Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n = 35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj = 6.73 × 10−6). Novel reciprocal case–control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to the deletion conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present

Blind people can actively manipulate virtual objects with a novel tactile device

Abstract Frequently in rehabilitation, visually impaired persons are passive agents of exercises with fixed environmental constraints. In fact, a printed tactile map, i.e. a particular picture with a specific spatial arrangement, can usually not be edited. Interaction with map content, instead, facilitates the learning of spatial skills because it exploits mental imagery, manipulation and strategic planning simultaneously. However, it has rarely been applied to maps, mainly because of technological limitations. This study aims to understand if visually impaired people can autonomously build objects that are completely virtual. Specifically, we investigated if a group of twelve blind persons, with a wide age range, could exploit mental imagery to interact with virtual content and actively manipulate it by means of a haptic device. The device is mouse-shaped and designed to jointly perceive, with one finger only, local tactile height and inclination cues of arbitrary scalar fields. Spatial information can be mentally constructed by integrating local tactile cues, given by the device, with global proprioceptive cues, given by hand and arm motion. The experiment consisted of a bi-manual task, in which one hand explored some basic virtual objects and the other hand acted on a keyboard to change the position of one object in real-time. The goal was to merge basic objects into more complex objects, like a puzzle. The experiment spanned different resolutions of the tactile information. We measured task accuracy, efficiency, usability and execution time. The average accuracy in solving the puzzle was 90.5%. Importantly, accuracy was linearly predicted by efficiency, measured as the number of moves needed to solve the task. Subjective parameters linked to usability and spatial resolutions did not predict accuracy; gender modulated the execution time, with men being faster than women. Overall, we show that building purely virtual tactile objects is possible in absence of vision and that the process is measurable and achievable in partial autonomy. Introducing virtual tactile graphics in rehabilitation protocols could facilitate the stimulation of mental imagery, a basic element for the ability to orient in space. The behavioural variable introduced in the current study can be calculated after each trial and therefore could be used to automatically measure and tailor protocols to specific user needs. In perspective, our experimental setup can inspire remote rehabilitation scenarios for visually impaired people

Robot therapy of the upper limb in stroke patients: preliminary experiences for the principle-based use of this technology

Robotic systems for neuromotor rehabilitation have been a part of clinical practice for more than a decade but the efficacy of this new technology is still debated. One reason for this, in our opinion, is that there is still no consensus on the most important features of these systems, or on the underlying theoretical basis, essential for the rational design of treatment protocols. The aim of this paper, born of our long experience in the study of the neural control of movement and the use of robots for characterizing motor control mechanisms, is to make a small contribution to clarifying this issue. What is needed in the future is a “research pipeline” encompassing experimentally validated models of neural control of movement, models of motor learning, models of functional recovery, and finally principle-based robot therapy control strategies. We believe this is a necessary prerequisite for carrying out well formulated comparisons of different control strategies as well as mixed strategies of robot/human treatment, in the framework of randomised, controlled clinical trial

Kinematic primitives in action similarity judgments : A human-centered computational model

This paper investigates the role that kinematic features play in human action similarity judgments. The results of three experiments with human participants are compared with the computational model that solves the same task. The chosen model has its roots in developmental robotics and performs action classification based on learned kinematic primitives. The comparative experimental results show that both model and human participants can reliably identify whether two actions are the same or not. Specifically, most of the given actions could be similarity judged based on very limited information from a single feature domain (velocity or spatial). Both velocity and spatial features were however necessary to reach a level of human performance on evaluated actions. The experimental results also show that human performance on an action identification task indicated that they clearly relied on kinematic information rather than on action semantics. The results show that both the model and human performance are highly accurate in an action similarity task based on kinematic-level features, which can provide an essential basis for classifying human actions. CC BY 4.0Copyright 2023 Elsevier B.V.Corresponding author: Vipul Nair.This work has been partially carried out at the Machine Learning Genoa (MaLGa) center, Università di Genova (IT). It has been partially supported by AFOSR, grant n. FA8655-20-1-7035, and research collaboration between University of Skövde and Istituto Italiano di Tecnologia, Genoa.</p

Cross-sectional study shows that impaired bone mineral status and metabolism are found in non mosaic triple X syndrome

The effect of a supernumerary X chromosome on bones has not been reported and this study evaluated bone mineral status and metabolism in non-mosaic triple X syndrome.AIM: The effect of a supernumerary X chromosome on bones has not been reported and this study evaluated bone mineral status and metabolism in non-mosaic triple X syndrome. METHODS: This cross-sectional study comprised 19 girls, with a median age of 10.9 years, with nonmosaic triple X syndrome and a control group matched for age and body size. We studied ionised and total calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase levels and urinary deoxypyridinoline concentrations. We also measured the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT) Z-scores. RESULTS: Patients with non-mosaic triple X showed significantly reduced AD-SoS (p&lt;0.005) and BTT Z-scores (p&lt;0.0001) compared to the control group and these results persisted when we divided the sample into prepubertal and pubertal patients (p&lt;0.05). These patients also had significantly reduced ionised calcium (p&lt;0.005) and 25(OH)D levels (p&lt;0.005) and higher phosphate (p&lt;0.0001) and PTH (p&lt;0.0001) levels. CONCLUSION: Subjects with non-mosaic triple X syndrome exhibited a significant impairment in bone mineral status and metabolism similar to other X polisomy, such as Klinefelter syndrome. This suggests the presence of a primary bone deficit and the need for regular and close monitoring of these subjects

Use of SCW4 gene primers in PCR methods for the identification of six medically important Aspergillus species

Aspergillus species are the cause of invasive mold infections in immunocompromised patients: Aspergillus fumigatus, A. flavus and A. terreus account for most cases of invasive aspergillosis (IA). As certain species are associated with higher mortality and vary in their resistance to antifungal therapy, diagnosis requires increasingly rapid molecular methods that enable sensitive detection and species discrimination. We have developed PCR and Multiplex PCR assays for the detection of six medically important Aspergillus spp. species DNA in bronchoalveolar lavage (BAL) specimens from hematology and intensive care unit (ICU) patients at risk of IA, using different species and genus-specific PCR primers, selected within the SCW4 gene, encoding a cell wall glucanase of A. fumigatus, similar to mannoprotein Mp65 of Candida albicans. The genus-specific PCR primers were able to amplify only Aspergillus DNAs but not that belonging to other fungal genera tested. The species-specific PCR primers allowed differentiation of each Aspergillus species by the amplicon length produced. The methods described in this study are rapid (less than 4 h), reproducible, simple and specific and demonstrate potential application in the clinical laboratory

Perioperative Interstitial Fluid Expansion Predicts Major Morbidity Following Pancreatic Surgery: Appraisal by Bioimpedance Vector Analysis

Objective: To evaluate whether perioperative bioimpedance vector analysis (BIVA) predicts the occurrence of surgery-related morbidity. Summary Background Data: BIVA is a reliable tool to assess hydration status and compartimentalized fluid distribution. Methods: The BIVA of patients undergoing resection for pancreatic malignancies was prospectively measured on the day prior to surgery and on postoperative day (POD)1. Postoperative morbidity was scored per the Clavien-Dindo classification (CDC), and the Comprehensive Complication Index (CCI). Results: Out of 249 patients, the overall and major complication rates were 61% and 16.5% respectively. The median CCI was 24 (IQR 0.0\u201324.2), and 24 patients (9.6%) had a complication burden with CCI 6540. At baseline the impedance vectors of severe complicated patients were shorter compared to the vectors of uncomplicated patients only for the female subgroup (P=0.016). The preoperative extracellular water (ECW) was significantly higher in patients who experienced severe morbidity according to the CDC or not [19.4L (17.5\u201322.0) vs. 18.2L (15.6\u201320.6), P=0.009, respectively] and CCI 6540, or not [20.3L (18.5\u201322.7) vs. 18.3L (15.6\u201320.6), P=0.002, respectively]. The hydration index on POD1 was significantly higher in patients who experienced major complications than in uncomplicated patients (P=0.020 and P=0.025 for CDC and CCI, respectively). At a linear regression model, age (\u3b2=0.14, P=0.035), sex female (\u3b2=0.40, P&lt;0.001), BMI (\u3b2=0.30, P&lt;0.001), and malnutrition (\u3b2=0.14, P=0.037) were independent predictors of postoperative ECW. Conclusion: The amount of extracellular fluid accumulation predicts major morbidity after pancreatic surgery. Female, obese and malnourished patients were at high risk of extracellular fluid accumulation

Refractive Outcome in Preterm Newborns With ROP After Propranolol Treatment. A Retrospective Observational Cohort Study

Background: Recent explorative studies suggest that propranolol reduces retinopathy of prematurity (ROP) progression, but the short-term effects of propranolol treatment at 1 year of corrected age have not been extensively evaluated. Methods: A multi-center retrospective observational cohort study was conducted to assess the physical development and the refractive outcome of infants with prior ROP treated with propranolol. Forty-nine infants treated with propranolol were compared with an equal number of patients who did not receive any propranolol therapy and represent the control group, with comparable anthropometrical characteristics and stages of ROP. Results: The weight, length, and head circumference at 1 year of corrected age were similar between infants who had been treated, or not, with propranolol, without any statistically significant differences. Refractive evaluation at 1 year showed spherical equivalent values decreasing with the progression of ROP toward more severe stages of the disease, together with an increasing number of infants with severe myopia. On the contrary, no differences were observed between infants who had been treated with propranolol and those who had not. Conclusion: This study confirms that the progression of ROP induces an increase of refractive errors and suggests that propranolol itself does not affect the refractive outcome. Therefore, if the efficacy of propranolol in counteracting ROP progression is confirmed by further clinical trials, the conclusion will be that propranolol might indirectly improve the visual outcome, reducing the progression of ROP