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

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

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

THE LENDER OF LAST RESORT: UNDERSTANDING THE DEBT DEPENDENCY OF HAGONOY RICE FARMERS ON LOAN SHARKS FOR CAPITALIZATION

In the agricultural sector, rice farmers face financial distress due to volatile market conditions and high operational costs, leading them to borrow from high-interest sources like loan sharks frequently. This study aimed to explore the pivotal moment that led to their dependence on loan sharks, their struggles, and coping mechanisms and to attain a thorough understanding of their lived experiences. This study used a phenomenological approach to assess the perceptions and experiences of an individual. The 12 participants are selected using snowball sampling and undergo an in-depth individual interview. Moreover, the thematic analysis was utilized to identify participant similarities and differences. This study determines that rice farmers in Hagonoy, Davao del Sur, have financial difficulties due to the lack of cash, prompting them to resort to loan sharks for unsecured loans since they are easy to access, emphasizing their financial exclusion. The rice farmers face high interest rates, financial struggles, debt burdens, constant debt cycles, dependency, limited options, emotional stress, and uncertainty. Gradually, they established coping techniques based on resilience and hard work, persistence and determination, financial management and planning, and community and government support. Hence, this study implies that the government may establish accessible financing organizations with obtainable terms to support farmers while also ensuring the transparent distribution of financial assistance, fair pricing, and fostering of agriculture's role in economic development.JEL: Q14, Q15, D14, G51, G23, O17  Article visualizations

Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

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