MicroRNAs distribution in different phenotypes of Aortic Stenosis

Aortic valve stenosis (AVS) represents a cluster of different phenotypes, considering gradient and flow pattern. Circulating micro RNAs may reflect specific pathophysiological processes and could be useful biomarkers to identify disease. We assessed 80 patients (81, 76.7-84 years; 46, 57.5%females) with severe AVS. We performed bio-humoral evaluation (including circulating miRNA-1, 21, 29, 133) and 2D-echocardiography. Patients were classified according to ACC/AHA groups (D1-D3) and flow-gradient classification, considering normal/low flow, (NF/LF) and normal/high gradient, (NG/HG). Patients with reduced ejection fractionwere characterized by higher levels of miRNA1 (p = 0.003) and miRNA 133 (p = 0.03). LF condition was associated with higher levels of miRNA1 (p = 0.02) and miRNA21 (p = 0.02). Levels of miRNA21 were increased in patients with reduced Global longitudinal strain (p = 0.03). LF-HG and LF-LG showed higher levels of miRNA1 expression (p = 0.005). At one-year follow-up miRNA21 and miRNA29 levels resulted significant independent predictors of reverse remodeling and systolic function increase, respectively. Different phenotypes of AVS may express differential levels and types of miRNAs, which may retain a pathophysiological role in pro-hypertrophic and pro-fibrotic processes

Elastic stable intramedullary fixation using epibloc versus crossed kirschner wires fixation for distal forearm fractures in children: A retrospective analysis

Background: Childrens' distal forearm fractures (DFFs) could be treated conservatively with closed reduction and immobilisation, but post-reduction displacements often occur. Displaced DFF should be surgically fixed, to avoid further displacement. Nevertheless, immobilisation after surgery is recommended. Epibloc system (ES), a system of stable elastic nail fixation, is widely used to stabilise adults extra-articular distal radius fractures, with advantages to not requiring post-surgical immobilisation. The present investigation represents a retrospective analysis of paediatric patients with DFF treated with ES applied with a minimal technical variation, to fix both ulna and radius fractures using a unique device. Materials and Methods: A retrospective analysis was performed on 44 children (age 6–11 years) who underwent closed reduction and internal fixation because of DFF (both ulna and radius). Group A (21 patients): ES fixation. Group B (23 patients): K-wires and short arm cast fixation. The primary outcome was the subsistence of reduction monitored through X-rays. The secondary outcome was the measurement of active range of motion (AROM) and the time of recovery. Results: No differences were observed comparing Group A and B in terms of the maintenance of reduction (P > 0.05). Seven days after the implant removal, patients in Group A reached significantly better results compared to patients in Group B in terms of AROM (P < 0.05). No differences were revealed in terms of complications between the two groups. Conclusion: ES applied with a minimal technical variation is safe and effective in treating distal ulna and radius fractures, with minimal requirement of post-surgical rehabilitation

Surgical treatment of carpometacarpal thumb arthritis with trapeziectomy and intra-tendon (FCR) suspension with one-loop APL: comparative cohort study

Abstract Background One of the current choices of treatment for Trapeziometacarpal (TMC) joint arthritis is trapeziectomy with ligament reconstruction and tendon interposition arthroplasty. The Ceruso’s technique consists of complete trapezial excision and abductor pollicis longus (APL) tendon suspension. The APL tendon is tied to the flexor carpi radialis (FCR) tendon with two loops, one around it and one inside, and then used as interposition tissue. The purpose of the present study was to compare two different techniques of a trapeziectomy with ligament reconstruction and tendon interposition arthroplasty using the Abductor Pollicis Longus (APL) tendon, which is only Once Looped Around (OLA) versus Once Looped Inside (OLI) the Flexor Carpi Radialis (FCR) tendon. Methods A single-center, retrospective study (Level of evidence: III) has been conducted on sixty-seven patients older than 55 years (33 OLI, 35 OLA), assessing clinical outcomes for at least 2 years of post-surgery follow-up. The outcomes were to assess and compare surgical outcomes comparing the two groups, in terms of subjective and objective evaluation for both groups at the last follow-up (primary outcome), and at the intermediate follow-ups (three and six months). Complications were also assessed. Results The authors found an improvement in pain, range of motion, and function, with equivalent results for both techniques. No subsidence was observed. FCR tendinitis was significantly reduced with OLI, as well as the need of post-operative physiotherapy. Conclusions The one-loop technique allows for reduced surgical exposure, providing excellent suspension and clinical outcomes. Intra FCR loop should be preferred to improve post-surgical recovery. Level of evidence Level III study. This is a retrospective cohort study (written according to STROBE guidelines)

The Italian Version of the Michigan Hand Outcomes Questionnaire (MHQ): Translation, Cross-Cultural Adaptation and Validation

Background: Patient-reported outcome measures are largely used in clinical practice and scientific community. Michigan hand questionnaire (MHQ) is widely recognized as a standardized reliable instrument for the assessment of any kind of hand disorders.Aim of the study: translation, cross-cultural adaptation and validation of the Italian version of MHQ.Methods: The study was composed by two phases. Phase 1 consisted in translation and cross-cultural adaptation of MHQ, from original language version (English) into Italian, according to the standard procedure of translation and back translation. The final Italian version of MHQ was tested on 136 Italian patients with hand disorders (Phase 2), in addition to Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, Visual analogue scale (VAS) for pain assessment and grip strength, to psychometric properties of the new version, 55 patients repeated the questionnaire after 7 days for test-retest to assess the reproducibility of the questionnaire. All data were subsequently analyzed (descriptive statistics, multitrait analysis, reliability and construct validity assessment).Results: Phase 1 was performed without major problems, thus the final Italian version was approved for Phase 2. The questionnaire was clear and easily understood (missing data 0-2.9%). Multitrait analysis brought very good results for each outcome measure. High reliability (Cronbach's alpha: 0.91-0.99) and very good reproducibility (Intraclass correlation coefficients: 0.83-0.98) were revealed. High to moderate correlation was found between MHQ and DASH, grip strength and VAS.Conclusions: The Italian version of MHQ has demonstrated to be reliable and valid

Three-Dimensional Automated, Machine-Learning-Based Left Heart Chamber Metrics: Associations with Prevalent Vascular Risk Factors and Cardiovascular Diseases

Background. Three-dimensional transthoracic echocardiography (3DE) powered by artificial intelligence provides accurate left chamber quantification in good accordance with cardiac magnetic resonance and has the potential to revolutionize our clinical practice. Aims. To evaluate the association and the independent value of dynamic heart model (DHM)-derived left atrial (LA) and left ventricular (LV) metrics with prevalent vascular risk factors (VRFs) and cardiovascular diseases (CVDs) in a large, unselected population. Materials and Methods. We estimated the association of DHM metrics with VRFs (hypertension, diabetes) and CVDs (atrial fibrillation, stroke, ischemic heart disease, cardiomyopathies, &gt;moderate valvular heart disease/prosthesis), stratified by prevalent disease status: participants without VRFs or CVDs (healthy), with at least one VRFs but without CVDs, and with at least one CVDs. Results. We retrospectively included 1069 subjects (median age 62 [IQR 49&ndash;74]; 50.6% women). When comparing VRFs with the healthy, significant difference in maximum and minimum indexed atrial volume (LAVi max and LAVi min), left atrial ejection fraction (LAEF), left ventricular mass/left ventricular end-diastolic volume ratio, and left ventricular global function index (LVGFI) were recorded (p &lt; 0.05). In the adjusted logistic regression, LAVi min, LAEF, LV ejection fraction, and LVGFI showed the most robust association (OR 3.03 [95% CI 2.48&ndash;3.70], 0.45 [95% CI 0.39&ndash;0.51], 0.28 [95% CI 0.22&ndash;0.35], and 0.22 [95% CI 0.16&ndash;0.28], respectively, with CVDs. Conclusions. The present data suggested that novel 3DE left heart chamber metrics by DHM such as LAEF, LAVi min, and LVGFI can refine our echocardiographic disease discrimination capacity

Ventricular and Atrial Remodeling after Transcatheter Edge-to-Edge Repair: A Pilot Study

The aim of this study was to determine the impact of transcatheter edge-to-edge repair (TEER) on left and right ventricular (LV, RV) and left and right atrial (LA, RA) remodeling according to the mechanism of mitral regurgitation (MR) and history of atrial fibrillation (AF)

CCL8/MCP-2 is a target for mir-146a in HIV-1-infected human microglial cells

MicroRNA-mediated regulation of gene expression appears to be involved in a variety of cellular processes, including development, differentiation, proliferation, and apoptosis. Mir-146a is thought to be involved in the regulation of the innate immune response, and its expression is increased in tissues associated with chronic inflammation. Among the predicted gene targets for mir-146a, the chemokine CCL8/MCP-2 is a ligand for the CCR5 chemokine receptor and a potent inhibitor of CD4/CCR5-mediated HIV-1 entry and replication. In the present study, we have analyzed changes in the expression of mir-146a in primary human fetal microglial cells upon infection with HIV-1 and found increased expression of mir-146a. We further show that CCL8/MCP-2 is a target for mir-146a in HIV-1 infected microglia, as overexpression of mir-146a prevented HIV-induced secretion of MCP-2 chemokine. The clinical relevance of our findings was evaluated in HIV-encephalitis (HIVE) brain samples in which decreased levels of MCP-2 and increased levels of mir-146a were observed, suggesting a role for mir-146a in the maintenance of HIV-mediated chronic inflammation of the brain.—Rom, S., Rom, I., Passiatore, G., Pacifici, M., Radhakrishnan, S., Del Valle, L., Piña-Oviedo, S., Khalili, K., Eletto, D., Peruzzi, F. CCL8/MCP-2 is a target for mir-146a in HIV-1 infected human microglial cells

Thalamic connectivity measured with fMRI is associated with a polygenic index predicting thalamo-prefrontal gene co-expression

The functional connectivity between thalamic medio-dorsal nucleus (MD) and cortical regions, especially the dorsolateral prefrontal cortex (DLPFC), is implicated in attentional processing and is anomalous in schizophrenia, a brain disease associated with polygenic risk and attentional deficits. However, the molecular and genetic underpinnings of thalamic connectivity anomalies are unclear. Given that gene co-expression across brain areas promotes synchronous interregional activity, our aim was to investigate whether coordinated expression of genes relevant to schizophrenia in MD and DLPFC may reflect thalamic connectivity anomalies in an attention-related network including the DLPFC. With this aim, we identified in datasets of post-mortem prefrontal mRNA expression from healthy controls a gene module with robust overrepresentation of genes with coordinated MD-DLPFC expression and enriched for schizophrenia genes according to the largest genome-wide association study to date. To link this gene cluster with imaging phenotypes, we computed a Polygenic Co-Expression Index (PCI) combining single-nucleotide polymorphisms predicting module co-expression. Finally, we investigated the association between PCI and thalamic functional connectivity during attention through fMRI Independent Component Analysis in 265 healthy participants. We found that PCI was positively associated with connectivity strength of a thalamic region overlapping with the MD within an attention brain circuit. These findings identify a novel association between schizophrenia-related genes and thalamic functional connectivity. Furthermore, they highlight the association between gene expression co-regulation and brain connectivity, such that genes with coordinated MD-DLPFC expression are associated with coordinated activity between the same brain regions. We suggest that gene co-expression is a plausible mechanism underlying biological phenotypes of schizophrenia

The interaction between cannabis use and a CB1-related polygenic co-expression index modulates dorsolateral prefrontal activity during working memory processing

Convergent findings indicate that cannabis use and variation in the cannabinoid CB1 receptor coding gene (CNR1) modulate prefrontal function during working memory (WM). Other results also suggest that cannabis modifies the physiological relationship between genetically induced expression of CNR1 and prefrontal WM processing. However, it is possible that cannabis exerts its modifying effect on prefrontal physiology by interacting with complex molecular ensembles co-regulated with CB1. Since co-regulated genes are likely co-expressed, we investigated how genetically predicted co-expression of a molecular network including CNR1 interacts with cannabis use in modulating WM processing in humans. Using post-mortem human prefrontal data, we first computed a polygenic score (CNR1-PCI), combining the effects of single nucleotide polymorphisms (SNPs) on co-expression of a cohesive gene set including CNR1, and positively correlated with such co-expression. Then, in an in vivo study, we computed CNR1-PCI in 88 cannabis users and 147 non-users and investigated its interaction with cannabis use on brain activity during WM. Results revealed an interaction between cannabis use and CNR1-PCI in the dorsolateral prefrontal cortex (DLPFC), with a positive relationship between CNR1-PCI and DLPFC activity in cannabis users and a negative relationship in non-users. Furthermore, DLPFC activity in cannabis users was positively correlated with the frequency of cannabis use. Taken together, our results suggest that co-expression of a CNR1-related network predicts WM-related prefrontal activation as a function of cannabis use. Furthermore, they offer novel insights into the biological mechanisms associated with the use of cannabis