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1.
BMC Geriatr ; 24(1): 50, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212690

RESUMO

BACKGROUND: Multimorbidity is increasing among adults in the United States. Yet limited research has examined multimorbidity clusters in persons aged 50 years and older with and without a history of cancer. An increased understanding of multimorbidity clusters may improve the cancer survivorship experience for survivors with multimorbidity. METHODS: We identified 7580 adults aged 50 years and older with 2 or more diseases-including 811 adults with a history of primary breast, colorectal, cervical, prostate, or lung cancer-from the 2018 National Health Interview Survey. Exploratory factor analysis identified clusters of multimorbidity among cancer survivors and individuals without a history of cancer (controls). Frequency tables and chi-square tests were performed to determine overall differences in sociodemographic characteristics, health-related characteristics, and multimorbidity between groups. RESULTS: Cancer survivors reported a higher prevalence of having 4 or more diseases compared to controls (57% and 38%, respectively). Our analysis identified 6 clusters for cancer survivors and 4 clusters for controls. Three clusters (pulmonary, cardiac, and liver) included the same diseases for cancer survivors and controls. CONCLUSIONS: Diseases clustered differently across adults ≥ 50 years of age with and without a history of cancer. Findings from this study may be used to inform clinical care, increase the development and dissemination of multilevel public health interventions, escalate system improvements, and initiate innovative policy reform.


Assuntos
Multimorbidade , Neoplasias , Masculino , Humanos , Estados Unidos/epidemiologia , Pessoa de Meia-Idade , Idoso , Inquéritos e Questionários , Sobreviventes , Prevalência , Neoplasias/diagnóstico , Neoplasias/epidemiologia , Neoplasias/terapia , Doença Crônica
2.
Prev Chronic Dis ; 21: E22, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573795

RESUMO

Introduction: Social risk factors such as food insecurity and lack of transportation can negatively affect health outcomes, yet implementation of screening and referral for social risk factors is limited in medical settings, particularly in cancer survivorship. Methods: We conducted 18 qualitative, semistructured interviews among oncology teams in 3 health systems in Washington, DC, during February and March 2022. We applied the Exploration, Preparation, Implementation, Sustainment Framework to develop a deductive codebook, performed thematic analysis on the interview transcripts, and summarized our results descriptively. Results: Health systems varied in clinical and support staff roles and capacity. None of the participating clinics had an electronic health record (EHR)-based process for identifying patients who completed their cancer treatment ("survivors") or a standardized cancer survivorship program. Their capacities also differed for documenting social risk factors and referrals in the EHR. Interviewees expressed awareness of the prevalence and effect of social risk factors on cancer survivors, but none employed a systematic process for identifying and addressing social risk factors. Recommendations for increasing screening for social risk factors included designating a person to fulfill this role, improving data tracking tools in the EHR, and creating systems to maintain up-to-date information and contacts for community-based organizations. Conclusion: The complexity of cancer care workflows and lack of reimbursement results in a limited ability for clinic staff members to screen and make referrals for social risk factors. Creating clinical workflows that are flexible and tailored to staffing realities may contribute to successful implementation of a screening and referral program. Improving ongoing communication with community-based organizations to address needs was deemed important by interviewees.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Detecção Precoce de Câncer , Pesquisa Qualitativa , Fatores de Risco , Encaminhamento e Consulta , Neoplasias/diagnóstico
3.
J Med Libr Assoc ; 112(1): 5-12, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38911525

RESUMO

Objective: While several studies have examined the effectiveness of librarian interactions with clinicians and impact of librarians on patient care, no studies have explored a library's effects on population care. The goal of this study was to investigate the library's impact on both patient and population care. Methods: Using a sequential exploratory mixed-methods design, we first interviewed a small set of clinicians and researchers active in patient and population care. Based on the themes that we discovered through coding the interviews, we created a survey that was sent to faculty in the health sciences and the health system. Results: We collected data from a representative sample of our population. We discovered that all respondents value the library and informationists, using our services most for teaching, publishing, presenting, and professional development. Conclusion: We now have data to support our value to our population and to show where we can do more work to improve the use of our services. Our study shows the value of doing a mixed-methods sequential exploration in which themes that are important to our user community were identified prior to launching a large-scale survey.


Assuntos
Bibliotecários , Bibliotecas Médicas , Humanos , Bibliotecas Médicas/organização & administração , Serviços de Biblioteca/organização & administração , Serviços de Biblioteca/estatística & dados numéricos , Assistência ao Paciente , Inquéritos e Questionários , Feminino
4.
J Elder Abuse Negl ; 36(2): 174-197, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38459784

RESUMO

Adult child to parent violence is a growing international social problem that needs to be better understood to develop clinical interventions. An exploratory study on the antecedents of early life adversity on adult child to parent violence/elder mistreatment was carried out using secondary analysis. Directed content analysis was used based on life course theory with a data set of older mothers all > 57 years old (J. R. Smith 2021, 2022). Measurement of instances of child abuse, domestic violence, and birth trauma among abused older mothers was conducted. All the older women had reported being negatively affected by their adult children's problems and 56% reported being physically attacked. A case example is presented to illustrate how repeated incidents of abuse or neglect in early life might explain an older woman's inability to take actions for her own safety.


Assuntos
Mães , Humanos , Feminino , Mães/psicologia , Pessoa de Meia-Idade , Idoso , Filhos Adultos , Relações Mãe-Filho , Abuso de Idosos , Violência Doméstica , Idoso de 80 Anos ou mais
5.
Gynecol Oncol ; 174: 213-223, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37229879

RESUMO

OBJECTIVE: To determine the effects of using National Comprehensive Cancer Network (NCCN) guidelines to estimate renal function on carboplatin dosing and explore adverse effects associated with a more accurate estimation of lower creatinine clearance (CrCl). METHODS: Retrospective data were obtained for 3830 of 4312 patients treated on GOG182 (NCT00011986)-a phase III trial of platinum-based chemotherapy for advanced-stage ovarian cancer. Carboplatin dose per patient on GOG182 was determined using the Jelliffe formula. We recalculated CrCl to determine dosing using Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault (with/without NCCN recommended modifications) formulas. Associations between baseline CrCl and toxicity were described using the area under the receiver operating characteristic curve (AUC). Sensitivity and positive predictive values described the model's ability to discriminate between subjects with/without the adverse event. RESULTS: AUC statistics (range, 0.52-0.64) showed log(CrClJelliffe) was not a good predictor of grade ≥3 adverse events (anemia, thrombocytopenia, febrile neutropenia, auditory, renal, metabolic, neurologic). Of 3830 patients, 628 (16%) had CrCl <60 mL/min. Positive predictive values for adverse events ranged from 1.8%-15%. Using the Cockcroft-Gault, Cockcroft-Gault with NCCN modifications, and MDRD (instead of Jelliffe) formulas to estimate renal function resulted in a >10% decrease in carboplatin dosing in 16%, 32%, and 5.2% of patients, respectively, and a >10% increase in carboplatin dosing in 41%, 9.6% and 12% of patients, respectively. CONCLUSION: The formula used to estimate CrCl affects carboplatin dosing. Estimated CrCl <60 mL/min (by Jelliffe) did not accurately predict adverse events. Efforts continue to better predict renal function. Endorsing National Cancer Institute initiatives to broaden study eligibility, our data do not support a minimum threshold CrCl <60 mL/min as an exclusion criterion from clinical trials.


Assuntos
Neoplasias Ovarianas , Feminino , Humanos , Carboplatina , Creatinina , Taxa de Filtração Glomerular , Testes de Função Renal , Neoplasias Ovarianas/tratamento farmacológico , Estudos Retrospectivos
6.
PLoS Pathog ; 16(10): e1009020, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33108406

RESUMO

Brucellosis, caused by a number of Brucella species, remains the most prevalent zoonotic disease worldwide. Brucella establish chronic infections within host macrophages despite triggering cytosolic innate immune sensors, including Stimulator of Interferon Genes (STING), which potentially limit infection. In this study, STING was required for control of chronic Brucella infection in vivo. However, early during infection, Brucella down-regulated STING mRNA and protein. Down-regulation occurred post-transcriptionally, required live bacteria, the Brucella type IV secretion system, and was independent of host IRE1-RNase activity. STING suppression occurred in MyD88-/- macrophages and was not induced by Toll-like receptor agonists or purified Brucella lipopolysaccharide (LPS). Rather, Brucella induced a STING-targeting microRNA, miR-24-2, in a type IV secretion system-dependent manner. Furthermore, STING downregulation was inhibited by miR-24 anti-miRs and in Mirn23a locus-deficient macrophages. Failure to suppress STING expression in Mirn23a-/- macrophages correlated with diminished Brucella replication, and was rescued by exogenous miR-24. Mirn23a-/- mice were also more resistant to splenic colonization one week post infection. Anti-miR-24 potently suppressed replication in wild type, but much less in STING-/- macrophages, suggesting most of the impact of miR-24 induction on replication occurred via STING suppression. In summary, Brucella sabotages cytosolic surveillance by miR-24-dependent suppression of STING expression; post-STING activation "damage control" via targeted STING destruction may enable establishment of chronic infection.


Assuntos
Brucella/metabolismo , Brucelose/metabolismo , Proteínas de Membrana/biossíntese , MicroRNAs/metabolismo , Animais , Brucella/genética , Brucelose/genética , Feminino , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/genética , RNA Mensageiro/genética , Sistemas de Secreção Tipo IV/genética , Sistemas de Secreção Tipo IV/metabolismo
7.
J Gen Intern Med ; 37(2): 375-389, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34027605

RESUMO

BACKGROUND: Given increasing numbers of people experiencing transitions in health insurance due to declines in employer-sponsored insurance and changes in health policy, the understanding and application of health insurance terms and concepts (health insurance literacy) may be important for navigating use of health care. The study objective was to systematically review evidence on the relationship between health insurance literacy and health care utilization. METHODS: Medline, SCOPUS, Web of Science, CINAHL, PsychInfo, Cochrane Library, and reference lists of published literature were searched in August 2019. Quantitative, qualitative, and intervention studies that assessed the association of health insurance literacy as the exposure and health care utilization as the outcome were identified, without language or date restrictions. Outcomes were independently assessed by 2-3 reviewers. RESULTS: Twenty-one studies including a total of 62,416 subjects met inclusion criteria: three interventional trials, two mixed-methods studies, and sixteen cross-sectional studies. Ten of thirteen preventive care studies suggested that higher health insurance literacy was associated with greater utilization of primary care and other preventive services. Eight of nine studies of care avoidance demonstrated that individuals with lower health insurance literacy were more likely to delay or avoid care. A few studies had mixed results regarding the utilization of emergency department, inpatient, and surgical care. DISCUSSION: The emerging literature in this area suggests that health insurance literacy is an important factor that can enable effective utilization of health care, including primary care and preventive services. However, the literature is limited by a paucity of studies using validated tools that broadly measure health insurance literacy (rather than testing knowledge of specific covered services). Improving health insurance literacy of the general public and increasing plain language communication of health insurance plan features at the point of health care navigation may encourage more effective and cost-conscious utilization.


Assuntos
Letramento em Saúde , Seguro Saúde , Estudos Transversais , Letramento em Saúde/métodos , Humanos , Aceitação pelo Paciente de Cuidados de Saúde , Serviços Preventivos de Saúde
8.
J Anim Ecol ; 91(9): 1826-1841, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35678697

RESUMO

Invasive species pose a significant threat to biodiversity and agriculture world-wide. Natural enemies play an important part in controlling pest populations, yet we understand very little about the presence and prevalence of natural enemies during the early invasion stages. Microbial natural enemies of fall armyworm Spodoptera frugiperda are known in its native region, however, they have not yet been identified in Africa where fall armyworm has been an invasive crop pest since 2016. Larval samples were screened from Malawi, Rwanda, Kenya, Zambia, Sudan and Ghana for the presence of four different microbial natural enemies; two nucleopolyhedroviruses, Spodoptera frugiperda NPV (SfMNPV) and Spodoptera exempta NPV (SpexNPV); the fungal pathogen Metarhizium rileyi; and the bacterium Wolbachia. This study aimed to identify which microbial pathogens are present in invasive fall armyworm, and determine the geographical, meteorological and temporal variables that influence prevalence. Within 3 years of arrival, fall armyworm was exposed to all four microbial natural enemies. SfMNPV probably arrived with fall armyworm from the Americas, but this is the first putative evidence of host spillover from Spodoptera exempta (African armyworm) to fall armyworm for the endemic pathogen SpexNPV and for Wolbachia. It is also the first confirmed incidence of M. rileyi infecting fall armyworm in Africa. Natural enemies were localised, with variation being observed both nationally and temporally. The prevalence of SfMNPV (the most common natural enemy) was predominantly explained by variables associated with the weather; declining with increasing rainfall and increasing with temperature. However, virus prevalence also increased as the growing season progressed. The infection of an invasive species with a natural enemy from its native range and novel pathogens specific to its new range has important consequences for understanding the population ecology of invasive species and insect-pathogen interactions. Additionally, while it is widely known that temporal and geographic factors affect insect populations, this study reveals that these are important in understanding the distribution of microbial natural enemies associated with invasive pests during the early stages of invasion, and provide baseline data for future studies.


Assuntos
Nucleopoliedrovírus , Wolbachia , Animais , Espécies Introduzidas , Quênia , Spodoptera
9.
Matern Child Health J ; 26(10): 2126-2136, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35960420

RESUMO

INTRODUCTION: The 2030 health agenda for the United Nations Sustainable Development Goals promote exclusive breastfeeding (EBF) for the first 6 months of life as a central step towards ensuring the survival of infants. As Jamaica attempts to achieve this goal, monitoring the rates of EBF is desirable. Currently, EBF rate is measured by questionnaires which are subject to recall and social desirability biases. We determined the rate of EBF using the Deuterium-oxide dose-to-mother (DTM) method and 24-h recall. The concordance of both methods and urban-rural differences of EBF were evaluated. Additionally, the growth of infants who were exclusively breastfed was compared to the infants who were mixed-fed. METHODS: Sixty-one healthy mother-child pairs were followed from birth. EBF was measured at 6 weeks. Growth was determined using standard anthropometric measurements. Differences in means were assessed by independent t-test or ANOVA. The agreement between the DTM and 24-h recall method was assessed with the kappa statistic. Differences in anthropometry and location were determined using a repeated measure model approach. RESULTS: Thirty (49%) women exclusively breastfed their infants with mean breast milk intake of 1024.3 ± 256.9 g/day. There was moderate agreement between the methods (Agreement 69%, kappa 0.37, p = 0.002). Rural women (65%) were more likely to practice exclusive breastfeeding. There was no significant difference between the growth of the exclusively breastfed infant and mixed-fed infants. CONCLUSION: EBF rate was successfully measured using the DTM method. Women from urban settings are less likely to practice EBF. Further research may be needed to gain an in-depth understanding of the factors affecting breastfeeding practices in urban Jamaica.


Assuntos
Aleitamento Materno , Mães , Deutério , Feminino , Humanos , Lactente , Jamaica , Masculino , Óxidos
10.
Blood ; 133(17): 1888-1898, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30814063

RESUMO

Standard analyses applied to genome-wide association data are well designed to detect additive effects of moderate strength. However, the power for standard genome-wide association study (GWAS) analyses to identify effects from recessive diplotypes is not typically high. We proposed and conducted a gene-based compound heterozygosity test to reveal additional genes underlying complex diseases. With this approach applied to iron overload, a strong association signal was identified between the fibroblast growth factor-encoding gene, FGF6, and hemochromatosis in the central Wisconsin population. Functional validation showed that fibroblast growth factor 6 protein (FGF-6) regulates iron homeostasis and induces transcriptional regulation of hepcidin. Moreover, specific identified FGF6 variants differentially impact iron metabolism. In addition, FGF6 downregulation correlated with iron-metabolism dysfunction in systemic sclerosis and cancer cells. Using the recessive diplotype approach revealed a novel susceptibility hemochromatosis gene and has extended our understanding of the mechanisms involved in iron metabolism.


Assuntos
Exoma/genética , Fator 6 de Crescimento de Fibroblastos/genética , Regulação da Expressão Gênica , Predisposição Genética para Doença , Hemocromatose/patologia , Hepcidinas/metabolismo , Sobrecarga de Ferro/patologia , Ferro/metabolismo , Sequência de Aminoácidos , Estudos de Casos e Controles , Diploide , Feminino , Fator 6 de Crescimento de Fibroblastos/metabolismo , Seguimentos , Genes Recessivos , Estudo de Associação Genômica Ampla , Hemocromatose/genética , Hepcidinas/genética , Humanos , Sobrecarga de Ferro/genética , Masculino , Pessoa de Meia-Idade , Neoplasias/genética , Neoplasias/patologia , Mapas de Interação de Proteínas , Escleroderma Sistêmico/genética , Escleroderma Sistêmico/patologia , Homologia de Sequência
11.
J Immunol ; 202(9): 2671-2681, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30894428

RESUMO

Brucella abortus is a facultative intracellular bacterium that causes brucellosis, a prevalent zoonosis that leads to abortion and infertility in cattle, and undulant fever, debilitating arthritis, endocarditis, and meningitis in humans. Signaling pathways triggered by B. abortus involves stimulator of IFN genes (STING), which leads to production of type I IFNs. In this study, we evaluated the pathway linking the unfolded protein response (UPR) and the endoplasmic reticulum-resident transmembrane molecule STING, during B. abortus infection. We demonstrated that B. abortus infection induces the expression of the UPR target gene BiP and XBP1 in murine macrophages through a STING-dependent pathway. Additionally, we also observed that STING activation was dependent on the bacterial second messenger cyclic dimeric GMP. Furthermore, the Brucella-induced UPR is crucial for induction of multiple molecules linked to type I IFN signaling pathway, such as IFN-ß, IFN regulatory factor 1, and guanylate-binding proteins. Furthermore, IFN-ß is also important for the UPR induction during B. abortus infection. Indeed, IFN-ß shows a synergistic effect in inducing the IRE1 axis of the UPR. In addition, priming cells with IFN-ß favors B. abortus survival in macrophages. Moreover, Brucella-induced UPR facilitates bacterial replication in vitro and in vivo. Finally, these results suggest that B. abortus-induced UPR is triggered by bacterial cyclic dimeric GMP, in a STING-dependent manner, and that this response supports bacterial replication. In summary, association of STING and IFN-ß signaling pathways with Brucella-induced UPR unravels a novel link between innate immunity and endoplasmic reticulum stress that is crucial for bacterial infection outcome.


Assuntos
Brucella abortus/fisiologia , Brucelose/imunologia , Interações Hospedeiro-Patógeno/imunologia , Proteínas de Membrana/imunologia , Nucleotídeos Cíclicos/imunologia , Resposta a Proteínas não Dobradas/imunologia , Animais , Brucelose/genética , Interações Hospedeiro-Patógeno/genética , Humanos , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Nucleotídeos Cíclicos/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia
12.
J Clin Apher ; 36(4): 533-546, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33648025

RESUMO

BACKGROUND: During the pandemic in the spring of 2020 with no vaccine or treatment for SARS-CoV-2 and its associated disease, COVID-19, convalescent plasma from recovered COVID-19 (CCP) patients offered a potential therapy. In March 2020, the United States (U.S.) Food and Drug Administration (FDA) authorized CCP under emergency Investigational New Drug (eIND) exemption and an IRB-approved Expanded Access Program (EAP) to treat severe COVID-19. Hospital demand grew rapidly in the Southeastern U.S., resulting in backlogs of CCP orders. We describe a large U.S. blood center's (BC) rapid implementation of a CCP program in response to community needs. STUDY DESIGN AND METHODS: From April 2 to May 17, 2020, CCP was collected by whole blood or apheresis. Initial manual approaches to donor intake, collection, and distribution were rapidly replaced with automated processes. All CCP donors and products underwent FDA-required screening and testing. RESULTS: A total of 619 CCP donors (299 females, 320 males) presented for CCP donation (161 [25.7%] whole blood, 466 [74.3%] plasmapheresis) resulting in 1219 CCP units. Production of CCP increased as processes were automated and streamlined, from a mean of 11 donors collected/day for the first month to a mean of 25 donors collected/day in the subsequent 2 weeks. Backlogged orders were cleared, and inventory began to accumulate 4 weeks after project initiation. CONCLUSION: The BC was able to implement an effective de novo CCP collection program within 6 weeks in response to a community need in a global pandemic. Documentation of the experience may inform preparedness for future pandemics.


Assuntos
COVID-19/terapia , SARS-CoV-2 , Adulto , Coleta de Amostras Sanguíneas , Comunicação , Feminino , Humanos , Imunização Passiva/métodos , Masculino , Pessoa de Meia-Idade , Garantia da Qualidade dos Cuidados de Saúde , Soroterapia para COVID-19
13.
Prev Chronic Dis ; 18: E39, 2021 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-33890569

RESUMO

INTRODUCTION: Little is known about perceived health status and behavioral risk factors among prostate cancer survivors. The objective of this study was to describe racial and ethnic differences in self-reported health status, chronic conditions, and selected behavioral risk factors among prostate cancer survivors in the US. METHODS: We used data from the 2015 National Health Interview Survey to calculate the prevalence of various levels of health status, chronic conditions, behavioral risk factors, and sociodemographic characteristics among prostate cancer survivors aged 50 years or older. We stratified results by race and ethnicity. RESULTS: Of the 317 prostate cancer survivors in our sample, 33.1% reported no physical activity, 64.2% reported being current drinkers, 26.1% characterized their drinking as moderate/heavy, 42.3% reported being former smokers, and 8.7% were current smokers. Nearly one-third (29.1%) of survivors were obese (body mass index ≥30), and 15.1% had 3 to 6 chronic conditions. A greater percentage of White (29.7%) than Black (14.2%) or Hispanic (16.3%) survivors were moderate/heavy drinkers. A greater percentage of Black (16.2%) than White (7.5%) or Hispanic (7.3%) survivors were current smokers. A greater percentage of Black (25.1%) or Hispanic (27.7%) than White (11.4%) survivors had 3 to 6 chronic conditions. CONCLUSION: As the population of older men increases, prostate cancer diagnoses and those surviving the disease will also increase. Significant racial and ethnic group differences in behavioral risk factors and chronic conditions exist among prostate cancer survivors. Public health could prioritize efforts to improve health behaviors among prostate cancer survivors and use targeted interventions to address disparities.


Assuntos
Sobreviventes de Câncer , Neoplasias da Próstata , Idoso , Etnicidade , Nível de Saúde , Disparidades nos Níveis de Saúde , Hispânico ou Latino , Humanos , Masculino , Fatores de Risco , Sobreviventes , Estados Unidos/epidemiologia
14.
Am J Respir Cell Mol Biol ; 62(6): 783-792, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32078788

RESUMO

Polymorphism at the 17q21 gene locus and wheezing responses to rhinovirus (RV) early in childhood conspire to increase the risk of developing asthma. However, the mechanisms mediating this gene-environment interaction remain unclear. In this study, we investigated the impact of one of the 17q21-encoded genes, ORMDL3 (orosomucoid-like 3), on RV replication in human epithelial cells. ORMDL3 knockdown inhibited RV-A16 replication in HeLa, BEAS-2B, A549, and NCI-H358 epithelial cell lines and primary nasal and bronchial epithelial cells. Inhibition varied by RV species, as both minor and major group RV-A subtypes RV-B52 and RV-C2 were inhibited but not RV-C15 or RV-C41. ORMDL3 siRNA did not affect expression of the major group RV-A receptor ICAM-1 or initial internalization of RV-A16. The two major outcomes of ORMDL3 activity, SPT (serine palmitoyl-CoA transferase) inhibition and endoplasmic reticulum (ER) stress induction, were further examined: silencing ORMDL3 decreased RV-induced ER stress and IFN-ß mRNA expression. However, pharmacologic induction of ER stress and concomitant increased IFN-ß inhibited RV-A16 replication. Conversely, blockade of ER stress with tauroursodeoxycholic acid augmented replication, pointing to an alternative mechanism for the effect of ORMDL3 knockdown on RV replication. In comparison, the SPT inhibitor myriocin increased RV-A16 but not RV-C15 replication and negated the inhibitory effect of ORMDL3 knockdown. Furthermore, lipidomics analysis revealed opposing regulation of specific sphingolipid species (downstream of SPT) by myriocin and ORMDL3 siRNA, correlating with the effect of these treatments on RV replication. Together, these data revealed a requirement for ORMDL3 in supporting RV replication in epithelial cells via SPT inhibition.


Assuntos
Células Epiteliais/virologia , Proteínas de Membrana/fisiologia , Rhinovirus/fisiologia , Replicação Viral , Células A549 , Asma/etiologia , Brônquios/citologia , Células Cultivadas , Cromossomos Humanos Par 17/genética , Estresse do Retículo Endoplasmático , Ácidos Graxos Monoinsaturados/farmacologia , Predisposição Genética para Doença , Genótipo , Células HeLa , Humanos , Interferon beta/biossíntese , Interferon beta/genética , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Mucosa Nasal/citologia , Infecções por Picornaviridae/complicações , Interferência de RNA , RNA Interferente Pequeno/genética , Proteínas Recombinantes/metabolismo , Rhinovirus/genética , Serina C-Palmitoiltransferase/antagonistas & inibidores , Serina C-Palmitoiltransferase/metabolismo , Esfingolipídeos/metabolismo , Ácido Tauroquenodesoxicólico/farmacologia , Replicação Viral/efeitos dos fármacos
15.
Cancer Causes Control ; 31(11): 965-977, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32840707

RESUMO

PURPOSE: Despite widespread promotion of breast and cervical cancer (BCC) screening, uptake remains low in rural communities. Barriers to healthcare, which often result in poorer health outcomes, differentially impact residents of rural communities. Effective interventions addressing the unique needs of rural women may target these barriers and increase BCC screening participation. Our objective is to review and assess the published literature on interventions to increase BCC screening in rural communities. METHODS: A systematic scoping review of PubMed/Medline was performed to identify BCC screening interventions conducted in rural settings. English language articles from peer-reviewed journals published from January 2006 to October 2019 were included if they reported results for BCC screening interventions in rural communities in the United States. RESULTS: We reviewed 228 articles and identified eight articles consistent with our inclusion criteria. Studies varied in sample population characteristics, geographic location, design, and mode of intervention delivery. Interventions included patient navigation strategies, educational outreach programs, peer counseling, and small media initiatives. Interventions focused on promoting uptake of initial or one-time screening rather than targeted repeat screening, and few studies detailed the cost-effectiveness of the interventions. CONCLUSION: This review may inform efforts to develop strategies to increase BCC screening among rural women. Additional cancer prevention and control research gaps in rural communities include the examination of the theoretical foundations, design, delivery, and cost-effectiveness of BCC screening interventions for rural communities. Future research might focus on methods to promote repeat BCC screening and effective translation of these interventions for other rural populations.


Assuntos
Neoplasias da Mama/diagnóstico , Programas de Rastreamento/estatística & dados numéricos , Neoplasias do Colo do Útero/diagnóstico , Neoplasias da Mama/prevenção & controle , Atenção à Saúde , Detecção Precoce de Câncer , Feminino , Humanos , Navegação de Pacientes , População Rural , Estados Unidos , Neoplasias do Colo do Útero/epidemiologia
16.
J Immunol ; 200(2): 607-622, 2018 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-29203515

RESUMO

Immunity against microbes depends on recognition of pathogen-associated molecular patterns by innate receptors. Signaling pathways triggered by Brucella abortus DNA involves TLR9, AIM2, and stimulator of IFN genes (STING). In this study, we observed by microarray analysis that several type I IFN-associated genes, such as IFN-ß and guanylate-binding proteins (GBPs), are downregulated in STING knockout (KO) macrophages infected with Brucella or transfected with DNA. Additionally, we determined that STING and cyclic GMP-AMP synthase (cGAS) are important to engage the type I IFN pathway, but only STING is required to induce IL-1ß secretion, caspase-1 activation, and GBP2 and GBP3 expression. Furthermore, we determined that STING but not cGAS is critical for host protection against Brucella infection in macrophages and in vivo. This study provides evidence of a cGAS-independent mechanism of STING-mediated protection against an intracellular bacterial infection. Additionally, infected IFN regulatory factor-1 and IFNAR KO macrophages had reduced GBP2 and GBP3 expression and these cells were more permissive to Brucella replication compared with wild-type control macrophages. Because GBPs are critical to target vacuolar bacteria, we determined whether GBP2 and GBPchr3 affect Brucella control in vivo. GBPchr3 but not GBP2 KO mice were more susceptible to bacterial infection, and small interfering RNA treated-macrophages showed reduction in IL-1ß secretion and caspase-1 activation. Finally, we also demonstrated that Brucella DNA colocalizes with AIM2, and AIM2 KO mice are less resistant to B. abortus infection. In conclusion, these findings suggest that the STING-dependent type I IFN pathway is critical for the GBP-mediated release of Brucella DNA into the cytosol and subsequent activation of AIM2.


Assuntos
Brucella abortus/imunologia , Brucelose/imunologia , Brucelose/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Inflamassomos/metabolismo , Proteínas de Membrana/metabolismo , Transdução de Sinais , Animais , Brucella abortus/genética , Brucelose/genética , Brucelose/microbiologia , GMP Cíclico/análogos & derivados , GMP Cíclico/metabolismo , Citocinas/metabolismo , Proteínas de Ligação ao GTP/genética , Expressão Gênica , Perfilação da Expressão Gênica , Granuloma/metabolismo , Granuloma/microbiologia , Granuloma/patologia , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Mediadores da Inflamação , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/genética , Interferon Tipo I/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Proteínas de Membrana/genética , Camundongos , Camundongos Knockout , Modelos Biológicos , NF-kappa B/metabolismo
17.
J Am Pharm Assoc (2003) ; 60(6): e319-e323, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32690445

RESUMO

OBJECTIVE: To develop an alternative approach to provide oncology pharmacy practice residents' education and training in the management of gynecologic malignancies in the absence of a specialist in this area at their institution. SETTING: Gynecologic oncology is a unique specialty in oncology. There is a need for more oncology clinical pharmacy specialists to participate in the care of patients with gynecologic malignancies as many do not have specific education in this area. PRACTICE DESCRIPTION: A virtual learning experience was developed that included all aspects of a typical experience with the exception of direct patient care. Postgraduate year 2 oncology pharmacy residents from 3 different programs were included. PRACTICE INNOVATION: Although the number of oncology clinical pharmacy specialists who are subspecialized in gynecologic oncology has grown, it is difficult to find experienced preceptors in gynecology oncology. We set to offer a virtual learning environment for programs that did not have a dedicated or highly specialized pharmacist in this area. EVALUATION: A pre- and postlearning assessment of the resident's knowledge of gynecologic malignancies was administered. Each trainee independently completed a validated 20-question gynecologic oncology knowledge assessment tool before and again after completion of all sessions. Midpoint and end-of-experience evaluations were completed via the phone with each resident. All evaluations were documented in PharmAcademic (McCreadie Group, Ann Arbor, MI), a required software program for postgraduate residency training programs. RESULTS: To date, 7 oncology pharmacy practice residents completed the virtual experience. A 42% improvement in scores pertaining to gynecologic oncology knowledge was identified. Residents were also satisfied with the overall virtual experience. Based on the assessment tool, all the residents gave positive evaluations with "always true" for 6 of the 7 questions. CONCLUSIONS: This pilot of a virtual experience was a successful platform to provide clinical knowledge and skills for oncology pharmacy residents in gynecologic oncology.


Assuntos
Educação em Farmácia , Neoplasias dos Genitais Femininos , Internato e Residência , Residências em Farmácia , Farmácia , Avaliação Educacional , Feminino , Humanos
18.
Palliat Support Care ; 18(2): 220-240, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31588882

RESUMO

OBJECTIVE: Informal caregiving may likely increase as the number of cancer survivors grows. Caregiving responsibilities can impact caregivers' quality of life (QOL). Understanding the current state of the science regarding caregiving QOL could help inform future research and intervention development. METHODS: A systematic literature review in PubMed/Medline examined research on QOL among informal cancer caregivers and related psychosocial health outcomes. Original research articles in English, published between 2007 and 2017 about caregivers (aged >18 years) of adult cancer patients in the United States were included. Abstracted articles were categorized according to caregiving recipient's phase of survivorship (acute, middle to long-term, end of life/bereavement). RESULTS: Of 920 articles abstracted, 60 met inclusion criteria. Mean caregiver age ranged from 37 to 68 with the majority being female, non-Hispanic white, with at least a high school degree, and middle income. Almost half of the studies focused on caregivers who provided care for survivors from diagnosis through the end of active treatment. Studies examined physical health, spirituality, psychological distress, and social support. Differences in QOL were noted by caregiver age, sex, and employment status. SIGNIFICANCE OF RESULTS: Additional research includes the examination of the needs of diverse cancer caregivers and determines how additional caregiver characteristics (e.g., physical functioning, financial burden, etc.) affect QOL. This includes studies examining caregiver QOL in the phases following the cessation of active treatment and assessments of health systems, support services, and insurance to determine barriers and facilitators needed to meet the immediate and long-term needs of cancer caregivers.


Assuntos
Cuidadores/psicologia , Neoplasias/enfermagem , Qualidade de Vida/psicologia , Adaptação Psicológica , Humanos , Neoplasias/complicações , Neoplasias/psicologia , Assistência ao Paciente/efeitos adversos , Assistência ao Paciente/métodos , Apoio Social
19.
Hepatology ; 67(6): 2375-2383, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29272043

RESUMO

Patients with cirrhosis seek improvement in their symptoms, functioning, quality of life, and satisfaction with the care they receive. However, these patient-reported outcomes (PROs) are not routinely measured for clinical care, research, or quality improvement. The members of the American Association for the Study of Liver Diseases Practice Metrics Committee, charged with developing quality indicators for clinical practice, performed a scoping review of PROs in cirrhosis. The aim is to synthesize a comprehensive set of PROs for inclusion into a standard patient-centered outcome set. We searched Medline, Embase, the Cumulative Index to Nursing and Allied Health Literature, PsycINFO, and the Cochrane Trial Library since inception, with final searches run between April 20 and June 1, 2017. Studies were included if they reported the construction and/or validation of a PRO instrument for patients with cirrhosis or if they assessed the clinical (case-mix) variables determining responses to established PRO scales. Eleven studies were selected that yielded 259 items specific to patients with cirrhosis. After removing duplicates, 152 unique items were isolated. These items were consolidated into seven domains: physical symptoms, physical function, mental health, general function, cognition, social life, and satisfaction with care. The seven domains included 52 subdomains (e.g., physical domain, abdominal pain subdomain). Twelve variables were identified that independently modified established PRO scales. These included clinical factors (severity of liver disease and its complications, medication burden, and comorbidities), specific PROs (cramps, pruritis), and surrogate outcome measures (falls, hospitalization). CONCLUSION: This scoping review identified and categorized a large existing set of PRO concepts that matter to patients with cirrhosis; these outcomes may now be translated into usable measures both for the assessment of the quality of cirrhosis care in clinical practice and to perform research from the patient's perspective. (Hepatology 2018;67:2375-2383).


Assuntos
Cirrose Hepática/terapia , Medidas de Resultados Relatados pelo Paciente , Humanos
20.
Exp Eye Res ; 187: 107756, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31421136

RESUMO

Endoplasmic reticulum (ER) stress is recognized as a contributing factor to various ocular neurovascular pathologies including retinitis pigmentosa, glaucoma, and diabetic retinopathy (DR). ER stress in particular is implicated in the development of DR, which is significantly influenced by inflammation driven retinal vascular degeneration and dysfunction. Ultimately, loss of vision occurs if left untreated. However, the identity of the target cells and their temporal involvement in diabetes-mediated dysfunction need further investigation. Early diabetes-induced stress in photoreceptor cells is proposed as the driver of inflammatory mediated neurovascular changes during diabetes. Although tunicamycin induced ER stress results in photoreceptor loss, its consequences for retinal vascular degeneration and retinal ganglion (RGC) and pigment epithelium (RPE) cell loss remains unclear. Here we show intravitreal delivery of tunicamycin primarily induced ER stress in photoreceptor cells resulting in their loss by apoptosis. This was concomitant with induced expression of the unfolded protein response marker CHOP in these cells. We also demonstrated significant degeneration of retinal capillaries following the loss of photoreceptor cells with minimal impact on loss of RGC and RPE cells. However, activation of retinal microglial and Muller cells were noticeable. Thus, our data support the notion that ER stress mediated dysfunction and/or loss of photoreceptor cells in response to inflammation and oxidative stress could precede retinal vascular and neuronal dysfunction and degeneration.


Assuntos
Antibacterianos/farmacologia , Células Fotorreceptoras de Vertebrados/patologia , Degeneração Retiniana/patologia , Células Ganglionares da Retina/patologia , Epitélio Pigmentado da Retina/patologia , Vasos Retinianos/patologia , Tunicamicina/farmacologia , Animais , Atrofia , Capilares/patologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Feminino , Técnica Indireta de Fluorescência para Anticorpo , Marcação In Situ das Extremidades Cortadas , Injeções Intravítreas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , N-Metilaspartato/farmacologia , Estresse Oxidativo , Células Fotorreceptoras de Vertebrados/metabolismo , Degeneração Retiniana/metabolismo , Células Ganglionares da Retina/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo
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