Macular Choroidal Thickness: Evaluation of Variability among Measurements and Assessment of Predictive Value of Glaucomatous Visual Field Damag

Introduction: This study aimed to investigate the relationship between the choroidal circulation and glaucoma, assessing macular choroidal thickness (MCT) as a predictive value of glaucomatous visual field damage. Methods: Twenty primary open-angle glaucoma patients were recruited. Patients underwent 2 SS-OCT scans: one with DRI OCT (Topcon) and the other with PLEX Elite 9000 (Zeiss). Standard OCT parameters were acquired by DRI OCT, while MCT was manually measured in 5 points on Plex ELITE 9000 images. The relationship among MCT, standard OCT parameters, and visual field indices was evaluated. Pearson''s r correlation was calculated to evaluate these relationships. Reproducibility of measurements was analyzed. Results: MCT measurements showed a good intra- and interobserver repeatability. A negative correlation appeared between MCT and BMI (r = -0.518, p = 0.023). Mean deviation showed a statistically significant correlation with MCT measured at subfoveal and at 1, 000 µm nasally (r = 0.50, p = 0.03, and r = 0.52, p = 0.023). A correlation was found between the 2 MCT (Zeiss vs. Topcon) measurements and between MCT and peripapillary choroidal thickness (r = 0.944 and r = 0.740, p < 0.001, respectively). Conclusions: A good intra- and interobserver reproducibility was found. MCT showed a weak predictive value of glaucomatous visual field damage. A significant correlation was found between MCT and BMI. © 202

Route knowledge and configural knowledge in typical and atypical development: a comparison of sparse and rich environments

Background: Individuals with Down syndrome (DS) and individuals with Williams syndrome (WS) have poor navigation skills, which impact their potential to become independent. Two aspects of navigation were investigated in these groups, using virtual environments (VE): route knowledge (the ability to learn the way from A to B by following a fixed sequence of turns) and configural knowledge (knowledge of the spatial relationships between places within an environment). Methods: Typically developing (TD) children aged 5 to 11 years (N = 93), individuals with DS (N = 29) and individuals with WS (N = 20) were presented with a sparse and a rich VE grid maze. Within each maze, participants were asked to learn a route from A to B and a route from A to C before being asked to find a novel shortcut from B to C. Results: Performance was broadly similar across sparse and rich mazes. The majority of participants were able to learn novel routes, with poorest performance in the DS group, but the ability to find a shortcut, our measure of configural knowledge, was limited for all three groups. That is, 59 % TD participants successfully found a shortcut, compared to 10 % participants with DS and 35 % participants with WS. Differences in the underlying mechanisms associated with route knowledge and configural knowledge and in the developmental trajectories of performance across groups were observed. Only the TD participants walked a shorter distance in the last shortcut trial compared to the first, indicative of increased configural knowledge across trials. The DS group often used an alternative strategy to get from B to C, summing the two taught routes together. Conclusions: Our findings demonstrate impaired configural knowledge in DS and in WS, with the strongest deficit in DS. This suggests that these groups rely on a rigid route knowledge based method for navigating and as a result are likely to get lost easily. Route knowledge was also impaired in both DS and WS groups and was related to different underlying processes across all three groups. These are discussed with reference to limitations in attention and/or visuo-spatial processing in the atypical groups

A homozygous MED11 C-terminal variant causes a lethal neurodegenerative disease

Purpose: The mediator (MED) multisubunit-complex modulates the activity of the transcriptional machinery, and genetic defects in different MED subunits (17, 20, 27) have been implicated in neurologic diseases. In this study, we identified a recurrent homozygous variant in MED11 (c.325C>T; p.Arg109Ter) in 7 affected individuals from 5 unrelated families. Methods: To investigate the genetic cause of the disease, exome or genome sequencing were performed in 5 unrelated families identified via different research networks and Matchmaker Exchange. Deep clinical and brain imaging evaluations were performed by clinical pediatric neurologists and neuroradiologists. The functional effect of the candidate variant on both MED11 RNA and protein was assessed using reverse transcriptase polymerase chain reaction and western blotting using fibroblast cell lines derived from 1 affected individual and controls and through computational approaches. Knockouts in zebrafish were generated using clustered regularly interspaced short palindromic repeats/Cas9. Results: The disease was characterized by microcephaly, profound neurodevelopmental impairment, exaggerated startle response, myoclonic seizures, progressive widespread neurodegeneration, and premature death. Functional studies on patient-derived fibroblasts did not show a loss of protein function but rather disruption of the C-terminal of MED11, likely impairing binding to other MED subunits. A zebrafish knockout model recapitulates key clinical phenotypes. Conclusion: Loss of the C-terminal of MED subunit 11 may affect its binding efficiency to other MED subunits, thus implicating the MED-complex stability in brain development and neurodegeneration

Conservation of leathercraft and related objects tensioning gilded and painted leather

Edinburgh (UK

CTLA-4 is not restricted to the lymphoid cell lineage and can function as a target molecule for apoptosis induction of leukemic cells.

none17noThe expression of cytotoxic T-lymphocyte antigen-4 (CTLA-4) molecule in human normal and neoplastic hematopoietic cells, both on the cell membrane and in the intracellular compartment, was evaluated. Flow cytometric analysis carried out with a panel of anti-CTLA-4 human single-chain fragment of variable domain (scFv) antibodies revealed that CTLA-4 was not expressed on the surface, whereas it was highly expressed within the cytoplasm, in freshly isolated peripheral blood mononuclear cells (PBMCs), T cells, B cells, CD34+ stem cells, and granulocytes. Various treatments with agents able to specifically activate each cell type induced CTLA-4 expression on the surface of these cells. Similarly, increased CTLA-4 expression Was observed in different hematopoietic cell lines although they also expressed surface CTLA-4, at different degrees of intensity, before activation. Surprisingly, CTLA-4 RNA transcripts were detectable in such cell lines only after nested polymerase chain reaction (PCR) specific for CTLA-4 extracellular domain, suggesting a very fast CTLA-4 RNA processing accompanied by prolonged CTLA-4 protein accumulation. We further demonstrated surface expression of CTLA-4 in a variety of acute and chronic myeloid leukemias (AMLs and CMLs) and B- and T-lymphoid leukemias, either adult or pediatric. CTLA-4 was expressed in 25% to 85% of AMLs and CMLs depending on the leukemia subtype and the epitope analyzed, whereas in acute B-and T-leukemias CTLA-4 expression was mainly cytoplasmic. Chronic B leukemias appeared to express CTLA-4, both on the surface and in cytoplasm, whereas few cases tested of chronic T leukemias were negative. Two anti-CTLA-4 immunotoxins (scFvs-saporin) induced in vitro apoptosis of neoplastic cells from a representative AML, suggesting a novel immunotherapeutic approach to AM L based on CTLA-4 targeting. © 2003 by The American Society of Hematology.mixedPistillo M.P.; Tazzari P.L.; Palmisano G.L.; Pierri I.; Bolognesi A.; Ferlito F.; Capanni P.; Polito L.; Ratta M.; Pileri S.; Piccioli M.; Basso G.; Rissotto L.; Conte R.; Gobbi M.; Stirpe F.; Ferrara G.B.Pistillo M.P.; Tazzari P.L.; Palmisano G.L.; Pierri I.; Bolognesi A.; Ferlito F.; Capanni P.; Polito L.; Ratta M.; Pileri S.; Piccioli M.; Basso G.; Rissotto L.; Conte R.; Gobbi M.; Stirpe F.; Ferrara G.B

A normative study of the Italian printed word version of the free and cued selective reminding test

According to the new research criteria for the diagnosis of Alzheimer's disease, episodic memory impairment, not significantly improved by cueing, is the core neuropsychological marker, even at a pre-dementia stage. The FCSRT assesses verbal learning and memory using semantic cues and is widely used in Europe. Standardization values for the Italian population are available for the colored picture version, but not for the 16-item printed word version. In this study, we present age- and education-adjusted normative data for FCSRT-16 obtained using linear regression techniques and generalized linear model, and critical values for classifying sub-test performance into equivalent scores. Six scores were derived from the performance of 194 normal subjects (MMSE score, range 27-30, mean 29.5\ua0\ub1\ua00.5) divided per decade (from 20 to 90), per gender and per level of education (4 levels: 3-5, 6-8, 9-13,\ua0>13\ua0years): immediate free recall (IFR), immediate total recall (ITR), recognition phase (RP), delayed free recall (DFR), delayed total recall (DTR), Index of Sensitivity of Cueing (ISC), number of intrusions. This study confirms the effect of age and education, but not of gender on immediate and delayed free and cued recall. The Italian version of the FCSRT-16 can be useful for both clinical and research purposes