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1.
Cancers (Basel) ; 16(9)2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38730618

RESUMO

Dysregulated DNA methylation in cancer is critical in the transcription machinery associated with cancer progression. Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype, but no treatment targeting TNBC biomarkers has yet been developed. To identify specific DNA methylation patterns in TNBC, methyl-binding domain protein 2 (MBD) sequencing data were compared in TNBC and the three other major breast cancer subtypes. Integrated analysis of DNA methylation and gene expression identified a gene set showing a correlation between DNA methylation and gene expression. ATPase Na+/K+-transporting subunit alpha 1 (ATP1A1) was found to be specifically hypomethylated in the coding sequence (CDS) region and to show increased expression in TNBC. The Cancer Genome Atlas (TCGA) database also showed that hypomethylation and high expression of ATP1A1 were strongly associated with poor survival in patients with TNBC. Furthermore, ATP1A1 knockdown significantly reduced the viability and tumor-sphere formation of TNBC cells. These results suggest that the hypomethylation and overexpression of ATP1A1 could be a prognostic marker in TNBC and that the manipulation of ATP1A1 expression could be a therapeutic target in this disease.

2.
J Racial Ethn Health Disparities ; 11(1): 313-325, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37043167

RESUMO

OBJECTIVE: To assess overall and by neighborhood risk environments whether multilevel resilience resources were associated with HIV virologic suppression among African American/Black adults in the Southeastern United States. SETTING AND METHODS: This clinical cohort sub-study included 436 African American/Black participants enrolled in two parent HIV clinical cohorts. Resilience was assessed using the Multilevel Resilience Resource Measure (MRM) for African American/Black adults living with HIV, where endorsement of a MRM statement indicated agreement that a resilience resource helped a participant continue HIV care despite challenges or was present in a participant's neighborhood. Modified Poisson regression models estimated adjusted prevalence ratios (aPRs) for virologic suppression as a function of categorical MRM scores, controlling for demographic, clinical, and behavioral characteristics at or prior to sub-study enrollment. We assessed for effect measure modification (EMM) by neighborhood risk environments. RESULTS: Compared to participants with lesser endorsement of multilevel resilience resources, aPRs for virologic suppression among those with greater or moderate endorsement were 1.03 (95% confidence interval: 0.96-1.11) and 1.03 (0.96-1.11), respectively. Regarding multilevel resilience resource endorsement, there was no strong evidence for EMM by levels of neighborhood risk environments. CONCLUSIONS: Modest positive associations between higher multilevel resilience resource endorsement and virologic suppression were at times most compatible with the data. However, null findings were also compatible. There was no strong evidence for EMM concerning multilevel resilience resource endorsement, which could have been due to random error. Prospective studies assessing EMM by levels of the neighborhood risk environment with larger sample sizes are needed.


Assuntos
Infecções por HIV , Resiliência Psicológica , Adulto , Humanos , Estados Unidos , Negro ou Afro-Americano , Estudos Prospectivos , Sudeste dos Estados Unidos , Infecções por HIV/tratamento farmacológico , Características de Residência
3.
Prehosp Disaster Med ; 39(1): 3-12, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38108128

RESUMO

INTRODUCTION: Displaced populations face disproportionately high risk of communicable disease outbreaks given the strains of travel, health care circumstances in their country of origin, and limited access to health care in receiving countries. STUDY OBJECTIVE: Understanding the role of demographic characteristics in outbreaks is important for timely and efficient control measures. Accordingly, this study assesses chickenpox outbreaks in three large refugee camps on mainland Greece from 2016 - 2017, using clinical line-list data from Médecins du Monde (MdM) clinics. METHODS: Clinical line-list data from MdM clinics operating in Elliniko, Malakasa, and Raidestos camps in mainland Greece were used to characterize chickenpox outbreaks in these camps. Logistic regression was used to compare the odds of chickenpox by sex, camp, and yearly increase in age. Incidences were calculated for age categories and for sex for each camp outbreak. RESULTS: Across camps, the median age was 19 years (IQR: 7.00 - 30.00 years) for all individuals and five years (IQR: 2.00 - 8.00 years) for cases. Males were 55.94% of the total population and 51.32% of all cases. There were four outbreaks of chickenpox across Elliniko (n = 1), Malakasa (n = 2), and Raidestos (n = 1) camps. The odds of chickenpox when controlling for age and sex was lower for Malakasa (OR = 0.46; 95% CI, 0.38 - 0.78) and Raidestos (OR = 0.36; 95% CI, 0.24 - 0.56) when compared Elliniko. Odds of chickenpox were comparable between Malakasa and Raidestos (OR = 1.49; 95% CI, 0.92 - 2.42). Across all camps, the highest incidence was among children zero-to-five years of age. The sex-specific incidence chickenpox was higher for males than females in Elliniko and Malakasa, while the incidence was higher among females in Raidestos. CONCLUSION: As expected, individuals five years of age and under made up the majority of chickenpox cases. However, 12% of cases were teenagers or older, highlighting the need to consider atypical age groups in vaccination strategies and control measures. To support both host and displaced populations, it is important to consider risk-reduction needs for both groups. Including host communities in vaccination campaigns and activities can help reduce the population burden of disease for both communities.


Assuntos
Varicela , Criança , Masculino , Feminino , Adolescente , Humanos , Adulto Jovem , Adulto , Estudos Retrospectivos , Varicela/epidemiologia , Campos de Refugiados , Grécia/epidemiologia , Surtos de Doenças
4.
BMC Public Health ; 23(1): 1715, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667247

RESUMO

BACKGROUND: Despite the importance of baseline health data for evidence-informed decision-making, these data are rarely available for displaced populations. At the height of the European refugee crisis, most of those seeking asylum in Europe were from regions with high prevalences of communicable and non-communicable diseases. To create an epidemiologic profile for refugees in camps on mainland Greece, this study assessed the prevalence of 11 communicable and non-communicable diseases among refugees utilizing Médecins du Monde (MdM) in-camp clinics. METHODS: The proportional morbidity of selected diseases among individuals utilizing MdM services were determined from data collected at refugee camp clinics on mainland Greece from April 2016 - July 2017. Overall and age-specific proportional morbidities were reported. Differences in disease burden among refugees from the largest sending countries - Afghanistan and Syria - were compared using proportional morbidity ratios and 95% confidence intervals. Patterns in results were compared with disease burden estimates in sending countries and with findings from comparable settings. RESULTS: Respiratory tract infections (RTIs) were the most prevalent outcome. Among RTIs, upper RTIs were most common, with a proportional morbidity of nearly 40%; throughout the study period, over 46% of children under 18 years had at least one upper RTI consultation. Musculoskeletal conditions (3.64%), were the most prevalent non-communicable outcome, followed by hypertension (2.21%) and asthma (1.28%). Afghans were 31.68% more likely than Syrians to have a consultation for at least one condition (PR: 1.32; 95% CI: 1.25, 1.39). The proportional morbidity of RTIs was comparable to sending countries, but there was a comparatively lower burden of other conditions among refugees than literature estimates from sending countries. CONCLUSION: Refugees utilizing MdM clinics in camps had higher burdens of communicable diseases - predominantly RTIs - relative to non-communicable diseases. Non-communicable disease burdens were comparatively lower than reported prevalences from in-country populations. These findings can be attributed to a range of considerations including differences in demographic profiles between sending countries and refugee populations and missed opportunities for utilizing clinical care. Further investment is needed to capture the health profiles of displaced populations to support evidence-informed decision-making processes in humanitarian emergency responses.


Assuntos
Doenças não Transmissíveis , Refugiados , Infecções Respiratórias , Criança , Humanos , Adolescente , Grécia/epidemiologia , Estudos Transversais , Doenças não Transmissíveis/epidemiologia , Estudos Retrospectivos , Infecções Respiratórias/epidemiologia , Efeitos Psicossociais da Doença
5.
Am J Epidemiol ; 192(11): 1864-1881, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37442807

RESUMO

We examined relationships between resilience resources (optimism, social support, and neighborhood social cohesion) and cardiovascular disease (CVD) incidence and assessed potential effect-measure modification by psychosocial risk factors (e.g., stress, depression) among adults without CVD in 3 cohort studies (2000-2018): the Jackson Heart Study, the Multi-Ethnic Study of Atherosclerosis, and the Mediators of Atherosclerosis in South Asians Living in America (MASALA) Study. We fitted adjusted Cox models accounting for within-neighborhood clustering while censoring at dropout or non-CVD death. We assessed for effect-measure modification by psychosocial risks. In secondary analyses, we estimated standardized risk ratios using inverse-probability-weighted Aalen-Johansen estimators to account for confounding, dropout, and competing risks (non-CVD deaths) and obtained 95% confidence intervals (CIs) using cluster bootstrapping. For high and medium (versus low) optimism (n = 6,243), adjusted hazard ratios (HRs) for incident CVD were 0.94 (95% CI: 0.78, 1.13) and 0.90 (95% CI: 0.75, 1.07), respectively. Corresponding HRs were 0.88 (95% CI: 0.74, 1.04) and 0.92 (95% CI: 0.79, 1.06) for social support (n = 7,729) and 1.10 (95% CI: 0.94, 1.29) and 0.99 (95% CI: 0.85, 1.16) for social cohesion (n = 7,557), respectively. Some psychosocial risks modified CVD HRs. Secondary analyses yielded similar findings. For optimism and social support, an inverse relationship was frequently most compatible with the data, but a positive relationship was also compatible. For neighborhood social cohesion, positive and null relationships were most compatible. Thus, specific resilience resources may be potential intervention targets, especially among certain subgroups.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Adulto , Humanos , Doenças Cardiovasculares/epidemiologia , Incidência , Estudos Longitudinais , Fatores de Risco , População do Sul da Ásia , Estados Unidos
6.
SSM Popul Health ; 20: 101284, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36387018

RESUMO

Purpose: Social support may have benefits on cardiovascular health (CVH). CVH is evaluated using seven important metrics (Life's Simple 7; LS7) established by the American Heart Association (e.g., smoking, diet). However, evidence from longitudinal studies is limited and inconsistent. The objective of this study is to examine the longitudinal relationship between social support and CVH, and assess whether psychosocial risks (e.g., anger and stress) modify the relationship in a racially/ethnically diverse population. Methods: Participants from three harmonized cohort studies - Jackson Heart Study, Mediators of Atherosclerosis in South Asians Living in America, and Multi-Ethnic Study of Atherosclerosis - were included. Repeated-measures modified Poisson regression models were used to examine the overall relationship between social support (in tertiles) and CVH (LS7 metric), and to assess for effect modification by psychosocial risk. Results: Among 7724 participants, those with high (versus low) social support had an adjusted prevalence ratio (aPR) and 95% confidence interval (CI) for ideal or intermediate (versus poor) CVH of 0.99 (0.96-1.03). For medium (versus low) social support, the aPR (95% CI) was 1.01 (0.98-1.05). There was evidence for modification by employment and anger. Those with medium (versus low) social support had an aPR (95% CI) of 1.04 (0.99-1.10) among unemployed or low anger participants. Corresponding results for employed or high anger participants were 0.99 (0.94-1.03) and 0.97 (0.91-1.03), respectively. Conclusion: Overall, we observed no strong evidence for an association between social support and CVH. However, some psychosocial risks may be modifiers. Prospective studies are needed to assess the social support-CVH relationship by psychosocial risks in racially/ethnically diverse populations.

7.
Int J Sex Health ; 34(3): 462-473, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387612

RESUMO

Objective: Examine prospective relationships between erectile dysfunction (ED) drugs EDand CD4 and CD8 T-cells, and immune markers among men who have sex with men (MSM). Methods: Data from Multicenter AIDS Cohort Study, an observational prospective cohort study, with semi-annual follow-ups conducted in four U.S. centers from 1998 onwards was used. Marginal structural models using g-computation was fitted to estimate the mean differences for the effects of self-reported ED drug use on CD4 and CD8 T-cell outcomes and immune biomarkers. Results: Total of 1,391 men with HIV (MWH) and 307 men without HIV (MWOH) was included. Baseline mean CD4 cell count among MWH and MWOH was 499.9 cells/µL and 966.7 cells/µL, respectively. At baseline, 41.8% of MWH were virally suppressed. ED drug users reported a mean of 44.4 months of exposure to ED drugs. ED drug use was associated with increased CD4 cell outcomes among MWH but not MWOH. Mean differences in CD4 cell counts after 1 year of ED drug use was 57.6 cells/µL and increased to 117.7 after 10 years among MWH. CD8 counts were higher in ED drug users among MWH over 10 years than non-users; no consistent differences were found among MWOH. ED drug use appeared to reduce immune marker levels, such as IL-6 and increase markers, such as IL-10. We observed similar effects of ED drug use on biomarker levels among MWOH. Conclusion: Long-term use of ED drugs do not adversely affect immune function among MWH or MWOH. Future studies on the relationships between different types of ED drugs and effects on T-cell subtypes are warranted.

8.
BMC Public Health ; 22(1): 1890, 2022 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-36221065

RESUMO

BACKGROUND: Psychosocial stressors increase the risks for cardiovascular disease across diverse populations. However, neighborhood level resilience resources may protect against poor cardiovascular health (CVH). This study used data from three CVH cohorts to examine longitudinally the associations of a resilience resource, perceived neighborhood social cohesion (hereafter referred to as neighborhood social cohesion), with the American Heart Association's Life's Simple 7 (LS7), and whether psychosocial stressors modify observed relationships. METHODS: We examined neighborhood social cohesion (measured in tertiles) and LS7 in the Jackson Heart Study, Multi-Ethnic Study of Atherosclerosis, and Mediators of Atherosclerosis in South Asians Living in America study. We used repeated-measures, modified Poisson regression models to estimate the relationship between neighborhood social cohesion and LS7 (primary analysis, n = 6,086) and four biological metrics (body mass index, blood pressure, cholesterol, blood glucose; secondary analysis, n = 7,291). We assessed effect measure modification by each psychosocial stressor (e.g., low educational attainment, discrimination). RESULTS: In primary analyses, adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) for ideal/intermediate versus poor CVH among high or medium (versus low) neighborhood social cohesion were 1.01 (0.97-1.05) and 1.02 (0.98-1.06), respectively. The psychosocial stressors, low education and discrimination, functioned as effect modifiers. Secondary analyses showed similar findings. Also, in the secondary analyses, there was evidence for effect modification by income. CONCLUSION: We did not find much support for an association between neighborhood social cohesion and LS7, but did find evidence of effect modification. Some of the effect modification results operated in unexpected directions. Future studies should examine neighborhood social cohesion more comprehensively and assess for effect modification by psychosocial stressors.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Glicemia , Doenças Cardiovasculares/epidemiologia , Colesterol , Humanos , Fatores de Risco , Coesão Social , Estados Unidos
9.
Oncogene ; 41(22): 3151-3161, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35490208

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer; however, specific prognostic biomarkers have not yet been developed. In this study, we identified dysregulated microRNAs (miRNAs) in TNBC by profiling miRNA and mRNA expression. In patients with TNBC, miR-371b-5p expression was reduced, and miR-371b-5p overexpression significantly mitigated TNBC cell growth, migration, and invasion. In addition, we found that expression of cold shock domain-containing protein E1 (CSDE1), a direct target gene of miR-371b-5p, was upregulated in TNBC cells, and inhibition of CSDE1 expression alleviated TNBC cell growth by regulating RAC1 transcription. Mechanistically, CSDE1, phosphorylated C-terminal domain (p-CTD) of RNA polymerase II (RNAPII), and CDK7 form a complex, and downregulation of CSDE1 leads to weak interaction between RNAPII p-CTD and CDK7, resulting in a decrease in RNAPII p-CTD expression to reduce RAC1 transcript levels in CSDE1-deficient TNBC cells. Our data demonstrate that miR-371b-5p is a tumor-suppressive miRNA that regulates the CSDE1/Rac1 axis and could be a potential prognostic biomarker for TNBC.


Assuntos
Proteínas de Ligação a DNA , MicroRNAs , Proteínas de Ligação a RNA , Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Proteínas de Ligação a DNA/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica/genética , Proteínas de Ligação a RNA/genética , Neoplasias de Mama Triplo Negativas/patologia , Proteínas rac1 de Ligação ao GTP/genética
10.
Mol Oncol ; 16(9): 1857-1875, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35029026

RESUMO

Autophagy has a dual role in the maintenance of cancer stem cells (CSCs), but the precise relationship between autophagy and cancer stemness requires further investigation. In this study, it was found that luminal and triple-negative breast cancers require distinct therapeutic approaches because of their different amounts of autophagy flux. We identified that autophagy flux was inhibited in triple-negative breast cancer (TNBC) CSCs. Moreover, miRNA-181a (miR-181a) expression is upregulated in both TNBC CSCs and patient tissues. Autophagy-related 5 (ATG5) and autophagy-related 2B (ATG2B) participate in the early formation of autophagosomes and were revealed as targets of miR-181a. Inhibition of miR-181a expression led to attenuation of TNBC stemness and an increase in autophagy flux. Furthermore, treatment with curcumin led to attenuation of cancer stemness in TNBC CSCs; the expression of ATG5 and ATG2B was enhanced and there was an increase of autophagy flux. These results indicated that ATG5 and ATG2B are involved in the suppression of cancer stemness in TNBC. In summary, autophagy inhibits cancer stemness through the miR-181a-regulated mechanism in TNBC. Promoting tumor-suppressive autophagy using curcumin may be a potential method for the treatment of TNBC.


Assuntos
Curcumina , MicroRNAs , Neoplasias de Mama Triplo Negativas , Autofagia/genética , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular Tumoral , Curcumina/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Proteínas de Transporte Vesicular/metabolismo
11.
Health Psychol ; 41(4): 278-290, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34138614

RESUMO

Objective: This systematic review and meta-analysis aimed to quantify the relationship between resilience resources at the individual (e.g., optimism), interpersonal (e.g., social support), and neighborhood (e.g., social environment) levels, and cardiovascular outcomes among adults in the United States. Method: On 9/25/2020, electronic databases (PubMed, Embase, CINAHL, PsycINFO) were systematically searched for randomized controlled trials, nonrandomized intervention studies, and prospective cohort studies that examined the relationship between resilience resources at the individual, interpersonal, or neighborhood level and cardiovascular outcomes. Studies that met the eligibility criteria were summarized narratively and quantitatively. Because relevant search results yielded only observational studies, risk of bias was assessed using an adapted version of the Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool. Results: From 4,103 unique records, 13 prospective cohort studies with a total of 310,906 participants met the eligibility criteria, and six of these studies were included in the meta-analyses. Most relevant studies found that higher levels of individual-level resilience resources were associated with lower incidence of adverse cardiovascular outcomes, with point estimates ranging from .46 to 1.18. Interpersonal-level resilience resources (i.e., social network) were associated with a lower coronary heart disease risk (risk ratio, .76; 95% CI [.56, 1.02]). Neighborhood-level resilience resources (i.e., perceived social cohesion and residential stability) were associated with a lower odds of stroke (odds ratio, .92; 95% CI [.84, 1.01]). Conclusions: Evidence suggests that higher levels of resilience resources are associated with better cardiovascular outcomes. However, more prospective studies with diverse populations are needed to strengthen the evidence. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Doenças Cardiovasculares , Acidente Vascular Cerebral , Adulto , Doenças Cardiovasculares/epidemiologia , Humanos , Estudos Prospectivos , Estados Unidos/epidemiologia
12.
Arch Sex Behav ; 50(7): 2887-2896, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34590217

RESUMO

We investigated the longitudinal relationship between erectile dysfunction (ED) drug use with behavioral factors, including substance use and sexual activities in men who have sex with men from the Multicenter AIDS Cohort Study during 1998-2016 (n = 1636). We used a bivariate random-intercept model to evaluate ED drug use along with other behavioral factors to assess relationships between the two outcomes over time on a population level and also at the individual level. Average ED drug use among men who have sex with men (MSM) with HIV was positively correlated with average use of marijuana (r = .19), poppers (r = .27), and stimulants (r = .25). In this group, testosterone use (r = .32), multiple partners (r = .41), insertive anal intercourse with condom (r = .40), and insertive anal intercourse without condom (r = .43) all showed moderate correlations over time with average ED use (p < .001). Associations among MSM without HIV were similar, with average marijuana use (r = .19) and stimulant use (r = .22) being positively correlated with average ED drug use, and were also correlated with having multiple partners (r = .36), insertive anal intercourse with condom (r = .22), and insertive anal intercourse without condom (r = .18) over time. Positive within-individual associations between ED drug use and multiple partners and insertive anal intercourse with and without condom were observed regardless of HIV serostatus. This study showed that MSM who reported use of ED drugs were also, on average, more likely to use recreational drugs and engage in sexual activities, such as having multiple partners and insertive anal intercourse. Within individuals, average ED drug use was also positively correlated with sexual behaviors.


Assuntos
Disfunção Erétil , Preparações Farmacêuticas , Minorias Sexuais e de Gênero , Transtornos Relacionados ao Uso de Substâncias , Estudos de Coortes , Disfunção Erétil/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Comportamento Sexual , Transtornos Relacionados ao Uso de Substâncias/epidemiologia
13.
Front Cardiovasc Med ; 8: 788194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34977194

RESUMO

Background: Optimism has been shown to be positively associated with better cardiovascular health (CVH). However, there is a dearth of prospective studies showing the benefits of optimism on CVH, especially in the presence of adversities, i.e., psychosocial risks. This study examines the prospective relationship between optimism and CVH outcomes based on the Life's Simple 7 (LS7) metrics and whether multilevel psychosocial risks modify the aforementioned relationship. Methods: We examined self-reported optimism and CVH using harmonized data from two U.S. cohorts: Multi-Ethnic Study of Atherosclerosis (MESA) and Jackson Heart Study (JHS). Modified Poisson regression models were used to estimate the relationship between optimism and CVH using LS7 among MESA participants (N = 3,520) and to examine the relationship of interest based on four biological LS7 metrics (body mass index, blood pressure, cholesterol, and blood glucose) among JHS and MESA participants (N = 5,541). For all CVH outcomes, we assessed for effect measure modification by psychosocial risk. Results: Among MESA participants, the adjusted risk ratio (aRR) for ideal or intermediate CVH using LS7 comparing participants who reported high or medium optimism to those with the lowest level of optimism was 1.10 [95% Confidence Interval (CI): 1.04-1.16] and 1.05 (95% CI: 0.99-1.11), respectively. Among MESA and JHS participants, the corresponding aRRs for having all ideal or intermediate (vs. no poor) metrics based on the four biological LS7 metrics were 1.05 (0.98-1.12) and 1.04 (0.97-1.11), respectively. The corresponding aRRs for having lower cardiovascular risk (0-1 poor metrics) based on the four biological LS7 metrics were 1.01 (0.98-1.03) and 1.01 (0.98-1.03), respectively. There was some evidence of effect modification by neighborhood deprivation for the LS7 outcome and by chronic stress for the ideal or intermediate (no poor) metrics outcome based on the four biological LS7 metrics. Conclusion: Our findings suggest that greater optimism is positively associated with better CVH based on certain LS7 outcomes among a racially/ethnically diverse study population. This relationship may be effect measure modified by specific psychosocial risks. Optimism shows further promise as a potential area for intervention on CVH. However, additional prospective and intervention studies are needed.

14.
Oncogenesis ; 9(10): 91, 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33041328

RESUMO

Checkpoint kinase 1 (Chk1) expression is enhanced in most cancers owing to oncogenic activation and constant replicative stress. Chk1 inactivation is a promising cancer therapy, as its inactivation leads to genomic instability, chromosomal catastrophe, and cancer cell death. Herein, we observed that miR-320c, downregulated in triple-negative breast cancer (TNBC) patients, can target Chk1. In addition, downregulated miR-320c expression was associated with poor overall survival in TNBC patients. As Chk1 was associated with the DNA damage response (DDR), we investigated the effect of miR-320c on DDR in TNBC cells. To induce DNA damage, we used platinum-based drugs, especially oxaliplatin, which is most effective with miR-320c. We observed that overexpression of miR-320c in TNBC regulated the oxaliplatin responsiveness by mediating DNA damage repair through the negative regulation of Chk1 in vitro. Furthermore, using a xenograft model, a combination of miR-320c mimic and oxaliplatin effectively inhibited tumor progression. These investigations indicate the potential of miR-320c as a marker of oxaliplatin responsiveness and a therapeutic target to increase the efficacy of chemotherapy in TNBC.

15.
Cancer Lett ; 454: 224-233, 2019 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-31004703

RESUMO

Triple negative breast cancer (TNBC) has higher aggressiveness and poorer outcomes compared with other subtypes of breast cancer. However, the genomic and molecular aberrations of TNBC are largely unknown. In this study, miR-374a-5p was discovered as a novel TNBC-specific miRNA and its functions and the molecular mechanisms involved were investigated. Combined gene expression profiling of miRNA-microarray and human transcriptome dataset analysis revealed that miR-374a-5p is specifically upregulated in TNBC patients. Functional studies using in vitro and in vivo models indicated that upregulated miR-374a-5p promotes tumor progression in TNBC. miR-374a-5p was also found to directly target arrestin beta 1 (ARRB1) that is specifically downregulated in TNBC patients in several human genomic datasets. Overexpressed ARRB1 reduced TNBC cell growth and migration, and the ARRB1 expression level is inversely correlated with the histological grade of the breast cancer and positively associated with TNBC patient survival, suggestive of a tumor-suppressive function of ARRB1 in breast cancer. Interestingly, increased ARRB1 activates AMPK in TNBC cells, associated with the expression of miR-374a-5p. Taken together, the findings suggest that miR-374a-5p is a potential prognostic marker of TNBC.


Assuntos
MicroRNAs/genética , Neoplasias de Mama Triplo Negativas/genética , beta-Arrestina 1/genética , Proteínas Quinases Ativadas por AMP/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Sobrevivência Celular/fisiologia , Progressão da Doença , Ativação Enzimática , Feminino , Células HEK293 , Humanos , Células MCF-7 , MicroRNAs/metabolismo , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/patologia , Regulação para Cima , beta-Arrestina 1/biossíntese , beta-Arrestina 1/metabolismo
16.
Sci Rep ; 8(1): 4700, 2018 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-29549324

RESUMO

This study aimed to test the hypothesis that the risk of major adverse cardiovascular events (MACE) is similar for subjects with asymptomatic mild and moderate carotid artery stenosis (CAS). We enrolled a total of 453 subjects with asymptomatic CAS (30-69%) detected on baseline screening Doppler ultrasound (DUS) examination between January 2008 and December 2010. The follow-up DUS findings and MACE occurrence (fatal or nonfatal myocardial infarction or stroke and all-cause mortality) were compared between subjects with mild (30-49%) and moderate (50-69%) CAS during the 8-year follow-up period. There was no significant difference in the occurrence of MACE between subjects with mild (n = 289) and moderate (n = 164) CAS (13.8% vs. 15.9%, respectively; p = 0.56), although there was a nonsignificant trend toward an increased risk of major ipsilateral stroke in subjects with moderate CAS (1.4% vs. 4.3%; p = 0.06). Multivariate regression analysis indicated that worsening CAS was independently associated with MACE occurrence (hazard ratio [HR], 4.40; 95% confidence interval [CI], 2.65-7.27; p < 0.01), whereas an increased serum high-density lipoprotein cholesterol level was correlated with a decreased risk of MACE (HR, 0.42; 95% CI, 0.23-0.75; p < 0.01). The cumulative risk of MACE in subjects with asymptomatic mild CAS is similar to that in subjects with asymptomatic moderate CAS.


Assuntos
Doenças Cardiovasculares/etiologia , Estenose das Carótidas/complicações , Idoso , Estenose das Carótidas/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
17.
Ultrasonography ; 35(4): 327-34, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27184652

RESUMO

PURPOSE: The aim of this study was to evaluate whether malignant-looking thyroid nodules with size reduction were malignant or not. METHODS: From November 2010 to July 2011, we retrospectively enrolled 16 patients with 16 nodules (11 females and five males; mean age, 55 years) who underwent core needle biopsy (CNB), and whose thyroid nodules had malignant ultrasonographic (US) features, although they showed size reduction (>20% decrease in maximum diameter) during the follow-up period (mean, 37±27 months). The histologic findings of the CNB specimen were reviewed and correlated with the US findings. US studies were analyzed for their internal content, shape, margin, echogenicity, the presence of microcalcification and macrocalcification, inner isoechoic rim, and low-echoic halo. RESULTS: All nodules were confirmed as benign by CNB. Pathologic analysis was available for 12 CNB specimens. US imaging showed central hypoechogenicity or marked hypoechogenicity in all cases and a peripheral isoechoic rim in 15 nodules. US-pathologic correlation showed that the central hypoechoic area was primarily composed of fibrosis (12/12) and hemorrhage (8/12) and that the isoechoic rim was composed of follicular cells. CONCLUSION: In our study, the CNB results of all of the malignant-looking thyroid nodules with size reduction were benign and were primarily composed of internal fibrosis and hemorrhage. Understanding these US and pathologic features could prevent repeated fine-needle aspiration or unnecessary diagnostic surgery.

18.
J Korean Acad Nurs ; 46(1): 149-58, 2016 Feb.
Artigo em Coreano | MEDLINE | ID: mdl-26963424

RESUMO

PURPOSE: This study was done to develop of the Korean intensive care delirium screening tool (KICDST). METHODS: The KICDST was developed in 5 steps: Configuration of conceptual frame, development of preliminary tool, pilot study, reliability and validity test, development of final KICDST. Reliability tests were done using degree of agreement between evaluators and internal consistency. For validity tests, CVI (Content Validity Index), ROC (Receiver Operating Characteristics) analysis, known group technique and factor analysis were used. RESULTS: In the reliability test, the degree of agreement between evaluators showed .80~1.00 and the internal consistency was KR-20=.84. The CVI was .83~1.00. In ROC analysis, the AUC (Area Under the ROC Curve) was .98. Assessment score was 4 points. The values for sensitivity, specificity, correct classification rate, positive predictive value, and negative predictive value were found to be 95.0%, 93.7%, 94.4%, 95.0% and 93.7%, respectively. In the known group technique, the average delirium screening tool score of the non-delirium group was 1.25±0.99 while that of delirium group was 5.07±1.89 (t=-16.33, p<.001). The factors were classified into 3 factors (cognitive change, symptom fluctuation, psychomotor retardation), which explained 67.4% of total variance. CONCLUSION: Findings show that the KICDST has high sensitivity and specificity. Therefore, this screening tool is recommended for early identification of delirium in intensive care patients.


Assuntos
Delírio/diagnóstico , Psicometria , Idoso , Área Sob a Curva , Cuidados Críticos , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Valor Preditivo dos Testes , Curva ROC , República da Coreia , Sensibilidade e Especificidade , Inquéritos e Questionários
19.
Nurse Educ Today ; 38: 48-53, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26804941

RESUMO

BACKGROUND: Program outcome evaluation is important because it is an indicator for good quality of education. Course-embedded assessment is one of the program outcome evaluation methods. However, it is rarely used in Korean nursing education. OBJECTIVES: The study purpose was to develop and apply preliminarily a course-embedded assessment system to evaluate one program outcome and to share our experiences. DESIGN AND SETTINGS: This was a methodological study to develop and apply the course-embedded assessment system based on the theoretical framework in one nursing program in South Korea. DATA: Scores for 77 students generated from the three practicum courses were used. METHODS: The course-embedded assessment system was developed following the six steps suggested by Han's model as follows. 1) One program outcome in the undergraduate program, "nursing process application ability", was selected and 2) the three clinical practicum courses related to the selected program outcome were identified. 3) Evaluation tools including rubric and items were selected for outcome measurement and 4) performance criterion, the educational goal level for the program, was established. 5) Program outcome was actually evaluated using the rubric and evaluation items in the three practicum courses and 6) the obtained scores were analyzed to identify the achievement rate, which was compared with the performance criterion. RESULTS: Achievement rates for the selected program outcome in adult, maternity, and pediatric nursing practicum were 98.7%, 100%, and 66.2% in the case report and 100% for all three in the clinical practice, and 100%, 100%, and 87% respectively for the conference. These are considered as satisfactory levels when compared with the performance criterion of "at least 60% or more". CONCLUSION: Course-embedded assessment can be used as an effective and economic method to evaluate the program outcome without running an integrative course additionally. Further studies to develop course-embedded assessment systems for other program outcomes in nursing education are needed.


Assuntos
Bacharelado em Enfermagem , Avaliação Educacional/métodos , Avaliação de Programas e Projetos de Saúde/métodos , Competência Clínica/normas , Pesquisa em Educação em Enfermagem , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto , República da Coreia
20.
Collegian ; 22(3): 299-305, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26552201

RESUMO

The purpose of this study was to examine the effectiveness of team-based learning (a well-recognized learning and teaching strategy), applied in a health assessment subject, on nursing students' perceived teamwork (team-efficacy and team skills) and academic performance (individual and team readiness assurance tests, and examination scores). A prospective, one-group, pre- and post-test design enrolled a convenience sample of 74 second-year nursing students at a university in Suwon, Korea. Team-based learning was applied in a 2-credit health assessment subject over a 16-week semester. All students received written material one week before each class for readiness preparation. After administering individual- and team-readiness assurance tests consecutively, the subject instructor gave immediate feedback and delivered a mini-lecture to the students. Finally, students carried out skill based application exercises. The findings showed significant improvements in the mean scores of students' perceived teamwork after the introduction of team-based learning. In addition, team-efficacy was associated with team-adaptability skills and team-interpersonal skills. Regarding academic performance, team readiness assurance tests were significantly higher than individual readiness assurance tests over time. Individual readiness assurance tests were significantly related with examination scores, while team readiness assurance tests were correlated with team-efficacy and team-interpersonal skills. The application of team-based learning in a health assessment subject can enhance students' perceived teamwork and academic performance. This finding suggests that team-based learning may be an effective learning and teaching strategy for improving team-work of nursing students, who need to collaborate and effectively communicate with health care providers to improve patients' health.


Assuntos
Comportamento Cooperativo , Bacharelado em Enfermagem/métodos , Avaliação Educacional/métodos , Educação em Saúde/métodos , Aprendizagem Baseada em Problemas/métodos , Estudantes de Enfermagem , Adulto , Currículo , Feminino , Humanos , Masculino , Estudos Prospectivos , República da Coreia , Adulto Jovem
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