Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold

A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives

Application of laboratory methods for understanding fish responses to black soldier fly (Hermetia illucens) based diets

A major challenge for development of sustainable aquafeeds is its dependence on fish meal and fish oil. Replacement with more sustainable, nutritious and safe ingredients is now a priority. Over the last years, among several alternatives proposed, insects have received great attention as possible candidates. In particular, the black soldier fly (Hermetia illucens; BSF) represents a concrete example of how the circular economy concept can be applied to fish culture, providing a valuable biomass rich in fat and protein valorising organic by-products. In the last decade, several studies have been published about the use of different BSF dietary inclusion levels for various fish species including experimental models. Varying and encouraging results have been obtained in this research field using a plethora of laboratory methodological approaches that can be applied and coupled to obtain a comprehensive view of the BSF-based diets effects on fish physiology, health, and quality. The present review aims to explore some of the most promising laboratory approaches like histology, infrared spectroscopy, gut microbiome sequencing, molecular biology, fish fillets’ physico-chemical and sensory properties, essential for a better understanding of fish welfare and fillet quality, when BSF is used as aquafeed ingredient. In particular, great importance has been given to European finfish species and experimental models.publishedVersio

Variation of the Myelin Oligodendrocyte Glycoprotein gene is not primarily associated with multiple sclerosis in the Sardinian population

Background. Multiple sclerosis (MS) is consistently associated with particular HLA-DRB1-DQB1 haplotypes. However, existing evidence suggests that variation at these loci does not entirely explain association of the HLA region with the disease. The MOG locus is a prime positional and functional candidate for such additional predisposing effects but the analysis is complicated by the strong, albeit labyrinthine pattern of linkage disequilibrium in the region. Here we have assessed the association of MOG variation with MS in the Sardinian population to see if it represents an independent contributor to MS predisposition. Results. After re-sequencing the MOG gene in 21 healthy parents of MS patients we detected 134 variants, 33 of which were novel. A set of 40 informative SNPs was then selected and assessed for disease association together with 1 intragenic microsatellite in an initial data set of 239 MS families. This microsatellite and 11 SNPs were found to be positively associated with MS, using the transmission disequilibrium test, and were followed up in an additional 158 families (total families analysed = 397). While in these 397 families, 8 markers showed significant association with MS, through conditional tests we determined that these MOG variants were not associated with MS independently of the main DRB1-DQB1 disease associations. Conclusion. These results indicate that variation within the MOG gene is not an important independent determinant of MS-inherited risk in the Sardinian population

The quest for companions to post-common envelope binaries: I. Searching a sample of stars from the CSS and SDSS

As part of an ongoing collaboration between student groups at high schools and professional astronomers, we have searched for the presence of circum-binary planets in a bona-fide unbiased sample of twelve post-common envelope binaries (PCEBs) from the Catalina Sky Survey (CSS) and the Sloan Digital Sky Survey (SDSS). Although the present ephemerides are significantly more accurate than previous ones, we find no clear evidence for orbital period variations between 2005 and 2011 or during the 2011 observing season. The sparse long-term coverage still permits O-C variations with a period of years and an amplitude of tens of seconds, as found in other systems. Our observations provide the basis for future inferences about the frequency with which planet-sized or brown-dwarf companions have either formed in these evolved systems or survived the common envelope (CE) phase.Comment: accepted by A&

Integration of priority population, health and nutrition interventions into health systems: systematic review

Objective of the study was to assess the effects of strategies to integrate targeted priority population, health and nutrition interventions into health systems on patient health outcomes and health system effectiveness and thus to compare integrated and non-integrated health programmes. Systematic review using Cochrane methodology of analysing randomised trials, controlled before-and-after and interrupted time series studies. We defined specific strategies to search PubMed, CENTRAL and the Cochrane Effective Practice and Organisation of Care Group register, considered studies published from January 1998 until September 2008, and tracked references and citations. Two reviewers independently agreed on eligibility, with an additional arbiter as needed, and extracted information on outcomes: primary (improved health, financial protection, and user satisfaction) and secondary (improved population coverage, access to health services, efficiency, and quality) using standardised, pre-piloted forms. Two reviewers in the final stage of selection jointly assessed quality of all selected studies using the GRADE criteria. Of 8,274 citations identified 12 studies met inclusion criteria. Four studies compared the benefits of Integrated Management of Childhood Illnesses in Tanzania and Bangladesh, showing improved care management and higher utilisation of health facilities at no additional cost. Eight studies focused on integrated delivery of mental health and substance abuse services in the United Kingdom and United States of America. Integrated service delivery resulted in better clinical outcomes and greater reduction of substance abuse in specific sub-groups of patients, with no significant difference found overall. Quality of care, patient satisfaction, and treatment engagement were higher in integrated delivery models. Targeted priority population health interventions we identified led to improved health outcomes, quality of care, patient satisfaction and access to care. Limited evidence with inconsistent findings across varied interventions in different settings means no general conclusions can be drawn on the benefits or disadvantages of integrated service delivery

Genetic loci linked to Type 1 Diabetes and Multiple Sclerosis families in Sardinia

<p>Abstract</p> <p>Background</p> <p>The Mediterranean island of Sardinia has a strikingly high incidence of the autoimmune disorders Type 1 Diabetes (T1D) and Multiple Sclerosis (MS). Furthermore, the two diseases tend to be co-inherited in the same individuals and in the same families. These observations suggest that some unknown autoimmunity variant with relevant effect size could be fairly common in this founder population and could be detected using linkage analysis.</p> <p>Methods</p> <p>To search for T1D and MS loci as well as any that predispose to both diseases, we performed a whole genome linkage scan, sequentially genotyping 593 microsatellite marker loci in 954 individuals distributed in 175 Sardinian families. In total, 413 patients were studied; 285 with T1D, 116 with MS and 12 with both disorders. Model-free linkage analysis was performed on the genotyped samples using the Kong and Cox logarithm of odds (LOD) score statistic.</p> <p>Results</p> <p>In T1D, aside from the HLA locus, we found four regions showing a lod-score ≥1; 1p31.1, 6q26, 10q21.2 and 22q11.22. In MS we found three regions showing a lod-score ≥1; 1q42.2, 18p11.21 and 20p12.3. In the combined T1D-MS scan for shared autoimmunity loci, four regions showed a LOD >1, including 6q26, 10q21.2, 20p12.3 and 22q11.22. When we typed more markers in these intervals we obtained suggestive evidence of linkage in the T1D scan at 10q21.2 (LOD = 2.1), in the MS scan at 1q42.2 (LOD = 2.5) and at 18p11.22 (LOD = 2.6). When all T1D and MS families were analysed jointly we obtained suggestive evidence in two regions: at 10q21.1 (LOD score = 2.3) and at 20p12.3 (LOD score = 2.5).</p> <p>Conclusion</p> <p>This suggestive evidence of linkage with T1D, MS and both diseases indicates critical chromosome intervals to be followed up in downstream association studies.</p