Telepractice for Pediatric Dysphagia: A Case Study

A closed-ended intensive pediatric swallowing telepractice program was developed and piloted in one pediatric patient with Opitz BBB/G and Asperger’s Syndromes, oropharyngeal dysphagia and aerophagia. The present study is a case report. Outcome variables included behavioral, swallowing and quality of life variables, and were assessed at baseline and at the end of the four-week program. Selective variables were also assessed at a follow-up family interview four weeks post program completion. Over the four-week intervention period, the patient demonstrated substantial improvements in: oral acceptance of eating-related objects and a variety of foods (behavioral variable), timing of voluntary saliva swallows and aerophagia levels (swallowing variables) and quality of life. Follow-up interview analysis showed that most skills were retained or improved one-month post intervention. This intensive telepractice program proved to be feasible and effective for this pediatric patient with dysphagia

Non-isothermal kinetic analysis of the crystallization of metallic glasses using the master curve method

The non-isothermal transformation rate curves of metallic glasses are analyzed with the Master Curve method grounded in the Kolmogorov-Johnson-Mehl-Avrami theory. The method is applied to the study of two different metallic glasses determining the activation energy of the transformation and the experimental kinetic function that is analyzed using Avrami kinetics. The analysis of the crystallization of Cu47Ti33Zr11Ni8Si1 metallic glassy powders gives Ea = 3.8 eV, in good agreement with the calculation by other methods, and a transformation initiated by an accelerating nucleation and diffusion-controlled growth. The other studied alloy is a Nanoperm-type Fe77Nb7B15Cu1 metallic glass with a primary crystallization of bcc-Fe. An activation energy of Ea = 5.7 eV is obtained from the Master Curve analysis. It is shown that the use of Avrami kinetics is not able to explain the crystallization mechanisms in this alloy giving an Avrami exponent of n = 1

Effect of minor Co additions on the crystallization and magnetic properties of Fe(Co)NbBCu alloys

The effect of partial replacement of Fe by Co (up to 8 %) on thermal stability, structure and magnetic properties of FeNbBCu alloys has been explored in this paper. The results indicate that Co reduces the stability against crystallization of the amorphous alloy and stabilizes the nanocrystalline phase prior to the further precipitation of metastable boride phases. Transmission Mössbauer spectroscopy reveals differences in the hyperfine interactions between the alloys: Co raises the mean hyperfine field of the amorphous state and differences in the nanocrystalline bcc-Fe(Co) environments between the alloys occur depending on the amount of Co near-neighbours in the bcc-Fe structure. The addition of Co has also a notable effect on the magnetic properties of both amorphous and nanocrystalline alloys increasing the Curie temperature, which shows a linear dependence with the Co composition, and the saturation polarization.Peer ReviewedPostprint (author’s final draft

The Walnuts and Healthy Aging study (WAHA): Protocol for a Nutritional Intervention Trial with Walnuts on Brain Aging

Introduction: An unwanted consequence of population aging is the growing number of elderly at risk of neurodegenerative disorders, including dementia and macular degeneration. As nutritional and behavioral changes can delay disease progression, we designed the Walnuts and Healthy Aging (WAHA) study, a two-center, randomized, 2-year clinical trial conducted in free-living, cognitively healthy elderly men and women. Our interest in exploring the role of walnuts in maintaining cognitive and retinal health is based on extensive evidence supporting their cardio-protective and vascular health effects, which are linked to bioactive components, such as n-3 fatty acids and polyphenols. Methods: The primary aim of WAHA is to examine the effects of ingesting walnuts daily for 2 years on cognitive function and retinal health, assessed with a battery of neuropsychological tests and optical coherence tomography, respectively. All participants followed their habitual diet, adding walnuts at 15% of energy (≈30-60 g/day) (walnut group) or abstaining from walnuts (control group). Secondary outcomes include changes in adiposity, blood pressure, and serum and urinary biomarkers in all participants and brain magnetic resonance imaging in a subset. Results: From May 2012 to May 2014, 708 participants (mean age 69 years, 68% women) were randomized. The study ended in May 2016 with a 90% retention rate. Discussion: The results of WAHA might provide high-level evidence of the benefit of regular walnut consumption in delaying the onset of age-related cognitive impairment and retinal pathology. The findings should translate into public health policy and sound recommendations to the general population

Acetylation increases access of remodelling complexes to their nucleosome targets to enhance initiation of V(D)J recombination

Targeted chromatin remodelling is essential for many nuclear processes, including the regulation of V(D)J recombination. ATP-dependent nucleosome remodelling complexes are important players in this process whose activity must be tightly regulated. We show here that histone acetylation regulates nucleosome remodelling complex activity to boost RAG cutting during the initiation of V(D)J recombination. RAG cutting requires nucleosome mobilization from recombination signal sequences. Histone acetylation does not stimulate nucleosome mobilization per se by CHRAC, ACF or their catalytic subunit, ISWI. Instead, we find the more open structure of acetylated chromatin regulates the ability of nucleosome remodelling complexes to access their nucleosome templates. We also find that bromodomain/acetylated histone tail interactions can contribute to this targeting at limited concentrations of remodelling complex. We therefore propose that the changes in higher order chromatin structure associated with histone acetylation contribute to the correct targeting of nucleosome remodelling complexes and this is a novel way in which histone acetylation can modulate remodelling complex activity

Structure detection and segmentation of documents using 2D stochastic context-free grammars

[EN] In this paper we define a bidimensional extension of stochastic context-free grammars for structure detection and segmentation of images of documents. Two sets of text classification features are used to perform an initial classification of each zone of the page. Then, the document segmentation is obtained as the most likely hypothesis according to a stochastic grammar. We used a dataset of historical marriage license books to validate this approach. We also tested several inference algorithms for probabilistic graphical models and the results showed that the proposed grammatical model outperformed the other methods. Furthermore, grammars also provide the document structure along with its segmentation. & 2014 Elsevier B.V. All rights reserved.Work is partially supported by the Spanish MEC under the STraDA Research Project (TIN2012-37475-C02-01), the Spanish Project 2010-CONES-00029, the FPU Grant (AP2009-4363), and through the EU 7th Framework Programme Grant tranScriptorium (Ref: 600707).Álvaro Muñoz, F.; Cruz Fernández, F.; Sánchez Peiró, JA.; Ramos Terrades, O.; Benedí Ruiz, JM. (2015). Structure detection and segmentation of documents using 2D stochastic context-free grammars. Neurocomputing. 150:147-154. https://doi.org/10.1016/j.neucom.2014.08.076S14715415

Hematological Changes as Prognostic Indicators of Survival: Similarities Between Gottingen Minipigs, Humans, and Other Large Animal Models

The animal efficacy rule addressing development of drugs for selected disease categories has pointed out the need to develop alternative large animal models. Based on this rule, the pathophysiology of the disease in the animal model must be well characterized and must reflect that in humans. So far, manifestations of the acute radiation syndrome (ARS) have been extensively studied only in two large animal models, the non-human primate (NHP) and the canine. We are evaluating the suitability of the minipig as an additional large animal model for development of radiation countermeasures. We have previously shown that the Gottingen minipig manifests hematopoietic ARS phases and symptoms similar to those observed in canines, NHPs, and humans.We establish here the LD50/30 dose (radiation dose at which 50% of the animals succumb within 30 days), and show that at this dose the time of nadir and the duration of cytopenia resemble those observed for NHP and canines, and mimic closely the kinetics of blood cell depletion and recovery in human patients with reversible hematopoietic damage (H3 category, METREPOL approach). No signs of GI damage in terms of diarrhea or shortening of villi were observed at doses up to 1.9 Gy. Platelet counts at days 10 and 14, number of days to reach critical platelet values, duration of thrombocytopenia, neutrophil stress response at 3 hours and count at 14 days, and CRP-to-platelet ratio were correlated with survival. The ratios between neutrophils, lymphocytes and platelets were significantly correlated with exposure to irradiation at different time intervals.As a non-rodent animal model, the minipig offers a useful alternative to NHP and canines, with attractive features including ARS resembling human ARS, cost, and regulatory acceptability. Use of the minipig may allow accelerated development of radiation countermeasures

2022 update

Funding Information: This study was funded by European League Against Rheumatism. Publisher Copyright: © Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.Objectives: To provide an update of the EULAR rheumatoid arthritis (RA) management recommendations addressing the most recent developments in the field. Methods: An international task force was formed and solicited three systematic literature research activities on safety and efficacy of disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids (GCs). The new evidence was discussed in light of the last update from 2019. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned to and participants finally voted on the level of agreement with each item. Results: The task force agreed on 5 overarching principles and 11 recommendations concerning use of conventional synthetic (cs) DMARDs (methotrexate (MTX), leflunomide, sulfasalazine); GCs; biological (b) DMARDs (tumour necrosis factor inhibitors (adalimumab, certolizumab pegol, etanercept, golimumab, infliximab including biosimilars), abatacept, rituximab, tocilizumab, sarilumab and targeted synthetic (ts) DMARDs, namely the Janus kinase inhibitors tofacitinib, baricitinib, filgotinib, upadacitinib. Guidance on monotherapy, combination therapy, treatment strategies (treat-to-target) and tapering in sustained clinical remission is provided. Safety aspects, including risk of major cardiovascular events (MACEs) and malignancies, costs and sequencing of b/tsDMARDs were all considered. Initially, MTX plus GCs is recommended and on insufficient response to this therapy within 3-6 months, treatment should be based on stratification according to risk factors; With poor prognostic factors (presence of autoantibodies, high disease activity, early erosions or failure of two csDMARDs), any bDMARD should be added to the csDMARD; after careful consideration of risks of MACEs, malignancies and/or thromboembolic events tsDMARDs may also be considered in this phase. If the first bDMARD (or tsDMARD) fails, any other bDMARD (from another or the same class) or tsDMARD (considering risks) is recommended. With sustained remission, DMARDs may be tapered but should not be stopped. Levels of evidence and levels of agreement were high for most recommendations. Conclusions: These updated EULAR recommendations provide consensus on RA management including safety, effectiveness and cost.publishersversionepub_ahead_of_prin

Low Cost Tuberculosis Vaccine Antigens in Capsules: Expression in Chloroplasts, Bio-Encapsulation, Stability and Functional Evaluation In Vitro

Tuberculosis (TB) caused by Mycobacterium tuberculosis is one of the leading fatal infectious diseases. The development of TB vaccines has been recognized as a major public health priority by the World Health Organization. In this study, three candidate antigens, ESAT-6 (6kDa early secretory antigenic target) and Mtb72F (a fusion polyprotein from two TB antigens, Mtb32 and Mtb39) fused with cholera toxin B-subunit (CTB) and LipY (a cell wall protein) were expressed in tobacco and/or lettuce chloroplasts to facilitate bioencapsulation/oral delivery. Site-specific transgene integration into the chloroplast genome was confirmed by Southern blot analysis. In transplastomic leaves, CTB fusion proteins existed in soluble monomeric or multimeric forms of expected sizes and their expression levels varied depending upon the developmental stage and time of leaf harvest, with the highest-level of accumulation in mature leaves harvested at 6PM. The CTB-ESAT6 and CTB-Mtb72F expression levels reached up to 7.5% and 1.2% of total soluble protein respectively in mature tobacco leaves. Transplastomic CTB-ESAT6 lettuce plants accumulated up to 0.75% of total leaf protein. Western blot analysis of lyophilized lettuce leaves stored at room temperature for up to six months showed that the CTB-ESAT6 fusion protein was stable and preserved proper folding, disulfide bonds and assembly into pentamers for prolonged periods. Also, antigen concentration per gram of leaf tissue was increased 22 fold after lyophilization. Hemolysis assay with purified CTB-ESAT6 protein showed partial hemolysis of red blood cells and confirmed functionality of the ESAT-6 antigen. GM1-binding assay demonstrated that the CTB-ESAT6 fusion protein formed pentamers to bind with the GM1-ganglioside receptor. The expression of functional Mycobacterium tuberculosis antigens in transplastomic plants should facilitate development of a cost-effective and orally deliverable TB booster vaccine with potential for long-term storage at room temperature. To our knowledge, this is the first report of expression of TB vaccine antigens in chloroplasts