Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer's disease: a longitudinal analysis.

Introduction: The adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods: All data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted. Results: Leptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population. Discussion: The evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.

Atrial Fibrillation and Dementia: Focus on Shared Pathophysiological Mechanisms and Therapeutic Implications.

OBJECTIVES: Atrial fibrillation (AF) and dementia are highly prevalent chronic and debilitating conditions, especially affecting the older population. This review focuses on possible common pathophysiological mechanisms that could explain the association between the 2 conditions. DESIGN: Narrative review. SETTING AND PARTICIPANTS: Evidence from epidemiologic, observational, and interventional studies evaluating prevalence and incidence of cognitive impairment in patients with AF. METHODS: Broad literature search between December 2022 and May 2023. Eligible categories for inclusion comprised interventional studies, observational studies, systematic reviews, and meta-analysis. RESULTS: Evidence from different cohorts has shown that AF increases the risk of dementia, although the association with dementia subtypes is not always unequivocal. According to recent evidence, common pathophysiological mechanisms include thromboembolism and hypercoagulable states, proinflammatory state, infection, cerebral hypoperfusion, and brain atrophy. Moreover, we reviewed the evidence on therapeutic measures to prevent dementia in patients with AF. CONCLUSIONS AND IMPLICATIONS: Screening for cognition in patients with AF is of paramount importance, given the shared risk factors and common pathophysiological mechanisms. More evidence is needed to clarify whether antiarrhythmic and anticoagulant therapy have an impact on cognitive outcomes in AF patients.

Intricate relationship between obstructive sleep apnea and dementia in older adults.

Numerous evidence reports direct correlation between cognitive impairment, Alzheimer's disease and sleep disorders, in particular obstructive sleep apnea. Both obstructive sleep apnea and Alzheimer's disease are highly prevalent conditions whose incidence increases with age. Several studies demonstrate how sleep-disordered breathing may lead to poor cognition, even though the underlying mechanisms of this association remain partially unclear. According to the most recent studies, obstructive sleep apnea may be considered a modifiable risk factor for cognitive dysfunction. In the present review, the authors aim to integrate recent research examining obstructive sleep apnea and Alzheimer's disease biomarkers, also focusing on the mechanisms that support this correlation, including but not limited to the role of hypoxia and cardiovascular risk. Moreover, the potential favourable effect of obstructive sleep apnea therapy on cognitive function is discussed, to evaluate the benefits deriving from appropriate treatment of sleep-disordered breathing on cognition.

Neuropsychiatric symptoms and their neural correlates in individuals with mild cognitive impairment.

OBJECTIVES: Neuropsychiatric symptoms are common in subjects with MCI and associated with higher risk of progression to AD. The cognitive and neuroanatomical correlates of neuropsychiatric symptoms in MCI have not been fully elucidated. In this study, we sought to evaluate the association between neuropsychiatric symptoms, cognitive function, regional tau deposition, and brain volumes in MCI subjects. METHODS: A total of 233 MCI and 305 healthy comparisons were selected from the ADNI-3 cohort. All the subjects underwent a comprehensive neuropsychological assessment, volumetric MR brain scan, and Flortaucipir PET for in vivo assessment of regional tau deposition. Prevalence of neuropsychiatric symptoms was evaluated by means of the NPI questionnaire. Multivariate analyses of variance were used to detect differences in cognitive and imaging markers in MCI subjects with and without neuropsychiatric symptoms. RESULTS: 61.4% MCI subjects showed at least one neuropsychiatric symptom, with the most prevalent ones being depression (26.1%), irritability (23.6%), and sleep disturbances (23.6%). There was a significant effect of neuropsychiatric symptoms on cognitive tests of frontal and executive functions. MCI subjects with neuropsychiatric symptoms showed reduced brain volumes in the orbitofrontal and posterior cingulate cortices, while no effects were detected on regional tau deposition. Posterior cingulate cortex volume was the only predictor of global neuropsychiatric burden in this MCI population. CONCLUSIONS: Neuropsychiatric symptoms occur early in the AD trajectory and are mainly related to defects of control executive abilities and to the reduction of gray matter volume in the orbitofrontal and posterior cingulate cortices. A better understanding of the cognitive and neuroanatomical mechanisms of neuropsychiatric symptoms in MCI could help develop more targeted and efficacious treatment alternatives.

Supraventricular Tachycardia Following Mitral Valve Surgery.

A man in his mid-50s with a history of mitral valve repair presented to the emergency department with complaints of recent-onset palpitation. The QRS complexes displayed pairs of beats exhibiting complete right bundle branch block and QRS duration of 140 milliseconds followed by a third beat with normal configuration and QRS duration of 70 milliseconds. What would you do next?

Wolff-Parkinson-White pattern on alternate beats: What is the mechanism?

The Holter electrocardiogram from an asymptomatic man shows intermittent preexcitation. At the lowest rates all the QRS complexes display a WPW pattern. As the rate increases, preexcitation fails to occur and all the QRS complexes become persistently narrow. With a further increase in sinus rate the WPW occurs on alternate beats and this alternation is maintained for a while. A careful analysis of the accessory pathway conduction in relation to sinus-cycle length and morphology of the prior beat strongly supports the supernormal conduction through the Kent bundle associated with linking as the key mechanism underlying the preexcitation on alternate beats.

Corneal light backscattering after transepithelial corneal crosslinking using iontophoresis in donor human corneal tissue.

PURPOSE: To analyze the spatial distribution and time course of corneal light backscattering before and after transepithelial corneal crosslinking using iontophoresis. SETTING: Fondazione G.B. Bietti-IRCCS, Rome, Italy. DESIGN: Experimental study. METHODS: Three donor human eyes with an intact corneal epithelium had transepithelial iontophoresis corneal crosslinking (using rapid ultraviolet-A [UVA] irradiation), and 3 donor eyes without corneal epithelium had standard corneal crosslinking (using standard UVA irradiation). In addition, 3 donor eyes had iontophoresis and rapid corneal crosslinking after corneal deepithelialization (epi-off iontophoresis corneal crosslinking). Scheimpflug images (Pentacam HR) of each eye globe were acquired before and immediately after administration of riboflavin 0.1% solutions and 5, 10, 30, and 120 minutes after the corneal crosslinking procedures. Corneal light backscattering was quantified across the anterior 280 µm thickness at several points from the optical center to 3.0 mm from the center. RESULTS: Light backscattering significantly increased after iontophoresis (P < .001) in specimens with and without intact epithelium. It decreased significantly after transepithelial iontophoresis corneal crosslinking and epi-off iontophoresis corneal crosslinking (P < .001), approaching the baseline values. After standard stromal soaking with riboflavin, a large increase in corneal light backscattering was found compared with baseline measurements (P < .001) that remained unchanged up to 30 minutes after standard corneal crosslinking (P = .92). The light backscattering increase after iontophoresis in corneas with epithelium was lower than after standard soaking (P = .01). No differences were found between specimens without epithelium after iontophoresis and standard stromal soaking (P = .06). CONCLUSIONS: Scheimpflug photography provided an indirect biomarker of stromal permeation of riboflavin. Iontophoresis efficiently delivered riboflavin through the epithelium. FINANCIAL DISCLOSURE: No author has a financial or proprietary interest in any material or method mentioned.

Biomechanics of the anterior human corneal tissue investigated with atomic force microscopy.

PURPOSE: To investigate the biomechanics of the anterior human corneal stroma using atomic force microscopy (AFM). METHODS: AFM measurements were performed in liquid on the anterior stroma of human corneas, after gently removing the epithelium, using an atomic force microscope in the force spectroscopy mode. Rectangular silicon cantilevers with tip radius of 10 nm and spring elastic constants of 25- and 33-N/m were used. Each specimen was subjected to increasing loads up to a maximum of 2.7 µN with scan speeds ranging between 3- and 95-µm/s. The anterior stromal hysteresis during the extension-retraction cycle was quantified as a function of the application load and scan rate. The elastic modulus of the anterior stroma was determined by fitting force curve data to the Sneddon model. RESULTS: The anterior stroma exhibited significant viscoelasticity at micrometric level: asymmetry in the curve loading-unloading response with considerable hysteresis dependent both on the application load and scan rate (P < 0.01). The mean elastic modulus ranged between 1.14 and 2.63 MPa and was constant over the range of indentation depths between 1.0 and 2.7 µm in the stroma. CONCLUSIONS: At microscale level, the mechanical response of the most anterior stroma is complex and nonlinear. The microstructure (fibers' packing, number of cross-links, water content) and the combination of elastic (collagen fibers) and viscous (matrix) components of the tissue influence the type of viscoelastic response. Efforts in modeling the biomechanics of human corneal tissue at micrometric level are needed.

Direct nanomechanical measurement of layer thickness and compressibility of smectic liquid crystals.

Using an atomic force microscope (AFM) we confined a smectic-A liquid crystal (LC) between a flat glass plate and a 10-µm glass sphere attached to the free end of the AFM cantilever. Both surfaces were treated with a surfactant that induces normal alignment of the LC molecules. We measured the force F acting on the cantilever while varying the plate-sphere distance D with subnanometer precision. For D < 50 nm, the force was periodically oscillating and decayed as D was increased. Analyzing the force in the framework of a simple model of elastic deformation of the smectic layers, we have evaluated the undeformed layer thickness a(0) and compressibility modulus B. Compared to other techniques used to determine a(0) and B, AFM measurements are faster and require a much smaller amount (microliters) of LC. Moreover, they are based on purely mechanical deformations of the LC structure and do not require any static or radiative electromagnetic field.

Unwinding of the uniform lying helix structure in cholesteric liquid crystals next to a spatially uniform aligning surface.

The symmetry of the cholesteric uniform lying helix (ULH) structure, where the helix axis is aligned in a single direction parallel to the device substrates, is not compatible with a uniform surface alignment and an unwinding of the helical structure is expected at the interface. Fluorescence confocal polarizing microscopy experiments are performed on the interface between a bulk ULH and a uniform aligning surface (for both planar and homeotropic alignments). The results are analyzed in the framework of a finite difference numerical simulation based on the Frank elastic distortion, to determine relevant director structures. An optical model is introduced to predict three-dimensional fluorescence profiles for the structures. Comparison of experimental and theoretical results shows that the equilibrium structure of the system involves a continuous unwinding of the helix close to the surface.

Mechanically induced biaxial transition in a nanoconfined nematic liquid crystal with a topological defect.

Using an atomic force microscopy, we have measured the separation dependence of the force between an atomically flat mica sheet and a micrometer-sized glass sphere immersed in the nematic liquid crystal. As the mica surface induces a strong parallel alignment and the treated glass sphere induces a strong perpendicular alignment on the liquid crystal, a repulsive force is observed due to the elastically deformed nematic liquid crystal. We observe that below a critical separation d(th) approximately 10 nm, the system undergoes a structural transition, thus relaxing the distortion. The results are interpreted within the eigenvalue exchange mechanism using the Landau-de Gennes tensorial approach.

Side-chain modified bile acids: chromatographic separation of 23-methyl epimers.

Owing to the re-flourished interest towards the bile acids (BAs) as versatile signalling hormones endowed with diverse endocrine functions, the development of reliable analytical protocols monitoring the synthesis of new BA-based receptor modulators, still represents a cogent concern. On this basis, for the first time, a HPLC study has been engaged with the aim to set up suitable chromatographic conditions for the analysis of three different epimeric couples of 23-methyl-substituted unconjugated BAs. Three different methods (one for each couple) have been successfully established and then validated. Good precision and accuracy (evaluated both in the short and long period) as well as appreciably low LOD and LOQ values have turned out. Moreover, the engagement of an evaporative light scattering detector (ELSD) has proven its high effectiveness for the analysis of such steroidal species.

Analysis of intraocular lens surface adhesiveness by atomic force microscopy.

PURPOSE: To analyze intraocular lens (IOL) optic surface adhesiveness using atomic force microscopy (AFM). SETTING: LiCryL Laboratory, University of Calabria, Rende, Italy. METHODS: The surface adhesive properties of poly(methyl methacrylate) (PMMA), silicone, hydrophilic acrylic, and hydrophobic acrylic IOLs were evaluated by AFM. Analysis was performed at room temperature (21 degrees C) in a liquid environment using the force-versus-distance mode of a commercial instrument (NanoScope III). Measurements were acquired with rectangular silicon cantilevers of a nominal elastic constant of 10 Newton/m. The nominal value of the tip's radius of curvature was 1 mum, and the scanning speed during the acquisitions ranged from 10 to 400 nm/s. RESULTS: The adhesion force measurements showed different characteristics for the various types of IOLs (P<.001, analysis of variance). The hydrophobic acrylic IOL had the largest mean adhesive force (283.75 nanoNewton [nN] +/- 0.14 [SD]) followed by the hydrophilic acrylic (84.76 +/- 0.94 nN), PMMA (45.77 +/- 0.47 nN), and silicone (2.10 +/- 0.01 nN) IOLs. CONCLUSIONS: The surface properties of the biomaterials used to manufacture IOLs are important because they can influence the incidence and severity of posterior capsule opacification (PCO). Although further studies are necessary to elucidate the mechanism of PCO development and the interface interactions between the IOL and capsule, the results in this study may bolster the theory of manufacturing more-adhesive materials to prevent PCO.

The effect of the copper(II) salt anion in the Chiral Ligand-Exchange Chromatography of amino acids.

Due to the strong involvement in numerous biochemical processes, the separation and resolution of amino acids is a continuously challenging task. Among the experimental parameters affecting the performances in a Chiral Ligand-Exchange Chromatography (CLEC) environment, the effect of the copper(II) salt counter-ion has received very limited attention. Aimed at evaluating the Cu(II) counter-ion effect upon the overall chromatographic performances when the S-trityl-(R)-cysteine is adopted as the chiral selector for the coated stationary phase, a number of both organic (acetate, formate, trifluoromethane-sulfonate) and inorganic (bromide, chloride, nitrate, perchlorate, sulfate) salts has been engaged for the enantiomer separation of a selected set of aliphatic (Allo-Ile, Ile, Leu, Nor-Leu, Nor-Val, Val) and aromatic (AIDA, ATIDA, His, Phe, Phg, Tyr) amino acids. By varying the physico-chemical nature of the Cu(II) anion, a pronounced impact upon the resolution factor (R(S)) has been observed. Even if to a lesser extent, the enantioseparation factor values (alpha) underwent variation, as well. A molecular modelling investigation has also been carried out as a rationalization attempt of the observed chromatographic outcomes.

Derived chromatographic indices as effective tools to study the self-aggregation process of bile acids.

Reversed-phase high-performance liquid chromatography (RP-HPLC) is more and more adopted as a fruitful tool for the estimation of several physico-chemical properties of diverse classes of organic compounds. In this frame, derived chromatographic indices have been proposed as effective parameters to measure the lipophilicity (log P or log D) of compounds. Instead, a limited attention has been directed towards the chromatographic evaluation of the Critical Micellar Concentration (CMC), one of the most important parameters employed to study the bile acid physico-chemical profile. We have recently reported on the effectiveness of the derived chromatographic index phi(0) for the study of the self-aggregation process of bile acids. Here we show that this index is independent upon the adopted chromatographic environment so as to be instrumental for the evaluation of the hydrophobic/hydrophilic balance of bile acids. Molecular modelling studies have also been undertaken with the aim of rationalizing the experimental findings.

Bend-induced melting of the smectic-A phase: analogy to a type-I superconductor.

Using an atomic force microscope to nanopattern a substrate for liquid crystal alignment, a bend distortion is imposed on a liquid crystal. In regions of large bend the smectic-A phase melts into the nematic phase, and the width of the melted region is measured as a function of temperature. The results are consistent with type-I superconducting (nematic-smectic-A) behavior, wherein a large magnetic field (bend or twist distortion) induces an order to disorder transition. A model that accounts for non-mean-field behavior is presented.

Quasidivergent nematic surface electroclinic effect.

A polyimide coated substrate is treated so that vertical liquid crystal alignment (theta=0) obtains over the temperature range T(NA)< T < T(a), where T(NA) is the nematic-smectic-A transition temperature. When the cell is filled with a chiral liquid crystal whose helical pitch is unwound (surface stabilized), application of an in-plane electric field for T(NA)< T < T(a) induces a nonzero polar tilt theta proportional to E of the liquid crystal director at the surface, where the tilted orientation propagates elastically into the bulk. On heating toward T(a), this surface electroclinic response becomes large, corresponding to the onset of a surface tilt transition at T(a) from theta=0 to nonzero theta.

Rayleigh-Taylor instability for immiscible fluids of arbitrary viscosities: a magnetic levitation investigation and theoretical model.

A magnetic field gradient was used to draw down a low density paramagnetic fluid below a more dense fluid in a Hele-Shaw cell. On turning off the field a Rayleigh-Taylor instability was observed in situ, and the growth of the most unstable wave vector was measured versus time. A theory for the instability that permits different viscosities for two immiscible fluids was developed, and good agreement was found with the experimental results. The technique of magnetic levitation promises to broaden significantly the accessible parameter space of gravitational interfacial instability experiments.

Smectic tilt susceptibility: anharmonic behavior in surface-induced smectic layers above the nematic--smectic-a transition temperature.

Fréedericksz transition measurements were performed on the Merck liquid crystal SCE12R. The results were used to determine the quartic contribution to the free energy associated with molecular tilt relative to the layer normal in the surface-induced smectic layers above the nematic-smectic-A transition temperature T(NA) . Both the quadratic and quartic coefficients are consistent with the scaling relation (T- T(NA))(-3nu) , where nu is the correlation length critical exponent, and their ratio was approximately constant with T . The dielectric constants, the refractive indices, and the bend elastic constant for SCE12R also are reported.

Polar anchoring strength of a tilted nematic: confirmation of the dual easy axis model.

The polar anchoring strength coefficient W and polar pretilt angle theta0 were measured simultaneously for the liquid crystal pentylcyanobiphenyl at a rubbed polyimide alignment layer that is ordinarily used for vertical alignment. It was found that W proportional theta(2)0 over the range 0 degrees < or =theta0 less or similar to 35 degrees . The results provide a confirmation of the dual easy axis model, wherein the liquid crystal director adopts an equilibrium orientation theta0 at the substrate that is determined by competition between a pair of preferred orientation directions.