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1.
Vaccine ; 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38853035

RESUMO

PURPOSE: The current study sought to determine if the release of COVID-19 vaccines influenced Alabama mothers' attitudes and behaviors regarding HPV vaccination of their adolescent children. METHODS: A social media survey was conducted August - September 2022 among mothers of adolescents ages 9-18, who self-identified as Alabama residents and their child(ren)'s primary medical decision maker. The survey assessed demographics, vaccine knowledge and opinions, vaccination history, influences on vaccination decisions, and how COVID-19 vaccine release affected vaccine opinions. Univariable and multivariable analyses were conducted. RESULTS: Of 241 responses, most participants were white (82.0 %, n = 196), non-Hispanic (96.6 %, n = 230), and privately insured (64.5 %, n = 151), with annual household incomes ≥$61,000 (45.4 %, n = 103). The majority (60.8 %) reported that their child either had or planned to receive the HPV vaccine. The release of COVID-19 vaccines did not change the majority of parental opinions towards HPV, with 78.5 % (n = 161) reporting no change. Among those who experienced a change, 25 % (n = 5) reported an increased likelihood of having their child vaccinated for HPV and 75 % (n = 15) reported a decrease in likelihood. Moderate and high HPV knowledge scores were associated in multivariable analysis with increased likelihood of having their child vaccinated for HPV ("moderate" knowledge AOR: 12.4, 95 % CI: 1.98-78.1; "high" knowledge AOR: 12.8, 95 % CI: 2.00-82.1). Positive HPV opinion scores in the univariable analysis similarly showed increased odds (AOR = 1.5). CONCLUSIONS: These findings indicate that, in this population, COVID-19 vaccine release did not significantly impact subsequent HPV vaccination decision making. Parental perceptions regarding vaccination are critical to informing future interventions.

2.
Plant Mol Biol ; 114(3): 65, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816532

RESUMO

Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3). Here we show that AN3-deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a -deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro. Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Divisão Celular , Telomerase , Telômero , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Telômero/genética , Telômero/metabolismo , Divisão Celular/genética , Telomerase/genética , Telomerase/metabolismo , Homeostase do Telômero/genética , Regulação da Expressão Gênica de Plantas , Mutação , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proliferação de Células/genética , Meristema/genética , Meristema/metabolismo
3.
Res Sq ; 2023 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-37961382

RESUMO

Telomeres are conserved chromosomal structures necessary for continued cell division and proliferation. In addition to the classical telomerase pathway, multiple other genes including those involved in ribosome metabolism and chromatin modification contribute to telomere length maintenance. We previously reported that Arabidopsis thaliana ribosome biogenesis genes OLI2/NOP2A, OLI5/RPL5A and OLI7/RPL5B have critical roles in telomere length regulation. These three OLIGOCELLULA genes were also shown to function in cell proliferation and expansion control and to genetically interact with the transcriptional co-activator ANGUSTIFOLIA3 (AN3). Here we show that AN3-deficient plants progressively lose telomeric DNA in early homozygous mutant generations, but ultimately establish a new shorter telomere length setpoint by the fifth mutant generation with a telomere length similar to oli2/nop2a - deficient plants. Analysis of double an3 oli2 mutants indicates that the two genes are epistatic for telomere length control. Telomere shortening in an3 and oli mutants is not caused by telomerase inhibition; wild type levels of telomerase activity are detected in all analyzed mutants in vitro. Late generations of an3 and oli mutants are prone to stem cell damage in the root apical meristem, implying that genes regulating telomere length may have conserved functional roles in stem cell maintenance mechanisms. Multiple instances of anaphase fusions in late generations of oli5 and oli7 mutants were observed, highlighting an unexpected effect of ribosome biogenesis factors on chromosome integrity. Overall, our data implicate AN3 transcription coactivator and OLIGOCELLULA proteins in the establishment of telomere length set point in plants and further suggest that multiple regulators with pleiotropic functions can connect telomere biology with cell proliferation and cell expansion pathways.

4.
Nat Commun ; 14(1): 7854, 2023 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-38030615

RESUMO

Spaceflight-induced changes in astronaut telomeres have garnered significant attention in recent years. While plants represent an essential component of future long-duration space travel, the impacts of spaceflight on plant telomeres and telomerase have not been examined. Here we report on the telomere dynamics of Arabidopsis thaliana grown aboard the International Space Station. We observe no changes in telomere length in space-flown Arabidopsis seedlings, despite a dramatic increase in telomerase activity (up to 150-fold in roots), as well as elevated genome oxidation. Ground-based follow up studies provide further evidence that telomerase is induced by different environmental stressors, but its activity is uncoupled from telomere length. Supporting this conclusion, genetically engineered super-telomerase lines with enhanced telomerase activity maintain wildtype telomere length. Finally, genome oxidation is inversely correlated with telomerase activity levels. We propose a redox protective capacity for Arabidopsis telomerase that may promote survivability in harsh environments.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Telomerase , Homeostase do Telômero , Arabidopsis/metabolismo , Telomerase/genética , Telomerase/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteínas de Ligação a Telômeros/metabolismo , Telômero/genética , Telômero/metabolismo , Plantas/metabolismo
5.
JCO Oncol Pract ; 18(12): e1943-e1952, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36306496

RESUMO

PURPOSE: Despite evidence of clinical benefits, widespread implementation of remote symptom monitoring has been limited. We describe a process of adapting a remote symptom monitoring intervention developed in a research setting to a real-world clinical setting at two cancer centers. METHODS: This formative evaluation assessed core components and adaptations to improve acceptability and fit of remote symptom monitoring using Stirman's Framework for Modifications and Adaptations. Implementation outcomes were evaluated in pilot studies at the two cancer centers testing technology (phase I) and workflow (phase II and III) using electronic health data; qualitative evaluation with semistructured interviews of clinical team members; and capture of field notes from clinical teams and administrators regarding barriers and recommended adaptations for future implementation. RESULTS: Core components of remote symptom monitoring included electronic delivery of surveys with actionable symptoms, patient education on the intervention, a system to monitor survey compliance in real time, the capacity to generate alerts, training nurses to manage alerts, and identification of personnel responsible for managing symptoms. In the pilot studies, while most patients completed > 50% of expected surveys, adaptations were identified to address barriers related to workflow challenges, patient and clinician access to technology, digital health literacy, survey fatigue, alert fatigue, and data visibility. CONCLUSION: Using an implementation science approach, we facilitated adaptation of remote symptom monitoring interventions from the research setting to clinical practice and identified key areas to promote effective uptake and sustainability.


Assuntos
Medidas de Resultados Relatados pelo Paciente , Humanos , Inquéritos e Questionários , Projetos Piloto
6.
Int J Mol Sci ; 23(9)2022 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-35563379

RESUMO

Chemical modifications in DNA impact gene regulation and chromatin structure. DNA oxidation, for example, alters gene expression, DNA synthesis and cell cycle progression. Modification of telomeric DNA by oxidation is emerging as a marker of genotoxic damage and is associated with reduced genome integrity and changes in telomere length and telomerase activity. 8-oxoguanine (8-oxoG) is the most studied and common outcome of oxidative damage in DNA. The G-rich nature of telomeric DNA is proposed to make it a hotspot for oxidation, but because telomeres make up only a tiny fraction of the genome, it has been difficult to directly test this hypothesis by studying dynamic DNA modifications specific to this region in vivo. Here, we present a new, robust method to differentially enrich telomeric DNA in solution, coupled with downstream methods for determination of chemical modification. Specifically, we measure 8-oxoG in Arabidopsis thaliana telomeres under normal and oxidative stress conditions. We show that telomere length is unchanged in response to oxidative stress in three different wild-type accessions. Furthermore, we report that while telomeric DNA comprises only 0.02-0.07% of the total genome, telomeres contribute between 0.2 and 15% of the total 8-oxoG. That is, plant telomeres accumulate 8-oxoG at levels approximately 100-fold higher than the rest of the genome under standard growth conditions. Moreover, they are the primary targets of further damage upon oxidative stress. Interestingly, the accumulation of 8-oxoG in the chromosome body seems to be inversely proportional to telomere length. These findings support the hypothesis that telomeres are hotspots of 8-oxoG and may function as sentinels of oxidative stress in plants.


Assuntos
Telomerase , Telômero , DNA/química , Dano ao DNA , Guanina/análogos & derivados , Guanina/química , Telomerase/genética , Telomerase/metabolismo , Telômero/genética , Telômero/metabolismo
7.
Int J Gynecol Cancer ; 31(11): 1403-1407, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34088749

RESUMO

OBJECTIVE: To describe the participation of minority women in clinical trials using immunologic agents for breast and gynecologic cancers. METHODS: A retrospective review of completed clinical trials involving immunotherapy for breast and gynecologic cancers was performed. Completed trials were examined for data on race, tumor type, and start year. Minority enrollment was stratified by tumor site. Based on Center for Disease Control and Prevention age-adjusted incidence for race, expected and observed ratios of racial participation were calculated and compared using Χ2 testing, p≤0.05. RESULTS: A total of 53 completed immunotherapy clinical trials involving 8820 patients were reviewed. Breast cancer trials were most common (n=24) and involved the most patients (n=6248, 71%). Racial breakdown was provided in 41 studies (77%) for a total of 7201 patients. Race reporting was lowest in uterine (n=4, 67%) and cervical cancer trials (n=6, 67%), and highest in ovarian cancer trials (n=12, 86%). White patients comprised 70% (n=5022) of all the patients included. Only 5% of patients involved were black (n=339), and 83% of these patients (n=282) were enrolled in breast cancer trials. Observed enrollment of black women was 32-fold lower for ovarian, 19-fold lower for cervical, 15-fold lower for uterine, and 11-fold lower for breast cancer than expected. While all trials reported race between 2013 and 2015, no consistent trend was seen towards increasing race reporting or in enrollment of black patients over time. CONCLUSION: Racial disparities exist in clinical trials evaluating immunologic agents for breast and gynecologic cancers. Recruitment of black women is particularly low. In order to address inequity in outcomes for these cancers, it is crucial that significant attention be directed towards minority representation in immuno-oncologic clinical trials.


Assuntos
Neoplasias da Mama/etnologia , Ensaios Clínicos como Assunto/estatística & dados numéricos , Neoplasias dos Genitais Femininos/etnologia , Disparidades nos Níveis de Saúde , Negro ou Afro-Americano/estatística & dados numéricos , Neoplasias da Mama/imunologia , Feminino , Neoplasias dos Genitais Femininos/imunologia , Hispânico ou Latino/estatística & dados numéricos , Humanos , Imunoterapia , Seleção de Pacientes , Estudos Retrospectivos , População Branca/estatística & dados numéricos
8.
Plant Cell ; 33(4): 1118-1134, 2021 05 31.
Artigo em Inglês | MEDLINE | ID: mdl-33580702

RESUMO

Telomeres are highly repetitive DNA sequences found at the ends of chromosomes that protect the chromosomes from deterioration duringcell division. Here, using whole-genome re-sequencing and terminal restriction fragment assays, we found substantial natural intraspecific variation in telomere length in Arabidopsis thaliana, rice (Oryza sativa), and maize (Zea mays). Genome-wide association study (GWAS) mapping in A. thaliana identified 13 regions with GWAS-significant associations underlying telomere length variation, including a region that harbors the telomerase reverse transcriptase (TERT) gene. Population genomic analysis provided evidence for a selective sweep at the TERT region associated with longer telomeres. We found that telomere length is negatively correlated with flowering time variation not only in A. thaliana, but also in maize and rice, indicating a link between life-history traits and chromosome integrity. Our results point to several possible reasons for this correlation, including the possibility that longer telomeres may be more adaptive in plants that have faster developmental rates (and therefore flower earlier). Our work suggests that chromosomal structure itself might be an adaptive trait associated with plant life-history strategies.


Assuntos
Flores/fisiologia , Variação Genética , Fenômenos Fisiológicos Vegetais/genética , Telômero/genética , Arabidopsis/genética , Tamanho do Genoma , Genoma de Planta , Estudo de Associação Genômica Ampla , Oryza/genética , Seleção Genética , Sequências de Repetição em Tandem , Telomerase/genética , Fatores de Tempo , Zea mays/genética
9.
Hum Vaccin Immunother ; 17(4): 1033-1043, 2021 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-33325794

RESUMO

Human papillomavirus (HPV) remains the most common sexually transmitted infection (STI) in the U.S. despite widespread availability of a safe, effective vaccine. Although young adults are at greatest risk of HPV infection, extensive vaccine promotion and intervention efforts has been directed toward 11-12-year-olds. College students represent an ideal audience for HPV vaccine "catch-up;" however, research indicates inconsistent HPV vaccination rates within this demographic. An online survey assessing HPV and HPV vaccine knowledge and behaviors was distributed to all undergraduate college students at a large, public university in the Deep South region of the U.S. The primary outcome was receipt of HPV vaccination (binary response options of Yes/No). Logistic regression analyses were performed to determine predictors of HPV vaccination. Of the 1,725 who completed the survey, 47.0% reported having received at least one dose of HPV vaccine; overall series completion (series = 3 doses for this population) was 17.4%. The primary outcome was HPV initiation among college students, defined as having received at least one dose of the HPV vaccine. Results indicated substantial gaps in participants' knowledge of their vaccination status. Provider and parental recommendations as well as social influences were shown to significantly impact student vaccination status, emphasizing the importance of incorporating these elements in future interventions, potentially as multi-level strategies. Future college interventions should address HPV and vaccination knowledge and the importance of provider and parental recommendations.


Assuntos
Infecções por Papillomavirus , Vacinas contra Papillomavirus , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Papillomaviridae , Aceitação pelo Paciente de Cuidados de Saúde , Estudantes , Estados Unidos , Vacinação , Adulto Jovem
10.
Cancer Med ; 9(22): 8423-8431, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32955793

RESUMO

BACKGROUND: Burdens related to time spent receiving cancer care may be substantial for patients with incurable, life-limiting cancers such as metastatic breast cancer (MBC). Estimates of time spent on health care are needed to inform treatment-related decision-making. METHODS: Estimates of time spent receiving cancer-related health care in the initial 3 months of treatment for patients with MBC were calculated using the following data sources: (a) direct observations from a time-in-motion quality improvement evaluation (process mapping); (b) cross-sectional patient surveys; and (c) administrative claims. Average ambulatory, inpatient, and total health care time were calculated for specific treatments which differed by antineoplastic type and administration method, including fulvestrant (injection, hormonal), letrozole (oral, hormonal), capecitabine (oral, chemotherapy), and paclitaxel (infusion, chemotherapy). RESULTS: Average total time spent on health care ranged from 7% to 10% of all days included within the initial 3 months of treatment, depending on treatment. The greatest time contributions were time spent traveling for care and on inpatient services. Time with providers contributed modestly to total care time. Patients receiving infusion/injection treatments, compared with those receiving oral therapy, spent more time in ambulatory care. Health care time was higher for patients receiving chemotherapeutic agents compared to those receiving hormonal agents. CONCLUSION: Time spent traveling and receiving inpatient care represented a substantial burden to patients with MBC, with variation in time by treatment type and administration method.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/economia , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Idoso , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Estudos Transversais , Bases de Dados Factuais , Feminino , Estresse Financeiro/economia , Gastos em Saúde , Custos Hospitalares , Humanos , Pacientes Internados , Pessoa de Meia-Idade , Metástase Neoplásica , Serviço Hospitalar de Oncologia/economia , Estudos Prospectivos , Qualidade de Vida , Programa de SEER , Fatores de Tempo , Transporte de Pacientes/economia
11.
Autophagy ; 15(6): 941-959, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30734619

RESUMO

Macroautophagy is a process through which eukaryotic cells degrade large substrates including organelles, protein aggregates, and invading pathogens. Over 40 autophagy-related (ATG) genes have been identified through forward-genetic screens in yeast. Although homology-based analyses have identified conserved ATG genes in plants, only a few atg mutants have emerged from forward-genetic screens in Arabidopsis thaliana. We developed a screen that consistently recovers Arabidopsis atg mutations by exploiting mutants with defective LON2/At5g47040, a protease implicated in peroxisomal quality control. Arabidopsis lon2 mutants exhibit reduced responsiveness to the peroxisomally-metabolized auxin precursor indole-3-butyric acid (IBA), heightened degradation of several peroxisomal matrix proteins, and impaired processing of proteins harboring N-terminal peroxisomal targeting signals; these defects are ameliorated by preventing autophagy. We optimized a lon2 suppressor screen to expedite recovery of additional atg mutants. After screening mutagenized lon2-2 seedlings for restored IBA responsiveness, we evaluated stabilization and processing of peroxisomal proteins, levels of several ATG proteins, and levels of the selective autophagy receptor NBR1/At4g24690, which accumulates when autophagy is impaired. We recovered 21 alleles disrupting 6 ATG genes: ATG2/At3g19190, ATG3/At5g61500, ATG5/At5g17290, ATG7/At5g45900, ATG16/At5g50230, and ATG18a/At3g62770. Twenty alleles were novel, and 3 of the mutated genes lack T-DNA insertional alleles in publicly available repositories. We also demonstrate that an insertional atg11/At4g30790 allele incompletely suppresses lon2 defects. Finally, we show that NBR1 is not necessary for autophagy of lon2 peroxisomes and that NBR1 overexpression is not sufficient to trigger autophagy of seedling peroxisomes, indicating that Arabidopsis can use an NBR1-independent mechanism to target peroxisomes for autophagic degradation. Abbreviations: ATG: autophagy-related; ATI: ATG8-interacting protein; Col-0: Columbia-0; DSK2: dominant suppressor of KAR2; EMS: ethyl methanesulfonate; GFP: green fluorescent protein; IAA: indole-3-acetic acid; IBA: indole-3-butyric acid; ICL: isocitrate lyase; MLS: malate synthase; NBR1: Next to BRCA1 gene 1; PEX: peroxin; PMDH: peroxisomal malate dehydrogenase; PTS: peroxisomal targeting signal; thiolase: 3-ketoacyl-CoA thiolase; UBA: ubiquitin-associated; WT: wild type.


Assuntos
Proteases Dependentes de ATP/genética , Aminopeptidases/genética , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Proteínas Relacionadas à Autofagia/genética , Macroautofagia/genética , Proteases Dependentes de ATP/metabolismo , Alelos , Aminopeptidases/metabolismo , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/metabolismo , Proteínas de Transporte/genética , Indóis/farmacologia , Macroautofagia/efeitos dos fármacos , Mutação , Peroxissomos/efeitos dos fármacos , Peroxissomos/genética , Peroxissomos/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo
12.
J Cancer Educ ; 34(5): 1014-1023, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30054900

RESUMO

Human papillomavirus (HPV) causes over 39,000 cancers annually in the US. The HPV vaccine is safe and effective but underutilized to prevent cancer. In the US, only 37% of adolescents ages 13-17 have received the full vaccine series. Ineffective messages and misinformation about the vaccine have negatively impacted its uptake in the US. It was initially only approved for girls and early marketing focused on cervical cancer prevention and prevention of HPV as a sexually transmitted infection. Understanding effective messages and methods of dissemination is critical to address suboptimal vaccine uptake. Qualitative interviews were conducted with 34 participants to identify best practices for HPV vaccination messaging in SC. Participants included state leaders representing public health, medical associations, K-12 public schools, universities, insurers, and cancer advocacy organizations. Recommended HPV vaccine messages included focusing on cancer prevention rather than sexual transmission, routinizing the vaccine, and highlighting risks/costs of HPV. Targeting messages to specific demographics and utilizing multiple media platforms to disseminate consistent, scientifically accurate messages were recommended. Strategies such as appealing to parents' moral responsibility to protect their children against cancer and addressing the ubiquity of HPV and sharing growing evidence that HPV may be transmitted independent of sexual activity were also recommended. Suggested HPV vaccine messengers included trusted peers, medical professionals, and health associations. Culture-centered narratives to raise the voices of cancer survivors and parents were also recommended. This study provides an array of HPV vaccination messages and dissemination strategies for optimizing HPV vaccination rates.


Assuntos
Comunicação em Saúde , Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/administração & dosagem , Pais/educação , Aceitação pelo Paciente de Cuidados de Saúde , Vacinação/psicologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Narração , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/psicologia , Infecções por Papillomavirus/virologia , Pais/psicologia , Comportamento Sexual , Vacinação/estatística & dados numéricos , Adulto Jovem
13.
Papillomavirus Res ; 5: 21-31, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29248818

RESUMO

OBJECTIVE: The objective was to investigate how state level strategies in South Carolina could maximize HPV vaccine uptake. DESIGN: An environmental scan identified barriers, facilitators, and strategies for improving HPV vaccination in South Carolina. Interviews were conducted with state leaders from relevant organizations such as public health agencies, medical associations, K-12 schools, universities, insurers, and cancer advocacy organizations. A thematic content analysis design was used. Digital interview files were transcribed, a data dictionary was created and data were coded using the data dictionary. RESULTS: Thirty four interviews were conducted with state leaders. Barriers to HPV vaccination included lack of HPV awareness, lack of provider recommendation, HPV vaccine concerns, lack of access and practice-level barriers. Facilitators included momentum for improving HPV vaccination, school-entry Tdap requirement, pharmacy-based HPV vaccination, state immunization registry, HEDIS measures and HPV vaccine funding. Strategies for improving HPV vaccination fell into three categories: 1) addressing lack of awareness about the importance of HPV vaccination among the public and providers; 2) advocating for policy changes around HPV vaccine coverage, vaccine education, and pharmacy-based vaccination; and 3) coordination of efforts. DISCUSSION: A statewide environmental scan generated a blueprint for action to be used to improve HPV vaccination in the state.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Programas de Imunização/legislação & jurisprudência , Vacinas contra Papillomavirus/administração & dosagem , Aceitação pelo Paciente de Cuidados de Saúde , Cobertura Vacinal/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Pessoal de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Infecções por Papillomavirus/prevenção & controle , South Carolina/epidemiologia , Inquéritos e Questionários , Neoplasias do Colo do Útero/prevenção & controle , Neoplasias do Colo do Útero/virologia , Cobertura Vacinal/legislação & jurisprudência
14.
Int J Gynecol Pathol ; 36(6): 540-549, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28114190

RESUMO

African American (AA) females with endometrial carcinoma have a significantly worse prognosis with regard to disease-free survival and overall survival than their European American (EA) counterparts and this finding is true across all stages and grades. The presence of tumor-infiltrating lymphocytes (TILs) has been demonstrated to be of prognostic significance in a variety of malignancies, including endometrial cancers. This study aims to determine whether clinically significant differences in levels of CD8+ cytotoxic T lymphocytes, FoxP3+ regulatory T lymphocytes, and CD45RO+ memory T lymphocytes exist between races and to document the clinical impact of TILs. One hundred ten patients with endometrial adenocarcinoma, treated with hysterectomy from 2003 to 2011 were studied. Patients were selected to provide equal representation across type and grade for both EAs and AAs. Immunohistochemical stains were used to highlight CD8-positive, FoxP3-positive, and CD45RO-positive TILs at the endometrial-myometrial interface on slides from paraffin-embedded tissue. Patients with "high" or "low" levels of TILs were compared with respect to the race, tumor type, and survival. High levels of CD45RO+ TILs were associated with improved overall survival in EA women (hazard ratio, 0.32; 95% confidence interval, 0.11-0.92; P=0.034). Comparatively, AA women with high levels of CD45RO+ TILs received no survival benefit (hazard ratio, 0.96; 95% confidence interval, 0.35-2.64; P=0.94). High levels of CD8-positive or FoxP3-positive TILs, alone, had no impact on survival. EA patients with TILs containing high levels of CD45RO cells but low levels of CD8+ cells lost the survival benefit; however, limited numbers preclude significant conclusions from this observation. Neither tumor type nor race were predictive of the levels of TILs of any type. Further study with a larger sample size is required to determine the impact of TIL subtype combinations on survival.


Assuntos
Neoplasias do Endométrio/diagnóstico , Negro ou Afro-Americano , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfócitos T CD8-Positivos/patologia , Intervalo Livre de Doença , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Fatores de Transcrição Forkhead/metabolismo , Humanos , Antígenos Comuns de Leucócito/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Estados Unidos/etnologia , População Branca
15.
Biochim Biophys Acta ; 1863(5): 999-1005, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26348128

RESUMO

Peroxisomes are dynamic, vital organelles that sequester a variety of oxidative reactions and their toxic byproducts from the remainder of the cell. The oxidative nature of peroxisomal metabolism predisposes the organelle to self-inflicted damage, highlighting the need for a mechanism to dispose of damaged peroxisomes. In addition, the metabolic requirements of plant peroxisomes change during development, and obsolete peroxisomal proteins are degraded. Although pexophagy, the selective autophagy of peroxisomes, is an obvious mechanism for executing such degradation, pexophagy has only recently been described in plants. Several recent studies in the reference plant Arabidopsis thaliana implicate pexophagy in the turnover of peroxisomal proteins, both for quality control and during functional transitions of peroxisomal content. In this review, we describe our current understanding of the occurrence, roles, and mechanisms of pexophagy in plants.


Assuntos
Proteases Dependentes de ATP/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Autofagia/genética , Peroxissomos/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Proteases Dependentes de ATP/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Retículo Endoplasmático/química , Retículo Endoplasmático/metabolismo , Regulação da Expressão Gênica de Plantas , Oxirredução , Receptor 2 de Sinal de Orientação para Peroxissomos , Receptor 1 de Sinal de Orientação para Peroxissomos , Peroxissomos/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteólise , Receptores Citoplasmáticos e Nucleares/genética , Transdução de Sinais , Ubiquitinação
17.
Clin Ther ; 36(1): 38-45, 2014 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-24417784

RESUMO

OBJECTIVE: The goal of this study was to determine the prevalence of vaginitis and its association with high-risk human papillomavirus (HR HPV) in women undergoing cervical cancer screening in rural Tanzania. METHODS: For the purpose of cervical cancer screening, cytology and HR HPV polymerase chain reaction data were collected from 324 women aged between 30 and 60 years. Microscopy and gram stains were used to detect yeast and bacterial vaginosis. Cervical nucleic acid amplification test specimens were collected for the detection of Trichomonas vaginalis (TV), Chlamydia trachomatis, and Neisseria gonorrhoeae. RESULTS: The majority of women were married (320 of 324) and reported having a single sexual partner (270 of 324); the median age of participants was 41 years. HR HPV was detected in 42 participants. Forty-seven percent of women had vaginitis. Bacterial vaginosis was the most common infection (32.4%), followed by TV (10.4%), and yeast (6.8%). In multivariable logistic regression analysis, TV was associated with an increased risk of HR HPV (odds ratio, 4.2 [95% CI, 1.7-10.3]). Patients with TV were 6.5 times more likely to have HPV type 16 than patients negative for TV (50% vs 13.3%) (odds ratio, 6.5 [95% CI, 1.1-37]). CONCLUSIONS: Among rural Tanzanian women who presented for cervical cancer screening, Trichomonas vaginitis was significantly associated with HR HPV infection (specifically type 16).


Assuntos
Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Vaginite por Trichomonas/complicações , Trichomonas vaginalis/isolamento & purificação , Neoplasias do Colo do Útero/diagnóstico , Cervicite Uterina/epidemiologia , Adulto , Chlamydia trachomatis/isolamento & purificação , Coinfecção/epidemiologia , Coinfecção/parasitologia , Coinfecção/virologia , Detecção Precoce de Câncer/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , Papillomaviridae/classificação , Infecções por Papillomavirus/parasitologia , Infecções por Papillomavirus/virologia , Fatores de Risco , População Rural , Tanzânia/epidemiologia , Vaginite por Trichomonas/diagnóstico , Vaginite por Trichomonas/epidemiologia , Neoplasias do Colo do Útero/virologia , Cervicite Uterina/diagnóstico , Vaginite/diagnóstico , Vaginite/epidemiologia , Vaginite/microbiologia , Vaginite/virologia
18.
Autophagy ; 10(3): 518-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24413187

RESUMO

Peroxisomes are critical organelles housing various, often oxidative, reactions. Pexophagy, the process by which peroxisomes are selectively targeted for destruction via autophagy, is characterized in yeast and mammals but had not been reported in plants. In this article, we describe how the peroxisome-related aberrations of a mutant defective in the LON2 peroxisomal protease are suppressed when autophagy is prevented by mutating any of several key autophagy-related (ATG) genes. Our results reveal that plant peroxisomes can be degraded by selective autophagy and suggest that pexophagy is accelerated when the LON2 protease is disabled.


Assuntos
Proteases Dependentes de ATP/genética , Proteínas de Arabidopsis/genética , Arabidopsis/genética , Autofagia/fisiologia , Mutação/genética , Peroxissomos/genética , Autofagia/genética
19.
Plant Cell ; 25(10): 4085-100, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24179123

RESUMO

Peroxisomes house critical metabolic reactions that are essential for seedling development. As seedlings mature, metabolic requirements change, and peroxisomal contents are remodeled. The resident peroxisomal protease LON2 is positioned to degrade obsolete or damaged peroxisomal proteins, but data supporting such a role in plants have remained elusive. Arabidopsis thaliana lon2 mutants display defects in peroxisomal metabolism and matrix protein import but appear to degrade matrix proteins normally. To elucidate LON2 functions, we executed a forward-genetic screen for lon2 suppressors, which revealed multiple mutations in key autophagy genes. Disabling core autophagy-related gene (ATG) products prevents autophagy, a process through which cytosolic constituents, including organelles, can be targeted for vacuolar degradation. We found that atg2, atg3, and atg7 mutations suppressed lon2 defects in auxin metabolism and matrix protein processing and rescued the abnormally large size and small number of lon2 peroxisomes. Moreover, analysis of lon2 atg mutants uncovered an apparent role for LON2 in matrix protein turnover. Our data suggest that LON2 facilitates matrix protein degradation during peroxisome content remodeling, provide evidence for the existence of pexophagy in plants, and indicate that peroxisome destruction via autophagy is enhanced when LON2 is absent.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Autofagia/genética , Peroxissomos/metabolismo , Proteólise , Serina Proteases/metabolismo , Aminopeptidases/genética , Aminopeptidases/metabolismo , Arabidopsis/enzimologia , Proteínas de Arabidopsis/genética , Proteínas Relacionadas à Autofagia , Ácidos Indolacéticos/metabolismo , Mutação , Serina Proteases/genética
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