Measurement of thoraco-abdominal synchrony using respiratory inductance plethysmography: technical aspects and a proposal to overcome its limitations.

BACKGROUND: Thoraco-abdominal asynchrony (TAA) is usually assessed by respiratory inductance plethysmography. The main parameter used for its assessment is the calculation of the phase angle based on Lissajous plots. However, there are some mathematical limitations to its use. RESEARCH DESIGN AND METHODS: Sequences of five breaths were selected from a) normal subjects, b) COPD patients, both at rest and during exercise, and c) patients with obstructive apnea syndrome. Automated analysis was performed calculating phase angle, loop rotation (clockwise or counterclockwise), global phase delay and loop area. TAA severity was estimated quantitatively and in subgroups. RESULTS: 2290 cycles were analyzed (55% clockwise rotation). Phase angle ranged from -86.90 to + 88.4 degrees, while global phase delay ranged from -179.75 to + 178.54. Despite a good correlation with global phase delay (p < 0.01, ANOVA test), phase angle and loop area were not able to correctly classify breaths with severe deviation and paradoxical movements (p=ns, Bonferroni post hoc test). CONCLUSIONS: Global phase delay covers the whole spectrum of TAA situations in a single value. It may be a relevant parameter for diagnosis and follow-up of clinical conditions leading to TAA. CLINICAL TRIAL REGISTRATION: The trial from which the traces were obtained was registered at ClinicalTrials.gov ;(identifier: NCT04597606).

Predictors of mental health in healthcare workers during the COVID-19 pandemic: The role of experiential avoidance, emotion regulation and resilience.

AIMS: This study explores the mediational role of resilience, experiential avoidance and emotion regulation in the levels of anxiety, depression and posttraumatic stress disorder (PTSD) of healthcare workers during the COVID-19 pandemic. Additionally, we explored the association of such levels with personal and professional variables. DESIGN: Cross-sectional study. METHODS: Healthcare professionals working in Spain (N = 786) were recruited following a snowball approach in November and December 2021. Resilience, emotion regulation, experiential avoidance, depression, anxiety, PTSD and work-related variables were measured. Mean differences and correlations were computed, and a path analysis with latent variables (PALV) model was tested. RESULTS: In total, 18.8% of the sample scored above the cut-off score for depression, 24.6% for anxiety and 36.4% for PTSD. Higher resilience and lower experiential avoidance and expression suppression were correlated with better mental health. The PALV model explained 42%-53% of mental health outcomes. Experiential avoidance showed the greatest explanatory power and mediated the impact that stressors had on mental health. Some work-related variables correlated with greater psychological impact. These factors encompassed being a nurse, feeling that their job remained stressful and had not yet returned to its pre-pandemic state and having interacted with individuals facing economic difficulties due to the pandemic, and those who had lost their lives to COVID-19. CONCLUSION: Healthcare workers showed high levels of psychological impact during the COVID-19 pandemic. Such impact was predicted from some work-stress variables and the reliance on maladaptive strategies such as experiential avoidance and expressive suppression. IMPACT: Training healthcare professionals to use coping strategies incompatible with experiential avoidance may improve their mental health. Additionally, better working conditions are fundamental for reducing the impact of critical situations on healthcare workers' mental health. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Analysis of Gut Characteristics and Microbiota Changes with Maternal Supplementation in a Neural Tube Defect Mouse Model.

Adequate nutrient supply is crucial for the proper development of the embryo. Although nutrient supply is determined by maternal diet, the gut microbiota also influences nutrient availability. While currently there is no cure for neural tube defects (NTDs), their prevention is largely amenable to maternal folic acid and inositol supplementation. The gut microbiota also contributes to the production of these nutrients, which are absorbed by the host, but its role in this context remains largely unexplored. In this study, we performed a functional and morphological analysis of the intestinal tract of loop-tail mice (Vangl2 mutants), a mouse model of folate/inositol-resistant NTDs. In addition, we investigated the changes in gut microbiota using 16S rRNA gene sequencing regarding (1) the host genotype; (2) the sample source for metagenomics analysis; (3) the pregnancy status in the gestational window of neural tube closure; (4) folic acid and (5) D-chiro-inositol supplementation. We observed that Vangl2+/Lp mice showed no apparent changes in gastrointestinal transit time or fecal output, yet exhibited increased intestinal length and cecal weight and gut dysbiosis. Moreover, our results showed that the mice supplemented with folic acid and D-chiro-inositol had significant changes in their microbiota composition, which are changes that could have implications for nutrient absorption.

The loop-tail mouse model displays open and closed caudal neural tube defects.

Neural tube defects (NTDs) are the second most common cause of congenital malformations and are often studied in animal models. Loop-tail (Lp) mice carry a mutation in the Vangl2 gene, a member of the Wnt-planar cell polarity pathway. In Vangl2+/Lp embryos, the mutation induces a failure in the completion of caudal neural tube closure, but only a small percentage of embryos develop open spina bifida. Here, we show that the majority of Vangl2+/Lp embryos developed caudal closed NTDs and presented cellular aggregates that may facilitate the sealing of these defects. The cellular aggregates expressed neural crest cell markers and, using these as a readout, we describe a systematic method to assess the severity of the neural tube dorsal fusion failure. We observed that this defect worsened in combination with other NTD mutants, Daam1 and Grhl3. Besides, we found that in Vangl2+/Lp embryos, these NTDs were resistant to maternal folic acid and inositol supplementation. Loop-tail mice provide a useful model for research on the molecular interactions involved in the development of open and closed NTDs and for the design of prevention strategies for these diseases.

Report on the FEBS-IUBMB-ENABLE 1st International Molecular Biosciences PhD and Postdoc Conference.

The FEBS-IUBMB-ENABLE 1st International Molecular Biosciences PhD and Postdoc Conference was held in Seville, Spain, from the 16-18th of November 2022. Nearly 300 participants from all over the globe were welcomed by the host institution, the Institute of Biomedicine of Seville (IBiS). Following the theme "The perfect tandem: How technology expands the frontiers of biomedicine", the Scientific Symposium of the conference hosted eight world-renowned keynote speakers who presented their work in one of the four sessions: Innovation, Basic Research, Translational and Clinical Research, and Computational Biology and Artificial Intelligence. Participants had the chance to present their research to their peers: more than 200 posters were presented during the dedicated poster sessions and 19 selected PhD students and postdocs presented their work as short talks. The Career Day featured a wide range of workshops fully devoted to trainees' professional development, as well as a job fair and career chats with professionals to discuss future perspectives. Besides, several outreach activities were organised before and during the conference to engage with the general public and bring science closer to society. The success of this conference will be followed by the next FEBS-IUBMB-ENABLE conferences in Cologne, Germany, in 2023 and Singapore in 2024.

Effectiveness of trauma-informed care interventions at the organizational level: A systematic review.

Due to the recognition of the high prevalence and widespread effects of trauma, trauma-informed care (TIC) framework has emerged to address its impact and prevent retraumatization in the systems of care. Since organizational support has been identified as crucial in TIC implementation and sustainability, this systematic review assessed the status quo of TIC interventions which explicitly incorporate an organizational component. Our search yielded 880 articles, and 15 met the inclusion criteria. All the studies were carried out in the United States, more than half in mental health and Child Welfare Services, through longitudinal designs with no randomization or control group. All the studies utilized one to six organizational components, the most frequent related to presence of a defined leadership, procedures against retraumatization and provision of strength-based services. A wide variety of measures were used to assess the effectiveness of TIC interventions, with staff perceptions and safety management indicators being the most frequently used. In summary, the review indicates a positive trend in relation to the effectiveness of the interventions included in the study, with an improved functioning of beneficiaries, enhanced accessibility, and quality of services. However, the low quality and high heterogeneity of the studies make it difficult to draw conclusions with certainty. Therefore, the primary endeavor in TIC research is to provide more solid evidence. Partnerships between academic and community stakeholders will be of high value in this process. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Does the Efficacy of High Intensity Ventilation in Stable COPD Depend on the Ventilator Model? A Bench-to-Bedside Study.

PURPOSE: The European Task Force for chronic non-invasive ventilation in stable COPD recommends the use of high pressure-support (PS) level to maximize the decrease in PaCO2. It is possible that the ventilator model can influence the need for higher or lower pressure levels. RESEARCH QUESTION: To determine the differences between ventilators in a bench model with an increased inspiratory demand; and to compare the degree of muscular unloading measured by parasternal electromyogram (EMGpara) provided by the different ventilators in real patients with stable COPD. PATIENTS AND METHODS: Bench: four levels of increasing progressive effort were programmed. The response of nine ventilators to four levels of PS and EPAP of 5 cm H2O was studied. The pressure-time product was determined at 300 and 500 msec (PTP 300/500). CLINICAL STUDY: The ventilators were divided into two groups, based on the result of the bench test. Severe COPD patients with non-invasive ventilation (NIV) were studied, randomly comparing the performance of one ventilator from each group. Muscle unloading was measured by the decrease in EMGpara from its baseline value. RESULTS: There were significant differences in PTP 300 and PTP 500 in the bench study. Based on these results, home ventilators were classified into two groups; group 1 included four models with higher PTP 300. Ten COPD patients were recruited for the clinical study. Group 1 ventilators showed greater muscle unloading at the same PS than group 2. CONCLUSION: The scale of pressure support in NIV for high intensity ventilation may be influenced by the ventilator model. CLINICAL TRIALSGOV: NCT03373175.

A bench-to-bedside study about trigger asynchronies induced by the introduction of external gas into the non-invasive mechanical ventilation circuit.

Treatments that require the introduction of external gas into the non-invasive ventilation (NIV) circuit, such as aerosol and oxygen therapy, may influence the performance of the ventilator trigger system. The aim of the study was to determine the presence and type of asynchronies induced by external gas in the NIV circuit in a bench model and in a group of patients undergoing chronic NIV. Bench study: Four ventilators (one with two different trigger design types) and three gas sources (continuous flow at 4 and 9 l/min and pulsatile flow at 9 l/min) were selected in an active simulator model. The sensitivity of the trigger, the gas introduction position, the ventilatory pattern and the level of effort were also modified. The same ventilators and gas conditions were used in patients undergoing chronic NIV. Bench: the introduction of external gas caused asynchronies in 35.9% of cases (autotriggering 73%, ineffective effort 27%). Significant differences (p < 0.01) were detected according to the ventilator model and the gas source. In seven patients, the introduction of external gas induced asynchrony in 20.4% of situations (77% autotriggering). As in the bench study, there were differences in the occurrence of asynchronies depending on the ventilator model and gas source used. The introduction of external gas produces alterations in the ventilator trigger. These alterations are variable, and depend on the ventilator design and gas source. This phenomenon makes it advisable to monitor the patient at the start of treatment.

Nutraceuticals in the Prevention of Neonatal Hypoxia-Ischemia: A Comprehensive Review of their Neuroprotective Properties, Mechanisms of Action and Future Directions.

Neonatal hypoxia-ischemia (HI) is a brain injury caused by oxygen deprivation to the brain due to birth asphyxia or reduced cerebral blood perfusion, and it often leads to lifelong limiting sequelae such as cerebral palsy, seizures, or mental retardation. HI remains one of the leading causes of neonatal mortality and morbidity worldwide, and current therapies are limited. Hypothermia has been successful in reducing mortality and some disabilities, but it is only applied to a subset of newborns that meet strict inclusion criteria. Given the unpredictable nature of the obstetric complications that contribute to neonatal HI, prophylactic treatments that prevent, rather than rescue, HI brain injury are emerging as a therapeutic alternative. Nutraceuticals are natural compounds present in the diet or used as dietary supplements that have antioxidant, anti-inflammatory, or antiapoptotic properties. This review summarizes the preclinical in vivo studies, mostly conducted on rodent models, that have investigated the neuroprotective properties of nutraceuticals in preventing and reducing HI-induced brain damage and cognitive impairments. The natural products reviewed include polyphenols, omega-3 fatty acids, vitamins, plant-derived compounds (tanshinones, sulforaphane, and capsaicin), and endogenous compounds (melatonin, carnitine, creatine, and lactate). These nutraceuticals were administered before the damage occurred, either to the mothers as a dietary supplement during pregnancy and/or lactation or to the pups prior to HI induction. To date, very few of these nutritional interventions have been investigated in humans, but we refer to those that have been successful in reducing ischemic stroke in adults. Overall, there is a robust body of preclinical evidence that supports the neuroprotective properties of nutraceuticals, and these may represent a safe and inexpensive nutritional strategy for the prevention of neonatal HI encephalopathy.

Expression and Roles of Teneurins in Zebrafish.

The teneurins, also known as Ten-m/Odz, are highly conserved type II transmembrane glycoproteins widely expressed throughout the nervous system. Functioning as dimers, these large cell-surface adhesion proteins play a key role in regulating neurodevelopmental processes such as axon targeting, synaptogenesis and neuronal wiring. Synaptic specificity is driven by molecular interactions, which can occur either in a trans-homophilic manner between teneurins or through a trans-heterophilic interaction across the synaptic cleft between teneurins and other cell-adhesion molecules, such as latrophilins. The significance of teneurins interactions during development is reflected in the widespread expression pattern of the four existing paralogs across interconnected regions of the nervous system, which we demonstrate here via in situ hybridization and the generation of transgenic BAC reporter lines in zebrafish. Focusing on the visual system, we will also highlight the recent developments that have been made in furthering our understanding of teneurin interactions and their functionality, including the instructive role of teneurin-3 in specifying the functional wiring of distinct amacrine and retinal ganglion cells in the vertebrate visual system underlying a particular functionality. Based on the distinct expression pattern of all teneurins in different retinal cells, it is conceivable that the combination of different teneurins is crucial for the generation of discrete visual circuits. Finally, mutations in all four human teneurin genes have been linked to several types of neurodevelopmental disorders. The opportunity therefore arises that findings about the roles of zebrafish teneurins or their orthologs in other species shed light on the molecular mechanisms in the etiology of such human disorders.

Differential Free Intracellular Calcium Release by Class II Antiarrhythmics in Cancer Cell Lines.

Class II antiarrhythmics or ß-blockers are antisympathetic nervous system agents that act by blocking ß-adrenoceptors. Despite their common clinical use, little is known about the effects of ß-blockers on free intracellular calcium (Ca2+ i), an important cytosolic second messenger and a key regulator of cell function. We investigated the role of four chemical analogs, commonly prescribed ß-blockers (atenolol, metoprolol, propranolol, and sotalol), on Ca2+ i release and whole-cell currents in mammalian cancer cells (PC3 prostate cancer and MCF7 breast cancer cell lines). We discovered that only propranolol activated free Ca2+ i release with distinct kinetics, whereas atenolol, metoprolol, and sotalol did not. The propranolol-induced Ca2+ i release was significantly inhibited by the chelation of extracellular calcium with ethylene glycol tetraacetic acid (EGTA) and by dantrolene, an inhibitor of the endoplasmic reticulum (ER) ryanodine receptor channels, and it was completely abolished by 2-aminoethoxydiphenyl borate, an inhibitor of the ER inositol-1,4,5-trisphosphate (IP3) receptor channels. Exhaustion of ER stores with 4-chloro-m-cresol, a ryanodine receptor activator, or thapsigargin, a sarco/ER Ca2+ ATPase inhibitor, precluded the propranolol-induced Ca2+ i release. Finally, preincubation of cells with sotalol or timolol, nonselective blockers of ß-adrenoceptors, also reduced the Ca2+ i release activated by propranolol. Our results show that different ß-blockers have differential effects on whole-cell currents and free Ca2+ i release and that propranolol activates store-operated Ca2+ i release via a mechanism that involves calcium-induced calcium release and putative downstream transducers such as IP3 The differential action of class II antiarrhythmics on Ca2+ i release may have implications on the pharmacology of these drugs.

Targeting TAO Kinases Using a New Inhibitor Compound Delays Mitosis and Induces Mitotic Cell Death in Centrosome Amplified Breast Cancer Cells.

Thousand-and-one amino acid kinases (TAOK) 1 and 2 are activated catalytically during mitosis and can contribute to mitotic cell rounding and spindle positioning. Here, we characterize a compound that inhibits TAOK1 and TAOK2 activity with IC50 values of 11 to 15 nmol/L, is ATP-competitive, and targets these kinases selectively. TAOK inhibition or depletion in centrosome-amplified SKBR3 or BT549 breast cancer cell models increases the mitotic population, the percentages of mitotic cells displaying amplified centrosomes and multipolar spindles, induces cell death, and inhibits cell growth. In contrast, nontumorigenic and dividing bipolar MCF-10A breast cells appear less dependent on TAOK activity and can complete mitosis and proliferate in the presence of the TAOK inhibitor. We demonstrate that TAOK1 and TAOK2 localize to the cytoplasm and centrosomes respectively during mitosis. Live cell imaging shows that the TAOK inhibitor prolongs the duration of mitosis in SKBR3 cells, increases mitotic cell death, and reduces the percentages of cells exiting mitosis, whereas MCF-10A cells continue to divide and proliferate. Over 80% of breast cancer tissues display supernumerary centrosomes, and tumor cells frequently cluster extra centrosomes to avoid multipolar mitoses and associated cell death. Consequently, drugs that stimulate centrosome declustering and induce multipolarity are likely to target dividing centrosome-amplified cancer cells preferentially, while sparing normal bipolar cells. Our results demonstrate that TAOK inhibition can enhance centrosome declustering and mitotic catastrophe in cancer cells, and these proteins may therefore offer novel therapeutic targets suitable for drug inhibition and the potential treatment of breast cancers, where supernumerary centrosomes occur. Mol Cancer Ther; 16(11); 2410-21. ©2017 AACR.