CELL-LINED, NONWOVEN MICROFIBER SCAFFOLDS AS A BLOOD INTERFACE *

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73137/1/j.1749-6632.1977.tb41787.x.pd

Real-time marker-less multi-person 3D pose estimation in RGB-Depth camera networks

This paper proposes a novel system to estimate and track the 3D poses of multiple persons in calibrated RGB-Depth camera networks. The multi-view 3D pose of each person is computed by a central node which receives the single-view outcomes from each camera of the network. Each single-view outcome is computed by using a CNN for 2D pose estimation and extending the resulting skeletons to 3D by means of the sensor depth. The proposed system is marker-less, multi-person, independent of background and does not make any assumption on people appearance and initial pose. The system provides real-time outcomes, thus being perfectly suited for applications requiring user interaction. Experimental results show the effectiveness of this work with respect to a baseline multi-view approach in different scenarios. To foster research and applications based on this work, we released the source code in OpenPTrack, an open source project for RGB-D people tracking.Comment: Submitted to the 2018 IEEE International Conference on Robotics and Automatio

Risk and protective factors associated with mental health status in an Italian sample of students during the fourth wave of COVID-19 pandemic

BackgroundIt is well known that the COVID-19 pandemic has caused a global health crisis, especially for young people. However, most studies were conducted during the first waves of the pandemic. Few Italian studies specifically attempted to broadly assess young people's mental health status during the fourth wave of the pandemic.MethodsThis study aimed at evaluating the mental health status among a group of Italian adolescents and young adults during the fourth wave of the COVID-19 pandemic. 11,839 high school students and 15,000 university students (age range 14-25) were asked to complete a multidimensional online survey, of which 7,146 (26,6%) agreed to participate. The survey also included standardized measures for depression, anxiety, anger, somatic symptoms, resilience, loneliness and post-traumatic growth. Two separate clusters were identified through cluster analysis. Random forest, classification tree and logistic regressions analyses were applied to identify factors associated to a good or a poor level of mental health and, thus, to define students' mental health profiles.ResultsOverall, the students in our sample showed high levels of psychopathology. The clustering methods performed identified two separate clusters reflecting groups of students with different psychological features, that we further defined as "poor mental health" and "good mental health". The random forest and the logistic regressions found that the most discriminating variables among those two groups were: UCLA Loneliness Scale score, self-harm behaviors, Connor-Davidson Resilience Scale-10 score, satisfaction with family relationships, Fear of COVID-19 Scale score, gender and binge eating behaviors. The classification tree analysis identified students' profiles, showing that, globally, poor mental health was defined by higher scores of loneliness and self-harm, followed by being of female gender, presenting binge eating behaviors and, finally, having unsatisfying family relationships.ConclusionsThe results of this study confirmed the major psychological distress caused by the COVID-19 pandemic in a large sample of Italian students, and provided further insights regarding those factors associated with a good or poor mental health status. Our findings suggest the importance of implementing programs targeting aspects that have been found to be associated to a good mental health

Bioactive phytochemicals of tree nuts. Determination of the melatonin and sphingolipid content in almonds and pistachios

Tree nuts are healthy foods rich in bioactive phytochemicals. Their regular, moderate consumption has been associated with a reduced risk of chronic-degenerative diseases, in the context of a healthy diet and lifestyle. This study aimed to investigate the phytochemical profile of almonds and pistachios, in order to add new elements in the complex scenario of nut chemistry. A LC-MS/MS method was developed to quantify melatonin and ceramides in almonds and pistachios. In general, pistachios were richer in melatonin (2609\u2009\ub1\u20093096 vs 1222\u2009\ub1\u2009500 pg/g) and total ceramides (302\u2009\ub1\u200977 vs 165\u2009\ub1\u200921\u2009pmol/g) than almonds. Among total ceramides fatty acyl homologs, the most represented was the C16:0 species, both for ceramides and dihydroceramides, and both in almonds (37-40%) and pistachios (51-74%). Overall, these results add a piece of information to elucidate the chemical composition of almonds and pistachios and provide a rationale for the nutraceutical potential of nuts in the Mediterranean diet

Determination of the serine palmitoyl transferase inhibitor Myriocin by electrospray and Q-trap mass spectrometry

Myriocin, is a potent inhibitor of serine-palmitoyl-transferase, the \ufb01rst and rate-determining enzyme in the sphingolipids biosynthetic pathway. This study developed, validated and applied a LC-MS/MS method to measure Myriocin in minute specimens of animal tissue. The chemical analog 14-OH-Myriocin is used as the internal standard. The two molecules are extracted from the tissue homogenate by solid-phase extraction, separated by gradient reverse-phase liquid chromatography and measured by negative ion electrospray mass spectrometry in the triple quadrupole. Detection is accomplished by Multiple Reaction Monitoring, employing the most representative transitions: 400@104 and 402@104 for Myriocin and 14-OH-Myriocin, respectively. The typical LoD and LLoQ of the optimized method are 0.9 pmoles/mL (approx. 0.016 pmoles injected) and 2.3 pmoles/mL, respectively, and the method is linear up to 250 pmoles/mL range (r2= 0.9996). The intra-and between-day repeatability affords a CV% 64 7.0. Applications included quantification of Myriocin in mouse lungs after 24 hrs from administration of ~4 nmoles by intra-trachea delivery. Measured levels ranged from 4.11 (median; 2.3-7.4 IQR, n=4) to 11.7 (median; 7.6-22.7 IQR, n=6) pmoles/lung depending on the different formulations used. Myriocin was also measured in retinas of mice treated by intravitreal injection and ranged from 0.045 (<LoD) to 0.35 pmoles/retina

A Genome-Wide Screening and SNPs-to-Genes Approach to Identify Novel Genetic Risk Factors Associated with Frontotemporal Dementia

Frontotemporal dementia (FTD) is the second most prevalent form of early onset dementia after Alzheimer’s disease (AD). We performed a case-control association study in an Italian FTD cohort (n = 530) followed by the novel SNPs-to-genes approach and functional annotation analysis. We identified two novel potential loci for FTD. Suggestive SNPs reached p-values ~10-7 and OR > 2.5 (2p16.3) and 1.5 (17q25.3). Suggestive alleles at 17q25.3 identified a disease-associated haplotype causing decreased expression of -cis genes such as RFNG and AATK involved in neuronal genesis and differentiation, and axon outgrowth, respectively. We replicated this locus through the SNPs-to-genes approach. Our functional annotation analysis indicated significant enrichment for functions of the brain (neuronal genesis, differentiation and maturation), the synapse (neurotransmission and synapse plasticity), and elements of the immune system, the latter supporting our recent international FTD-GWAS. This is the largest genome-wide study in Italian FTD to date. Although our results are not conclusive, we set the basis for future replication studies and identification of susceptible molecular mechanisms involved in FTD pathogenesis

De novo ceramide synthesis is involved in acute inflammation during labor

Gestation is regulated by an inflammatory process that allows implantation and parturition. The comprehension of such inflammatory switches is important for the identification of therapeutic targets in pregnancy defects. Sphingolipids are a class of structural membrane components with important signaling functions. Among sphingolipids, ceramide is a well-known mediator of stress signals and pro-inflammatory responses. In this paper, we evaluated the association between ceramide increase and the inflammatory process of labor, comparing placentas from vaginal deliveries, including both spontaneous and induced labor, versus elective cesarean. We demonstrated that: (i) the inflammatory marker IL-6 is upregulated in labored placentas; (ii) IL-6 content inversely correlates with labor duration; (iii) ceramide content and expression of serine palmitoyl transferase (SPT, rate limiting enzyme for de novo ceramide synthesis) are increased in labored placentas; (iv) the expression of SPT directly correlates with inflammation and inversely with labor duration. These observations suggest that ceramide metabolism and signaling may be implicated in controlling important inflammatory mechanisms driving gestation: we hypothesize that ceramide can be a therapeutic target in inflammatory complications of parturition

Brain-derived tau: a novel blood-based biomarker for Alzheimer's disease-type neurodegeneration

Blood-based biomarkers for amyloid beta and phosphorylated tau show good diagnostic accuracies and agreements with their corresponding CSF and neuroimaging biomarkers in the amyloid/tau/neurodegeneration [A/T/(N)] framework for Alzheimer's disease. However, the blood-based neurodegeneration marker neurofilament light is not specific to Alzheimer's disease while total-tau shows lack of correlation with CSF total-tau. Recent studies suggest that blood total-tau originates principally from peripheral, non-brain sources. We sought to address this challenge by generating an anti-tau antibody that selectively binds brain-derived tau and avoids the peripherally expressed 'big tau' isoform. We applied this antibody to develop an ultrasensitive blood-based assay for brain-derived tau, and validated it in five independent cohorts (n = 609) including a blood-to-autopsy cohort, CSF biomarker-classified cohorts and memory clinic cohorts. In paired samples, serum and CSF brain-derived tau were significantly correlated (rho = 0.85, P < 0.0001), while serum and CSF total-tau were not (rho = 0.23, P = 0.3364). Blood-based brain-derived tau showed equivalent diagnostic performance as CSF total-tau and CSF brain-derived tau to separate biomarker-positive Alzheimer's disease participants from biomarker-negative controls. Furthermore, plasma brain-derived tau accurately distinguished autopsy-confirmed Alzheimer's disease from other neurodegenerative diseases (area under the curve = 86.4%) while neurofilament light did not (area under the curve = 54.3%). These performances were independent of the presence of concomitant pathologies. Plasma brain-derived tau (rho = 0.52-0.67, P = 0.003), but not neurofilament light (rho = -0.14-0.17, P = 0.501), was associated with global and regional amyloid plaque and neurofibrillary tangle counts. These results were further verified in two memory clinic cohorts where serum brain-derived tau differentiated Alzheimer's disease from a range of other neurodegenerative disorders, including frontotemporal lobar degeneration and atypical parkinsonian disorders (area under the curve up to 99.6%). Notably, plasma/serum brain-derived tau correlated with neurofilament light only in Alzheimer's disease but not in the other neurodegenerative diseases. Across cohorts, plasma/serum brain-derived tau was associated with CSF and plasma AT(N) biomarkers and cognitive function. Brain-derived tau is a new blood-based biomarker that outperforms plasma total-tau and, unlike neurofilament light, shows specificity to Alzheimer's disease-type neurodegeneration. Thus, brain-derived tau demonstrates potential to complete the AT(N) scheme in blood, and will be useful to evaluate Alzheimer's disease-dependent neurodegenerative processes for clinical and research purposes

Pharmacokinetic of myriocin in rabbit&#8217;s eyes

Myriocin (Myr) is a suicide inactivator of ceramide synthesis with a complex lipid multifunctional structure. Its biological activity is exerted at very low doses, and thus highly performing quantitative method are needed [1]. The pharmacological development of Myr to modulate ceramide levels also requires currently unavailable ADME information in healthy and pathological animal models

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD