Anabolic resistance of muscle protein turnover comes in various shapes and sizes

Anabolic resistance is defined by a blunted stimulation of muscle protein synthesis rates (MPS) to common anabolic stimuli in skeletal muscle tissue such as dietary protein and exercise. Generally, MPS is the target of most exercise and feeding interventions as muscle protein breakdown rates seem to be less responsive to these stimuli. Ultimately, the blunted responsiveness of MPS to dietary protein and exercise underpins the loss of the amount and quality of skeletal muscle mass leading to decrements in physical performance in these populations. The increase of both habitual physical activity (including structured exercise that targets general fitness characteristics) and protein dense food ingestion are frontline strategies utilized to support muscle mass, performance, and health. In this paper, we discuss anabolic resistance as a common denominator underpinning muscle mass loss with aging, obesity, and other disease states. Namely, we discuss the fact that anabolic resistance exists as a dimmer switch, capable of varying from higher to lower levels of resistance, to the main anabolic stimuli of feeding and exercise depending on the population. Moreover, we review the evidence on whether increased physical activity and targeted exercise can be leveraged to restore the sensitivity of skeletal muscle tissue to dietary amino acids regardless of the population

The Respiratory Syncytial Virus G Protein Conserved Domain Induces a Persistent and Protective Antibody Response in Rodents

Respiratory syncytial virus (RSV) is an important cause of severe upper and lower respiratory disease in infants and in the elderly. There are 2 main RSV subtypes A and B. A recombinant vaccine was designed based on the central domain of the RSV-A attachment G protein which we had previously named G2Na (aa130–230). Here we evaluated immunogenicity, persistence of antibody (Ab) response and protective efficacy induced in rodents by: (i) G2Na fused to DT (Diphtheria toxin) fragments in cotton rats. DT fusion did not potentiate neutralizing Ab responses against RSV-A or cross-reactivity to RSV-B. (ii) G2Nb (aa130–230 of the RSV-B G protein) either fused to, or admixed with G2Na. G2Nb did not induce RSV-B-reactive Ab responses. (iii) G2Na at low doses. Two injections of 3 µg G2Na in Alum were sufficient to induce protective immune responses in mouse lungs, preventing RSV-A and greatly reducing RSV-B infections. In cotton rats, G2Na-induced RSV-reactive Ab and protective immunity against RSV-A challenge that persisted for at least 24 weeks. (iv) injecting RSV primed mice with a single dose of G2Na/Alum or G2Na/PLGA [poly(D,L-lactide-co-glycolide]. Despite the presence of pre-existing RSV-specific Abs, these formulations effectively boosted anti-RSV Ab titres and increased Ab titres persisted for at least 21 weeks. Affinity maturation of these Abs increased from day 28 to day 148. These data indicate that G2Na has potential as a component of an RSV vaccine formulation

Screening audiologico

Saranno descritti i principali aspetti organizzativi che devono essere affrontati nello screening audiologico di primo, secondo e terzo livello. L\u2019attuale modello di screening \ue8 quello universale, a due stadi. lo screening uditivo neonatale deve essere eseguito dopo le prime 24 ore di vita e prima della dimissione del neonato. il protocollo diagnostico prevede l\u2019anamnesi, l\u2019osservazione ed esame obiettivo che si svolge mediante i test di audiometria comportamentale (BOR, COR/VRA e play audiometry), la valutazione strumentale e la valutazione delle abilita\u2019 comunicative. Saranno poi descritti nuovi test come l\u2019audiometria motoria, il Matrix sentence test per l\u2019ascolto nel rumore e la verifica della protesizzazione nel bambino e il dichotic digit test Rper la valutazione delle riisposte attentive

The imbalance between dynamic and stable microtubules underlies neurodegeneration induced by 2,5-hexanedione

Exposure to environmental toxins, including hydrocarbon solvents, increases the risk of developing Parkinson's disease. An emergent hypothesis considers microtubule dysfunction as one of the crucial events in triggering neuronal degeneration in Parkinson's disease. Here, we used 2,5-hexanedione (2,5-HD), the toxic metabolite of n-hexane, to analyse the early effects of toxin-induced neurodegeneration on the cytoskeleton in multiple model systems. In PC12 cells differentiated with nerve growth factor for 5 days, we found that 2,5-HD treatment affected all the cytoskeletal components. Moreover, we observed alterations in microtubule distribution and stability, in addition to the imbalance of post-translational modifications of \u3b1-tubulin. Similar defects were also found in vivo in 2,5-HD-intoxicated mice. Interestingly, we also found that 2,5-HD exposure induced significant changes in microtubule stability in human skin fibroblasts obtained from Parkinson's disease patients harbouring mutations in PRKN gene, whereas it was ineffective in healthy donor fibroblasts, suggesting that the genetic background may really make the difference in microtubule susceptibility to this environmental Parkinson's disease-related toxin. In conclusion, by showing the imbalance between dynamic and stable microtubules in hydrocarbon-induced parkinsonism, our data support the crucial role of microtubule defects in triggering neurodegeneration

Gain More for Less: The Surprising Benefits of QoS Management in Constrained NDN Networks

Quality of Service (QoS) in the IP world mainly manages forwarding resources, i.e., link capacities and buffer spaces. In addition, Information Centric Networking (ICN) offers resource dimensions such as in-network caches and forwarding state. In constrained wireless networks, these resources are scarce with a potentially high impact due to lossy radio transmission. In this paper, we explore the two basic service qualities (i) prompt and (ii) reliable traffic forwarding for the case of NDN. The resources we take into account are forwarding and queuing priorities, as well as the utilization of caches and of forwarding state space. We treat QoS resources not only in isolation, but correlate their use on local nodes and between network members. Network-wide coordination is based on simple, predefined QoS code points. Our findings indicate that coordinated QoS management in ICN is more than the sum of its parts and exceeds the impact QoS can have in the IP world

Estudo clínico duplo cego comparando praziquantel com oxamniquine

Com objetivo de se compararem a tolerabilidade e eficácia do praziquantel e oxamniquine, procedeu-se a um estudo prospectivo duplo-cego envolvendo 120 pacientes com esquistossomose intestinal ou hepatintestinal. Os pacientes foram randomizados em dois grupos. Um foi tratado com praziquantel, na dose de 55 mg/kg de peso, o outro com oxamniquine, 15 mg/kg de peso, sempre administrados em dose única por via oral. O diagnóstico e seguimento parasitológicos basearam-se ho exame de fazes peio método de Kate Katz. Em 73 de 77 casos negativos após tratamento, executaram-se biópsias retais. Efeitos colaterais, principalmente tontura, sonolência, dores abdominais, cefaléia, náuseas e diarréia foram observados em 87% dos casos. Sua incidência, intensidade e duração foram semelhantes em ambos os grupos, mas a dor abdominal foi significativamente mais freqüente após praziquantel, havendo maior tendência para tontura intensa após oxamniquine. Observou-se aumento significante de alamina-aminotransferase e gama-glutamiltransferase após oxamniquine e de bilirrubina total após praziquantel. Um total de 48 pacientes tratados com praziquantel e 46 com oxamniquine completaram os exames de controle até o sexto mês. As percentages de cura foram de 79,2% e de 84,8% respectivamente, diferença não significativa. Os pacientes não curados mostraram redução média do número de ovos de 93,5% e de 84,1%, diferença não significativa. Cinco pacientes retratados com praziquantel curaram-se, mas somente um de três retratados com oxamniquine. Estes resultados mostram, que ambas as drogas-apesar de diferentes propriedades farmacológicas provocam reações colaterais semelhantes e apresentam eficácia terapêutica comparável.A double-blind clinical trial involving 120 patients with chronic schistosomiasis was carried out to compare the tolerability and efficacy of praziquantel and oxamniquine. The patients were randomly allocated into two groups. One was treated with praziquantel, 55 mg/kg of body weight CBWT), and the other one with oxamniquine, 15mg/kg bwt, administered in a single oral dose. The diagnosis and the parasitological follow-up was based on stool examinations by quantitative Kato-Katz method and on rectal biopsies. Side-effects mainly dizziness, sleepness, abdominal distress, headache, nausea and diarrhea were observed in 87% of the cases. Their incidence, intensity and duration were similar for both drugs but abdominal pain was significantly more frequent after praziquantel intake and severe dizziness was more commonly reported after oxamniquine. A significant increase of alanine-aminotransferase and y-glutamyltransferase was found with the latter drug and of total bilirubin with the former one. A total of 48 patients treated with praziquantel and 46 with oxamniquine completed with negative findings the required three post-treatment parasitological controls three slides of each stool sample on the first, third and sixth month. The achieved cure rates were 79.2% and 84.8%, respectively, a difference without statistical significance. The non-cured cases showed a mean reduction in the number of eggs per gram of feces of 93.5% after praziquantel and of 84.1% after oxamniquine. This diference also was not significant. Five patients retreated with praziquantel were cured but only one out of three treated a second time with oxamniquine. These findings show that both drugs despite their different chemical structures, pharmacological properties and mechanisms-of-action induce similar side-effects as well as a comparable therapeutical efficacy, in agreement with the results reported from analogous investigations

Results of a combined monolithic crystal and an array of ASICs controlled SiPMs

[EN] In this work we present the energy and spatial resolutions we have obtained for a γ ray detector based on a monolithic LYSO crystal coupled to an array of 256 SiPMs. Two crystal configurations of the same trapezoidal shape have been tried. In one approach all surfaces were black painted but the exit one facing the photosensor array which was polished. The other approach included a retroreflector (RR) layer coupled to the entrance face of the crystal powering the amount of transmitted light to the photosensors. Two coupling media between the scintillator and the SiPM array were used, namely direct coupling by means of optical grease and coupling through an array of light guides. Since the same operational voltage was supplied to the entire array, it was needed to equalize their gains before feeding their signals to the Data Acquisition system. Such a job was performed by means of 4 scalable Application Specific Circuits (ASICs). An energy resolution of about 24.4% has been achieved for the direct coupling with the RR layer together with a spatial resolution of approximately 2.9 mm at the detector center. With the light guides coupling the effects of image compression at the edges are significantly minimized, but worsening the energy resolution to about 33.1% with a spatial resolution nearing 4 mm at the detector center. & 2013 Elsevier B.V. All rights reserved.cknowledgments This work was supported by the Centre for Industrial Technological Development co-funded by FEDER through the Technology Fund (DREAM Project, IDI-20110718), the Spanish Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (IþDþI) under Grant no. FIS2010-21216-CO2-01 and the Valencian Local Government under Grant PROMETEO 2008/114Conde Castellanos, PE.; González Martínez, AJ.; Hernández Hernández, L.; Bellido, P.; Iborra Carreres, A.; Crespo Navarro, E.; Moliner Martínez, L.... (2014). Results of a combined monolithic crystal and an array of ASICs controlled SiPMs. Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment. 734:132-136. https://doi.org/10.1016/j.nima.2013.08.079S13213673

World Workshop on Oral Medicine VIII: Development of a core outcome set for oral lichen planus: a systematic review of outcome domains

Objective: There is a lack of consensus regarding clinician- and patient-reported oral lichen planus (OLP) outcomes. The World Workshop on Oral Medicine Outcomes Initiative for the Direction of Research (WONDER) Project aims to develop a core outcome set (COS) for OLP, which would inform the design of clinical trials and, importantly, facilitate meta-analysis, leading to the establishment of more robust evidence for the management of this condition and hence improved patient care. Study Design: Ovid MEDLINE, Embase, CINAHL, CENTRAL, and Clinicaltrials.gov were searched for interventional studies (randomized controlled trials, controlled clinical trials, and case series including ≥5 participants) on OLP and oral lichenoid reactions published between January 2001 and March 2022 without language restriction. All reported primary and secondary outcomes were extracted. Results: The searches yielded 9,135 records, and 291 studies were included after applying the inclusion criteria. A total of 422 outcomes were identified. These were then grouped based on semantic similarity, condensing the list to 69 outcomes. The most frequently measured outcomes were pain (51.9%), clinical grading of the lesions (29.6%), lesion size/extension/area (27.5%), and adverse events (17.5%). Conclusion: As a first step in developing a COS for OLP, we summarized the outcomes that have been used in interventional studies over the past 2 decades, which are numerous and heterogeneous.S