Mutations in protein N-arginine methyltransferases are not the cause of FTLD-FUS

The nuclear protein fused in sarcoma (FUS) is found in cytoplasmic inclusions in a subset of patients with the neurodegenerative disorder frontotemporal lobar degeneration (FTLD-FUS). FUS contains a methylated arginine–glycine–glycine domain that is required for transport into the nucleus. Recent findings have shown that this domain is hypomethylated in patients with FTLD-FUS. To determine whether the cause of hypomethylation is the result of mutations in protein N-arginine methyltransferases (PRMTs), we selected 3 candidate genes (PRMT1, PRMT3, and PRMT8) and performed complete sequencing analysis and real-time polymerase chain reaction mRNA expression analysis in 20 FTLD-FUS cases. No mutations or statistically significant changes in expression were observed in our patient samples, suggesting that defects in PRMTs are not the cause of FTLD-FUS.     

Beyond physiotherapy and pharmacological treatment for fibromyalgia syndrome: tailored tACS as a new therapeutic tool

European Archives of Psychiatry and Clinical Neuroscience - Fibromyalgia syndrome (FMS) is a complex pain disorder, characterized by diffuse pain and cognitive disturbances. Abnormal cortical...     

Influence of a metaphylactic treatment with Baycox® Bovis on the reproductive performances of Fresian heifers: a preliminary study

A blind, randomised, controlled, multicentric field trial was conducted to assess the influence of a metaphylactic treatment with an oral solution of toltrazuril on some reproductive parameters of Italian Fresian heifers during the first 18–20 months of life. For this goal 40 calves were selected from two dairy farms and randomly divided into two homogeneous groups: MTol, treated with toltrazuril and NegC, left untreated. The calves were clinically and coprologically examined over the entire study period. The body condition scores, the body weights and the age at the first service were recorded and compared between the two groups, in addition to some other reproductive parameters including number of pregnancies, average service per pregnancy, conception rate, conception rate at first service and post first service conception rate. The analysis of the results showed that the metaphylactic treatment with toltrazuril influenced positively the average age of the first service (MTol 461.4 days versus NegC 485.45 days), the overall conception rate (MTol 95 % versus NegC 85 %), the success at first (MTol 60 % versus NegC 45 %) and second (MTol 75 % versus NegC 45 %) services and, consequently, the mean number of services to be carried out for each animal (MTol 1.4?±?0.6 versus NegC 1.6?±?0.79). Furthermore, the results confirmed that toltrazuril treatment, applied in accordance with the epidemiological aspects of each farm, is highly efficacious in persistent reduction of oocyst excretions with particular reference to Eimeria zuernii, Eimeria bovis, considered to be mainly responsible for clinical coccidiosis.     

A role for TASK2 channels in the human immunological synapse

The immunological synapse is a transient junction that occurs when the plasma membrane of a T cell comes in close contact with an APC after recognizing a peptide from the antigen-MHC. The interaction starts when CRAC channels embedded in the T cell membrane open, flowing calcium ions into the cell. To counterbalance the ion influx and subsequent depolarization, K_v1.3 and KCa3.1 channels are recruited to the immunological synapse, increasing the extracellular K⁺ concentration. These processes are crucial as they initiate gene expression that drives T cell activation and proliferation. The T cell-specific function of the K_2P channel family member TASK2 channels and their role in autoimmune processes remains unclear. Using mass spectrometry analysis together with epifluorescence and super-resolution single-molecule localization microscopy, we identified TASK2 channels as novel players recruited to the immunological synapse upon stimulation. TASK2 localizes at the immunological synapse, upon stimulation with CD3 antibodies, likely interacting with these molecules. Our findings suggest that, together with K_v1.3 and KCa3.1 channels, TASK2 channels contribute to the proper functioning of the immunological synapse, and represent an interesting treatment target for T cell-mediated autoimmune disorders.     

Joint action as a practice of memory transmission in a poor urban neighborhood of Santiago,Chile

In Latin America, one of the key tasks of Community and Liberation Psychology has been to recover the memories of marginalized and excluded communities that have experienced multiple pasts marked by political violence. In Chile, researchers have focused on poor urban neighborhoods, where the question of how memories are transmitted in areas where conflicts and violence are still present has been overlooked. In this context, the following article aims to analyze the ways in which memories are transmitted in a neighborhood that has a long organizational history in the struggle against social inequalities; while at the same time being classified as a critical area by the state due to its current levels of violence and social conflict. The researchers led a 3‐year case study from an ethnographic perspective, and applied a collaborative methodology that brought together the research team and the members of a territorial organization. The analysis is based on 72 interviews, 5 conversation groups and ethnographic observation. The data was analyzed using discourse analysis. The results revealed that the main form of memory transmission is not based on intergenerational narratives of the past, but rather on joint action; namely, dialogical practices among neighborhood residents that generate an ethos; a common way of life.     

Alternative Approach to Varicella Zoster Virus Prevention in a Child with Lymphopenia

Journal of Clinical Immunology -     

White matter alteration and cerebellar atrophy are hallmarks of brain MRI in alpha-mannosidosis

ObjectiveDespite profound neurological symptomatology there are only few MRI studies focused on the brain abnormalities in alpha-mannosidosis (AM). Our aim was to characterize brain MRI findings in a large cohort of AM patients along with clinical manifestations.MethodsTwenty-two brain MRIs acquired in 13 untreated AM patients (8 M/5F; median age 17 years) were independently assessed by three experienced readers and compared to 16 controls.ResultsFocal and/or diffuse hyperintense signals in the cerebral white matter were present in most (85%) patients. Cerebellar atrophy was common (62%), present from the age of 5 years. Progression was observed in two out of 6 patients with follow-up scans. Cortical atrophy (62%) and corpus callosum thinning (23%) were already present in a 13-month-old child. The presence of low T₂ signal intensity in basal ganglia and thalami was excluded by the normalized signal intensity profiling. The enlargement of perivascular spaces in white matter (38%), widening of perioptic CSF spaces (62%), and enlargement of cisterna magna (85%) were also observed. Diploic space thickening (100%), mucosal thickening (69%) and sinus hypoplasia (54%) were the most frequent non-CNS abnormalities.ConclusionWhite matter changes and cerebellar atrophy are proposed to be the characteristic brain MRI features of AM. The previously reported decreased T₂ signal intensity in basal ganglia and thalami was not detected in this quantitative study. Rather, this relative MR appearance seems to be related to the diffuse high T₂ signal in the adjacent white matter and not the gray matter iron deposition that has been hypothesized.     

Impact of sex differences on outcomes in patients with non-valvular atrial fibrillation undergoing left atrial appendage closure: A single-center experience

Female patients affected by non-valvular atrial fibrillation (NVAF) have a higher risk of stroke compared with male patients. Left atrial appendage (LAA) closure has been demonstrated as a reasonable alternative to warfarin therapy for stroke prevention in patients with NVAF. However, the impact of sex-related differences on outcomes in patients undergoing LAA closure (LAAC) remains unclear. Our study investigated the differences in LAAC efficacy and safety endpoints between sexes. 387 consecutive patients undergoing WATCHMAN device implantation were enrolled and stratified by sex. Baseline clinical characteristics, procedural data, severe peri-procedural complications and long-term outcomes were compared between men and women. Measurements of LAA width and depth, device implantation success rate, and the frequency of severe peri-procedural complications were comparable between the two groups. After an average follow-up length of two years post LAAC, no significant differences were observed in the risks for composite thromboembolic events (P = 0.096), major bleeding (P = 0.129), and combined primary (co-primary) efficacy events (P = 0.231) between sexes, but the risk of all-cause death decreased significantly in women compared with men (P = 0.045). After performing propensity matching adjustment for residual confounders, the sex-related differences in the cumulative ratio of freedom from all-cause death did not reach statistical significance (P = 0.062), as was also observed with the cumulative ratio of freedom from composite thromboembolic events (P = 0.104), major bleeding (P = 0.134), and co-primary efficacy events (P = 0.241). The observed annual rate of thromboembolic events was significantly decreased by 67.1% (P < 0.01) and 52.5% (P < 0.05) and the observed annual rate of bleeding was reduced by 33.6% (P < 0.05) and 43.5% (P < 0.05) in men and women when compared with the predicted risk based on CHA₂DS₂VASc score and HAS-BLED score, respectively. LAAC can be considered as an effective and safe strategy in preventing thromboembolic events and decreasing bleeding risks in NVAF patients, regardless of sex. LAAC appears to normalize the sex-specific differences in NVAF patients both in terms of safety and efficacy.