Curr Protoc. 2023 Apr;3(4):e759. doi: 10.1002/cpz1.759.

ABSTRACT

Mother-to-fetus transmission of the SARS-CoV-2 virus via the placenta has been reported but cannot readily be studied in pregnant women. This protocol describes an in vitro method to investigate SARS-CoV-2 infection of human embryonic stem cells (hESCs), which are similar to epiblast cells in young postimplantation embryos. First, SARS-CoV-2 viral pseudoparticles, which contain the spike protein and a fluorescent reporter, are incorporated into a lentivirus backbone that is expanded in HEK 293T cells. Then, an infection assay based on hESCs is used with the viral pseudoparticles. An application of the infection assay in therapeutic drug screening is provided. This protocol allows infection of hESCs by SARS-CoV-2 pseudoparticles to be studied in vitro and can be used in conjunction with other assays to understand and potentially prevent infection. hESCs could also be differentiated to study infection in the three germ layers and their fetal cell derivatives. This disease-in-a-dish model could be readily applied to other hESC lines, and to other viral infections, that affect human prenatal development. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparing HEK 293T cells for lentiviral vector transfection Support Protocol 1: Visual inspection of transfected HEK 293T cells Basic Protocol 2: Generating viral pseudoparticles Support Protocol 2: Determining viral titer with HEK 293T-ACE2 cells Basic Protocol 3: Plating hESCs for the infection assay Support Protocol 3: Evaluating transduction efficiency.

PMID:37098759 | DOI:10.1002/cpz1.759

Cell Stem Cell. 2023 Apr 19:S1934-5909(23)00119-4. doi: 10.1016/j.stem.2023.04.001. Online ahead of print.

ABSTRACT

Inter-patient variability and the similarity of healthy and leukemic stem cells (LSCs) have impeded the characterization of LSCs in acute myeloid leukemia (AML) and their differentiation landscape. Here, we introduce CloneTracer, a novel method that adds clonal resolution to single-cell RNA-seq datasets. Applied to samples from 19 AML patients, CloneTracer revealed routes of leukemic differentiation. Although residual healthy and preleukemic cells dominated the dormant stem cell compartment, active LSCs resembled their healthy counterpart and retained erythroid capacity. By contrast, downstream myeloid progenitors constituted a highly aberrant, disease-defining compartment: their gene expression and differentiation state affected both the chemotherapy response and leukemia's ability to differentiate into transcriptomically normal monocytes. Finally, we demonstrated the potential of CloneTracer to identify surface markers misregulated specifically in leukemic cells. Taken together, CloneTracer reveals a differentiation landscape that mimics its healthy counterpart and may determine biology and therapy response in AML.

PMID:37098346 | DOI:10.1016/j.stem.2023.04.001

Cell Host Microbe. 2023 Apr 18:S1931-3128(23)00147-6. doi: 10.1016/j.chom.2023.04.003. Online ahead of print.

ABSTRACT

Clostridioides difficile infections (CDIs) remain a healthcare problem due to high rates of relapsing/recurrent CDIs (rCDIs). Breakdown of colonization resistance promoted by broad-spectrum antibiotics and the persistence of spores contribute to rCDI. Here, we demonstrate antimicrobial activity of the natural product class of chlorotonils against C. difficile. In contrast to vancomycin, chlorotonil A (ChA) efficiently inhibits disease and prevents rCDI in mice. Notably, ChA affects the murine and porcine microbiota to a lesser extent than vancomycin, largely preserving microbiota composition and minimally impacting the intestinal metabolome. Correspondingly, ChA treatment does not break colonization resistance against C. difficile and is linked to faster recovery of the microbiota after CDI. Additionally, ChA accumulates in the spore and inhibits outgrowth of C. difficile spores, thus potentially contributing to lower rates of rCDI. We conclude that chlorotonils have unique antimicrobial properties targeting critical steps in the infection cycle of C. difficile.

PMID:37098342 | DOI:10.1016/j.chom.2023.04.003

Sci Signal. 2023 Apr 25;16(782):eabp8923. doi: 10.1126/scisignal.abp8923. Epub 2023 Apr 25.

ABSTRACT

DDX RNA helicases promote RNA processing, but DDX3X also activates casein kinase 1 (CK1ε). We show that other DDX proteins also stimulate the protein kinase activity of CK1ε and that this extends to casein kinase 2 (CK2). CK2 enzymatic activity was stimulated by various DDX proteins at high substrate concentrations. DDX1, DDX24, DDX41, and DDX54 were required for full kinase activity in vitro and in Xenopus embryos. Mutational analysis of DDX3X indicated that CK1 and CK2 kinase stimulation engages its RNA binding but not catalytic motifs. Mathematical modeling of enzyme kinetics and stopped-flow spectroscopy showed that DDX proteins function as nucleotide exchange factors toward CK2 and reduce unproductive reaction intermediates and substrate inhibition. Our study reveals protein kinase stimulation by nucleotide exchange as important for kinase regulation and as a generic function of DDX proteins.

PMID:37098120 | DOI:10.1126/scisignal.abp8923

J Agric Food Chem. 2023 Apr 25. doi: 10.1021/acs.jafc.3c00301. Online ahead of print.

ABSTRACT

Transgenic soybean is the commercial crop with the largest cultivation area worldwide. During transgenic soybean cultivation, exogenous genes may be transferred to wild relatives through gene flow, posing unpredictable ecological risks. Accordingly, an environmental risk assessment should focus on fitness changes and underlying mechanisms in hybrids between transgenic and wild soybeans (Glycine soja). Matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) was used for in situ detection and imaging of protein changes in the seeds of transgenic herbicide-resistant soybean harboring epsps and pat genes, non-transgenic soybean, wild soybean, and their F2 hybrid. Protein data clearly distinguished wild soybeans, while the F2 seeds had protein characteristics of both parents and were distinguished from wild soybean seeds. Using UPLC-Q-TOF-MS, 22 differentially expressed proteins (DEPs) were identified, including 13 specific to wild soybean. Sucrose synthase and stress response-related DEPs were differentially expressed in parental and offspring. Differences in these may underpin the greater adaptability of the latter. MSI revealed DEP distribution in transgenic, wild, and F2 seeds. Identifying DEPs related to fitness may elucidate mechanisms underlying fitness differences among the studied varieties. Our study shows that MALDI-MSI has the potential to become a visual method for transgenic soybean analysis.

PMID:37098110 | DOI:10.1021/acs.jafc.3c00301

Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2207537120. doi: 10.1073/pnas.2207537120. Epub 2023 Apr 25.

ABSTRACT

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

PMID:37098064 | DOI:10.1073/pnas.2207537120

J Biomol Struct Dyn. 2023 Apr 25:1-10. doi: 10.1080/07391102.2023.2202270. Online ahead of print.

ABSTRACT

Quorum sensing plays a major role in the expression of virulence and development of biofilm in the human pathogen Pseudomonas aeruginosa. Natural compounds are well-known for their antibacterial characteristics by blocking various metabolic pathways. The goal of this study is to find natural compounds that mimic AHL (Acyl homoserine lactone) and suppress virulence in P. aeruginosa, which is triggered by quorum sensing-dependent pathways as an alternative drug development strategy. To support this rationale, functional network analysis and in silico investigations were carried out to find natural AHL analogues, followed by molecular docking studies. Out of the 16 top-hit AHL analogues derived from phytochemicals, seven ligands were found to bind to the quorum sensing activator proteins. Cassialactone, an AHL analogue, exhibited the highest binding affinity for RhlI, RhlR, and PqsE of P. aeruginosa, with a docking score of -9.4, -8.9, and -8.7 kcal/mol, respectively. 2(5H)-Furanone, a well-known inhibitor, was also docked to compare the docking score and intermolecular interactions between the ligand and the target protein. Furthermore, molecular dynamics simulations and binding free energy calculations were performed to determine the stability of the docked complexes. Additionally, the ADME properties of the analogues were also analyzed to evaluate the pharmacological parameters. Functional network analysis further showed that the interconnectedness of proteins such as RhlI, RhlR, LasI, and PqsE with the virulence and biofilm phenotype of the pathogen could offer potential as a therapeutic target.Communicated by Ramaswamy H. Sarma.

PMID:37097921 | DOI:10.1080/07391102.2023.2202270

New Phytol. 2023 Apr 25. doi: 10.1111/nph.18832. Online ahead of print.

NO ABSTRACT

PMID:37097258 | DOI:10.1111/nph.18832

Microbiol Spectr. 2023 Apr 25:e0049823. doi: 10.1128/spectrum.00498-23. Online ahead of print.

ABSTRACT

Candida auris, a multidrug-resistant human fungal pathogen that causes outbreaks of invasive infections, emerged as four distinct geographical clades. Previous studies identified genomic and proteomic differences in nutrient utilization on comparison to Candida albicans, suggesting that certain metabolic features may contribute to C. auris emergence. Since no high-throughput clade-specific metabolic characterization has been described yet, we performed a phenotypic screening of C. auris strains from all 4 clades on 664 nutrients, 120 chemicals, and 24 stressors. We identified common and clade- or strain-specific responses, including the preferred utilization of various dipeptides as nitrogen source and the inability of the clade II isolate AR 0381 to withstand chemical stress. Further analysis of the metabolic properties of C. auris isolates showed robust growth on intermediates of the tricarboxylic acid cycle, such as citrate and succinic and malic acids. However, there was reduced or no growth on pyruvate, lactic acid, or acetate, likely due to the lack of the monocarboxylic acid transporter Jen1, which is conserved in most pathogenic Candida species. Comparison of C. auris and C. albicans transcriptomes of cells grown on alternative carbon sources and dipeptides as a nitrogen source revealed common as well as species-unique responses. C. auris induced a significant number of genes with no ortholog in C. albicans, e.g., genes similar to the nicotinic acid transporter TNA1 (alternative carbon sources) and to the oligopeptide transporter (OPT) family (dipeptides). Thus, C. auris possesses unique metabolic features which could have contributed to its emergence as a pathogen. IMPORTANCE Four main clades of the emerging, multidrug-resistant human pathogen Candida auris have been identified, and they differ in their susceptibilities to antifungals and disinfectants. Moreover, clade- and strain-specific metabolic differences have been identified, but a comprehensive overview of nutritional characteristics and resistance to various stressors is missing. Here, we performed high-throughput phenotypic characterization of C. auris on various nutrients, stressors, and chemicals and obtained transcriptomes of cells grown on selected nutrients. The generated data sets identified multiple clade- and strain-specific phenotypes and induction of C. auris-specific metabolic genes, showing unique metabolic properties. The presented work provides a large amount of information for further investigations that could explain the role of metabolism in emergence and pathogenicity of this multidrug-resistant fungus.

PMID:37097196 | DOI:10.1128/spectrum.00498-23

Elife. 2023 Apr 25;12:e74915. doi: 10.7554/eLife.74915. Online ahead of print.

ABSTRACT

The immune system plays a major role in maintaining many physiological processes in the reproductive system. However, a complete characterization of the immune milieu in the ovary, and particularly how it is affected by female aging, is still lacking. Here, we utilize single-cell RNA sequencing and flow cytometry to construct the complete description of the murine ovarian immune system. We show that the composition of the immune cells undergoes an extensive shift with age towards adaptive immunity. We analyze the effect of aging on gene expression and chemokine and cytokine networks and show an overall decreased expression of inflammatory mediators together with an increased expression of senescent cells recognition receptors. Our results suggest that the fertile female's ovarian immune aging differs from the suggested female post-menopause inflammaging as it copes with the inflammatory stimulations during repeated cycles and the increasing need for clearance of accumulating atretic follicles.

PMID:37096871 | DOI:10.7554/eLife.74915

Elife. 2023 Apr 25;12:e84360. doi: 10.7554/eLife.84360. Online ahead of print.

ABSTRACT

During the rapid and reductive cleavage divisions of early embryogenesis, subcellular structures such as the nucleus and mitotic spindle scale to decreasing cell size. Mitotic chromosomes also decrease in size during development, presumably to scale coordinately with mitotic spindles, but underlying mechanisms are unclear. Here we combine in vivo and in vitro approaches using eggs and embryos from the frog Xenopus laevis to show that mitotic chromosome scaling is mechanistically distinct from other forms of subcellular scaling. We found that mitotic chromosomes scale continuously with cell, spindle and nuclear size in vivo. However, unlike for spindles and nuclei, mitotic chromosome size cannot be re-set by cytoplasmic factors from earlier developmental stages. In vitro, increasing nuclear-cytoplasmic (N/C) ratio is sufficient to recapitulate mitotic chromosome scaling, but not nuclear or spindle scaling, through differential loading of maternal factors during interphase. An additional pathway involving importin a scales mitotic chromosomes to cell surface area/volume ratio (SA/V) during metaphase. Finally, single-chromosome immunofluorescence and Hi-C data suggest that mitotic chromosomes shrink during embryogenesis through decreased recruitment of condensin I, resulting in major rearrangements of DNA loop architecture to accommodate the same amount of DNA on a shorter axis. Together, our findings demonstrate how mitotic chromosome size is set by spatially and temporally distinct developmental cues in the early embryo.

PMID:37096661 | DOI:10.7554/eLife.84360

Arthritis Rheumatol. 2023 Apr 25. doi: 10.1002/art.42536. Online ahead of print.

ABSTRACT

OBJECTIVE: Systemic sclerosis (SSc) is a multifactorial autoimmune fibrotic disorder involving complex rewiring of cell-intrinsic and cell-extrinsic signaling co-expression networks involving a range of cell types. However, the rewired circuits as well as corresponding cell-cell interactions remain poorly understood. To address this, we first used a predictive machine learning framework to analyze single-cell RNA-seq data from 24 SSc patients across the severity (as quantified by the Modified Rodnan Skin Score) spectrum.

METHODS: We used a LASSO-based predictive machine learning approach on the scRNA-seq dataset to identify predictive biomarkers of SSc severity, both across and within cell types. The use of L1 regularization helps prevent overfitting on high-dimensional data. Correlation network analyses were coupled to the LASSO model to identify cell-intrinsic and cell-extrinsic co-correlates of the identified biomarkers of SSc severity.

RESULTS: We found that the uncovered cell-type-specific predictive biomarkers of MRSS included previously implicated genes in fibroblast and myeloid cell subsets (e.g., SFPR2+ fibroblasts and monocytes), as well as novel gene biomarkers of MRSS, especially in keratinocytes. Correlation network analyses unveiled novel cross-talk between immune pathways as well as implicated keratinocytes in addition to fibroblast and myeloid cells as key cell-types involved in SSc pathogenesis. We then validated the uncovered association of key gene expression and protein markers in keratinocytes, KRT6A and S100A8, with SSc skin disease severity.

CONCLUSION: Our global systems analyses uncover previous uncharacterized cell-intrinsic and cell-extrinsic signaling co-expression networks underlying SSc severity that involve keratinocytes, myeloid cells and fibroblasts. This article is protected by copyright. All rights reserved.

PMID:37096444 | DOI:10.1002/art.42536

Elife. 2023 Apr 25;12:e84395. doi: 10.7554/eLife.84395.

ABSTRACT

Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to Escherichia coli in the presence of key AMPs from humans and agricultural animals by increasing AMP resistance. Moreover, MCR promotes bacterial growth in human serum and increases virulence in a Galleria mellonella infection model. Our study shows how the anthropogenic use of AMPs can drive the accidental evolution of resistance to the innate immune system of humans and animals. These findings have major implications for the design and use of therapeutic AMPs and suggest that MCR may be difficult to eradicate, even if colistin use is withdrawn.

PMID:37094804 | DOI:10.7554/eLife.84395

J Labelled Comp Radiopharm. 2023 Apr 24. doi: 10.1002/jlcr.4025. Online ahead of print.

ABSTRACT

The beta-site amyloid precursor protein cleaving enzyme (BACE1) is responsible for initiating the generation of beta-amyloid, the major constituent of amyloid plaques in Alzheimer's disease (AD). The purpose of this study was to develop a specific BACE1 radioligand for visualization of the distribution pattern and quantification of the BACE1 protein in the rodent and monkey brain both in vitro by autoradiography and in vivo by positron emission tomography (PET). The BACE1 inhibitor RO6807936 originating from an in-house chemical drug optimization program was selected based on its PET tracer like physicochemical properties and a favorable pharmacokinetic profile. Saturation binding analysis of [3 H]RO6807936 revealed specific and high affinity binding (KD = 2.9 nM) and a low Bmax value (4.3 nM) of the BACE1 protein in native rat brain membranes. [3 H]RO6807936 binding showed a ubiquitous distribution on rat brain slices in vitro with higher levels in the CA3 8 cell layer and the granule cell layer of the hippocampus. In a next step, RO6807936 was successfully radiolabelled with carbon-11 and showed acceptable uptake in the baboon brain as well as a widespread and rather homogeneous distribution consistent with rodent data. In vivo blockade studies with a specific BACE1 inhibitor reduced uptake of the tracer to homogenous levels across brain regions and demonstrated specificity of the signal. Our data warrant further profiling of this PET tracer candidate in humans to investigate BACE1 expression in normal individuals and those with AD and as an imaging biomarker for target occupancy studies in clinical drug trials.

PMID:37095603 | DOI:10.1002/jlcr.4025

Microbiome. 2023 Apr 24;11(1):88. doi: 10.1186/s40168-023-01506-0.

ABSTRACT

BACKGROUND: Psychological health risk is one of the most severe and complex risks in manned deep-space exploration and long-term closed environments. Recently, with the in-depth research of the microbiota-gut-brain axis, gut microbiota has been considered a new approach to maintain and improve psychological health. However, the correlation between gut microbiota and psychological changes inside long-term closed environments is still poorly understood. Herein, we used the "Lunar Palace 365" mission, a 1-year-long isolation study in the Lunar Palace 1 (a closed manned Bioregenerative Life Support System facility with excellent performance), to investigate the correlation between gut microbiota and psychological changes, in order to find some new potential psychobiotics to maintain and improve the psychological health of crew members.

RESULTS: We report some altered gut microbiota that were associated with psychological changes in the long-term closed environment. Four potential psychobiotics (Bacteroides uniformis, Roseburia inulinivorans, Eubacterium rectale, and Faecalibacterium prausnitzii) were identified. On the basis of metagenomic, metaproteomic, and metabolomic analyses, the four potential psychobiotics improved mood mainly through three pathways related to nervous system functions: first, by fermenting dietary fibers, they may produce short-chain fatty acids, such as butyric and propionic acids; second, they may regulate amino acid metabolism pathways of aspartic acid, glutamic acid, tryptophan, etc. (e.g., converting glutamic acid to gamma-aminobutyric acid; converting tryptophan to serotonin, kynurenic acid, or tryptamine); and third, they may regulate other pathways, such as taurine and cortisol metabolism. Furthermore, the results of animal experiments confirmed the positive regulatory effect and mechanism of these potential psychobiotics on mood.

CONCLUSIONS: These observations reveal that gut microbiota contributed to a robust effect on the maintenance and improvement of mental health in a long-term closed environment. Our findings represent a key step towards a better understanding the role of the gut microbiome in mammalian mental health during space flight and provide a basis for future efforts to develop microbiota-based countermeasures that mitigate risks to crew mental health during future long-term human space expeditions on the moon or Mars. This study also provides an essential reference for future applications of psychobiotics to neuropsychiatric treatments. Video Abstract.

PMID:37095530 | DOI:10.1186/s40168-023-01506-0

Nat Med. 2023 Apr 24. doi: 10.1038/s41591-023-02317-4. Online ahead of print.

ABSTRACT

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the Stratify Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities.

PMID:37095248 | DOI:10.1038/s41591-023-02317-4

Nat Commun. 2023 Apr 24;14(1):2359. doi: 10.1038/s41467-023-38119-y.

ABSTRACT

Synthetic sRNAs allow knockdown of target genes at translational level, but have been restricted to a limited number of bacteria. Here, we report the development of a broad-host-range synthetic sRNA (BHR-sRNA) platform employing the RoxS scaffold and the Hfq chaperone from Bacillus subtilis. BHR-sRNA is tested in 16 bacterial species including commensal, probiotic, pathogenic, and industrial bacteria, with >50% of target gene knockdown achieved in 12 bacterial species. For medical applications, virulence factors in Staphylococcus epidermidis and Klebsiella pneumoniae are knocked down to mitigate their virulence-associated phenotypes. For metabolic engineering applications, high performance Corynebacterium glutamicum strains capable of producing valerolactam (bulk chemical) and methyl anthranilate (fine chemical) are developed by combinatorial knockdown of target genes. A genome-scale sRNA library covering 2959 C. glutamicum genes is constructed for high-throughput colorimetric screening of indigoidine (natural colorant) overproducers. The BHR-sRNA platform will expedite engineering of diverse bacteria of both industrial and medical interest.

PMID:37095132 | DOI:10.1038/s41467-023-38119-y

Aliment Pharmacol Ther. 2023 May;57(10):1180-1182. doi: 10.1111/apt.17491.

NO ABSTRACT

PMID:37094315 | DOI:10.1111/apt.17491

Eur J Sport Sci. 2023 Apr 24:1-27. doi: 10.1080/17461391.2023.2207082. Online ahead of print.

ABSTRACT

AbstractEvidence suggests that preterm birth is associated with an impaired physical fitness later in life, but whether these effects are already visible since early childhood remains unknown. We aimed to compare the physical fitness of preterm preschoolers with that of children born at term. Children aged three to six years and born preterm (<35 weeks) were recruited from a Neonatal Intensive Care Unit, and children born at term (>37 weeks) were included as controls. A variety of physical fitness indicators (strength, cardiorespiratory fitness, agility, flexibility, and balance) were assessed with the PREFIT battery and the adapted sit and reach test. Physical activity levels were measured through the PrePAQ questionnaire. A total of 98 preterm children (gestational age 32.4 ± 2.3 weeks, age 5.1 ± 0.8 years) and 74 controls (gestational age 39.9 ± 1.0 weeks, age 4.8 ± 0.9 years) were analyzed. Despite no significant differences in physical activity levels (p > 0.05), preterm children showed an overall poorer physical fitness compared to controls. Specifically, preterm children had an impaired handgrip strength (-13.95%, p < 0.001), lower-limb muscle strength (-12.67%, p = 0.003), agility (-14.9%, p = 0.001), cardiorespiratory fitness (-12.73% p = 0.005) and flexibility (-17.04%, p = 0.001) compared to controls. An inverse dose-response association was observed between the level of prematurity and physical fitness, with very preterm children (gestational age ≤32 weeks) presenting the poorest fitness levels. In summary, prematurity seems to impair physical fitness since early childhood, which might support the need for promoting preventive strategies (e.g., fitness monitoring and applying exercise interventions).

PMID:37093663 | DOI:10.1080/17461391.2023.2207082

Microbiol Spectr. 2023 Apr 24:e0488122. doi: 10.1128/spectrum.04881-22. Online ahead of print.

ABSTRACT

The increased transmissibility of SARS-CoV-2 variants of concern (VOCs) has raised questions regarding the environmental stability of these viruses. Although a prolonged survival time has been reported for SARS-CoV-2, how long new variants can persist on contaminated surfaces and how environmental factors affect the persistence time are not fully characterized. The present study provides a comprehensive assessment of the stability of Omicron variants BA.1 and BA.5, which are currently circulating strains, on the surfaces of widely used transport packaging materials. By monitoring viable virus detection over a 7-day period under different environmental conditions, it was found that the environmental stability of SARS-CoV-2 Omicron variants depended heavily on the surface type, temperature, and virus concentration. In addition, virus nucleic acid exhibited high stability on the material surface independent of whether viable virus was detected. These findings provide useful information for logistics practitioners and the general public to appropriately deal with transport items under different conditions to minimize the risk of epidemic transmission. IMPORTANCE This study shows the environmental stability of SARS-CoV-2 Variants Omicron BA.1 and BA.5 on surfaces of widely used transport packaging materials. The findings demonstrate that the environmental stability of the SARS-CoV-2 Omicron variants varies based on material type. The viability of SARS-CoV-2 on material surfaces depends heavily on temperature and viral titer. Low temperatures and high viral titers promote virus survival. Moreover, in contrast to virus viability, virus nucleic acid exhibits high stability on the surfaces of widely used materials, making the detection of virus nucleic acid unsuitable for evaluating the risk of epidemic transmission.

PMID:37092817 | DOI:10.1128/spectrum.04881-22