Search

Background: TAVR is a safe alternative to surgical aortic valve replacement (SAVR); how-ever, sex-related differences are still debated. This research aimed to examine gender differences in a real-world transcatheter aortic valve replacement (TAVR) cohort. Methods: All-comer aor-tic stenosis (AS) patients undergoing TAVR with a Medtronic valve across 19 Italian sites were prospectively included in the Italian Clinical Service Project (NCT01007474) between 2007 and 2019. The primary endpoint was 1-year mortality. We also investigated 3-year mortality, and ischemic and hemorrhagic endpoints, and we performed a propensity score matching to assemble patients with similar baseline characteristics. Results: Out of 3821 patients, 2149 (56.2%) women were en-rolled. Compared with men, women were older (83 ± 6 vs. 81 ± 6 years, p < 0.001), more likely to present severe renal impairment (GFR ≤ 30 mL/min, 26.3% vs. 16.3%, p < 0.001) but had less previous cardiovascular events (all p < 0.001), with a higher mean Society of Thoracic Surgeons (STS) score (7.8% ± 7.1% vs. 7.2 ± 7.5, p < 0.001) and a greater mean aortic gradient (52.4 ± 15.3 vs. 47.3 ± 12.8 mmHg, p < 0.001). Transfemoral TAVR was performed more frequently in women (87.2% vs. 82.1%, p < 0.001), with a higher rate of major vascular complications and life-threatening bleeding (3.9% vs. 2.4%, p = 0.012 and 2.5% vs. 1.4%, p = 0.024). One-year mortality differed between female and male (11.5% vs. 15.0%, p = 0.002), and this difference persisted after adjustment for sig-nificant confounding variables (Adj.HR1yr 1.47, 95%IC 1.18–1.82, p < 0.001). Three-year mortality was also significantly lower in women compared with men (19.8% vs. 24.9%, p < 0.001) even after adjustment for age, STS score, eGFR, diabetes and severe COPD (Adj.HR3yr 1.42, 95%IC 1.21–1.68, p < 0.001). These results were confirmed in 689 pairs after propensity score matching. Conclusion: Despite higher rates of peri-procedural compl

Background: Recent evidence suggests that psychiatric symptoms share a common genetic liability across diagnostic categories. The present study investigated the effects of variants within previously identified relevant genes on specific symptom clusters, independently from the diagnosis. Methods: 1550 subjects affected by Schizophrenia (SCZ), Major Depressive Disorder or Bipolar Disorder were included. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and the Hamilton Depression Rating Scale (HDRS). Principal component analysis and a further clinical refinement were used to define symptom clusters. Clusters scores were tested for association with 46 genetic variants within nine genes previously linked to one or more major psychiatric disorders by large genome wide association studies (ANK3, CACNA1C, CACNB2, FKBP5, FZD3, GRM7, ITIH3, SYNE1, TCF4). Exploratory analyses were performed in each disorder separately to further elucidate the SNPs effects. Results: five PANSS clusters (Negative; Impulsiveness; Cognitive; Psychotic; Depressive) and four HDRS clusters (Core Depressive; Somatic; Psychotic-like; Insomnia) were identified. CACNA1C rs11615998 was associated with HDRS Psychotic cluster in the whole sample. In the SCZ sample, CACNA1C rs11062296 was associated with PANSS Impulsiveness cluster and CACNA1C rs2238062 was associated with PANSS negative cluster. Discussion: CACNA1C rs11615998 was associated with psychotic symptoms (C-allele carriers have decreased psychotic-risk) independently from the diagnosis, in line with the evidence of a cross disorder effect of many risk variants. This gene was previously associated with SCZ and cross-disorder liability to psychiatric disorders. Our findings confirmed that deep phenotyping is pivotal to clarify the role of genetic variants on symptoms patterns.

Background: Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ). Methods: Using MassARRAY high-throughput DNA analysis with matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry, we genotyped patients with sAPL (n 20) developed after treatment of MS (18 out 20 treated with MTZ) for the presence of 210 SNPs of 22 genes mostly involved in DNA repair and drug detoxification. Patients with MS who did not develop sAPL including 41 treated with MTZ (n 253 and 41, respectively) and healthy blood donors (n 310) were also genotyped as controls. Results: We observed risk allele frequency between MS and sAPL for BRCA2 (rs1801406): 6% and 26%, p 0.007; XRCC5 (rs207906): 2.5% and 15%, p 0.016; CYP3A4 (rs2740574): 4.5% and 25%, p 0.0035. The association of homozygous variants of BRCA2 and XRCC5 yielded higher risk of sAPL (MS vs sAPL: 0.4% and 18%, p 0.001). We also observed a significant association between a SNP in the promoter region (rs2740574) of CYP3A4, an enzyme involved in the metabolism of chemotherapeutic agents and development of sAPL. Conclusions: Increased susceptibility to develop sAPL in patients with MS receiving MTZ may be linked to genetic variants in DNA repair and drug-metabolizing enzymes that result in impaired detoxification of chemotherapy or inefficient repair of drug-induced genetic damage. Neurology, Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ).

Single nucleotide polymorphisms (SNPs) in double-strand break repair genes may alter DNA repair capacity and, in turn, confer predisposition to leukemia. We analyzed polymorphic variants of DNA repair and detoxification genes in patients with multiple sclerosis (MS) who developed secondary acute promyelocytic leukemia (sAPL), in most cases after treatment with mitoxantrone (MTZ).

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells

Mitochondrial optic neuropathies, that is, Leber hereditary optic neuropathy and dominant optic atrophy, selectively affect retinal ganglion cells, causing visual loss with relatively preserved pupillary light reflex. The mammalian eye contains a light detection system based on a subset of retinal ganglion cells containing the photopigment melanopsin. These cells give origin to the retinohypothalamic tract and support the non-image-forming visual functions of the eye, which include the photoentrainment of circadian rhythms, light-induced suppression of melatonin secretion and pupillary light reflex. We studied the integrity of the retinohypothalamic tract in five patients with Leber hereditary optic neuropathy, in four with dominant optic atrophy and in nine controls by testing the light-induced suppression of nocturnal melatonin secretion. This response was maintained in optic neuropathy subjects as in controls, indicating that the retinohypothalamic tract is sufficiently preserved to drive light information detected by melanopsin retinal ganglion cells. We then investigated the histology of post-mortem eyes from two patients with Leber hereditary optic neuropathy and one case with dominant optic atrophy, compared with three age-matched controls. On these retinas, melanopsin retinal ganglion cells were characterized by immunohistochemistry and their number and distribution evaluated by a new protocol. In control retinas, we show that melanopsin retinal ganglion cells are lost with age and are more represented in the parafoveal region. In patients, we demonstrate a relative sparing of these cells compared with the massive loss of total retinal ganglion cells, even in the most affected areas of the retina. Our results demonstrate that melanopsin retinal ganglion cells resist neurodegeneration due to mitochondrial dysfunction and maintain non-image-forming functions of the eye in these visually impaired patients. We also show that in normal human retinas, these cells

Low temperature photoluminescence spectroscopy is used to analyze the effects of the Ga coverage and of the postgrowth thermal annealing on the electronic properties of low density (approximate to1x10(9)cm(-2)) self-assembled GaAs/AlGaAs quantum dots (QDs) grown by modified droplet epitaxy (MDE). We demonstrate that with the MDE method it is possible to obtain low density and high efficiency QD samples with high photoluminescence efficiency. Large modifications of the photoluminescence band, which depend on Ga coverage and thermal annealing, are found and quantitatively interpreted by means of a simple model based on the Al-Ga interdiffusion. (C) 2004 American Institute of Physics.

We present a detailed analysis of the Ga coverage and of the post-growth annealing effects on the optical properties of verv-low-density self-assembled GaAs/AlGaAs quantum dots grown by modified droplet epitaxy. Through theoretical calculation of the QD electronic states, including thermally activated Al-Ga interdiffusion processes, we were able to relate our spectroscopic observations to QD structural properties. (C) 2003 Elsevier B.V. All rights reserved.