Depression,Dietary Habits,and Cardiovascular Events Among Women with Suspected Myocardial Ischemia

Background

Dietary habits and depression are associated with cardiovascular disease risk. Patients with depression often report poor eating habits, and dietary factors may help explain commonly observed associations between depression and cardiovascular disease.

MethodS

From 1996 to 2000, 936 women were enrolled in the Women's Ischemia Syndrome Evaluation at 4 US academic medical centers at the time of clinically indicated coronary angiography and then assessed (median follow-up, 5.9 years) for adverse outcomes (cardiovascular disease death, heart failure, myocardial infarction, stroke). Participants completed a protocol including coronary angiography (coronary artery disease severity) and depression assessments (Beck Depression Inventory scores, antidepressant use, and depression treatment history). A subset of 201 women (mean age, 58.5 years; standard deviation, 11.4) further completed the Food Frequency Questionnaire for Adults (1998 Block). We extracted daily fiber intake and daily servings of fruit and vegetables as measures of dietary habits.

Results

In separate Cox regression models adjusted for age, smoking, and coronary artery disease severity, Beck Depression Inventory scores (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01-1.10), antidepressant use (HR, 2.4; 95% CI, 1.01-5.9), and a history of treatment for depression (HR, 2.4; 95% CI, 1.1-5.3) were adversely associated with time to cardiovascular disease outcomes. Fiber intake (HR, 0.87; 95% CI, 0.78-0.97) and fruit and vegetable consumption (HR, 0.36; 95% CI, 0.19-0.70) were associated with a decreased time to cardiovascular disease event risk. In models including dietary habits and depression, fiber intake and fruit and vegetable consumption remained associated with time to cardiovascular disease outcomes, whereas depression relationships were reduced by 10% to 20% and nonsignificant.

Conclusions

Among women with suspected myocardial ischemia, we observed consistent relationships among depression, dietary habits, and time to cardiovascular disease events. Dietary habits partly explained these relationships. These results suggest that dietary habits should be included in future efforts to identify mechanisms linking depression to cardiovascular disease.     

BclAF1 restriction factor is neutralized by proteasomal degradation and microRNA repression during human cytomegalovirus infection

Cell proteins can restrict the replication of viruses. Here, we identify the cellular BclAF1 protein as a human cytomegalovirus restriction factor and describe two independent mechanisms the virus uses to decrease its steady-state levels. Immediately following infection, the viral pp71 and UL35 proteins, which are delivered to cells within virions, direct the proteasomal degradation of BclAF1. Although BclAF1 reaccumulates through the middle stages of infection, it is subsequently down-regulated at late times by miR-UL112-1, a virus-encoded microRNA. In the absence of BclAF1 neutralization, viral gene expression and replication are inhibited. These data identify two temporally and mechanistically distinct functions used by human cytomegalovirus to down-regulate a cellular antiviral protein.     

An RNA virus hijacks an incognito function of a DNA repair enzyme

A previously described mammalian cell activity, called VPg unlinkase, specifically cleaves a unique protein-RNA covalent linkage generated during the viral genomic RNA replication steps of a picornavirus infection. For over three decades, the identity of this cellular activity and its normal role in the uninfected cell had remained elusive. Here we report the purification and identification of VPg unlinkase as the DNA repair enzyme, 5'-tyrosyl-DNA phosphodiesterase-2 (TDP2). Our data show that VPg unlinkase activity in different mammalian cell lines correlates with their differential expression of TDP2. Furthermore, we show that recombinant TDP2 can cleave the protein-RNA linkage generated by different picornaviruses without impairing the integrity of viral RNA. Our results reveal a unique RNA repair-like function for TDP2 and suggest an unusual role in host-pathogen interactions for this cellular enzyme. On the basis of the identification of TDP2 as a potential antiviral target, our findings may lead to the development of universal therapeutics to treat the millions of individuals afflicted annually with diseases caused by picornaviruses, including myocarditis, aseptic meningitis, encephalitis, hepatitis, and the common cold.     

How national context,project design,and local community characteristics influence success in community-based conservation projects

Community-based conservation (CBC) promotes the idea that conservation success requires engaging with, and providing benefits for, local communities. However, CBC projects are neither consistently successful nor free of controversy. Innovative recent studies evaluating the factors associated with success and failure typically examine only a single resource domain, have limited geographic scope, consider only one outcome, or ignore the nested nature of socioecological systems. To remedy these issues, we use a global comparative database of CBC projects identified by systematic review to evaluate success in four outcome domains (attitudes, behaviors, ecological, economic) and explore synergies and trade-offs among these outcomes. We test hypotheses about how features of the national context, project design, and local community characteristics affect these measures of success. Using bivariate analyses and multivariate proportional odds logistic regressions within a multilevel analysis and model-fitting framework, we show that project design, particularly capacity-building in local communities, is associated with success across all outcomes. In addition, some characteristics of the local community in which projects are conducted, such as tenure regimes and supportive cultural beliefs and institutions, are important for project success. Surprisingly, there is little evidence that national context systematically influences project outcomes. We also find evidence of synergies between pairs of outcomes, particularly between ecological and economic success. We suggest that well-designed and implemented projects can overcome many of the obstacles imposed by local and national conditions to succeed in multiple domains.     

Interventions to increase osteoporosis treatment in patients with 'incidentally' detected vertebral fractures

BackgroundMost vertebral compression fractures are not recognized or treated. We conducted a controlled trial in older patients with vertebral fractures incidentally reported on chest radiographs, comparing usual care with osteoporosis interventions directed at physicians (opinion-leader-endorsed evidence summaries and reminders) or physicians+patients (adding activation with leaflets and telephone counseling).MethodsPatients aged >60 years who were discharged home from emergency departments and who had vertebral fractures reported but were not treated for osteoporosis were allocated to usual care (control) or physician intervention using alternate-week time series. After 3 months, untreated controls were re-allocated to physician+patient intervention. Allocation was concealed, outcomes ascertainment blinded, and analyses intent-to-treat. Primary outcome was starting osteoporosis treatment within 3 months.ResultsThere were 1315 consecutive patients screened, and 240 allocated to control (n = 123) or physician intervention (n = 117). Groups were similar at baseline (average age 74 years, 45% female, 58% previous fractures). Compared with controls, physician interventions significantly (all P <.001) increased osteoporosis treatment (20 [17%] vs 2 [2%]), bone mineral density testing (51 [44%] vs 5 [4%]), and bone mineral density testing or treatment (57 [49%] vs 7 [6%]). Three months after controls were re-allocated to physician+patient interventions, 22% had started treatment and 65% had bone mineral density testing or treatment (P <.001 vs controls). Physician+patient interventions increased bone mineral density testing or treatment an additional 16% compared with physician interventions (P = .01).ConclusionsAn opinion-leader-based intervention targeting physicians substantially improved rates of bone mineral density testing and osteoporosis treatment in patients with incidental vertebral fractures, compared with usual care. Even better osteoporosis management was achieved by adding patient activation to physician interventions [NCT00388908].     

Hepatocyte polarization is essential for the productive entry of the hepatitis B virus

Human hepatitis B virus (HBV) is characterized by a high species specificity and a distinct liver tropism. Within the liver, HBV replication occurs in differentiated and polarized hepatocytes. Accordingly, the in vitro HBV infection of primary human hepatocytes (PHHs) and the human hepatoma cell line, HepaRG, is restricted to differentiated, hepatocyte-like cells. Though preparations of PHH contain up to 100% hepatic cells, cultures of differentiated HepaRG cells are a mixture of hepatocyte-like and biliary-like epithelial cells. We used PHH and HepaRG cells and compared the influence of virus inoculation dose, cell differentiation, and polarization on productive HBV infection. At multiplicities of genome equivalents (mge) >8,000, almost 100% of PHHs could be infected. In contrast, only a subset of HepaRG cells stained positive for HBcAg at comparable or even higher mge. Infection predominantly occurred at the edges of islands of hepatocyte-like HepaRG cells. This indicates a limited accessibility of the HBV receptor, possibly as a result of its polar sorting. Multidrug resistance protein 2 (MRP2), a marker selectively transported to the apical (i.e., canalicular) cell membrane, revealed two polarization phenotypes of HepaRG cells. HBV infection within the islands of hepatocyte-like HepaRG cells preferentially occurred in cells that resemble PHH, exhibiting canalicular structures. However, disruption of cell-cell junctions allowed the additional infection of cells that do not display a PHH-like polarization. CONCLUSION: HBV enters hepatocytes via the basolateral membrane. This model, at least partially, explains the difference of PHH and HepaRG cells in infection efficacy, provides insights into natural HBV infection, and establishes a basis for optimization of the HepaRG infection system.     

Hematologic responses to deferasirox therapy in transfusion-dependent patients with myelodysplastic syndromes

Background

Reductions in transfusion requirements/improvements in hematologic parameters have been associated with iron chelation therapy in transfusion-dependent patients, including those with myelodysplastic syndromes; data on there reductions/improvements have been limited to case reports and small studies.

Design and Methods

To explore this observation in a large population of patients, we report a post-hoc analysis evaluating hematologic response to deferasirox in a cohort of iron-overloaded patients with myelodysplastic syndromes enrolled in the Evaluation of Patients’ Iron Chelation with Exjade^® (EPIC) study using International Working Group 2006 criteria.

Results

Two-hundred and forty-seven, 100 and 50 patients without concomitant medication for myelodysplastic syndromes were eligible for analysis of erythroid, platelet and neutrophil responses, respectively. Erythroid, platelet and neutrophil responses were observed in 21.5% (53/247), 13.0% (13/100) and 22.0% (11/50) of the patients after a median of 109, 169 and 226 days, respectively. Median serum ferritin reductions were greater in hematologic responders compared with non-responders at end of study, although these differences were not statistically significant. A reduction in labile plasma iron to less than 0.4 μmol/L was observed from week 12 onwards; this change did not differ between hematologic responders and non-responders.

Conclusions

This analysis suggests that deferasirox treatment for up to 1 year could lead to improvement in hematologic parameters in some patients with myelodysplastic syndromes.