Aims: This prospective, non-randomised, observational study conducted in Europe was designed in order to assess the long-term safety and efficacy of the Parachute device in ischaemic heart failure subjects as a result of left ventricle remodelling after anterior wall myocardial infarction. Methods and results:One hundred subjects with New York Heart Association Class II-IV ischaemic heart failure (HF), ejection fraction (EF) between 15% and 40%, and dilated akinetic or dyskinetic anteriorapical wall without the need to be revascularised were enrolled. The primary safety endpoint was procedural-or device-related major adverse cardiac cerebral events (MACCE). The secondary safety endpoint was the composite of mortality and morbidity. Secondary efficacy endpoints included haemodynamic measurements determined by echocardiography, LV volume indices, and assessment of functional improvement measured by a standardised six-minute walk test. Of the 100 subjects enrolled, device implantation was successful in 97 (97%) subjects. The one-year rates of the primary and secondary safety endpoints were 7% and 32.3%, respectively. The secondary endpoints, LV volume reduction (p<0.0001) and six-minute walk distance improvement (p<0.01), were achieved. Conclusions:The favourable outcomes observed in this high-risk population provide reassuring safety and efficacy data to support adoption of this technology as a therapeutic option for HF subjects. Clinical registration: www.clinicaltrials.gov numbers are NCT01297296 (PARACHUTE III) and NCT01286116 (cohort B subjects). KEYWORDS• ischaemic heart failure • left ventricle remodelling • structural heart

a b s t r a c tCONTEXT: Most double-blind studies of efficacy and tolerability of sertraline as compared to tricyclics in the treatment of late-life major depression have used amitriptyline as a standard, leading to the inevitable conclusion that the former drug is better tolerated than the latter, with both being equally efficacious. OBJECTIVE:To compare the antidepressant efficacy and tolerability of sertraline (50 mg/day) and imipramine (150 mg/day) in the first 6 weeks of the treatment of major depression in the elderly. DESIGN:A randomized double-blind parallel study with 6 weeks of follow-up. SETTING:The psychogeriatric clinic at the Institute of Psychiatry, Hospital das Clínicas, Faculty of Medicine of the University of São Paulo.PARTICIPANTS: 55 severe and moderately depressed non-demented outpatients aged 60 years or more. INTERVENTION:Patients were assigned to sertraline 50 mg/day or imipramine 150 mg/day. MAIN MEASUREMENTS:CAMDEX interview. Psychiatric diagnosis followed the guidelines for "Major Depressive Episode" according to DSM-IV criteria. Severity of symptoms was evaluated using the "CGI" and "MADRS" scales. Cognitive state was assessed using the Mini-Mental State Examination. Side effects were assessed using the "Safetee-Up" schedule. RESULTS:Both groups had a significant decrease in depressive symptoms according to the MADRS scores after 6 weeks of treatment (P = 0.01). No significant differences between groups were detected regarding treatment outcome (t = 0.4; P = 0.7). Although the dropout rate was greater in the imipramine group, the overall tolerability among patients who completed the 6-week trial was similar in both test groups. CONCLUSIONS:Both sertraline and imipramine exhibited good efficacy and an acceptable side-effect profile for elderly depressed patients after 6 weeks of antidepressant treatment.KEY WORDS: Depression. Elderly. Antidepressant drugs. Tricyclics. Sertraline. SSRI's.• and are among the most widely prescribed of such medications. 9-11A recent meta-analysis study of efficacy, safety and tolerability of four antidepressant classes concluded there were no differences between outcomes in the management of late-life major depression, 12 suggesting that there is little advantage for each antidepressant class over the others, namely SSRI's, tricyclics, reversible inhibitors of monoamine oxidase-A and atypical antidepressants. Nevertheless, such finding can only be generalized for samples of selected patients. In the presence of concurrent medical illnesses, or physical and cognitive conditions, accurate clinical judgement must be relied upon for the correct choice of antidepressant, as the use of certain drugs is limited by the risk of toxicity, pharmacokinetic interactions or intolerable side-effects.Although more risky and laborious to prescribe, the clinician must be aware of the putative benefits of tricyclic antidepressants in the treatment of depressive disorders in the elderly. Besides being effective, tricyclics are cheaper and more widely available than the new c...

CS should be considered in babies with low birth weight and congenital cataract.

These authors contributed equally.1 The maintenance of a diverse, naïve T cell repertoire arising from the thymus (recent thymic emigrants: RTEs) is critical for health 1 . Recent studies have reported a unique naïve CD4 + T cell subset in neonates and early childhood characterized by IL-8 production 2,3 . Here we demonstrate that IL-8 production is a characteristic feature of RTEs in adults, children and neonates and that a hallmark of these cells is the expression of complement receptor 2 (CR2) and the preferential production of IL-8 after activation. Although decreasing in number with age due to thymic involution and homeostatic expansion of naïve CD4 + T cell in humans 4 , CR2 + RTEs persist into old age, have the highest levels of T cell receptor excision circles (TRECs), co-express complement receptor 1 (CR1), TLR1 and produce IL-8 upon TCR stimulation. We have observed these phenotypes in the vast majority of cord blood naïve CD4 + T cells and in newly-generated naïve T cells appearing during reconstitution of the immune system in adults depleted of T cells through treatment for multiple sclerosis. A memory subset of CR2 + CD4 + T cells expressing high levels of CR1 and producing IL-8 following activation was also discovered, consistent with the hypothesis that RTE-specific gene expression confers a functional competence retained by particular memory T cells possibly because of their complement-dependent reactivity to pathogens. We suggest that assessing CR2 expression on naïve CD4 + T cells will give a measure of thymic function during aging of the immune system and in a number of clinical situations including bone marrow transplantation 5 , HIV infection 6 , and immune reconstitution following immune depletion 7 or chemotherapy 8 .Thymic involution decreases naïve CD4 + T cell production with age in humans and is compensated for by the homeostatic expansion of naïve cells that have emigrated from the thymus earlier in life 1,4 . Naïve T cells that have undergone decades of homeostatic expansion show reduced T cell receptor diversity that potentially negatively impacts host defence 9 . CD31 (PECAM-1) expression identifies cells that have divided more often in the periphery (CD31 − ) from those that have not (CD31 + ), although CD31 + T cells still divide with age as evidenced by the dilution of TRECs 10 and, therefore, better markers of undivided naïve T cells are clearly needed 11 . As we and others have reported 12,13 , CD25 is an additional marker of naïve T cells that have expanded in the periphery. CD31 + CD25 − naïve CD4 + T cells predominate at birth and contain the highest content of TRECs as compared to their CD31 − and CD25 + counterparts 12 .Here, we assessed the heterogeneity of four naïve CD4 + T cell subsets defined by CD31 and CD25 expression in neonates and adults in a population study of 391 donors ( Fig. 1a, Supplementary Fig. 1a). CD31 + CD25 − naïve CD4 + T cells decreased with age and this decrease was compensated for by 2 the homeostatic expansion of three subsets of naïve T cells:...