Polygenic risk prediction models for colorectal cancer: a systematic review

Background Risk prediction models incorporating single nucleotide polymorphisms (SNPs) could lead to individualized prevention of colorectal cancer (CRC). However, the added value of incorporating SNPs into models with only traditional risk factors is still not clear. Hence, our primary aim was to summarize literature on risk prediction models including genetic variants for CRC, while our secondary aim was to evaluate the improvement of discriminatory accuracy when adding SNPs to a prediction model with only traditional risk factors. Methods We conducted a systematic review on prediction models incorporating multiple SNPs for CRC risk prediction. We tested whether a significant trend in the increase of Area Under Curve (AUC) according to the number of SNPs could be observed, and estimated the correlation between AUC improvement and number of SNPs. We estimated pooled AUC improvement for SNP-enhanced models compared with non-SNP-enhanced models using random effects meta-analysis, and conducted meta-regression to investigate the association of specific factors with AUC improvement. Results We included 33 studies, 78.79% using genetic risk scores to combine genetic data. We found no significant trend in AUC improvement according to the number of SNPs (p for trend = 0.774), and no correlation between the number of SNPs and AUC improvement (p = 0.695). Pooled AUC improvement was 0.040 (95% CI: 0.035, 0.045), and the number of cases in the study and the AUC of the starting model were inversely associated with AUC improvement obtained when adding SNPs to a prediction model. In addition, models constructed in Asian individuals achieved better AUC improvement with the incorporation of SNPs compared with those developed among individuals of European ancestry. Conclusions Though not conclusive, our results provide insights on factors influencing discriminatory accuracy of SNP-enhanced models. Genetic variants might be useful to inform stratified CRC screening in the future, but further research is needed

Probing the chemical environment of 3-hydroxyflavone doped ormosils by a spectroscopic study of excited state intramolecular proton transfer

Abstract The spectroscopic properties of 3-hydroxyflavone (3-HF) molecules entrapped in films and in monoliths of sol–gel derived organically modified silicates (Ormosils) xerogels are studied by excitation and fluorescence spectroscopy as a function of the sol–gel precursors used for the synthesis. Different molar ratios of tetraethoxysilane (TEOS), methyltriethoxysilane (MTES) and phenyltriethoxysilane (PTES) as precursors are used for the sol preparation. Emission and excitation spectra in the ultraviolet–visible range and photo-degradation curves as a function of time are collected with a spectrofluorimeter. The 3-hydroxyflavone optical properties change in the different networks, owing to the effects of the chemical environment on the excited state intramolecular proton transfer and to the solubility of the dye molecules in the different sol–gel systems. It turns out that the spectroscopic features can be used to probe the chemical state of the dye molecules microenvironment

Determinants of within-country variation in traffic accident mortality in Italy: a geographical analysis

Objective: To identify determinants of regional differences in traffic accident mortality in Italy. Data and methods: Multiple linear regression models were conducted assessing the associations between regional differences in traffic mortality, case fatality and accident rates (dependent variables) with socio-demographic factors, and variables describing road behaviour, vehicles, infrastructure and medical care (independent variables). Data were derived from the National Institute of Statistics, the National Institute of Health and the Italian Automobile Club. In addition to analyses for the whole country of Italy, separate models were conducted for Northern and southern regions. Results: In Italy large regional differences in traffic mortality rates can be observed, ranging from 5.5 to 20 per 100.000 person-years. There is a North-South gradient with higher mortality rates in the Northern part of Italy. S

Porphyrin-containing polyimide films deposited by high vacuum co-evaporation

Abstract Thin films of porphyrin-containing polyimide were produced by high vacuum co-evaporation of 4,4′-hexafluoroisopropylidene diphthalic anhydride (6FDA), 3,3′-diaminodiphenyl sulfone (DDS) and 5,10,15,20 meso-tetraphenyl porphyrin (TPP). The films were characterized by FT-IR analysis, optical absorption and emission spectroscopy. FT-IR analysis shows that the film matrix is comprised of only unreacted monomers. The conversion of monomers to polyamic acid and the following condensation to polyimide were studied by curing the samples at temperatures up to 240 °C. The amount of polyamic acid increases from room temperature to 120 °C, while at higher temperature it starts to condense to polyimide. Optical analysis shows that TPP is incorporated in the film matrix and its chemical state is determined by the interaction with the monomers, polyamic acid and polyimide. After curing the TPP molecules are finely dispersed in the polyimide matrix and their absorption and fluorescence properties are wholly preserved

Optical and Scintillation Properties of Polydimethyl-Diphenylsiloxane Based Organic Scintillators

Polysiloxane based scintillators with high light yield have been synthesized. The polymer consists in cross-linked polydimethyl-co-diphenylsiloxane with different molar percentages of phenyl units. 2,5-diphenyl oxazole (PPO) and 2,5-bis(5-ter-butyl-2-benzoxazolyl)thiophene (BBOT) have been dispersed in the polymer as dopants. The energy transfer and scintillation capabilities have been investigated, for two different amounts of phenyl groups in the polymer network and for different concentrations of dye molecules, by means of fluorescence spectroscopy, ion beam induced luminescence (IBIL) and scintillation yield measurements with ? particles from an 241Am source. The luminescence features and the scintillation yields have been correlated to the composition of the scintillators

Different Cognitive Frailty Models and Health- and Cognitive-related Outcomes in Older Age: From Epidemiology to Prevention

Frailty, a critical intermediate status of the aging process that is at increased risk for negative health-related events, includes physical, cognitive, and psychosocial domains or phenotypes. Cognitive frailty is a condition recently defined by operationalized criteria describing coexisting physical frailty and mild cognitive impairment (MCI), with two proposed subtypes: potentially reversible cognitive frailty (physical frailty/MCI) and reversible cognitive frailty (physical frailty/pre- MCI subjective cognitive decline). In the present article, we reviewed the framework for the definition, different models, and the current epidemiology of cognitive frailty, also describing neurobiological mechanisms, and exploring the possible prevention of the cognitive frailty progression. Several studies suggested a relevant heterogeneity with prevalence estimates ranging 1.0–22.0% (10.7–22.0% in clinical-based settings and 1.0–4.4% in population-based settings). Cross-sectional and longitudinal population-based studies showed that different cognitive frailty models may be associated with increased risk of functional disability, worsened quality of life, hospitalization, mortality, incidence of dementia, vascular dementia, and neurocognitive disorders. The operationalization of clinical constructs based on cognitive impairment related to physical causes (physical frailty, motor function decline, or other physical factors) appears to be interesting for dementia secondary prevention given the increased risk for progression to dementia of these clinical entities. Multidomain interventions have the potential to be effective in preventing cognitive frailty. In the near future, we need to establish more reliable clinical and research criteria, using different operational definitions for frailty and cognitive impairment, and useful clinical, biological, and imaging markers to implement intervention programs targeted to improve frailty, so preventing also late-life cognitive disorders