The Effects of Health Sector Fiscal Decentralisation on Availability, Accessibility, and Utilisation of Healthcare Services: A Panel Data Analysis.

BACKGROUND: Fiscal decentralisation (FD) is a widely implemented decentralisation policy consisting of the allocation of pooling and spending responsibilities from the central government to lower levels of governance within a country. In 2001, The Italian National Health System (Servizio Sanitario Nazionale, SSN) has introduced a strong element of FD, making regions responsible for their own pooling of resources and for their budgets. Despite the relevance, only few studies exist on health sector-FD in Italy, mostly looking at the effects of FD on infant mortality. METHODS: This study performs a fixed-effects panel data analysis of Italian Regions and Autonomous provinces between the years 2001 and 2017, to investigate the effects of health sector-FD on availability, accessibility, and utilisation of healthcare services in Italy. RESULTS: FD decreases availability of staff and hospital beds, decreases utilisation of care, measured by hospitalisation rates, and increases interregional patients' mobility for healthcare purposes, a finding suggesting increased disparities in access to healthcare. These effects seem to be stronger for public - rather than private - services, and are more prominent in poorer areas. CONCLUSION: This evidence suggest that FD has created a fragmented and unequal healthcare system, in which levels of availability, utilisation of, and accessibility to resources - as well as the extent of public sector's retrenchment - coincide with the wealth of the area.

Development and validation of a gas chromatography-mass spectrometric method for the determination of sildenafil and desmethyl-sildenafil in whole blood.

Sildenafil (SDL) is a phosphodiesterase type 5 inhibitor and it is approved for the treatment of erectile dysfunction and pulmonary hypertension. SDL is extensively metabolized to its pharmacologically active metabolite, desmethyl-sildenafil (DSDL). A sensitive and specific GC/MS method for the determination of SDL and DSDL in whole blood was developed and validated to support therapeutic drug monitoring of SDL patients. The combination of solid-phase extraction with derivatization using BSTFA with 1% TMCS in acetonitrile efficiently reduced matrix effect and improved sensitivity of the method. In this assay, protriptyline was used as internal standard for both analytes. The LODs were 1.50 and 5.00 ng/mL for SDL and DSDL, respectively, whereas the respective LOQs were 5.00 and 15.0 ng/mL. The calibration curves were linear up to 500.0 ng/mL (SDL: R(2) 0.992, DSDL: R(2) 0.990). Absolute recovery values for both analytes ranged from 83.1 to 93.2%. Within- and between-batch accuracy was less than 11.8 and 10.2%, respectively, whereas within- and between-batch precision was less than 8.1 and 10.8%, correspondingly. The developed method is suitable for the determination of SDL and DSDL concentrations in blood samples obtained from patients under Viagra(®) treatment, for pharmacokinetic studies or for the investigation of related forensic cases.

The use of premature chromosome condensation to study in interphase cells the influence of environmental factors on human genetic material.

Nowadays, there is a constantly increasing concern regarding the mutagenic and carcinogenic potential of a variety of harmful environmental factors to which humans are exposed in their natural and anthropogenic environment. These factors exert their hazardous potential in humans' personal (diet, smoking, pharmaceuticals, cosmetics) and occupational environment that constitute part of the anthropogenic environment. It is well known that genetic damage due to these factors has dramatic implications for human health. Since most of the environmental genotoxic factors induce arrest or delay in cell cycle progression, the conventional analysis of chromosomes at metaphase may underestimate their genotoxic potential. Premature Chromosome Condensation (PCC) induced either by means of cell fusion or specific chemicals, enables the microscopic visualization of interphase chromosomes whose morphology depends on the cell cycle stage, as well as the analysis of structural and numerical aberrations at the G1 and G2 phases of the cell cycle. The PCC has been successfully used in problems involving cell cycle analysis, diagnosis and prognosis of human leukaemia, assessment of interphase chromosome malformations resulting from exposure to radiation or chemicals, as well as elucidation of the mechanisms underlying the conversion of DNA damage into chromosomal damage. In this report, particular emphasis is given to the advantages of the PCC methodology used as an alternative to conventional metaphase analysis in answering questions in the fields of radiobiology, biological dosimetry, toxicogenetics, clinical cytogenetics and experimental therapeutics.

The Elongator subunit Elp3 contains a Fe4S4 cluster and binds S-adenosylmethionine.

The Elp3 subunit of the Elongator complex is highly conserved from archaea to humans and contains a well-characterized C-terminal histone acetyltransferase (HAT) domain. The central region of Elp3 shares significant sequence homology to the Radical SAM superfamily. Members of this large family of bacterial proteins contain a FeS cluster and use S-adenosylmethionine (SAM) to catalyse a variety of radical reactions. To biochemically characterize this domain we have expressed and purified the corresponding fragment of the Methanocaldococcus jannaschii Elp3 protein. The presence of a Fe4S4 cluster has been confirmed by UV-visible spectroscopy and electron paramagnetic resonance (EPR) spectroscopy and the Fe content determined by both a colorimetric assay and atomic absorption spectroscopy. The cysteine residues involved in cluster formation have been identified by site-directed mutagenesis. The protein binds SAM and the binding alters the EPR spectrum of the FeS cluster. Our results provide biochemical support to the hypothesis that Elp3 does indeed contain the Fe4S4 cluster which characterizes the Radical SAM superfamily and binds SAM, suggesting that Elp3, in addition to its HAT activity, has a second as yet uncharacterized catalytic function. We also present preliminary data to show that the protein cleaves SAM.