Role of surface states in the Casimir force between semiconducting films

We present results of first principle calculations of the Casimir force between Si films of nanometric size, which show that it depends significantly upon the configuration of the surface atoms, and give evidence of the importance of surface states.Comment: to be published on J.Phys.

Evidence for a GABAergic system in rodent and human testis: Local GABA production and GABA receptors

The major neurotransmitter of the central nervous system, gamma-aminobutyric acid (GABA), exerts its actions through GABA(A), GABA(B) and GABA(C) receptors. GABA and GABA receptors are, however, also present in several non-neural tissues, including the endocrine organs pituitary, pancreas and testis. In the case of the rat testis, GABA appears to be linked to the regulation of steroid synthesis by Leydig cells via GABA(A) receptors, but neither testicular sources of GABA, nor the precise nature of testicular GABA receptors are fully known. We examined these points in rat, mouse, hamster and human testicular samples. RT-PCR followed by sequencing showed that the GABA-synthesizing enzymes glutamate decarboxylase (GAD) 65 and/or GAD67, as well as the vesicular GABA transporter vesicular inhibitory amino acid transporter (VIAAT/VGAT) are expressed. Testicular GAD in the rat was shown to be functionally active by using a GAD assay, and Western blot analysis confirmed the presence of GAD65 and GAD67. Interstitial cells, most of which are Leydig cells according to their location and morphological characteristics, showed positive immunoreaction for GAD and VIAAT/VGAT proteins. In addition, several GABA(A) receptor subunits (alpha1-3, beta1-3, gamma1-3), as well as GABAB receptor subunits R1 and R2, were detected by RT-PCR. Western blot analysis confirmed the results for GABA(A) receptor subunits beta2/3 in the rat, and immunohistochemistry identified interstitial Leydig cells to possess immunoreactive GABA(A) receptor subunits beta2/3 and alpha1. The presence of GABA(A) receptor subunit alpha1 mRNA in interstitial cells of the rat testis was further shown after laser microdissection followed by RT-PCR analysis. In summary, these results describe molecular details of the components of an intratesticular GABAergic system expressed in the endocrine compartment of rodent and human testes. While the physiological significance of this peripheral neuroendocrine system conserved throughout species remains to be elucidated, its mere presence in humans suggests the possibility that clinically used drugs might be able to interfere with testicular function. Copyright (C) 2003 S. Karger AG, Basel

Rotigotine Objectively Improves Sleep in Parkinson's Disease: An Open-Label Pilot Study with Actigraphic Recording

Sleep disturbances represent important predictors of poor quality of life (QoL) in Parkinson\u2019s disease (PD).This open-label pilot study aimed to objectively assess, by means of actigraphic recording, effect of rotigotine on sleep in PD patients with self-reported sleep complaints. 15 PDpatients underwent one-week actigraphic recording before (T0) and during (T1) rotigotine treatment, which was titrated to the dose subjectively improving motor symptoms (4\u20138mg/24 h). Sleep disturbances, daytime sleepiness, cognitive performance, QoL, and depression were also evaluated with questionnaires. Actigraphic recordings showed a significant reduction in nocturnalmotor activity andmean duration of wake episodes after sleep onset during rotigotine treatment compared to baseline. In 10 patients presenting objective evidence of poor sleep quality at T0 (sleep efficiency 64 85%), rotigotine also significantly improved other sleep parameters and further reduced nocturnal motor activity and mean duration of wake episodes. A significant decrease in number and duration of daytime sleep episodes was also observed at T1. Finally we confirmed that rotigotine significantly improves perceived sleep quality and QoL. Our study showed for the first time that rotigotine is associated with an objective improvement of nocturnal and diurnal sleep disturbances in PD patients with self-reported sleep complaints.This study is registered with AIFAobservational study registry number 12021

Can Extra Mixing in RGB and AGB Stars Be Attributed to Magnetic Mechanisms?

It is known that there must be some weak form of transport (called cool bottom processing, or CBP) acting in low mass RGB and AGB stars, adding nuclei, newly produced near the hydrogen-burning shell, to the convective envelope. We assume that this extra-mixing originates in a stellar dynamo operated by the differential rotation below the envelope, maintaining toroidal magnetic fields near the hydrogen-burning shell. We use a phenomenological approach to the buoyancy of magnetic flux tubes, assuming that they induce matter circulation as needed by CBP models. This establishes requirements on the fields necessary to transport material from zones where some nuclear burning takes place, through the radiative layer, and into the convective envelope. Magnetic field strengths are determined by the transport rates needed by CBP for the model stellar structure of a star of initially 1.5 solar mass, in both the AGB and RGB phases. The field required for the AGB star in the processing zone is B_0 ~ 5x10^6 G; at the base of the convective envelope this yields an intensity B_E < 10^4 G (approximately). For the RGB case, B_0 ~ 5x10^4 to 4x10^5 G, and the corresponding B_E are ~ 450 to 3500 G. These results are consistent with existing observations on AGB stars. They also hint at the basis for high field sources in some planetary nebulae and the very large fields found in some white dwarfs. It is concluded that transport by magnetic buoyancy should be considered as a possible mechanism for extra mixing through the radiative zone, as is required by both stellar observations and the extensive isotopic data on circumstellar condensates found in meteorites.Comment: 26 pages, 4 figures, accepted by Astrophysical Journa

Quantum ESPRESSO: a modular and open-source software project for quantum simulations of materials

Quantum ESPRESSO is an integrated suite of computer codes for electronic-structure calculations and materials modeling, based on density-functional theory, plane waves, and pseudopotentials (norm-conserving, ultrasoft, and projector-augmented wave). Quantum ESPRESSO stands for "opEn Source Package for Research in Electronic Structure, Simulation, and Optimization". It is freely available to researchers around the world under the terms of the GNU General Public License. Quantum ESPRESSO builds upon newly-restructured electronic-structure codes that have been developed and tested by some of the original authors of novel electronic-structure algorithms and applied in the last twenty years by some of the leading materials modeling groups worldwide. Innovation and efficiency are still its main focus, with special attention paid to massively-parallel architectures, and a great effort being devoted to user friendliness. Quantum ESPRESSO is evolving towards a distribution of independent and inter-operable codes in the spirit of an open-source project, where researchers active in the field of electronic-structure calculations are encouraged to participate in the project by contributing their own codes or by implementing their own ideas into existing codes.Comment: 36 pages, 5 figures, resubmitted to J.Phys.: Condens. Matte

Predictors of survival in progressive supranuclear palsy and multiple system atrophy: a systematic review and meta-analysis

Objective To undertake a systematic review and meta-analysis of studies that investigated prognostic factors and survival in patients with progressive supranuclear palsy (PSP) and multiple system atrophy (MSA). Methods Publications of at least 10 patients with a likely or confirmed diagnosis of PSP or MSA were eligible for inclusion. Methodological quality was rated using a modified version of the Quality in Prognostic Studies tool. For frequently examined prognostic factors, HRs derived by univariate and multivariate analysis were pooled in separate subgroups; other results were synthesised narratively and HRs could not be reported here. Results Thirty-seven studies presenting findings on 6193 patients (1911 PSP, 4282 MSA) fulfilled the inclusion criteria. We identified the following variables as unfavourable predictors of survival. In PSP, PSP-Richardson’s phenotype (univariate HR 2.53; 95% CI 1.69 to 3.78), early dysphagia and early cognitive symptoms. In MSA, severe dysautonomia and early development of combined autonomic and motor features but not MSA phenotype (multivariate HR 1.22; 95% CI 0.83 to 1.80). In PSP and MSA, survival was predicted by early falls (multivariate HR 2.32; 95% CI 1.94 to 2.77), the Neuroprotection and Natural History in Parkinson Plus Syndromes Parkinson Plus Score and the Clinical Global Impression Disease Severity Score but not sex (multivariate HR 0.93; 95% CI 0.67 to 1.28). There was conflicting evidence regarding the prognostic effect of age at onset and stridor. Conclusion Several clinical variables were strongly associated with shorter survival in PSP and MSA. Results on most prognostic factors were consistent across methodologically diverse studies; however, the lack of commonality of prognostic factors investigated is a significant limitation

Spectrum of mutations in Italian patients with familial hypercholesterolemia: New results from the LIPIGEN study

Background Familial hypercholesterolemia (FH) is an autosomal dominant disease characterized by elevated plasma levels of LDL-cholesterol that confers an increased risk of premature atherosclerotic cardiovascular disease. Early identification and treatment of FH patients can improve prognosis and reduce the burden of cardiovascular mortality. Aim of this study was to perform the mutational analysis of FH patients identified through a collaboration of 20 Lipid Clinics in Italy (LIPIGEN Study). Methods We recruited 1592 individuals with a clinical diagnosis of definite or probable FH according to the Dutch Lipid Clinic Network criteria. We performed a parallel sequencing of the major candidate genes for monogenic hypercholesterolemia (LDLR, APOB, PCSK9, APOE, LDLRAP1, STAP1). Results A total of 213 variants were detected in 1076 subjects. About 90% of them had a pathogenic or likely pathogenic variants. More than 94% of patients carried pathogenic variants in LDLR gene, 27 of which were novel. Pathogenic variants in APOB and PCSK9 were exceedingly rare. We found 4 true homozygotes and 5 putative compound heterozygotes for pathogenic variants in LDLR gene, as well as 5 double heterozygotes for LDLR/APOB pathogenic variants. Two patients were homozygous for pathogenic variants in LDLRAP1 gene resulting in autosomal recessive hypercholesterolemia. One patient was found to be heterozygous for the ApoE variant p.(Leu167del), known to confer an FH phenotype. Conclusions This study shows the molecular characteristics of the FH patients identified in Italy over the last two years. Full phenotypic characterization of these patients and cascade screening of family members is now in progress

Data-driven clustering of combined Functional Motor Disorders based on the Italian registry

Functional Motor Disorders (FMDs) represent nosological entities with no clear phenotypic characterization, especially in patients with multiple (combined FMDs) motor manifestations. A data-driven approach using cluster analysis of clinical data has been proposed as an analytic method to obtain non-hierarchical unbiased classifications. The study aimed to identify clinical subtypes of combined FMDs using a data-driven approach to overcome possible limits related to "a priori" classifications and clinical overlapping

mTORC1 is essential for early steps during Schwann cell differentiation of amniotic fluid stem cells and regulates lipogenic gene expression.

Schwann cell development is hallmarked by the induction of a lipogenic profile. Here we used amniotic fluid stem (AFS) cells and focused on the mechanisms occurring during early steps of differentiation along the Schwann cell lineage. Therefore, we initiated Schwann cell differentiation in AFS cells and monitored as well as modulated the activity of the mechanistic target of rapamycin (mTOR) pathway, the major regulator of anabolic processes. Our results show that mTOR complex 1 (mTORC1) activity is essential for glial marker expression and expression of Sterol Regulatory Element-Binding Protein (SREBP) target genes. Moreover, SREBP target gene activation by statin treatment promoted lipogenic gene expression, induced mTORC1 activation and stimulated Schwann cell differentiation. To investigate mTORC1 downstream signaling we expressed a mutant S6K1, which subsequently induced the expression of the Schwann cell marker S100b, but did not affect lipogenic gene expression. This suggests that S6K1 dependent and independent pathways downstream of mTORC1 drive AFS cells to early Schwann cell differentiation and lipogenic gene expression. In conclusion our results propose that future strategies for peripheral nervous system regeneration will depend on ways to efficiently induce the mTORC1 pathway

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH