Depression with comorbid anxiety or cognitive symptoms can vary in terms of symptoms, pathophysiology and antidepressant efficacy, but the underlying neurobiological mechanisms remain to be elucidated. Previous studies from our group and others have shown that as a classic animal model of depression, adolescent social stress (ASS) could stably induce a variety of emotional and cognitive alterations in adult animals, and accompanied by transcriptional decrease in brain-derived neurotrophic factor (BDNF) total and promoter IV levels in the medial prefrontal cortex (mPFC). The present study further identified the GABAergic synaptic and molecular changes downstream of BDNF signaling impairment in the mPFC and roles in various behavioral phenotypes induced by ASS. We found that ASS induced a set of emotional and cognitive symptoms, including decreased social interest, impaired cognitive function, and increased anxiety-like behavior, as well as decreased GABAergic transmission in the mPFC. The specific deletion of BDNF promoter IV directly caused impairments in social interest, cognitive function, and inhibition of GABAergic transmission, but no changes in anxiety-like behavior. Acute microinjections of tropomyosin-related kinase B (TrkB) agonists into the mPFC and chronic antidepressant treatment ameliorated the changes in social behavior and cognition, as well as the reduction in GABAergic synaptic transmission in the mPFC, but not anxiety in previously stressed adult mice. These results suggest that the downstream GABAergic transmission of BDNF signaling in the mPFC involved in depression with comorbid cognitive dysfunction induced by ASS and can be used as a therapeutic target for the treatment of cognitive dysfunction in depression. This article is part of the special issue on Stress, Addiction and Plasticity.
Differences in cardiovascular disease (CVD) risk between men and women have been widely reported. However, risk differences by gender-related characteristics (sociocultural characteristics) have been poorly studied, although these characteristics may associate with cardiovascular health. We explored associations of three gender-related characteristics with estimated CVD risk in men and women within various ethnic groups.
We used baseline data of 9185 participants of six ethnic groups of the HELIUS study (Amsterdam, the Netherlands), aged 40-65years, without CVD and diabetes. We studied the associations of three gender-related characteristics (time per week doing household work, primary earner status, performing a male- or female-dominated occupation) with CVD risk as estimated with SCORE algorithm using linear regression analyses. Analyses were stratified by sex, and adjusted for age and socioeconomic status. Next, we explored whether associations differed across ethnic groups.
Individuals who were no primary earners had a 6% (beta 0.94; 95% CI 0.88-1.01; men) and 8% (beta 0.92; 95% CI 0.90-0.95; women) lower CVD risk than primary earners. Veliparib Performing a female-dominated versus male-dominated occupation was associated with a 7% lower CVD risk in women (beta 0.93; 95% CI 0.88-0.99), but not in men. Time spent on household work was not associated with CVD risk. These associations were mostly consistent across ethnic groups.
Masculine gender-related characteristics were associated with a higher estimated CVD risk across ethnic groups, specifically, being the primary earner (men and women) and performing a male-dominated occupation (women). Our findings may in future help to identify specific high-risk groups.
Masculine gender-related characteristics were associated with a higher estimated CVD risk across ethnic groups, specifically, being the primary earner (men and women) and performing a male-dominated occupation (women). Our findings may in future help to identify specific high-risk groups.
Intracranial hemorrhage (ICH) represents the most serious complication of oral anticoagulant therapy (OAT) in patients with atrial fibrillation (AF), and AF patients with previous ICH are a challenge for clinicians. Left atrial appendage (LAA) occlusion has emerged as an alternative option for AF patients not suitable for OAT. Currently, few data are available on long term outcomes after LAA occlusion in this population. We evaluated the safety and efficacy of LAA occlusion in a cohort of patients with AF and previous ICH.
This is a multicenter, observational, retrospective study involving 5 LAA occlusion centers in Italy. It includes all consecutive patients (n=120) with previous ICH who underwent LAA occlusion for nonvalvular AF and high thromboembolic risk. Procedural outcomes, post-procedural therapies and 12-months follow-up data were analyzed.
The device was successfully implanted in 100% of cases, with a 6% of major peri-procedural complications. 59% had a prior ICH during OAT. The sample had a high risk of stroke (5.18%/year) and bleeding (6.62%/year). 30% were discharged on single and 54.2% on dual antiplatelet therapy. The expected annual risk for thromboembolism was 5.1%. Excluding periprocedural ischemic complications, the stroke annual rate was 1.8%. The expected annual risk of bleeding was 6.7%. The observed annual bleeding rate was 5.45%.
Percutaneous LAA occlusion is an effective option for AF patients and previous intracranial hemorrhage. After LAA occlusion, a single antiplatelet therapy strategy could be considered for patients with the highest risk of recurrent bleeding.
Percutaneous LAA occlusion is an effective option for AF patients and previous intracranial hemorrhage. After LAA occlusion, a single antiplatelet therapy strategy could be considered for patients with the highest risk of recurrent bleeding.Retinal microcirculation reflects retinal perfusion abnormalities and retinal arterial structural changes at relatively early stages of various cardiovascular diseases. Our objective has been to establish reference values for major functional and structural parameters of retinal microcirculation in a randomly selected urban population sample. A total of 398 randomly selected individuals from an urban population aged 25 to 65 years, resident in Pilsen, Czech Republic, were screened for major cardiovascular risk factors. Retinal microcirculation was assessed using scanning laser Doppler flowmetry (SLDF), with data evaluable in 343 patients. Of this number, complete data were available for 256 individuals free from manifest cardiovascular disease, diabetes and drug treatment for hypertension and/or dyslipidemia, constituting the reference value population. Juxtapapillary retinal capillary blood flow has increased significantly with age whereas vessel and luminal diameters have decreased. No sex differences in retinal microcirculation parameters have been found.Veliparib
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