The contribution of HERV-E clone 4-1 and other HERV-E members to the pathogenesis of rheumatic autoimmune diseases

Human endogenous retroviruses (HERV)-E consist of a family of more than 1300 elements, stably integrated in the human genome. Some of them are full-length proviruses able to synthesize the viral proteins gag, pol and env. The reactivation of HERV-E elements has been associated to placentation, cancer and autoimmunity. In this narrative review, we aimed to report the status of the art concerning the involvement of HERV-E in rheumatic autoimmune diseases. Following a research on PubMed database, a total of 87 articles were selected. The highest amount of evidence derives from studies on systemic lupus erythematosus (SLE), whereas a few to no data are available on other immune-mediated diseases. In SLE, the hyper-expression of HERV-E clone 4-1 in peripheral blood mononuclear cells or differentiated lymphocytes has been associated with disease activity and autoantibody production. It is likely that HERV-E take part to the pathogenesis of rheumatic autoimmune diseases but additional research is needed.     

Totally robotic soave pull-through procedure for Hirschsprung’s disease: lessons learned from 11 consecutive pediatric patients

Pediatric Surgery International - Since Hirschsprung’s disease (HSCR) already proved to benefit from robotic surgery, we aimed at describing a wider series of patients with this rare disease...     

Validation of the Italian version of the Kagan scales for people with aphasia and their conversation partners

Background: The importance of conversation partners (CPs) for persons with aphasia (PwA) was recently highlighted. Trained CPs are shown to increase communicative access and improve quality of life. The Kagan scales, i.e., “Measure of skills in Supported Conversation” and “Measure of Participation in Conversation” (the MSC-MPC scales), between PwA and their CPs were designed to assess the communication dyad. The MSC-MPC scales were translated and adapted to Italian in 2015.

Aim: To validate the Italian version of the MSC-MPC scales (I-MSC/MPC) by assessing intra- and inter-rater reliability and concurrent validity.

Methods & Procedures: Thirty-two couples formed by 16 PwA and two CPs (one trained and one untrained) for each PwA were enrolled in the study. Aphasia severity was staged by the Therapy Outcome Measures “Dysphasia” impairment scale. Functional communication and pragmatic abilities were assessed with the I-ASHA-FACS and the Pragmatic Protocol, respectively. The PwA were videotaped while communicating both with trained and untrained CPs. All videotapes were assessed using the I-MSC/MPC scales by one expert speech and language therapist and two trainee speech and language therapists. The Intraclass Correlation Coefficient (ICC) was used to calculate inter- and intra-rater reliability. Correlations between the I-MSC/MPC scales and the aphasia severity, the I-ASHA-FACS, and the Pragmatic Protocol results were calculated by the Spearman’s test. The Mann-Whitney test was used to separate the I-MSC/MPC results obtained by the trained CPs from the untrained CPs.

Outcomes & Results: Inter-rater and intra-rater reliability ICC results were highly significant and strong (ICC > .906, ICC > .978, p < .001, respectively). Significant correlations between the aphasia severity and the I-MSC/MPC scales ranged from moderate to strong (Spearman rho>.487, p < .005). Correlations between the I-MSC and the I-ASHA-FACS domains ranged from moderate to strong (rho >.458, p < .008). Correlation between the I-MPC and the I-ASHA-FACS domains were generally strong (rho > .569, p < .001) while correlations between the I-MSC and the I-ASHA-FACS domains ranged from moderate to strong (rho > .458, p = .008). Pragmatic aspects were shown to be mostly preserved in the PwA. All correlations between the I-MSC/MPC scales and the Pragmatic Protocol were strong (rho >.635, p < .008). The Mann-Whitney test showed significant results for the I-MSC scale (p < .026).

Conclusions: The I-MSC-MPC scales proved to be a valid and reliable instrument to assess the communicative dyad. The I-MSC scale was also used to distinguish trained from untrained CPs. The use of I-MSC-MPC scales is recommended in clinical practice.     

Anatomical and behavioral impact of a lentiviral tool tapping onto hippocampal serotonin reuptake in rats

We aimed at the further characterization of rats in which SERT gene silencing was achieved by hippocampal injection of a lentiviral vector, carrying three si-RNA to block SERT mRNA at 66% of normal levels. Improved self-control and reduced restlessness were already demonstrated in these rats. Present further studies consisted of male adult rats, bilaterally inoculated within the hippocampus; control rats received lentivirus particles inactivated with heat. Both groups were maintained in isolation for 5 months, starting from inoculation. Neurochemical changes were studied by proton magnetic resonance spectroscopy (1H-MRS): we found increased hippocampal viability and bioenergetic potential; however, rats showed a behaviorally depressive pattern, also characterized by enhanced affiliation. Based on the extent of such effects, the whole lenti-SERT group was divided into two subgroups, termed intermediate- and extreme- phenotype profiles. While all rats had a widespread modification within dorsal/ventral striatum, amygdala, and hypothalamus, only the former subgroup showed an involvement of Raphé medialis, while, for the latter subgroup, an increase of SERT within hippocampus was unexpectedly caused. Within the less-affected “intermediate” rats, hippocampal 5-HT7 receptors were down-modulated, and also similarly within substantia nigra, septum, and neocortex. This picture demonstrates that additional rather than fewer neurobiological changes accompany a lower phenotypic expression. Overall, tapping hippocampal SERT affected the balance between habits versus strategies of coping by promoting morphogenetic processes indicative of a serotonergic fiber plasticity. Supplementary studies about serotonergic dynamics and neurogenesis within fronto-striatal circuits are needed.     

Neural coding of action in three dimensions: Task- and time-invariant reference frames for visuospatial and motor-related activity in parietal area V6A

Goal-directed movements involve a series of neural computations that compare the sensory representations of goal location and effector position, and transform these into motor commands. Neurons in posterior parietal cortex (PPC) control several effectors (e.g., eye, hand, foot) and encode goal location in a variety of spatial coordinate systems, including those anchored to gaze direction, and to the positions of the head, shoulder, or hand. However, there is little evidence on whether reference frames depend also on the effector and/or type of motor response. We addressed this issue in macaque PPC area V6A, where previous reports using a fixate-to-reach in depth task, from different starting arm positions, indicated that most units use mixed body/hand-centered coordinates. Here, we applied singular value decomposition and gradient analyses to characterize the reference frames in V6A while the animals, instead of arm reaching, performed a nonspatial motor response (hand lift). We found that most neurons used mixed body/hand coordinates, instead of “pure” body-, or hand-centered coordinates. During the task progress the effect of hand position on activity became stronger compared to target location. Activity consistent with body-centered coding was present only in a subset of neurons active early in the task. Applying the same analyses to a population of V6A neurons recorded during the fixate-to-reach task yielded similar results. These findings suggest that V6A neurons use consistent reference frames between spatial and nonspatial motor responses, a functional property that may allow the integration of spatial awareness and movement control.