Outcomes after transcatheter aortic valve implantation with both Edwards-SAPIEN and CoreValve devices in a single center: the Milan experience.

Objectives: Our aim was to assess clinical outcome after transcatheter aortic valve implantation (TAVI) performed with the 2 commercially available valves with 3 delivery approaches selected in a stepwise fashion.

Background: Limited data exist on the results of a comprehensive TAVI program using different valves with transfemoral, transapical, and transaxillary approaches for treatment of severe aortic stenosis.

Methods: We report 30-day and 6-month outcomes of high-risk patients consecutively treated in a single center with either the Medtronic-CoreValve (MCV) (Medtronic, Minneapolis, Minnesota) or Edwards-SAPIEN valve (ESV) (Edwards Lifesciences, Irvine, California) delivered via the transfemoral or transaxillary approaches and ESV via the transapical approach.

Coronary left main and non-left main bifurcation angles: how are the angles modified by different bifurcation stenting techniques?

Background: Investigation of the correlation between bifurcation angles and outcomes is limited with discordant results. The aim of this study is to investigate left main (LM) and non-left main (N-LM) bifurcation angles and their modification after percutaneous coronary intervention (PCI). Measurement of all three angles adds to our understanding of bifurcation anatomy and the resultant effect of different stenting techniques.

Neurite outgrowth: this process, first discovered by Santiago Ramon y Cajal, is sustained by the exocytosis of two distinct types of vesicles.

Neurite outgrowth is a fundamental process in the differentiation of neurons. The first, seminal study documenting the generation of "appendages" (now known as filopodia and lamellipodia) on the "cones d'accroissement," the specialized growth cones at the tips of neurites, was reported by Cajal still in the XIXth century, investigating chicken neurons embryos stained by the Golgi's reazione nera. Since then, studies have continued using, in addition to brain tissues, powerful in vitro models, i.

Long-term follow-up (four years) of unprotected left main coronary artery disease treated with paclitaxel-eluting stents (from the TRUE Registry).

Aims: Limited data are available on the long-term outcome following PCI with paclitaxel-eluting stent (PES) implantation in patients with unprotected left main coronary artery (LMCA). The objective of this study was to evaluate "real world" long-term outcome following paclitaxel-eluting stent (PES) implantation for unprotected LMCA disease in patients enrolled in the TRUE registry.

Methods And Results: From March 2003 to October 2004, 93 consecutive patients (81.

Polarization dictates iron handling by inflammatory and alternatively activated macrophages.

Background: Macrophages play a key role in iron homeostasis. In peripheral tissues, they are known to polarize into classically activated (or M1) macrophages and alternatively activated (or M2) macrophages. Little is known on whether the polarization program influences the ability of macrophages to store or recycle iron and the molecular machinery involved in the processes.

A distinguishing gene signature shared by tumor-infiltrating Tie2-expressing monocytes, blood "resident" monocytes, and embryonic macrophages suggests common functions and developmental relationships.

We previously showed that Tie2-expressing monocytes (TEMs) have nonredundant proangiogenic activity in tumors. Here, we compared the gene expression profile of tumor-infiltrating TEMs with that of tumor-associated macrophages (TAMs), spleen-derived Gr1(+)Cd11b(+) neutrophils/myeloid-derived suppressor cells, circulating "inflammatory" and "resident" monocytes, and tumor-derived endothelial cells (ECs) by quantitative polymerase chain reaction-based gene arrays. TEMs sharply differed from ECs and Gr1(+)Cd11b(+) cells but were highly related to TAMs.

Clinical and angiographic follow-up of small vessel lesions treated with paclitaxel-eluting stents (from the TRUE Registry).

Several randomized trials have shown that sirolimus-eluting stents and paclitaxel-eluting stents (PES) are effective in reducing restenosis in respect to bare-metal stents, including the subset of small vessels. The objective of this study was to evaluate "real world" angiographic and clinical outcomes of a large series of patients enrolled in the TRUE registry and treated with PES for both small vessel and very small vessel lesions. A consecutive series of 675 patients (926 lesions) with reference vessel diameter <2.

Tumor-targeted interferon-alpha delivery by Tie2-expressing monocytes inhibits tumor growth and metastasis.

The use of type I interferons (IFNs) in cancer therapy has been limited by ineffective dosing and significant toxicity. Here, we exploited the tumor-homing ability of proangiogenic Tie2-expressing monocytes (TEMs) to deliver IFN-alpha to tumors. By transplanting hematopoietic progenitors transduced with a Tie2 promoter/enhancer-driven Ifna1 gene, we turned TEMs into IFN-alpha cell vehicles that efficiently targeted the IFN response to orthotopic human gliomas and spontaneous mouse mammary carcinomas and obtained significant antitumor responses and near complete abrogation of metastasis.

Inhibition of adipogenesis: a new job for the ER Ca2+ pool.

Adipogenesis is the process of differentiation of adipocytes from mesenchymal multipotent cells through adipocyte precursors. In this issue, a study by the groups of Opas and Michalak (Szabo, E., Y.

Serotonin transporter gene-linked polymorphic region: possible pharmacogenetic implications of rare variants.

A functional insertion/deletion (*l/*s) repeat polymorphism within the promoter region of the serotonin transporter (5-HTTLPR) has been described. An association between *l variant and a better and faster response to serotonin selective reuptake inhibitors in depressed patients was reported in Caucasians. The value of the explained variance due to the 5-HTTLPR, however, was 7% only, and different *l and *s variants were reported according to the nucleotide sequence of repeats.

Influence of postpartum onset on the course of mood disorders.

Background: To ascertain the impact of postpartum onset (PPO) on the subsequent time course of mood disorders.

Methods: This retrospective study compared per year rates of excited (manic or mixed) and depressive episodes between fifty-five women with bipolar (N = 22) or major depressive (N = 33) disorders with first episode occurring postpartum (within four weeks after childbirth according to DSM-IV definition) and 218 non-postpartum onset (NPPO) controls. Such patients had a traceable illness course consisting of one or more episodes alternating with complete symptom remission and no additional diagnoses of axis I disorders, mental retardation or brain organic diseases.

Temperament and character in mood disorders: influence of DRD4, SERTPR, TPH and MAO-A polymorphisms.

Gene variants exert a complex range of effects on human normal and abnormal behavior. We previously reported the effect of gene variants in serotoninergic and dopaminergic pathways, in a range of clinical features in mood disorders, such as symptomathology, periodicity, social adjustment and treatment response. In this paper we hypothesized that the same gene variants could influence temperamental traits in mood disorders patients.

Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors.

Bone marrow-derived cells contribute to tumor angiogenesis. Here, we demonstrate that monocytes expressing the Tie2 receptor (Tie2-expressing monocytes [TEMs]) (1) are a distinct hematopoietic lineage of proangiogenic cells, (2) are selectively recruited to spontaneous and orthotopic tumors, (3) promote angiogenesis in a paracrine manner, and (4) account for most of the proangiogenic activity of myeloid cells in tumors. Remarkably, TEM knockout completely prevented human glioma neovascularization in the mouse brain and induced substantial tumor regression.

The pattern recognition receptor PTX3 is recruited at the synapse between dying and dendritic cells, and edits the cross-presentation of self, viral, and tumor antigens.

Pentraxins are soluble pattern recognition receptors with a dual role: protection against extracellular microbes and autoimmunity. The mechanisms by which they accomplish these tasks are not yet fully understood. Here we show that the prototypic long pentraxin PTX3 is specifically recruited at both sides of the phagocytic synapse between dendritic cells (DCs) and dying cells and remains stably bound to the apoptotic membranes (estimated half-time > 36 hours).

Sertraline versus fluvoxamine in the treatment of elderly patients with major depression: a double-blind, randomized trial.

Background: Major depression is a common psychiatric disorder in the elderly population. The efficacy of tricyclic antidepressants is well established, and selective serotonin reuptake inhibitors appear to have a similar effectiveness along with advantages in terms of tolerability and safety. Given the lack of literature data regarding fluvoxamine in the treatment of depressed elderly patients, the aim of the present study was to compare its efficacy and tolerability with those of sertraline in a sample of elderly patients.

Fibronectin controls cap-dependent translation through beta1 integrin and eukaryotic initiation factors 4 and 2 coordinated pathways.

Fibronectin (FN) is a major matrix protein involved in multiple processes. Little is known about how adhesion to FN affects the translational machinery. We show that in fibroblasts adhesion to FN triggers translation through the coordinated regulation of eukaryotic initiation factors (eIFs) 4F and 2 and is impaired by blocking beta1 integrin engagement.

Social adjustment could be associated with the serotonin transporter gene in remitted patients with mood disorders and healthy subjects.

We investigated the serotonin transporter gene (5-HTTLPR) in the functioning of euthymic patients with mood disorders (n=285) and healthy controls (n=94). The 5-HTTLPR genotype showed marginal associations with working, familial and social adjustment, with marked differences between controls and patients. Because of the exploratory nature of our analyses, all results should be viewed with caution.

Spinal cord sonography in newborns: anatomy and diseases.

Sonography of the spinal cord is a relatively recent acquisition that makes it possible to evaluate the content of the vertebral canal and study its pathologies. The aim of this study was to verify the reliability of ultrasound images by comparing them with magnetic resonance ones in healthy controls as well as in patients referred to us between 1991 and 2004. In this period, we studied 436 newborns: 88 without any suspicion of disease as normal controls, and 348 with suspected congenital diseases or in order to screen the children of diabetic mothers, a group that has shown an increased incidence of dysraphism.

Profiles of "manic" symptoms in bipolar I, bipolar II and major depressive disorders.

Background: Classical authors such as Kraepelin, as well as the emerging literature during the past decade, indicate that manic-like signs and symptoms are present to a variable degree in all mood disorders. Current nosography does not differentiate between them and only the number of symptoms or severity is used for classification. This is particularly true for mania and hypomania.

Distribution and signaling of TREM2/DAP12, the receptor system mutated in human polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy dementia.

Together with its adaptor protein, the adaptor protein of 12 kDa also known as KARAP and TYROBP (DAP12), triggering receptor expressed in myeloid cells 2 (TREM2) is a stimulatory membrane receptor of the immunoglobulin/lectin-like superfamily, well known in myeloid cells. In humans, however, loss-of-function mutations of TREM2/DAP12 leave myeloid cells unaffected but induce an autosomal recessive disease characterized, together with bone cysts, by a spectrum of pathological lesions in the cortex, thalamus and basal ganglia with clinical symptoms of progressive dementia (polycystic lipomembraneous osteodysplasia with sclerosing leukoencephalopathy). Nothing was known about the role of TREM2/DAP12 in brain cell biology and physiology.

Inhibition of phosphatidylserine recognition heightens the immunogenicity of irradiated lymphoma cells in vivo.

Strategies to enhance the immunogenicity of tumors are urgently needed. Although vaccination with irradiated dying lymphoma cells recruits a tumor-specific immune response, its efficiency as immunogen is poor. Annexin V (AxV) binds with high affinity to phosphatidylserine on the surface of apoptotic and necrotic cells and thereby impairs their uptake by macrophages.

DRD4 exon 3 variants are not associated with symptomatology of major psychoses in a German population.

We previously reported an association of DRD4 exon 3 long alleles with delusional symptomatology, independently from psychiatric diagnoses [Am. J. Med.

Further evidence of a combined effect of SERTPR and TPH on SSRIs response in mood disorders.

We reported an independent association of the short variant of the serotonin transporter gene-linked polymorphic region (SERTPR) and tryptophan hydroxylase (TPH) genes with antidepressant response to selective serotonin reuptake inhibitors (SSRIs). The aim of the present study was to confirm the effect of the SERTPR and TPH gene variants on the SSRIs antidepressant activity in a new sample of major and bipolar depressives. Two hundred and twenty one inpatients (major depressives = 128, bipolar disorder = 93) were treated with SSRIs (fluvoxamine or paroxetine) for 6 weeks; the severity of depressive symptoms was weekly assessed with the Hamilton Rating Scale for Depression (HAMD).

Dimensions of major psychoses: a confirmatory factor analysis of six competing models.

The symptoms of major psychosis aggregate in factors. Models of one to eight dimensions have been reported. In the present study, we tested six competing factor models, based on the psychotic and affective items of the OPCRIT checklist, in a large sample (N = 1294) of patients diagnosed with DSM-IV schizophrenia (n = 460), bipolar disorder (n = 726) and delusional disorder (n = 108).