Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Measuring Psychological Inflexibility of Suicidal Thoughts: The Acceptance and Action Questionnaire for Suicidal Ideation (AAQ-SI)

Cognitive Therapy and Research - Despite interest in psychological inflexibility as a marker of suicide risk, no measure of psychological inflexibility specific to SI exists. The present study...     

我国家庭医生签约服务政策执行的制约因素与优化路径：基于史密斯政策执行过程模型

深化家庭医生签约服务是深化医药卫生体制改革、强化基层医疗卫生服务、实现"健康中国"战略目标的重要选择，也是当前更好维护人民群众健康的重要途径。为有效推进签约服务工作，国家陆续推出各项政策，全国各地也在积极进行实践探索，成效明显。但是，签约服务仍面临诸多问题，其中"执行难"是签约服务深度推进的一大困境。通过史密斯政策执行过程模型，结合签约服务政策执行过程，发现签约服务仍存在法治性不足、政策执行人员水平不高、激励不足、政策环境影响等诸多制约因素。因此，需要从法律和制度方面进行顶层设计、提升执行人员素质和职业认同、建立医患互信、优化政策执行环境等角度进行政策创新，探索家庭医生签约服务可持续发展的路径。     

PREDICT-GTN 1: Can we improve the FIGO scoring system in gestational trophoblastic neoplasia?

Gestational trophoblastic neoplasia (GTN) patients are treated according to the eight-variable International Federation of Gynaecology and Obstetrics (FIGO) scoring system, that aims to predict first-line single-agent chemotherapy resistance. FIGO is imperfect with one-third of low-risk patients developing disease resistance to first-line single-agent chemotherapy. We aimed to generate simplified models that improve upon FIGO. Logistic regression (LR) and multilayer perceptron (MLP) modelling (n = 4191) generated six models (M1-6). M1, all eight FIGO variables (scored data); M2, all eight FIGO variables (scored and raw data); M3, nonimaging variables (scored data); M4, nonimaging variables (scored and raw data); M5, imaging variables (scored data); and M6, pretreatment hCG (raw data) + imaging variables (scored data). Performance was compared to FIGO using true and false positive rates, positive and negative predictive values, diagnostic odds ratio, receiver operating characteristic (ROC) curves, Bland-Altman calibration plots, decision curve analysis and contingency tables. M1-6 were calibrated and outperformed FIGO on true positive rate and positive predictive value. Using LR and MLP, M1, M2 and M4 generated small improvements to the ROC curve and decision curve analysis. M3, M5 and M6 matched FIGO or performed less well. Compared to FIGO, most (excluding LR M4 and MLP M5) had significant discordance in patient classification (McNemar's test P < .05); 55-112 undertreated, 46-206 overtreated. Statistical modelling yielded only small gains over FIGO performance, arising through recategorisation of treatment-resistant patients, with a significant proportion of under/overtreatment as the available data have been used a priori to allocate primary chemotherapy. Streamlining FIGO should now be the focus.     

Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

Heart Failure Reviews - The nitric oxide (NO)–guanylate cyclase (GC)–cyclic guanosine monophosphate (cGMP) pathway plays an important role in cardiovascular, pulmonary and renal...     

Effect of iron deficiency without anaemia on days alive and out of hospital in patients undergoing valvular heart surgery

Comprehensive evidence regarding the treatment of non-anaemic iron deficiency in patients undergoing valvular heart surgery is lacking. This study aimed to investigate the association between non-anaemic iron deficiency and postoperative outcomes in these patients. We retrospectively analysed 321 patients of which 180 (56%) had iron deficiency (defined as serum ferritin < 100 ng.ml^-1 or < 300 ng.ml^-1 with transferrin saturation < 20%). While the iron-deficient group had lower pre-operative haemoglobin levels than the non-iron deficient group (median (IQR [range]) 134 (127–141 [120–172]) g.l^-1, 143 (133–150 [120–179]) g.l^-1, p = 0.001), there was no between-group difference in allogeneic red blood cell transfusion. Median (IQR [range]) days alive and out of hospital at postoperative day 90 was 1 day shorter in the iron-deficient group (80 (77–82 [9–85]) days vs. 81 (79–83 [0–85]) days, p = 0.026). In multivariable analysis, only cardiopulmonary bypass duration (p = 0.032) and intra-operative allogeneic red blood cell transfusion (p = 0.011) were significantly associated with reduced days alive and out of hospital at postoperative day 90. Iron deficiency did not exert any adverse influence on secondary outcomes except length of hospital stay. Our findings indicate that non-anaemic iron deficiency alone is not associated with adverse effects in patients undergoing valvular heart surgery when it does not translate into an increased risk of allogeneic transfusion.