Early impairment of endothelial structure and function in young normal-weight women with polycystic ovary syndrome

The aim of this study was to evaluate the presence of early vascular damage in young normal-weight women with polycystic ovary syndrome (PCOS).Thirty young normal-weight women with PCOS, who had no additional metabolic or cardiovascular diseases, and 30 healthy women (controls) matched for age and body mass index were studied. A complete hormonal assay was performed in each subject. Serum insulin and glucose levels were measured at baseline and after the oral glucose tolerance test. Plasma endothelin-1 levels and serum lipid profile were also assessed. The endothelial function was studied by flow-mediated dilation on the brachial artery, and arterial structure was evaluated by intima-media thickness measurement using Doppler ultrasound of both common carotid arteries.A significant (P < 0.05) difference in flow-mediated dilation (14.3 +/- 1.9% vs. 18.1 +/- 2.0% for PCOS patients and controls, respectively) and in intima-media thickness (0.53 +/- 0.09 mm vs. 0.39 +/- 0.08 mm for PCOS patients and controls, respectively) was found between PCOS and control subjects. Serum endothelin-1 levels were also significantly (P < 0.05) higher in PCOS patients compared with controls (1.1 +/- 0.4 pmol/liter vs. 0.5 +/- 0.2 pmol/liter for PCOS patients and controls, respectively).In conclusion, our data show that young, normal-weight, nondyslipidemic, nonhypertensive women with PCOS have an early impairment of endothelial structure and function

New insights on the mechanism of quinoline-based DNA methyltransferase inhibitors

Among the epigenetic marks, DNA methylation is one of the most studied. It is highly deregulated in numerous diseases, including cancer. Indeed, it has been shown that hypermethylation of tumor suppressor genes promoters is a common feature of cancer cells. Because DNA methylation is reversible, the DNA methyltransferases (DNMTs), responsible for this epigenetic mark, are considered promising therapeutic targets. Several molecules have been identified as DNMT inhibitors and, among the non-nucleoside inhibitors, 4-aminoquinoline-based inhibitors, such as SGI-1027 and its analogs, showed potent inhibitory activity. Here we characterized the in vitro mechanism of action of SGI-1027 and two analogs. Enzymatic competition studies with the DNA substrate and the methyl donor cofactor, S-adenosyl-L-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior. In addition, deviations from the Michaelis-Menten model in DNA competition experiments suggested an interaction with DNA. Thus their ability to interact with DNA was established; although SGI-1027 was a weak DNA ligand, analog 5, the most potent inhibitor, strongly interacted with DNA. Finally, as 5 interacted with DNMT only when the DNA duplex was present, we hypothesize that this class of chemical compounds inhibit DNMTs by interacting with the DNA substrate

Innovation in rehabilitation technology: technological opportunities and socio-economic implications

Innovation in stroke rehabilitation technology is discussed that, based on published epidemiological and economic data, represents an urgent case to deal with adopting a multidisciplinary perspective. A theoretical model is proposed for the evaluation of socioeconomic implications related to an early diagnosis and early and timely adjustments in the stroke treatment strategy. The model is applied to the case of a new rehabilitation technology: the ALLADIN diagnostic device. The model compares a traditional approach – ‘trial and error strategy’ – to the innovative one – ‘in progress evaluation’, considering the diagnostic and rehabilitative steps of the patient’s assistive route and assessing social and economic benefits of the innovative device. The new technology allows a precise initial assessment of both the severity of stroke and the level of lost functionality, as long as an evaluation of the expected return from different potential therapies. Moreover, supposing that higher severity of stroke implies higher level of disabilities and social costs, and that the negative impact increases as the level of disability increases, the use of innovative rehabilitation technologies would be more effective in the case of patients with severe and very severe stroke

Controlling electronic events through rational structural design in subphthalocyanine–corrole dyads: synthesis, characterization, and photophysical properties

Porphyrinoids are considered perfect candidates for their incorporation into electron donor–acceptor (D–A) arrays due to their remarkable optoelectronic properties and low reorganization energies. For the first time, a series of subphthalocyanine (SubPc) and corrole (Cor) were covalently connected through a short-range linkage. SubPc axial substitution strategies were employed, which allowed the synthesis of the target molecules in decent yields. In this context, a qualitative synthetic approach was performed to reverse the expected direction of the different electronic events. Consequently, in-depth absorption, fluorescence, and electrochemical assays enabled the study of electronic and photophysical properties. Charge separation was observed in cases of electron-donating Cors, whereas a quantitative energy transfer from the Cor to the SubPc was detected in the case of electron accepting Cors

A theory of ferromagnetism in planar heterostructures of (Mn,III)-V semiconductors

A density functional theory of ferromagnetism in heterostructures of compound semiconductors doped with magnetic impurities is presented. The variable functions in the density functional theory are the charge and spin densities of the itinerant carriers and the charge and localized spins of the impurities. The theory is applied to study the Curie temperature of planar heterostructures of III-V semiconductors doped with manganese atoms. The mean-field, virtual-crystal and effective-mass approximations are adopted to calculate the electronic structure, including the spin-orbit interaction, and the magnetic susceptibilities, leading to the Curie temperature. By means of these results, we attempt to understand the observed dependence of the Curie temperature of planar $\delta$-doped ferromagnetic structures on variation of their properties. We predict a large increase of the Curie Temperature by additional confinement of the holes in a $\delta$-doped layer of Mn by a quantum well.Comment: 8 pages, 7 figure

Co-ordination between Rashba spin-orbital interaction and space charge effect and enhanced spin injection into semiconductors

We consider the effect of the Rashba spin-orbital interaction and space charge in a ferromagnet-insulator/semiconductor/insulator-ferromagnet junction where the spin current is severely affected by the doping, band structure and charge screening in the semiconductor. In diffusion region, if the the resistance of the tunneling barriers is comparable to the semiconductor resistance, the magnetoresistance of this junction can be greatly enhanced under appropriate doping by the co-ordination between the Rashba effect and screened Coulomb interaction in the nonequilibrium transport processes within Hartree approximation.Comment: 4 pages, 3 figure

Neutralising reactivity against SARS-CoV-2 delta and omicron variants by vaccination and infection history.

BACKGROUND: The continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects. METHODS: Blood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo' cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61). RESULTS: We report on the results of the third serosurvey run in the Vo' cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo' inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain. CONCLUSIONS: These results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population

Spintronics: Fundamentals and applications

Spintronics, or spin electronics, involves the study of active control and manipulation of spin degrees of freedom in solid-state systems. This article reviews the current status of this subject, including both recent advances and well-established results. The primary focus is on the basic physical principles underlying the generation of carrier spin polarization, spin dynamics, and spin-polarized transport in semiconductors and metals. Spin transport differs from charge transport in that spin is a nonconserved quantity in solids due to spin-orbit and hyperfine coupling. The authors discuss in detail spin decoherence mechanisms in metals and semiconductors. Various theories of spin injection and spin-polarized transport are applied to hybrid structures relevant to spin-based devices and fundamental studies of materials properties. Experimental work is reviewed with the emphasis on projected applications, in which external electric and magnetic fields and illumination by light will be used to control spin and charge dynamics to create new functionalities not feasible or ineffective with conventional electronics.Comment: invited review, 36 figures, 900+ references; minor stylistic changes from the published versio

Impact of youth sports specialisation on career and task-specific athletic performance: A systematic review following the American Medical Society for Sports Medicine (AMSSM) Collaborative Research Network's 2019 Youth Early Sport Specialisation Summit

Objective The impact, positive or negative, of youth sport specialisation (YSS) on short-Term and long-Term performance is not fully understood; however, the desire to maximise performance goals is generally considered the primary reason children and adolescents specialise at a young age. We performed a systematic review of original research to establish the association of YSS and task-focused or career-focused performance outcomes. Design Systematic review. Data sources Databases searched include PubMed, EMBASE, Cochrane, CINAHL and SPORTDiscus. Eligibility criteria We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify peer-reviewed research articles published in English between 1 January 1990 and 31 December 2018 that reported original findings on the association of YSS and performance outcomes. Studies without an explicit measure of sport specialisation, for example, volume measures without measuring sport specialisation, were excluded. Results Twenty-Two articles were included in the final review; 15 addressed career performance outcomes and 7 considered task performance outcomes. All identified studies were cross-sectional or retrospective in design. The proportion of elite athletes who specialised early ranged between 7% and 85%, depending on sport and definition of specialisation. Elite athletes often specialised between the ages of 14 and 15 compared with their non-elite or semi-elite peers who typically specialised prior to 13 years. In addition, neuromuscular control, anterior reach asymmetry and physical task outcomes did not differ by specialisation status. Conclusion The volume and methodological rigour of published research in this field are limited. Our review suggests that YSS is not required to achieve success at elite levels. YSS also does not appear to improve task-related performance (eg, anterior reach, neuromuscular control) outcomes for specialised athletes when compared with non-specialised athletes during childhood and adolescence