FMRI resting slow fluctuations correlate with the activity of fast cortico-cortical physiological connections

Recording of slow spontaneous fluctuations at rest using functional magnetic resonance imaging (fMRI) allows distinct long-range cortical networks to be identified. The neuronal basis of connectivity as assessed by resting-state fMRI still needs to be fully clarified, considering that these signals are an indirect measure of neuronal activity, reflecting slow local variations in de-oxyhaemoglobin concentration. Here, we combined fMRI with multifocal transcranial magnetic stimulation (TMS), a technique that allows the investigation of the causal neurophysiological interactions occurring in specific cortico-cortical connections. We investigated whether the physiological properties of parieto-frontal circuits mapped with short-latency multifocal TMS at rest may have some relationship with the resting-state fMRI measures of specific resting-state functional networks (RSNs). Results showed that the activity of fast cortico-cortical physiological interactions occurring in the millisecond range correlated selectively with the coupling of fMRI slow oscillations within the same cortical areas that form part of the dorsal attention network, i.e., the attention system believed to be involved in reorientation of attention. We conclude that resting-state fMRI ongoing slow fluctuations likely reflect the interaction of underlying physiological cortico-cortical connections

Validation and Accuracy of Synovial Alpha Defensin in a Suburban Academic Center after Implantation as Part of the Workup for Periprosthetic Joint infections

Introduction Periprosthetic joint infection (PJI) is a leading cause of total hip and knee arthroplasty failure. The Musculoskeletal Infection Society (MSIS) criteria for PJI has allowed diagnosis standardization. To increase the MSIS criteria accuracy, synovial fluid biomarkers have been tested. Studies evaluating synovial alpha defensin have reported both sensitivity and specificity up to 100%. In this study, we report our analysis on the use of alpha defensin testing in a suburban academic tertiary referral center. Methods We performed a retrospective analysis of a prospectively collected database of 133 patients tested for PJI over a 6 year period. From 2014, our standard infection evaluation protocol included synovial alpha defensin fluid analysis. Complete testing data was available on 128 patients. Both primary and revision total hip and knee arthroplasty were included. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated using the 2011 MSIS criteria. T-tests were performed for parametric data. Results Synovial testing of alpha defensin for PJI had a 95.00% sensitivity, a 91.67% specificity, a 67.86% PPV and a 99.00% NPV. Positive alpha defensin tests were corelated with positive serum and synovial CRP, synovial WBC count, and synovial polymorphonuclear cell percent. There was no correlation between positive synovial alpha defensin and age, sex, smoking or diabetic status. Conclusion Synovial testing for alpha defensin in an unbiased cohort gives high sensitivity and NPV comparable to published literature. We recommend using synovial alpha defensin testing for suspected PJI cases, as an additional data point to help determine likelihood

Three-dimensional femtosecond laser nanolithography of crystals

Nanostructuring hard optical crystals has so far been exclusively feasible at their surface, as stress induced crack formation and propagation has rendered high precision volume processes ineffective. We show that the inner chemical etching reactivity of a crystal can be enhanced at the nanoscale by more than five orders of magnitude by means of direct laser writing. The process allows to produce cm-scale arbitrary three-dimensional nanostructures with 100 nm feature sizes inside large crystals in absence of brittle fracture. To showcase the unique potential of the technique, we fabricate photonic structures such as sub-wavelength diffraction gratings and nanostructured optical waveguides capable of sustaining sub-wavelength propagating modes inside yttrium aluminum garnet crystals. This technique could enable the transfer of concepts from nanophotonics to the fields of solid state lasers and crystal optics.Comment: Submitted Manuscript and Supplementary Informatio

Improved Outcomes in Auditory Brainstem Implantation with the Use of Near-Field Electrical Compound Action Potentials.

Among the 202 patients with auditory brainstem implants fitted and monitored with electrical auditory brainstem response during implant fitting, 9 also underwent electrical compound action potential recording. These subjects were matched retrospectively with a control group of 9 patients in whom only the electrical auditory brainstem response was recorded. Electrical compound action potentials were obtained using a cotton-wick recording electrode located near the surface of the cochlear nuclei and on several cranial nerves. Significantly lower potential thresholds were observed with the recording electrode located on the cochlear nuclei surface compared with the electrical auditory brainstem response (104.4 ± 32.5 vs 158.9 ± 24.2, P = .0030). Electrical brainstem response and compound action potentials identified effects on the neighboring cranial nerves on 3.2 ± 2.4 and 7.8 ± 3.2 electrodes, respectively (P = .0034). Open-set speech perception outcomes at 48-month follow-up had improved significantly in the near- versus far-field recording groups (78.9% versus 56.7%; P = .0051). Electrical compound action potentials during auditory brainstem implantation significantly improved the definition of the potential threshold and the number of auditory and extra-auditory waves generated. It led to the best coupling between the electrode array and cochlear nuclei, significantly improving the overall open-set speech perception

Processing and Quality Guidelines for Organic Food Processing

ForewordThese guidelines on quality and processing of organic foods have been prepared as part of the Core Organic Plus funded project “SusOrganic - Development of quality standards and optimi-sed processing methods for organic produce”. They intend to support actors in the organic food processing sector to simultaneously increase resource efficiency and product quality of their produce by providing deeper insights in raw material, process and product relevant aspects. The main focus of the presented work lies on the preservation of fruits, herbs, vegetables, fish and meat by the means of drying and chilling/freezing. THE AIMS OF THESE GUIDELINES ARE TO PROVIDE THE PROCESSORS WITH: • Drying related aspects • A deeper understanding for naturally occurring heterogeneities in raw materials and their impact on drying characteristics • Information on the impact of pre-treatment and holding time between preparation and drying on the resulting product quality • Information on the impact of drying and the related process settings on product quality • Information on improved drying strategies and process control concepts • Best practice examples for processing • Best practice based on LCA and LCCA • Food drying and related food logistics • Chilling and Freezing related aspects • General aspects of superchilling • Superchilling for organic meat and fish • Effects of freezing and freezing rate on organic fruit

Linear and nonlinear fractional hereditary constitutive laws of asphalt mixtures

The aim of this paper is to propose a fractional viscoelastic and viscoplastic model of asphalt mixtures using experimental data of several tests such as creep and creep recovery performed at different temperatures and at different stress levels. From a best fitting procedure it is shown that both the creep one and recovery curve follow a power law model. It is shown that the suitable model for asphalt mixtures is a dashpot and a fractional element arranged in series. The proposed model is also available outside of the linear domain but in this case the parameters of the model depend on the stress level

Architecture landscape

The network architecture evolution journey will carry on in the years ahead, driving a large scale adoption of 5th Generation (5G) and 5G-Advanced use cases with significantly decreased deployment and operational costs, and enabling new and innovative use-case-driven solutions towards 6th Generation (6G) with higher economic and societal values. The goal of this chapter, thus, is to present the envisioned societal impact, use cases and the End-to-End (E2E) 6G architecture. The E2E 6G architecture includes summarization of the various technical enablers as well as the system and functional views of the architecture

Esomeprazole for the treatment of erosive esophagitis in children: an international, multicenter, randomized, parallel-group, double-blind (for dose) study

<p>Abstract</p> <p>Background</p> <p>Acid suppression with a proton pump inhibitor is standard treatment for gastroesophageal reflux disease and erosive esophagitis in adults and increasingly is becoming first-line therapy for children aged 1-17 years. We evaluated endoscopic healing of erosive esophagitis with esomeprazole in young children with gastroesophageal reflux disease and described esophageal histology.</p> <p>Methods</p> <p>Children aged 1-11 years with endoscopically or histologically confirmed gastroesophageal reflux disease were randomized to esomeprazole 5 or 10 mg daily (< 20 kg) or 10 or 20 mg daily (≥ 20 kg) for 8 weeks. Patients with erosive esophagitis underwent an endoscopy after 8 weeks to assess healing of erosions.</p> <p>Results</p> <p>Of 109 patients, 49% had erosive esophagitis and 51% had histologic evidence of reflux esophagitis without erosive esophagitis. Of the 45 patients who had erosive esophagitis and underwent follow-up endoscopy, 89% experienced erosion resolution. Dilation of intercellular space was reported in 24% of patients with histologic examination.</p> <p>Conclusions</p> <p>Esomeprazole (0.2-1.0 mg/kg) effectively heals macroscopic and microscopic erosive esophagitis in this pediatric population with gastroesophageal reflux disease. Dilation of intercellular space may be an important histologic marker of erosive esophagitis in children.</p> <p>Trial Registration</p> <p>D9614C00097; ClinicalTrials.gov identifier NCT00228527.</p

TRAP1 regulates stemness through Wnt/β-catenin pathway in human colorectal carcinoma

Colorectal carcinoma (CRC) is a common cause of cancer-related death worldwide. Indeed, treatment failures are triggered by cancer stem cells (CSCs) that give rise to tumor repopulation upon initial remission. Thus, the role of the heat shock protein TRAP1 in stemness was investigated in CRC cell lines and human specimens, based on its involvement in colorectal carcinogenesis, through regulation of apoptosis, protein homeostasis and bioenergetics. Strikingly, co-expression between TRAP1 and stem cell markers was observed in stem cells located at the bottom of intestinal crypts and in CSCs sorted from CRC cell lines. Noteworthy, TRAP1 knockdown reduced the expression of stem cell markers and impaired colony formation, being the CSC phenotype and the anchorage-independent growth conserved in TRAP1-rich cancer cells. Consistently, the gene expression profiling of HCT116 cells showed that TRAP1 silencing results in the loss of the stem-like signature with acquisition of a more-differentiated phenotype and the downregulation of genes encoding for activating ligands and target proteins of Wnt/β-catenin pathway. Mechanistically, TRAP1 maintenance of stemness is mediated by the regulation of Wnt/β-catenin signaling, through the modulation of the expression of frizzled receptor ligands and the control of β-catenin ubiquitination/phosphorylation. Remarkably, TRAP1 is associated with higher expression of β-catenin and several Wnt/β-catenin target genes in human CRCs, thus supporting the relevance of TRAP1 regulation of β-catenin in human pathology. This study is the first demonstration that TRAP1 regulates stemness and Wnt/β-catenin pathway in CRC and provides novel landmarks in cancer biology and therapeutics

Accumulation of neutral lipids in peripheral blood mononuclear cells as a distinctive trait of Alzheimer patients and asymptomatic subjects at risk of disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease is the most common progressive neurodegenerative disease. In recent years, numerous progresses in the discovery of novel Alzheimer's disease molecular biomarkers in brain as well as in biological fluids have been made. Among them, those involving lipid metabolism are emerging as potential candidates. In particular, an accumulation of neutral lipids was recently found by us in skin fibroblasts from Alzheimer's disease patients. Therefore, with the aim to assess whether peripheral alterations in cholesterol homeostasis might be relevant in Alzheimer's disease development and progression, in the present study we analyzed lipid metabolism in plasma and peripheral blood mononuclear cells from Alzheimer's disease patients and from their first-degree relatives.</p> <p>Methods</p> <p>Blood samples were obtained from 93 patients with probable Alzheimer's disease and from 91 of their first-degree relatives. As controls we utilized 57, cognitively normal, over-65 year-old volunteers and 113 blood donors aged 21-66 years, respectively. Data are reported as mean ± standard error. Statistical calculations were performed using the statistical analysis software Origin 8.0 version. Data analysis was done using the Student t-test and the Pearson test.</p> <p>Results</p> <p>Data reported here show high neutral lipid levels and increased ACAT-1 protein in about 85% of peripheral blood mononuclear cells freshly isolated (<it>ex vivo</it>) from patients with probable sporadic Alzheimer's disease compared to about 7% of cognitively normal age-matched controls. A significant reduction in high density lipoprotein-cholesterol levels in plasma from Alzheimer's disease blood samples was also observed. Additionally, correlation analyses reveal a negative correlation between high density lipoprotein-cholesterol and cognitive capacity, as determined by Mini Mental State Examination, as well as between high density lipoprotein-cholesterol and neutral lipid accumulation. We observed great variability in the neutral lipid-peripheral blood mononuclear cells data and in plasma lipid analysis of the subjects enrolled as Alzheimer's disease-first-degree relatives. However, about 30% of them tend to display a peripheral metabolic cholesterol pattern similar to that exhibited by Alzheimer's disease patients.</p> <p>Conclusion</p> <p>We suggest that neutral lipid-peripheral blood mononuclear cells and plasma high density lipoprotein-cholesterol determinations might be of interest to outline a distinctive metabolic profile applying to both Alzheimer's disease patients and asymptomatic subjects at higher risk of disease.</p