Burning plasma achieved in inertial fusion.

Obtaining a burning plasma is a critical step towards self-sustaining fusion energy1. A burning plasma is one in which the fusion reactions themselves are the primary source of heating in the plasma, which is necessary to sustain and propagate the burn, enabling high energy gain. After decades of fusion research, here we achieve a burning-plasma state in the laboratory. These experiments were conducted at the US National Ignition Facility, a laser facility delivering up to 1.9 megajoules of energy in pulses with peak powers up to 500 terawatts. We use the lasers to generate X-rays in a radiation cavity to indirectly drive a fuel-containing capsule via the X-ray ablation pressure, which results in the implosion process compressing and heating the fuel via mechanical work. The burning-plasma state was created using a strategy to increase the spatial scale of the capsule2,3 through two different implosion concepts4-7. These experiments show fusion self-heating in excess of the mechanical work injected into the implosions, satisfying several burning-plasma metrics3,8. Additionally, we describe a subset of experiments that appear to have crossed the static self-heating boundary, where fusion heating surpasses the energy losses from radiation and conduction. These results provide an opportunity to study α-particle-dominated plasmas and burning-plasma physics in the laboratory.

Surgical Necrotizing Enterocolitis - Can We Predict the Need for Gastrostomy Tube Placement?

INTRODUCTION: Necrotizing enterocolitis (NEC) is a significant cause of morbidity and mortality among extremely premature infants. Approximately 50% of cases progress to surgery, frequently resulting in resection of necrotic bowel and ostomy creation. Premature neonates are at risk for bronchopulmonary dysplasia and feeding failure; surgery in these patients is higher risk. We evaluated the incidence of gastrostomy tube (GT) placement after ostomy reversal in surgical NEC to define a subset of patients who would benefit from concurrent ostomy reversal and GT placement. METHODS: A single-center retrospective study of infants with surgical NEC requiring ostomy creation between 2007 and 2021 was performed. RESULTS: Eighty patients met inclusion criteria. A GT was placed in 45/80 (56.3%), of which 3/45 (6.7%) were placed before, 20/45 (44.4%) concurrently with, and 22/45 (48.9%) after ostomy reversal. Between those who did and did not require GT placement, there were no significant differences in gestational age (27 versus 27 wk, P = 0.94) or birth weight (830 g versus 1055 g, P = 0.36). Hospital length of stay was longer in the GT group (128.2 versus 70.9 d, P < 0.0001). Time from ostomy reversal to hospital discharge was shorter when performed concurrently with GT (56 versus 77 d, P = 0.02). There were no differences in short-term or long-term GT related complications based on timing of GT placement. CONCLUSIONS: GT placement occurred in approximately 50% of patients with surgical NEC and GT may be accomplished safely at the time of ostomy reversal thus reducing the need for an additional procedure.

A multisystem model for understanding stress and adaptation in ethnically and racially diverse youth.

Contemporary biological and contextually based theoretical frameworks have conceptualized how stress exposure may influence adaptation in youth. However, nearly all of this scholarship neglects the role of specific contextual features and/or biological processes that are involved in ethnic-racial minority youth's responses and adaptation to sociocultural stressors. Drawing on the theoretical principles of the developmental psychopathology framework and contemporary models of stress and adaptation, this article proposes a new multisystem model that explains how multiple levels and systems within and outside of individual youth influence their sociocultural adaptation. We provide empirical evidence to support components of this multisystem model. We propose that research based on our new theoretical framework will capture the sociocultural experiences of ethnic-racial minority youth by centering processes that are relevant to their lived experiences, coping, and adjustment. In doing so, this model will inform psychosocial interventions focused on promoting healthy adaptation among ethnic and racial diverse youth. Finally, we offer recommendations to guide future research on stress and adaptation among ethnic and racial diverse youth, in particular, and developmental psychopathology more broadly.

A muscle cell-macrophage axis involving matrix metalloproteinase 14 facilitates extracellular matrix remodeling with mechanical loading.

The extracellular matrix (ECM) in skeletal muscle plays an integral role in tissue development, structural support, and force transmission. For successful adaptation to mechanical loading, remodeling processes must occur. In a large cohort of older adults, transcriptomics revealed that genes involved in ECM remodeling, including matrix metalloproteinase 14 (MMP14), were the most upregulated following 14 weeks of progressive resistance exercise training (PRT). Using single-cell RNA-seq, we identified macrophages as a source of Mmp14 in muscle following a hypertrophic exercise stimulus in mice. In vitro contractile activity in myotubes revealed that the gene encoding cytokine leukemia inhibitory factor (LIF) is robustly upregulated and can stimulate Mmp14 expression in macrophages. Functional experiments confirmed that modulation of this muscle cell-macrophage axis facilitated Type I collagen turnover. Finally, changes in LIF expression were significantly correlated with MMP14 expression in humans following 14 weeks of PRT. Our experiments reveal a mechanism whereby muscle fibers influence macrophage behavior to promote ECM remodeling in response to mechanical loading.

Direct frequency comb spectroscopy of HCN to evaluate line lists.

We report direct frequency comb spectroscopy of the 2ν1 band of H13CN in the short-wave infrared (λ = 1.56 µm) towards experimental validation of molecular line lists that support observatories like JWST. The laboratory measurements aim to test spectral reference data generated from an experimentally accurate potential energy surface (PES) and an ab initio dipole moment surface (DMS) calculated from quantum chemistry theory. Benchmarking theory with experiment will improve confidence in new astrophysics and astrochemistry inferred from spectroscopic observations of HCN and HNC. Here we describe our instrumentation and initial results using a cross-dispersed spectrometer with a virtually imaged phased array (VIPA).

Angiogenic and Inflammatory microRNA Regulation in a Mouse Model of Fetal Growth Restriction.

INTRODUCTION: Fetal growth restriction (FGR) is associated with impaired angiogenesis and chronic inflammation. MicroRNAs (miRs) are short noncoding RNAs that regulate gene expression at the post-transcriptional level by targeting messenger RNA (mRNA) for degradation or by suppressing translation. We hypothesize that dysregulation of miR-15b, an antiangiogenic miR, and miR-146a, an anti-inflammatory miR, are associated with the FGR's pathogenesis. METHODS: Pregnant mice were provided ad libitum access to food between E1 and E8. From E9-E18, dams received either a 50% caloric restricted diet (FGR) or continued ad libitum access (controls). Placentas were harvested at E18.5 and total RNA was extracted. Gene expression levels of miRs and mRNAs were compared between FGR and control placentas. RESULTS: Placentas affected by FGR demonstrated increased expression of miR-15b. Vascular endothelial growth factor alpha, which is downregulated in response to increased levels of miR-15b, was suppressed. The anti-inflammatory miR, miR-146a, was downregulated, resulting in upregulation of proinflammatory (IL-6, IL-8, and NFkB1) and oxidative stress (HIF-1α, SOD2, and Nox2) mediators. CONCLUSIONS: Aberrant angiogenesis and chronic inflammation seen in FGR appear to be associated with dysregulated miR-15b and miR-146a gene expression, respectively. This observation suggests these miRs play a post-transcriptional regulatory role in FGR, providing an insight into possible therapeutic targets.

Fetal lung volumes measured by MRI predict pulmonary morbidity among infants with giant omphaloceles.

OBJECTIVE: Giant omphaloceles (GO) have associated pulmonary hypoplasia and respiratory complications. Total lung volumes (TLV) on fetal MRI can prognosticate congenital diaphragmatic hernia outcomes; however, its applicability to GO is unknown. We hypothesize that late gestation TLV and observed-to-expected TLV (O/E TLV) on fetal MRI correlate with postnatal pulmonary morbidity in GO. METHOD: A single-institution retrospective review of GO evaluated between 2012 and 2022 was performed. Fetal MRI TLV between 32 and 36 weeks' gestation and O/E TLV throughout gestation were calculated and correlated with postnatal outcomes. RESULTS: 86 fetuses with omphaloceles were evaluated; however, only 26 met strict inclusion criteria. MRIs occurred between 18 and 36 weeks' gestation. Those requiring delivery room intubation had significantly lower late gestation TLV and O/E TLV. O/E TLV predicted tracheostomy placement and survival. Neither TLV nor O/E TLV predicted the length of hospitalization or supplemental oxygen after discharge. Three fetuses had a TLV less than 35 mL: one died of respiratory failure, and the other two required tracheostomy. CONCLUSIONS: Fetal MRI TLV measured between 32 and 36 weeks' gestation and O/E TLV predict the need for delivery room intubation and tracheostomy. O/E TLV correlated with survival. These data support fetal MRI as a prognostic tool to predict GO associated pulmonary morbidity.

An occupational health survey of the UK's mortuary workforce.

BACKGROUND: Mortuaries are predominantly staffed by anatomical pathology technologists (APTs) and pathologists, and the work they undertake carries implicit health risk due to its nature. Until now there has not been a nationwide assessment of the occupational health of these essential workers in the UK. AIMS: To assess the current occupational health status and needs of the mortuary workforce in the UK. METHODS: We created a bespoke, brief online survey which was approved by the professional bodies representing APTs and pathologists in the UK. The survey was disseminated electronically using these organizations' targeted mailing lists. RESULTS: Two hundred and thirty participants completed the survey, comprising 108 (47%) APTs and 122 (53%) pathologists. Most (89%) respondents reported that they have suffered from occupational health issues, the largest subcategory being musculoskeletal problems (77%). Almost half (48%) of APTs and around one-quarter (26%) of pathologists who responded have taken time off work in the last year because of occupational health problems, with almost one-fifth (19%) of the APTs having taken at least 4 weeks off. CONCLUSIONS: A significant number of workhours are lost per year to sick leave resulting from occupational health problems. Respondents' comments highlight issues in workspaces, rest facilities and staffing, and variability in working conditions across the country. We suggest that future workforce planning should prioritize good occupational health, with nationwide improvements in mortuary design.

Effects of Essential Oils on Scars and Wound Healing: A Systematic Review.

Essential oils (EOs) have been considered as a potential alternative therapy for wound healing and scar reduction. The aim of this article was to provide a comprehensive review examining the effects of EOs on wound healing and scars. PubMed, Cochrane, Ovid, and Embase computerized searches were performed through June 2020. Two independent reviewers conducted data extraction, with search results reviewed by the senior author following the PRISMA protocol. Three manuscripts examining three different EO-containing topical agents were analyzed. Outcomes include healing rate, erythema, pain, pruritus, patient discomfort, physician satisfaction, percent wound reduction, wound/scar surface perimeter area, and qualitative dermatological evaluation. All articles concluded that the EO-containing topical agents resulted in either superior or noninferior outcomes in comparison with controls. Hypericum-Calendula oil obtained lower wound surface perimeter area. Erythema (p = 0.001) was significantly decreased by the peppermint EO-containing topical agent. Physicians also reported greater satisfaction (p < 0.001) in wound appearance with use of the peppermint EO-containing topical agent. A paucity of studies have examined EO use for wound healing and scar reduction. Treatment with EO-containing topical agents resulted in decreased erythema with increased physician satisfaction of wound appearance. Future studies should assess what level of purity is needed for improved results and which EO, or combination of EOs, is most beneficial.

Mechanical overload-induced muscle-derived extracellular vesicles promote adipose tissue lipolysis.

How regular physical activity is able to improve health remains poorly understood. The release of factors from skeletal muscle following exercise has been proposed as a possible mechanism mediating such systemic benefits. We describe a mechanism wherein skeletal muscle, in response to a hypertrophic stimulus induced by mechanical overload (MOV), released extracellular vesicles (EVs) containing muscle-specific miR-1 that were preferentially taken up by epidydimal white adipose tissue (eWAT). In eWAT, miR-1 promoted adrenergic signaling and lipolysis by targeting Tfap2α, a known repressor of Adrß3 expression. Inhibiting EV release prevented the MOV-induced increase in eWAT miR-1 abundance and expression of lipolytic genes. Resistance exercise decreased skeletal muscle miR-1 expression with a concomitant increase in plasma EV miR-1 abundance, suggesting a similar mechanism may be operative in humans. Altogether, these findings demonstrate that skeletal muscle promotes metabolic adaptations in adipose tissue in response to MOV via EV-mediated delivery of miR-1.

Muscle transcriptional networks linked to resistance exercise training hypertrophic response heterogeneity.

The skeletal muscle hypertrophic response to resistance exercise training (RT) is highly variable across individuals. The molecular underpinnings of this heterogeneity are unclear. This study investigated transcriptional networks linked to RT-induced muscle hypertrophy, classified as 1) predictive of hypertrophy, 2) responsive to RT independent of muscle hypertrophy, or 3) plastic with hypertrophy. Older adults (n = 31, 18 F/13 M, 70 ± 4 yr) underwent 14-wk RT (3 days/wk, alternating high-low-high intensity). Muscle hypertrophy was assessed by pre- to post-RT change in mid-thigh muscle cross-sectional area (CSA) [computed tomography (CT), primary outcome] and thigh lean mass [dual-energy X-ray absorptiometry (DXA), secondary outcome]. Transcriptome-wide poly-A RNA-seq was performed on vastus lateralis tissue collected pre- (n = 31) and post-RT (n = 22). Prediction networks (using only baseline RNA-seq) were identified by weighted gene correlation network analysis (WGCNA). To identify Plasticity networks, WGCNA change indices for paired samples were calculated and correlated to changes in muscle size outcomes. Pathway-level information extractor (PLIER) was applied to identify Response networks and link genes to biological annotation. Prediction networks (n = 6) confirmed transcripts previously connected to resistance/aerobic training adaptations in the MetaMEx database while revealing novel member genes that should fuel future research to understand the influence of baseline muscle gene expression on hypertrophy. Response networks (n = 6) indicated RT-induced increase in aerobic metabolism and reduced expression of genes associated with spliceosome biology and type-I myofibers. A single exploratory Plasticity network was identified. Findings support that interindividual differences in baseline gene expression may contribute more than RT-induced changes in gene networks to muscle hypertrophic response heterogeneity. Code/Data: https://github.com/kallavin/MASTERS_manuscript/tree/master.

A best-practice guide to predicting plant traits from leaf-level hyperspectral data using partial least squares regression.

Partial least squares regression (PLSR) modelling is a statistical technique for correlating datasets, and involves the fitting of a linear regression between two matrices. One application of PLSR enables leaf traits to be estimated from hyperspectral optical reflectance data, facilitating rapid, high-throughput, non-destructive plant phenotyping. This technique is of interest and importance in a wide range of contexts including crop breeding and ecosystem monitoring. The lack of a consensus in the literature on how to perform PLSR means that interpreting model results can be challenging, applying existing models to novel datasets can be impossible, and unknown or undisclosed assumptions can lead to incorrect or spurious predictions. We address this lack of consensus by proposing best practices for using PLSR to predict plant traits from leaf-level hyperspectral data, including a discussion of when PLSR is applicable, and recommendations for data collection. We provide a tutorial to demonstrate how to develop a PLSR model, in the form of an R script accompanying this manuscript. This practical guide will assist all those interpreting and using PLSR models to predict leaf traits from spectral data, and advocates for a unified approach to using PLSR for predicting traits from spectra in the plant sciences.

In vivo analysis of γH2AX+ cells in skeletal muscle from aged and obese humans.

Over the past 20 years, various identifiers of cellular senescence have been used to quantify the abundance of these cells in different tissues. These include classic markers such as p16, senescence-associated ß-gal, and γH2AX, in addition to more recent markers (Sudan Black B and HMGB1). In vivo data on the usefulness of these markers in skeletal muscle are very limited and inconsistent. In the present study, we attempted to identify senescent cells in frozen human skeletal muscle biopsies using these markers to determine the effects of age and obesity on senescent cell burden; however, we were only able to assess the abundance of DNA-damaged nuclei using γH2AX immunohistochemistry. The abundance of γH2AX+ cells, including satellite cells, was not higher in muscle from old compared to young individuals; however, γH2AX+ cells were higher with obesity. Additionally, terminally differentiated, postmitotic myofiber nuclei from obese individuals had elevated γH2AX abundance compared to muscle from lean individuals. Analyses of gene expression support the conclusion that the elevated DNA damage and the senescence-associated secretory phenotype are preferentially associated with obesity in skeletal muscle. These data implicate obesity as a larger contributor to DNA damage in skeletal muscle than aging; however, more sensitive senescence markers for human skeletal muscle are needed to determine if these cells are in fact senescent.

Precision Spectroscopy of Nitrous Oxide Isotopocules with a Cross-Dispersed Spectrometer and a Mid-Infrared Frequency Comb.

As a potent greenhouse gas and an ozone-depleting agent, nitrous oxide (N2O) plays a critical role in the global climate. Effective mitigation relies on understanding global sources and sinks, which can be supported through isotopic analysis. We present a cross-dispersed spectrometer, coupled with a mid-infrared frequency comb, capable of simultaneously monitoring all singly substituted, stable isotopic variants of N2O. Rigorous evaluation of the instrument lineshape function and data treatment using a Doppler-broadened, low-pressure gas sample are discussed. Laboratory characterization of the spectrometer demonstrates sub-GHz spectral resolution and an average precision of 6.7 × 10-6 for fractional isotopic abundance retrievals in 1 s.

Pattern of failure in anaplastic glioma patients with an IDH1/2 mutation.

PURPOSE: The current study aimed to assess patterns of failure (PoF) in anaplastic glioma (AG) patients managed with intensity-modulated radiation therapy (IMRT) and their relationship to molecular subtype. METHODS: The outcomes of AG patients managed between 2008 and 2014 and entered into a prospective database were assessed, including PoF. AG was initially defined using the WHO 2007 classification, but for analysis, patients were subsequently recategorised based on WHO 2016 as anaplastic oligodendroglioma (AOD), astrocytoma isocitrate dehydrogenase (IDH) mutant (AAmut) or astrocytoma IDH wildtype (AAwt). Management involved IMRT and temozolomide (TMZ), including from 2011 patients with an IDH mutation (IDHmut) planned with 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET). PoF was local, marginal or distant in relation to the IMRT volume. Relapse-free survival (RFS) was calculated from the start of IMRT. RESULTS: A total of 156 patients were assessed, with median follow-up of 5.1 years. Of these patients, 75% were IDHmut, 44% were managed at first or later relapse and 73% received TMZ. Relapse occurred in 68 patients, with 6­year RFS of 75.0, 48.8 and 2.5% for AOD, AAmut and AAwt, respectively (p < 0.001). There was a component of local relapse in 63%, of marginal relapse in 19% and of distant relapse in 37% of relapses. Isolated local, marginal and distant relapse was evident in 51, 9 and 22%, respectively. A distant relapse pattern was more frequent in IDHmut compared to IDHwt patients (26% vs. 45%, p = 0.005), especially within the first 2 years post-IMRT. In multivariate analysis, distant relapse remained associated with AAmut (p < 0.002) and delayed IMRT until the second relapse (p < 0.001). CONCLUSION: Although patients with IDH-mutated AG have improved outcomes, there was a higher proportion of distant relapses occurring during the 2 years after IMRT.

Resident muscle stem cells are not required for testosterone-induced skeletal muscle hypertrophy.

It is postulated that testosterone-induced skeletal muscle hypertrophy is driven by myonuclear accretion as the result of satellite cell fusion. To directly test this hypothesis, we utilized the Pax7-DTA mouse model to deplete satellite cells in skeletal muscle followed by testosterone administration. Pax7-DTA mice (6 mo of age) were treated for 5 days with either vehicle [satellite cell replete (SC+)] or tamoxifen [satellite cell depleted (SC-)]. Following a washout period, a testosterone propionate or sham pellet was implanted for 21 days. Testosterone administration caused a significant increase in muscle fiber cross-sectional area in SC+ and SC- mice in both oxidative (soleus) and glycolytic (plantaris and extensor digitorum longus) muscles. In SC+ mice treated with testosterone, there was a significant increase in both satellite cell abundance and myonuclei that was completely absent in testosterone-treated SC- mice. These findings provide direct evidence that testosterone-induced muscle fiber hypertrophy does not require an increase in satellite cell abundance or myonuclear accretion.Listen to a podcast about this Rapid Report with senior author E. E. Dupont-Versteegden (https://ajpcell.podbean.com/e/podcast-on-paper-that-shows-testosterone-induced-skeletal-muscle-hypertrophy-does-not-need-muscle-stem-cells/).

7T quantitative magnetization transfer (qMT) of cortical gray matter in multiple sclerosis correlates with cognitive impairment.

Cognitive impairment (CI) is a major manifestation of multiple sclerosis (MS) and is responsible for extensively hindering patient quality of life. Cortical gray matter (cGM) damage is a significant contributor to CI, but is poorly characterized by conventional MRI let alone with quantitative MRI, such as quantitative magnetization transfer (qMT). Here we employed high-resolution qMT at 7T via the selective inversion recovery (SIR) method, which provides tissue-specific indices of tissue macromolecular content, such as the pool size ratio (PSR) and the rate of MT exchange (kmf). These indices could represent expected demyelination that occurs in the presence of gray matter damage. We utilized selective inversion recovery (SIR) qMT which provides a low SAR estimate of macromolecular-bulk water interactions using a tailored, B1 and B0 robust inversion recovery (IR) sequence acquired at multiple inversion times (TI) at 7T and fit to a two-pool model of magnetization exchange. Using this sequence, we evaluated qMT indices across relapsing-remitting multiple sclerosis patients (N = 19) and healthy volunteers (N = 37) and derived related associations with neuropsychological measures of cognitive impairment. We found a significant reduction in kmf in cGM of MS patients (15.5%, p = 0.002), unique association with EDSS (ρ = -0.922, p = 0.0001), and strong correlation with cognitive performance (ρ = -0.602, p = 0.0082). Together these findings indicate that the rate of MT exchange (kmf) may be a significant biomarker of cGM damage relating to CI in MS.

Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

BACKGROUND: Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T1- and T2-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM. OBJECTIVE: To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0 Tesla (7T). METHODS: A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI. RESULTS AND CONCLUSION: Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability (p < 0.05). In addition, glutamate-sensitive contrast in the prefrontal cortex was significantly correlated with symbol digit modality test (rS = -0.814) and choice reaction time (rS = 0.772) scores in patients (p < 0.05), suggesting that GluCEST MRI may have utility as a marker for GM pathology and CI.

Alleviating Social Pain: A Double-Blind, Randomized, Placebo-Controlled Trial of Forgiveness and Acetaminophen.

BACKGROUND: Research has suggested that physical pain (e.g., caused by injury) and social pain (e.g., caused by social rejection) are modulated by some of the same biological systems. Consequently, it is possible that acetaminophen, which is commonly used to alleviate physical pain through neurochemical pathways, may have social pain-relieving effects that interact with forgiveness, which reduces social pain through psychological pathways. To date, however, only a few studies have examined how experiences of social pain change over time, and none have examined how acetaminophen and forgiveness interact to influence these effects. PURPOSE: We addressed these issues by investigating how acetaminophen administration and daily forgiveness are associated with experiences of social pain over 21 days. We hypothesized that acetaminophen-related reductions in social pain across the 21-day study period would be greatest on days following high levels of forgiveness. METHOD: To test this hypothesis, we conducted a double-blind, randomized, placebo-controlled trial in which we randomly assigned 42 healthy young adults to an acetaminophen condition (1,000 mg of acetaminophen daily), placebo-control condition (400 mg of potassium daily), or empty-control (no pill) condition. We then assessed their levels of forgiveness and social pain for 20 consecutive days. RESULTS: As hypothesized, acetaminophen reduced participants' social pain levels over time but only for those exhibiting high levels of forgiveness (i.e., 18.5% reduction in social pain over 20 days). CONCLUSIONS: These data are the first to show that forgiveness and acetaminophen have interactive effects on experiences of social pain, which is one of the most common and impactful of all human experiences.