Modulation of memory formation following violations of conditioned expectations

Increment in attention to the conditioned stimulus (CS) leads to an increased rate of acquisition of new associations involving CS. While the neuroanatomical basis of the phenomenon is largely understood, little is known about the synaptic mechanisms underlying memory formation for prediction error. The current experiment tests the overall hypothesis that this specific form of memory depends on N-methyl-D-aspartate (NMDA) receptor activation

Modelling Head Impact Safety Performance of Polymer-based Foam Protective Devices

The aim of this paper is to investigate an iterative statistical procedure, based on a small and censored sample of impact test experiments, useful for interval estimation of head impact safety parameter as critical fall height of protective devices. An adaptive testing routine was developed that was mainly constituted by a series of at least four impact test experiments, followed by the comparison of at least two parameter estimates based on incremental exponential regression fittings and a final confirmation experiment. A total number of 23 protective devices, mainly made of polyethylene foam, were investigated in order to validate the adaptive routine. The routine, applied to critical fall height of protective devices, was 19 times convergent within a maximum of 6 impact test experiments. 4 times the sample was censored because the iterative procedure has exceeded the available number of specimens. Confidence intervals at the 90 % level were always less than 0.18 m. The applicability of the adaptive routine was satisfactory demonstrated with reference to devices made of PE-foam and safety threshold of peak acceleration a-max equal to 200 g. The target of a confidence interval below the state-of-art was achieved

Real-world implementation and adaptation to local settings of first trimester preeclampsia screening in Italy: a systematic review

Background: Preeclampsia (PE) is a multisystem disease of pregnancy representing a major cause of maternal and perinatal morbidity and mortality. Early identification of pregnancies at risk of developing PE is crucial for implementing preventive strategies. The effective- ness of PE screening in the first trimester is widely recognized and endorsed by several guidelines, but unfortunately real-world im- plementation of this practice within local settings remains difficult. Methods: We performed a systematic review of the literature to un- derstand the critical issues hampering the implementation of PE screening procedures in Italy. All studies on first trimester PE screen- ing in the Italian population were eligible for inclusion. Key-concepts relevant for implementation of PE screening in Italy were extracted and analysed qualitatively. Results: Nine articles were selected and included. Lack of evidence concerning the topic of PE screening in Italy was shown. Major critical issues found encompassed health- care personnel education, training of sonographers, economic cov- erage for biochemical markers and adjustment of algorithms based on population characteristics. Conclusions: Identification and adapta- tion of specific protocols to local settings and population characteris- tics is critical for successful implementation of early PE screening in Italy. This process has the potential to improve pregnancy outcomes and to save valuable health-care resources, particularly scarce in the COVID-19 era. There is an urgent need for research studies on specific local populations focussing on subtle details capable of maximizing PE screening uptake. This action will likely potentiate PE screening implementation reducing the burden and the cost of perinatal and maternal complications

Breast cancer genome-wide association studies: there is strength in numbers

Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-specific protein 1 (LSP1). The most strongly associated SNP was in intron 2 of the FGFR2 gene that is amplified and overexpressed in 5-10% of BC. rs3803662 of TNRC9 gene has been shown to be the SNP with the strongest association with BC, in particular, this polymorphism seems to be correlated with bone metastases and estrogen receptor positivity. Relevant data indicate that SNP rs889312 in MAP3K1 is correlated with BC susceptibility only in BRCA2 mutation carriers, but is not associated with an increased risk in BRCA1 carriers. Finally, different SNPs in LSP1 and H19 and in minor genes probably were associated with BC risk. New susceptibility allelic variants associated with BC risk were recently discovered including potential causative genes involved in regulation of cell cycle, apoptosis, metabolism and mitochondrial functions. In conclusion, the identification of disease susceptibility loci may lead to a better understanding of the biological mechanism for BC to improve prevention, early detection and treatment

ECLS in Pediatric Cardiac Patients

Extracorporeal life support (ECLS) is an important device in the management of children with severe refractory cardiac and or pulmonary failure. Actually, two forms of ECLS are available for neonates and children: extracorporeal membrane oxygenation (ECMO) and use of a ventricular assist device (VAD). Both these techniques have their own advantages and disadvantages. The intra-aortic balloon pump is another ECLS device that has been successfully used in larger children, adolescents, and adults, but has found limited applicability in smaller children. In this review, we will present the "state of art" of ECMO in neonate and children with heart failure. ECMO is commonly used in a variety of settings to provide support to critically ill patients with cardiac disease. However, a strict selection of patients and timing of intervention should be performed to avoid the increase in mortality and morbidity of these patients. Therefore, every attempt should be done to start ECLS "urgently" rather than "emergently," before the presence of dysfunction of end organs or circulatory collapse. Even though exciting progress is being made in the development of VADs for long-term mechanical support in children, ECMO remains the mainstay of mechanical circulatory support in children with complex anatomy, particularly those needing rapid resuscitation and those with a functionally univentricular circulation. With the increase in familiarity with ECMO, new indications have been added, such as extracorporeal cardiopulmonary resuscitation (ECPR). The literature supporting ECPR is increasing in children. Reasonable survival rates have been achieved after initiation of support during active compressions of the chest following in-hospital cardiac arrest. Contraindications to ECLS have reduced in the last 5 years and many centers support patients with functionally univentricular circulations. Improved results have been recently achieved in this complex subset of patients

Exosomal shuttling of miR-126 in endothelial cells modulates adhesive and migratory abilities of chronic myelogenous leukemia cells

BACKGROUND: Recent findings indicate that exosomes released from cancer cells contain microRNAs (miRNAs) that may be delivered to cells of tumor microenvironment. RESULTS: To elucidate whether miRNAs secreted from chronic myelogenous leukemia cells (CML) are shuttled into endothelial cells thus affecting their phenotype, we first analysed miRNAs content in LAMA84 exosomes. Among the 124 miRNAs identified in LAMA84 exosomes, we focused our attention on miR-126 which was found to be over-overexpressed in exosomes compared with producing parental cells. Transfection of LAMA84 with Cy3-labelled miR-126 and co-culture of leukemia cells with endothelial cells (EC) confirmed that miR-126 is shuttled into HUVECs. The treatment of HUVECs with LAMA84 exosomes for 24 hours reduced CXCL12 and VCAM1 expression, both at the mRNA and protein level, and negatively modulated LAMA84 motility and cells adhesion. Transfection in HUVECs of miR-126 inhibitor reversed the decrease of CXCL12 and restored the motility and adhesion of LAMA84 cells while the over-expression of miR-126, showed opposite effects. CONCLUSION: Our results show that the miR-126 shuttled by exosomes is biologically active in the target cells, and support the hypothesis that exosomal miRNAs have an important role in tumor-endothelial crosstalk occurring in the bone marrow microenvironment, potentially affecting disease progression

Outdoor Tests for the Validation of an Inertial System Able to Detect Illegal Steps in Race-walking

Abstract Aim of this study was to validate an inertial system able to detect the loss of ground contact (LOGC) in race-walking through outdoor tests in real training conditions. An inertial sensor was placed at L5/S1 of the vertebral column of a Italian national team athlete to acquire timing measurements of the LOGC. Data were encoded by a well-defined protocol. After a preliminary laboratory study, the athlete performed outdoor-field-tests at different velocities. A specific e-bike with a high-speed camera allowed to acquire a video and to validate sensor measurements. Results indicate that the inertial system can improve the accuracy in detecting the visible LOGC

Risk Factors and Outcomes of Children with Congenital Heart Disease on Extracorporeal Membrane Oxygenation-A Ten-Year Single-Center Report.

For children born with congenital heart defects (CHDs), extracorporeal life support may be necessary. This retrospective single-center study aimed to investigate the outcomes of children with CHDs on extracorporeal membrane oxygenation (ECMO), focusing on various risk factors. Among the 88 patients, 36 (41%) had a single-ventricle heart defect, while 52 (59%) had a biventricular defect. In total, 25 (28%) survived, with 7 (8%) in the first group and 18 (20%) in the latter. A p-value of 0.19 indicated no significant difference in survival rates. Children with biventricular hearts had shorter ECMO durations but longer stays in the intensive care unit. The overall rate of complications on ECMO was higher in children with a single ventricle (odds ratio [OR] 1.57, 95% confidence interval [CI] 0.67-3.7); bleeding was the most common complication in both groups. The occurrence of a second ECMO run was more frequent in patients with a single ventricle (22% vs. 9.6%). ECMO can be effective for children with congenital heart defects, including single-ventricle patients. Bleeding remains a serious complication associated with worse outcomes. Patients requiring a second ECMO run within 30 days have lower survival rates