Eumelanin broadband absorption develops from aggregation-modulated chromophore interactions under structural and redox control

Eumelanins, the chief photoprotective pigments in man and mammals, owe their black color to an unusual broadband absorption spectrum whose origin is still a conundrum. Excitonic effects from the interplay of geometric order and disorder in 5,6-dihydroxyindole (DHI)-based oligomeric/polymeric structures play a central role, however the contributions of structural (scaffold-controlled) and redox ( €-electron-controlled) disorder have remained uncharted. Herein, we report an integrated experimental-theoretical entry to eumelanin chromophore dynamics based on poly(vinyl alcohol)-controlled polymerization of a large set of 5,6-dihydroxyindoles and related dimers. The results a) uncover the impact of the structural scaffold on eumelanin optical properties, disproving the widespread assumption of a universal monotonic chromophore; b) delineate eumelanin chromophore buildup as a three-step dynamic process involving the rapid generation of oxidized oligomers, termed melanochromes (phase I), followed by a slow oxidant-independent band broadening (phase II) leading eventually to scattering (phase III); c) point to a slow reorganization-stabilization of melanochromes via intermolecular redox interactions as the main determinant of visible broadband absorption

Telomere length is independently associated with subclinical atherosclerosis in subjects with type 2 diabetes: a cross-sectional study

Aims: Individuals with type 2 diabetes show shorter leukocyte telomere length (LTL) compared to people without diabetes. Reduced LTL is associated with increased carotid intima-media thickness (IMT) in healthy subjects. The aim of the study is to assess whether LTL also correlates with IMT in patients with diabetes. Methods: In a cohort of 104 subjects with type 2 diabetes and atherogenic dyslipidemia, we assessed anthropometric, hemodynamic and metabolic parameters. Common carotid IMT was expressed as the maximum IMT. LTL was assessed by a specific real-time PCR reaction. Results: At univariate analysis, IMT values were positively correlated with age (p < 0.001), previous history of cardiovascular events (p < 0.005), fasting plasma glucose (p < 0.01), HbA1c (p < 0.05) and negatively correlated with LTL (p < 0.05). In a multivariate model, age (p < 0.001) and LTL (p < 0.05) were the only independent predictors of maximum IMT, with an adjusted R2 of 0.22. Conclusions: LTL is an independent predictor of subclinical atherosclerosis pointing to a role of LTL as an early marker of vascular burden and cardiovascular disease also in type 2 diabetes

"Delirium Day": A nationwide point prevalence study of delirium in older hospitalized patients using an easy standardized diagnostic tool

Background: To date, delirium prevalence in adult acute hospital populations has been estimated generally from pooled findings of single-center studies and/or among specific patient populations. Furthermore, the number of participants in these studies has not exceeded a few hundred. To overcome these limitations, we have determined, in a multicenter study, the prevalence of delirium over a single day among a large population of patients admitted to acute and rehabilitation hospital wards in Italy. Methods: This is a point prevalence study (called "Delirium Day") including 1867 older patients (aged 65 years or more) across 108 acute and 12 rehabilitation wards in Italian hospitals. Delirium was assessed on the same day in all patients using the 4AT, a validated and briefly administered tool which does not require training. We also collected data regarding motoric subtypes of delirium, functional and nutritional status, dementia, comorbidity, medications, feeding tubes, peripheral venous and urinary catheters, and physical restraints. Results: The mean sample age was 82.0 ± 7.5 years (58 % female). Overall, 429 patients (22.9 %) had delirium. Hypoactive was the commonest subtype (132/344 patients, 38.5 %), followed by mixed, hyperactive, and nonmotoric delirium. The prevalence was highest in Neurology (28.5 %) and Geriatrics (24.7 %), lowest in Rehabilitation (14.0 %), and intermediate in Orthopedic (20.6 %) and Internal Medicine wards (21.4 %). In a multivariable logistic regression, age (odds ratio [OR] 1.03, 95 % confidence interval [CI] 1.01-1.05), Activities of Daily Living dependence (OR 1.19, 95 % CI 1.12-1.27), dementia (OR 3.25, 95 % CI 2.41-4.38), malnutrition (OR 2.01, 95 % CI 1.29-3.14), and use of antipsychotics (OR 2.03, 95 % CI 1.45-2.82), feeding tubes (OR 2.51, 95 % CI 1.11-5.66), peripheral venous catheters (OR 1.41, 95 % CI 1.06-1.87), urinary catheters (OR 1.73, 95 % CI 1.30-2.29), and physical restraints (OR 1.84, 95 % CI 1.40-2.40) were associated with delirium. Admission to Neurology wards was also associated with delirium (OR 2.00, 95 % CI 1.29-3.14), while admission to other settings was not. Conclusions: Delirium occurred in more than one out of five patients in acute and rehabilitation hospital wards. Prevalence was highest in Neurology and lowest in Rehabilitation divisions. The "Delirium Day" project might become a useful method to assess delirium across hospital settings and a benchmarking platform for future surveys

Understanding Factors Associated With Psychomotor Subtypes of Delirium in Older Inpatients With Dementia

Objectives: Few studies have analyzed factors associated with delirium subtypes. In this study, we investigate factors associated with subtypes of delirium only in patients with dementia to provide insights on the possible prevention and treatments. Design: This is a cross-sectional study nested in the \u201cDelirium Day\u201d study, a nationwide Italian point-prevalence study. Setting and Participants: Older patients admitted to 205 acute and 92 rehabilitation hospital wards. Measures: Delirium was evaluated with the 4-AT and the motor subtypes with the Delirium Motor Subtype Scale. Dementia was defined by the presence of a documented diagnosis in the medical records and/or prescription of acetylcholinesterase inhibitors or memantine prior to admission. Results: Of the 1057 patients with dementia, 35% had delirium, with 25.6% hyperactive, 33.1% hypoactive, 34.5% mixed, and 6.7% nonmotor subtype. There were higher odds of having venous catheters in the hypoactive (OR 1.82, 95% CI 1.18-2.81) and mixed type of delirium (OR 2.23, CI 1.43-3.46), whereas higher odds of urinary catheters in the hypoactive (OR 2.91, CI 1.92-4.39), hyperactive (OR 1.99, CI 1.23-3.21), and mixed types of delirium (OR 2.05, CI 1.36-3.07). We found higher odds of antipsychotics both in the hyperactive (OR 2.87, CI 1.81-4.54) and mixed subtype (OR 1.84, CI 1.24-2.75), whereas higher odds of antibiotics was present only in the mixed subtype (OR 1.91, CI 1.26-2.87). Conclusions and Implications: In patients with dementia, the mixed delirium subtype is the most prevalent followed by the hypoactive, hyperactive, and nonmotor subtype. Motor subtypes of delirium may be triggered by clinical factors, including the use of venous and urinary catheters, and the use of antipsychotics. Future studies are necessary to provide further insights on the possible pathophysiology of delirium in patients with dementia and to address the optimization of the management of potential risk factors