Diastolic Mitral Regurgitation as a Rare Cause of Acute Respiratory Failure Following Complete Atrioventricular Block.

A 77-year-old male presented to the emergency department with dyspnea. A third-degree atrioventricular block was present in the electrocardiogram and an echocardiography showed a moderate mitral regurgitation with a diastolic functional insufficiency. Hemodynamic variations were assessed in the context of heart rhythm disturbances. (Level of Difficulty: Intermediate.).

Cross education is modulated by set configuration in knee extension exercise.

OBJECTIVES: The main aim of this study was to determine the effects of set configuration during five weeks of unilateral knee extension resistance training on untrained knee extensors performance. METHODS: Thirty-five subjects were randomly assigned to traditional training (TTG; n=14), rest-redistribution (RRG; n=10) and control group (CON; n=11). TTG and RRG groups trained the dominant knee extensors twice a week with the 10-repetition maximum (RM) load. TTG performed four sets of eight repetitions with three min-rest between sets and RRG 32 repetitions with 17.4 seconds of rest between each one. Before and after interventions, anthropometry, muscle thickness (MT), pennation angle (PA), 1RM, number of repetitions with 10RM pretest load (N10RM), maximum propulsive power (MPP) and maximum voluntary isometric contraction (MVIC) were measured. RESULTS: 1RM of the untrained leg increased only in the TTG group (p<0.001, 10.3% compared with Pre-test). 1RM, MPP and N10RM increased in the trained leg in both TTG (p<0.001) and RRG (p<0.001). No changes occurred in MT or PA. CONCLUSIONS: These results suggest that, when it is not possible to perform bilateral exercises (e.g., leg injury), traditional set configurations should be recommended to improve maximal voluntary force in the untrained leg.

NRF2 Activation Reprograms Defects in Oxidative Metabolism to Restore Macrophage Function in Chronic Obstructive Pulmonary Disease.

Rationale: Chronic obstructive pulmonary disease (COPD) is a disease characterized by persistent airway inflammation and disordered macrophage function. The extent to which alterations in macrophage bioenergetics contribute to impaired antioxidant responses and disease pathogenesis has yet to be fully delineated. Objectives: Through the study of COPD alveolar macrophages (AMs) and peripheral monocyte-derived macrophages (MDMs), we sought to establish if intrinsic defects in core metabolic processes drive macrophage dysfunction and redox imbalance. Methods: AMs and MDMs from donors with COPD and healthy donors underwent functional, metabolic, and transcriptional profiling. Measurements and Main Results: We observed that AMs and MDMs from donors with COPD display a critical depletion in glycolytic- and mitochondrial respiration-derived energy reserves and an overreliance on glycolysis as a source for ATP, resulting in reduced energy status. Defects in oxidative metabolism extend to an impaired redox balance associated with defective expression of the NADPH-generating enzyme, ME1 (malic enzyme 1), a known target of the antioxidant transcription factor NRF2 (nuclear factor erythroid 2-related factor 2). Consequently, selective activation of NRF2 resets the COPD transcriptome, resulting in increased generation of TCA cycle intermediaries, improved energetic status, favorable redox balance, and recovery of macrophage function. Conclusions: In COPD, an inherent loss of metabolic plasticity leads to metabolic exhaustion and reduced redox capacity, which can be rescued by activation of the NRF2 pathway. Targeting these defects, via NRF2 augmentation, may therefore present an attractive therapeutic strategy for the treatment of the aberrant airway inflammation described in COPD.

Acute psychophysiological responses during exercise while using resistive respiratory devices: A systematic review.

Different studies have observed that respiratory muscle training (RMT) improve the endurance and strength of the respiratory muscles, having a positive impact on performance of endurance sports. Nevertheless, it remains to be clarified how to improve the efficiency of such training. The objective of this systematic review was to evaluate the acute physiological responses produced by training the respiratory muscles during exercise with flow resistive devices because such information may support us improve the efficiency of this type of training. A search in the Medline, Science Direct, Web of Science and Scopus databases was conducted, following the PRISMA guidelines. The methodological quality of the articles was assessed using the PEDro scale. Nineteen studies met the inclusion criteria and a total of 212 subjects were included in the studies. The RMT method used in all studies was flow resistive loading, whereas the constant load exercise was the most common type of exercise among the studies. The results obtained seem to indicate that the use of this type of training during exercise reduces the performance, the lactate (La-) values and the ventilation, whereas the end - tidal partial pressure of carbon dioxide (PCO2) is increased.

Hypoxia shapes the immune landscape in lung injury and promotes the persistence of inflammation.

Hypoxemia is a defining feature of acute respiratory distress syndrome (ARDS), an often-fatal complication of pulmonary or systemic inflammation, yet the resulting tissue hypoxia, and its impact on immune responses, is often neglected. In the present study, we have shown that ARDS patients were hypoxemic and monocytopenic within the first 48 h of ventilation. Monocytopenia was also observed in mouse models of hypoxic acute lung injury, in which hypoxemia drove the suppression of type I interferon signaling in the bone marrow. This impaired monopoiesis resulted in reduced accumulation of monocyte-derived macrophages and enhanced neutrophil-mediated inflammation in the lung. Administration of colony-stimulating factor 1 in mice with hypoxic lung injury rescued the monocytopenia, altered the phenotype of circulating monocytes, increased monocyte-derived macrophages in the lung and limited injury. Thus, tissue hypoxia altered the dynamics of the immune response to the detriment of the host and interventions to address the aberrant response offer new therapeutic strategies for ARDS.

Comparison of Physical Fitness Profiles Obtained before and during COVID-19 Pandemic in Two Independent Large Samples of Children and Adolescents: DAFIS Project.

COVID-19 pandemic restrictions might have negatively affected the health-related physical fitness of children and adolescents. The aim of this study was to contrast the body composition and physical fitness data of two independent samples of children and adolescents obtained from an online database (DAFIS project) before (n = 15,287) and during (n = 2101) the first academic year of the COVID-19 pandemic. The results revealed higher values for the body mass index (p = 0.002), waist circumference (p < 0.001), and waist to hip and waist to height ratios (p < 0.001) during than before the pandemic, particularly in the case of boys. On the other hand, lower muscular fitness was observed for girls during the pandemic. Quantitative and qualitative analysis did not detect relevant changes in cardiorespiratory fitness in children or adolescents (p > 0.05). Our data suggested that pandemic constraints might have affected body composition and muscular fitness of children and adolescents. These results might be of interest for designing specific interventions oriented toward counteracting the negative effects of pandemic restrictions on health-related physical fitness.

Neurocognitive and emotional status after one-year of mindfulness-based intervention in patients with relapsing-remitting multiple sclerosis.

Multiple sclerosis (MS) is the most common disabling neurological disease among young adults. The diagnosis of this disease usually leads to uncertainty, stress, and anxiety, which in turn can lead to negative outcomes. Consequently, the development of healthy lifestyle strategies can lead to better emotional management of perceived stress. Due to the importance of the patient's emotional response during the development and management of the disease and the repercussions of the cognitive deficits, the objective of this study is to develop a mindfulness-based intervention to provide to patients a tool for stress management. This study offers data on neuropsychological, functional and emotional outcomes in a sample of 30 patients with remitting relapsing form of MS after one year of intervention compared to 30 controls. We tested a model of intervention with a program of Mindfulness-Based Cognitive Therapy, based on an adapted Jon Kabat-Zinn's MBSR program. Results showed cognitive and emotional benefits after one year following this program. Discussion about the opportunities of these types of intervention in neurological diseases is provided in light of results obtained. This study represents pioneering research in MS and psychological treatment of this neurological autoimmune disease and it offers positive results of applying mindfulness-based intervention in this population.

Communication Styles and Attention Performance in Primary School Children.

Communication styles are the three communication patterns that result from merging the verbal elements of communication, the non-verbal elements and the paraverbal elements. The objective of this study was to test what effect different communication styles have on attention performance in primary school children. We administered the assertive behavior scale for children (CABS), the symbol digit modalities test (SDMT) and the d2 attention test to a sample of 77 participants of primary school. A statistically significant and proportional correlation was found between the assertive communication style and the total number of correct answers of the SDMT. We also found positive correlations between the assertive communication style and d2 attention test performance. Children with an assertive communication style have better attention performance than children with passive or aggressive communication styles.

Non-productive angiogenesis disassembles Aß plaque-associated blood vessels.

The human Alzheimer's disease (AD) brain accumulates angiogenic markers but paradoxically, the cerebral microvasculature is reduced around Aß plaques. Here we demonstrate that angiogenesis is started near Aß plaques in both AD mouse models and human AD samples. However, endothelial cells express the molecular signature of non-productive angiogenesis (NPA) and accumulate, around Aß plaques, a tip cell marker and IB4 reactive vascular anomalies with reduced NOTCH activity. Notably, NPA induction by endothelial loss of presenilin, whose mutations cause familial AD and which activity has been shown to decrease with age, produced a similar vascular phenotype in the absence of Aß pathology. We also show that Aß plaque-associated NPA locally disassembles blood vessels, leaving behind vascular scars, and that microglial phagocytosis contributes to the local loss of endothelial cells. These results define the role of NPA and microglia in local blood vessel disassembly and highlight the vascular component of presenilin loss of function in AD.

Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation.

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Similarly, pharmacologic miR-210 inhibition improved the survival of septic mice. Mechanistically, miR-210 induction in activated macrophages supported a switch toward a proinflammatory state by lessening mitochondria respiration in favor of glycolysis, partly achieved by downmodulating the iron-sulfur cluster assembly enzyme ISCU. In humans, augmented miR-210 levels in circulating monocytes correlated with the incidence of sepsis, while serum levels of monocyte/macrophage-derived miR-210 were associated with sepsis mortality. Together, our data identify miR-210 as a fine-tuning regulator of macrophage metabolism and inflammatory responses, suggesting miR-210-based therapeutic and diagnostic strategies.

Percentiles and Principal Component Analysis of Physical Fitness From a Big Sample of Children and Adolescents Aged 6-18 Years: The DAFIS Project.

Assessing physical fitness has emerged as a proxy of the health status of children and adolescents and therefore as relevant from a public health point of view. DAFIS is a project included in Plan Galicia Saudable (Healthy Galicia Plan) of the regional government of Galicia (Spain). DAFIS consists of an on-line software devoted to record the results of a standard physical fitness protocol carried out as a part of the physical education curriculum. The aims of this study were: to obtain normative values of physical fitness of the Galician school population evaluated in the DAFIS project, and to identify a reduced number of components and tests able to capture a significant amount of the variability in the physical fitness of children and adolescents. From an initial sample of 27784 records, 15287 cases (7543 males, 7744 females) were considered after filtering. Generalized Additive Models for Location, Scale and Shape were used for obtaining percentile curves and tables for each sex. Furthermore, a principal components analysis was performed, selecting the number of components by applying the Kaiser's rule and selecting a subset of variables considering the correlation between each variable and the components. Percentile curves and normative values are reported for each test and sex. Physical fitness was better in boys than in girls throughout age groups, except for flexibility that was consistently higher in girls. Two main components were detected throughout age groups: the first one representing body composition and partially cardiorespiratory fitness and the second one muscular fitness. For boys and girls, waist to height ratio had the highest correlations with the first component in four out of six age groups. The highest correlation with the second component, was most frequently observed for the handgrip test both in boys and girls (four out of six age groups). This study provides evidence about the utility of school community actions like DAFIS aimed to track the health-related fitness of children and adolescents. The results suggest that fat mass distribution (i.e., waist to height ratio and waist circumference) and muscular performance (mainly handgrip) concentrate a high proportion physical fitness variance.

Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis.

Neutrophils can function and survive in injured and infected tissues, where oxygen and metabolic substrates are limited. Using radioactive flux assays and LC-MS tracing with U-13C glucose, glutamine, and pyruvate, we observe that neutrophils require the generation of intracellular glycogen stores by gluconeogenesis and glycogenesis for effective survival and bacterial killing. These metabolic adaptations are dynamic, with net increases in glycogen stores observed following LPS challenge or altitude-induced hypoxia. Neutrophils from patients with chronic obstructive pulmonary disease have reduced glycogen cycling, resulting in impaired function. Metabolic specialization of neutrophils may therefore underpin disease pathology and allow selective therapeutic targeting.

Set Configuration in Strength Training Programs Modulates the Cross Education Phenomenon.

ABSTRACT: Fariñas, J, Mayo, X, Giraldez-García, MA, Carballeira, E, Fernandez-Del-Olmo, M, Rial-Vazquez, J, Kingsley, JD, and Iglesias-Soler, E. Set configuration in strength training programs modulates the cross education phenomenon. J Strength Cond Res 35(9): 2414-2420, 2021-This study aimed to compare the strength gains in the nontrained arm after 2 independent unilateral training programs differing in the set configuration. Thirty-five subjects were randomly assigned to 3 groups: traditional training (TT; n = 12), cluster training (CT; n = 11), or control (CON; n = 12). The experimental groups performed a 5-week training program of a unilateral biceps curl exercise with the dominant limb using the 10 repetition maximum (10RM) load. Traditional training performed 5 sets of 6 repetitions and 135 seconds of rest between sets. Cluster training completed 30 repetitions with 18.5 seconds of rest between each repetition. Anthropometry (ANT), muscle thickness (MT), 1RM, the number of repetitions with 10RM (n10RM), and isometric maximal voluntary contraction (MVC) were measured before and after the intervention. Regarding the nontrained arm, TT improved 1RM (7.3%, p < 0.001). No changes were observed in CT. Regarding the trained arm, TT improved 1RM (9.1%, p < 0.001), n10RM (p = 0.005), and MVC (p = 0.011), whereas CT only showed a trend for improvement of 1RM (3.4%, p = 0.052). These results suggest that when total volume and repetition-to-rest ratio are equated, a more fatiguing set configuration causes a higher effect on the non-trained limb.

Hypoxia compromises the mitochondrial metabolism of Alzheimer's disease microglia via HIF1.

Genetic Alzheimer's disease (AD) risk factors associate with reduced defensive amyloid ß plaque-associated microglia (AßAM), but the contribution of modifiable AD risk factors to microglial dysfunction is unknown. In AD mouse models, we observe concomitant activation of the hypoxia-inducible factor 1 (HIF1) pathway and transcription of mitochondrial-related genes in AßAM, and elongation of mitochondria, a cellular response to maintain aerobic respiration under low nutrient and oxygen conditions. Overactivation of HIF1 induces microglial quiescence in cellulo, with lower mitochondrial respiration and proliferation. In vivo, overstabilization of HIF1, either genetically or by exposure to systemic hypoxia, reduces AßAM clustering and proliferation and increases Aß neuropathology. In the human AD hippocampus, upregulation of HIF1α and HIF1 target genes correlates with reduced Aß plaque microglial coverage and an increase of Aß plaque-associated neuropathology. Thus, hypoxia (a modifiable AD risk factor) hijacks microglial mitochondrial metabolism and converges with genetic susceptibility to cause AD microglial dysfunction.

Individualized Characterization of the Distribution of Collagen Fibril Dispersion Using Optical Aberrations of the Cornea for Biomechanical Models.

Purpose: The spatial distribution of collagen fibril dispersion has a significant impact on both corneal biomechanical and optical behaviors. The goal of this study was to demonstrate a novel method to characterize collagen fibril dispersion using intraocular pressure (IOP)-induced changes in corneal optical aberrations for individualized finite-element (FE) modeling. Methods: The method was tested through both numerical simulations and ex vivo experiments. Inflation tests were simulated in FE models with three assumed patterns of collagen fibril dispersion and experimentally on three rhesus monkey corneas. Geometry, matrix stiffness, and the IOP-induced changes in wavefront aberrations were measured, and the collagen fibril dispersion was characterized. An individualized corneal model with customized collagen fibril dispersion was developed, and the estimated optical aberrations were compared with the measured data. Results: For the theoretical investigations, three assumed distributions of fibril dispersion were all successfully characterized. The estimated optical aberrations closely matched the measured data, with average root-mean-square (RMS) differences of 0.29, 0.24, and 0.10 µm for the three patterns, respectively. The overall features of the IOP-induced changes in optical aberrations were estimated for two ex vivo monkey corneas, with average RMS differences of 0.57 and 0.43 µm. Characterization of the fibril dispersion in the third cornea might have been affected by corneal hydration, resulting in an increased RMS difference, 0.8 µm. Conclusions: A more advanced corneal model with individualized distribution of collagen fibril dispersion can be developed and used to improve our ability to understand both biomechanical and optical behaviors of the cornea.

Semaphorin 3F signaling actively retains neutrophils at sites of inflammation.

Neutrophilic inflammation is central to disease pathogenesis, for example, in chronic obstructive pulmonary disease, yet the mechanisms that retain neutrophils within tissues remain poorly understood. With emerging evidence that axon guidance factors can regulate myeloid recruitment and that neutrophils can regulate expression of a class 3 semaphorin, SEMA3F, we investigated the role of SEMA3F in inflammatory cell retention within inflamed tissues. We observed that neutrophils upregulate SEMA3F in response to proinflammatory mediators and following neutrophil recruitment to the inflamed lung. In both zebrafish tail injury and murine acute lung injury models of neutrophilic inflammation, overexpression of SEMA3F delayed inflammation resolution with slower neutrophil migratory speeds and retention of neutrophils within the tissues. Conversely, constitutive loss of sema3f accelerated egress of neutrophils from the tail injury site in fish, whereas neutrophil-specific deletion of Sema3f in mice resulted in more rapid neutrophil transit through the airways, and significantly reduced time to resolution of the neutrophilic response. Study of filamentous-actin (F-actin) subsequently showed that SEMA3F-mediated retention is associated with F-actin disassembly. In conclusion, SEMA3F signaling actively regulates neutrophil retention within the injured tissues with consequences for neutrophil clearance and inflammation resolution.

Agreement in component size between preoperative measurement, navigation and final implant in total knee replacement.

BACKGROUND: One of the possible causes of dissatisfaction reported by many patients after total knee replacement (TKR) is the lack of agreement between component size and bone structure. To avoid this complication and facilitate the procedure, preoperative planning with digitized templates is recommended. Surgical navigation indicates the best position and the most adequate size of arthroplasty and may therefore replace preoperative radiographic measurement. The objective of the study was to check agreement between the sizes of TKR components measured before surgery with digitized templates, the size recommended by the navigation and sizes actually implanted. METHODS: In 103 patients scheduled for TKR, preoperative full-limb radiography was performed to measure the mechanical and anatomical axes of the limb, femur and tibia. The most adequate size of the femoral and tibial components was planned by superimposing digitized templates. The size recommended in navigation and the size of the finally implanted components were also recorded. RESULTS: A high level of agreement was found between the sizes of femoral and tibial components measured by X-rays and in navigation (0.750 and 0.772, respectively) (intraclass correlation and Cronbach's alpha). Agreement between the sizes recommended by X-rays and navigation and those finally implanted was 0.886 for the femur and 0.891 for the tibia. Agreement levels were not different in cases with prior deformities of limb axis. CONCLUSIONS: The high level of agreement found in component sizes between radiographic measurement with digitized templates and navigation suggests that preoperative X-ray measurement is not needed when navigation is used for placement of implants during TKR. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Computer-assisted surgery may avoid preoperative measurement with templates in TKR.

Wireless Computer-Supported Cooperative Work: A Pilot Experiment on Art and Brain⁻Computer Interfaces.

The present case study looked into the feasibility of using brain-computer interface (BCI) technology combined with computer-supported cooperative work (CSCW) in a wireless network. We had two objectives; first, to test the wireless BCI-based configuration and the practical use of this idea we assessed workload perception in participants located several kilometers apart taking part in the same drawing task. Second, we studied the cortical activation patterns of participants performing the drawing task with and without the BCI technology. Results showed higher mental workload perception and broader cortical activation (frontal-temporal-occipital) under BCI experimental conditions. This idea shows a possible application of BCI research in the social field, where two or more users could engage in a computer networking task using BCI technology over the internet. New research avenues for CSCW are discussed and possibilities for future research are given.