bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Diindolylmethane on Estrogen-related Hormones, Metabolites and Tamoxifen Metabolism: Results of a Randomized, Placebo-controlled Trial
Authors: Thomson CA , Chow SHH , Roe D , Wertheim B , Chalasani P , Altbach M , Thompson P , Stopek A , Maskaranic G 
Published: March 2017

Abstract
Dietary supplement use is high among breast cancer survivors. One compound natural to cruciferous vegetables, diindolylmethane (DIM), is among the supplements commonly used. This bioactive compound has significant experimental evidence for bioactivity in breast chemoprevention. Sparse evidence in the form of well-designed human clinical trials exist to test its efficacy or safety. Methods: In this double-blind placebo-controlled study women taking tamoxifen for breast cancer primary or tertiary prevention were randomly assigned to receive 150 mg DIM (BioResponse(BR)-DIM) twice daily or a placebo for a minimum period of 12 months. Primary outcome was change in urinary estrogen metabolites 2-hydroxyestrone and 16α-hydroxyestrone (baseline to 6 weeks, 6 and 12 months). Secondary endpoints included breast density by mammogram and fat:water ratio MRI (baseline to 12 months) and serum estrogens (baseline to 6, 12 months). Safety data were also evaluated, including tamoxifen metabolites. Results: Adherence to study pills was &gt;91% by pill count and urinary DIM metabolite assessment. In participants assigned DIM there was a significant and sustained shift in urinary estrogen metabolism favoring a higher 2-OH:16α-OH ratio; sex hormone binding globulin (SHBG) was also increased. No change in breast density was demonstrated. Safety analysis showed no appreciable differences in adverse events by treatment arm; however, tamoxifen metabolism for the parent compound as well as endoxifen and 4-OH endoxifen were appreciably reduced in women assigned to the DIM arm. Conclusions In this first large study of DIM in the setting of breast cancer chemoprevention, a favorable shift in estrogen metabolism and SHBG was demonstrated. However, the reduction in tamoxifen metabolites raises concern regarding the potential interaction between DIM and tamoxifen, an area in need of continued research. Impact Given the widespread and generally unsupported use of dietary supplementation by breast cancer survivors, these data will help to inform the use of DIM as a dietary supplement for breast cancer patients receiving tamoxifen.
Racial/Ethnic Differences in the Use and Discontinuation of Adjuvant Endocrine Therapy by Hormone-Receptor Status in Association with Mortality among Breast Cancer Patients Enrolled in Medicare Part D
Authors: Farias AJ , Du XL 
Published: March 2017

Abstract
Purpose: To determine whether racial/ethnic differences in the use and discontinuation of adjuvant endocrine therapy (AET) differed by hormone-receptor status and was associated with an increased risk of mortality. Methods: We used the SEER/Medicare dataset to conduct a retrospective cohort study of women diagnosed with stage 0-IV breast cancer from 2007–2009 enrolled in Medicare Part D. Women were stratified based on tumor stage and hormone-receptor status (positive, negative, unknown). We performed multivariable logistic regression to assess racial differences in the odds of AET initiation and two Cox proportional hazards models to determine the risk of AET discontinuation and overall mortality. Discontinuation was defined as ≥120 consecutive days without AET medication. All analyses were adjusted for sociodemographic, comorbidities, treatment (surgery, chemotherapy, radiotherapy), and prognostic factors (tumor stage, size, grade, lymph node involvement). Results: Of the 19,960 women diagnosed with breast cancer, 59.3% initiated AET within 12 months of diagnosis. Among women with hormone receptor-positive breast cancer 70.6% initiated AET compared to 20.7% of women with hormone receptor-negative or unknown. Among women with hormone-positive stage I–III breast cancer, blacks were less likely to discontinue AET compared to non-Hispanic whites (HR: 0.89, 95% CI 0.80–0.98). Among women diagnosed with stage IV, hormone receptor-positive breast cancer, Hispanic women were more likely to discontinue AET compared to non-Hispanic whites (HR: 1.68, 95% CI: 1.01–2.78). Women who initiated with the aromatase inhibitors had a 12% increased risk of discontinuation compared to women who initiated with tamoxifen (HR: 1.12, 95% CI 1.05–1.20). In all racial/ethnic groups, regardless of stage and hormone-receptor status, discontinuation of AET was associated with a significantly higher risk of all-cause mortality (HR: 1.72, 95% CI: 1.54–1.93). Conclusions: Over two-third of patients with hormone receptor-positive breast cancer initiated AET and a substantial proportion of hormone receptor-negative women did as well. Discontinuation of AET was associated with a significantly higher risk of all-cause mortality regardless of hormone status and stage.
Cardiac Fibroblast–Specific Activating Transcription Factor 3 Protects Against Heart Failure by Suppressing MAP2K3-p38 Signaling
Authors: Li Yulin , Li Zhenya , Zhang Congcong , Li Ping , Wu Yina , Wang Chunxiao , Bond Lau Wayne , Ma Xin-liang , Du Jie 
Published: March 2017

Background:
Hypertensive ventricular remodeling is a common cause of heart failure. However, the molecular mechanisms regulating ventricular remodeling remain poorly understood.

Methods:
We used a discovery-driven/nonbiased approach to identify increased activating transcription factor 3 (ATF3) expression in hypertensive heart. We used loss/gain of function approaches to understand the role of ATF3 in heart failure. We also examined the mechanisms through transcriptome, chromatin immunoprecipitation sequencing analysis, and in vivo and in vitro experiments.

Results:
ATF3 expression increased in murine hypertensive heart and human hypertrophic heart. Cardiac fibroblast cells are the primary cell type expressing high ATF3 levels in response to hypertensive stimuli. ATF3 knockout (ATF3KO) markedly exaggerated hypertensive ventricular remodeling, a state rescued by lentivirus-mediated/miRNA-aided cardiac fibroblast–selective ATF3 overexpression. Conversely, conditional cardiac fibroblast cell–specific ATF3 transgenic overexpression significantly ameliorated ventricular remodeling and heart failure. We identified Map2K3 as a novel ATF3 target. ATF3 binds with the Map2K3 promoter, recruiting HDAC1, resulting in Map2K3 gene–associated histone deacetylation, thereby inhibiting Map2K3 expression. Genetic Map2K3 knockdown rescued the profibrotic/hypertrophic phenotype in ATF3KO cells. Last, we demonstrated that p38 is the downstream molecule of Map2K3 mediating the profibrotic/hypertrophic effects in ATF3KO animals. Inhibition of p38 signaling reduced transforming growth factor-β signaling-related profibrotic and hypertrophic gene expression, and blocked exaggerated cardiac remodeling in ATF3KO cells.

Conclusions:
Our study provides the first evidence that ATF3 upregulation in cardiac fibroblasts in response to hypertensive stimuli protects the heart by suppressing Map2K3 expression and subsequent p38-transforming growth factor-β signaling. These results suggest that positive modulation of cardiac fibroblast ATF3 may represent a novel therapeutic approach against hypertensive cardiac remodeling.
Distinct Frontoparietal Networks Underlying Attentional Effort and Cognitive Control
Authors: Berry Anne S. , Sarter Martin , Lustig Cindy 
Published: March 2017

Abstract
We investigated the brain activity patterns associated with stabilizing performance during challenges to attention. Our findings revealed distinct patterns of frontoparietal activity and functional connectivity associated with increased attentional effort versus preserved performance during challenged attention. Participants performed a visual signal detection task with and without presentation of a perceptual-attention challenge (changing background). The challenge condition increased activation in frontoparietal regions including right mid-dorsal/dorsolateral PFC (RPFC), approximating Brodmann's area 9, and superior parietal cortex. We found that greater behavioral impact of the challenge condition was correlated with greater RPFC activation, suggesting that increased engagement of cognitive control regions is not always sufficient to maintain high levels of performance. Functional connectivity between RPFC and ACC increased during the challenge condition and was also associated with performance declines, suggesting that the level of synchronized engagement of these regions reflects individual differences in attentional effort. Pretask, resting-state RPFC–ACC connectivity did not predict subsequent performance, suggesting that RPFC–ACC connectivity increased dynamically during task performance in response to performance decrement and error feedback. In contrast, functional connectivity between RPFC and superior parietal cortex not only during the task but also during pretask rest was associated with preserved performance in the challenge condition. Together, these data suggest that resting frontoparietal connectivity predicts performance on attention tasks that rely on those same cognitive control networks and that, under challenging conditions, other control regions dynamically couple with this network to initiate the engagement of cognitive control.
Assessing the Effect of Early Visual Cortex Transcranial Magnetic Stimulation on Working Memory Consolidation
Authors: van Lamsweerde Amanda E. , Johnson Jeffrey S. 
Published: March 2017

Abstract
Maintaining visual working memory (VWM) representations recruits a network of brain regions, including the frontal, posterior parietal, and occipital cortices; however, it is unclear to what extent the occipital cortex is engaged in VWM after sensory encoding is completed. Noninvasive brain stimulation data show that stimulation of this region can affect working memory (WM) during the early consolidation time period, but it remains unclear whether it does so by influencing the number of items that are stored or their precision. In this study, we investigated whether single-pulse transcranial magnetic stimulation (spTMS) to the occipital cortex during VWM consolidation affects the quantity or quality of VWM representations. In three experiments, we disrupted VWM consolidation with either a visual mask or spTMS to retinotopic early visual cortex. We found robust masking effects on the quantity of VWM representations up to 200 msec poststimulus offset and smaller, more variable effects on WM quality. Similarly, spTMS decreased the quantity of VWM representations, but only when it was applied immediately following stimulus offset. Like visual masks, spTMS also produced small and variable effects on WM precision. The disruptive effects of both masks and TMS were greatly reduced or entirely absent within 200 msec of stimulus offset. However, there was a reduction in swap rate across all time intervals, which may indicate a sustained role of the early visual cortex in maintaining spatial information.
Multimodal Imaging Evidence for a Frontoparietal Modulation of Visual Cortex during the Selective Processing of Conditioned Threat
Authors: Petro Nathan M. , Gruss L. Forest , Yin Siyang , Huang Haiqing , Miskovic Vladimir , Ding Mingzhou , Keil Andreas 
Published: March 2017

Abstract
Emotionally salient cues are detected more readily, remembered better, and evoke greater visual cortical responses compared with neutral stimuli. The current study used concurrent EEG-fMRI recordings to identify large-scale network interactions involved in the amplification of visual cortical activity when viewing aversively conditioned cues. To generate a continuous neural signal from pericalcarine visual cortex, we presented rhythmic (10/sec) phase-reversing gratings, the orientation of which predicted the presence (CS+) or absence (CS−) of a cutaneous electric shock (i.e., the unconditioned stimulus). The resulting single trial steady-state visual evoked potential (ssVEP) amplitude was regressed against the whole-brain BOLD signal, resulting in a measure of ssVEP-BOLD coupling. Across all trial types, ssVEP-BOLD coupling was observed in both primary and extended visual cortical regions, the rolandic operculum, as well as the thalamus and bilateral hippocampus. For CS+ relative to CS− trials during the conditioning phase, BOLD-alone analyses showed CS+ enhancement at the occipital pole, superior temporal sulci, and the anterior insula bilaterally, whereas ssVEP-BOLD coupling was greater in the pericalcarine cortex, inferior parietal cortex, and middle frontal gyrus. Dynamic causal modeling analyses supported connectivity models in which heightened activity in pericalcarine cortex for threat (CS+) arises from cortico-cortical top–down modulation, specifically from the middle frontal gyrus. No evidence was observed for selective pericalcarine modulation by deep cortical structures such as the amygdala or anterior insula, suggesting that the heightened engagement of pericalcarine cortex for threat stimuli is mediated by cortical structures that constitute key nodes of canonical attention networks.
Safety and Security of Daflon 500 mg in Venous Insufficiency and in Hemorrhoidal Disease
Authors: Meyer Olivier C. 
Published: March 2017

Daflon 500 mg* is a new flavonoid vasoprotector venotonic agent whose active principle is micronized and contains 90% diosmin and 10% flavonoids expressed as hesperidin. In animal studies, the safety of Daflon 500 mg is shown by an LD50 (lethal dose so) of more than 3 g/kg, ie, 180 times the daily therapeutic dose, as well as by the absence of any toxic effect after repeated oral dosing for thirteen and twenty-six weeks, using a dose representing 35 times the daily dosage, in the rate and primate. Daflon 500 mg has no mutagenic action nor any significant effect on reproductive function. Gastrointestinal tolerance is good when administered orally in the rat. Transplacental passage and passage into breast milk are minimal. In the rat, 0.003% of the administered dose has been found in each fetus and 1% in breast milk. Clinical trials fulfill international scientific requirements and have collected more than 2850 patients treated with Daflon 500 mg at the dosage of two tablets per day for six weeks to one year. The proportion of patients with side effects (10% of those treated), essentially of a gastrointestinal or autonomic nature and leading to a rate of only 1.1% trial dropouts, is less than described in 225 patients given a placebo (13.9%) in controlled trials. Satisfactory clinical acceptability already confirmed in the short term was equally found in long-term treatment. Hemodynamic parameters (systolic and diastolic blood pressure) as well as laboratory parameters (hematology, liver and renal function, metabolic) were uninfluenced even by prolonged treatment for one year at the dosage of two tablets per day. No contraindications have been found during the therapeutic use of Daflon 500 mg, even in the elderly and in pregnant women. No evidence has been found of any interference with combined drugs. Daflon 500 mg is free of any photosensitizing action. Daflon 500 mg combines thoroughly proven therapeutic efficacy with excellent safety of use confirmed in specific and methodologically reliable toxicologic studies as well as in a large number of clinical trials with patients treated daily for six weeks to one year.
Prevalence and risk factors of depression among garment workers in Bangladesh
Authors: Fitch Taylor Jennelle , Moran Jacxelyn , Villanueva Gabriela , Sagiraju Hari Krishna Raju , Quadir Mohammad Morshedul , Alamgir Hasanat 
Published: March 2017

Background: Depression is a growing health issue in both developed and developing countries. General unawareness at the population level, lack of training among health care providers and scarcity of resources including treatment opportunities may conceal the real burden of depression in developing countries, and more epidemiological studies on its prevalence and risk factors are critically needed. Aim: This study reports the prevalence of depression and its associated risk factors among female garment factory workers in Bangladesh – a major supplier country of clothes for the Western market. This research should generate useful evidence for national and international stakeholders who have an interest in improving health, safety and well-being of outsourced factory workers. Methods: A survey was conducted on a sample of 600 lower socio-economic status working women including garment workers. This survey collected data on demographic and health profile of these workers. The primary outcome was depression as measured by Patient Health Questionnaire 9. It also obtained data on traumatic life events and post-traumatic stress disorder. Results: The prevalence of depression was 23.5%: 20.9% among garment workers and 26.4% among others. Part-time employment (odds ratio-OR): 2.36, 95% confidence interval (95% CI): 1.01–5.51), chronic pain (OR: 1.67, 95% CI: 1.01–2.78), two or more traumatic life events (OR: 6.43, 95% CI: 2.85–14.55) and dysuria (OR: 2.50, 95% CI: 1.02–6.15) were found to be significantly associated with depression among these workers in multivariate regression model. Depression prevalene lowered by 11% among these workers for every additional monthly earning of 1,000 taka (US$12). Conclusion: Depression is a multifaceted health issue with many personal, social, economic and health determinants and consequences. This study demonstrates that the prevalence of moderate-to-severe depression among working women in Bangladesh is quite high. Prevention and treatment of depression in developing countries and societies can reduce suffering, lower incidence of suicide, and prevent economic loss. Creating awareness on outsourced workers’ poor mental health may help in developing initiatives to protect and preserve their well-being.
Predicting Adherence to Aromatase Inhibitor Therapy among Breast Cancer Survivors: An Application of the Protection Motivation Theory
Authors: Karmakar Monita , Pinto Sharrel L , Jordan Timothy R , Mohamed Iman , Holiday-Goodman Monica 
Published: March 2017

The purpose of this observational study was to determine if the Protection Motivation Theory could predict and explain adherence to aromatase inhibitor (AI) therapy among breast cancer survivors. Purposive sampling was used to identify 288 survivors who had been prescribed AI therapy. A valid and reliable survey was mailed to survivors. A total of 145 survivors completed the survey. The Morisky scale was used to measure adherence to AI. The survivors reported a mean score of 6.84 (±0.66) on the scale. Nearly 4 in 10 survivors (38%) were non-adherent. Adherence differed by age, marital status, insurance status, income, and presence of co-morbid conditions. Self-efficacy (r=0.485), protection motivation (r=0.310), and Response Efficacy (r=0.206) were positively and significantly correlated with adherence. Response Cost (r=-0.235) was negatively correlated with adherence. The coping appraisal constructs were statistically significant predictors medication adherence (β=0.437) with self-efficacy being the strongest significant predictor of adherence (β = 0.429).
Synthetic Growth Hormone-Releasing Peptides (GHRPs): A Historical Appraisal of the Evidences Supporting Their Cytoprotective Effects
Authors: Berlanga-Acosta Jorge , Abreu-Cruz Angel , Barco Herrera Diana García-del , Mendoza-Marí Yssel , Rodríguez-Ulloa Arielis , García-Ojalvo Ariana , Falcón-Cama Viviana , Hernández-Bernal Francisco , Beichen Qu , Guillén-Nieto Gerardo 
Published: March 2017

Background: Growth hormone-releasing peptides (GHRPs) constitute a group of small synthetic peptides that stimulate the growth hormone secretion and the downstream axis activity. Mounting evidences since the early 1980s delineated unexpected pharmacological cardioprotective and cytoprotective properties for the GHRPs. However, despite intense basic pharmacological research, alternatives to prevent cell and tissue demise before lethal insults have remained as an empty niche in the clinical armamentarium. Here, we have rigorously reviewed the investigational development of GHRPs and their clinical niching perspectives. Methodology: PubMed/MEDLINE databases, including original research and review articles, were explored. The search design was date escalated from 1980 and included articles in English only. Results and Conclusions: GHRPs bind to two different receptors (GHS-R1a and CD36), which redundantly or independently exert relevant biological effects. GHRPs’ binding to CD36 activates prosurvival pathways such as PI-3K/AKT1, thus reducing cellular death. Furthermore, GHRPs decrease reactive oxygen species (ROS) spillover, enhance the antioxidant defenses, and reduce inflammation. These cytoprotective abilities have been revealed in cardiac, neuronal, gastrointestinal, and hepatic cells, representing a comprehensive spectrum of protection of parenchymal organs. Antifibrotic effects have been attributed to some of the GHRPs by counteracting fibrogenic cytokines. In addition, GHRP family members have shown a potent myotropic effect by promoting anabolia and inhibiting catabolia. Finally, GHRPs exhibit a broad safety profile in preclinical and clinical settings. Despite these fragmented lines incite to envision multiple pharmacological uses for GHRPs, especially as a myocardial reperfusion damage-attenuating candidate, this family of “drugable” peptides awaits for a definitive clinical niche.
Comparison of 3 Different Perioperative Care Models for Patients With Hip Fractures Within 1 Health Service
Authors: Coventry Lillian Sarah , Nguyen Austin , Karahalios Amalia , Roshan-Zamir Sasha , Tran Phong 
Published: March 2017

Introduction: Orthogeriatric care models have been introduced within many health-care facilities to improve outcomes for hip fracture patients. This study aims to evaluate differences in care between 3 models, an orthopedic model, a geriatric model, and a comanaged model. Materials and Methods: A retrospective analysis was conducted for hip fracture patients treated at Western Health between November 2012 and March 2014. All patients aged 65 years or older were included in the analysis. Results: There were 183 patients in the orthopedic model, 137 in the geriatric model, and 126 in the comanaged model. Demographics and clinical characteristics were similar across the 3 models. Length of stay, mortality, and discharge destination were also consistent across the 3 groups. However, groups involving geriatricians were more likely to receive preoperative medical assessments, have greater recognition of postoperative medical problems, and have implementation of long-term osteoporosis management. Conclusion: The involvement of geriatricians in perioperative care models resulted in more comprehensive medical care without impacting length of stay, mortality, or discharge destination.