a higher stage in early AMD. These findings support the existence of early and progressive neurodegeneration. Neuronal retinal layer thicknesses might thus be used as quantitative biomarkers of disease progression in AMD. The presence of SDD is possibly associated to more prominent and faster neurodegeneration.


Asunto(s)
Degeneración Macular , Células Ganglionares de la Retina , Estudios Transversales , Humanos , Degeneración Macular/diagnóstico , Retina/diagnóstico por imagen , Tomografía de Coherencia Óptica
12.
Molecules ; 26(18)2021 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-34577134

RESUMEN

Solid waste silica fume was used to replace fly ash by different ratios to study the early-age hydration reaction and strength formation mechanism of concrete. The change pattern of moisture content in different phases and micro morphological characteristics of concrete at early age were analyzed by low field nuclear magnetic resonance (LF-NMR) and scanning electron microscope (SEM). The results showed that the compressive strength of concrete was enhanced optimally when the replacement ratio of solid waste silica fume was 50%. The results of LF-NMR analysis showed that the water content of modified concrete increased with the increase of solid waste silica fume content. The compressive strength of concrete grew faster within the curing age of 7 d, which means the hydration process of concrete was also faster. The micro morphological characteristics obtained by SEM revealed that the concrete was densest internally when 50% fly ash was replaced by the solid waste silica fume, which was better than the other contents.

13.
Artículo en Ruso | MEDLINE | ID: mdl-32306594

RESUMEN

The article is devoted to the contribution of academician G. N. Speransky, the prominent pediatrician, into becoming of the national system of medical and preventive care of children of early age and development of its staging.


Asunto(s)
Pediatría/historia , Niño , Historia del Siglo XIX , Historia del Siglo XX , Humanos , Federación de Rusia
14.
J Cell Mol Med ; 23(9): 6131-6139, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31282110

RESUMEN

Age-related cataract (ARC) is caused by the exposure of the lens to UVB which promotes oxidative damage and cell death. This study aimed to explore the role of lncRNA H19 in oxidative damage repair in early ARC. lncRNAs sequencing technique was used to identify different lncRNAs in the lens of early ARC patients. Human lens epithelial cells (HLECs) were exposed to ultraviolet irradiation; and 8-OHdG ELISA, Cell counting kit 8 (CCK8), EDU, flow cytometry and TUNEL assays were used to detect DNA damage, cell viability, proliferation and apoptosis. Luciferase assay was used to examine the interaction among H19, miR-29a and thymine DNA glycosylase (TDG) 3'UTR. We found that lncRNA H19 and TDG were highly expressed while miR-29a was down-regulated in the three types of early ARC and HLECs exposed to ultraviolet irradiation, compared to respective controls. lncRNA H19 knockdown aggravated oxidative damage, reduced cell viability and proliferation, and promoted apoptosis in HLECs, while lncRNA H19 overexpression led to opposite effects in HLECs. Mechanistically, miR-29a bound TDG 3'UTR to repress TDG expression. lncRNA H19 up-regulated the expression of TDG by repressing miR-29a because it acted as ceRNA through sponging miR-29a. In conclusion, the interaction among lncRNA H19, miR-29a and TDG is involved in early ARC. lncRNA H19 could be a useful marker of early ARC and oxidative damage repair pathway of lncRNA H19/miR-29a/TDG may be a promising target for the treatment of ARC.


Asunto(s)
Catarata/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Timina ADN Glicosilasa/genética , Envejecimiento/genética , Envejecimiento/patología , Envejecimiento/efectos de la radiación , Apoptosis/genética , Catarata/metabolismo , Catarata/patología , Línea Celular , Proliferación Celular/genética , Supervivencia Celular/genética , Células Epiteliales/metabolismo , Células Epiteliales/patología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Cristalino/metabolismo , Cristalino/efectos de la radiación , Estrés Oxidativo/genética , Estrés Oxidativo/efectos de la radiación , Transducción de Señal/efectos de la radiación , Rayos Ultravioleta/efectos adversos
15.
Curr Gastroenterol Rep ; 21(7): 28, 2019 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-31098760

RESUMEN

PURPOSE OF REVIEW: Colorectal cancer (CRC) screening is recommended to reduce CRC mortality. This review outlines key factors to consider when recommending screening, including disease burden, screening benefits and harms, and remaining knowledge gaps. RECENT FINDINGS: In response to increasing rates of CRC incidence among younger (age < 50 years) adults, the American Cancer Society published guidelines in May 2018 recommending average-risk CRC screening beginning at age 45 (vs. 50) years. Rates of young-onset CRC have increased in the USA since the early 1990s. However, there is very little empirical evidence of screening effectiveness in younger adults, and few studies have reported harms of routine screening in this age group. Further, we know little about the natural history of CRC in younger adults. Uncertainty surrounding the efficacy of CRC screening in younger adults suggests the benefits may be small. Precision cancer screening-or modified screening regimens based on risk-may improve the balance of screening benefits and harms beyond conventional age-based strategies.


Asunto(s)
Neoplasias Colorrectales/diagnóstico , Detección Precoz del Cáncer , Adulto , Factores de Edad , Neoplasias Colorrectales/epidemiología , Humanos , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Adulto Joven
16.
Ophthalmic Res ; 61(4): 226-235, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30820012

RESUMEN

PURPOSE: To describe the 6.5-year incidence and progression of age-related macular degeneration (AMD) in a coastal town of central Portugal. METHODS: Population-based cohort study. Participants underwent standardized interviews and ophthalmological examination. Color fundus photographs were graded according to the International Classification and Grading System for AMD and ARM. The crude and age-standardized incidence of early and late AMD was calculated, and progression was analyzed. RESULTS: The 6.5-year cumulative incidence of early AMD was 10.7%, and of late AMD it was 0.8%. The incidence of early AMD was 7.2, 13.1 and 17.7% for participants aged 55-64, 65-74 and 75-84 years (p < 0.001). The late AMD incidence was 0.3, 0.9 and 2.8% for the corresponding age groups (p = 0.003). The age-standardized incidence was 10.8% (95% CI, 10.74-10.80%) for early and 1.0% (95% CI, 1.00-1.02%) for late AMD. The incidence of both neovascular AMD and geographic atrophy was 0.4%. Progression occurred in 17.2% of patients. CONCLUSION: The early AMD incidence in a coastal town of central Portugal was found to be similar to that of major epidemiological studies of European-descent populations; however, the incidence of late AMD was lower, and further analysis on risk factors will be conducted.


Asunto(s)
Degeneración Macular/epidemiología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Portugal/epidemiología , Factores de Riesgo
17.
Proc Natl Acad Sci U S A ; 113(12): 3317-22, 2016 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-26951679

RESUMEN

Multiple factors, including host genetics, environmental factors, and Epstein-Barr virus (EBV) infection, contribute to nasopharyngeal carcinoma (NPC) development. To identify genetic susceptibility genes for NPC, a whole-exome sequencing (WES) study was performed in 161 NPC cases and 895 controls of Southern Chinese descent. The gene-based burden test discovered an association between macrophage-stimulating 1 receptor (MST1R) and NPC. We identified 13 independent cases carrying the MST1R pathogenic heterozygous germ-line variants, and 53.8% of these cases were diagnosed with NPC aged at or even younger than 20 y, indicating that MST1R germline variants are relevant to disease early-age onset (EAO) (age of ≤20 y). In total, five MST1R missense variants were found in EAO cases but were rare in controls (EAO vs. control, 17.9% vs. 1.2%, P = 7.94 × 10(-12)). The validation study, including 2,160 cases and 2,433 controls, showed that the MST1R variant c.G917A:p.R306H is highly associated with NPC (odds ratio of 9.0). MST1R is predominantly expressed in the tissue-resident macrophages and is critical for innate immunity that protects organs from tissue damage and inflammation. Importantly, MST1R expression is detected in the ciliated epithelial cells in normal nasopharyngeal mucosa and plays a role in the cilia motility important for host defense. Although no somatic mutation of MST1R was identified in the sporadic NPC tumors, copy number alterations and promoter hypermethylation at MST1R were often observed. Our findings provide new insights into the pathogenesis of NPC by highlighting the involvement of the MST1R-mediated signaling pathways.


Asunto(s)
Exoma , Predisposición Genética a la Enfermedad , Neoplasias Nasofaríngeas/genética , Proteínas Tirosina Quinasas Receptoras/genética , Análisis de Secuencia , Adolescente , Adulto , Carcinoma , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma Nasofaríngeo , Adulto Joven
18.
Subst Use Misuse ; 54(7): 1146-1153, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30676855

RESUMEN

BACKGROUND: Mechanisms underlying associations between early drinking and problems are largely unknown. OBJECTIVES: We investigated (a) associations between early age of first intoxication (≤15 years) and past year drinking in different contexts and (b) whether early age of first intoxication is differentially associated with problems in these contexts. METHODS: We used survey data collected in 2013-2014 from 405 past-year adolescent drinkers in 24 midsized California cities. Data included demographics; drinking behaviors; age of first intoxication; frequency of being at and drinking at restaurants, bars/nightclubs, outdoor places, and home; and problems. We used multilevel logistic and negative binomial models to account for the clustering of adolescents within cities. Probabilities were corrected to maintain family-wise error rates. RESULTS: Early age of first intoxication was associated with a 120% increase in the odds of drinking at outdoor settings (OR = 2.20, pc < .05). Early age of first intoxication was associated with increased numbers of problems related to drinking in restaurants (IRR = 5.72, pc < .001), outdoor settings (IRR = 3.40, pc < .001), and homes (IRR = 2.84, pc < .001). Later intoxication (≥16 years) was not significantly associated with increased drinking or problems in any of these contexts. CONCLUSIONS: Results suggest that underage drinkers who report early intoxication are more likely to drink at outdoor settings, but not other contexts. However, they may differentially experience drinking problems across contexts. To target youths who have experienced intoxication at an early age and to reduce problems, prevention interventions should focus on outdoor settings.


Asunto(s)
Edad de Inicio , Intoxicación Alcohólica/psicología , Consumo de Alcohol en Menores/psicología , Adolescente , California , Femenino , Humanos , Masculino , Encuestas y Cuestionarios
19.
BMC Ophthalmol ; 18(1): 184, 2018 Jul 28.
Artículo en Inglés | MEDLINE | ID: mdl-30055588

RESUMEN

BACKGROUND: To investigate the characteristics of retinal vessels and retinal thickness in eyes with early age-related macular degeneration (AMD) with or without reticular pseudodrusen. METHODS: We retrospectively evaluated the clinical history and optical coherence tomography (OCT) and OCT angiography images of consecutive patients with early AMD. We calculated the retinal vessel densities of the superficial and deep capillary plexus with the ImageJ software (National Institutes of Health, Bethesda, MD, USA) and investigated the relationship with mean retinal thickness and subfoveal choroidal thickness. RESULTS: We included 135 early AMD eyes and classified 60 of them into a reticular pseudodrusen group and 75 into a non-reticular pseudodrusen group. The vascular densities of the superficial and deep capillary plexus in the reticular pseudodrusen group (32.35% ± 3.67 and 26.71% ± 2.88%) were not different from those of the non-reticular pseudodrusen group (33.18% ± 2.2% and % 27.43 ± 1.79%; P = 0.546 and P = 0.318, respectively). The retinal thickness of the reticular pseudodrusen group (287.31 µm ± 24.36 µm) did not differ from that of the non-reticular pseudodrusen group (294.27 µm ± 20.71 µm; P = 0.493), while subfoveal choroidal thickness in the reticular pseudodrusen group (158.13 µm ± 42.53 µm) was lower than that in the non-reticular pseudodrusen group (237.89 µm ± 60.94 µm; P <  0.001). Multivariate analysis revealed that lower vascular density of the superficial capillary plexus and subfoveal choroidal thickness were associated with retinal thinning in reticular pseudodrusen group (P = 0.003 and P = 0.036) and older age was associated with retinal thickness in the non-reticular pseudodrusen group (P = 0.005). CONCLUSIONS: Retinal thinning in early AMD patients with reticular pseudodrusen was accompanied by choroidal and retinal vascular loss, which suggests a possible linkage of retinal thinning with vascular alterations.


Asunto(s)
Coroides/patología , Flujo Sanguíneo Regional/fisiología , Retina/fisiopatología , Drusas Retinianas/complicaciones , Degeneración Macular Húmeda/fisiopatología , Anciano , Femenino , Angiografía con Fluoresceína , Estudios de Seguimiento , Fondo de Ojo , Humanos , Masculino , Retina/diagnóstico por imagen , Drusas Retinianas/diagnóstico , Drusas Retinianas/fisiopatología , Estudios Retrospectivos , Factores de Tiempo , Tomografía de Coherencia Óptica/métodos , Degeneración Macular Húmeda/complicaciones , Degeneración Macular Húmeda/diagnóstico
20.
BMC Public Health ; 18(1): 234, 2018 02 12.
Artículo en Inglés | MEDLINE | ID: mdl-29433466

RESUMEN

BACKGROUND: Although alcohol is socially accepted in most Western societies, studies are clear about its associated negative consequences, especially among university and college students. Studies on the relationship between alcohol-related consequences and both beverage type and drinking onset, however, are scarce, especially in a European context. The aim of this research was, therefore, twofold: (1) What is the relationship between beverage type and the negative consequences experienced by students? and (2) Are these consequences determined by early drinking onset? We will examine these questions within the context of a wide range of alcohol-related consequences. METHODS: The analyses are based on data collected by the inter-university project 'Head in the clouds?', measuring alcohol use among students in Flanders (Belgium). In total, a large dataset consisting of information from 19,253 anonymously participating students was available. Negative consequences were measured using a shortened version of the Core Alcohol and Drug Survey (CADS_D). Data were analysed using negative binomial regression. RESULTS: Results vary depending on the type of alcohol-related consequences: Personal negative consequences occur frequently among daily beer drinkers. However, a high rate of social negative consequences was recorded for both daily beer drinkers and daily spirits drinkers. Finally, early drinking onset was significantly associated with both personal and social negative consequences, and this association was especially strong between beer and spirits drinking onset and social negative consequences. CONCLUSIONS: Numerous negative consequences, both personal and social, are related to frequent beer and spirits drinking. Our findings indicate a close association between drinking beer and personal negative consequences as well as between drinking beer and/or spirits and social negative consequences. Similarly, early drinking onset has a major influence on the rates of both personal and social negative consequences. The earlier students started drinking, the more negative consequences they experienced during college or university. Several (policy) interventions are discussed. This study is the first to incorporate detailed information on both beverage type and drinking onset, and its associated negative consequences, as measured by the CADS_D, in a large student population.


Asunto(s)
Consumo de Alcohol en la Universidad/psicología , Alcoholismo/epidemiología , Adolescente , Edad de Inicio , Bebidas Alcohólicas , Cerveza , Bélgica/epidemiología , Femenino , Humanos , Masculino , Estudios Retrospectivos , Encuestas y Cuestionarios , Adulto Joven
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