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Abstract Pre-pregnancy body mass index (BMI) is associated with adverse pregnancy and neonatal health outcomes, with differences in risk observed between sexes. Given that the placenta is a sexually dimorphic organ and critical regulator of development, examining differences in placental mRNA and miRNA expression in relation to pre-pregnancy BMI may provide insight into responses to maternal BMI in utero. Here, genome-wide mRNA and miRNA expression levels were assessed in the placentas of infants born extremely preterm. Differences in expression were evaluated according to pre-pregnancy BMI status (1) overall and (2) in male and female placentas separately. Overall, 719 mRNAs were differentially expressed in relation to underweight status. Unexpectedly, no genes were differentially expressed in relation to overweight or obese status. In male placentas, 572 mRNAs were associated with underweight status, with 503 (70%) overlapping genes identified overall. Notably, 43/572 (8%) of the mRNAs associated with underweight status in male placentas were also gene targets of two miRNAs (miR-4057 and miR-128-1-5p) associated with underweight status in male placentas. Pathways regulating placental nutrient metabolism and angiogenesis were among those enriched in mRNAs associated with underweight status in males. This study is among the first to highlight a sexually dimorphic response to low pre-pregnancy BMI in the placenta.

Background: During the COVID-19 pandemic, restrictions on carrying out face-to-face consultations were implemented. Thus, the performance of “long-distance consultations” (telemedicine) through different virtual platforms was implemented. Aim: The aim of the study was to document the experience with the mobile messaging application “WhatsApp” on the continuation of follow-up on acute lymphoblastic leukemia (ALL) survivors. Material and methods: A prospective, observational, and descriptive study of a telemedicine model using the WhatsApp application in the follow-up of pediatric ALL survivors at the Pediatric Hematology Department of the “Dr. José Eleuterio González” University Hospital during the COVID-19 pandemic. The study was carried out from March 2020 to March 2021. The patients were divided into two groups: those already under surveillance before the pandemic and those who began surveillance during the pandemic. Results: Seventy-three ALL survivors were included in the study, and follow-up was successfully carried out on 82.1% of patients. There were no relapses in the first group. However, three patients had a bone-marrow relapse in the second group. Conclusion: Follow-up of pediatric ALL survivors is essential for the suitable detection of relapses and long-term side effects of treatment. The use of the WhatsApp application aided us in the follow-up of patients during the COVID-19 pandemic when social distancing was mandatory.

Through ingestion and subsequent egestion, Arctic seabirds can bioaccumulate microplastics at and around their colony breeding sites. While microplastics in Arctic seabirds have been well documented, it is not yet understood to what extent these particles can act as transport vehicles for plastic-associated contaminants, including legacy persistent organic pollutants (POPs), trace metals, and organic additives. We investigated the occurrence and pattern of organic and inorganic co-contaminants of microplastics in two seabird species from the Canadian Arctic — northern fulmar (Fulmarus glacialis) and black-legged kittiwake (Rissa tridactyla). We found that fulmars had higher levels of plastic contamination and emerging organic compounds (known to be plastic additives) than kittiwakes, whereas higher concentrations of legacy POPs were found in kittiwakes than the fulmars. Furthermore, fulmars, the species with the much larger foraging range (∼200 km), had higher plastic pollution and overall contaminant burdens, indicating that birds may be acting as long-range transport vectors for plastic-associated pollution. Our results suggest a potential connection between plastic additive contamination and plastic pollution burdens in the bird stomachs, highlighting the importance of treating plastic particles and plastic-associated organic additives as co-contaminants rather than separate pollution issues.

Natural systems in Argentina have gradually faded as a consequence of land use change, resulting in a diminished capacity to provide the ecosystem services (ES) essential for the well-being of the communities. The basin of the Chocancharava River fits within that context and is immersed in an urban-agricultural matrix that has produced major forest fragmentation. Based on this socio-environmental problem, the present report recounts the challenges and possibilities pertaining to an experience in community management. First of all, a conservation-status assessment of the forest remnants was used as a steppingstone to convene the first meeting of institutions linked to the territory. This interagency coupling allowed for a more holistic diagnosis and the formulation of action plans. The first result was the creation of a peri-urban provincial reserve. Managing the reserve demanded a wider involvement from the community and the provision of a space where all possible voices could be heard. Therefore, the first participative workshop was held, in which ties with the environment were problematized through the ES framework. This experience was of importance when pondering about unilateral decision-making models and grasping the value of community-based networks to generate more inclusive policies. In addition, the workshop provided a space for the co-production of knowledge regarding main actors and tensions about natural resources uses. Furthermore, this process constituted a road of reflection regarding our practices, which are vital for new community processes with results that are legitimate and relevant for the socioecological transformation of the system.

Summary: Additively manufactured (AM) three-dimensional (3D) mesostructures can be designed to enhance mechanical, thermal, or optical properties, driving future device applications at the micron to millimeter scale. We present a protocol for transforming AM mesostructures into 3D electronics by growing nanoscale conducting films on 3D-printed polymers. In this generalizable approach, we describe steps to utilize precision thermal atomic layer deposition (ALD) of conducting, semiconducting, and dielectric metal oxides. This can be applied to ultrasmooth, customizable photopolymer lattices printed by high-resolution microstereolithography.For complete details on the use and execution of this protocol, please refer to Huddy et al. (2022). : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

In biogeography the competitive exclusion principle (CEP) has been confirmed in some cases but not in others. This has fueled an unresolved debate between those advocating niche theory or the neutral theory in biodiversity and biogeography. We suggest that this situation mainly arises from the use of crisp logic, where the CEP is defined as either completely true or false. We propose the application of the fuzzy concepts of favorability (the degree to which environmental conditions are propitious for the occurrence of individual species) and favorableness (the degree to which environmental conditions are simultaneously favorable for competing species) to operationalize a fuzzy version of the CEP. Favorability was obtained by performing species distribution models applying favorability functions, while favorableness was derived from the application of the fuzzy intersection between the favorability for competing species. Then we plotted individual favorability values along the gradient of favorableness. Two potentially competing species would coexist in high-favorableness locations, as the demands of both species would be well fulfilled. In locations of low favorableness, the result would be either autecological exclusion of both species or autecological segregation, as abiotic conditions are unfavorable for at least one of the species. Competitive exclusion would occur at the intermediate stretch of the favorableness gradient, as the conditions would be good enough for persistence of each species separately but not enough for permanent coexistence. According to this theoretical framework, the observed probability that a location belongs to the intermediate favorableness area given that the two species co-occur in this location should be lower than expected according to the environmental probability models for the two species. We tested this prediction on published data about the distribution of pairs of native and introduced deer species in Great Britain, using a Bayesian approach. In two thirds of comparisons between a native and an introduced deer species the predictions of the fuzzy CEP were corroborated, which suggests that these are the pairs of species and the specific geographical areas affected by competitive exclusion. This is important both theoretically and for biodiversity conservation planning.

Background: Environmental health research has recently undergone a dramatic shift, with ongoing technological advancements allowing for broader coverage of exposure and molecular biology signatures. Approaches to integrate such measures are still needed to increase understanding between systems-level exposure and biology. Objectives: We address this gap by evaluating placental tissues to identify novel chemical-biological interactions associated with preeclampsia. This study tests the hypothesis that understudied chemicals are present in the human placenta and associated with preeclampsia-relevant disruptions, including overall case status (preeclamptic vs. normotensive patients) and underlying transcriptomic/epigenomic signatures. Methods: A non-targeted analysis based on high-resolution mass spectrometry was used to analyze placental tissues from a cohort of 35 patients with preeclampsia (n = 18) and normotensive (n = 17) pregnancies. Molecular feature data were prioritized for confirmation based on association with preeclampsia case status and confidence of chemical identification. All molecular features were evaluated for relationships to mRNA, microRNA, and CpG methylation (i.e., multi-omic) signature alterations involved in preeclampsia. Results: A total of 183 molecular features were identified with significantly differentiated abundance in placental extracts of preeclamptic patients; these features clustered into distinct chemical groupings using unsupervised methods. Of these features, 53 were identified (mapping to 40 distinct chemicals) using chemical standards, fragmentation spectra, and chemical metadata. In general, human metabolites had the largest feature intensities and strongest associations with preeclampsia-relevant multi-omic changes. Exogenous drugs were second most abundant and had fewer associations with multi-omic changes. Other exogenous chemicals (non-drugs) were least abundant and had the fewest associations with multi-omic changes. Conclusions: These global data trends suggest that human metabolites are heavily intertwined with biological processes involved in preeclampsia etiology, while exogenous chemicals may still impact select transcriptomic/epigenomic processes. This study serves as a demonstration of merging systems exposures with systems biology to better understand chemical-disease relationships.

Nematode parasites of the genus Anisakis (Nematoda, Anisakidae) are considered among the most important biological hazards in seafood products worldwide. In temperate and tropical waters, the most common species appears to be Anisakis typica, generally found around the viscera and sporadically in the flesh of various fish host species. This study investigated the infection sites and genetic diversity of A. typica infecting commercial fishes from the South-West Indian Ocean. Largehead hairtail (N = 20) and brushtooth lizardfish (N = 72) fished off Tanzania were inspected for anisakid nematodes by UV-press. A subsample of 168 nematodes were identified by sequence analyses of the cox2 mtDNA gene and ITS region of rDNA. The species A. typica (s.l.) (N = 166), Pseudoterranova ceticola (N = 1) and Anisakis paggiae (N = 1) were molecularly identified. Phylogenetic analysis of A. typica (s.l.) sequences based on both genes, indicated the existence of two distinct phylogenetic lineages forming two well-supported clades. The first clade comprised 12 A. typica specimens including individuals from its type locality (central Atlantic Ocean). The second clade comprising 154 specimens, clustered with reference sequences retrieved from GenBank including one apparently undescribed taxon, i.e., Anisakis sp. 1, and A. typica var. indonesiensis. The two reciprocally monophyletic clades are closely related and correspond to two distinct sister species within A. typica (s.l.), presently indicated as A. typica sp. A and A. typica sp. B. Two and four fixed alternative nucleotide substitutions (SNPs), i.e., diagnostic positions, between the two taxa, respectively, were found at the mtDNA cox2 and the ITS region of rDNA. The genetic data, as well as their occurrence in sympatry, strengthens the hypothesis that the actual specimens represent two distinct gene pools. The occurrence of both A. typica sp. A and A. typica sp. B in the musculature of freshly examined T. lepturus and S. undosquamis, suggests that both species can migrate intra-vitam into the flesh. Although the zoonotic potential of A. typica s.l. is still unclear, the presence of these parasites in the musculature, edible part of the fish, raises health concerns for consumers.

Introduction: Wildfires are a threat to public health world-wide that are growing in intensity and prevalence. The biological mechanisms that elicit wildfire-associated toxicity remain largely unknown. The potential involvement of cross-tissue communication via extracellular vesicles (EVs) is a new mechanism that has yet to be evaluated. Methods: Female CD-1 mice were exposed to smoke condensate samples collected from the following biomass burn scenarios: flaming peat; smoldering peat; flaming red oak; and smoldering red oak, representing lab-based simulations of wildfire scenarios. Lung tissue, bronchoalveolar lavage fluid (BALF) samples, peripheral blood, and heart tissues were collected 4 and 24 h post-exposure. Exosome-enriched EVs were isolated from plasma, physically characterized, and profiled for microRNA (miRNA) expression. Pathway-level responses in the lung and heart were evaluated through RNA sequencing and pathway analyses. Results: Markers of cardiopulmonary tissue injury and inflammation from BALF samples were significantly altered in response to exposures, with the greatest changes occurring from flaming biomass conditions. Plasma EV miRNAs relevant to cardiovascular disease showed exposure-induced expression alterations, including miR-150, miR-183, miR-223-3p, miR-30b, and miR-378a. Lung and heart mRNAs were identified with differential expression enriched for hypoxia and cell stress-related pathways. Flaming red oak exposure induced the greatest transcriptional response in the heart, a large portion of which were predicted as regulated by plasma EV miRNAs, including miRNAs known to regulate hypoxia-induced cardiovascular injury. Many of these miRNAs had published evidence supporting their transfer across tissues. A follow-up analysis of miR-30b showed that it was increased in expression in the heart of exposed mice in the absence of changes to its precursor molecular, pri-miR-30b, suggesting potential transfer from external sources (e.g., plasma). Discussion: This study posits a potential mechanism through which wildfire exposures induce cardiopulmonary responses, highlighting the role of circulating plasma EVs in intercellular and systems-level communication between tissues.

Abstract Plants take up elements through their roots and transport them to their shoot systems for use in numerous biochemical, physiological, and structural functions. Elemental composition of above‐ground plant tissues, such as leaves, reflects both above‐ and below‐ground activities of the plant, as well the local environment. Perennial, grafted plants, where the root system of one individual is fused to the shoot system of a genetically distinct individual, offer a powerful experimental system in which to study how genetically distinct root systems influence the elemental composition of a common shoot system. We measured elemental composition of over 7,000 leaves in the grapevine cultivar “Chambourcin” growing ungrafted and grafted to three rootstock genotypes. Leaves were collected over multiple years and phenological stages (across the season) and along a developmental time series. Temporal components of this study had the largest effect on leaf elemental composition, and rootstock genotype interacted with year, phenological stage, and leaf age to differentially modulate leaf elemental composition. Further, the local, above‐ground environment affected leaf elemental composition, an effect influenced by rootstock genotype. This work highlights the dynamic nature by which root systems interact with shoot systems to respond to temporal and environmental variation.

Organisms that are similar in size, morphological characteristics, and adaptations, including vertebrates, often coexist by partitioning the available resources (food, space, and time). So, studies of the dynamics of these cases of coexistence are scientifically interesting. Here, we study a coexistence case of two species of freshwater turtles inhabiting the forest waterbodies of West Africa, focusing on the dietary habits of the two species. We found that both turtle species are omnivorous generalists, eating both vegetal and animal matter abundantly. However, there were clear interspecific differences, with the larger of the two species (P. cupulatta) eating more vertebrates (mainly fish but occasionally other vertebrates), whereas P. castaneus consumed more invertebrates. These patterns appeared consistently within the species and across sites, highlighting that the same patterns were likely in other conspecific populations from the Upper Guinean forest streams (Côte d’Ivoire and Liberia). Our study also showed that interspecific competition for food does not occur between these two species; instead, previous studies uncovered that a clear partitioning of the habitat niche occurs. We conclude that the food resource is likely unlimited in the study areas, as it is not the case in more arid environments (since food shortages may occur during the dry season). We anticipate that, within the Pelomedusidae communities throughout Africa, intense competition for food probably occurs in the Sahel and Sudanian vegetation zones, particularly during the dry months, but is unlikely within the Guinea and wet savannah region and even less likely in the Guineo-Congolian rainforest region.

Bacteria of the genus Streptomyces produce various specialized metabolites. Single biosynthetic gene clusters (BGCs) can give rise to different products that can vary in terms of their biological activities. For example, for alnumycin and the shunt product K115, antimicrobial activity was described, while no antimicrobial activity was detected for the shunt product 1,6-dihydro 8-propylanthraquinone. To investigate the antibacterial activity of 1,6-dihydro 8-propylanthraquinone, we produced alnumycin and 1,6-dihydro 8-propylanthraquinone from a Streptomyces isolate containing the alnumycin BGC. The strain was cultivated in liquid glycerol–nitrate–casein medium (GN), and both compounds were isolated using an activity and mass spectrometry-guided purification. The structures were validated via nuclear magnetic resonance (NMR) spectroscopy. A minimal inhibitory concentration (MIC) test revealed that 1,6-dihydro 8-propylanthraquinone exhibits antimicrobial activity against E. coli ΔtolC, B. subtilis, an S. aureus type strain, and a vancomycin intermediate-resistance S. aureus strain (VISA). Activity of 1,6-dihydro 8-propylanthraquinone against E. coli ΔtolC was approximately 10-fold higher than that of alnumycin. We were unable to confirm gyrase inhibition for either compound and believe that the modes of action of both compounds are worth reinvestigating.

1,4-Bis(5-phenyl-2-oxazolyl)benzene (POPOP) is a common scintillation fluorescent laser dye. In this manuscript, the synthesis of 2-Ar-5-(4-(4-Ar’-1H-1,2,3-triazol-1-yl)phenyl)-1,3,4-oxadiazoles (Ar, Ar’ = Ph, naphtalenyl-2, pyrenyl-1, triphenilenyl-2), as PAH-based aza-analogues of POPOP, by means of Cu-catalyzed click reaction between 2-(4-azidophenyl)-5-Ar-1,3,4-oxadiazole and terminal ethynyl-substituted PAHs is reported. An investigation of the photophysical properties of the obtained products was carried out, and their sensory response to nitroanalytes was evaluated. In the case of pyrenyl-1-substituted aza-POPOP, dramatic fluorescence quenching by nitroanalytes was observed.

Abstract Background The outbreak and global spread of COVID-19 was accompanied by an increase in reports of stigmatization of Chinese and Asian-looking people. The behavioral immune system provides a framework for stigmatization in response to infectious disease threats. Specifically, stigmatization might increase with rising levels of infectious disease threat. The present study aimed to examine this hypothesis during the early phase of the COVID-19 pandemic. Methods As part of the “EUCLID” project ( https://euclid.dbvis.de ), a total of 5011 persons from Germany were surveyed via an online-questionnaire between February 2nd and April 3rd, 2020, covering the progression of the COVID-19 pandemic over three time periods which were defined by critical events. Results There was no evidence for an increase in the stigmatization of Chinese and Asian-looking people across three topics, that is personal proximity, air travel, and medical measures upon arrival from China. Conclusions The present findings provide good news in that participants showed an adaptive response to the infectious disease threat rather than displaying increased stigmatization. Further research is necessary to specify the conditions that increase the risk of stigmatization in response to infectious disease threats.

Abstract Surgeons must visually distinguish soft-tissues, such as nerves, from surrounding anatomy to prevent complications and optimize patient outcomes. An accurate nerve segmentation and analysis tool could provide useful insight for surgical decision-making. Here, we present an end-to-end, automatic deep learning computer vision algorithm to segment and measure nerves. Unlike traditional medical imaging, our unconstrained setup with accessible handheld digital cameras, along with the unstructured open surgery scene, makes this task uniquely challenging. We investigate one common procedure, thyroidectomy, during which surgeons must avoid damaging the recurrent laryngeal nerve (RLN), which is responsible for human speech. We evaluate our segmentation algorithm on a diverse dataset across varied and challenging settings of operating room image capture, and show strong segmentation performance in the optimal image capture condition. This work lays the foundation for future research in real-time tissue discrimination and integration of accessible, intelligent tools into open surgery to provide actionable insights.

Abstract Primary spinal cord astrocytomas are rare, hence few data exist about the prognostic significance of molecular markers. Here we analyze a panel of molecular alterations in association with the clinical course. Histology and genome sequencing was performed in 26 spinal astrocytomas operated upon between 2000 and 2020. Next-generation DNA/RNA sequencing (NGS) and methylome analysis were performed to determine molecular alterations. Histology and NGS allowed the distinction of 5 tumor subgroups: glioblastoma IDH wildtype (GBM); diffuse midline glioma H3 K27M mutated (DMG-H3); high-grade astrocytoma with piloid features (HAP); diffuse astrocytoma IDH mutated (DA), diffuse leptomeningeal glioneural tumors (DGLN) and pilocytic astrocytoma (PA). Within all tumor entities GBM (median OS: 5.5 months), DMG-H3 (median OS: 13 months) and HAP (median OS: 8 months) showed a fatal prognosis. DMG-H3 tend to emerge in adolescence whereas GBM and HAP develop in the elderly. HAP are characterized by CDKN2A/B deletion and ATRX mutation. 50% of PA tumors carried a mutation in the PIK3CA gene which is seemingly associated with better outcome (median OS: PIK3CA mutated 107.5 vs 45.5 months in wildtype PA). This exploratory molecular profiling of spinal cord astrocytomas allows to identify distinct subgroups by combining molecular markers and histomorphology. DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.

Abstract Cerebral amyloid angiopathy (CAA) contributes to accelerated cognitive decline in Alzheimer’s disease (AD) dementia and is a common finding at autopsy. The APOEε4 allele and male sex have previously been reported to associate with increased CAA in AD. To inform biomarker and therapeutic target discovery, we aimed to identify additional genetic risk factors and biological pathways involved in this vascular component of AD etiology. We present a genome-wide association study of CAA pathology in AD cases and report sex- and APOE-stratified assessment of this phenotype. Genome-wide genotypes were collected from 853 neuropathology-confirmed AD cases scored for CAA across five brain regions, and imputed to the Haplotype Reference Consortium panel. Key variables and genome-wide genotypes were tested for association with CAA in all individuals and in sex and APOEε4 stratified subsets. Pathway enrichment was run for each of the genetic analyses. Implicated loci were further investigated for functional consequences using brain transcriptome data from 1,186 samples representing seven brain regions profiled as part of the AMP-AD consortium. We confirmed association of male sex, AD neuropathology and APOEε4 with increased CAA, and identified a novel locus, LINC-PINT, associated with lower CAA amongst APOEε4-negative individuals (rs10234094-C, beta = −3.70 [95% CI −0.49—−0.24]; p = 1.63E-08). Transcriptome profiling revealed higher LINC-PINT expression levels in AD cases, and association of rs10234094-C with altered LINC-PINT splicing. Pathway analysis indicates variation in genes involved in neuronal health and function are linked to CAA in AD patients. Further studies in additional and diverse cohorts are needed to assess broader translation of our findings.

Under physiological conditions, Escherichia coli RidA is an enamine/imine deaminase, which promotes the release of ammonia from reactive enamine/imine intermediates. However, when modified by hypochlorous acid (HOCl), it turns into a potent chaperone-like holdase that can effectively protect E. coli's proteome during oxidative stress. However, it is unknown, which residues need to be chlorinated for activation. Here, we employ a combination of LC-MS/MS analysis, a chemo-proteomic approach, and a mutagenesis study to identify residues responsible for RidA's chaperone-like function. Through LC-MS/MS of digested RidAHOCl, we obtained direct evidence of the chlorination of one arginine residue. To overcome the instability of the N-chloramine modification, we established a chemoproteomic approach using 5-(dimethylamino) naphthalene-1-sulfinic acid (DANSO2H) as a probe to label N-chlorinated lysines. Using this probe, we were able to detect the N-chlorination of six additional lysine residues. Moreover, using a mutagenesis study to genetically probe the role of single arginine and lysine residues, we found that the removal of arginines R105 and/or R128 led to a substantial reduction of RidAHOCl's chaperone activity. These results, together with structural analysis, confirm that the chaperone activity of RidA is concomitant with the loss of positive charges on the protein surface, leading to an increased overall protein hydrophobicity. Molecular modelling of RidAHOCl and the rational design of a RidA variant that shows chaperone activity even in the absence of HOCl further supports our hypothesis. Our data provide a molecular mechanism for HOCl-mediated chaperone activity found in RidA and a growing number of other HOCl-activated chaperones.

Manganese (Mn) plays a multifaceted role in the survival of pathogenic and symbiotic bacteria in eukaryotic hosts, and it is also important for free-living bacteria to grow in stressful environments. Previous research has uncovered components of the bacterial Mn homeostasis systems that control intracellular Mn levels, many of which are important for virulence. Multiple studies have also identified proteins that use Mn once it is inside the cell, including Mn-specific enzymes and enzymes transiently loaded with Mn for protection during oxidative stress. Emerging evidence continues to reveal proteins involved in maintaining Mn homeostasis, as well as enzymes that can bind Mn. For some of these enzymes, Mn serves as an essential cofactor. For other enzymes, mismetallation with Mn can lead to inactivation or poor activity. Some enzymes may even potentially be regulated by differential metallation with Mn or zinc (Zn). This review focuses on new developments in regulatory mechanisms that affect Mn homeostasis and usage, additional players in Mn import that increase bacterial survival during pathogenesis, and the interplay between Mn and other metals during Mn-responsive physiological processes. Lastly, we highlight lessons learned from fundamental research that are now being applied to bacterial interactions within larger microbial communities or eukaryotic hosts.

Objective: To provide qualitative empirical data on parental expectations of diagnostic prenatal genomic sequencing and the value of the results to families.Methods: We interviewed 15 families—mothers and/or fathers—who had had prenatal genomic sequencing about their expectations and their respective evaluations of the benefits of genomic sequencing.Results: Families’ hopes for genetic sequencing clustered around three themes: hoping to identify the cause of the fetal anomaly in a terminated pregnancy; hopes for guidance as to the likely outcome of current pregnancy; and hopes for information to support future family planning. In addition, hopes were discussed in terms of the potential for results to be beneficial in acquiring greater knowledge, while at the same time recognizing that new knowledge may raise more questions. Assessment of the value of sequencing largely mirrored these expectations when positive results seen. Negative results can also be seen as valuable in ruling out a genetic cause and in providing certainty that families had done everything that they could to know about the cause of fetal demise.Conclusion: It would appear that with guidance from genetic counsellors, families were largely able to navigate the many uncertainties of prenatal genomic sequencing and thus see themselves as benefitting from sequencing. However, support structures are essential to guide them through their expectations and interpretations of results to minimize possible harms. Engaging in the process of genomic sequencing was seen as beneficial in of itself to families who would otherwise be left without any options to seek diagnostic answers.

Research in environmental health is becoming increasingly reliant upon data science and computational methods that can more efficiently extract information from complex datasets. Data science and computational methods can be leveraged to better identify relationships between exposures to stressors in the environment and human disease outcomes, representing critical information needed to protect and improve global public health. Still, there remains a critical gap surrounding the training of researchers on these in silico methods. We aimed to address this gap by developing the inTelligence And Machine lEarning (TAME) Toolkit, promoting trainee-driven data generation, management, and analysis methods to “TAME” data in environmental health studies. Training modules were developed to provide applications-driven examples of data organization and analysis methods that can be used to address environmental health questions. Target audiences for these modules include students, post-baccalaureate and post-doctorate trainees, and professionals that are interested in expanding their skillset to include recent advances in data analysis methods relevant to environmental health, toxicology, exposure science, epidemiology, and bioinformatics/cheminformatics. Modules were developed by study coauthors using annotated script and were organized into three chapters within a GitHub Bookdown site. The first chapter of modules focuses on introductory data science, which includes the following topics: setting up R/RStudio and coding in the R environment; data organization basics; finding and visualizing data trends; high-dimensional data visualizations; and Findability, Accessibility, Interoperability, and Reusability (FAIR) data management practices. The second chapter of modules incorporates chemical-biological analyses and predictive modeling, spanning the following methods: dose-response modeling; machine learning and predictive modeling; mixtures analyses; -omics analyses; toxicokinetic modeling; and read-across toxicity predictions. The last chapter of modules was organized to provide examples on environmental health database mining and integration, including chemical exposure, health outcome, and environmental justice indicators. Training modules and associated data are publicly available online (https://uncsrp.github.io/Data-Analysis-Training-Modules/). Together, this resource provides unique opportunities to obtain introductory-level training on current data analysis methods applicable to 21st century science and environmental health.

BackgroundLong-term weight maintenance after weight loss is challenging, and innovative solutions are required. Digital technologies can support behavior change and, therefore, have the potential to be an effective tool for weight loss maintenance. However, to create meaningful and effective digital behavior change interventions that support end user values and needs, a combination of persuasive system design (PSD) principles and behavior change techniques (BCTs) might be needed. ObjectiveThis study aimed to investigate how an evidence-informed digital behavior change intervention can be designed and developed by combining PSD principles and BCTs into design features to support end user values and needs for long-term weight loss maintenance. MethodsThis study presents a concept for how PSD principles and BCTs can be translated into design features by combining design thinking and Agile methods to develop and deliver an evidence-informed digital behavior change intervention aimed at supporting weight maintenance. Overall, 45 stakeholders participated in the systematic and iterative development process comprising co-design workshops, prototyping, Agile development, and usability testing. This included prospective end users (n=17, 38%; ie, people with obesity who had lost ≥8% of their weight), health care providers (n=9, 20%), healthy volunteers (n=4, 9%), a service designer (n=1, 2%), and stakeholders from the multidisciplinary research and development team (n=14, 31%; ie, software developers; digital designers; and eHealth, behavior change, and obesity experts). Stakeholder input on how to operationalize the design features and optimize the technology was examined through formative evaluation and qualitative analyses using rapid and in-depth analysis approaches. ResultsA total of 17 design features combining PSD principles and BCTs were identified as important to support end user values and needs based on stakeholder input during the design and development of eCHANGE, a digital intervention to support long-term weight loss maintenance. The design features were combined into 4 main intervention components: Week Plan, My Overview, Knowledge and Skills, and Virtual Coach and Smart Feedback System. To support a healthy lifestyle and continued behavior change to maintain weight, PSD principles such as tailoring, personalization, self-monitoring, reminders, rewards, rehearsal, praise, and suggestions were combined and implemented into the design features together with BCTs from the clusters of goals and planning, feedback and monitoring, social support, repetition and substitution, shaping knowledge, natural consequences, associations, antecedents, identity, and self-belief. ConclusionsCombining and implementing PSD principles and BCTs in digital interventions aimed at supporting sustainable behavior change may contribute to the design of engaging and motivating interventions in line with end user values and needs. As such, the design and development of the eCHANGE intervention can provide valuable input for future design and tailoring of evidence-informed digital interventions, even beyond digital interventions in support of health behavior change and long-term weight loss maintenance. Trial RegistrationClinicalTrials.gov NCT04537988; https://clinicaltrials.gov/ct2/show/NCT04537988

ABSTRACT: Ethanol is one of the most widely used and abused drugs. Following ethanol consumption, ethanol enters the bloodstream from the small intestine where it gets distributed to peripheral tissues. In the bloodstream, ethanol is cleared from the system by the liver. The primary metabolism of ethanol uses alcohol dehydrogenase (ADH). In mammals, females appear to have higher ADH activity in liver samples than males. The purpose of the first experiment was to analyze sex differences in ADH levels following 12 d of ethanol administration (i.e., water or 2 g/kg) in male and female quail. Following the last daily treatment of ethanol, quail were euthanized, their livers were extracted, and ADH was analyzed in liver homogenate samples. Results showed that female quail had higher ADH levels, heavier livers, and a greater liver to body weight ratio than male quail. In a second experiment, we aimed to develop a blood ethanol concentration (BEC) profile for both male and female quail. Quail were administered 0.75 or 2 g/kg of ethanol and blood was collected at 0.5, 1, 2, 4, 6, 8, 12, 24 h after gavage administration. Blood ethanol concentration was analyzed using an Analox. We found that quail had a fairly rapid increase in BECs followed by a steady and slow disappearance of ethanol from the blood samples. Female quail had a lower peak of ethanol concentration and a smaller area under the curve (AUC) than male quail. The current research suggests that higher ADH levels in female quail may be responsible for increased metabolism of ethanol. In general, quail appear to eliminate ethanol more slowly than rodents. Thus, as a model, they may allow for a prolonged window with which to investigate the effects of ethanol.

The capacity for inhibitory control is an important cognitive process that undergoes dynamic changes over the course of the lifespan. Robust characterization of this trajectory, considering age continuously and using flexible modeling techniques, is critical to advance our understanding of the neural mechanisms that differ in healthy aging and neurological disease. The interleaved pro/anti-saccade task (IPAST), in which pro- and anti-saccade trials are randomly interleaved within a block, provides a simple and sensitive means of assessing the neural circuitry underlying inhibitory control. We utilized IPAST data collected from a large cross-sectional cohort of normative participants (n = 604, 5–93 years of age), standardized pre-processing protocols, generalized additive modeling, and change point analysis to investigate the effect of age on saccade behavior and identify significant periods of change throughout the lifespan. Maturation of IPAST measures occurred throughout adolescence, while subsequent decline began as early as the mid-20s and continued into old age. Considering pro-saccade correct responses and anti-saccade direction errors made at express (short) and regular (long) latencies was crucial in differentiating developmental and aging processes. We additionally characterized the effect of age on voluntary override time, a novel measure describing the time at which voluntary processes begin to overcome automated processes on anti-saccade trials. Drawing on converging animal neurophysiology, human neuroimaging, and computational modeling literature, we propose potential frontal-parietal and frontal-striatal mechanisms that may mediate the behavioral changes revealed in our analysis. We liken the models presented here to “cognitive growth curves” which have important implications for improved detection of neurological disease states that emerge during vulnerable windows of developing and aging.

Background: Methodological comparisons of hormone quantification techniques have repeatedly demonstrated that, in adults, enzyme immunoassay (EIA) inflates steroid hormone concentrations relative to mass spectrometry. However, methodological comparisons in adolescent samples remain rare, and few studies have examined how chemiluminescent immunoassay (CLIA), another popular immunoassay, compares to mass spectrometry. Additionally, no studies have examined how differences in analytical techniques may be affecting relationships between steroid hormone levels and outcomes of interest, such as psychopathology. This pre-registered analysis of an existing dataset measured salivary cortisol and testosterone using both CLIA and liquid chromatography dual mass spectrometry (LC-MS/MS) in a repeated measures (516 samples) sample of 207 9th graders. Methods: In aim 1, this study sought to expand on past findings by 1) measuring inflation of testosterone and cortisol by CLIA in a relatively large adolescent sample, and 2) showing that CLIA (like EIA) testosterone inflation was especially true in groups with low ‘true’ testosterone levels. In aim 2, this study sought to examine the impact of hormone quantification method on relationships between hormone levels and psychopathological measures (the Children's Depression Inventory, the Perceived Social Stress Scale, the UCLA Loneliness Scale, and the Anxious Avoidant and Negative Self Evaluation subscales of the Social Anxiety Scale for Adolescents). Results: We found that CLIA, like EIA, inflated testosterone and cortisol levels and overestimated female testosterone resulting in suppressed sex differences in testosterone. We did not observe these same patterns when examining testosterone in individuals with differing levels of pubertal development. Results of psychopathology analyses demonstrated no significant method differences in hormone-psychopathology relationships. Conclusions: Our findings show that CLIA introduces proportional bias in cortisol and testosterone in a manner that suppresses sex differences in testosterone. Steroid measurement method did not significantly moderate the relationship between hormones and psychopathology in our sample, though more work is needed to investigate this question in larger, clinical samples.

Genomic sequencing has been increasingly utilized for prenatal diagnosis in recent years and this trend is likely to continue. However, decision-making for parents in the prenatal period is particularly fraught, and prenatal sequencing would significantly expand the complexity of managing health risk information, reproductive options, and healthcare access. This qualitative study investigates decision-making processes amongst parents who enrolled or declined to enroll in the prenatal arm of the California-based Program in Prenatal and Pediatric Genome Sequencing (P3EGS), a study in the Clinical Sequencing Evidence-Generating Research (CSER) consortium that offered whole exome sequencing for fetal anomalies with a focus on underrepresented groups in genomic research. Drawing on the views of 18 prenatal families who agreed to be interviewed after enrolling (n = 15) or declining to enroll (n = 3) in P3EGS, we observed that the timing of sequencing, coupled with unique considerations around experiences of time during pregnancy and prenatal testing, intersect with structural supports beyond the clinic to produce preferences for and against prenatal sequencing and to contain the threat of unwelcome, uncertain knowledge. Particularly for those without structural supports, finding out consequential information may be more palatable after the birth, when the first stage of the uncertain future has been revealed. Future research should examine the role of temporality in decision-making around prenatal genomic sequencing across diverse population cohorts, in order to observe more precisely the role that structural barriers play in patient preferences.

Abstract The Global Carbon Project estimates that the terrestrial biosphere has absorbed about one‐third of anthropogenic CO2 emissions during the 1959–2019 period. This sink‐estimate is produced by an ensemble of terrestrial biosphere models and is consistent with the land uptake inferred from the residual of emissions and ocean uptake. The purpose of our study is to understand how well terrestrial biosphere models reproduce the processes that drive the terrestrial carbon sink. One challenge is to decide what level of agreement between model output and observation‐based reference data is adequate considering that reference data are prone to uncertainties. To define such a level of agreement, we compute benchmark scores that quantify the similarity between independently derived reference data sets using multiple statistical metrics. Models are considered to perform well if their model scores reach benchmark scores. Our results show that reference data can differ considerably, causing benchmark scores to be low. Model scores are often of similar magnitude as benchmark scores, implying that model performance is reasonable given how different reference data are. While model performance is encouraging, ample potential for improvements remains, including a reduction in a positive leaf area index bias, improved representations of processes that govern soil organic carbon in high latitudes, and an assessment of causes that drive the inter‐model spread of gross primary productivity in boreal regions and humid tropics. The success of future model development will increasingly depend on our capacity to reduce and account for observational uncertainties.

Despite problem posing's prominence in mathematics education research, its implementation in classrooms is limited. Therefore, teacher educators should incorporate problem posing tasks into preparation programs to help prospective teachers gain confidence in their abilities. One approach to teaching problem posing includes providing examples. The Common Core State Standards Initiative provides taxonomies with examples of one-step word problems for all four basic operations. Through this mixed-methods study, preservice teachers (N = 44) regularly identified and posed word problems within the addition and subtraction taxonomy. Before and after the intervention, the preservice teachers answered survey questions and posed problems to model given equations. The researchers analyzed the preservice teachers' abilities to pose logical word problems and to match given equations before and after instruction. They also quantitatively analyzed Likert-style survey responses on perceptions of posing the various types of word problems and integrated the results with a qualitative analysis of open-ended responses expanding on the same questions. Results showed participants' abilities to pose problems increased after the intervention. Additionally, participants felt problems with the unknown information at the beginning or middle were harder to pose than those with the unknown information at the end.

Abstract Background Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists. Methods Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms “human” and “English” and limited the search to the relevant subject age range with the term “adult.” Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance. Results Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination. Interpretation This review provides the first Canadian guidance regarding assessment of an adolescent and adult with a suspected allergy to one of the COVID-19 vaccines currently available, or any of their known allergenic components, and for patients who are immunocompromised who require vaccination for COVID-19. As information is updated this guidance will be updated accordingly.

Relevance. Arterial hypertension (AH) and anxiety-depressive disorders (ADD) are comorbid pathologies that are common in clinical practice. At the same time, the possibility of including an antidepressant in antihypertensive therapy for optimal control of hypertension, as well as to ensure a vasoprotective effect, has not been studied enough. Aim. To compare the effect of traditional antihypertensive therapy and therapy, including an antidepressant, on indicators of the daily profile of blood pressure (BP), stiffness of the vascular wall and central aortic pressure (CAP), the severity of anxiety and depression, as well as on cognitive function (CF) in patients AH and ADD. Materials and methods. The study included 90 patients with AH and ADD, who were randomized into two groups: group 1 patients who received a fixed combination of an angiotensin II receptor blocker and a diuretic, a b-blocker and an antidepressant; group 2 persons who took only three-component antihypertensive therapy. Before and after 24 weeks, all patients underwent a general clinical examination, 24-hour BP monitoring ABPM (BpLab Vasotens, Petr Telegin, Russia) with an assessment of the daily profile of BP, CAP and vascular stiffness. In addition, testing was carried out on the HADS, CES-D scales; CF were rated according to the Montreal scale. Results. In the group of patients treated with an antidepressant, it was noted that the target BP level was achieved more quickly when lower doses of angiotensin II receptor blockers were prescribed. After 6 months of therapy in both groups, there was a comparable positive dynamics of the main indicators of ABPM. In group 1, a statistically more pronounced decrease in both peripheral and CAP at night was recorded. In both groups of patients, a decrease in the augmentation index was noted; however, a statistically significant improvement in the parameters of the speed of propagation of the pulse wave in the aorta and the time of propagation of the reflected wave was recorded only in persons receiving antidepressant. In group 1, there was a regression of ADD, as well as a significant improvement in CF. Conclusions. The use of sertraline as part of a combination antihypertensive therapy in patients with AH and ADD contributed to a more rapid achievement of target BP values, a significant improvement in ABPM (especially at night), vascular wall stiffness and CAP. It is also important that the appointment of sertraline was accompanied by a regression of anxiety-depressive symptoms, an improvement in CF.

Abstract Background Ethnographic approaches offer a method and a way of thinking about implementation. This manuscript applies a specific case study method to describe the impact of the longitudinal interplay between implementation stakeholders. Growing out of science and technology studies (STS) and drawing on the latent archaeological sensibilities implied by ethnographic methods, the STS case-study is a tool for implementors to use when a piece of material culture is an essential component of an innovation. Methods We conducted an ethnographic process evaluation of the clinical implementation of tele-critical care (Tele-CC) services in the Department of Veterans Affairs. We collected fieldnotes and conducted participant observation at virtual and in-person education and planning events (n = 101 h). At Go-Live and 6-months post-implementation, we conducted site visits to the Tele-CC hub and 3 partnered ICUs. We led semi-structured interviews with ICU staff at Go-Live (43 interviews with 65 participants) and with ICU and Tele-CC staff 6-months post-implementation (44 interviews with 67 participants). We used verification strategies, including methodological coherence, appropriate sampling, collecting and analyzing data concurrently, and thinking theoretically, to ensure the reliability and validity of our data collection and analysis process. Results The STS case-study helped us realize that we must think differently about how a Tele-CC clinician could be noticed moving from communal to intimate space. To understand how perceptions of surveillance impacted staff acceptance, we mapped the materials through which surveillance came to matter in the stories staff told about cameras, buttons, chimes, motors, curtains, and doorbells. Conclusions STS case-studies contribute to the literature on longitudinal qualitive research (LQR) in implementation science, including pen portraits and periodic reflections. Anchored by the material, the heterogeneity of an STS case-study generates questions and encourages exploring differences. Begun early enough, the STS case-study method, like periodic reflections, can serve to iteratively inform data collection for researchers and implementors. The next step is to determine systematically how material culture can reveal implementation barriers and direct attention to potential solutions that address tacit, deeply rooted challenges to innovations in practice and technology.

Abstract Background Mosses in high-latitude ecosystems harbor diverse bacterial taxa, including N2-fixers which are key contributors to nitrogen dynamics in these systems. Yet the relative importance of moss host species, and environmental factors, in structuring these microbial communities and their N2-fixing potential remains unclear. We studied 26 boreal and tundra moss species across 24 sites in Alaska, USA, from 61 to 69° N. We used cultivation-independent approaches to characterize the variation in moss-associated bacterial communities as a function of host species identity and site characteristics. We also measured N2-fixation rates via 15N2 isotopic enrichment and identified potential N2-fixing bacteria using available literature and genomic information. Results Host species identity and host evolutionary history were both highly predictive of moss microbiome composition, highlighting strong phylogenetic coherence in these microbial communities. Although less important, light availability and temperature also influenced composition of the moss microbiome. Finally, we identified putative N2-fixing bacteria specific to some moss hosts, including potential N2-fixing bacteria outside well-studied cyanobacterial clades. Conclusions The strong effect of host identity on moss-associated bacterial communities demonstrates mosses’ utility for understanding plant-microbe interactions in non-leguminous systems. Our work also highlights the likely importance of novel bacterial taxa to N2-fixation in high-latitude ecosystems. Video Abstract

Abstract Background Double J ureteral stents are widely used on urological patients to provide drainage of the upper urinary tract. Unfourtunately, ureteral stents are not free from complications, as bacterial colonization and require a second procedure for removal. The purpose of the current comparative experimental study is to evaluate a new heparin-coated biodegradable antireflux ureteral stent (BraidStent®-H) to prevent urinary bacterial colonization. Methods A total of 24 female pigs were underwent determination of bacteriuria and nephrosonographic, endoscopic and contrast fluoroscopy assessment of the urinary tract. Afterward, were randomly assigned animals to Group-I, in which a 5Fr double-pigtail ureteral stent was placed for 6 weeks, or Group-II, in which a BraidStent®-H was placed. Follow-up assessments were performed at 1, 3, 6, 8, 12 weeks. The final follow-up includes the above methods and an exhaustive pathological study of the urinary tract was accomplished after 20 weeks. Results Bacteriuria findings in the first 48 h were significant between groups at 6 h and 12 h. Asymptomatic bacteriuria does not reach 100% of the animals in Group-II until 48 h versus Group-I where it appears at 6 h. The weekly bacteriuria mean rate was 27.7% and 44.4% in Group I and II respectively, without statistical significance. In Group II there were no animals with vesicoureteral reflux, with statistical significance at 3 and 6 weeks with Group-I. The 91.2% of stents in Group-II were degraded between 3 and 6 weeks, without obstructive fragments. Distal ureteral peristalsis was maintained in 66.6–75% in Group-II at 1–6 weeks. Conclusions The heparin coating of BraidStent® allows an early decrease of bacterial colonization, but its effectiveness is low at the long term. Heparin coating did not affect scheduled degradation rate or size of stents fragments. BraidStent®-H avoids the side effects associated with current ureteral stents, thus should cause less discomfort to patients.

Abstract Delayed emergence from anesthesia was previously reported in a case study of a child with Glycine Encephalopathy. To investigate the neural basis of this delayed emergence, we developed a zebrafish glial glycine transporter (glyt1 − / −) mutant model. We compared locomotor behaviors; dose–response curves for tricaine, ketamine, and 2,6-diisopropylphenol (propofol); time to emergence from these anesthetics; and time to emergence from propofol after craniotomy in glyt1−/− mutants and their siblings. To identify differentially active brain regions in glyt1−/− mutants, we used pERK immunohistochemistry as a proxy for brain-wide neuronal activity. We show that glyt1−/− mutants initiated normal bouts of movement less frequently indicating lethargy-like behaviors. Despite similar anesthesia dose–response curves, glyt1−/− mutants took over twice as long as their siblings to emerge from ketamine or propofol, mimicking findings from the human case study. Reducing glycine levels rescued timely emergence in glyt1−/− mutants, pointing to a causal role for elevated glycine. Brain-wide pERK staining showed elevated activity in hypnotic brain regions in glyt1−/− mutants under baseline conditions and a delay in sensorimotor integration during emergence from anesthesia. Our study links elevated activity in preoptic brain regions and reduced sensorimotor integration to lethargy-like behaviors and delayed emergence from propofol in glyt1−/− mutants.

Abstract A significant number of Baka Pygmies in Cameroon have been sedentarised in roadside villages, in contrast to their nomadic hunter-gatherer existence of the past. Although this change in lifestyle has had important consequences on health, most Baka villages still supplement their diets from forest products, especially wild meat. We used a combination of participatory methods and monitoring of individual hunters to map hunting territories in 10 Baka villages in southeastern Cameroon. From these, we determined whether wild meat extraction levels per village were related to the size of hunting territories, measured habitat use by hunters and finally defined the overlap between hunting territories and extractive industries in the region. Mapped village hunting areas averaged 205.2 ± 108.7 km2 (range 76.8–352.0 km2); all villages used a total of 2052 km2. From 295 tracks of 51 hunters, we showed that hunters travelled an average of 16.5 ± 13.5 km (range 0.9–89.8 km) from each village. Home ranges, derived from kernel utilization distributions, were correlated with village offtake levels, but hunter offtake and distance travelled were not significantly related, suggesting that enough prey was available even close to the villages. Hunters in all village areas exhibited a clear bias towards certain habitats, as indicated by positive Ivlev’s index of selectivity values. We also showed that all village hunting territories and hunter home ranges fall within mining and logging concessions. Our results are important for local understanding of forest land uses and to reconcile these with the other land uses in the region to better inform decisions concerning land use policy and planning.

Background and Objectives: Remote patient monitoring (RPM) of vital signs and symptoms for lung transplant recipients (LTRs) has become increasingly relevant in many situations. Nevertheless, RPM research integrating multisensory home monitoring in LTRs is scarce. We developed a novel multisensory home monitoring device and tested it in the context of COVID-19 vaccinations. We hypothesize that multisensory RPM and smartphone-based questionnaire feedback on signs and symptoms will be well accepted among LTRs. To assess the usability and acceptability of a remote monitoring system consisting of wearable devices, including home spirometry and a smartphone-based questionnaire application for symptom and vital sign monitoring using wearable devices, during the first and second SARS-CoV-2 vaccination. Materials and Methods: Observational usability pilot study for six weeks of home monitoring with the COVIDA Desk for LTRs. During the first week after the vaccination, intensive monitoring was performed by recording data on physical activity, spirometry, temperature, pulse oximetry and self-reported symptoms, signs and additional measurements. During the subsequent days, the number of monitoring assessments was reduced. LTRs reported on their perceptions of the usability of the monitoring device through a purpose-designed questionnaire. Results: Ten LTRs planning to receive the first COVID-19 vaccinations were recruited. For the intensive monitoring study phase, LTRs recorded symptoms, signs and additional measurements. The most frequent adverse events reported were local pain, fatigue, sleep disturbance and headache. The duration of these symptoms was 5–8 days post-vaccination. Adherence to the main monitoring devices was high. LTRs rated usability as high. The majority were willing to continue monitoring. Conclusions: The COVIDA Desk showed favorable technical performance and was well accepted by the LTRs during the vaccination phase of the pandemic. The feasibility of the RPM system deployment was proven by the rapid recruitment uptake, technical performance (i.e., low number of errors), favorable user experience questionnaires and detailed individual user feedback.

Plastics are synthetic materials made from organic polymers that are ubiquitous in daily living and are especially important in the healthcare setting. However, recent advances have revealed the pervasive nature of microplastics, which are formed by degradation of existing plastic products. Although the impact on human health has yet to be fully characterised, there is increasing evidence that microplastics can trigger inflammatory damage, microbial dysbiosis, and oxidative stress in humans. Although there are limited studies investigating their effect on the ocular surface, studies of microplastics on other organs provide some insights. The prevalence of plastic waste has also triggered public outcry, culminating in the development of legislation aimed at reducing microplastics in commercial products. We present a review outlining the possible sources of microplastics leading to ocular exposure, and analyse the possible mechanisms of ocular surface damage. Finally, we examine the utility and consequences of current legislation surrounding microplastic regulation.

Abstract Background Chronic myeloid leukemia (CML) and chronic neutrophilic leukemia (CNL) are two myeloproliferative neoplasms with mutually exclusive diagnostic criteria. A hallmark of CML is the Philadelphia chromosome (Ph), which results in a BCR-ABL1 fusion gene and constitutive tyrosine kinase activity. CNL is a Ph-negative neoplasm and is defined in part by the presence of CSF3R mutations, which drive constative JAK/STAT signaling. Case presentation Here, we report the exceedingly rare co-occurrence of two granulocytic myeloproliferative neoplasms in a 69-year old male patient. After an initial diagnosis of chronic myeloid leukemia, the patient’s clinical course was shaped by hematologic toxicity, the emergence of treatment-resistant BCR-ABL1 clones, and the expansion of a CSF3R-mutant clone without ABL1 mutations under selective pressure from tyrosine kinase inhibitors. The emergence of the CSF3R-mutant, neutrophilic clone led to the diagnosis of CNL as a second myeloproliferative neoplasm in the same patient. Conclusions This is the first reported case of CNL arising subsequent to CML, which occurred under selective pressure from targeted therapy in a patient with complex clonal architecture. Patients with such molecularly complex disease may ultimately benefit from combination therapy that targets multiple oncogenic pathways.

Marine plastic is a ubiquitous environmental problem that can have an impact on a variety of marine biota, such as seabirds, making it an important concern for scientists and policy makers. Although research on plastic ingestion by seabirds is increasing, few studies have examined policies and long-term monitoring programs to reduce marine plastic in the Arctic. This paper provides a review of international, national, and regional policies and long-term monitoring programs that address marine plastic in relation to seabirds in the Arctic countries: Canada, the Kingdom of Denmark (Greenland and the Faroe Islands), Finland, Iceland, Norway, the Russian Federation, Sweden, and the United States of America. Results show that a broad range of international, national, regional and local policies address marine debris, specifically through waste management and the prevention of pollution from ships. However, few policies directly address seabirds and other marine biota. Further, policies are implemented inconsistently across regions, making it difficult to enforce and monitor the efficacy of these policies given the long-range transport of plastic pollution globally. To reduce marine plastic pollution in the Arctic environment, pan-Arctic and international collaboration is needed to implement standardized policies and long-term monitoring programs for marine plastic in the Arctic and worldwide.

Abstract The brain-expressed ubiquilins, UBQLNs 1, 2 and 4, are highly homologous proteins that participate in multiple aspects of protein homeostasis and are implicated in neurodegenerative diseases. Studies have established that UBQLN2 forms liquid-like condensates and accumulates in pathogenic aggregates, much like other proteins linked to neurodegenerative diseases. However, the relative condensate and aggregate formation of the three brain-expressed ubiquilins is unknown. Here we report that the three ubiquilins differ in aggregation propensity, revealed by in-vitro experiments, cellular models, and analysis of human brain tissue. UBQLN4 displays heightened aggregation propensity over the other ubiquilins and, like amyloids, UBQLN4 forms ThioflavinT-positive fibrils in vitro. Measuring fluorescence recovery after photobleaching (FRAP) of puncta in cells, we report that all three ubiquilins undergo liquid–liquid phase transition. UBQLN2 and 4 exhibit slower recovery than UBQLN1, suggesting the condensates formed by these brain-expressed ubiquilins have different compositions and undergo distinct internal rearrangements. We conclude that while all brain-expressed ubiquilins exhibit self-association behavior manifesting as condensates, they follow distinct courses of phase-separation and aggregation. We suggest that this variability among ubiquilins along the continuum from liquid-like to solid informs both the normal ubiquitin-linked functions of ubiquilins and their accumulation and potential contribution to toxicity in neurodegenerative diseases.

The synthesis, anti-inflammatory and antioxidant properties of novel 5-hydroxy-7-methyl-3H-thiazolo[4,5-b]pyridin-2-one derivatives were discussed. Fused thiazolo[4,5-b]pyridin-2-ones were synthesized and modified at the N3, C5 and C6 positions of the main core in order to obtain the compounds with a satisfactory pharmacological profile. The synthesized compounds were preselected via molecular docking for further testing of their anti-inflammatory activity in vitro. Evaluation of novel compounds over the carageenin induced rat paw edema revealed strong anti-inflammatory action of some compounds including (thiazolo[4,5-b]pyridin-3(2H)-yl) propanenitrile (5) and thiazolo[4,5-b]pyridin-3(2H)-yl) propanoic acid (6) even exceeding the standard – Ibuprofen. The antioxidant activity of the synthesized compounds was measured in vitro by the method of scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals.

The authors of this article examine wisdom as an internal resource in a sample of medical workers that can prevent the development of unhealthy deviations and preserve professional and life longevity. The aim of this work was to study the relationship between wisdom and emotional burnout in medical personnel. The article provides a theoretical analysis of the study of emotional burnout in medical workers, offers a description of the phenomenon of wisdom, and describes foreign empirical research on wisdom in the medical field. To collect data, the authors used The Level of Wisdom Questionnaire by N.N. Mehtikhanova and The Inventory for Diagnosing Emotional Burnout by V.V. Boyko. An empirical study conducted with 184 employees of the Tyumen Regional Clinical Hospital found signs of emotional burnout in 53.8% of the respondents. A comparison of groups of the surveyed medical workers having different levels of emotional burnout revealed significant differences in terms of wisdom. A correlation analysis showed a negative relationship between wisdom and emotional burnout of the medical personnel ( rs = -0.48, p 0.001). A comparison between the groups of male and female respondents showed significant differences in terms of wisdom ( U = 1267.50, p = 0.016) and in terms of emotional burnout ( U = 1253.00, p = 0.013): wisdom was higher in the group of men, while emotional burnout was higher in the group of women. A pairwise comparison using the Mann - Whitney U -test revealed differences in wisdom between the groups of junior medical personnel and managers ( U = 31.00, p = 0.007) as well as between the groups of nurses and managers ( U = 326.00, p 0.001). Wisdom in both cases was higher for the group of managers. In sum, results of this study found that wisdom helps medical personnel resist burnout syndrome. The formation of this quality will help medical workers to better preserve their mental health and professional longevity.

Normal vaginal microflora consists of a wide range of microorganisms that maintain optimal vaginal milieu, preventing the development of infectious and inflammatory diseases of the vulva and vagina. However, the use of drugs, changes in hormonal status, urinary incontinence and pelvic floor dysfunction can disrupt the optimal balance of the vaginal microbiota, which leads to the development of dysbiotic pathological processes. The first-line treatment for stress urinary incontinence is the installation of suburethral slings. If incontinence is combined with a cystocele, it is advisable to perform reconstructive surgery for anterior vaginal wall, which has high both anatomical and functional efficacy. Surgical correction of genital prolapse and stress urinary incontinence requires bladder catheterization, which further increases the risk for dysbiotic and inflammatory diseases of the urogenital tract. The widespread use of antibiotic therapy leads to the formation of resistant strains of microorganisms and is not always fully realized, especially in the presence of post void residual urine in the postoperative period. Vaginal Zalain suppositories are highly sensitive to Candida species, and the use of Zalagel Intim gel is associated not only with antifungal, but also anti-inflammatory effect. Complex therapy with Zalain suppositories and Zalagel Intim gel is highly effective in the treatment of cytolytic, bacterial vaginosis, vulvovaginal candidiasis, and can also be used as the prevention of infectious complications after corrective interventions for pelvic organ prolapse and stress urinary incontinence.

In empirical studies of environmental law and policy, an important place is occupied by the issue of the underlying mechanisms that determine the relationship between territorial state structure and environmental performance. Duplication is among such mechanisms in the federations, including Russia. This paper addresses a specific aspect of the problem, i. e. the duplication in the establishment of regional categories of specially protected natural territories. The goal of the research is to determine the combination of originality and duplication among regional categories and to provide a legal interpretation of the observed phenomena. The objectives are (1) to collect a database of legal information about all regional categories; (2) to compare each federal category with each regional category and to find out whether the given regional category is original or duplicated; and (3) to aggregate the results of the comparison and make their legal interpretation. The main method of the study is a comparison made with a special quantitative technique. Additional methods are analysis, synthesis, induction, deduction, abstraction. Also, a few methods of statistical data analysis are used. As a result of the research, it is determined that duplication among regional categories in Russia often prevails over originality, and the median level of similarity between federal and regional categories is higher than the normal level of similarity. Most likely, part of the duplication results is explained by the fact that regional legislators do not sufficiently regulate the specifics of regional categories. Duplication has negative and positive consequences; i. e. it could result in lax legal protection of valuable territories, but it also could act as a compensatory mechanism overcoming the drawbacks of the federal regulation, and as a safeguard against negative changes of federal legislation. Thus, it may be proved that duplication could be unreasonable or justified. The regional legislators should avoid unreasonable duplication and regulate in detail the specifics of regional categories.

This research aims to investigate the way different unique cultural phenomena are reflected in the English financial and economic terminology. By using the special lexicographical sources, contemporary books and publications on economics, we choose three most representative groups of metaphors built on colorful and easy recognizable features of an individual culture such as national symbols, ethnic names and cuisines. First, this study examines various terminological units drawing on metaphors in terms of their semantics and structure. Second, we analyze their potential for term-building modeling. The results show that in the English professional language nationally marked metaphors become increasingly popular. They have an advantage to evoke strong associations and thus to create motivation base for a term. The latter is of paramount importance from pragmatic perspective since any term is designed to serve as a useful tool of an expert. Our findings also suggest that the process of term-building in the English financial and economic language is typically based on existing models. This provides another clear practical advantage to facilitate international communication.