Telemedicine Beyond Borders: A Mixed-Methods Approach to Understanding Cross-National Usage Intention.

Introduction: Drawing on the Unified Theory of Acceptance and Use of Technology 2 and the Diffusion of Innovation Theory, this article investigates the adoption of telemedicine services from a patient perspective in Germany, Spain, and the United States using a mixed-methods approach. Digital health technologies have the potential to improve access to care and to alleviate the burden on traditional health care systems and are becoming more integrated into everyday medicine. Therefore, understanding the factors that impact patients' intentions to use telemedicine is crucial to ensure successful development. Methods: Based on 1,200 surveys collected in Germany, Spain, and the United States, structural equation modeling (IBM SPSS Amos 24) is employed to test the hypotheses. The article also explores how age and gender moderate the proposed relationships. Results: Seven out of the 10 hypotheses (performance expectancy, hedonic motivation, habit, relative advantage, and perceived security) are found to be positive, direct, and statistically significant. Furthermore, findings suggest stronger effects for telemedicine usage intention for younger female users than their male counterparts. Discussion: With digital health technologies becoming more prevalent, the outcomes of this study can endorse the development of effective strategies to promote the adoption of telemedicine, ultimately improving access to care and contributing to the advancement of and modern health care.

New Insights into the Pro-Inflammatory and Osteoclastogenic Profile of Circulating Monocytes in Osteoarthritis Patients.

Osteoarthritis (OA) is a degenerative condition of the articular cartilage with chronic low-grade inflammation. Monocytes have a fundamental role in the progression of OA, given their implication in inflammatory responses and their capacity to differentiate into bone-resorbing osteoclasts (OCLs). This observational-experimental study attempted to better understand the molecular pathogenesis of OA through the examination of osteoclast progenitor (OCP) cells from both OA patients and healthy individuals (25 OA patients and healthy samples). The expression of osteoclastogenic and inflammatory genes was analyzed using RT-PCR. The OA monocytes expressed significantly higher levels of CD16, CD115, TLR2, Mincle, Dentin-1, and CCR2 mRNAs. Moreover, a flow cytometry analysis showed a significantly higher surface expression of the CD16 and CD115 receptors in OA vs. healthy monocytes, as well as a difference in the distribution of monocyte subsets. Additionally, the OA monocytes showed a greater osteoclast differentiation capacity and an enhanced response to an inflammatory stimulus. The results of this study demonstrate the existence of significant differences between the OCPs of OA patients and those of healthy subjects. These differences could contribute to a greater understanding of the molecular pathogenesis of OA and to the identification of new biomarkers and potential drug targets for OA.

PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.

Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the order Lithistida, family Theonellidae, genus Discodermia (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin ßIII isotype overexpression). Furthermore, PM534 induces significant inhibition of tumor growth in mouse xenograft models of human non-small cell lung cancer. Our results present PM534, a highly effective new compound in the preclinical evaluation that is currently in its first human Phase I clinical trial.

Validation of an in vivo transit dosimetry algorithm using Monte Carlo simulations and ionization chamber measurements.

PURPOSE: Transit dosimetry is a safety tool based on the transit images acquired during treatment. Forward-projection transit dosimetry software, as PerFRACTION, compares the transit images acquired with an expected image calculated from the DICOM plan, the CT, and the structure set. This work aims to validate PerFRACTION expected transit dose using PRIMO Monte Carlo simulations and ionization chamber measurements, and propose a methodology based on MPPG5a report. METHODS: The validation process was divided into three groups of tests according to MPPG5a: basic dose validation, IMRT dose validation, and heterogeneity correction validation. For the basic dose validation, the fields used were the nine fields needed to calibrate PerFRACTION and three jaws-defined. For the IMRT dose validation, seven sweeping gaps fields, the MLC transmission and 29 IMRT fields from 10 breast treatment plans were measured. For the heterogeneity validation, the transit dose of these fields was studied using three phantoms: 10 , 30 , and a 3 cm cork slab placed between 10 cm of solid water. The PerFRACTION expected doses were compared with PRIMO Monte Carlo simulation results and ionization chamber measurements. RESULTS: Using the 10 cm solid water phantom, for the basic validation fields, the root mean square (RMS) of the difference between PerFRACTION and PRIMO simulations was 0.6%. In the IMRT fields, the RMS of the difference was 1.2%. When comparing respect ionization chamber measurements, the RMS of the difference was 1.0% both for the basic and the IMRT validation. The average passing rate with a γ(2%/2 mm, TH = 20%) criterion between PRIMO dose distribution and PerFRACTION expected dose was 96.0% ± 5.8%. CONCLUSION: We validated PerFRACTION calculated transit dose with PRIMO Monte Carlo and ionization chamber measurements adapting the methodology of the MMPG5a report. The methodology presented can be applied to validate other forward-projection transit dosimetry software.

MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).

The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.

Development of a Ready-to-Eat Fish Product Enriched with Fish Oil Entrapped in a κ-Carrageenan Egg White Fish Protein Hydrolysate Dry Powder.

This work describes the development of a ready-to-eat (RTE) product based on an equal mixture of fish mince from three undervalued fish species with different fat contents and protein gelling capacity, which was enriched with fish oil entrapped in a κ-carrageenan egg white fish protein hydrolysate powder, obtained by either spray drying (SD) or heat drying (HD) at 80 °C (HD80). Previously, the spray-dried (SD) powder and heat-dried powders obtained at 45 °C, 60 °C and 80 °C (HD45, HD60 and HD80) were characterised in terms of water solubility, lipid oxidation (TBARS), hygroscopicity and ζ potential. All HD powders showed higher hygroscopicity and lower TBARS than the SD powder. The dry powder was incorporated into a blend composed of salt-ground batter and raw mince to improve binding and textural properties. Changes in water-holding capacity, colour, shear strength and microorganisms were monitored during the processing steps. The RTE product presented a high protein content and a noticeable amount of long-chain ω-3 fatty acids. The use of undervalued fish species together with fish oil and a protein hydrolysate from fish waste contribute to improving the sustainability of fishery resources, being conducive to obtaining a potentially functional RTE product.

Hypothalamic JNK1-hepatic fatty acid synthase axis mediates a metabolic rewiring that prevents hepatic steatosis in male mice treated with olanzapine via intraperitoneal: Additional effects of PTP1B inhibition.

Olanzapine (OLA), a widely used second-generation antipsychotic (SGA), causes weight gain and metabolic alterations when administered orally to patients. Recently, we demonstrated that, contrarily to the oral treatment which induces weight gain, OLA administered via intraperitoneal (i.p.) in male mice resulted in body weight loss. This protection was due to an increase in energy expenditure (EE) through a mechanism involving the modulation of hypothalamic AMPK activation by higher OLA levels reaching this brain region compared to those of the oral treatment. Since clinical studies have shown hepatic steatosis upon chronic treatment with OLA, herein we further investigated the role of the hypothalamus-liver interactome upon OLA administration in wild-type (WT) and protein tyrosine phosphatase 1B knockout (PTP1B-KO) mice, a preclinical model protected against metabolic syndrome. WT and PTP1B-KO male mice were fed an OLA-supplemented diet or treated via i.p. Mechanistically, we found that OLA i.p. treatment induces mild oxidative stress and inflammation in the hypothalamus in a JNK1-independent and dependent manner, respectively, without features of cell dead. Hypothalamic JNK activation up-regulated lipogenic gene expression in the liver though the vagus nerve. This effect concurred with an unexpected metabolic rewiring in the liver in which ATP depletion resulted in increased AMPK/ACC phosphorylation. This starvation-like signature prevented steatosis. By contrast, intrahepatic lipid accumulation was observed in WT mice treated orally with OLA; this effect being absent in PTP1B-KO mice. We also demonstrated an additional benefit of PTP1B inhibition against hypothalamic JNK activation, oxidative stress and inflammation induced by chronic OLA i.p. treatment, thereby preventing hepatic lipogenesis. The protection conferred by PTP1B deficiency against hepatic steatosis in the oral OLA treatment or against oxidative stress and neuroinflammation in the i.p. treatment strongly suggests that targeting PTP1B might be also a therapeutic strategy to prevent metabolic comorbidities in patients under OLA treatment in a personalized manner.

Gamma passing rates of daily EPID transit images correlate to PTV coverage for breast cancer IMRT treatment plans.

PURPOSE: The use of the transit image obtained with the electronic portal-imaging device (EPID) is becoming an extended method to perform in-vivo dosimetry. The transit images acquired during each fraction can be compared with a predicted image, if available, or with a baseline image, usually the obtained in the first fraction. This work aims to study the dosimetric impact of the failing fractions and to evaluate the appropriateness of using a baseline image in breast plans. MATERIAL AND METHODS: Twenty breast patients treated in a Halcyon were retrospectively selected. For each patient and fraction, the treatment plan was calculated over the daily CBCT image. For each fraction, the differences respect to the treatment plan values of OARs and PTV dosimetric parameters were analyzed: ΔDmean , ΔD95%, ΔD98%, ΔD2%, ΔV36Gy, ΔV38.5Gy, and ΔV43.5Gy. Daily fractions were ranked according to the differences found in the dosimetric parameters between the treatment plan and the daily CBCT to establish the best fraction. The daily transit images acquired in every fraction were compared to the first fraction using the global gamma index with the Portal Dosimetry tool. The comparison was repeated using the best fraction image as a baseline. We assessed the correlation of the dosimetric differences obtained from the CBCT images-based treatment plans with the gamma index passing rates obtained using first fraction and best fraction as baseline. RESULTS: Average values of -11.6% [-21.4%, -3.3%] and -3.2% [-1.0%, -10.3%] for the ∆PTVD98% and ∆PTVD95% per every 10% decrease in the passing rate were found, respectively. When using the best fraction as baseline patients were detected with failing fractions that were not detected with the first fraction as baseline. CONCLUSION: The gamma passing rates of daily transit images correlate with the coverage loss parameters in breast IMRT plans. Using first fraction image as baseline can lead to the non-detectability of failing fractions.

Neuroimaging uncovers neuronal and metabolic changes in pain modulatory brain areas in a rat model of chemotherapy-induced neuropathy - MEMRI and ex vivo spectroscopy studies.

Chemotherapy-induced neuropathy (CIN) is one of the most common complications of cancer treatment with sensory dysfunctions which frequently include pain. The mechanisms underlying pain during CIN are starting to be uncovered. Neuroimaging allows the identification of brain circuitry involved in pain processing and modulation and has recently been used to unravel the disruptions of that circuitry by neuropathic pain. The present study evaluates the effects of paclitaxel, a cytostatic drug frequently used in cancer treatment, at the neuronal function in the anterior cingulate cortex (ACC), hypothalamus and periaqueductal gray (PAG) using manganese-enhanced magnetic resonance imaging (MEMRI). We also studied the metabolic profile at the prefrontal cortex (PFC) and hypothalamus using ex vivo spectroscopy. Wistar male rats were intraperitoneal injected with paclitaxel or vehicle solution (DMSO). The evaluation of mechanical sensitivity using von Frey test at baseline (BL), 21 (T21), 28 (T28), 49 (T49) and 56 days (T56) after CIN induction showed that paclitaxel-injected rats presented mechanical hypersensitivity from T21 until T56 after CIN induction. The evaluation of the locomotor activity and exploratory behaviors using open-field test at T28 and T56 after the first injection of paclitaxel revealed that paclitaxel-injected rats walked higher distance with higher velocity at late point of CIN accompanied with a sustained exhibition of anxiety-like behaviors. Imaging studies performed using MEMRI at T28 and T56 showed that paclitaxel treatment increased the neuronal activation in the hypothalamus and PAG at T56 in comparison with the control group. The analysis of data from ex vivo spectroscopy demonstrated that at T28 paclitaxel-injected rats presented an increase of N-acetyl aspartate (NAA) levels in the PFC and an increase of NAA and decrease of lactate (Lac) concentration in the hypothalamus compared to the control group. Furthermore, at T56 the paclitaxel-injected rats presented lower NAA and higher taurine (Tau) levels in the PFC. Together, MEMRI and metabolomic data indicate that CIN is associated with neuroplastic changes in brain areas involved in pain modulation and suggests that other events involving glial cells may be happening.

Different measures for auditory hallucinations in populations with psychosis. The Validation of the Spanish versions of the Auditory Vocal Hallucination Rating Scale (AVHRS) and the Positive and Useful Voices Inquiry (PUVI).

INTRODUCTION: An updated summary of the most used instruments assessing auditory hallucinations in population with psychosis, allows us to underline the scarceness and need of Spanish versions of important instruments. The aim of the study is to examine the psychometric characteristics of two different and complementary instruments for assessing auditory hallucinations, the Spanish version of the Auditory Vocal Hallucination Scale (AVHRS) and the Spanish version of the Positive and Useful Voices Inquiry (PUVI). MATERIALS AND METHODS: A sample of 68 patients from four different centres, with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder presenting with auditory hallucinations were included. Apart from the AVHRS and the PUVI, the Psychotic Symptom Rating Scales-Auditory Hallucinations subscale (PSYRATS-AH) and the Positive and Negative Syndrome Scale (PANSS) were also administered to all patients, plus an acceptability questionnaire. RESULTS: The Spanish version of the AVHRS showed a good internal consistency, a moderate to high inter-rater reliability, a medium to moderate test-retest reliability, and a good convergent and discriminant validity. The Spanish version of the PUVI showed a good internal consistency and a heterogeneous, but in general moderate, test-retest reliability. CONCLUSIONS: The Spanish versions of the AVHRS and the PUVI have good psychometric properties and are well accepted among patients.

Physical and Oxidative Water-in-Oil Emulsion Stability by the Addition of Liposomes from Shrimp Waste Oil with Antioxidant and Anti-Inflammatory Properties.

Liposomes made of partially purified phospholipids (PL) from Argentine red shrimp waste oil were loaded with two antioxidant lipid co-extracts (hexane-soluble, Hx and acetone-soluble, Ac) to provide a higher content of omega-3 fatty acids. The physical properties of the liposomes were characterized by Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS) and Differential Scanning Calorimetry (DSC). The antioxidant and anti-inflammatory activity of the lipid extracts and liposomal suspensions were evaluated in terms of Superoxide and ABTS radical scavenging capacities and TNF-α inhibition. Uni-lamellar spherical liposomes (z-average ≈ 145 nm) with strong negative ζ potential (≈ -67 mV) were obtained in all cases. The high content of neutral lipids in the Hx extract caused structural changes in the bilayer membrane and decreased entrapment efficiency regarding astaxanthin and EPA + DHA contents. The liposomes loaded with the Hx/Ac extracts showed higher antioxidant and anti-inflammatory activity compared with empty liposomes. The liposomal dispersions improved the physical and oxidative stability of water-in-oil emulsions as compared with the PL extract, inducing pronounced close packing of water droplets. The liposomes decreased hydroperoxide formation in freshly made emulsions and prevented thio-barbituric acid-reactive substances (TBARS) accumulation during chilled storage. Liposomes from shrimp waste could be valuable nanocarriers and stabilizers in functional food emulsions.

Cellular and Molecular Targets of Extracellular Vesicles from Mesenchymal Stem/Stromal Cells in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes progressive joint destruction. Despite the advances in the treatment of this condition there remains a clinical need for safe therapies leading to clinical remission. Mesenchymal stem/stromal cells (MSCs) play immunomodulatory and regenerative roles which can be partly mediated by their secretome. In recent years, the important contribution of extracellular vesicles (EVs) to MSC actions has received an increasing interest as a new therapeutic approach. We provide an extensive overview of the immunomodulatory properties of MSC EVs and their effects on articular cells such as fibroblast-like synoviocytes that play a central role in joint destruction. This review discusses the anti-arthritic effects of MSC EVs in vitro and in animal models of RA as well as their potential mechanisms. Recent preclinical data suggest that transfer of non-coding RNAs by MSC EVs regulates key signaling pathways involved in the pathogenesis of RA. We also examine a number of EV modifications for improving their anti-arthritic efficacy and carrier ability for drug delivery.

Modulation of hypothalamic AMPK phosphorylation by olanzapine controls energy balance and body weight.

BACKGROUND: Second-generation antipsychotics (SGAs) are a mainstay therapy for schizophrenia. SGA-treated patients present higher risk for weight gain, dyslipidemia and hyperglycemia. Herein, we evaluated the effects of olanzapine (OLA), widely prescribed SGA, in mice focusing on changes in body weight and energy balance. We further explored OLA effects in protein tyrosine phosphatase-1B deficient (PTP1B-KO) mice, a preclinical model of leptin hypersensitivity protected against obesity. METHODS: Wild-type (WT) and PTP1B-KO mice were fed an OLA-supplemented diet (5 mg/kg/day, 7 months) or treated with OLA via intraperitoneal (i.p.) injection or by oral gavage (10 mg/kg/day, 8 weeks). Readouts of the crosstalk between hypothalamus and brown or subcutaneous white adipose tissue (BAT and iWAT, respectively) were assessed. The effects of intrahypothalamic administration of OLA with adenoviruses expressing constitutive active AMPKα1 in mice were also analyzed. RESULTS: Both WT and PTP1B-KO mice receiving OLA-supplemented diet presented hyperphagia, but weight gain was enhanced only in WT mice. Unexpectedly, all mice receiving OLA via i.p. lost weight without changes in food intake, but with increased energy expenditure (EE). In these mice, reduced hypothalamic AMPK phosphorylation concurred with elevations in UCP-1 and temperature in BAT. These effects were also found by intrahypothalamic OLA injection and were abolished by constitutive activation of AMPK in the hypothalamus. Additionally, OLA i.p. treatment was associated with enhanced Tyrosine Hydroxylase (TH)-positive innervation and less sympathetic neuron-associated macrophages in iWAT. Both central and i.p. OLA injections increased UCP-1 and TH in iWAT, an effect also prevented by hypothalamic AMPK activation. By contrast, in mice fed an OLA-supplemented diet, BAT thermogenesis was only enhanced in those lacking PTP1B. Our results shed light for the first time that a threshold of OLA levels reaching the hypothalamus is required to activate the hypothalamus BAT/iWAT axis and, therefore, avoid weight gain. CONCLUSION: Our results have unraveled an unexpected metabolic rewiring controlled by hypothalamic AMPK that avoids weight gain in male mice treated i.p. with OLA by activating BAT thermogenesis and iWAT browning and a potential benefit of PTP1B inhibition against OLA-induced weight gain upon oral treatment.

Different measures for auditory hallucinations in populations with psychosis. The Validation of the Spanish versions of the Auditory Vocal Hallucination Rating Scale (AVHRS) and the Positive and Useful Voices Inquiry (PUVI) / Diferentes medidas para las alucinaciones auditivas en poblaciones con psicosis. Validación de las versiones españolas de la Escala de Valoración de Alucinaciones Auditivas Vocales (AVHRS) y de la Encuesta sobre Voces Positivas y Útiles (PUVI)

Introduction: An updated summary of the most used instruments assessing auditory hallucinations in population with psychosis, allows us to underline the scarceness and need of Spanish versions of important instruments. The aim of the study is to examine the psychometric characteristics of two different and complementary instruments for assessing auditory hallucinations, the Spanish version of the Auditory Vocal Hallucination Scale (AVHRS) and the Spanish version of the Positive and Useful Voices Inquiry (PUVI). Materials and methods: A sample of 68 patients from four different centres, with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder presenting with auditory hallucinations were included. Apart from the AVHRS and the PUVI, the Psychotic Symptom Rating Scales-Auditory Hallucinations subscale (PSYRATS-AH) and the Positive and Negative Syndrome Scale (PANSS) were also administered to all patients, plus an acceptability questionnaire. Results: The Spanish version of the AVHRS showed a good internal consistency, a moderate to high inter-rater reliability, a medium to moderate test–retest reliability, and a good convergent and discriminant validity. The Spanish version of the PUVI showed a good internal consistency and a heterogeneous, but in general moderate, test–retest reliability. Conclusions: The Spanish versions of the AVHRS and the PUVI have good psychometric properties and are well accepted among patients. (AU)

Introducción: Un resumen actualizado de los instrumentos más utilizados en la evaluación de las alucinaciones auditivas en poblaciones con psicosis, nos permite subrayar la escasez y necesidad de versiones españolas de importantes instrumentos. El objetivo del estudio es examinar las características psicométricas de dos instrumentos para la evaluación de las alucinaciones auditivas diferentes y complementarios, la versión española de la Escala de Valoración de Alucinaciones Auditivas Vocales (AVHRS) y la versión española de la Encuesta sobre Voces Positivas y Útiles (PUVI). Material y métodos: Se incluyó una muestra de 68 pacientes de cuatro centros diferentes, con diagnóstico de esquizofrenia o trastorno esquizoafectivo según el DSM-IV, que presentaban alucinaciones auditivas. Además de la AVHRS y de la PUVI, se administraron también a todos los pacientes la subescala de Alucinaciones Auditivas de la Escalas de Evaluación de Síntomas Psicóticos (PSYRATS-AH) y la Escala de Evaluación de Síndrome Positivo y Negativo (PANSS), además de un cuestionario de aceptabilidad. Resultados: La versión española de la AVHRS mostró una buena consistencia interna, una fiabilidad inter-jueces de moderada a alta, una fiabilidad re-test de media a moderada, y una buena validez convergente y discriminante. La versión española de la PUVI mostró una buena consistencia interna y una fiabilidad test-retest heterogénea pero, en general, moderada. Conclusiones: Las versiones españolas de la AVHRS y la PUVI tienes buenas propiedades psicométricas y son bien aceptadas entre los pacientes. (AU)

Extracorporeal photopheresis in paediatric patients: A retrospective comparison between different 'off-line' protocols.

BACKGROUND AND OBJECTIVES: Extracorporeal photopheresis (ECP) has been shown to be an effective treatment for graft-versus-host disease (GvHD). However, information regarding lymphocyte collection for ECP in children is limited. The aim of this study was to analyse and compare lymphocyte collection for ECP in children using different devices and protocols. Moreover, we have studied both safety and variables of the infused product related to treatment efficacy. PATIENTS AND METHODS: This was a retrospective study of 91 patients who underwent 1524 apheresis procedures with either the COBE Spectra or Spectra Optia system. The comparison study between the Optia protocols (MNC and CMNC) was prioritized. We analysed 578 procedures using the Optia blood cell separator: 204 and 374 using the MNC and the CMNC protocol, respectively. RESULTS: The Optia CMNC protocol showed better collection efficiency, with increased lymphocyte collection per kg of body weight (p < 0.001). On multivariate analysis, the type of protocol showed no relationship with haematocrit or platelet loss. Most procedures were well-tolerated, with the most frequent adverse events related to venous access (21.7%). Seventy-one percent of patients had either partial or complete clinical GvHD response. In the multivariate model, only two variables were associated with a better response to ECP, younger age and a greater increase of B lymphocytes after treatment. CONCLUSION: Lymphocyte collection for ECP is well-tolerated in most children, achieving complete or partial response in more than half of GvHD patients. CMNC is the optimal software to perform lymphocyte collection in children.

Individual and Joint Effect of Alpha-Tocopherol and Hydroxytyrosol Acetate on the Oxidation of Sunflower Oil Submitted to Oxidative Conditions: A Study by Proton Nuclear Magnetic Resonance.

This study tackles the individual and joint effect of alpha-tocopherol and hydroxytyrosol acetate on the oxidation of sunflower oil submitted to accelerated storage conditions at intermediate temperature, in order to deepen the understanding of antioxidant-prooxidant behaviour. This was accomplished by 1H Nuclear Magnetic Resonance. For this purpose, the evolution of the degradation of both the main components of the oil and the aforementioned added compounds was monitored by this technique throughout the storage time. Furthermore, the formation of a very large number of oxylipins and the evolution of their concentration up to a very advanced stage of oil oxidation, as well as the occurrence of lipolysis, were also simultaneously studied. The results obtained show very clearly and thoroughly that in the oxidation process of the oil enriched in binary mixtures, interactions occur between alpha-tocopherol and hydroxytyrosol acetate that notably reduce the antioxidant effect of the latter compound with the corresponding negative consequences that this entails. The methodology used here has proved to be very efficient to evaluate the antioxidant power of mixtures of compounds.

Connection between Mesenchymal Stem Cells Therapy and Osteoclasts in Osteoarthritis.

The use of mesenchymal stem cells constitutes a promising therapeutic approach, as it has shown beneficial effects in different pathologies. Numerous in vitro, pre-clinical, and, to a lesser extent, clinical trials have been published for osteoarthritis. Osteoarthritis is a type of arthritis that affects diarthritic joints in which the most common and studied effect is cartilage degradation. Nowadays, it is known that osteoarthritis is a disease with a very powerful inflammatory component that affects the subchondral bone and the rest of the tissues that make up the joint. This inflammatory component may induce the differentiation of osteoclasts, the bone-resorbing cells. Subchondral bone degradation has been suggested as a key process in the pathogenesis of osteoarthritis. However, very few published studies directly focus on the activity of mesenchymal stem cells on osteoclasts, contrary to what happens with other cell types of the joint, such as chondrocytes, synoviocytes, and osteoblasts. In this review, we try to gather the published bibliography in relation to the effects of mesenchymal stem cells on osteoclastogenesis. Although we find promising results, we point out the need for further studies that can support mesenchymal stem cells as a therapeutic tool for osteoclasts and their consequences on the osteoarthritic joint.

Alpha-Tocopherol, a Powerful Molecule, Leads to the Formation of Oxylipins in Polyunsaturated Oils Differently to the Temperature Increase: A Detailed Study by Proton Nuclear Magnetic Resonance of Walnut Oil Oxidation.

Lipid oxidation causes food degradation and the formation of toxic compounds. Therefore, the addition to foods of compounds able to avoid, delay or minimize this degradative process is a commonly used strategy. Nevertheless, neither the identity of most of the formed compounds in this complex process nor the way in which their formation is affected by the strategy used are well known. In this context, the effect the temperature increase and the enrichment level in alpha-tocopherol on the evolution of the walnut oil oxidation, as a model of an oil rich in polyunsaturated omega-6 acyl groups, submitted to storage conditions, are tackled by 1H NMR. The study has allowed knowing the degradation kinetic of both the oil acyl groups and alpha-tocopherol, the identification of a very high number of oxylipins and the kinetic of their formation. The temperature increase accelerates the formation of all oxylipins, favouring the formation of hydroperoxy conjugated E,E-dienes and related derivatives versus that of the Z,E-isomers. The enrichment in alpha-tocopherol accelerates the formation of hydroperoxy conjugated Z,E-dienes and related derivatives, and delays in relation to the formation of the former that of the E,E-isomers and related derivatives, hindering, to a certain extent, the formation of the latter in line with the enrichment level.

Influence of Hydroxytyrosol Acetate Enrichment of an Oil Rich in Omega-6 Groups on the Evolution of Its Oxidation and Oxylipin Formation When Subjected to Accelerated Storage. A Global Study by Proton Nuclear Magnetic Resonance.

Sunflower oil samples, both unenriched and enriched with four different concentrations of hydroxytyrosol acetate, were subjected to accelerated storage at 70 °C until a very advanced oxidation stage and the process was monitored by 1H NMR spectroscopy. The aim of the study is to know the effect that the presence of this antioxidant has on the oxidation process of sunflower oil under the aforementioned conditions, as well as on the formation and evolution of the concentration of a significant number of oxylipins. The oxidation process was studied globally by monitoring, during storage time, the degradation of both the linoleic acyl group of sunflower oil, which is the main component of sunflower oil, and the added hydroxytyrosol acetate. Simultaneously, the identification of up to twenty-six different types of oxylipins formed in the oxidation process and the monitoring of the evolution of their concentration over the storage time were carried out. In this way, essential information about the effect that hydroxytyrosol acetate provokes on the oxidation of this oil rich in omega-6 polyunsaturated acyl groups, has been obtained. It has also been shown that the enrichment of sunflower oil with this antioxidant under the conditions tested does not prevent the oxidation process but slows it down, affecting the entire oxidation process.

Anti-Inflammatory Properties, Bioaccessibility and Intestinal Absorption of Sea Fennel (Crithmum maritimum) Extract Encapsulated in Soy Phosphatidylcholine Liposomes.

A sea fennel (Crithmum maritimum) aqueous extract was prepared and loaded into soybean phosphatidylcholine liposomes. Both the free extract (FE), and the empty (L) and loaded (L-FE) liposomes were shown to be non-cytotoxic to THP-1 and Caco-2 cells. The anti-inflammatory effect was tested on THP-1 cells differentiated into macrophages. FE showed anti-inflammatory activity, revealed by the induced secretion of IL-10 cytokines in macrophages that were subsequently stimulated with LPS. Also, a decrease in TNF-α production by L was observed, evidencing that liposomes reduced the pro-inflammatory mediators' secretion. The liposomes (L) showed protective anti-inflammatory activity and also were able to downregulate the inflammation. Furthermore, L-FE were also found to downregulate the inflammation response, as they were able to decrease TNF-α secretion in macrophages previously exposed to LPS. The simulated in vitro gastrointestinal digestion (GID) of FE diminished the chlorogenic acid content (the main polyphenolic compound of the extract) by 40%, while in L-FE, the amount of this phenolic compound increased with respect to the undigested liposomes. The amount of bioaccessible chlorogenic, however, was similar for FE and L-FE. The percentage of chlorogenic acid absorbed through a Caco-2 cell monolayer after 3 h of incubation, was significantly similar for the extract and the liposomes (~1.5%), without finding significant differences once the extract and liposomes were digested.