Designing an Informative App for Neurorehabilitation: A Feasibility and Satisfaction Study by Physiotherapists.

BACKGROUND: New technologies have gained popularity, especially the use of mobile phone applications, in neurorehabilitation. The aim of this paper was (1) to develop a free mobile application (NeurorehAPP) that provides information about and helps to select the appropriate mobile application related to a list of neurological disorders (cognitive impairment, Alzheimer's disease, Parkinson's disease, multiple sclerosis, traumatic brain injury, stroke, cerebral palsy, muscular dystrophy, spina bifida, and facial paralysis), based on different objectives such as healthy habits, information, assessment, and treatment; and (2) to assess the feasibility, acceptability, and degree of satisfaction by physiotherapists after using NeurorehAPP for a minimum of three months. METHODS: A free application was created to work with the Android® operating system. The degree of satisfaction and acceptance with the application was assessed with an adaptation of the Customer Satisfaction Questionnaire through a survey via email applied to physiotherapists from hospitals and neurological rehabilitation centers in Spain after using the application. RESULTS: NeurorehAPP includes a total of 131 apps. A total of 121 physiotherapists completed a satisfaction survey. The total sample showed 85.41% satisfaction with the service provided by the app and 86.41% overall satisfaction with NeurorehAPP. CONCLUSIONS: NeurorehAPP is a free, intuitive, and friendly app used with the Android® operating system that allows the selection of the most appropriate app according to the type of user, neurological disorder, objective, and FDA criteria. Physiotherapists showed a high degree of satisfaction and acceptance with NeurorehAPP.

Workshop for Basic Gynaecological Examinations: Improving Medical Student Learning through Clinical Simulation.

INTRODUCTION: This study was designed to evaluate whether the Workshop on Basic Principles for Clinical Gynaecological Exploration, offered to medical students, improves theoretical-practical knowledge, safety, confidence, global satisfaction and the achievement of the proposed objectives in the area of gynaecological clinical examinations. MATERIALS AND METHODS: This was a quasi-experimental pre-post-learning study carried out at the Gynaecology and Obstetrics department of Gregorio Marañón Hospital in Madrid (Spain). The volunteer participants were 4th-year students earning a degree in Medicine during the 2020-2021 and 2021-2022 academic years. The study period was divided into the following stages: pre-workshop, intra-workshop and 2 weeks post-workshop. In the pre-workshop stage, students completed a brief online course to prepare for the workshop. The effectiveness of the workshop was evaluated through multiple-choice tests and self-administered questionnaires to assess self-assurance, self-confidence, self-satisfaction and the achievement of the objectives. RESULTS: Of the 277 students invited in both academic years, 256 attended the workshop (92.4%), with a total participation in the different stages of the study greater than 70%. A total of 82.5% of the students in the 2020-2021 academic year and 80.6% of students in the 2021-2022 academic year did not have any type of experience performing gynaecological clinical examinations. Between the pre-workshop and 2 weeks post-workshop stages, there was significant improvement in theoretical-practical knowledge (improvement mean = 1.38 and 1.21 in 2020-2021 and 2021-2022 academic years, respectively). The security and confidence of the students prior to the workshop were low (average scores less than 5 points) in both academic years. However, post-workshop scores for satisfaction and the achievement of objectives were high in the two academic years; all the values approached or exceeded 8 points. CONCLUSIONS: Our students, after outstanding participation, evaluated the BPCGE, and improved their theoretical and practical knowledge, as well as their skills in a gynaecological clinical examination. Moreover, in their view, after the workshop, they felt very satisfied, far outreaching the proposed aims. In addition, excellent results were maintained over time, year after year.

A multistrain probiotic increases the serum glutamine/glutamate ratio in patients with cirrhosis: a metabolomic analysis.

To explore the potential mechanisms underlying the effects of a probiotic in cirrhotic patients, we analyzed the blood metabolome using proton nuclear magnetic resonance (1H-NMR) spectroscopy in 32 patients with cirrhosis and cognitive dysfunction or falls. Patients were randomized to receive a multistrain probiotic or placebo for 12 weeks. Among the 54 metabolites identified, the only significant changes in the probiotic group were an increase in glutamine, a decrease in glutamate, and an increase in the glutamine/glutamate ratio. In the placebo group, glutamate increased and the glutamine/glutamate ratio decreased. Our results suggest the multistrain probiotic could influence glutamine/glutamate metabolism, increasing the capacity of ammonia detoxification.

Essential role for albumin in preserving liver cells from TNFα-induced mitochondrial injury.

Cytokine-induced inflammation and mitochondrial oxidative stress are key drivers of liver tissue injury. Here, we describe experiments modeling hepatic inflammatory conditions in which plasma leakage leads to large amounts of albumin to reach the interstitium and parenchymal surfaces to explore whether this protein plays a role in preserving hepatocyte mitochondria against the damaging actions of the cytotoxic cytokine tumor necrosis factor alpha (TNFα). Hepatocytes and precision-cut liver slices were cultured in the absence or presence of albumin in the cell media and then exposed to mitochondrial injury with the cytokine TNFα. The homeostatic role of albumin was also investigated in a mouse model of TNFα-mediated liver injury induced by lipopolysaccharide and D-galactosamine (LPS/D-gal). Mitochondrial ultrastructure, oxygen consumption, ATP and reactive oxygen species (ROS) generation, fatty acid ß-oxidation (FAO), and metabolic fluxes were assessed by transmission electron microscopy (TEM), high-resolution respirometry, luminescence-fluorimetric-colorimetric assays and NADH/FADH2 production from various substrates, respectively. TEM analysis revealed that in the absence of albumin, hepatocytes were more susceptible to the damaging actions of TNFα and showed more round-shaped mitochondria with less intact cristae than hepatocytes cultured with albumin. In the presence of albumin in the cell media, hepatocytes also showed reduced mitochondrial ROS generation and FAO. The mitochondria protective actions of albumin against TNFα damage were associated with the restoration of a breakpoint between isocitrate and α-ketoglutarate in the tricarboxylic acid cycle and the upregulation of the antioxidant activating transcription factor 3 (ATF3). The involvement of ATF3 and its downstream targets was confirmed in vivo in mice with LPS/D-gal-induced liver injury, which showed increased hepatic glutathione levels, indicating a reduction in oxidative stress after albumin administration. These findings reveal that the albumin molecule is required for the effective protection of liver cells from mitochondrial oxidative stress induced by TNFα. These findings emphasize the importance of maintaining the albumin levels in the interstitial fluid within the normal range to protect the tissues against inflammatory injury in patients with recurrent hypoalbuminemia.

Redundancy Analysis to Reduce the High-Dimensional Near-Infrared Spectral Information to Improve the Authentication of Olive Oil.

The high price of marketing of extra virgin olive oil (EVOO) requires the introduction of cost-effective and sustainable procedures that facilitate its authentication, avoiding fraud in the sector. Contrary to classical techniques (such as chromatography), near-infrared (NIR) spectroscopy does not need derivatization of the sample with proper integration of separated peaks and is more reliable, rapid, and cost-effective. In this work, principal component analysis (PCA) and then redundancy analysis (RDA)─which can be seen as a constrained version of PCA─are used to summarize the high-dimensional NIR spectral information. Then PCA and RDA factors are contemplated as explanatory variables in models to authenticate oils from qualitative or quantitative analysis, in particular, in the prediction of the percentage of EVOO in blended oils or in the classification of EVOO or other vegetable oils (sunflower, hazelnut, corn, or linseed oil) by the use of some machine learning algorithms. As a conclusion, the results highlight the potential of RDA factors in prediction and classification because they appreciably improve the results obtained from PCA factors in calibration and validation.

Reduced Plasma Extracellular Vesicle CD5L Content in Patients With Acute-On-Chronic Liver Failure: Interplay With Specialized Pro-Resolving Lipid Mediators.

Acute-on chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated cirrhosis (AD). It is characterized by a systemic hyperinflammatory state, leading to multiple organ failure. Our objective was to analyze macrophage anti-inflammatory protein CD5L in plasma extracellular vesicles (EVs) and assess its as yet unknown relationship with lipid mediators in ACLF. With this aim, EVs were purified by size exclusion chromatography from the plasma of healthy subjects (HS) (n=6) and patients with compensated cirrhosis (CC) (n=6), AD (n=11) and ACLF (n=11), which were defined as positive for CD9, CD5L and CD63 and their size, number, morphology and lipid mediator content were characterized by NTA, EM, and LC-MS/MS, respectively. Additionally, plasma CD5L was quantified by ELISA in 10 HS, 20 CC and 149 AD patients (69 ACLF). Moreover, macrophage CD5L expression and the biosynthesis of specialized lipid mediators (SPMs) were characterized in vitro in primary cells. Our results indicate that circulating EVs were significantly suppressed in cirrhosis, regardless of severity, and showed considerable alterations in CD5L and lipid mediator content as the disease progressed. In AD, levels of EV CD5L correlated best with those of the SPM RvE1. Analysis of total plasma supported these data and showed that, in ACLF, low CD5L levels were associated with circulatory (p<0.001), brain (p<0.008) and respiratory (p<0.05) failure (Mann-Whitney test). Functional studies in macrophages indicated a positive feedback loop between CD5L and RvE1 biosynthesis. In summary, we have determined a significant alteration of circulating EV contents in ACLF, with a loss of anti-inflammatory and pro-resolving molecules involved in the control of acute inflammation in this condition.

Functional approach and agro-climatic information to improve the estimation of olive oil fatty acid content from near-infrared data.

Extra virgin olive oil (EVOO) is very appreciated by its taste, flavor, and benefits for health, and so, it has a high price of commercialization. This fact makes it necessary to provide reliable and cost-effective analytical procedures, such as near-infrared (NIR) spectroscopy, to analyze its traceability and purity, in combination with chemometrics. Fatty acids profile of EVOO, considered as a quality parameter, is estimated, firstly, from NIR data and, secondly, by adding agro-climatic information. NIR and agro-climatic data sets are summarized by using principal component analysis (PCA) and treated by both scalar and functional approaches. The corresponding PCA and FPCA are progressively introduced in regression models, whose goodness of fit is evaluated by the dimensionless root-mean-square error. In general, SFAs, MUFAs, and PUFAs (and disaggregated fatty acids) estimations are improved by adding agro-climatic besides NIR information (mainly, temperature or evapotranspiration) and considering a functional point of view for both NIR and agro-climatic data.

Convolutional Neural Networks Approach for Solar Reconstruction in SCAO Configurations.

Correcting atmospheric turbulence effects in light with Adaptive Optics is necessary, since it produces aberrations in the wavefront of astronomical objects observed with telescopes from Earth. These corrections are performed classically with reconstruction algorithms; between them, neural networks showed good results. In the context of solar observation, the usage of Adaptive Optics on solar differs from nocturnal operations, bringing up a challenge to correct the image aberrations. In this work, a convolutional approach is given to address this issue, considering SCAO configurations. A reconstruction algorithm is presented, "Shack-Hartmann reconstruction with deep learning on solar-prototype" (proto-HELIOS), to correct on fixed solar images, achieving an average 85.39% of precision in the reconstruction. Additionally, results encourage to continue working with these techniques to achieve a reconstruction technique for all the regions of the sun.

The endocannabinoid 2-arachidonoylglycerol regulates oligodendrocyte progenitor cell migration.

While the endocannabinoid 2-arachidonoylglycerol (2-AG) is thought to enhance the proliferation and differentiation of oligodendrocyte progenitor cells (OPCs) in vitro, less is known about how endogenous 2-AG may influence the migration of these cells. When we assessed this in Agarose drop and Boyden chemotaxis chamber assays, inhibiting the sn-1-diacylglycerol lipases α and ß (DAGLs) that are responsible for 2-AG synthesis significantly reduced the migration of OPCs stimulated by platelet-derived growth factor-AA (PDGF) and basic fibroblast growth factor (FGF). Likewise, antagonists of the CB1 and CB2 cannabinoid receptors (AM281 and AM630, respectively) produced a similar inhibition of OPC migration. By contrast, increasing the levels of endogenous 2-AG by blocking its degradation (impairing monoacylglycerol lipase activity with JZL-184) significantly increased OPC migration, as did agonists of the CB1, CB2 or CB1/CB2 cannabinoid receptors. This latter effect was abolished by selective CB1 or CB2 antagonists, strongly suggesting that cannabinoid receptor activation specifically potentiates OPC chemotaxis and chemokinesis in response to PDGF/FGF. Furthermore, the chemoattractive activity of these cannabinoid receptor agonists on OPCs was even evident in the absence of PDGF/FGF. In cultured brain slices prepared from the corpus callosum of postnatal rat brains, DAGL or cannabinoid receptor inhibition substantially diminished the in situ migration of Sox10+ OPCs. Overall, these results reveal a novel function of endogenous 2-AG in PDGF and FGF induced OPC migration, highlighting the importance of the endocannabinoid system in regulating essential steps in oligodendrocyte development.

Valor pronóstico de los instrumentos de evaluación de enfermedad avanzada y de final de vida en ancianos ingresados en un centro sociosanitario / Prognostic value of assessment tools on elderly patients with chronic advanced disease and end of life, admitted to an intermediate care centre

Objetivo. Aplicar 3instrumentos de evaluación de enfermedad avanzada en ancianos ingresados en un centro sociosanitario y evaluar su relación con la mortalidad. Métodos. Se aplicaron los instrumentos NECPAL, índice PROFUND e índice de comorbilidad de Charlson a 87 pacientes. Resultados. El instrumento NECPAL identificó a 31 pacientes (35,6%) en situación de necesidad de atención paliativa; según el índice PROFUND, 45 (54,7%) tenían riesgo alto/muy alto de mortalidad (≥7 puntos) y según el índice de Charlson, 31 (35,6%) tenían carga de morbilidad alta (≥4 puntos). Pacientes NECPAL positivos: el 80,5% tenían puntuación ≥7 en índice PROFUND y 48,3% un Charlson ≥ 4; dichas proporciones fueron 34,4 y 28,5% en los NECPAL negativos (p<0,001 y p≤0,06, respectivamente). Correlaciones entre los 3instrumentos: cuantitativas (Spearman): número de respuestas NECPAL con PROFUND (r=0,57; p<0,001); con Charlson (r=0,214; p=0,047) y entre PROFUND y Charlson (r=0,157; p=0,148). Cualitativas (kappa) NECPAL (positivo/negativo) con PROFUND (corte 6/7) (0,40; p<0,001), con Charlson (corte 3/4) (0,19; p=0,080) y entre PROFUND y Charlson (0,08; p=0,399). Predicción de mortalidad (área bajo la curva): NECPAL 3 meses 0,81 (IC: 0,62-1,00); 6 meses 0,71 (IC: 0,53-0,89) y 12 meses 0,67 (IC: 0,52-0,82). PROFUND 3 meses 0,71 (IC: 0,50-0,91); 6 meses 0,73 (IC: 0,58-0,87) y 12 meses 0,69 (IC: 0,57-0,81). Charlson 3 meses 0,72 (IC: 0,52-0,91); 6 meses 0,62 (IC: 0,45-0,80) y 12 meses 0,64 (IC: 0,50-0,78). Conclusiones. Los 3instrumentos se relacionaron de forma significativa con una mayor mortalidad. La concordancia entre los resultados de los distintos instrumentos fue baja (AU)

Objective. To apply 3advanced chronic disease evaluation tools in elderly patients admitted to an intermediate and long-term care centre, and evaluate its relationship with mortality. Methods. The NECPAL tool, PROFUND prognostic index, and Charlson comorbidity index were applied to 87 patients. Results. The NECPAL tool identified 31 patients (35.6%) in need of palliative care, and according to the PROFUND index, 45 (54.7%) had high/very high risk of mortality (≥7 points), and according to Charlson index, 31 (35.6%) had high comorbidity (≥4 points). Of the NECPAL positive patients, 80.5% had a PROFUND index score ≥7, and 48.3% a Charlson index ≥ 4. These percentages were 34.4% and 28.5% in negative NECPAL patients (P<.001 and P≤.06, respectively). Correlations between the 3tools: quantitative (Spearman) number of responses in NECPAL with PROFUND (r=.57; P<.001); with Charlson (r=.214; P<.047) and between PROFUND and Charlson (r=.157; P=.148). Qualitative (kappa) NECPAL (positive/negative) with PROFUND (cut-off 6/7) (0.40; P<.001), and Charlson (cut-off 3/4) (0.19; P=.080) and between PROFUND and Charlson (0.08; P=.399). Mortality prediction (area under the curve): NECPAL 3 months 0.81 (95% CI: 0.62-1.00); 6 months 0.71 (95% CI: 0.53-0.89) and 12 months 0.67 (95% CI: 0.52-0.82). PROFUND 3 months 0.71 (95% CI: 0.50-0.91); 6 months 0.73 (95% CI: 0.58-0.87), and 12 months 0.69 (95% CI: 0.57-0.81). Charlson 3 months 0.72 (95% CI: 0.52-0.91); 6 months 0.62 (95% CI: 0.45-0.80), and 12 months 0.64 (95% CI: 0.50-0.78). Conclusions. The 3tools were significantly associated with high mortality. A low concordance was found between the results of the different tools (AU)

[Prognostic value of assessment tools on elderly patients with chronic advanced disease and end of life, admitted to an intermediate care centre]. / Valor pronóstico de los instrumentos de evaluación de enfermedad avanzada y de final de vida en ancianos ingresados en un centro sociosanitario.

OBJECTIVE: To apply 3advanced chronic disease evaluation tools in elderly patients admitted to an intermediate and long-term care centre, and evaluate its relationship with mortality. METHODS: The NECPAL tool, PROFUND prognostic index, and Charlson comorbidity index were applied to 87 patients. RESULTS: The NECPAL tool identified 31 patients (35.6%) in need of palliative care, and according to the PROFUND index, 45 (54.7%) had high/very high risk of mortality (≥7 points), and according to Charlson index, 31 (35.6%) had high comorbidity (≥4 points). Of the NECPAL positive patients, 80.5% had a PROFUND index score ≥7, and 48.3% a Charlson index ≥ 4. These percentages were 34.4% and 28.5% in negative NECPAL patients (P<.001 and P≤.06, respectively). Correlations between the 3tools: quantitative (Spearman) number of responses in NECPAL with PROFUND (r=.57; P<.001); with Charlson (r=.214; P<.047) and between PROFUND and Charlson (r=.157; P=.148). Qualitative (kappa) NECPAL (positive/negative) with PROFUND (cut-off 6/7) (0.40; P<.001), and Charlson (cut-off 3/4) (0.19; P=.080) and between PROFUND and Charlson (0.08; P=.399). Mortality prediction (area under the curve): NECPAL 3 months 0.81 (95% CI: 0.62-1.00); 6 months 0.71 (95% CI: 0.53-0.89) and 12 months 0.67 (95% CI: 0.52-0.82). PROFUND 3 months 0.71 (95% CI: 0.50-0.91); 6 months 0.73 (95% CI: 0.58-0.87), and 12 months 0.69 (95% CI: 0.57-0.81). Charlson 3 months 0.72 (95% CI: 0.52-0.91); 6 months 0.62 (95% CI: 0.45-0.80), and 12 months 0.64 (95% CI: 0.50-0.78). CONCLUSIONS: The 3tools were significantly associated with high mortality. A low concordance was found between the results of the different tools.

A Basal Tone of 2-Arachidonoylglycerol Contributes to Early Oligodendrocyte Progenitor Proliferation by Activating Phosphatidylinositol 3-Kinase (PI3K)/AKT and the Mammalian Target of Rapamycin (MTOR) Pathways.

A basal tone of the endocannabinoid 2-arachidonoylglycerol (2-AG) enhances late oligodendrocyte progenitor cell (OPC) differentiation. Here, we investigated whether endogenous 2-AG may also promote OPC proliferation in earlier stages. We found that the blockade of 2-AG synthesizing enzymes, sn-1-diacylglycerol lipases α and ß (DAGLs), with RHC-80267 or the antagonism of either CB1 or CB2 cannabinoid receptors with AM281 and AM630, respectively, impaired early OPC proliferation stimulated by platelet-derived growth factor (PDGF-AA) and basic fibroblast growth factor (bFGF). On the contrary, increasing the levels of endogenous 2-AG by blocking the degradative enzyme monoacylglycerol lipase (MAGL) with JZL-184, significantly increased OPC proliferation as did agonists of cannabinoid receptor CB1 (ACEA), CB2 (JWH133) or both (HU-210). To elucidate signaling pathways underlying OPC proliferation, we studied the involvement of phosphatidylinositol 3-kinase (PI3K)/Akt and its downstream target mammalian target of rapamycin (mTOR). We show that phosphorylation of Akt and mTOR is required for OPC proliferation stimulated by growth factors (PDGF-AA and bFGF) or by CB1/CB2 agonists (ACEA/JWH133), since it was strongly decreased after LY294002 or rapamycin treatment. In line with this, blockade of CB1 (AM281), CB2 (AM630) or DAGLs (RHC-80267), decreased phosphorylation of Akt, mTOR and 4E-BP1, diminished cyclin E-cdk2 complex association and increased p27(kip1) levels. Our data suggest that proliferation of early OPCs stimulated by PDGF-AA and bFGF depends on the tonic activation of cannabinoid receptors by endogenous 2-AG and provide further evidence on the role of endocannabinoids in oligodendrocyte development, being important for the maintenance and self-renewal of the OPCs. The results highlight the therapeutic potential of the endocannabinoid signaling in the emerging field of brain repair.

Modeling and partial least squares approaches in OODA.

This is a discussion of the following paper: "Overview of object oriented data analysis" by J. Steve Marron and Andrés M. Alonso.

The constitutive production of the endocannabinoid 2-arachidonoylglycerol participates in oligodendrocyte differentiation.

Endocannabinoids have recently emerged as instructive cues in the developing central nervous system, and, based on the expression of their receptors, we identified oligodendrocytes as potential targets of these molecules. Here, we show that the enzymes responsible for the synthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG), diacylglycerol lipase alpha (DAGLα) and beta (DAGLß), and degradation, monoacylglycerol lipase (MAGL), can be found in oligodendrocytes at different developmental stages. Moreover, cultured oligodendrocyte progenitor cells (OPCs) express DAGLα and ß abundantly, resulting in the stronger production of 2-AG than in differentiated oligodendrocytes. The opposite is observed with MAGL. CB1 and CB2 receptor antagonists (SR141716 and AM630) impaired OPC differentiation into mature oligodendrocytes and likewise, inhibiting DAGL activity with RHC-80267 or tetrahydrolipstatin also blocked oligodendrocyte maturation, an effect reversed by the addition of exogenous 2-AG. Likewise, 2-AG synthesis disruption using specific siRNAs against DAGLα and DAGLß significantly reduced myelin protein expression in vitro, whereas a pharmacological gain-of-function approach by using cannabinoid agonists or MAGL inhibition had the opposite effects. ERK/MAPK pathway is implicated in oligodendrocyte differentiation because PD98059, an inhibitor of MEK1, abrogated oligodendrocyte maturation. The cannabinoid receptor antagonists and RHC-80267 all diminished basal ERK1/2 phosphorylation, effects that were partially reversed by the addition of 2-AG. Overall, our data suggest a novel role of endocannabinoids in oligodendrocyte differentiation such that constitutive release of 2-AG activates cannabinoid receptors in an autocrine/paracrine way in OPCs, stimulating the ERK/MAPK signaling pathway.