Detection of phylogenetically informative polymorphisms in the entire euchromatic portion of human Y chromosome from a Sardinian sample

Background: Next-Generation Sequencing methods have led to a great increase in phylogenetically useful markers within the male specific portion of the Y chromosome, but previous studies have limited themselves to the study of the X-degenerate regions. Methods: DNA was extracted from peripheral blood samples of adult males whose paternal grandfathers were born in Sardinia. The DNA samples were sequenced, genotyped and subsequently analysed for variant calling for approximately 23.1 Mbp of the Y chromosome. A phylogenetic tree was built using Network 4.6 software. Results: From low coverage whole genome sequencing of 1,194 Sardinian males, we extracted 20,155 phylogenetically informative single nucleotide polymorphisms from the whole euchromatic region, including the X-degenerate, X-transposed, and Ampliconic regions, along with variants in other unclassified chromosome intervals and in the readable sequences of the heterochromatic region. Conclusions: The non X-degenerate classes contain a significant portion of the phylogenetic variation of the whole chromosome and their inclusion in the analysis, almost doubling the number of informative polymorphisms, refining the known molecular phylogeny of the human Y chromosome

Population- and individual-specific regulatory variation in Sardinia

Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.M.P. is supported by the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 633964 (ImmunoAgeing). Z.Z. is supported by the National Science Foundation (NSF) GRFP (DGE- 114747) and by the Stanford Center for Computational, Evolutionary, and Human Genomics (CEHG). Z.Z., J.R.D., and G.T.H. also acknowledge support from the Stanford Genome Training Program (SGTP; NIH/NHGRI T32HG000044). J.R.D. is supported by the Stanford Graduate Fellowship. K.R.K. is supported by Department of Defense, Air Force Office of Scientific Research, National Defense Science and Engineering Graduate (NDSEQ) Fellowship 32 CFR 168a. S.J.S. is supported by the NIHR Cambridge Biomedical Research Centre. The SardiNIA project is supported in part by the intramural program of the National Institute on Aging through contract HHSN271201100005C to the Consiglio Nazionale delle Ricerche of Italy. The RNA sequencing was supported by the PB05 InterOmics MIUR Flagship grant; by the FaReBio2011 “Farmaci e Reti Biotecnologiche di Qualità” grant; and by Sardinian Autonomous Region (L.R. no. 7/2009) grant cRP3-154 to F. Cucca, who is also supported by the Italian Foundation for Multiple Sclerosis (FISM 2015/R/09) and by the Fondazione di Sardegna (ex Fondazione Banco di Sardegna, Prot. U1301.2015/AI.1157.BE Prat. 2015-1651). S.B.M. is supported by the US National Institutes of Health through R01HG008150, R01MH101814, U01HG007436, and U01HG009080. All of the authors would like to thank the CRS4 and the SCGPM for the computational infrastructure supporting this project

The PRO‐HOME Project. A multicomponent intervention for the protected discharge from the hospital of multimorbid and polytreated older individuals by using innovative technologies: A pilot study

BackgroudDischarge planning from the hospital of frail older patients is an important step to avoid inappropriate long-stay hospitalizations and to prevent the risks related to the prolonged hospitalization. In this frame, we developed an experimental trial-'PRO-HOME', a multicomponent programme of interventions for multimorbid and polytreated hospitalized older patients.AimThe main aim of the study was to develop a protected discharge facility using a mini apartment equipped with advanced architectural and technological components to reduce the length of hospital stay of older participants (aged 65+ years old) admitted to the hospital for an acute event, deemed stable and dischargeable.Materials and MethodsThis is a pilot randomized controlled study, comparing 30 hospitalized participants included in a multidimensional, transitional care programme based on information and communication technologies to 30 patients in standard usual care until hospital discharge.ResultsWe presented the study design of the PRO-HOME programme, including architectural and technological components, the enrolment procedures, the components of the intervention that is physical activity, cognitive training and life-style education and the evaluation method of the intervention based on the Comprehensive Geriatric Assessment to explore the changes in the individual domains that are target of the multicomponent intervention.ConclusionsThe final results will suggest whether the PRO-HOME programme represents a useful and feasible intervention to reduce the length of hospital stay of multimorbid and polytreated hospitalized older patients and improve their physical and cognitive performances and overall quality of life.Patient or Public ContributionDue to the characteristics of the population of interest of the PRO-HOME study, we involved in the study design and programme of the activities the participants enrolled in a previous smart home-based project named MoDiPro carried-out during a 3-year period. The elderly participants from the local population involved were asked, by means of focus groups, for feedback on their experience in MoDiPro, and their suggestions were integrated into the design phase of the current PRO-HOME project. The focus groups included open group interviews with a qualitative collection of the patients' feedback so that the participants could interact with each other

Effects of fiber-glass-reinforced composite restorations on fracture resistance and failure mode of endodontically treated molars

Objectives The study evaluated the fracture resistance and fracture patterns of endodontically treated mandibular first molars restored with glass-fiber-reinforced direct composite restorations. Methods In total, 60 extracted intact first molars were treated endodontically; a mesio-occluso-distal (MOD) cavity was prepared and specimens were then divided into six groups: sound teeth (G1), no restoration (G2), direct composite restoration (G3), fiber-post-supported direct composite restoration (G4), direct composite reinforced with horizontal mesio-distal glass-fibers (G5), and buccal-palatal glass-fibers (G6). Specimens were subjected to 5000 thermocycles and 20,000 cycles of 45\ub0 oblique loading force at 1.3\ua0Hz and 50\ua0N; they were then loaded until fracture. The maximum fracture loads were recorded in Newtons (N) and data were analyzed with one-way ANOVA and post-hoc Tukey tests (p\ua0<\ua00.05). Fractured specimens were analyzed with a scanning electron microscope (SEM). Results The mean static loads (in Newtons) were: G1, 831.83; G2, 282.86; G3, 364.18; G4, 502.93; G5, 499.26; and G6, 582.22. Fracture resistance did not differ among G4, G5, and G6, but was significantly higher than G3 (p\ua0=\ua00.001). All specimens fractured in a catastrophic way. In G6, glass fibers inducted a partial deflection of the fracture, although they were not able to stop crack propagation. Conclusions For the direct restoration of endodontically treated molars, reinforcement of composite resins with glass-fibers or fiber posts can enhance fracture resistance. The SEM analysis showed a low ability of horizontal glass-fibers to deviate the fracture, but this effect was not sufficient to lead to more favorable fracture patterns above the cement-enamel junction (CEJ). Clinical significance The fracture resistance of endodontically treated molars restored with direct composite restorations seems to be increased by reinforcement with fibers, even if it is insufficient to restore sound molar fracture resistance and cannot avoid vertical fractures

Effects of fiber-glass-reinforced composite restorations on fracture resistance and failure mode of endodontically treated molars

OBJECTIVES: The study evaluated the fracture resistance and fracture patterns of endodontically treated mandibular first molars restored with glass-fiber-reinforced direct composite restorations. METHODS: In total, 60 extracted intact first molars were treated endodontically; a mesio-occluso-distal (MOD) cavity was prepared and specimens were then divided into six groups: sound teeth (G1), no restoration (G2), direct composite restoration (G3), fiber-post-supported direct composite restoration (G4), direct composite reinforced with horizontal mesio-distal glass-fibers (G5), and buccal-palatal glass-fibers (G6). Specimens were subjected to 5000 thermocycles and 20,000 cycles of 45° oblique loading force at 1.3Hz and 50N; they were then loaded until fracture. The maximum fracture loads were recorded in Newtons (N) and data were analyzed with one-way ANOVA and post-hoc Tukey tests (p<0.05). Fractured specimens were analyzed with a scanning electron microscope (SEM). RESULTS: The mean static loads (in Newtons) were: G1, 831.83; G2, 282.86; G3, 364.18; G4, 502.93; G5, 499.26; and G6, 582.22. Fracture resistance did not differ among G4, G5, and G6, but was significantly higher than G3 (p=0.001). All specimens fractured in a catastrophic way. In G6, glass fibers inducted a partial deflection of the fracture, although they were not able to stop crack propagation. CONCLUSIONS: For the direct restoration of endodontically treated molars, reinforcement of composite resins with glass-fibers or fiber posts can enhance fracture resistance. The SEM analysis showed a low ability of horizontal glass-fibers to deviate the fracture, but this effect was not sufficient to lead to more favorable fracture patterns above the cement-enamel junction (CEJ). CLINICAL SIGNIFICANCE: The fracture resistance of endodontically treated molars restored with direct composite restorations seems to be increased by reinforcement with fibers, even if it is insufficient to restore sound molar fracture resistance and cannot avoid vertical fractures