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1.
J Pers Assess ; : 1-9, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38489487

RESUMEN

Shedding light on the validity of sentence completion test (SCT) verbal defensiveness as an index of defensive behavior, the current two-part study examined the relationship between psychological threat and verbal defensiveness among military security and mission-critical team candidates using SCTs. Our study showed that as the threatening nature of SCT stems increased, defensive responses also increased, substantiating the link between psychological threat and defensive behavior. In addition, expert ratings of stem content revealed moderately strong relationships with defensive responses across two different SCTs, irrespective of their structural characteristics. In contrast to previous studies using total verbal defensiveness scores, we examined specific defensive response types and their associations with stem threat ratings, finding that omissions, denial, and comments about the test were linked to stem threat levels. Lastly, our study extends the application of the SCT verbal defensiveness index beyond specialized personnel selection, finding no significant differences in verbal defensiveness based on gender or military status. Overall, these findings contribute to a comprehensive understanding of defensive behavior and its contextual variations.

2.
Diabetologia ; 66(10): 1943-1958, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37460827

RESUMEN

AIMS/HYPOTHESIS: Diabetes is associated with epigenetic modifications including DNA methylation and miRNA changes. Diabetic complications in the cornea can cause persistent epithelial defects and impaired wound healing due to limbal epithelial stem cell (LESC) dysfunction. In this study, we aimed to uncover epigenetic alterations in diabetic vs non-diabetic human limbal epithelial cells (LEC) enriched in LESC and identify new diabetic markers that can be targeted for therapy to normalise corneal epithelial wound healing and stem cell expression. METHODS: Human LEC were isolated, or organ-cultured corneas were obtained, from autopsy eyes from non-diabetic (59.87±20.89 years) and diabetic (71.93±9.29 years) donors. The groups were not statistically different in age. DNA was extracted from LEC for methylation analysis using Illumina Infinium 850K MethylationEPIC BeadChip and protein was extracted for Wnt phospho array analysis. Wound healing was studied using a scratch assay in LEC or 1-heptanol wounds in organ-cultured corneas. Organ-cultured corneas and LEC were transfected with WNT5A siRNA, miR-203a mimic or miR-203a inhibitor or were treated with recombinant Wnt-5a (200 ng/ml), DNA methylation inhibitor zebularine (1-20 µmol/l) or biodegradable nanobioconjugates (NBCs) based on polymalic acid scaffold containing antisense oligonucleotide (AON) to miR-203a or a control scrambled AON (15-20 µmol/l). RESULTS: There was significant differential DNA methylation between diabetic and non-diabetic LEC. WNT5A promoter was hypermethylated in diabetic LEC accompanied with markedly decreased Wnt-5a protein. Treatment of diabetic LEC and organ-cultured corneas with exogenous Wnt-5a accelerated wound healing by 1.4-fold (p<0.05) and 37% (p<0.05), respectively, and increased LESC and diabetic marker expression. Wnt-5a treatment in diabetic LEC increased the phosphorylation of members of the Ca2+-dependent non-canonical pathway (phospholipase Cγ1 and protein kinase Cß; by 1.15-fold [p<0.05] and 1.36-fold [p<0.05], respectively). In diabetic LEC, zebularine treatment increased the levels of Wnt-5a by 1.37-fold (p<0.01)and stimulated wound healing in a dose-dependent manner with a 1.6-fold (p<0.01) increase by 24 h. Moreover, zebularine also improved wound healing by 30% (p<0.01) in diabetic organ-cultured corneas and increased LESC and diabetic marker expression. Transfection of these cells with WNT5A siRNA abrogated wound healing stimulation by zebularine, suggesting that its effect was primarily due to inhibition of WNT5A hypermethylation. Treatment of diabetic LEC and organ-cultured corneas with NBC enhanced wound healing by 1.4-fold (p<0.01) and 23.3% (p<0.05), respectively, with increased expression of LESC and diabetic markers. CONCLUSIONS/INTERPRETATION: We provide the first account of epigenetic changes in diabetic corneas including dual inhibition of WNT5A by DNA methylation and miRNA action. Overall, Wnt-5a is a new corneal epithelial wound healing stimulator that can be targeted to improve wound healing and stem cells in the diabetic cornea. DATA AVAILABILITY: The DNA methylation dataset is available from the public GEO repository under accession no. GSE229328 ( https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE229328 ).


Asunto(s)
Diabetes Mellitus , MicroARNs , Humanos , Represión Epigenética , Proteína Wnt-5a/genética , Proteína Wnt-5a/metabolismo , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Células Madre/metabolismo , ARN Interferente Pequeño/metabolismo , Cicatrización de Heridas/genética , Células Epiteliales/metabolismo
3.
Exp Eye Res ; 202: 108398, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33316263

RESUMEN

In the past few years we have seen a great acceleration of discoveries in the field of keratoconus including new treatments, diagnostic tools, genomic and molecular determinants of disease risk. Recent genome-wide association studies (GWAS) of keratoconus cases and population wide studies of variation in central corneal thickness and in corneal biomechanical properties confirmed already identified genes and found many new susceptibility variants and biological pathways. Recent findings in genetic determinants of familial keratoconus revealed functionally important variants and established first mouse model of keratoconus. Latest transcriptomic and expression studies started assessing novel non-coding RNA targets in addition to identifying tissue specific effects of coding genes. First genomic insights into better prediction of treatment outcomes are bringing the advent of genomic medicine into keratoconus clinical practice.


Asunto(s)
Colágeno/uso terapéutico , Reactivos de Enlaces Cruzados/uso terapéutico , Estudio de Asociación del Genoma Completo , Queratocono/genética , Fotoquimioterapia/métodos , Riboflavina/uso terapéutico , Animales , Humanos , Queratocono/tratamiento farmacológico , Queratocono/metabolismo , Fármacos Fotosensibilizantes/uso terapéutico , Rayos Ultravioleta
4.
Exp Eye Res ; 202: 108328, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33172608

RESUMEN

Both genetic and environmental factors have been considered to play a role in the etiology keratoconus. Eye rubbing, and more recently eye compression due to sleeping position, have been identified to be highly related to the condition, and are present in a high percentage of patients. Today, the predominant model is that these factors can provide the "second hit" necessary to generate the condition in a genetically susceptible individual. In addition, the extremely high prevalence in Arab populations, where endogamy could play a role, the high concordance rate in monozygotic twins, and the presence of family history of the condition between 5 and 23% of cases, support a genetic influence. Segregation analysis studies suggest that keratoconus is a complex non-Mendelian disease. Results from linkage analysis, next generation sequencing studies and genome-wide association studies also have suggested that genetic factors are involved in the condition. Recently, it has been proposed that mechanical trauma (i.e. eye rubbing or eye compression at night), is a sine quanon condition for the onset of keratoconus, and quite possibly its only cause. There are various arguments for and against this hypothesis. Indeed, it is possible, as initially suggested around 55 years ago, that the term "keratoconus" include diverse phenotypically similar conditions, which are actually of different etiology.


Asunto(s)
Lesiones de la Cornea/complicaciones , Queratocono/etiología , Queratocono/genética , Fenómenos Mecánicos , Enfermedad Crónica , Topografía de la Córnea , Estudio de Asociación del Genoma Completo , Humanos
5.
Nanomedicine ; 32: 102332, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33181273

RESUMEN

Human diabetic corneas develop delayed wound healing, epithelial stem cell dysfunction, recurrent erosions, and keratitis. Adenoviral gene therapy modulating c-Met, cathepsin F and MMP-10 normalized wound healing and epithelial stem cells in organ-cultured diabetic corneas but showed toxicity in stem cell-enriched cultured limbal epithelial cells (LECs). For a safer treatment, we engineered a novel nanobiopolymer (NBC) that carried antisense oligonucleotide (AON) RNA therapeutics suppressing cathepsin F or MMP-10, and miR-409-3p that inhibits c-Met. NBC was internalized by LECs through transferrin receptor (TfR)-mediated endocytosis, inhibited cathepsin F or MMP-10 and upregulated c-Met. Non-toxic NBC modulating c-Met and cathepsin F accelerated wound healing in diabetic LECs and organ-cultured corneas vs. control NBC. NBC treatment normalized levels of stem cell markers (keratins 15 and 17, ABCG2, and ΔNp63), and signaling mediators (p-EGFR, p-Akt and p-p38). Non-toxic nano RNA therapeutics thus present a safe alternative to viral gene therapy for normalizing diabetic corneal cells.


Asunto(s)
Córnea/patología , Diabetes Mellitus/patología , Células Epiteliales/patología , Nanopartículas/química , Polímeros/química , ARN/uso terapéutico , Células Madre/patología , Cicatrización de Heridas , Adenoviridae/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Supervivencia Celular , Células Cultivadas , Córnea/efectos de los fármacos , Células Epiteliales/efectos de los fármacos , Células Epiteliales/virología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nanopartículas/ultraestructura , Oligonucleótidos Antisentido/farmacología , ARN/farmacología , Receptores de Superficie Celular/metabolismo , Transducción de Señal/efectos de los fármacos , Células Madre/efectos de los fármacos , Cicatrización de Heridas/efectos de los fármacos
8.
World J Urol ; 34(4): 561-7, 2016 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-26253654

RESUMEN

PURPOSE: Renal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses. However, no study has yet examined the effect of Tim-3 on tumor infiltrating lymphocytes (TILs) in RCC. METHODS: We investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients. RESULTS: Levels of Tim-3 were significantly increased on both TIL CD4+ T cells and TIL CD8+ T cells and were associated with higher stages of the cancer. Also, GATA-3 and interferon gamma (IFN-γ) were down-regulated, whereas T-bet was up-regulated in TIL Tim-3+ T cells, indicating that Tim-3 expression defined a population of dysfunctional TIL Th1/Tc1 cells. Mechanism analyses showed that TIL Tim-3-expressing CD8+ T cells exhibited impaired Stat5 and p38 signaling pathway. Blocking the Tim-3 pathway restored cell proliferation and increased IFN-γ production in TIL CD4+ and CD8+ T cells of RCC. CONCLUSIONS: These results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment.


Asunto(s)
Carcinoma de Células Renales/genética , Regulación Neoplásica de la Expresión Génica , Receptor 2 Celular del Virus de la Hepatitis A/genética , Neoplasias Renales/genética , Riñón/patología , Linfocitos Infiltrantes de Tumor/patología , ARN Neoplásico/genética , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/metabolismo , Proliferación Celular , Femenino , Citometría de Flujo , Receptor 2 Celular del Virus de la Hepatitis A/biosíntesis , Humanos , Riñón/metabolismo , Neoplasias Renales/diagnóstico , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico
9.
Mol Vis ; 21: 1357-67, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26788028

RESUMEN

PURPOSE: To examine the expression of putative limbal epithelial stem cell (LESC) markers and wound healing rates in primary healthy and diabetic human limbal epithelial cells (LECs) cultured on different substrata. METHODS: Primary limbal epithelial cells were isolated from human autopsy corneas and discarded corneoscleral rims with dispase II treatment. LECs were cultured in EpiLife medium on human amniotic membrane (AM) denuded with mild alkali treatment, on plastic dishes and on glass slides coated with a mixture of human fibronectin, collagen type IV, and laminin (FCL). Cultured LECs were fixed in p-formaldehyde or methanol, and the expression of the putative LESC markers ΔNp63α, PAX6, and ABCG2 and keratins K12, K15, and K17 was examined with immunostaining. Wound healing was evaluated in scratch wound assay in LECs cultured on FCL-coated plates 20 h after wounding. RESULTS: LECs cultured on denuded AM expressed ΔNp63α, PAX6 (both showed nuclear staining), K15, K17 (cytoskeleton staining), and ABCG2 (cytoplasmic and/or plasma membrane staining). LECs cultured on FCL-coated slides also expressed these markers, whereas no expression was detected for differentiated corneal epithelial cell marker K12. Decreased expression of LESC markers was observed in diabetic LECs compared to healthy LECs cultured on the FCL-coated slides. This reduction was most prominent for K15 and K17. Diabetic LECs were found to heal scratch wounds slower than healthy cells in accordance with previous results in corneal organ cultures. CONCLUSIONS: Healthy human LECs cultured either on AM or FCL-coated slides preserved LESC marker expression. The observed reduction in LESC marker expression and slower wound healing in cultured diabetic LECs are in line with our earlier reports and may account for diabetic LESC dysfunction and clinically observed impaired corneal epithelial wound healing.


Asunto(s)
Complicaciones de la Diabetes/metabolismo , Limbo de la Córnea/metabolismo , Células Madre/metabolismo , Cicatrización de Heridas/fisiología , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Células Cultivadas , Enfermedades de la Córnea/etiología , Enfermedades de la Córnea/metabolismo , Enfermedades de la Córnea/patología , Medios de Cultivo , Complicaciones de la Diabetes/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Epitelio Corneal/metabolismo , Epitelio Corneal/patología , Femenino , Humanos , Limbo de la Córnea/patología , Masculino , Persona de Mediana Edad , Células Madre/patología
10.
Hum Mol Genet ; 21(2): 421-9, 2012 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-21979947

RESUMEN

Keratoconus is a condition in which the cornea progressively thins over time, and is a major cause for cornea transplantation. To identify keratoconus susceptibility regions, we performed a comprehensive genome-wide association study (GWAS) using a discovery and replication design. A discovery panel of 222 keratoconus Caucasian patients and 3324 Caucasian controls was genotyped using Illumina 370K beadchips. Further associated and fine-mapping single nucleotide polymorphisms (SNPs) (n= 4905) were genotyped in an independent replication case-control panel of 304 cases and 518 controls and a family panel of 307 subjects in 70 families. Logistic regression models implemented in PLINK were performed to test associations in case-control samples with and without principal component (PC) adjustments. Generalized estimation equation models accounting for familial correlations implemented in GWAF were used for association testing in families. No genome-wide associations were identified in the discovery GWAS panel. From the initial testing without adjustments for PCs, the top three SNPs located at 3p26 (rs6442925), 2q21.3 (rs4954218) and 19q13.3 (rs1428642) were identified with unadjusted P-values of 6.5 × 10(-8), 2.4 × 10(-7) and 3.1 × 10(-7), respectively. After adjustments for PCs, rs1428642 became the most significant through the genome with a P-value of 1.4 × 10(-6), while rs6442925 and rs4954218 were less significant (P= 1.9 × 10(-5) and 2.6 × 10(-4)). SNP rs4954218 was confirmed in two independent replication panels with P-values of 0.004 and 0.009, respectively. Meta-analysis revealed a highest association at rs4954218 with adjusted P= 1.6 × 10(-7) (unadjusted P= 1.2 × 10(-9)). These findings suggest SNP rs4954218, located near the RAB3GAP1 gene, previously reported to be associated with corneal malformation, is a potential susceptibility locus for keratoconus.


Asunto(s)
Trasplante de Córnea , Países Desarrollados , Estudio de Asociación del Genoma Completo , Queratocono/genética , Estudios de Casos y Controles , Cromosomas Humanos Par 2 , Estudios de Cohortes , Humanos , Polimorfismo de Nucleótido Simple
11.
J Refract Surg ; 30(2): 80-7, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24763472

RESUMEN

PURPOSE: To develop parameters using a combination of optical coherence tomography (OCT) and videokeratography to detect early keratoconus. METHODS: Videokeratography, wavefront analysis, and measured OCT indices were performed on 180 normal eyes, 46 eyes with moderate keratoconus, 54 eyes with early keratoconus, 7 eyes with forme fruste keratoconus, and 16 eyes with keratoconus "suspect" to determine the most sensitive parameters for separating these groups. RESULTS: A combination of videokeratography and OCT indices (inferior-superior [I-S] value and minimum pachymetry) was statistically the most significant in separating the keratoconus groups from normal eyes (P < .001). Using a newly derived index, the minimum pachymetry divided by the I-S value (pachymetry/asymmetry [PA]/I-S index) with a cut-off of 100, 100% of early and forme fruste keratoconus could be identified as being abnormal with 7 normals misclassified (misclassification rate 2.7%). By adding keratoconus "suspect" to the analysis and an I-S value of 1.2 as a cut-off point, 5 "suspects" were classified as normal and 11 normals as abnormal (misclassification rate 7.8%). The PA/I-S index, with a cut-off point of 100, reduced this misclassification rate to 4.4%. CONCLUSIONS: These results suggest that OCT combined with videokeratography may be more useful for differentiating mild forms of keratoconus than videokeratography alone.


Asunto(s)
Topografía de la Córnea , Queratocono/clasificación , Queratocono/diagnóstico , Tomografía de Coherencia Óptica , Aberrometría , Adolescente , Adulto , Paquimetría Corneal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Adulto Joven
12.
Behav Sci Law ; 32(3): 269-85, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24549687

RESUMEN

The purpose of this project was to assess the detecting deception efficacy of three well-validated "detecting deception" methods - i.e., forced choice testing (FCT), modified cognitive interviewing (MCI) and autobiographical implicit association testing (aIAT) - when applied to the issue of bio-threat. The detecting deception accuracies of FCT and MCI were 81% and 75%, respectively. Although the aIAT mean response times in block 5 differed significantly between deceptive and truthful persons, the classification accuracy was low. FCT alone reduced the group of 64 persons to 11 and detected 50% of the liars; the false positive rate was 9%. MCI alone reduced the group of 64 to 24 and detected 92% of the liars; the false positive rate was 54%. When FCT was paired with MCI, 75% of liars were detected and the false positive rate was 13%. Forced choice testing and MCI show promise as methods for detecting deception related to bio-threat under low-base-rate conditions. These methods took little time, enhanced the odds of detecting deceptive individuals and exhibited high positive likelihood ratios, suggesting that they have merit as screening tools. The aIAT required more time and was less accurate but may still serve as a useful screening tool.


Asunto(s)
Bioterrorismo , Entrevistas como Asunto/métodos , Detección de Mentiras , Adolescente , Adulto , Bioterrorismo/psicología , Conducta de Elección , Femenino , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Investigación Cualitativa , Adulto Joven
13.
Photodiagnosis Photodyn Ther ; 42: 103521, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36931367

RESUMEN

PURPOSE: To evaluate the safety and efficacy of epithelium-off (epi­off) corneal cross-linking (CXL) in patients with post-LASIK corneal ectasia (PLE) SETTING: Private clinical practice DESIGN: Prospective clinical trial METHODS: 82 eyes of adult patients post-LASIK, ages 21-67, with a topography pattern consistent with corneal ectasia, corrected distance visual acuity (CDVA) worse than 20/20, and minimum corneal pachymetry > 400 µm underwent epi­off CXL. Exclusion criteria were patients with corneas that were thinner than 400 µm or demonstrated central corneal scarring, history of herpetic eye disease, pregnancy or nursing. Follow up examinations of spherical equivalent, uncorrected distance visual acuity (UDVA), CDVA, steep keratometry (KSteep) and minimum pachymetry occurred on different but highly overlapping subsets of the operated eyes yearly until 5 years post-CXL. RESULTS: Over the 5 years of follow up, spherical equivalent did not significantly change while UCVA and CDVA stabilized or improved to a non-significant degree. KSteep and minimum pachymetry continued to be decreased to a statistically significant degree (p < 0.05 at 5 years). CONCLUSIONS: CXL in PLE patients is safe and efficacious: it halts progression of PLE and may improve visual function. KSteep and minimum pachymetry decrease post-CXL. Patients with PLE should be encouraged to stop progression of the disease by undergoing epi­off CXL once progression is established.


Asunto(s)
Queratomileusis por Láser In Situ , Fotoquimioterapia , Adulto , Humanos , Reticulación Corneal , Sustancia Propia , Topografía de la Córnea , Reactivos de Enlaces Cruzados/uso terapéutico , Dilatación Patológica/tratamiento farmacológico , Estudios de Seguimiento , Queratomileusis por Láser In Situ/efectos adversos , Queratomileusis por Láser In Situ/métodos , Rayos Láser , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Riboflavina/uso terapéutico , Rayos Ultravioleta
14.
J Cataract Refract Surg ; 47(10): 1333-1337, 2021 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33769766

RESUMEN

PURPOSE: To evaluate the safety and efficacy of epithelium-off (epi-off) corneal crosslinking (CXL) in adolescents with progressive keratoconus (KC). SETTING: Private clinical practice. DESIGN: Nonrandomized prospective clinical trial. METHODS: 230 adolescent patients aged 10 to 19 years with progressive KC (increasing maximum keratometry [Kmax] or astigmatism of 1.00 diopter or greater associated with decreased corrected distance visual acuity [CDVA]) underwent CXL. Exclusion criteria were age at time of CXL younger than 10 years or older than 19 years, corneas that were thinner than 400 µm or demonstrated central corneal scarring, history of herpetic eye disease, or pregnancy or nursing. Follow-up examinations of uncorrected distance visual acuity (UDVA), CDVA, Kmax, and minimum pachymetry occurred on 130 eyes at 1 year, 77 eyes at 2 years, and 55 eyes at 3 years post-CXL. RESULTS: In this study, 230 eyes of adolescent patients were evaluated. UDVA significantly improved from preoperatively to 1 year, 2 years, and 3 years post-CXL. CDVA values significantly improved from preoperatively to 1 year, 2 years, and 3 years post-CXL. Kmax values significantly reduced (improved) from preoperatively to 1 year and 3 years post-CXL and reduced (improved) (P = .22) from preoperatively to 2 years post-CXL. Minimum pachymetry decreased significantly from preoperatively to 1 year, 2 years, and 3 years post-CXL. CONCLUSIONS: CXL in patients aged 10 to 19 years was safe and efficacious, halted progression of KC and could improve UCVA, CDVA, and Kmax. Minimum pachymetry decreased and stabilized post-CXL. Ophthalmologists should encourage adolescent patients with KC to obtain prompt evaluation and possible CXL to halt progression of the disease.


Asunto(s)
Queratocono , Fotoquimioterapia , Adolescente , Colágeno/uso terapéutico , Córnea , Paquimetría Corneal , Sustancia Propia , Topografía de la Córnea , Reactivos de Enlaces Cruzados/uso terapéutico , Humanos , Queratocono/tratamiento farmacológico , Fármacos Fotosensibilizantes/uso terapéutico , Estudios Prospectivos , Riboflavina/uso terapéutico , Rayos Ultravioleta
15.
Alzheimer Dis Assoc Disord ; 24 Suppl: S35-41, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-22720320

RESUMEN

Despite an increasing awareness of the problem, clinical research continues to include lesser numbers of ethnic minority participants disproportionate to their population percentages. To rectify this problem, this article attempts to identify key barriers to minority recruitment and retention as well as specific strategies and methods successful in the past. We propose specific recommendations to address these barriers, and formulate a 3-prong approach to increasing minority recruitment and retention, with emphasis on elderly participants. The article discusses such concerns as building trust in the target community, using appropriate methods of outreach, and providing culturally sensitive written materials at appropriate health literacy levels. Through an awareness of and attention to cultural differences and sensitivities, researchers can and must address the chronic underrepresentation of ethnic minorities in clinical research.


Asunto(s)
Investigación Biomédica/tendencias , Competencia Cultural , Etnicidad , Grupos Minoritarios , Selección de Paciente , Anciano , Participación de la Comunidad , Relaciones Comunidad-Institución , Características Culturales , Demencia , Humanos , Estados Unidos
16.
J Relig Health ; 49(4): 498-512, 2010 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19904608

RESUMEN

The current study explored the relationship between religious coping and cumulative health risk associated with health behavior patterns in a sample of 256 Latina and Caucasian female caregivers of elderly relatives with dementia. Primary analyses examined the relationship between religious coping (both positive and negative) and an overall index of cumulative health risk. Secondary analyses were conducted on the individual health behaviors subsumed in the broader index. Findings revealed that negative religious coping was significantly associated with increased cumulative health risk. Positive religious coping was predictive of decreased cumulative health risk among Latina caregivers but not among Caucasians. Negative religious coping was significantly associated with both an increased likelihood for weight gain and increased dietary restriction. Positive religious coping was associated with decreased likelihood for weight gain in Latinas. Implications for both caregivers and clinicians are discussed.


Asunto(s)
Actividades Cotidianas/psicología , Enfermedad de Alzheimer , Cuidadores/psicología , Conductas Relacionadas con la Salud , Hispánicos o Latinos/psicología , Población Blanca/psicología , Adaptación Psicológica , Adulto , Anciano , Dieta/psicología , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Religión y Psicología , Autoeficacia , Estrés Psicológico/psicología , Aumento de Peso , Adulto Joven
17.
JAMA Ophthalmol ; 138(2): 174-181, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-31855235

RESUMEN

Importance: Keratoconus is a condition in which the cornea progressively thins and protrudes in a conical shape, severely affecting refraction and vision. It is a major indication for corneal transplant. To discover new genetic loci associated with keratoconus and better understand the causative mechanism of this disease, we performed a genome-wide association study on patients with keratoconus. Objective: To identify genetic susceptibility regions for keratoconus in the human genome. Design, Setting, and Participants: This study was conducted with data from eye clinics in Australia, the United States, and Northern Ireland. The discovery cohort of individuals with keratoconus and control participants from Australia was genotyped using the Illumina HumanCoreExome single-nucleotide polymorphism array. After quality control and data cleaning, genotypes were imputed against the 1000 Genomes Project reference panel (phase III; version 5), and association analyses were completed using PLINK version 1.90. Single-nucleotide polymorphisms with P < 1.00 × 10-6 were assessed for replication in 3 additional cohorts. Control participants were drawn from the cohorts of the Blue Mountains Eye Study and a previous study of glaucoma. Replication cohorts were from a previous keratoconus genome-wide association study data set from the United States, a cohort of affected and control participants from Australia and Northern Ireland, and a case-control cohort from Victoria, Australia. Data were collected from January 2006 to March 2019. Main Outcomes and Measures: Associations between keratoconus and 6 252 612 genetic variants were estimated using logistic regression after adjusting for ancestry using the first 3 principal components. Results: The discovery cohort included 522 affected individuals and 655 control participants, while the replication cohorts included 818 affected individuals (222 from the United States, 331 from Australia and Northern Ireland, and 265 from Victoria, Australia) and 3858 control participants (2927 from the United States, 229 from Australia and Northern Ireland, and 702 from Victoria, Australia). Two novel loci reached genome-wide significance (defined as P < 5.00 × 10-8), with a P value of 7.46 × 10-9 at rs61876744 in patatin-like phospholipase domain-containing 2 gene (PNPLA2) on chromosome 11 and a P value of 6.35 × 10-12 at rs138380, 2.2 kb upstream of casein kinase I isoform epsilon gene (CSNK1E) on chromosome 22. One additional locus was identified with a P value less than 1.00 × 10-6 in mastermind-like transcriptional coactivator 2 (MAML2) on chromosome 11 (P = 3.91 × 10-7). The novel locus in PNPLA2 reached genome-wide significance in an analysis of all 4 cohorts (P = 2.45 × 10-8). Conclusions and Relevance: In this relatively large keratoconus genome-wide association study, we identified a genome-wide significant locus for keratoconus in the region of PNPLA2 on chromosome 11.


Asunto(s)
Queratocono/genética , Polimorfismo de Nucleótido Simple , Adulto , Femenino , Distrofia Endotelial de Fuchs/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Humanos , Lipasa/genética , Modelos Logísticos , Masculino , Persona de Mediana Edad
18.
Alzheimer Dis Assoc Disord ; 23(4): 389-94, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19935146

RESUMEN

PURPOSE: The purpose of the current study was to explore the moderating effect of 3 domains of caregiver self-efficacy on the relationship between exogenous caregiving stressors (care recipient memory and behavioral problems) and depression. DESIGN AND METHODS: Moderator analyses were used to analyze data for 256 caregivers of elder relatives with dementia recruited at the Palo-Alto site of the National REACH (Resources for Enhancing Alzheimer's Caregiver Health) Project. Significant interactions between the stressor and self-efficacy indicated a potential moderating effect. Post hoc analyses were then conducted to determine the nature of the interaction(s). RESULTS: Self-efficacy for managing disruptive behaviors and self-efficacy for controlling upsetting thoughts had a direct effect on depression. Self-efficacy for responding to disruptive behaviors moderated the relationship between care recipient memory and behavioral problems and symptoms of depression. IMPLICATIONS: Self-efficacy may be an important clinical tool for identifying the caregivers who are most vulnerable to depression. Self-efficacy for responding to disruptive behaviors may be especially helpful in identifying caregivers at the greatest risk for depression when care recipient memory and behavior problems are high.


Asunto(s)
Cuidadores/psicología , Demencia/psicología , Depresión/psicología , Trastornos Mentales/psicología , Autoeficacia , Adaptación Psicológica , Adulto , Anciano , Demencia/complicaciones , Demencia/terapia , Depresión/etiología , Femenino , Humanos , Trastornos de la Memoria/complicaciones , Trastornos de la Memoria/psicología , Trastornos de la Memoria/terapia , Trastornos Mentales/complicaciones , Trastornos Mentales/terapia , Persona de Mediana Edad
19.
Aging Ment Health ; 13(6): 788-98, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19888699

RESUMEN

The current study explored the relationship between three dimensions of religiosity: (a) organizational religiosity (e.g. attendance at religious events), (b) non-organizational religiosity (e.g. prayer), and (c) subjective religiosity (e.g. importance of religion) and caregiver health behavior patterns in a sample of Latina and Caucasian female caregivers of older adult relatives with dementia. It was hypothesized that religiosity would have a significant association with reduced cumulative health risk as determined by an index of health behaviors. It was also hypothesized that, when examining the individual health behaviors subsumed in the overarching index, religiosity would be positively associated with adaptive health behaviors like exercise and negatively associated with health risk behaviors like smoking. Amongst Caucasians, increased subjective religiosity was related to increased cumulative health risk. Conversely, in Latinas, non-organizational religiosity was positively correlated with improved dietary practices (reduced dietary restriction). Increased levels of subjective religiosity were significantly associated with decreased maintenance of a routine exercise regimen across ethnic groups. Recommendations for clinicians and religious leaders, and avenues of future research are discussed.


Asunto(s)
Enfermedad de Alzheimer , Cuidadores/psicología , Conductas Relacionadas con la Salud , Religión y Psicología , Actividades Cotidianas/psicología , Adaptación Psicológica , Anciano , Consumo de Bebidas Alcohólicas/psicología , Cuidadores/estadística & datos numéricos , Dieta/métodos , Dieta/psicología , Dieta/estadística & datos numéricos , Ejercicio Físico/psicología , Femenino , Hispánicos o Latinos/psicología , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Persona de Mediana Edad , Asunción de Riesgos , Índice de Severidad de la Enfermedad , Fumar/psicología , Estrés Psicológico/psicología , Aumento de Peso , Población Blanca/psicología , Población Blanca/estadística & datos numéricos
20.
Mil Med ; 174(4): 358-62, 2009 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19485104

RESUMEN

The current military battlefield requires aviators to make split-second decisions that often have life-and-death consequences, making identifying predictors of diminished cognitive performance a vital aeromedical and safety concern. The current study explored the relationship between aviator effectiveness, as determined by sleep-wake patterns, and neurocognitive functioning in a brigade-size rotary wing aviation element deployed in Iraq. Actigraphy and the Fatigue Avoidance Scheduling Tool (FAST) were used to assess the ratio of sleep-wake patterns over a 24-hour time period, and a computerized multitasking measure, which mimics the task demands of flying, was utilized to evaluate neurocognitive functioning during preflight operations. Results showed a significant positive association between level of effectiveness and neurocognitive functioning before flight operations. The reported sleep habits and trends in types of sleep difficulties are noted. The results speak to the potential efficacy of using actigraphy and software to evaluate a pilot's effectiveness before flight operations, and suggest that flight surgeons and psychologists may be able to play a vital role in improving overall sleep patterns and enhancing the warfighting efforts of aviators in combat. They also suggest that mandated crew rest and evaluation of total reported sleep time may not be sufficient to ensure optimum performance levels.


Asunto(s)
Accidentes de Aviación/prevención & control , Medicina Aeroespacial , Trastornos del Conocimiento/prevención & control , Fatiga/prevención & control , Adulto , Ritmo Circadiano , Trastornos del Conocimiento/etiología , Fatiga/etiología , Femenino , Humanos , Masculino , Salud Laboral , Descanso , Estudios Retrospectivos , Privación de Sueño/prevención & control , Encuestas y Cuestionarios , Análisis y Desempeño de Tareas , Estados Unidos , Vigilia , Tolerancia al Trabajo Programado , Carga de Trabajo
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