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Background: Cognitive and functional abilities in individuals with Alzheimer's disease (AD) pathology (ADP) are highly variable. Factors contributing to this variability are not well understood. Previous research indicates that higher educational attainment (EA) correlates with reduced cognitive impairments among those with ADP. While cognitive and functional impairments are correlated, they are distinguishable in their manifestations. Objective: To investigate whether levels of education are associated with functional impairments among those with ADP. Methods: This research involved 410 African American (AA) individuals (Institutional Review Boards 20070307, 01/27/2023) to ascertain whether EA correlates with functional resilience and if this effect varies between APOE É4 carriers and non-carriers. Utilizing EA as a cognitive reserve proxy, CDR-FUNC as a functional difficulties measure, and blood pTau181 as an ADP proxy, the non-parametric Mann-Whitney U test assessed the relationship between EA and CDR-FUNC in individuals with advanced pTau181 levels. Results: The results showed that EA correlated with functional difficulties in AA individuals with high levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (Wâ=â730.5, pâ=â0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in É4 non-carriers compared to É4 carriers (Wâ=â555.5, pâ=â0.022). Conclusion: This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele É4.
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Doença de Alzheimer , Disfunção Cognitiva , Resiliência Psicológica , Humanos , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Disfunção Cognitiva/genética , EscolaridadeRESUMO
OBJECTIVE: Explore predictors of early COVID-19 vaccine adoption on a university campus. PARTICIPANTS: Students, faculty, staff, and administration (N = 1,234) completed an online survey exploring COVID-19 vaccine-related experiences, perspectives, and knowledge, from September to October 2021. METHODS: Based on vaccination status participants were identified as vaccine hesitant or early vaccine adopters. Binary logistic regression was used to examine association between independent variables and vaccine adoption status. RESULTS: Democrats (OR = 4.3, p = <.001), participants without a positive COVID-19 test (OR = 2.5, p = <.001), noted seeing/hearing COVID-19 misinformation (OR = 1.8, p = 0.27), and reported trust in public health agencies (OR = 26.2, p = <.001) were more likely to be early COVID-19 vaccine adopters, compared to Republicans, those with a positive COVID-19 test, those who had not seen/heard COVID-19 misinformation, and those reporting distrust in public health agencies, respectively. CONCLUSION: Findings indicate that COVID-19 vaccine adoption is multifactorial. Future research should focus on vaccination status-related trust and health communication.
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BACKGROUND: There are significant implications for both patients and providers when patients do not attend outpatient specialist appointments. Nonattendance has an impact on the efficiency of health care, provider resources and patient health outcomes. AIMS: In this qualitative study we aimed to gather insights on how Dunedin Hospital notifies patients about their appointments, the implications for the hospital and for patients and how the system could be improved. METHODS: We interviewed 13 hospital staff members and nine patients who volunteered to participate because they had missed appointments as a result of communication problems. Interviews were transcribed and analysed thematically using NVivo software. RESULTS: Dunedin Hospital relies heavily on posted letters to inform people about their appointments, with some also receiving reminder texts closer to the time of the appointment. Frustration with the current system was a common theme among both patients and staff. Almost all patients had missed an appointment because of a letter not arriving. While most patients found that the text reminders were helpful, most said they were sent too late and did not allow enough time for arrangements to be made for their appointments. Almost all patients experienced treatment delays, which caused distress. Most patients believed a self-booking system would improve the ability to attend their appointments, and most of them wanted to be notified of appointments via email. CONCLUSIONS: We recommend that a patient-oriented approach to communication should be implemented, and alternative methods of communication should be explored.
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Hospitais , Pacientes Ambulatoriais , Humanos , Nova Zelândia , Comunicação , Pesquisa QualitativaRESUMO
BACKGROUND: Effective physical activity interventions are needed for children because health behaviors track into adulthood, and risk factors for diseases begin early in life. No study has determined whether an intervention designed using a Community-Based Participatory Research approach can improve moderate to vigorous physical activity (MVPA) and the related psychosocial constructs in underserved children. This study determined whether improvements in MVPA and related psychosocial constructs (self-efficacy, knowledge, beliefs, attitudes, and skills) occurred following a Community-Based Participatory Research intervention in underserved, rural children. It was then determined if these constructs were mediators of MVPA. METHODS: Two fifth-grade classes at a school (n = 19 and n = 20) were randomly assigned to an intervention or comparison group. The intervention group participated in a 4-week intervention designed to improve MVPA (wGT3X-BT accelerometer; ActiGraph, Pensacola, FL) and the related psychosocial constructs (written survey). Groups were assessed prior to and immediately following the intervention. RESULTS: There were no differences at baseline between groups. MVPA (30.0 [4.4] min), knowledge, and skill scores were significantly higher in the intervention group compared with the comparison group at follow-up (P < .05). Knowledge and skills were mediating variables of MVPA. CONCLUSIONS: Priority should be placed on research that determines the sustained impact of similar Community-Based Participatory Research interventions.
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Exercício Físico/psicologia , Psicologia/métodos , Criança , Pesquisa Participativa Baseada na Comunidade , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Masculino , Grupos Minoritários , População Rural , Populações VulneráveisRESUMO
BACKGROUND: Obesity among children is increasing nationwide, and creative solutions beyond traditional programs designed exclusively by academics are needed to achieve lasting success. One innovative approach that departs from the typical model of exclusive academic design incorporates local community input in designing health-related programs. Such input can lead to more relevant programs and community "buy in," thereby increasing the likelihood of the effectiveness of the program. One approach that incorporates local community input is called community-based participatory research (CBPR) whereby researchers and community partners work together and use the CBPR principles to create and sustain culturally relevant, impactful programs. OBJECTIVES: This paper describes how a mixed-methods CBPR approach was used to formulate and implement a needs assessment survey, and how mini-focus groups were used to reinforce the survey findings. METHODS: A survey seeking information about physical activity (PA) and dietary behavior was given to 27 families at a school-based event, and a forward stepwise regression was run to identify significant determinants. The results were presented and discussed with community mini-focus groups (n = 20). RESULTS: The regression models were significant (P < 0.05), where parental support of PA and PA beliefs were significant determinants of moderate to vigorous PA, and water intake, whole grain intake, and fruit and vegetable consumption were the top three significant determinants of dietary behavior. Mini-focus groups reinforced the model results. CONCLUSIONS: This approach helped identify the determinants that should be addressed when designing an after school program targeting PA and dietary behavior for minority students attending a school in an underserved community.
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Pesquisa Participativa Baseada na Comunidade , Exercício Físico , Criança , Promoção da Saúde , Humanos , Instituições Acadêmicas , VerdurasRESUMO
When devising strategies to combat obesity, strategies focusing on children should be utilized since health-related behaviors track into adulthood. One strategy that begins to address, and brings awareness to, the rising obesity rates and other health disparities in adults is the utilization of community health fairs. Previous literature has described how to conduct an adult health fair using a community-based participatory research (CBPR) approach, but no study has shown how to conduct a health fair for children. This article explains how a CBPR approach was used to develop a health fair focused on obesity prevention for children. A partnership between the community and a local university was formed to assist in the planning and implementation of a health fair. While the data obtained from the health fair served as a needs assessment for future projects, the health fair was also a good first step in developing relationships and trust among the partners.
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Serviços de Saúde da Criança/organização & administração , Pesquisa Participativa Baseada na Comunidade , Exposições Educativas/organização & administração , Obesidade Infantil/prevenção & controle , Criança , Relações Comunidade-Instituição , Humanos , Avaliação das Necessidades , Confiança , UniversidadesRESUMO
The overall objective of Project SHAPE (Shaping Health using Activity Photovoice and E-Video) was to improve physical activity levels of rural, medically underserved children by designing and implementing a culturally relevant physical activity intervention. This objective was met by using a community-based participatory research approach to design and implement an intervention that would positively affect the psychosocial constructs related to increasing physical activity, which, in turn, would lead to increases in the time spent in daily physical activity. This article describes the unique design of the intervention including its theoretical framework, its interrelated components, and the logistics involved.
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Pesquisa Participativa Baseada na Comunidade/métodos , Exercício Físico/fisiologia , Criança , Feminino , Humanos , Masculino , Projetos de Pesquisa , População RuralRESUMO
Cultural competency, trust, and research literacy can affect the planning and implementation of sustainable community-based participatory research (CBPR). The purpose of this manuscript is to highlight: (1) the development of a CBPR pilot grant request for application; and (2) a comprehensive program supporting CBPR obesity-related grant proposals facilitated by activities designed to promote scholarly collaborations between academic researchers and the community. After a competitive application process, academic researchers and non-academic community leaders were selected to participate in activities where the final culminating project was the submission of a collaborative obesity-related CBPR grant application. Teams were comprised of a mix of academic researchers and non-academic community leaders, and each team submitted an application addressing obesity-disparities among rural predominantly African American communities in the US Deep South. Among four collaborative teams, three (75%) successfully submitted a grant application to fund an intervention addressing rural and minority obesity disparities. Among the three submitted grant applications, one was successfully funded by an internal CBPR grant, and another was funded by an institutional seed funding grant. Preliminary findings suggest that the collaborative activities were successful in developing productive scholarly relationships between researchers and community leaders. Future research will seek to understand the full-context of our findings.
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Negro ou Afro-Americano , Pesquisa Participativa Baseada na Comunidade/métodos , Comportamento Cooperativo , Disparidades nos Níveis de Saúde , Obesidade/terapia , Apoio à Pesquisa como Assunto , Saúde da População Rural/etnologia , Alabama/epidemiologia , Pesquisa Participativa Baseada na Comunidade/economia , Pesquisa Participativa Baseada na Comunidade/organização & administração , Humanos , Obesidade/etnologia , Desenvolvimento de ProgramasRESUMO
Alzheimer's disease (AD) and related dementias are a major public health challenge and present a therapeutic imperative for which we need additional insight into molecular pathogenesis. We performed a genome-wide association study and analysis of known genetic risk loci for AD dementia using neuropathologic data from 4,914 brain autopsies. Neuropathologic data were used to define clinico-pathologic AD dementia or controls, assess core neuropathologic features of AD (neuritic plaques, NPs; neurofibrillary tangles, NFTs), and evaluate commonly co-morbid neuropathologic changes: cerebral amyloid angiopathy (CAA), Lewy body disease (LBD), hippocampal sclerosis of the elderly (HS), and vascular brain injury (VBI). Genome-wide significance was observed for clinico-pathologic AD dementia, NPs, NFTs, CAA, and LBD with a number of variants in and around the apolipoprotein E gene (APOE). GalNAc transferase 7 (GALNT7), ATP-Binding Cassette, Sub-Family G (WHITE), Member 1 (ABCG1), and an intergenic region on chromosome 9 were associated with NP score; and Potassium Large Conductance Calcium-Activated Channel, Subfamily M, Beta Member 2 (KCNMB2) was strongly associated with HS. Twelve of the 21 non-APOE genetic risk loci for clinically-defined AD dementia were confirmed in our clinico-pathologic sample: CR1, BIN1, CLU, MS4A6A, PICALM, ABCA7, CD33, PTK2B, SORL1, MEF2C, ZCWPW1, and CASS4 with 9 of these 12 loci showing larger odds ratio in the clinico-pathologic sample. Correlation of effect sizes for risk of AD dementia with effect size for NFTs or NPs showed positive correlation, while those for risk of VBI showed a moderate negative correlation. The other co-morbid neuropathologic features showed only nominal association with the known AD loci. Our results discovered new genetic associations with specific neuropathologic features and aligned known genetic risk for AD dementia with specific neuropathologic changes in the largest brain autopsy study of AD and related dementias.
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Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Demência/diagnóstico , Demência/etiologia , Estudo de Associação Genômica Ampla , Membro 1 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Transportadores de Cassetes de Ligação de ATP/genética , Encéfalo/patologia , Estudos de Casos e Controles , Mapeamento Cromossômico , Cromossomos Humanos Par 18 , Cromossomos Humanos Par 9 , Predisposição Genética para Doença , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , N-Acetilgalactosaminiltransferases/genética , Razão de Chances , Fenótipo , Placa Amiloide , Locos de Características QuantitativasRESUMO
OBJECTIVE: This study compared BMD relative to body weight following a â¼6-month weight loss program and a 1-year weight maintenance phase in premenopausal women and determined whether African American (AA) and European-American (EA) women's BMD respond similarly during weight loss. DESIGN AND METHODS: Premenopausal women (n = 115, 34 ± 5 years) were evaluated in an overweight state (BMI between 27 and 30 kg/m(2) ), following an 800 kcal/day diet/exercise program designed to reduce BMI<25 kg/m(2) , and 1-year following weight loss. RESULTS: BMD relative to body weight (Z-scores) increased after weight loss, but decreased during the 1-year weight maintenance phase. All 1-year follow-up BMD Z-scores were increased (except L1) compared to baseline measurements (P < 0.05). These sites included the hip neck (+0.088, P = 0.014), total hip (+0.099, P = 0.001), L2 (+0.127, P = 0.013), L3 (+0.135, P = 0.014), and L4 (+0.199, P = 0.002). AAs had significantly higher absolute BMD at all sites (P < 0.05) compared to EAs, but no time by race interactions were evident during weight loss (except in L3). CONCLUSION: These results may indicate that weight loss is safe with regard to bone health for overweight premenopausal women.
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Densidade Óssea , Pré-Menopausa , Redução de Peso , Adulto , Negro ou Afro-Americano , Composição Corporal , Índice de Massa Corporal , Dieta , Exercício Físico , Feminino , Quadril , Humanos , Pessoa de Meia-Idade , Sobrepeso/terapia , População Branca , Adulto JovemRESUMO
Recently, a hexanucleotide repeat expansion in the C9ORF72 gene has been identified to account for a significant portion of Caucasian families affected by frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Given the clinical overlap of FTD with Alzheimer's disease (AD), we hypothesized that C9ORF72 expansions might contribute to AD. In Caucasians, we found C9ORF72 expansions in the pathogenic range of FTD/ALS (>30 repeats) at a proportion of 0.76% in AD cases versus 0 in control subjects (p = 3.3E-03; 1182 cases, 1039 controls). In contrast, no large expansions were detected in individuals of African American ethnicity (291 cases, 620 controls). However, in the range of normal variation of C9ORF72 expansions (0-23 repeat copies), we detected significant differences in distribution and mean repeat counts between Caucasians and African Americans. Clinical and pathological re-evaluation of identified C9ORF72 expansion carriers revealed 9 clinical and/or autopsy confirmed AD and 2 FTD final diagnoses. Thus, our results support the notion that large C9ORF72 expansions lead to a phenotypic spectrum of neurodegenerative disease including AD.
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Doença de Alzheimer/etnologia , Doença de Alzheimer/genética , Expansão das Repetições de DNA/genética , Demência Frontotemporal/etnologia , Demência Frontotemporal/genética , Proteínas/genética , População Branca/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Proteína C9orf72 , Comorbidade , Feminino , Marcadores Genéticos/genética , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Testes Genéticos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a devastating disease usually diagnosed at a late stage when cure rates are 40%. We examined a simple and inexpensive molecular tool that may aid HNSCC detection. METHODS: Building on prior findings that total protein levels are elevated in 102 HNSCC cases versus 84 control subjects, we further analyzed these levels with respect to important risk and demographic variables and compared the results to soluble CD44 (solCD44). Using multivariate adaptive regression splines (MARSs)-logit modeling and logistic regression, we determined whether total protein, solCD44, or the combination best identifies HNSCC. RESULTS: Combined higher levels of solCD44 and protein were significantly associated with HNSCC (odds ratio [OR] = 24.90; 95% confidence interval [CI], 9.04-68.57; area under the curve [AUC] = 0.786). A model including protein plus solCD44 resulted in a better area (AUC 0.796) than either marker alone. CONCLUSION: Oral rinse levels of solCD44 and protein seem to hold promise for detection of HNSCC.
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Carcinoma de Células Escamosas/diagnóstico , Diagnóstico Precoce , Neoplasias de Cabeça e Pescoço/diagnóstico , Receptores de Hialuronatos/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas/metabolismo , Curva ROC , Saliva/metabolismo , Sensibilidade e Especificidade , Fumar/metabolismoRESUMO
Epilepsy co-occurs frequently in autism spectrum disorders (ASD). Understanding this co-occurrence requires a better understanding of the ASD-epilepsy phenotype (or phenotypes). To address this, we conducted latent class cluster analysis (LCCA) on an ASD dataset (N = 577) which included 64 individuals with epilepsy. We identified a 5-cluster solution with one cluster showing a high rate of epilepsy (29%), earlier age at first recognition, and high rates of repetitive object use and unusual sensory interests. We also conducted LCCA on an ASD-epilepsy subset from the overall dataset (N = 64) which yielded three clusters, the largest of which had impairments in language and motor development; the remaining clusters, while not as developmentally impaired were characterized by different levels of repetitive and sensory behaviors.
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Transtornos Globais do Desenvolvimento Infantil/complicações , Epilepsia/complicações , Adolescente , Criança , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Pré-Escolar , Análise por Conglomerados , Epilepsia/diagnóstico , Feminino , Humanos , Masculino , FenótipoRESUMO
The cellular mechanisms that drive growth and remodeling of the early intestinal epithelium are poorly understood. Current dogma suggests that the murine fetal intestinal epithelium is stratified, that villi are formed by an epithelial remodeling process involving the de novo formation of apical surface at secondary lumina, and that radial intercalation of the stratified cells constitutes a major intestinal lengthening mechanism. Here, we investigate cell polarity, cell cycle dynamics and cell shape in the fetal murine intestine between E12.5 and E14.5. We show that, contrary to previous assumptions, this epithelium is pseudostratified. Furthermore, epithelial nuclei exhibit interkinetic nuclear migration, a process wherein nuclei move in concert with the cell cycle, from the basal side (where DNA is synthesized) to the apical surface (where mitosis takes place); such nuclear movements were previously misinterpreted as the radial intercalation of cells. We further demonstrate that growth of epithelial girth between E12.5 and E14.5 is driven by microtubule- and actinomyosin-dependent apicobasal elongation, rather than by progressive epithelial stratification as was previously thought. Finally, we show that the actin-binding protein Shroom3 is crucial for the maintenance of the single-layered pseudostratified epithelium. In mice lacking Shroom3, the epithelium is disorganized and temporarily stratified during villus emergence. These results favor an alternative model of intestinal morphogenesis in which the epithelium remains single layered and apicobasally polarized throughout early intestinal development.
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Mucosa Intestinal/embriologia , Animais , Ciclo Celular , Polaridade Celular , Forma Celular , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Mucosa Intestinal/citologia , Mucosa Intestinal/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Morfogênese , GravidezRESUMO
Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case-control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes (CSRP3, LDB3, MYH7, SCN5A, TCAP, and TNNT2) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM. Common variants in genes known to be causative of DCM may play a role in genetic susceptibility to DCM. Our results suggest that examination of common genetic variants may be warranted in future studies of DCM and other Mendelian-like disorders.
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Cardiomiopatia Dilatada/genética , Predisposição Genética para Doença , Estudos de Casos e Controles , Humanos , Análise MultivariadaRESUMO
BACKGROUND: Studies suggest that institutional case volume and teaching status significantly affect patient survival. We sought to compare outcomes of surgical resection for lung cancer at teaching facilities (TF) and at high-volume centers (HVC). METHODS: Patients undergoing lung cancer resection with curative intent were examined using a linked dataset from 1998 to 2002 between the Florida Cancer Data System and the Florida Agency for Health Care Administration. RESULTS: A total of 13,469 patients were analyzed and outcomes adjusted for comorbidities. Median survival time (MST) was superior for patients treated at TF versus nonteaching facilities (NTF) (47.1 versus 40.5 months, P < 0.001). Mortality rates at NTF were higher at 30 days (2.6% versus 1.1%, P < 0.001), 90 days (6.8% versus 3.8%, P < 0.001), and at 5 years (63.9% versus 59.2%, P = 0.005). Similarly, MST was superior in the cohort treated at HVC versus low-volume center (LVC) (45.1 versus 39.8 months, P < 0.001). Mortality was observed to be higher in LVC than HVC at 30 days (2.7% versus 1.6%, P < 0.001), 90 days (7.5% versus 4.0%, P < 0.001), and at 5 years (63.5% versus 59.3%, P = 0.002). Significant preoperative, independent predictors of survival include age, sex, smoking status, and the existence of certain comorbidities. Treatment at a TF or HVC were independent predictors of better outcome. Race, use of chemotherapy or radiation did not affect outcomes. CONCLUSION: Surgical treatment for lung cancer at TF or HVC results in significantly better short- and long-term patient outcomes.
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Institutos de Câncer , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Hospitais de Ensino , Neoplasias Pulmonares/cirurgia , Avaliação de Resultados em Cuidados de Saúde , Carcinoma de Pequenas Células do Pulmão/cirurgia , Adulto , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Florida , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Procedimentos Cirúrgicos Pulmonares , Garantia da Qualidade dos Cuidados de Saúde , Carcinoma de Pequenas Células do Pulmão/mortalidade , Taxa de SobrevidaRESUMO
PURPOSE: To determine the incidence of second primary cancers (SPCs) and radiotherapy-induced SPCs (RTSPCs). PATIENTS AND METHODS: The incidence of SPCs and RTSPCs was compared among four treatment groups with locoregional prostate adenocarcinoma in the 1973-2002 Surveillance, Epidemiology, and End Results database. These groups were no radiotherapy (RT), no surgery (Group 1); external beam RT (EBRT) (Group 2); brachytherapy (Group 3); and a combination of EBRT and brachytherapy (Group 4). RESULTS: The age-adjusted estimates of SPCs were greater with EBRT than with brachytherapy (2,178 vs. 1,901 SPCs/100,000; p = 0.025) or with the no RT, no surgery group (1,971 SPCs/100,000; p <0.0001). The age-adjusted rate of late SPC (>or=5 years) for EBRT (2,425 SPCs/100,000) was only significantly greater (p <0.0001) than that for no RT, no surgery (1,950 SPCs/100,000). The hazard ratio adjusted for age, race/ethnicity, and grade was constant at 1.263 for EBRT compared with no RT, no surgery (p <0.0001) but varied with the length of follow-up in both the brachytherapy (0.721 at 5 years to 1.200 at 9 years) and combination (0.920 at 5 years to 1.317 at 9 years) groups. The incidence of RTSPCs was only significantly different between the no RT, no surgery group and the EBRT group, with an increase of 162 cases/100,000 or a 0.16% increased SPC risk (p = 0.023). No significant differences in the incidence of RTSPC were seen between the RT groups. CONCLUSION: No significant differences were seen in the incidence of RTSPCs between the RT groups. The initial smaller relative risk of overall SPCs in the brachytherapy group increased with time until the curves converged, suggesting that the effect had resulted from patient selection bias.
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Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Neoplasias da Próstata/radioterapia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Fatores Etários , Idoso , Análise de Variância , Braquiterapia/efeitos adversos , Distribuição de Qui-Quadrado , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/cirurgia , Risco , Programa de SEERRESUMO
INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is a devastating and deadly disease, largely because it is diagnosed in late stage. Cure rates, currently at 50%, could increase to >80% with early detection. In this study, we evaluate soluble CD44 (solCD44) as an early detection tool for HNSCC by determining whether it reliably distinguishes HNSCC from benign disease of the upper aerodigestive tract. METHODS: We carried out the solCD44 ELISA on oral rinses from 102 patients with HNSCC and 69 control patients with benign diseases of upper aerodigestive tract to determine the sensitivity and specificity of the test for differentiating HNSCC from benign disease. Furthermore, we did a pilot study using methylation-specific PCR primers on oral rinses from 11 HNSCC patients with low solCD44 levels and 10 benign disease controls. RESULTS: Mean salivary solCD44 levels were 24.4 +/- 32.0 ng/mL for HNSCC patients (range, 0.99-201 ng/mL) and 9.9 +/- 16.1 ng/mL (range, 0.73-124 ng/mL) for the patients with benign disease (P < 0.0001). Depending on cutoff point and HNSCC site, sensitivity ranged from 62% to 70% and specificity ranged from 75% to 88%. Nine of 11 HNSCC and 0 of 10 controls with low solCD44 levels showed hypermethylation of the CD44 promoter. CONCLUSIONS: SolCD44 is elevated in the majority of HNSCC and distinguishes cancer from benign disease with high specificity. Whereas the solCD44 test lacks sensitivity by itself, methylation status of the CD44 gene seems to complement the solCD44 test. Our pilot data indicate that, together, these markers will detect HNSCC with very high sensitivity and specificity.
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Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Receptores de Hialuronatos/metabolismo , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Metilação de DNA , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Projetos Piloto , Prognóstico , Saliva/metabolismo , Sensibilidade e EspecificidadeRESUMO
Head and neck squamous cell carcinoma (HNSCC) is a debilitating and deadly disease that is only cured 50% of the time. A better understanding of the molecular mechanisms involved in HNSCC progression may lead to earlier detection and improved cure rates. CD44 is a ubiquitous transmembrane glycoprotein comprising a family of alternatively spliced isoforms involved in cell migration and cell proliferation. CD44 isoforms containing the variant 3 (v3) exon include a growth factor binding site and may be involved in tumor progression. To characterize CD44v3-containing isoforms expression in HNSCC we purified RNA from four HNSCC cell lines and performed RT-PCR using junction primer strategies followed by gel elecrophoresis. Cloning and sequencing of HNSCC cell line PCR products revealed two isoforms. One of these, CD44v3-10, has been previously described. The other isoform, CD44v3, has not been characterized in HNSCC tissues. To further study this isoform, we purified RNA from 19 HNSCC tissues, 7 normal margin tissues and 5 true normal tissues. Following reverse-transcription, we performed quantitative PCR using junction primers specific for CD44v3. Results show that HNSCC tumor tissues expressed mean CD44v3 levels that were elevated 4.5 times more than true normal tissues (p < 0.01). Mean CD44v3 values for HNSCC tumors were 0.43 +/- 0.44 while mean levels for true normal tissues were 0.10 +/- 0.11. Levels in tumor tissue did not vary significantly with tumor characteristics such as site, stage, prior treatment, or nodal status. In addition, to characterize the role of this molecule plays in tumor progression, we overexpressed CD44v3 in a HNSCC cell line. Our results indicate that although higher levels of CD44v3 did not affect the rate of proliferation, a significant increase in migration was observed. CD44v3 may provide a target for future diagnostic and therapeutic interventions for HNSCC.
Assuntos
Carcinoma de Células Escamosas/imunologia , Neoplasias de Cabeça e Pescoço/imunologia , Receptores de Hialuronatos/biossíntese , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Processos de Crescimento Celular/fisiologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/imunologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , TransfecçãoRESUMO
PURPOSE: To determine quality of life (QOL) after hyperfractionated radiation and chemotherapy. MATERIALS AND METHODS: Functional Assessment of Cancer Therapy (FACT) and the Functional Assessment of Cancer Therapy-Head and Neck (FACT H-N) questionnaires were administered to protocol patients at baseline study entry, during and at the completion of therapy, and during subsequent follow-up. RESULTS: Twenty-four patients completed baseline QOL questionnaires. Six subsequent assessments were given to patients who were available for follow-up. Social/family well-being and relationship with doctor subscores were not significantly different from baseline. Emotional well-being was not different from baseline initially, but actually showed a significant increase 6 months after completion of radiation, seen on assessments 5 and 6 (P < 0.01). Physical and functional well-being subscores, total FACT-G score, head and neck subscores, and total FACT H-N score all showed initial decreases during, at the completion of radiation, or, in some subscores, up to 3 months postradiation. However, all these scores recovered to baseline levels. These scores subsequently showed a significant increase after 6 months to 1 year in all but the physical well-being and head and neck subscores, which remained at baseline. CONCLUSION: QOL scores returned to baseline levels or increased at 6 to 12 months postradiation in long-term survivors who completed QOL questionnaires.