Dynamic characterization of a periodic microstructured flexural system with rotational inertia.

We consider the propagation of waves in a flexural medium composed of massless beams joining a periodic array of elements, elastically supported and possessing mass and rotational inertia. The dispersion properties of the system are determined and the influence and interplay between the dynamic parameters on the structure of the pass and stop bands are analysed in detail. We highlight the existence of three special dynamic regimes corresponding to a low stiffness in the supports and/or low rotational inertia of the masses; to a high stiffness and/or high rotational inertia regime; and to a transition one where dispersion degeneracies are encountered. In the low-frequency regime, a rigorous asymptotic analysis shows that the structure approximates a continuous Rayleigh beam on an elastic foundation. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

Flexural vibration systems with gyroscopic spinners.

In this paper, we study the spectral properties of a finite system of flexural elements connected by gyroscopic spinners. We determine how the eigenfrequencies and eigenmodes of the system depend on the gyricity of the spinners. In addition, we present a transient numerical simulation that shows how a gyroscopic spinner attached to the end of a hinged beam can be used as a 'stabilizer', reducing the displacements of the beam. We also discuss the dispersive properties of an infinite periodic system of beams with gyroscopic spinners at the junctions. In particular, we investigate how the band-gaps of the structure can be tuned by varying the gyricity of the spinners. This article is part of the theme issue 'Modelling of dynamic phenomena and localization in structured media (part 1)'.

The O-glycosylated ectodomain of FXYD5 impairs adhesion by disrupting cell-cell trans-dimerization of Na,K-ATPase ß1 subunits.

FXYD5 (also known as dysadherin), a regulatory subunit of the Na,K-ATPase, impairs intercellular adhesion by a poorly understood mechanism. Here, we determined whether FXYD5 disrupts the trans-dimerization of Na,K-ATPase molecules located in neighboring cells. Mutagenesis of the Na,K-ATPase ß1 subunit identified four conserved residues, including Y199, that are crucial for the intercellular Na,K-ATPase trans-dimerization and adhesion. Modulation of expression of FXYD5 or of the ß1 subunit with intact or mutated ß1-ß1 binding sites demonstrated that the anti-adhesive effect of FXYD5 depends on the presence of Y199 in the ß1 subunit. Immunodetection of the plasma membrane FXYD5 was prevented by the presence of O-glycans. Partial FXYD5 deglycosylation enabled antibody binding and showed that the protein level and the degree of O-glycosylation were greater in cancer than in normal cells. FXYD5-induced impairment of adhesion was abolished by both genetic and pharmacological inhibition of FXYD5 O-glycosylation. Therefore, the extracellular O-glycosylated domain of FXYD5 impairs adhesion by interfering with intercellular ß1-ß1 interactions, suggesting that the ratio between FXYD5 and α1-ß1 heterodimer determines whether the Na,K-ATPase acts as a positive or negative regulator of intercellular adhesion.

Clinical predictors of candidemia in medical non-neutropenic, non-ICU patients. The CaMed score.

INTRODUCTION: Candida species are the leading cause of invasive fungal infections in hospitalised patients and are the fourth most common isolates recovered from patients with bloodstream infection. Few data exist on risk factors for candidemia in non-ICU patients. We performed a population-based case-control study to evaluate the main predictors for candidemia in non-ICU patients. METHODS AND FINDINGS: We included all non-neutropenic, non-critically ill and non-surgical adult patients with candidemia between January 2010 and June 2014. Patients with positive, non-candidal blood culture obtained at the same day (±2 days) were selected as controls. Cases and controls were matched according to hospital ward and clinical characteristics. Risk factors for candidemia were identified through a logistic regression. We included 56 candidemic and 512 bacteriemic non-candidemic patients. Most of candidemic patients (52) had received antibiotics prior to candidemia. Among them, the 30-day mortality rate was 34% (19/56). Multivariate analysis identified male sex, prior use of steroids, prior use of antibiotics, total parenteral nutrition and urinary catheterisation as independent predictors of candidemia. To develop the CaMed score, we rounded up weights of different risk factors as follows; total parenteral nutrition (+2), prior antibiotic therapy (+5), each of the other risk factors (+1). A score ≥ 7 identified patients at high risk of candidemia (P < 0.001; RR 29.805; CI 95% 10.652-83.397; sensitivity 79.2, specificity 82.6%, Youden index 0,62). CONCLUSIONS: Our set of easy independent predictors of candidemia in non-neutropenic, non-ICU, non-surgical patients provide a rationale for early initiation of antifungals and could reduce candidemia-related mortality.

Phonological, lexical, and semantic errors produced by impairment at the output buffer in a Spanish aphasic patient.

We present a single case of a right-handed female patient, RH, who was categorized as suffering from conduction aphasia. She presented no articulatory problems during spontaneous speech but made a significant number of phonological paraphasias in naming and repetition tasks. The number of errors increased for long words and pseudowords. This pattern of results points to damage in the "Phonological Output Buffer" (POB) as the basis of this disorder. However, this patient did not make mistakes when reading words and pseudowords aloud, even when we introduced a delay between the presentation of the word and its production to test the working memory resources of the phonological buffer. Furthermore, the patient's ability to name objects, repeat words, and write to dictation improved with her degree of familiarity with the items. The damage could be situated at the point where phonemes are selected and ordered to produce words. We posit that the deficits observed in this patient, and the differences encountered between her performance and that of others described in the literature, in particular in reading tasks, can be explained by considering POB damage to be gradual in nature. According to this explanation, the performance of patients with damage to the POB will depend on the amount of information provided by the stimulus (word/nonword), the language particularities (regular/irregular), and the nature of the task demands (repetition, writing, naming, or reading).

Effect of aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing amino acids on Leishmania spp. chemotaxis.

In the sand-fly mid gut, Leishmania promastigotes are exposed to acute changes in nutrients, e.g. amino acids (AAs). These metabolites are the main energy sources for the parasite, crucial for its differentiation and motility. We analysed the migratory behaviour and morphological changes produced by aliphatic, monocarboxylic, dicarboxylic, heterocyclic and sulphur-containing AAs in Leishmania amazonensis and Leishmania braziliensis and demonstrated that L-methionine (10-12 m), L-tryptophan (10-11 m), L-glutamine and L-glutamic acid (10-6 m), induced positive chemotactic responses, while L-alanine (10-7 m), L-methionine (10-11 and 10-7 m), L-tryptophan (10-11 m), L-glutamine (10-12 m) and L-glutamic acid (10-9 m) induced negative chemotactic responses. L-proline and L-cysteine did not change the migratory potential of Leishmania. The flagellum length of L. braziliensis, but not of L. amazonensis, decreased when incubated in hyperosmotic conditions. However, chemo-repellent concentrations of L-alanine (Hypo-/hyper-osmotic conditions) and L-glutamic acid (hypo-osmotic conditions) decreased L. braziliensis flagellum length and L-methionine (10-11 m, hypo-/hyper-osmotic conditions) decreased L. amazonensis flagellum length. This chemotactic responsiveness suggests that Leishmania discriminate between slight concentration differences of small and structurally closely related molecules and indicates that besides their metabolic effects, AAs play key roles linked to sensory mechanisms that might determine the parasite's behaviour.

Novel concepts of acute lung injury and alveolar-capillary barrier dysfunction.

In this review we summarize recent major advances in our understanding on the molecular mechanisms, mediators, and biomarkers of acute lung injury (ALI) and alveolar-capillary barrier dysfunction, highlighting the role of immune cells, inflammatory and noninflammatory signaling events, mechanical noxae, and the affected cellular and molecular entities and functions. Furthermore, we address novel aspects of resolution and repair of ALI, as well as putative candidates for treatment of ALI, including pharmacological and cellular therapeutic means.

Impact of outdoor air pollution on severity and mortality in COVID-19 pneumonia.

The relationship between exposure to air pollution and the severity of coronavirus disease 2019 (COVID-19) pneumonia and other outcomes is poorly understood. Beyond age and comorbidity, risk factors for adverse outcomes including death have been poorly studied. The main objective of our study was to examine the relationship between exposure to outdoor air pollution and the risk of death in patients with COVID-19 pneumonia using individual-level data. The secondary objective was to investigate the impact of air pollutants on gas exchange and systemic inflammation in this disease. This cohort study included 1548 patients hospitalised for COVID-19 pneumonia between February and May 2020 in one of four hospitals. Local agencies supplied daily data on environmental air pollutants (PM10, PM2.5, O3, NO2, NO and NOX) and meteorological conditions (temperature and humidity) in the year before hospital admission (from January 2019 to December 2019). Daily exposure to pollution and meteorological conditions by individual postcode of residence was estimated using geospatial Bayesian generalised additive models. The influence of air pollution on pneumonia severity was studied using generalised additive models which included: age, sex, Charlson comorbidity index, hospital, average income, air temperature and humidity, and exposure to each pollutant. Additionally, generalised additive models were generated for exploring the effect of air pollution on C-reactive protein (CRP) level and SpO2/FiO2 at admission. According to our results, both risk of COVID-19 death and CRP level increased significantly with median exposure to PM10, NO2, NO and NOX, while higher exposure to NO2, NO and NOX was associated with lower SpO2/FiO2 ratios. In conclusion, after controlling for socioeconomic, demographic and health-related variables, we found evidence of a significant positive relationship between air pollution and mortality in patients hospitalised for COVID-19 pneumonia. Additionally, inflammation (CRP) and gas exchange (SpO2/FiO2) in these patients were significantly related to exposure to air pollution.

The Burden and Impacts of Mealtime Insulin from the Perspective of People with Diabetes.

INTRODUCTION: While there have been continued advances in insulin treatment for diabetes since the discovery of insulin 100 years ago, some unmet needs still remain, including those related to mealtime insulin (MTI). The objective of this study was to explore the impacts related to MTI and the relative burden of the impacts on people with diabetes. METHODS: This study was conducted across two phases, namely, a qualitative and quantitative phase. People with type 1 and 2 diabetes using MTI in the USA and UK were recruited for the study. The qualitative phase involved 30 interviews to explore the impacts associated with MTI. Based on the results of the qualitative phase, a list of impacts was developed to evaluate the importance of MTI impacts using best-worst scaling. RESULTS: A total of 30 participants completed interviews, and 336 completed the quantitative phase. Participants described a range of impacts associated with MTI, including psychological (72.0%), social (63.0%), work/school (53.8%), and sleep (51.7%). Impacts for the quantitative phase were categorized under the following domains: diabetes distress, diabetes management, work productivity, and social. The three most burdensome impacts were related to diabetes distress, but the diabetes management domain contributed more than diabetes distress to the relative burden. There were minor differences in the relative importance of impacts by diabetes type, diabetes duration, and experience with continuous glucose monitoring. CONCLUSION: This study confirms that people with diabetes using MTI still have an array of unmet needs, including those related to the management of their diabetes and the emotional distress of having diabetes. These findings may be useful for healthcare provider (HCP)-patient interactions to ensure HCPs are allowing patients an opportunity to discuss their experiences with MTI.

Megalin mediates transepithelial albumin clearance from the alveolar space of intact rabbit lungs.

The alveolo-capillary barrier is effectively impermeable to large solutes such as proteins. A hallmark of acute lung injury/acute respiratory distress syndrome is the accumulation of protein-rich oedema fluid in the distal airspaces. Excess protein must be cleared from the alveolar space for recovery; however, the mechanisms of protein clearance remain incompletely understood. In intact rabbit lungs 29.8 ± 2.2% of the radio-labelled alveolar albumin was transported to the vascular compartment at 37°C within 120 min, as assessed by real-time measurement of 125I-albumin clearance from the alveolar space. At 4°C or 22°C significantly lower albumin clearance (3.7 ± 0.4 or 16.2 ± 1.1%, respectively) was observed. Deposition of a 1000-fold molar excess of unlabelled albumin into the alveolar space or inhibition of cytoskeletal rearrangement or clathrin-dependent endocytosis largely inhibited the transport of 125I-albumin to the vasculature, while administration of unlabelled albumin to the vascular space had no effect on albumin clearance. Furthermore, albumin uptake capacity was measured as about 0.37 mg ml−1 in cultured rat lung epithelial monolayers, further highlighting the (patho)physiological relevance of active alveolar epithelial protein transport. Moreover, gene silencing and pharmacological inhibition of the multi-ligand receptor megalin resulted in significantly decreased albumin binding and uptake in monolayers of primary alveolar type II and type I-like and cultured lung epithelial cells. Our data indicate that clearance of albumin from the distal air spaces is facilitated by an active, high-capacity, megalin-mediated transport process across the alveolar epithelium. Further understanding of this mechanism is of clinical importance, since an inability to clear excess protein from the alveolar space is associated with poor outcome in patients with acute lung injury/acute respiratory distress syndrome.

A new perspective on diabetes distress using the type 2 diabetes distress assessment system (T2-DDAS): Prevalence and change over time.

AIMS: To establish cut-points and thresholds for elevated diabetes distress; document change over time; and define minimal clinically important differences (MCID) using the new Type 2 Diabetes Distress Assessment System (T2-DDAS). METHODS: A national sample of adults with type 2 diabetes completed the T2-DDAS CORE distress scale and the 7 T2-DDAS SOURCE distress scales at baseline and 6-months. Scores were computed separately for insulin- and non-insulin users. Spline regression models defined CORE cut-points and SEM formulas defined MCID. A rational "threshold" approach defined elevated SOURCE scores. RESULTS: 471 participants (205 insulin, 266 non-insulin) completed both assessments. Analyses yielded ≥2.0 as the cut-point for both elevated CORE and elevated SOURCE. Prevalence of elevated CORE was 61.8 % (69.9 % over 6 months). Elevated SOURCE scores varied from 30.6 % (Stigma/Shame) to 76.4 % (Management); 87.5 % indicated at least 1 elevated SOURCE score. Most (77.1 %) reported multiple elevated SOURCES. 81.8 % with elevated CORE distress at baseline remained elevated at 6 months. MCID analyses yielded +/- 0.25 as significant change. Few differences between insulin- and non-insulin users occurred. CONCLUSIONS: Elevated CORE distress is highly prevalent and persistent over time; most participants reported multiple SOURCES of distress. Findings highlight the need for comprehensive assessment of diabetes distress.

Genome size of two cebus species (primates: platyrrhini) with a fertile hybrid and their quantitative genomic differences.

Genome size or C-value is defined as the total amount of DNA contained within a haploid chromosome set and is regarded as a species-specific constant. Speciation among neotropical primates seems to be accompanied by marked quantitative changes in DNA content. A direct correlation between genome size and the presence of heterochromatin has also been proposed. In this work, we analyzed the genome of a female fertile hybrid between Cebus libidinosus and C. nigritus using interspecies comparative genomic hybridization (iCGH), in order to detect quantitative differences between the hybrid and the parental genomes. We also estimated the genome sizes of C. libidinosus and C. nigritus. Both species, considered subspecies of C. apella until 2001, have a highly homologous karyotype but are easily distinguishable at the chromosomal level due to the noncentromeric heterochromatin block on C. libidinosus chromosome 11. Our findings on C-value quantification support the species status for C. libidinosus and C. nigritus, each having a different genome size. The iCGH analysis of the hybrid revealed quantitative differences in comparison to both parental species. The hybrid genome contains a greater amount of DNA in the heterochromatic blocks related to those in the genomes of both parental species. In view of observations in previous and the present work, some hypotheses about genome dynamics of neotropical primates are proposed and discussed.

Chromosome painting in two genera of South American monkeys: species identification, conservation, and management.

Cytogenetic studies showed that a number of New World primate taxa, particularly the genera Alouatta, Aotus, and Callicebus, have highly derived karyotypes. Cytogenetics in these primates, at every level of analysis, has contributed to the recognition of species and revealed that their number was certainly underestimated by researchers relying solely on traditional morphological data. Further attention was drawn to Alouatta and Aotus because they are characterized by translocations of the Y chromosome to autosomes, generating multiple sex chromosome systems. Here we present a report on the hybridization of human chromosome-specific paints on metaphases from 4 individuals originally assigned to Alouatta caraya and 1 individual of Aotuslemurinus. This is only the third karyotype studied with chromosome painting out of more than 10 known karyomorphs in Aotus. The banded chromosomes matched those of karyotype II as defined by Ma et al. [1976a], and we were able to more precisely assign the origin of the sample to A. l. griseimembra. Our results on the Argentinean Alouatta caraya samples were generally comparable to the banding and hybridization pattern of previous studies of A. caraya including the presence of an X(1)X(1)X(2)X(2)/X(1)X(2)Y(1)Y(2) sex chromosome system. The karyotype of the Brazilian Alouatta sample labeled as A. caraya differs from the 3 Argentinean samples by at least 10 chromosome rearrangements. The diploid number, G banding, and hybridization pattern of this female cell line was almost identical to previous painting results on Alouatta guariba guariba. Therefore we must conclude that this cell line is actually from an A. guariba guariba individual. The contribution of cytogenetic tools in identifying species or in this case assigning individuals or cell lines to their precise taxonomic allocation is stressed. Gathering further molecular cytogenetic data on New World primates should be conservation and management priorities.

TRAF2 Is a Novel Ubiquitin E3 Ligase for the Na,K-ATPase ß-Subunit That Drives Alveolar Epithelial Dysfunction in Hypercapnia.

Several acute and chronic lung diseases are associated with alveolar hypoventilation leading to accumulation of CO2 (hypercapnia). The ß-subunit of the Na,K-ATPase plays a pivotal role in maintaining epithelial integrity by functioning as a cell adhesion molecule and regulating cell surface stability of the catalytic α-subunit of the transporter, thereby, maintaining optimal alveolar fluid balance. Here, we identified the E3 ubiquitin ligase for the Na,K-ATPase ß-subunit, which promoted polyubiquitination, subsequent endocytosis and proteasomal degradation of the protein upon exposure of alveolar epithelial cells to elevated CO2 levels, thus impairing alveolar integrity. Ubiquitination of the Na,K-ATPase ß-subunit required lysine 5 and 7 and mutating these residues (but not other lysines) prevented trafficking of Na,K-ATPase from the plasma membrane and stabilized the protein upon hypercapnia. Furthermore, ubiquitination of the Na,K-ATPase ß-subunit was dependent on prior phosphorylation at serine 11 by protein kinase C (PKC)-ζ. Using a protein microarray, we identified the tumor necrosis factor receptor-associated factor 2 (TRAF2) as the E3 ligase driving ubiquitination of the Na,K-ATPase ß-subunit upon hypercapnia. Of note, prevention of Na,K-ATPase ß-subunit ubiquitination was necessary and sufficient to restore the formation of cell-cell junctions under hypercapnic conditions. These results suggest that a hypercapnic environment in the lung may lead to persistent epithelial dysfunction in affected patients. As such, the identification of the E3 ligase for the Na,K-ATPase may provide a novel therapeutic target, to be employed in patients with acute or chronic hypercapnic respiratory failure, aiming to restore alveolar epithelial integrity.

Cebus paraguayanus and Cebus nigritus (Primates, Platyrrhini): a comparative genomic hybridization analysis.

Primate genomes show a great karyological variability while the DNA content variation is scarce. The biggest genome size occurs in Cercophitecus cephus (Catarrhini, Cercophitecidae) with 5.26 pg whereas the smallest one is described for Callicebus torquatus (Platyrrhini, Callithricidae) with 2.26 pg. Over the last 20 years different authors have been studying the Platyrrhini genomes on a chromosomal level. Among them, Cebus (Cebidae) being considered the most ancestral and conserved karyotype in relation to human karyotype has been extensively studied. Cebus genome sizes range from 3.40 to 3.98 pg. The species that inhabit Argentina, where they reach the most southern natural distribution, Cebus paraguayanus (CPA) and Cebus nigritus (CNI), have been extensively studied with classical cytogenetic comparisons focusing on banding pattern behavior. In the present study we performed comparative genomic hybridization (CGH) between these two closely related species with the aim of going a step further in the dissection of Cebus genomes. CGH evidenced that the DNA imbalances between them involved different genome regions, i.e. preferentially repetitive DNA in CPA and coding or very disperse DNA in CNI. Particularly, CNI showed species-specific DNA in more than 9 chromosomal pairs with a red/green (r/g) ratio ranging from 1.7 to 4, meaning that CNI presents at least twice as much DNA than CPA in those chromosomal segments. CPA showed species-specific DNA in the telomeric region of at least 3 chromosomal pairs with an r/g ratio of 0.5. They also showed a DNA gain in the chromosomal pairs with extracentromeric heterochromatin. Our findings modify the widespread idea of considering the heterochromatin proportion as the only difference between CPA and CNI. In Cebus then, the diversification process could be mediated by little changes in DNA content accompanied by a euchromatin-heterochromatin interaction although maintaining a minimum proportion like the one observed in CNI.

Clinical efficacy of fosfomycin combinations against a variety of gram-positive cocci.

INTRODUCTION: Over recent years we have witnessed an increase in the resistance of microorganisms to the available antimicrobials and a decrease in the number of new antimicrobials. Fosfomycin is a safe and cheap broad-spectrum antibiotic which has shown very promising results in combination therapy, mainly against gram-negative microorganisms. Little is known, however, about its clinical efficacy against gram-positive microorganisms. METHODS: We performed a retrospective review of all patients with severe gram-positive infections who received fosfomycin as part of their treatment from 2011 to 2017. We also performed in vitro time-kill assays to study the behaviour of fosfomycin with different antimicrobials against two strains of methicillin-resistant Staphylococcus aureus (MRSA) and two strains of methicillin-susceptible S. aureus (MSSA). RESULTS: Seventy-five patients were treated with different fosfomycin combinations. Among them, 61 (81%) were successfully treated. Daptomycin plus fosfomycin was the most effective combination. Overall, the treatment with fosfomycin was safe, and side effects were minor. There was only one major side effect that resolved after discontinuation of therapy. Time-kill studies demonstrated increased activity of fosfomycin combinations, with daptomycin-fosfomycin being the most active combination against both MRSA and MSSA strains. CONCLUSIONS: Our results suggest that antimicrobial combinations including fosfomycin are an alternative and effective approach for gram-positive infections.

Guidelines for seizure management in palliative care: Proposal for an updated clinical practice model based on a systematic literature review. / Guía para el manejo de las crisis epilépticas en cuidados paliativos: propuesta de un modelo actualizado de práctica clínica basado en una revisión sistemática de la literatura.

INTRODUCTION: Very little has been written on seizure management in palliative care (PC). Given this situation, and considering the forthcoming setting up of the Palliative Care Unit at our neurorehabilitation centre, the Clínica San Vicente, we decided to establish a series of guidelines on the use of antiepileptic drugs (AEDs) for handling seizures in PC. METHODS: We conducted a literature search in PubMed to identify articles, recent manuals, and clinical practice guidelines on seizure management in PC published by the most relevant scientific societies. RESULTS: Clinical practice guidelines are essential to identify patients eligible for PC, manage seizures adequately, and avoid unnecessary distress to these patients and their families. Given the profile of these patients, we recommend choosing AEDs with a low interaction potential and which can be administered by the parenteral route, preferably intravenously. Diazepam and midazolam appear to be the most suitable AEDs during the acute phase whereas levetiracetam, valproic acid, and lacosamide are recommended for refractory cases and long-term treatment. CONCLUSIONS: These guidelines provide general recommendations that must be adapted to each particular clinical case. Nevertheless, we will require further well-designed randomised controlled clinical trials including large samples of patients eligible for PC to draft a consensus document recommending adequate, rational, and effective use of AEDs, based on a high level of evidence, in this highly complex area of medical care.

[Current evidence on virtual reality and its potential usefulness in post-stroke neurorehabilitation]. / Evidencias actuales sobre la realidad virtual y su utilidad potencial en la neurorrehabilitación postictus.

INTRODUCTION: Virtual reality therapy (VRT) constitutes a powerful and motivating tool for stroke patients to actively participate in the process of neurorehabilitation, providing augmented performance feedback, with the aim of achieving better therapeutic results owing to the enhancing of neuroplasticity mechanisms. AIM: To report the most relevant data about the applications of VRT in the post-stroke neurorehabilitation. DEVELOPMENT: We conducted a PubMed search for articles, latest books, leading clinical practice guidelines, and scientific societies, regarding such applications. CONCLUSIONS: Different performed randomized clinical trials (RCT) show that VRT safely facilitates in a statistically significant way motor and functional recovery of upper limb, gait, balance, quality of life related to health, and activities of daily living, together with conventional therapy, but have no clearly demonstrated overall superiority to conventional therapy. In this regard, underlying specific mechanisms remain elusive at this stage. Future RCT should define the good responder stroke patient profile based on the VRT used in conjunction with conventional therapy, allowing the generation of neurorehabilitation approaches that combine a customized immersive VRT with the clinical experience of the therapists, to maximize the results. It is necessary to carry out well-designed RCT, including larger samples of appropriately selected stroke subjects, to draft a consensus document that allows recommending, with a greater level of evidence and on a widespread basis, the implementation of VRT as add-on therapy in post-stroke neurorehabilitation. As well as to determine if the beneficial effects are maintained in the long term and to clarify the most suitable treatment schedule.

TITLE: Evidencias actuales sobre la realidad virtual y su utilidad potencial en la neurorrehabilitación postictus.Introducción. La terapia con realidad virtual (TRV) constituye una herramienta poderosa que motiva a los pacientes con ictus a participar activamente en su neurorrehabilitación, y proporciona retroalimentación aumentada del rendimiento, con objeto de obtener mejores resultados terapéuticos gracias a la potenciación de los mecanismos de neuroplasticidad. Objetivo. Exponer los datos más relevantes sobre las aplicaciones de la TRV en la neurorrehabilitación postictus. Desarrollo. Búsqueda de artículos en PubMed, últimos libros y principales guías de práctica clínica y sociedades científicas publicados con respecto a dichas aplicaciones. Conclusiones. Los diferentes ensayos clínicos aleatorizados (ECA) realizados demuestran que la TRV facilita, de forma segura y estadísticamente significativa, la recuperación motora y funcional del miembro superior, la marcha, el equilibrio, la calidad de vida relacionada con la salud y las actividades de la vida diaria, junto con la terapia convencional, sin ser globalmente superior a la terapia convencional. Aún no se conocen los mecanismos específicos subyacentes. Los ECA futuros deberán definir el perfil de paciente respondedor según la TRV empleada, permitiendo generar enfoques de neurorrehabilitación que conjuguen una TRV personalizada inmersiva y la experiencia clínica de los terapeutas para maximizar los resultados. Son precisos ECA bien diseñados, incluyendo muestras amplias de pacientes adecuadamente seleccionados, para redactar un documento de consenso que permita recomendar, con un mayor nivel de evidencia y de forma generalizada, la implementación de la TRV como terapia complementaria en la neurorrehabilitación postictus, determinar si los efectos beneficiosos se mantienen a largo plazo y clarificar qué esquema de tratamiento es el más apropiado.

Beneficial Effects of Inspiratory Muscle Training Combined With Multicomponent Training in Elderly Active Women.

Purpose: This study aims to analyze changes in Maximum Inspiratory Pressure (MIP), lung function, cardiorespiratory fitness, and blood pressure, in 10 healthy active elderly women, following 7 weeks of inspiratory muscle training (IMT) combined with a multicomponent training program (MCTP). The association among these health parameters, their changes after training (deltas), and the influence of MIP at baseline (MIPpre) are also considered. Methods: IMT involved 30 inspirations at 50% of the MIP, twice daily, 7 days a week, while MCTP was 1 hr, twice a week. MIP, lung function (FVC, FEV1, FEV1/FVC, FEF25-75%, PEF), 6MWT, and blood pressure (SBP, DBP), jointly with body composition, were assessed before and after the intervention. Results: Seven weeks were enough to improved MIP (p = .019; d = 1.397), 6MWT (p = .012; d = .832), SBP (p = .003; d = 1.035) and DBP (p = .024; d = .848). Despite the high physical fitness (VO2 peak: M = 23.38, SD = 3.39 ml·min·Kg-1), MIPpre was low (M = 39.00, SD = 7.63 cmH2O) and displayed a significant negative correlation with ΔMIPpre-post (r = -.821; p < .004), showing that women who started the intervention with lower MIP achieved higher improvements in inspiratory muscle strength after training. Conclusions: No significant changes in spirometric parameters may signal that lung function is independent of early improvements in inspiratory muscles and cardiorespiratory fitness. Absence of correlation between physical fitness and respiratory outcomes suggests that being fit does not ensure cardiorespiratory health in active elderly women, so IMT might be beneficial and should supplement the MCTP in this population.