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1.
J Genet Couns ; 28(2): 292-303, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30741463

RESUMO

Increased usage of exome and genome sequencing has made uncertainties associated with genomic sequencing methods more prevalent within medicine. Current research focuses on patients' perceptions of uncertainty related to genomic sequencing, but there is limited knowledge of the perspectives of providers. The aim of this study was to explore how professionals in genomics perceive uncertainties involved in genomic sequencing, and if or how this impacts their approach to pretest counseling. We performed 20 semi-structured interviews with genetic counselors in the United States and Canada who provide pretest genetic counseling for genomic sequencing. Interviews explored participating genetic counselors' views of uncertainty regarding genomic sequencing, how they classify it, how it manifests, and how they manage it during pretest counseling. Thematic analysis showed that genetic counselors acknowledge concepts of uncertainty that map to existing frameworks of uncertainty for genomic sequencing. Genetic counselors also perceived incongruencies between patients' and providers' expectations of genomic sequencing, which prompted them to modify patients' perceptions of uncertainty related to genomic sequencing. All genetic counselors agreed that guidance and strategies for genomic sequencing pretest counseling would be helpful, particularly for novice genetic counselors and non-genetics providers. These findings highlight the need and potential for conceptual models of uncertainty and uncertainty management strategies to facilitate patient-centered pretest counseling for genomic sequencing.


Assuntos
Conselheiros/psicologia , Aconselhamento Genético , Incerteza , Canadá , Feminino , Humanos , Masculino , Pesquisa Qualitativa
2.
J Genet Couns ; 28(3): 641-653, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30720922

RESUMO

It is becoming increasingly common for people to openly identify as transgender, yet there is little research in the field of genetic counseling regarding this community's unique medical needs. Transgender patients are likely to present with issues that cross genetics and gender-related care in a cancer genetic counseling session, and empiric data about these differences is needed to provide adequate care. In order to investigate what specific health topics and concerns are addressed in cancer genetic counseling sessions with transgender patients, 21 cancer genetic counselors who have seen transgender patients were interviewed. Through inductive analysis, six themes emerged: (1) documentation systems are not inclusive or clear; (2) genetic counselors feel unprepared for these sessions; (3) gender affirming hormones impact risk assessment; (4) genetic testing affects gender affirming surgical decisions; (5) transgender patients present at younger ages to clinic; and (6) pathogenic variants allow for insurance coverage for gender affirming surgeries. This study's findings point to opportunities for the field of genetic counseling to enhance services for transgender patients by reporting distinctive situations that may arise in clinic with these patients and providing training recommendations for genetic counselors.


Assuntos
Conselheiros/psicologia , Pessoas Transgênero , Adulto , Emoções , Feminino , Aconselhamento Genético , Testes Genéticos , Humanos , Cobertura do Seguro , Masculino , Pesquisa Qualitativa
3.
Prev Chronic Dis ; 15: E09, 2018 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-29346063

RESUMO

INTRODUCTION: Monitoring and understanding population health requires conducting health-related surveys and surveillance. The objective of our study was to assess whether data from self-administered surveys could be collected electronically from patients in urban, primary-care, safety-net clinics and subsequently linked and compared with the same patients' electronic health records (EHRs). METHODS: Data from self-administered surveys were collected electronically from a convenience sample of 527 patients at 2 Chicago health centers from September through November, 2014. Survey data were linked to EHRs. RESULTS: A total of 251 (47.6%) patients who completed the survey consented to having their responses linked to their EHRs. Consenting participants were older, more likely to report fair or poor health, and took longer to complete the survey than those who did not consent. For 8 of 18 categorical variables, overall percentage of agreement between survey data and EHR data exceeded 80% (sex, race/ethnicity, pneumococcal vaccination, self-reported body mass index [BMI], diabetes, high blood pressure, medication for high blood pressure, and hyperlipidemia), and of these, the level of agreement was good or excellent (κ ≥0.64) except for pneumococcal vaccination (κ = 0.40) and hyperlipidemia (κ = 0.47). Of 7 continuous variables, agreement was substantial for age and weight (concordance coefficients ≥0.95); however, with the exception of calculated survey BMI and EHR-BMI (concordance coefficient = 0.88), all other continuous variables had poor agreement. CONCLUSIONS: Self-administered and web-based surveys can be completed in urban, primary-care, safety-net clinics and linked to EHRs. Linking survey and EHR data can enhance public health surveillance by validating self-reported data, completing gaps in patient data, and extending sample sizes obtained through current methods. This approach will require promoting and sustaining patient involvement.


Assuntos
Registros Eletrônicos de Saúde , Inquéritos Epidemiológicos/métodos , Armazenamento e Recuperação da Informação/métodos , Registro Médico Coordenado , Adulto , Idoso , Chicago , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Participação do Paciente , Vigilância da População/métodos , Autorrelato , Fatores Socioeconômicos , Adulto Jovem
4.
PLoS Med ; 13(7): e1002074, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27403739

RESUMO

BACKGROUND: In 2015, the United States Preventive Services Task Force (USPSTF) recommended targeted screening for prediabetes and diabetes (dysglycemia) in adults who are aged 40 to 70 y old and overweight or obese. Given increasing prevalence of dysglycemia at younger ages and lower body weight, particularly among racial/ethnic minorities, we sought to determine whether the current screening criteria may fail to identify some high-risk population subgroups. METHODS AND FINDINGS: We investigated the performance of the 2015 USPSTF screening recommendation in detecting dysglycemia among US community health center patients. A retrospective analysis of electronic health record (EHR) data from 50,515 adult primary care patients was conducted. Longitudinal EHR data were collected in six health centers in the Midwest and Southwest. Patients with a first office visit between 2008 and 2010 were identified and followed for up to 3 y through 2013. We excluded patients who had dysglycemia at baseline and those with fewer than two office visits during the follow-up period. The exposure of interest was eligibility for screening according to the 2015 USPSTF criteria. The primary outcome was development of dysglycemia during follow-up, determined by: (1) laboratory results (fasting/2-h postload/random glucose ≥ 100/140/200 mg/dL [5.55/7.77/11.10 mmol/L] or hemoglobin A1C ≥ 5.7% [39 mmol/mol]); (2) diagnosis codes for prediabetes or type 2 diabetes; or (3) antidiabetic medication order. At baseline, 18,846 (37.3%) participants were aged ≥40 y, 33,537 (66.4%) were overweight or obese, and 39,061 (77.3%) were racial/ethnic minorities (34.6% Black, 33.9% Hispanic/Latino, and 8.7% Other). Overall, 29,946 (59.3%) patients had a glycemic test within 3 y of follow-up, and 8,478 of them developed dysglycemia. Only 12,679 (25.1%) patients were eligible for screening according to the 2015 USPSTF criteria, which demonstrated the following sensitivity and specificity (95% CI): 45.0% (43.9%-46.1%) and 71.9% (71.3%-72.5%), respectively. Racial/ethnic minorities were significantly less likely to be eligible for screening yet had higher odds of developing dysglycemia than whites (odds ratio [95% CI]: Blacks 1.24 [1.09-1.40]; Hispanics 1.46 [1.30-1.64]; and Other 1.33 [1.16-1.54]). In addition, the screening criteria had lower sensitivity in all racial/ethnic minority groups compared to whites. Limitations of this study include the ascertainment of dysglycemia only among patients with available test results and findings that may not be generalizable at the population level. CONCLUSIONS: Targeted diabetes screening based on new USPSTF criteria may detect approximately half of adult community health center patients with undiagnosed dysglycemia and proportionately fewer racial/ethnic minorities than whites. Future research is needed to estimate the performance of these screening criteria in population-based samples.


Assuntos
Centros Comunitários de Saúde/estatística & dados numéricos , Estado Pré-Diabético/diagnóstico , Adulto , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/prevenção & controle , Feminino , Humanos , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Grupos Raciais/estatística & dados numéricos , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
5.
Cancer Causes Control ; 27(7): 881-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27228991

RESUMO

PURPOSE: Fecal occult blood testing (FOBT) is a pragmatic screening option for many community health centers (CHCs), but FOBT screening programs will not reduce mortality if patients with positive results do not undergo diagnostic colonoscopy (DC). This study was conducted to investigate DC completion among CHC patients. METHODS: This retrospective cohort study used data from three CHCs in the Midwest and Southwest. The primary study outcome was DC completion within 6 months of positive FOBT among adults age 50-75. Patient data was collected using automated electronic queries. Manual chart reviews were conducted if queries produced no evidence of DC. Poisson regression models described adjusted relative risks (RRs) of DC completion. RESULTS: The study included 308 patients; 63.3 % were female, 48.7 % were Spanish speakers and 35.7 % were uninsured. Based on combined query and chart review findings, 51.5 % completed DC. Spanish speakers were more likely than English speakers to complete DC [RR 1.19; 95 % confidence interval (CI) 1.04-1.36; P = 0.009], and DC completion was lower among patients with 0 visits than those with 1-2 visits (RR 2.81; 95% CI 1.83-4.33; P < 0.001) or ≥3 visits (RR 3.06; 95% CI 1.57-5.95; P = 0.001). CONCLUSIONS: DC completion was low overall, which raises concerns about whether FOBT can reduce CRC mortality in practice. Further research is needed to understand whether CHC navigator programs can achieve very high DC rates. If organizations use FOBT as their primary CRC screening approach and a substantial number of patients receive positive results, both screening rates and DC rates should be measured.


Assuntos
Colonoscopia , Neoplasias Colorretais/diagnóstico , Detecção Precoce de Câncer/métodos , Sangue Oculto , Idoso , Centros Comunitários de Saúde , Feminino , Hispânico ou Latino , Humanos , Masculino , Programas de Rastreamento/métodos , Pessoas sem Cobertura de Seguro de Saúde , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Retrospectivos , Estados Unidos/epidemiologia
6.
Prenat Diagn ; 34(12): 1161-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24996053

RESUMO

OBJECTIVE: Although prenatal/preconception carrier screening recommendations for individuals of Ashkenazi Jewish descent (AJ) were published by American College of Medical Genetics and Genomics (2008) and American College of Obstetrics and Gynecology (2009), scientific advances have led to widely varied screening panels. Mutation carrier frequencies are sometimes based on small, homogeneous AJ populations. This study sought to update the state of AJ screening for the obstetrician by assessing laboratory screening panel compositions as well as assessing literature and laboratory carrier frequencies for common AJ mutations. METHODS: A literature review (1991-2013) was performed for AJ disease carrier frequencies. AJ screening data from six screening laboratories were collected. AJ panel composition was compared across 16 commercial and academic laboratories. RESULTS: Overall literature and laboratory carrier frequencies of AJ mutations were similar, although the Walker-Warburg syndrome laboratory carrier frequency was almost twice that in the literature. Laboratory AJ disease panel composition varied widely, from 8 to 25 diseases. CONCLUSIONS: Current AJ panels vary widely by laboratory, resulting in disparate levels of screening. Consideration of an updated professional standard for prenatal/preconception AJ screening based on carrier frequency rates, level of disease burden, availability of screening, and cost of technology may be useful in providing equitable and appropriate care for those planning a pregnancy.


Assuntos
Triagem de Portadores Genéticos , Doenças Genéticas Inatas/etnologia , Testes Genéticos/estatística & dados numéricos , Judeus/genética , Frequência do Gene , Humanos
7.
Infect Control Hosp Epidemiol ; 45(2): 237-240, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37702088

RESUMO

Infection prevention program leaders report frequent use of criteria to distinguish recently recovered coronavirus disease 2019 (COVID-19) cases from actively infectious cases when incidentally positive asymptomatic patients were identified on routine severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. Guidance on appropriate interpretation of high-sensitivity molecular tests can prevent harm from unnecessary precautions that delay admission and impede medical care.


Assuntos
COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/prevenção & controle , SARS-CoV-2 , Teste para COVID-19
8.
Infect Control Hosp Epidemiol ; : 1-4, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38440877

RESUMO

We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020-2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates (P < .001) and a 52% lesser rise in resident case-rates (P < .001) versus control.

9.
Org Biomol Chem ; 11(1): 69-77, 2013 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-23064223

RESUMO

The use of the copper(I)-assisted azide-alkyne cycloaddition (CuAAC, or "click" reaction) as a method of ß-hairpin stabilization was investigated at several different positions to determine the impact on hairpin structure and function, including hydrogen bonded sites, non-hydrogen bonded sites, and at the peptide termini. The role of the turn sequence in the peptide and the chain length of the azide were also investigated. It was determined that the CuAAC reaction was a suitable method for locking in ß-hairpin structure in peptides possessing either the type I' turn, VNGO and the type II' turn, VpGO. Moreover, all cyclic variants exhibited improved thermal stability and resistance to proteolysis as compared to the non-cyclic peptides, regardless of the position in the strand. Additionally, the function of the CuAAC cyclized peptides was not altered as exhibited by similar binding affinities for ATP as the WKWK peptide. These studies provide a comprehensive investigation of CuAAC cyclization of ß-hairpin peptides, which could further be applied to the inhibition of protein-protein and protein-nucleic acid interactions.


Assuntos
Alcinos/química , Azidas/química , Peptídeos/química , Química Click , Cobre/química , Ciclização , Ligação de Hidrogênio , Conformação Molecular , Simulação de Dinâmica Molecular , Estabilidade Proteica , Temperatura
10.
F S Rep ; 4(4): 384-389, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38204949

RESUMO

Objective: To describe the clinical experience of managing expanded carrier screening (ECS) results in sperm donor applicants at a sperm bank in the United States, including considerations around suitability determination and appropriate education of prospective donors and recipients. Design: A retrospective review of donor genetic screening records from July 2017 to December 2021. Setting: A U.S.-based sperm bank. Patients: Donor applicants at a sperm bank. Intervention: Not applicable. Main Outcome Measures: To examine the rate of potentially significant health risks on the basis of ECS results to inform donor management and donor/recipient counseling considerations. Results: Nearly 2% of donor applicants were identified as having potentially significant health risks on the basis of their ECS results, and most individuals had no clinical manifestations related to these findings. Conclusion: There are unique challenges related to ECS in third-party reproduction for gamete providers, recipients, and their healthcare providers. A collaborative, multidisciplinary approach is necessary to help mitigate risks to donor offspring and maximize patient experience. Informed consent and access to a trained genetics professional are paramount when facilitating ECS on donor applicants and disseminating results to recipients.

11.
Ticks Tick Borne Dis ; 13(4): 101962, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35525214

RESUMO

Ticks are hematophagous ectoparasites that transmit a wide range of pathogens. The lone star tick, Amblyomma americanum, is one of the most widely distributed ticks in the Midwest and Eastern United States. Lone star ticks, as other three-host ixodid ticks, can survive in harsh environments for extended periods without a blood meal. Physiological mechanisms that allow them to survive during hot and dry seasons include thermal tolerance and water homeostasis. Dermal fluid secretions have been described in metastriate ticks including A. americanum. We hypothesized that tick dermal secretion in the unfed tick plays a role in thermoregulation, as described in other hematophagous arthropods during blood feeding. In this study, we found that physical contact with a heat probe at 45 °C or high environmental temperature at ∼50 °C can trigger dermal secretion in A. americanum and other metastriate ticks in the off-host period. We demonstrated that dermal secretion plays a role in evaporative cooling when ticks are exposed to high temperatures. We find that type II dermal glands, having paired two cells and forming large glandular structures, are the source of dermal secretion. The secretion was triggered by an injection of serotonin, and the serotonin-mediated secretion was suppressed by a pretreatment with ouabain, a Na/K-ATPase blocker, implying that the secretion is controlled by serotonin and the downstream Na/K-ATPase.


Assuntos
Ixodidae , Carrapatos , Adenosina Trifosfatases , Amblyomma , Animais , Regulação da Temperatura Corporal , Ixodidae/fisiologia , Serotonina , Estados Unidos
12.
Biochemistry ; 50(13): 2575-84, 2011 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-21332166

RESUMO

A ß-sheet miniprotein based on the FBP11 WW1 domain sequence has been redesigned for the molecular recognition of ssDNA. A previous report showed that a ß-hairpin peptide dimer, (WKWK)(2), binds ssDNA with low micromolar affinity but with little selectivity over duplex DNA. This report extends those studies to a three-stranded ß-sheet miniprotein designed to mimic the OB-fold. The new peptide binds ssDNA with low micromolar affinity and shows about 10-fold selectivity for ssDNA over duplex DNA. The redesigned peptide no longer binds its native ligand, the polyproline helix, confirming that the peptide has been redesigned for the function of binding ssDNA. Structural studies provide evidence that this peptide consists of a well-structured ß-hairpin made of strands 2 and 3 with a less structured first strand that provides affinity for ssDNA but does not improve the stability of the full peptide. These studies provide insight into protein-DNA interactions as well as a novel example of protein redesign.


Assuntos
Proteínas de Transporte/química , DNA de Cadeia Simples/metabolismo , Proteínas de Ligação a DNA/metabolismo , Fragmentos de Peptídeos/metabolismo , Engenharia de Proteínas , Domínios e Motivos de Interação entre Proteínas , Proteínas de Transporte/genética , Dicroísmo Circular , Proteínas de Ligação a DNA/química , Dimerização , Polarização de Fluorescência , Humanos , Cinética , Ligantes , Proteínas Mutantes/química , Proteínas Mutantes/metabolismo , Ressonância Magnética Nuclear Biomolecular , Fragmentos de Peptídeos/química , Peptídeos/metabolismo , Desnaturação Proteica , Redobramento de Proteína , Estabilidade Proteica , Temperatura
13.
JPEN J Parenter Enteral Nutr ; 44(5): 831-836, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-31621088

RESUMO

BACKGROUND: Minimal information is available to validate measurement of respiratory muscle strength (RMS) in the clinical setting. The purpose of this study was to determine the correlation between maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and sniff nasal inspiratory pressure (SNIP) with handgrip strength (HGS) and cross sectional muscle area obtained via diagnostic abdominal computed tomography (CT). MATERIALS AND METHODS: Measures of MIP, MEP, SNIP, and HGS were obtained from individuals that participated in a previously published study; individuals who had an abdominal CT completed with (±)7 days of obtaining RMS measures were included. Both RMS and HGS were measured within 48-72 hours of admission; for RMS, the highest absolute (cm H2 O) and percent predicted values were recorded, and the average of 3 HGS measurements (kg) was documented. Cross-sectional muscle area (cm2 ) at the third lumbar region was recorded. Spearman's correlation coefficient was used to assess the relationship between variables. RESULTS: A total of 35 participants were included. HGS was correlated to absolute MIP (rs = 0.62, rs = 0.61), MEP (rs = 0.74, rs = 0.73), and SNIP (rs = 0.58, rs = 0.54) for males and females, respectively. Crosss-sectional muscle area was correlated with absolute MIP (rs = 0.66), MEP (rs = 0.58), and SNIP (rs = 0.783) for men and absolute SNIP (rs = 0.56) among women. CONCLUSION: Measures of RMS represent a promising assessment of muscle mass and function among hospitalized patients.


Assuntos
Força Muscular , Músculos Respiratórios , Estudos Transversais , Feminino , Força da Mão , Humanos , Masculino , Pressões Respiratórias Máximas
14.
Int J Radiat Oncol Biol Phys ; 71(4): 1028-33, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18280056

RESUMO

PURPOSE: To report prostate-specific antigen (PSA) relapse-free survival and distant metastases-free survival (DMFS) outcomes for patients with clinically localized prostate cancer treated with high-dose conformal radiotherapy. METHODS AND MATERIALS: Between 1988 and 2004, a total of 2,047 patients with clinically localized prostate cancer were treated with three-dimensional conformal radiotherapy or intensity-modulated radiotherapy. Prescribed dose levels ranged from 66-86.4 Gy. Median follow-up was 6.6 years (range, 3-18 years). RESULTS: Although no differences were noted among low-risk patients for the various dose groups, significant improvements were observed with higher doses for patients with intermediate- and high-risk features. In patients with intermediate-risk features, multivariate analysis showed that radiation dose was an important predictor for improved PSA relapse-free survival (p < 0.0001) and improved DMFS (p = 0.04). In patients with high-risk features, multivariate analysis showed that the following variables predict for improved PSA relapse-free survival: dose (p < 0.0001); age (p = 0.0005), and neoadjuvant-concurrent androgen deprivation therapy (ADT; p = 0.01). In this risk group, only higher radiation dose was an important predictor for improved DMFS (p = 0.04). CONCLUSIONS: High radiation dose levels were associated with improved biochemical tumor control and decreased risk of distant metastases. For high-risk patients, despite the delivery of high radiation dose levels, the use of ADT conferred an additional benefit for improved tumor control outcomes. We observed a benefit for ADT in high-risk patients who received higher doses.


Assuntos
Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/prevenção & controle , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/terapia , Radioterapia/estatística & dados numéricos , Medição de Risco/métodos , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Intervalo Livre de Doença , Fracionamento da Dose de Radiação , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , New York/epidemiologia , Prevalência , Prognóstico , Fatores de Risco , Resultado do Tratamento
15.
Brachytherapy ; 7(1): 1-6, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18299108

RESUMO

PURPOSE: To report the acute and late treatment-related toxicities of combined permanent interstitial (125)I implantation delivered via real-time intraoperative planning and supplemental intensity-modulated radiotherapy (IMRT) for patients with clinically localized prostate cancer. METHODS AND MATERIALS: One hundred twenty-seven patients were treated with a combined modality (CM) regimen consisting of (125)I implantation (110Gy) using a transrectal ultrasound-guided approach followed 2 months later by 50.4Gy of IMRT directed to the prostate and seminal vesicles. Late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events toxicity scale. The acute and late toxicities were compared to a contemporaneously treated cohort of 216 patients treated with (125)I alone to a prescribed dose of 144Gy. RESULTS: The incidence of Grade 2 acute rectal and urinary side effects was 1% and 10%, respectively, and 2 patients developed Grade 3 acute urinary toxicities. The 4-year incidence of late Grade 2 gastrointestinal toxicity was 9%, and no Grade 3 or 4 complications have been observed. The 4-year incidence of late Grade 2 gastrourinary toxicities was 15% and 1 patient developed a Grade 3 urethral stricture, which was corrected with urethral dilatation. The percentage of patients who experienced resolution of late rectal and urinary symptoms was 92% and 65%, respectively. Multivariate analysis revealed that in addition to higher baseline International Prostate Symptom Score, those patients treated with implant alone compared to CM were more likely to experience Grade 2 acute urinary symptoms. Increased Grade 2 late rectal toxicities were noted for CM patients (9% vs. 1%; p=0.001) as well as a significant increase for late Grade 2 urinary toxicities (15% vs. 9%; p=0.004). CONCLUSIONS: Adherence to dose constraints with combination real-time brachytherapy using real-time intraoperative planning and IMRT is associated with a low incidence of acute and late toxicities. Acute urinary side effects were significantly less common for CM patients compared to those treated with implantation alone. Late Grade 2 rectal and urinary toxicities were more common for patients treated with CM compared to implant alone.


Assuntos
Adenocarcinoma/radioterapia , Braquiterapia/métodos , Neoplasias da Próstata/radioterapia , Radioterapia Conformacional/métodos , Idoso , Braquiterapia/efeitos adversos , Terapia Combinada/métodos , Relação Dose-Resposta à Radiação , Seguimentos , Trato Gastrointestinal/efeitos da radiação , Humanos , Radioisótopos do Iodo , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Lesões por Radiação/classificação , Dosagem Radioterapêutica
17.
Behav Brain Res ; 292: 500-7, 2015 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-26151286

RESUMO

Xenopsin (XPN), an extract from frog skin, is comprised of 80 amino acids and exerts effects on the mammalian digestive tract. The purpose of the study presented here was to determine if XPN would affect food intake using chicks as models. Chicks which had been fasted for 180 min did not change food or water intake after central injection of XPN. However, ab libitum fed chicks which received 1 and 3 nmol central XPN increased food intake while water intake was not affected. When the dose was increased to 9 nmol chicks did not increase food intake but their water intake was reduced suggesting malaise. Chicks injected with XPN had increased c-Fos immunoreactivity in the lateral hypothalamus, but other hypothalamic appetite-associated nuclei were not affected. When XPN was directly injected into the lateral hypothalamus food intake was increased, suggesting a primary site of action. When the expression of appetite-associated neuropeptide mRNA was quantified chicks injected with XPN had increased proopiomelanocortin mRNA. Lastly, a comprehensive behavior analysis was performed and while XPN injected chicks had an increase in the number of feeding pecks, jumping, preening, deep rest and sitting were all decreased. Thus, we conclude that exogenous XPN functions as an orexigenic factor in chicks and its effects are mediated by the lateral hypothalamus.


Assuntos
Estimulantes do Apetite/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/metabolismo , Peptídeos/administração & dosagem , Proteínas de Xenopus/administração & dosagem , Animais , Comportamento Animal/efeitos dos fármacos , Galinhas , Ingestão de Líquidos/efeitos dos fármacos , Feminino , Hipotálamo/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Pró-Opiomelanocortina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , RNA Mensageiro/metabolismo
18.
Prev Med Rep ; 2: 886-91, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26844165

RESUMO

OBJECTIVE: Colorectal cancer (CRC) screening rates remain lower among some racial/ethnic groups and individuals with low income or educational attainment who are often cared for within community health centers (CHCs). We surveyed clinicians in a network of CHCs to understand their attitudes, practice patterns, and perceived barriers to CRC screening. METHODS: A clinician survey was conducted in 2013 within the Community Health Applied Research Network (CHARN). RESULTS: 180 clinicians completed the survey (47.9% response rate). Participants had an average of 11.5 (SD: 9.8) years in practice, 62% were female, and 57% were physicians. The majority of respondents somewhat agreed (30.2%) or strongly agreed (57.5%) that colonoscopy was the best screening test. However, only 15.8% of respondents strongly agreed and 32.2% somewhat agreed that colonoscopy was readily available for their patients. Fecal immunochemical testing (FIT), a type of fecal occult blood test (FOBT), was viewed less favorably; 24.6% rated FIT as very effective. CONCLUSIONS: Although there are no data showing that screening colonoscopy is superior to FIT, CHC clinicians believe colonoscopy is the best CRC screening test for their patients, despite the high prevalence of financial barriers to colonoscopy. These attitudes could be due to lack of knowledge about the evidence supporting long-term benefits of fecal occult blood testing (FOBT), lack of awareness about the improved test characteristics of FIT compared to older guaiac-based FOBT, or the absence of systems to ensure adherence to regular FOBT screening. Interventions to improve CRC screening at CHCs must address clinicians' negative attitudes towards FIT.

19.
Cell Biochem Biophys ; 67(1): 75-89, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23686610

RESUMO

The ubiquitin-proteasome system (UPS) is the primary pathway responsible for the recognition and degradation of misfolded, damaged, or tightly regulated proteins in addition to performing essential roles in DNA repair, cell cycle regulation, cell migration, and the immune response. While traditional biochemical techniques have proven useful in the identification of key proteins involved in this pathway, the implementation of novel reporters responsible for measuring enzymatic activity of the UPS has provided valuable insight into the effectiveness of therapeutics and role of the UPS in various human diseases such as multiple myeloma and Huntington's disease. These reporters, usually consisting of a recognition sequence fused to an analytical handle, are designed to specifically evaluate enzymatic activity of certain members of the UPS including the proteasome, E3 ubiquitin ligases, and deubiquitinating enzymes. This review highlights the more commonly used reporters employed in a variety of scenarios ranging from high-throughput screening of novel inhibitors to single cell microscopy techniques measuring E3 ligase or proteasome activity. Finally, a recent study is presented highlighting the development of a novel degron-based substrate designed to overcome the limitations of current reporting techniques in measuring E3 ligase and proteasome activity in patient samples.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina/metabolismo , Transferência Ressonante de Energia de Fluorescência , Proteínas de Fluorescência Verde/metabolismo , Humanos , Microscopia Confocal , Análise de Célula Única , Especificidade por Substrato , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação , beta Catenina/metabolismo
20.
PLoS One ; 8(10): e78082, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24205101

RESUMO

The ubiquitin proteasome system (UPS) is the primary pathway responsible for the recognition and degradation of misfolded, damaged, or tightly regulated proteins. The conjugation of a polyubiquitin chain, or polyubiquitination, to a target protein requires an increasingly diverse cascade of enzymes culminating with the E3 ubiquitin ligases. Protein recognition by an E3 ligase occurs through a specific sequence of amino acids, termed a degradation sequence or degron. Recently, degrons have been incorporated into novel reporters to monitor proteasome activity; however only a limited few degrons have successfully been incorporated into such reporters. The goal of this work was to evaluate the ubiquitination kinetics of a small library of portable degrons that could eventually be incorporated into novel single cell reporters to assess proteasome activity. After an intensive literary search, eight degrons were identified from proteins recognized by a variety of E3 ubiquitin ligases and incorporated into a four component degron-based substrate to comparatively calculate ubiquitination kinetics. The mechanism of placement of multiple ubiquitins on the different degron-based substrates was assessed by comparing the data to computational models incorporating first order reaction kinetics using either multi-monoubiquitination or polyubiquitination of the degron-based substrates. A subset of three degrons was further characterized to determine the importance of the location and proximity of the ubiquitination site lysine with respect to the degron. Ultimately, this work identified three candidate portable degrons that exhibit a higher rate of ubiquitination compared to peptidase-dependent degradation, a desired trait for a proteasomal targeting motif.


Assuntos
Complexo de Endopeptidases do Proteassoma/metabolismo , Células HL-60 , Células HeLa , Humanos , Cinética , Células U937 , Ubiquitinação/genética , Ubiquitinação/fisiologia
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