Introduction
Isolated, confined, extreme (ICE) environments are accompanied by a host of stress-inducing circumstances: operational pressure, interpersonal dynamics, limited communication with ...friends and family, and environmental hazards. We evaluated the effectiveness of attention-restoration-therapy-based immersive Virtual Reality (VR) in three ICE environments: the Canadian Forces Station—Alert (CFS Alert), the 12-month HI-SEAS IV expedition, and the 8-month HI-SEAS V expedition.
Methods
Thirty-one individuals (29 male, 2 female) at CFS Alert, and 12 total crewmembers (7 male, 5 female, six crewmembers per sessions) at HI-SEAS participated. All participants viewed immersive VR scenes, but scene content varied by deployment. Data collection included pre- and post-intervention surveys and semi-structured post-mission interviews. Survey data were analyzed by scene content within each analog using nonparametric approaches.
Results
Acceptability and desirability of the VR content varied significantly by ICE analog, as well as by participants within a given analog. The two initial exploratory protocols enabled a more directed study in HI-SEAS V to identify the importance of differences in scene content.
Discussion
Use and perceived utility of the VR varied considerably across participants, indicating that psychological support needs to be individualized. Overall, natural scene VR was broadly considered restorative, but after long periods of isolation, dynamic and familiar scenes including those with people were also appealing. Immersive, nature-based VR was highly valued by some, but not all participants, suggesting that this intervention tool holds promise for use in ICE settings but needs to be tailored to the setting and individual.
The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of ...CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro.
Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets).
Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts.
Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.
Objective
This paper surveys the existing literature surrounding problem-solving and team dynamics in complex and unpredictable scenarios, and evaluates the applicability of studying Earth-based ...construction teams to identify training needs for Lunar construction crews.
Background
Lunar and other space exploration construction crews will work in extreme environments and face unpredictable challenges, necessitating real-time problem-solving to address unexpected contingencies. This work will require coordination with Mission Control and autonomous assistants, so crew training must account for multi-agent, distributed teamwork.
Method
A narrative literature review identified processes, attributes, and skills necessary for the success of Lunar construction teams. We summarized relevant frameworks and synthesized collective findings into over-arching trends and remaining research gaps.
Results
While significant literature exists surrounding team performance, very little systematic inquiry has been done with a focus on Lunar construction crews and operations, particularly with respect to dynamic problem-solving and team-based decision-making. Established and standardized metrics for evaluating team performance are lacking, resulting in significant variation in reported outcomes between studies.
Conclusion
Lunar and other space exploration construction teams will need training that focuses on developing the right approach to team-based problem-solving, rather than on preparing response execution for known contingencies. An investigation of successful Earth-based construction crews may facilitate the development of relevant metrics for training future Lunar construction crews.
Application
Metrics and team training protocols developed for future Lunar construction teams may be adaptable and applicable to a wide range of extreme teams facing uncertain challenges, such as aircrews, surgical teams, first responders, and construction crews.
Detrimental molecular processes in multiple sclerosis (MS) lead to the cellular accumulation of lipid peroxidation products and iron in the CNS, which represents the main driving force for ...ferroptosis. Ferroptosis is an iron-dependent form of regulated cell death, with proposed roles in neurodegeneration, oligodendrocyte loss and neuroinflammation in the pathogenesis of MS. Ferroptosis-related gene expression signature and molecular markers, which could reflect MS severity and progression, are currently understudied in humans. To tackle these challenges, we have applied a curated approach to create and experimentally analyze a comprehensive panel of ferroptosis-related genes covering a wide range of biological processes associated with ferroptosis. We performed the first ferroptosis-related targeted RNAseq on PBMCs from highly distinctive MS phenotype groups: mild relapsing-remitting (RR) (n = 24) and severe secondary progressive (SP) (n = 24), along with protein detection of GPX4 and products of lipid peroxidation (MDA and 4-HNE). Out of 138 genes, 26 were differentially expressed genes (DEGs), indicating changes in both pro- and anti-ferroptotic genes, representing a molecular signature associated with MS severity. The top three DEGs, as non-core ferroptosis genes,
,
and
, were replicated by qPCR to validate findings in independent patient groups (16 RR and 16 SP MS). Co-expression and interactions of DEGs were presented as additional valuable assets for deeper understanding of molecular mechanisms and key targets related to MS severity. Our study integrates a wide genetic signature and biochemical markers related to ferroptosis in easily obtainable PBMCs of MS patients with clinical data and disease severity, thus providing novel molecular markers which can complement disease-related changes in the brain and undergo further research as potential therapeutic targets.
Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The ...study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA's expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484
KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484
KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.
Aim: It was the aim of the study to identify commonly deregulated miRNAs in oral cancer patients by performing a meta-analysis of previously published miRNA expression profiles in cancer and matched ...normal non-cancerous tissue in such patients.
Material and methods: Meta-analysis included seven independent studies analyzed by a vote-counting method followed by bioinformatic enrichment analysis.
Results: Amongst seven independent studies included in the meta-analysis, 20 miRNAs were found to be deregulated in oral cancer when compared with non-cancerous tissue. Eleven miRNAs were consistently up-regulated in three or more studies (miR-21-5p, miR-31-5p, miR-135b-5p, miR-31-3p, miR-93-5p, miR-34b-5p, miR-424-5p, miR-18a-5p, miR-455-3p, miR-450a-5p, miR-21-3p), and nine were down-regulated (miR-139-5p, miR-30a-3p, miR-376c-3p, miR-885-5p, miR-375, miR-486-5p, miR-411-5p, miR-133a-3p, miR-30a-5p). The meta-signature of identified miRNAs was functionally characterized by KEGG enrichment analysis. Twenty-four KEGG pathways were significantly enriched, and TGF-beta signaling was the most enriched signaling pathway. The highest number of meta-signature miRNAs was involved in the sphingolipid signaling pathway. Natural killer cell-mediated cytotoxicity was the pathway with most genes regulated by identified miRNAs. The rest of the enriched pathways in our miRNA list describe different malignancies and signaling.
Conclusions: The identified miRNA meta-signature might be considered as a potential battery of biomarkers when distinguishing oral cancer tissue from normal, non-cancerous tissue. Further mechanistic studies are warranted in order to confirm and fully elucidate the role of deregulated miRNAs in oral cancer.
Galectin-3 is encoded by
, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r
> 0.8) of the genetic variance of this ...HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and
mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and
mRNA expression were detected using TaqMan
technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 0.05-0.72,
= 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 37.3-59.4 ng/mL vs. 18.9 14.5-23.4 ng/mL,
< 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging
HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.
Background and Objectives: The relationship between osteoarthritis (OA) and osteoporosis (OP) has been analysed for over four decades. However, this relationship has remained controversial. Numerous ...observational and longitudinal studies have shown an inverse association between the two diseases and a protective effect of one against the other. On the other hand, some studies show that patients with OA have impaired bone strength and are more prone to fractures. The study’s main objective was to determine the bone mineral density (BMD) of the spine and hip (femoral neck) of postmenopausal women of different ages, with radiologically determined OA of the hip and knee, as well as to determine the correlation between BMD values and age in the experimental group. Materials and Methods: The retrospective cohort study included 7018 patients with osteoarthritis of peripheral joints and the spine, examined by a rheumatologist in an outpatient rheumatology clinic at the Institute for Treatment and Rehabilitation, Niška Banja from July 2019 to March 2021. A nested anamnestic study was conducted within the cohort study of patients, and it included two groups: an experimental group composed of 60 postmenopausal women, and a control group composed of the same number of women. Out of 120 patients, 24 did not meet the criteria for the continuation of the study (due to technical errors—radiographic and/or densitometry artefacts). Fifty-six postmenopausal women (aged 45−77 years) with hip and knee radiological OA were examined as an experimental group. The participants were divided into two subgroups according to age (45−60 years and over 61 years). The control group included 40 healthy postmenopausal women of the same age range, without radiological OA, with normal BMD of the hip and spine. All patients with OA met the American College of Radiology (ACR) criteria. OA of the hip and knee was determined radiologically according to Kellgren and Lawrence (K&L) classification, and patients were included in the study if a K&L grade of at least ≥ 2 was present. Hip and spine BMD was measured by dual-energy X-ray absorptiometry (DXA). Results: Compared to the control group, we found statistically significantly lower BMD and T-scores of the spine in older postmenopausal women: BMD (g/cm2), p = 0.014; T-score, p = 0.007, as well as of the hip: BMD (g/cm2), p = 0.024; T-score p < 0.001. The values of BMD and T-score of the spine and hip are lower in more severe forms of OA (X-ray stage 3 and 4, according to K&L), p < 0.001. We found negative correlation between BMD and T-score and age only for the hip: BMD (g/cm2), ρ = 0.378, p = 0.005; T-score ρ = −0.349, p = 0.010. Conclusions: Older postmenopausal women with radiographic hip and knee OA had significantly lower BMD of the hip and spine as compared to the control group without OA, pointing to the need for the prevention and treatment of OA, as well as early diagnosis, monitoring, and treatment of low bone mineral density.
Objective
This project quantifies operationally relevant measures of flight performance and workload in a high-fidelity long-duration spaceflight analog, longitudinally across mission duration, using ...a portable simulation platform.
Background
Real-time performance measures allow for the objective assessment of task performance and the timely identification of performance degradations.
Methods
Measures of flight performance on a piloted lunar lander task were collected on 32 total crewmembers across 8 simulated space missions of 45 days each (623 total sessions).
Results
Mission duration demonstrated a significant effect on measures of flight performance across all campaigns. Flight measures showed a general pattern of peaking in accuracy during the middle-late quartiles of overall mission time, then degrading again towards baseline. On the workload measure, however, a general linear decrease in workload consistent with progressive task learning was observed in both campaigns.
Conclusion
This investigation demonstrated the disruptive effect of time in mission on some, but not all, aspects of task performance. While mission interval differentially impacted measures of flight accuracy, workload, by contrast, seemed to steadily decrease with in-mission time.
Application
While more work is needed, the observed discrepancy between progression of flight performance and workload assessment highlights the importance of sensitive and specific measurement tools for the tracking of distinct performance metrics.
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