How neurotypical listeners recognize emotions expressed through vocal cues by speakers with high-functioning autism

Trials

Brain-derived neurotrophic factor (BDNF) is essential for antidepressant treatment of major depressive disorder (MDD). Our repeated studies suggest that DNA methylation of a specific CpG site in the promoter region of exon IV of the BDNF gene (CpG -87) might be predictive of the efficacy of monoaminergic antidepressants such as selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and others. This trial aims to evaluate whether knowing the biomarker is non-inferior to treatment-as-usual (TAU) regarding remission rates while exhibiting significantly fewer adverse events (AE). The BDNF trial is a prospective, randomized, rater-blinded diagnostic study conducted at five university hospitals in Germany. The study’s main hypothesis is that {1} knowing the methylation status of CpG -87 is non-inferior to not knowing it with respect to the remission rate while it significantly reduces the AE rate in patients experiencing at least one AE. The baseline assessment will occur upon hospitalization and a follow-up assessment on day 49 (± 3). A telephone follow-up will be conducted on day 70 (± 3). A total of 256 patients will be recruited, and methylation will be evaluated in all participants. They will be randomly assigned to either the marker or the TAU group. In the marker group, the methylation results will be shared with both the patient and their treating physician. In the TAU group, neither the patients nor their treating physicians will receive the marker status. The primary endpoints include the rate of patients achieving remission on day 49 (± 3), defined as a score of ≤ 10 on the Hamilton Depression …

During the last 30 years, a large number of behavioral studies have investigated the effect of simultaneous exercise on cognitive functions The heterogeneity of the results has been attributed to different parameters, such as intensity or modality of physical activity, and the investigated cognitive processes. More recent methodological improvements have enabled to record electroencephalography (EEG) during physical exercise. EEG studies combining cognitive tasks with exercise have described predominantly detrimental effects on cognitive processes and EEG parameters. However, differences in the underlying rationale and the design of EEG versus behavioral studies make direct comparisons between both types of studies difficult. In this narrative review of dual-task experiments we evaluated behavioral and EEG studies and discuss possible explanations for the heterogeneity of results and for the discrepancy between behavioral and EEG studies. Furthermore, we provide a proposal for future EEG studies on simultaneous motion to be a useful complement to behavioral studies. A crucial factor might be to find for each cognitive function the motor activity that matches this function in terms of attentional focus. This hypothesis should be investigated systematically in future studies.

Frontiers in Neuroscience

IntroductionAuditory-motor interactions can support the preparation for expected sensory input. We investigated the periodic modulation of beta activity in the electroencephalogram to assess the role of active auditory-motor synchronization. Pre-stimulus beta activity (13–30 Hz) has been interpreted as a neural signature of the preparation for expected sensory input.MethodsIn the current study, participants silently counted frequency deviants in sequences of pure tones either during a physically inactive control condition or while pedaling on a cycling ergometer. Tones were presented either rhythmically (at 1 Hz) or arrhythmically with variable intervals. In addition to the pedaling conditions with rhythmic (auditory-motor synchronization, AMS) or arrhythmic stimulation, a self-generated stimulus condition was used in which tones were presented in sync with the participants’ spontaneous pedaling. This condition served to explore whether sensory predictions are driven primarily by the auditory or by the motor system.ResultsPre-stimulus beta power increased for rhythmic compared to arrhythmic stimulus presentation in both sitting and pedaling conditions but was strongest in the AMS condition. Furthermore, beta power in the AMS condition correlated with motor performance, i.e., the better participants synchronized with the rhythmic stimulus sequence, the higher was pre-stimulus beta power. Additionally, beta power was increased for the self-generated stimulus condition compared with arrhythmic pedaling, but there was no difference between the self-generated and the AMS condition.DiscussionThe current data pattern indicates that pre-stimulus …

Plos one

Extracorporeal Photopheresis (ECP) is a leukapheresis based treatment for Cutaneous T-Cell Lymphoma, which takes advantage of the cellular lethal effects of UVA light in combination with a photoactivated drug, 8-methoxypsoralen. 25% of patients treated with ECP do not respond to treatment, however the underlying mechanisms for this lack of response remain unknown. Platelets, a rich source of extracellular vesicles (EVs) and key mediators in thromboinflammatory oncological progression, as well as leukocytes, are both processed through ECP and are subsequently transfused back into the patient, delivering potent immunomodulation. The effect of exposing platelets and their EVs directly to Ultra Violet A light (UVA)/8-methoxypsoralen is currently unknown. Platelet-rich plasma (PRP) was isolated from healthy donors and exposed to UVA light and/or 8-methoxysporalen in vitro and platelet activation and aggregation was assessed. EV size and concentration were also characterised by Nanoparticle Tracking Analysis and Flow Cytometry. We found that UVA light and 8-methoxypsoralen treatment in vitro does not induce platelet aggregation or significantly alter levels of the platelet activation markers, soluble P-selectin or platelet factor 4, with circulating levels of small and large EV size and concentration remaining constant. Therefore, utilising the combination of UVA light and 8-methoxypsoralen used in ECP in vitro does not activate platelets or alter important circulating EVs. Further studies will be needed to validate if our observations are consistent in vivo.

Plos one

The motion of a single active particle in one dimension with quenched disorder under the external force is investigated. Within the tailored parameter range, anomalous diffusion that displays weak ergodicity breaking is observed, i.e., non-ergodic subdiffusion and non-ergodic superdiffusion. This non-ergodic anomalous diffusion is analyzed through the time-dependent probability distributions of the particle’s velocities and positions. Its origin is attributed to the relative weights of the locked state (predominant in the subdiffusion state) and running state (predominant in the superdiffusion state). These results may contribute to understanding the dynamical behavior of self-propelled particles in nature and the extraordinary response of nonlinear dynamics to the externally biased force.

Plos one

Rhodococcus equi pneumonia is an important cause of mortality in foals worldwide. Virulent equine isolates harbour an 80-85kb virulence plasmid encoding six virulence-associated proteins (Vaps). VapA, the main virulence factor of this intracellular pathogen, is known to be a cell surface protein that creates an intracellular niche for R. equi growth. In contrast, VapC, VapD and VapE are secreted into the intracellular milieu. Although these Vaps share very high degree of sequence identity in the C-terminal domain, the N-terminal domain (N-domain) of VapA is distinct. It has been proposed that this domain plays a role in VapA surface localization but no direct experimental data provides support to such hypothesis. In this work, we employed R. equi 103S harbouring an unmarked deletion of vapA (R. equi ΔvapA) as the genetic background to express C-terminal Strep-tagged Vap-derivatives integrated in the chromosome. The surface localization of these proteins was assessed by flow cytometry using the THE2122;-NWSHPQFEK Tag FITC-antibody. We show that VapA is the only cell surface Vap encoded in the virulence plasmid. We present compelling evidence for the role of the N-terminal domain of VapA on cell surface localization using fusion proteins in which the N-domain of VapD was exchanged with the N-terminus of VapA. Lastly, using an N-terminally Strep-tagged VapA, we found that the N-terminus of VapA is exposed to the extracellular environment. Given the lack of a lipobox in VapA and the exposure of the N-terminal Strep-tag, it is possible that VapA localization on the cell surface is mediated by interactions between the N-domain …

Plos one

We identified two different inherited mutations in KCNH2 gene, or human ether-a-go-go related gene (hERG), which are linked to Long QT Syndrome. The first mutation was in a 1-day-old infant, whereas the second was in a 14-year-old girl. The two KCNH2 mutations were transiently transfected into either human embryonic kidney (HEK) cells or human induced pluripotent stem-cell derived cardiomyocytes. We performed associated multiscale computer simulations to elucidate the arrhythmogenic potentials of the KCNH2 mutations. Genetic screening of the first and second index patients revealed a heterozygous missense mutation in KCNH2, resulting in an amino acid change (P632L) in the outer loop of the channel and substitution at position 428 from serine to proline (S428P), respectively. Heterologous expression of P632L and S428P into HEK cells produced no hERG current compared to the wild type (WT). Moreover, the co-transfection of WT and P632L yielded no hERG current; however, the co-transfection of WT and S428P yielded partial hERG current. Action potentials were prolonged in a complete or partial blockade of hERG current from computer simulations which was more severe in Purkinje than ventricular myocytes. Three dimensional simulations revealed a higher susceptibility to reentry in the presence of hERG current blockade. Our experimental findings suggest that both P632L and S428P mutations may impair the KCNH2 gene. The Purkinje cells exhibit a more severe phenotype than ventricular myocytes, and the hERG current blockade renders the ventricles an arrhythmogenic substrate from computer modeling.

Plos one

Study design Single-cohort longitudinal survey design. Objectives To identify what ongoing impact the COVID-19 pandemic has on functioning and health in individuals with SCI. Using the ICF model as a guide, outcome measures were chosen to explore potential constructs and aspects of health and functioning which may have been affected by regulations. Setting Online, Canada. Methods Participants provided demographic and clinical characteristics at baseline. They completed standardized online measures at three time points, each roughly one month apart (June, July, and August of 2020). The measures assessed mental health, resilience, boredom, social support, technology use, life space, and participation. Repeated measures ANOVAs were used to identify longitudinal changes for each measure. Results We collected data from 21 participants with SCI (mean age 54 years, 12 male). We found a large effect size for participation (η2 = 0.20), which increased over time. We also found medium effect sizes in both anxiety (η2 = 0.12) and social network usage (η2 = 0.12). Anxiety decreased over time and social networking usage fluctuated slightly but with an increase from time point one to time point two. Conclusion The results indicate that individuals with spinal cord injury appear to be staying relatively stable during the pandemic with improvements in a few key aspects, such as potentially increased participation and decreased anxiety. The results also suggest that it is important to continue fostering ways for individuals with spinal cord injury to stay connected, engaged, and informed.

Plos one

The popularity of martial arts in the present times has become apparent, therefore, it is necessary to explore martial artists’ preferences and the schools’ competitiveness. The purpose of this study was to assess martial artists’ preferences concerning the services offered by martial arts schools. Conjoint analysis was utilized to analyze the responses of fifty-five (55) martial artists based on the seven (7) martial arts schools’ attributes. The results showed that the type of martial arts was found to be the most important attribute (30.449%) followed by distance (27.970%), price range (22.706%), social environment (11.097%), class preference (5.080%), goal (1.562%), and schedule (1.135%). Furthermore, Muay Thai or Kickboxing was the most preferred martial art, Mixed Martial Arts (MMA) was the second priority, next was Taekwondo, then Karate, and finally Boxing. In addition, the martial artists’ preferred distance was less than 8 km, and a monthly training cost of 150,000 to 450,000 IDR (10 to 20 USD). Martial artists liked attending open classes, treated martial arts as a hobby, and favored attending classes once or twice weekly. With the lack of conjoint-related studies in the martial arts industry, the findings contributed to academicians and addressed issues of inadequate studies. Most importantly, the researchers presented managerial implications to leverage marketing techniques and develop the business operations of martial arts schools.

Plos one

Background Stunting and wasting are key public health problems in Ghana that are significantly linked with mortality and morbidity risk among children. However, information on their associated factors using nationally representative data is scanty in Ghana. This study investigated the influence of Infant and Young Child Feeding (IYCF) indicators, socio-demographic and economic related factors, and water and sanitation on stunting and wasting, using nationally representative data in Ghana. Methods This is a secondary data analysis of the most recent (2017/2018) Ghana Multi-Indicator Cluster Survey (MICS) datasets. The multi-indicator cluster survey is a national cross-sectional household survey with rich data on women of reproductive age and children under the age of five. The survey used a two-stage sampling method in the selection of respondents and a computer-assisted personal interviewing technique to administer structured questionnaires from October 2017 to January 2018. The present study involved 2529 mother-child pairs, with their children aged 6 to 23 months. We used the Complex Sample procedures in SPSS, adjusting for clustering and stratification effects. In a bivariate logistic regression, variables with P-values ≤ 0.05 were included in a backward multivariate logistic regression to identify the significant factors associated with stunting and wasting. Results The mean age of children was 14.32 ± 0.14 months, with slightly more being males (50.4%). About 12% and 16% of the children were wasted and stunted, respectively. There were 39.4%, 25.9%, and 13.7% of children who, respectively, satisfied the minimum meal …

Plos one

Wildlife conservation strategies focused on one season or population segment may fail to adequately protect populations, especially when a species’ habitat preferences vary among seasons, age-classes, geographic regions, or other factors. Conservation of golden eagles (Aquila chrysaetos) is an example of such a complex scenario, in which the distribution, habitat use, and migratory strategies of this species of conservation concern vary by age-class, reproductive status, region, and season. Nonetheless, research aimed at mapping priority use areas to inform management of golden eagles in western North America has typically focused on territory-holding adults during the breeding period, largely to the exclusion of other seasons and life-history groups. To support population-wide conservation planning across the full annual cycle for golden eagles, we developed a distribution model for individuals in a season not typically evaluated–winter–and in an area of the interior western U.S. that is a high priority for conservation of the species. We used a large GPS-telemetry dataset and library of environmental variables to develop a machine-learning model to predict spatial variation in the relative intensity of use by golden eagles during winter in Wyoming, USA, and surrounding ecoregions. Based on a rigorous series of evaluations including cross-validation, withheld and independent data, our winter-season model accurately predicted spatial variation in intensity of use by multiple age- and life-history groups of eagles not associated with nesting territories (i.e., all age classes of long-distance migrants, and resident non-adults and adult “floaters …

Plos one

This paper investigates models of working memory in which memory traces evolve according to stochastic attractor dynamics. These models have previously been shown to account for response-biases that are manifest across multiple trials of a visual working memory task. Here we adapt this approach by making the stable fixed points correspond to the multiple items to be remembered within a single-trial, in accordance with standard dynamical perspectives of memory, and find evidence that this multi-item model can provide a better account of behavioural data from continuous-report tasks. Additionally, the multi-item model proposes a simple mechanism by which swap-errors arise: memory traces diffuse away from their initial state and are captured by the attractors of other items. Swap-error curves reveal the evolution of this process as a continuous function of time throughout the maintenance interval and can be inferred from experimental data. Consistent with previous findings, we find that empirical memory performance is not well characterised by a purely-diffusive process but rather by a stochastic process that also embodies error-correcting dynamics.

Plos one

Detecting epistatic drivers of human phenotypes is a considerable challenge. Traditional approaches use regression to sequentially test multiplicative interaction terms involving pairs of genetic variants. For higher-order interactions and genome-wide large-scale data, this strategy is computationally intractable. Moreover, multiplicative terms used in regression modeling may not capture the form of biological interactions. Building on the Predictability, Computability, Stability (PCS) framework, we introduce the epiTree pipeline to extract higher-order interactions from genomic data using tree-based models. The epiTree pipeline first selects a set of variants derived from tissue-specific estimates of gene expression. Next, it uses iterative random forests (iRF) to search training data for candidate Boolean interactions (pairwise and higher-order). We derive significance tests for interactions, based on a stabilized likelihood ratio test, by simulating Boolean tree-structured null (no epistasis) and alternative (epistasis) distributions on hold-out test data. Finally, our pipeline computes PCS epistasis p-values that probabilisticly quantify improvement in prediction accuracy via bootstrap sampling on the test set. We validate the epiTree pipeline in two case studies using data from the UK Biobank: predicting red hair and multiple sclerosis (MS). In the case of predicting red hair, epiTree recovers known epistatic interactions surrounding MC1R and novel interactions, representing non-linearities not captured by logistic regression models. In the case of predicting MS, a more complex phenotype than red hair, epiTree rankings prioritize novel interactions surrounding …

Plos one

In commercial laying hens, keel bone damage (KBD) is a severe health and welfare problem leading to pain, reduced mobility and decreased laying performance. Flocks of all production systems and hybrid lines can be affected. KBD is a multifactorial welfare issue and, among other factors, associated with a high laying performance which negatively affects the calcium deposit in the medullary bones. Therefore, mature hens of local breeds with much lower egg production than commercial hybrids may be expected to show less or even no keel bone damage. This study evaluates (i) the prevalence of KBD in local breeds, (ii) the difference in type and level of damages, and (iii) if roosters and pullets are also affected. In total, we palpated 343 mature hens, 40 pullets, and 18 roosters of 13 different local breeds and one commercial hybrid. The animals were kept on eight different farms in free-range or floor-housing systems. Our results showed that on average 44.2% of mature hens per local breed were affected by KBD (range: 11.1%-84.7%). We found deviation of less than 1 cm in 26.9%, deviations of more than 1 cm in 6.4% and palpable fractures in 23.8% of the mature hens of local breeds. The tip was damaged in 23.6% of the mature hens. Also, pullets and roosters were affected by KBD. Finally, we found that KBD also occurs in local breeds. Therefore, we conclude that even the low laying performance of local breeds does not prevent them from the occurrence of KBD.KBD in local breeds may rather be associated with genetics (breed) as well as management and housing. Thus, breeders of local breeds should include bone health as a selection …

Plos one

Hepatitis A virus (HAV) infection has disproportionately affected more men who have sex with men (MSM), occurring in outbreaks, despite being vaccine-preventable. We determined the prevalence and factors associated with HAV susceptibility among cisgender MSM on HIV pre-exposure prophylaxis (PrEP) in Northeastern Brazil. From September 30, 2021 to June 19, 2023, 282 cisgender MSM receiving HIV PrEP were enrolled into this cross-sectional study. Sociodemographic and clinical information were collected. Blood samples were collected for screening of sexually transmitted infections (STIs) and serum samples were tested for IgM and total anti-HAV antibodies. Non-reactive results for total anti-HAV antibodies were found in 106 of 282 (37.6%) participants. Factors associated with HAV susceptibility included age <30 years (prevalence ratio [PR]: 2.02; 95% confidence interval [95% CI]: 1.61–2.53), having health insurance (PR: 1.39; 95% CI: 1.19–1.64), sex only with cisgender men (PR: 1.52; 95% CI: 1.23–1.89), non-steady partner (PR: 1.20; 95% CI: 1.01–1.43) and no lifetime history of STIs (PR: 1.25; 95% CI: 1.03–1.53). Identifying clinical correlates of HAV susceptibility in key populations is a fundamental step towards development of public policy focused on prevention, especially following the recent hepatitis A outbreak in Brazil.

Plos one

The material properties of some bones are known to vary with anatomical location, orientation and position within the bone (e.g., cortical and trabecular bone). Details of the heterogeneity and anisotropy of bone is an important consideration for biomechanical studies that apply techniques such as finite element analysis, as the outcomes will be influenced by the choice of material properties used. Datasets detailing the regional variation of material properties in the bones of the skull are sparse, leaving many finite element analyses of skulls no choice but to employ homogeneous, isotropic material properties, often using data from a different species to the one under investigation. Due to the growing significance of investigating the cranial biomechanics of the rabbit in basic science and clinical research, this study used nanoindentation to measure the elastic modulus of cortical and trabecular bone throughout the skull. The elastic moduli of cortical bone measured in the mediolateral and ventrodorsal direction were found to decrease posteriorly through the skull, while it was evenly distributed when measured in the anteroposterior direction. Furthermore, statistical tests showed that the variation of elastic moduli between separate regions (anterior, middle and posterior) of the skull were significantly different in cortical bone, but was not in trabecular bone. Elastic moduli measured in different orthotropic planes were also significantly different, with the moduli measured in the mediolateral direction consistently lower than that measured in either the anteroposterior or ventrodorsal direction. These findings demonstrate the significance of regional and …

Plos one

Background Poor mental health is associated with obesity, but existing studies are either cross-sectional or have long time periods between measurements of mental health and weight. It is, therefore, unclear how small fluctuations in mental wellbeing within individuals predict bodyweight over short time periods, e.g. within the next month. Studying this could identify modifiable determinants of weight changes and highlight opportunities for early intervention. Methods 2,133 UK adults from a population-based cohort completed monthly mental health and weight measurements using a mobile app over a period of 6–9 months. We used random intercept regression models to examine longitudinal associations of depressive symptoms, anxiety symptoms and stress with subsequent weight. In sub-group analyses, we included interaction terms of mental health variables with baseline characteristics. Mental health variables were split into “between-individual” measurements (= the participant’s median score across all timepoints) and “within-individual” measurements (at each timepoint, the difference between the participant’s current score and their median). Results Within-individual variation in depressive symptoms predicted subsequent weight (0.045kg per unit of depressive symptom severity, 95% CI 0.021–0.069). We found evidence of a moderation effect of baseline BMI on the association between within-individual fluctuation in depressive symptoms and subsequent weight: The association was only apparent in those with overweight/obesity, and it was stronger in those with obesity than those with overweight (BMI<25kg/m2: 0.011kg per unit of …

Plos one

The global population consumes more seafood from aquaculture today than from capture fisheries and although the aquaculture industry continues to grow, both seafood sectors will continue to be important to the global food supply into the future. As farming continues to expand into ocean systems, understanding how wild populations and fisheries will interact with farms will be increasingly important to informing sustainable ocean planning and management. Using a spatially explicit population and fishing model we simulate several impacts from ocean aquaculture (i.e., aggregation, protection from fishing, and impacts on fitness) to evaluate the mechanisms underlying interactions between aquaculture, wild populations and fisheries. We find that aggregation of species to farms can increase the benefits of protection from fishing that a farm provides and can have greater impacts on more mobile species. Splitting total farm area into smaller farms can benefit fishery catches, whereas larger farms can provide greater ecological benefits through conservation of wild populations. Our results provide clear lessons on how to design and co-manage expanding ocean aquaculture along with wild capture ecosystem management to benefit fisheries or conservation objectives.

Plos one

In our study, we introduce indicators that quantify the influence of each country in complex trade scenarios involving the exchange of raw materials, intermediate goods, and final products across multiple countries. We systematically employ an agent-based model to simulate the propagation of failures from one node to the entire network. This approach allows for the assessment of the impact of each country and the identification of patterns of interaction in the multi-step trade network. Unlike conventional analyses of trade networks, which depict straightforward single-step import/export transactions, our approach captures the intricate realities of processes like raw material procurement, production, and sales in numerous countries from a macroscopic perspective. The findings of our analysis of trade data spanning from 1990 to 2022 reveal several key insights. Firstly, sensitivity to changes in trade volume leading to global failures within interconnected networks has intensified over time. The potential of failure propagation across countries has increased over time, as has the interconnectedness of countries in the global trade landscape. Secondly, despite the increased sensitivity to changes in global trade volume, many countries have become less vulnerable to the influence of others within their multi-step trade networks. This trend aligns with deglobalization, which is evidenced by events such as Brexit and the surge in protectionist measures; these changes indicate a shift in the balance of influence within global trade networks. Thirdly, the results of our analysis of the relationship between load changes and global failures from a regional …

Plos one

Purpose To compare the relationship between macular ganglion cell layer (mGCL) thickness and 10–2 visual field (VF) sensitivity using different stimulus sizes in patients with temporal hemianopia from chiasmal compression. Methods A cross-sectional study was conducted involving 30 eyes from 25 patients with temporal VF loss on 24–2 SITA standard automated perimetry due to previous chiasmal compression and 30 healthy eyes (23 controls). Optical coherence tomography (OCT) of the macular area and 10–2 VF testing using Goldmann stimulus size I (GI), II (GII), and III (GIII) were performed in the Octopus 900 perimeter. For the sake of analysis, mGCL thickness and VF data were segregated into four quadrants (two temporal and two nasal) and two halves (temporal and nasal) centered on the fovea, in order to evaluate separately both the severely affected nasal hemi-retina corresponding to the temporal VF sectors and the subclinically affected temporal hemi-retina corresponding to the nasal VF sectors. Data from patients and controls were compared using generalized estimated equations. The discrimination ability of GI, GII, and GIII was evaluated, as was the correlation between mGCL and 10–2 VF sensitivity using GI, GII, and GIII. Results All mGCL parameters in the nasal and temporal halves of the retina were significantly reduced in patients compared to controls. 10–2 VF test sensitivity using GI, GII, and GIII was significantly lower in patients than in controls (p≤0.008) for all parameters, except the three nasal divisions when using GI (p = 0.41, 0.07 and 0.18) Significant correlations were found between temporal VF sectors (all …

Plos one

Anti-VEGF (vascular endothelial growth factor) drugs such as aflibercept (AFL) and bevacizumab (BVZ) inhibit pathological neo-angiogenesis and vascular permeability in retinal vascular diseases. As cytokines and growth factors are produced by Müller glial cells under stressful and pathological conditions, we evaluated the in vitro effect of AFL (Eylea®, 0.5 mg/mL) and BVZ (Avastin®, 0.5 mg/mL) on cell viability/metabolism, and cytokine/growth factor production by Müller cells (MIO-M1) under cobalt chloride (CoCl2)-induced hypoxia after 24h, 48h and 72h. Cell viability/metabolism were analyzed by Trypan Blue and MTT assays and cytokine/growth factors in supernatants by Luminex xMAP-based multiplex bead-based immunoassay. Cell viability increased with AFL at 48h and 72h and decreased with BVZ or hypoxia at 24h. BVZ-treated cells showed lower cell viability than AFL at all exposure times. Cell metabolism increased with AFL but decreased with BVZ (72h) and hypoxia (48h and72h). As expected, AFL and BVZ decreased VEGF levels. AFL increased PDGF-BB, IL-6 and TNF-α (24h) and BVZ increased PDGF-BB (72h). Hypoxia reduced IL-1β, -6, -8, TNF-α and PDGF-BB at 24h, and its suppressive effect was more prominent than AFL (EGF, PDGF-BB, IL-1β, IL-6, IL-8, and TNF-α) and BVZ (PDGF-BB and IL-6) effects. Hypoxia increased bFGF levels at 48h and 72h, even when combined with anti-VEGFs. However, the stimulatory effect of BVZ predominated over hypoxia for IL-8 and TNF-α (24h), as well as for IL-1β (72h). Thus, AFL and BVZ exhibit distinct exposure times effects on MIO-M1 cells viability, metabolism, and cytokines …

Plos one

Background The Awakening, Breathing Coordination, Delirium monitoring and Early mobility bundle (ABCDE) is associated with lower mortality for intensive care unit (ICU) patients. However, efforts to improve ABCDE are variably successful, possibly due to lack of clarity about who are the team members interacting when caring for each patient, each shift. Lack of patient shift-level information regarding who is interacting with whom limits the ability to tailor interventions to the specific ICU team to improve ABCDE. Objective Determine the number and types of individuals (i.e., clinicians and family members) interacting in the care of mechanically ventilated (MV) patients, as reported by the patients’ assigned physician, nurse, and respiratory therapist (RT) each shift, using a network science lens. Methods We conducted a prospective, patient-shift-level survey in 2 medical ICUs. For each patient, we surveyed the assigned physician, nurse, and RT each day and night shift about who they interacted with when providing ABCDE for each patient-shift. We determined the number and types of interactions, reported by physicians, nurses, and RTs and day versus night shift. Results From 1558 surveys from 404 clinicians who cared for 169 patients over 166 shifts (65% response rate), clinicians reported interacting with 2.6 individuals each shift (physicians: 2.65, nurses: 3.33, RTs: 1.86); this was fewer on night shift compared to day shift (1.99 versus 3.02). Most frequent interactions were with the bedside nurse, attending, resident, intern, and RT; family member interactions were reported in less than 1 in 5 surveys (12.2% of physician surveys, 19.7% of …

Plos one

The resilience of a country during the COVID-19 pandemic was determined based in whether it was holistically prepared and responsive. This resilience can only be identified through systematic data collection and analysis. Historical evidence-based response indicators have been proven to mitigate pandemics like COVID-19. However, most databases are outdated, requiring updating, derivation, and explicit interpretation to gain insight into the impact of COVID-19. Outdated databases do not show a country’s true preparedness and response capacity, therefore, it undermines pandemic threat. This study uses up-to-date evidence-based pandemic indictors to run a cross-country comparative analysis of COVID-19 preparedness, response capacity, and healthcare resilience. PROMETHEE—a multicriteria decision making (MCDM) technique—is used to quantify the strengths (positive) and weaknesses (negative) of each country’s COVID-19 responses, with full ranking (net) from best to least responsive. From 22 countries, South Korea obtained the highest net outranking value of 0.1945, indicating that it was the most resilient, while Mexico had the lowest (-0.1428). Although countries were underprepared, there was a robust response to the pandemic, especially in developing countries. This study demonstrates the performance and response capacity of 22 key countries to resist COVID-19, from which other countries can compare their statutory capacity ranking in order to learn/adopt the evidence-based responses of better performing countries to improve their resilience.