Retinal Vessel Functionality Is Linked With ARMS2 A69S and CFH Y402H Polymorphisms and Choroidal Status in AMD Patients

PurposeWe aimed to investigate the reactivity of retinal vessels to a flickering stimulus in patients with age-related macular degeneration (AMD) and healthy participants. We also assessed whether the parameters of retinal vessels are dependent on genetic predisposition.MethodsA total of 354 patients with AMD and 121 controls were recruited for the study. All participants underwent thorough ophthalmologic examination and static and dynamic retinal vessel analysis. AMD risk polymorphisms were genotyped in the CFH and ARMS2 genes.ResultsWe found no differences between the AMD group and controls in central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriovenous ratio (AVR), dynamic analysis of arteries (DAAs), or dynamic analysis of veins (DAVs). Eyes with early AMD presented with significantly higher AVR values than eyes with late AMD. In the AMD group, DAA correlated positively with both choroidal thickness (Rs = 0.14, P = 0.00096) and choroidal volume (Rs = 0.23, P < 0.0001), and no such associations were observed in the controls. We found significantly lower DAA (1.47 ± 1.50) in TT homozygotes for the ARMS2 A69S polymorphism in comparison with GG homozygotes (2.38 ± 1.79) and patients with GG + GT genotypes (2.28 ± 1.84). We also observed less prominent DAV (3.24 ± 1.71) in patients with TC + CC genotypes in the CFH Y402H polymorphism compared with TT homozygotes (3.83 ± 1.68).ConclusionsOur findings suggest that retinal microcirculation appears to be associated with the genetic background, choroidal parameters, and clinical features of the patients with AMD.     

Lanthanide complexes based on a new bis-chelating carbacylamidophosphate (CAPh) scorpionate-like ligand

The novel bis-chelating carbacylamidophosphate type ligand, tetramethyl[pyridine-2,6-diyldi(iminocarbonyl)]diamidophosphate (H₂L), and its sodium salt, NaHL, have been synthesized and their structural properties have been investigated. Coordination compounds of lanthanides [Ln(HL)₂NO₃]·i-PrOH (Ln = Eu³⁺, Tb³⁺) were obtained for the first time, isolated in the individual state and characterized by means of IR and NMR spectroscopies, electrospray ionization mass spectrometry (ESI-MS), potentiometric titration, and elemental, thermal gravimetric and X-ray diffraction analyses. It was shown that H₂L behaves like a scorpionate type ligand and in a mono-deprotonated form coordinates in a tridentate manner via the oxygen atoms of phosphoryl and carbonyl groups with formation of a mononuclear metal complex. The protonation constants of H₂L and stability constants of Eu³⁺ and Tb³⁺ complexes have been determined. According to the results of X-ray diffraction analysis the H₂L and [Ln(HL)₂NO₃]·i-PrOH molecules have monomeric structure but NaHL is a dimer. The Hirshfeld surface and fingerprint plots of the compounds have been used to analyze various hydrogen bonds and intermolecular interactions displayed in the crystal structure.

A new bis-chelating scorpionate type CAPh ligand and its lanthanide complexes in solid state and solution.     

Rett syndrome: an eye‐tracking study of attention and recognition memory

Aim

The aim of this study was to examine attention and recognition memory for faces and patterns in Rett syndrome, a severely disabling neurodevelopmental disorder caused by mutations in the X‐linked MECP2 gene.

Method

Because Rett syndrome impairs speech and hand use, precluding most neuropsychological testing, the visual paired‐comparison paradigm (VPC) was used, together with eye tracking. In the VPC, two identical stimuli are presented for familiarization. On test, the familiar stimulus and a new one are paired, and recognition inferred from preferential looking to the novel target. Attention is measured by looking time, gaze dispersion, and number/length of fixations. Twenty‐seven female patients with Rett syndrome (mean age 10y 6mo; SD 6y 8mo, age range 2–22y) from the Rett clinic at a children's hospital were assessed in this study, along with 30 age‐ and sex‐matched typically developing participants (outpatients from the same hospital).

Results

Although patients with Rett syndrome showed recognition of both faces and patterns, with novelty scores greater than chance (50%), their performance was significantly poorer than that of the typically developing comparison group. Their attention to both was less mature and marked by a more narrowly focused gaze, with fewer and longer fixations. When inspecting faces, attention to the eyes was similar in both groups; however, patients with Rett syndrome tended to ignore the nose and mouth.

Interpretation

This is one of the first studies to characterize attention and memory in individuals with Rett syndrome. Visually based techniques, such as the VPC, open a new avenue for quantifying the cognitive phenotype associated with this syndrome.     

A common polymorphism in the brain-derived neurotrophic factor gene in patients with adult-onset primary focal and segmental dystonia

Brain-derived neurotrophic factor (BDNF) modulates neuroplasticity. A functional polymorphism [Val66Met (G196A)] in BDNF has been reported to modify cortical plasticity in humans. Physiologic investigations have revealed that dystonia might be a consequence of the pathologic plasticity of the sensorimotor cortex. We aimed to investigate the role of the Val66Met polymorphism in a cohort of Serbian patients with adult-onset primary focal and segmental dystonia (PTD). One hundred and forty-nine patients with primary adult-onset PTD, 194 patients with Parkinson’s disease (PD), and 366 healthy control subjects were recruited for the study. Patients with PTD and PD, as well as healthy controls had a similar distribution of genotypes and allele frequencies. There was no any significant difference in the allelic distribution at the Val66Met SNP of the BDNF gene among patients with adult-onset PTD, PD, and healthy volunteers from the same geographic areas. In addition, the presence of the Met allele did not influence the clinical characteristics of PTD patients. Patients with the Met variant did not differ by age at onset, number of affected regions, and efficacy of a sensory trick. Met66Met is not associated with an increased risk of dystonia.     

Validation and cross-cultural adaptation of the Self-Assessment Disability Scale in patients with Parkinson’s disease in Serbia

The symptoms of Parkinson’s disease (PD) worsen over time affecting performance and causing disability. The purpose of this study was to translate the Self-Assessment Disability Scale in patients with Parkinson's disease (SADS-PD) into the Serbian language and assess its validity and reliability. From January to July 2012, 114 consecutive PD patients were recruited at the Neurology Clinic in Belgrade. The inclusion criteria were: ability to walk independently for at least 10 m, ability to stand for at least 90 s. The exclusion criteria were: cognitive impairment, the presence of other major neurologic, psychiatric, visual, audio-vestibular, and orthopedic disturbances. The 25-item SADS-PD was translated according to internationally-accepted methodology. The internal consistency of the scale was evaluated using Cronbach’s alpha coefficient. Test–retest reliability was evaluated using Kendall’s concordance coefficient for total scores. To evaluate construct validity, an exploratory factor analysis (principal component analysis, varimax rotation) was performed. Cronbach’s alpha coefficient was 0.984. Kendall’s concordance coefficient was 0.994. Duration of the disease, Hoehn & Yahr (H&Y) stage, Unified Parkinson’s Disease Rating Scale (UPDRS) motor score, history of falls, Hamilton’s Depression and Anxiety Rating Scales (HDRS and HARS) scores were significantly correlated with the total SADS-PD score. On factor analysis 25 items in the SADS-PD questionnaire were separated in two clusters with total matrix variance of 79.7 %. The psychometric properties of the cross-culturally adapted SADS-PD questionnaire (Serbian version) have outstanding validity and reliability as an instrument for evaluation of the extent of disability in patients with PD.     

Mechanisms of Pediatric Cerebral Arteriopathy: An Inflammatory Debate

Arteriopathy is the leading cause of childhood arterial ischemic stroke, but its mechanisms are poorly understood. This review explores the possible role of inflammatory mechanisms and evidence for inflammatory pathophysiology in specific pediatric cerebral arteriopathies. Pathologically proven small-vessel central nervous system vasculitis provides a definitive inflammatory model where available treatments are likely improving outcomes. In contrast, a common large-vessel arteriopathy presents many features suggestive of inflammation, but definitive proof remains elusive. Recent advances and future research directions, including biomarker, neuroimaging, and pathologic approaches and how they might address these important clinical questions, are discussed.     

Pharmacoepigenetics: an element of personalized therapy?

Introduction: Epigenetics is a rapidly growing field describing heritable alterations in gene expression that do not involve DNA sequence variations. Advances in epigenetics and epigenomics have influenced pharmacology, leading to the development of a new specialty, pharmacoepigenetics, the study of the epigenetic basis for the individual variation in drug response.

Areas covered: We present an overview of the major epigenetic mechanisms and their effects on the expression of drug metabolizing enzymes and drug transporters, as well as the epigenetic status of drug protein targets affecting therapy response. Recent advances in the development of pharmacoepigenetic biomarkers and epidrugs are also discussed.

Expert opinion: There is growing evidence that pharmacoepigenetics has the potential to become an important element of personalized medicine. Epigenetic modifications influence drug response, but they can also be modulated by drugs. Moreover, they can be monitored not only in the affected tissue, but also in body fluids. Nevertheless, there are very few examples of epigenetic biomarkers implemented in the clinical setting. Explanation of the interplay between genomic and epigenomic changes will contribute to the personalized medicine approach. Ultimately, both genetic biomarkers and epigenetic mechanisms should be taken into consideration in predicting drug response in the course of successful personalized therapy.