Ischemic preconditioning: what else can it do...? Review Article.

Ischemic preconditioning (IPC) can enhance maximal strength likely due to neural priming. Cruz et al., (2024) examined the neurophysiological mechanisms responsible for the ergogenic effect. Although key neurophysiological measures remained largely unchanged, voluntary activation and maximal strength were greater following IPC than sham-IPC. While the mechanistic evidence remains inconclusive, the greater maximal strength provides further evidence of the ergogenic benefit of IPC. Researchers should continue examining the broader functional implications of IPC.

Development of a broad-spectrum therapeutic Fc-nanobody for human noroviruses.

Human norovirus was discovered more than five decades ago and is a widespread cause of outbreaks of acute gastroenteritis. There are no approved vaccines or antivirals currently available. However, norovirus inhibitors, including capsid-specific monoclonal antibodies (Mabs) and nanobodies, have recently shown promising results. Several Mabs and nanobodies were found to inhibit norovirus replication using a human intestinal enteroid (HIE) culture system and/or could block norovirus attachment to histo-blood group antigen (HBGA) co-factors. In our pursuit to develop a single broad-spectrum norovirus therapeutic, we continued our analysis and development of a cross-reactive and HBGA interfering nanobody (NB26). To improve NB26 binding capacity and therapeutic potential, we conjugated NB26 onto a human IgG Fc domain (Fc-NB26). We confirmed that Fc-NB26 cross-reacts with genetically diverse GII genotype capsid protruding (P) domains (GII.8, GII.14, GII.17, GII.24, GII.26, and GII.NA1) using a direct enzyme-linked immunosorbent assay. Furthermore, X-ray crystallography structures of these P domains and structures of other GII genotypes reveal that the NB26 binding site is largely conserved, validating its broad reactivity. We showed that Fc-NB26 has ~100-fold higher affinity toward the norovirus P domain compared to native NB26. We also found that both NB26 and Fc-NB26 neutralize human norovirus replication in the HIE culture system. Furthermore, the mode of inhibition confirmed that like NB26, Fc-NB26 caused norovirus particle disassembly and aggregation. Overall, these new findings demonstrate that structural modifications to nanobodies can improve their therapeutic potential.IMPORTANCEDeveloping vaccines and antivirals against norovirus remains a challenge, mainly due to the constant genetic and antigenic evolution. Moreover, re-infection with genetically related and/or antigenic variants is not uncommon. We further developed our leading norovirus nanobody (NB26) that indirectly interfered with norovirus binding to HBGAs, by converting NB26 into a dimeric Fc-linked Nanobody (Fc-NB26). We found that Fc-NB26 had improved binding affinity and neutralization capacity compared with native NB26. Using X-ray crystallography, we showed this nanobody engaged highly conserved capsid residues among genetically diverse noroviruses. Development of such broadly reactive potent therapeutic nanobodies delivered as a slow-releasing prophylactic could be of exceptional value for norovirus outbreaks, especially for the prevention or treatment of severe acute gastroenteritis in high-risk groups such as the young, elderly, and immunocompromised.

Enzyme purification and sustained enzyme activity for pharmaceutical biocatalysis by fusion with phase-separating intrinsically disordered protein.

In recent decades, biocatalysis has emerged as an important alternative to chemical catalysis in pharmaceutical manufacturing. Biocatalysis is attractive because enzymatic cascades can synthesize complex molecules with incredible selectivity, yield, and in an environmentally benign manner. Enzymes for pharmaceutical biocatalysis are typically used in their unpurified state, since it is time-consuming and cost-prohibitive to purify enzymes using conventional chromatographic processes at scale. However, impurities present in crude enzyme preparations can consume substrate, generate unwanted byproducts, as well as make the isolation of desired products more cumbersome. Hence, a facile, nonchromatographic purification method would greatly benefit pharmaceutical biocatalysis. To address this issue, here we have captured enzymes into membraneless compartments by fusing enzymes with an intrinsically disordered protein region, the RGG domain from LAF-1. The RGG domain can undergo liquid-liquid phase separation, forming liquid condensates triggered by changes in temperature or salt concentration. By centrifuging these liquid condensates, we have successfully purified enzyme-RGG fusions, resulting in significantly enhanced purity compared to cell lysate. Furthermore, we performed enzymatic reactions utilizing purified fusion proteins to assay enzyme activity. Results from the enzyme assays indicate that enzyme-RGG fusions purified by the centrifugation method retain enzymatic activity, with greatly reduced background activity compared to crude enzyme preparations. Our work focused on three different enzymes-a kinase, a phosphorylase, and an ATP-dependent ligase. The kinase and phosphorylase are components of the biocatalytic cascade for manufacturing molnupiravir, and we demonstrated facile co-purification of these two enzymes by co-phase separation. To conclude, enzyme capture by RGG tagging promises to overcome difficulties in bioseparations and biocatalysis for pharmaceutical synthesis.

The effects of acute versus repeated cannabidiol administration on trauma-relevant emotional reactivity: A double-blind, randomized, placebo-controlled trial.

Despite the widespread use and perceived efficacy of cannabidiol (CBD) as an anxiolytic, few controlled studies have evaluated the effects of CBD on anxiety-relevant indications, and only one has done so in the context of trauma-related symptoms. The current study was designed to address this gap in the literature. Participants were 42 trauma-exposed individuals (Mage = 23.12 years, SDage = 6.61) who endorsed elevated stress. They were randomly assigned to take 300 mg of oral CBD or placebo daily for 1 week. Acute (i.e., following an initial 300 mg dose) and repeated (i.e., following 1 week of daily 300 mg dosing) effects of CBD were evaluated in relation to indicators of anxious arousal (i.e., anxiety, distress, heart rate) in response to idiographic trauma script presentation. The results of the current study suggest that relative to placebo, 300 mg CBD did not significantly reduce anxiety, B = 13.37, t(37) = 1.71, p = .096, d = 0.09, Bayes factor (BF10) = 0.54; distress, B = 15.20, t(37) = 1.31, p = .197, d = 0.07, BF10 = 0.51; or heart rate, B = -1.09, t(36) = -0.32, p = .755, d = 0.02, BF10 = 0.29, evoked by idiographic trauma script presentation in the context of acute or repeated administration. These data suggest that CBD may not effectively reduce trauma-relevant emotional arousal; however, more work is needed to confidently assert such claims due to the small sample size. The current study extends the groundwork for additional studies in this important area.

E3 ligases: a ubiquitous link between DNA repair, DNA replication and human disease.

Maintenance of genome stability is of paramount importance for the survival of an organism. However, genomic integrity is constantly being challenged by various endogenous and exogenous processes that damage DNA. Therefore, cells are heavily reliant on DNA repair pathways that have evolved to deal with every type of genotoxic insult that threatens to compromise genome stability. Notably, inherited mutations in genes encoding proteins involved in these protective pathways trigger the onset of disease that is driven by chromosome instability e.g. neurodevelopmental abnormalities, neurodegeneration, premature ageing, immunodeficiency and cancer development. The ability of cells to regulate the recruitment of specific DNA repair proteins to sites of DNA damage is extremely complex but is primarily mediated by protein post-translational modifications (PTMs). Ubiquitylation is one such PTM, which controls genome stability by regulating protein localisation, protein turnover, protein-protein interactions and intra-cellular signalling. Over the past two decades, numerous ubiquitin (Ub) E3 ligases have been identified to play a crucial role not only in the initiation of DNA replication and DNA damage repair but also in the efficient termination of these processes. In this review, we discuss our current understanding of how different Ub E3 ligases (RNF168, TRAIP, HUWE1, TRIP12, FANCL, BRCA1, RFWD3) function to regulate DNA repair and replication and the pathological consequences arising from inheriting deleterious mutations that compromise the Ub-dependent DNA damage response.

Medical School Characteristics Associated with Matched Otolaryngology Residency Applicants.

OBJECTIVE: Identify which medical schools produce the most otolaryngology residents, and associated characteristics which may contribute to this productivity. DESIGN: The medical school and residency program of each otolaryngology-matched student was identified. Various characteristics for each medical school and residency were compared in univariate and multivariate analysis after adjusting for class size. Percentage of matched students relative to class size was identified and compared for each geographic region. SETTING: Cross-sectional study of publicly available match data from otomatch.com and otolaryngology residency program websites from 2020-2023. PARTICIPANTS: 1411 students from 174 medical schools matched into 126 otolaryngology residencies were identified. RESULTS: Private medical schools (ß = 0.50, p = 0.03), larger otolaryngology departments (ß = 0.01, p = 0.04), and higher U.S. News and World Report (USNWR) ranking (ß = -0.01, p = 0.02) was associated with a greater percentage of otolaryngology-matched students while schools in the Mountain region were associated with a lower percentage of matched students (ß = -1.08, p = 0.02). A difference in percentage of matched students was observed when comparing across all regions (p < 0.01) but no significant differences were observed between any individual regions. The East North Central Region and the Middle Atlantic regions were more likely to match students from their respective regions compared to the Mountain region (OR: 4.98, 95% CI: 1.18, 21.01; OR: 8.20, 95% CI: 1.92, 34.99, respectively). Additionally, the Mountain region was less likely to match students from their own region compared to the Pacific (OR: 0.21, 95% CI: 0.05, 0.90), South Atlantic (OR: 0.20, 95% CI: 0.05, 0.85), and West South Central (OR: 0.15, 95% CI: 0.03, 0.67) regions. CONCLUSIONS: Medical school characteristics such as private vs public status, size of otolaryngology department, higher USNWR ranking, and geographic region impact the number of otolaryngology-matched students. Applicants should consider the impact of their geographic region when allocating signals during the residency application process.

Writing about a stressful experience can impair visual working memory.

Acute stress has been well-established to impair working memory. However, less is known about how writing about an unresolved stressor may influence working memory or working memory processes. We addressed these issues in the present study (N = 282) by randomly assigning participants to write about an unresolved stressful experience (stressful writing condition or the events of the previous day). We then both measured performance on a change detection task and used computational modeling to estimate the processes underlying performance: attention, capacity, and guessing bias. We found that, relative to the control condition, writing about a stressful experience impaired change detection task performance and significantly impaired task attention. These results show that the effects of writing about an unresolved stressor may mimic the effects of acute stress on working memory, rather than conforming to expectations from mood-as-information theory.

Safety and efficacy of tofacitinib for the treatment of patients with juvenile idiopathic arthritis: preliminary results of an open-label, long-term extension study.

OBJECTIVES: We report the safety, tolerability and efficacy of tofacitinib in patients with juvenile idiopathic arthritis (JIA) in an ongoing long-term extension (LTE) study. METHODS: Patients (2-<18 years) with JIA who completed phase 1/3 index studies or discontinued for reasons excluding treatment-related serious adverse events (AEs) entered the LTE study and received tofacitinib 5 mg two times per day or equivalent weight-based doses. Safety outcomes included AEs, serious AEs and AEs of special interest. Efficacy outcomes included improvement since tofacitinib initiation per the JIA-American College of Rheumatology (ACR)70/90 criteria, JIA flare rate and disease activity measured by Juvenile Arthritis Disease Activity Score (JADAS)27, with inactive disease corresponding to JADAS ≤1.0. RESULTS: Of 225 patients with JIA (median (range) duration of treatment, 41.6 (1-103) months), 201 (89.3%) had AEs; 34 (15.1%) had serious AEs. 10 patients developed serious infections; three had herpes zoster. Two patients newly developed uveitis. Among patients with polyarticular course JIA, JIA-ACR70/90 response rates were 60.0% (78 of 130) and 33.6% (47 of 140), respectively, at month 1, and generally improved over time. JIA flare events generally occurred in <5% of patients through to month 48. Observed mean (SE) JADAS27 was 22.0 (0.6) at baseline, 6.2 (0.7) at month 1 and 2.8 (0.5) at month 48, with inactive disease in 28.8% (36 of 125) of patients at month 1 and 46.8% (29 of 82) at month 48. CONCLUSIONS: In this interim analysis of LTE study data in patients with JIA, safety findings were consistent with the known profile of tofacitinib, and efficacy was maintained up to month 48. TRIAL REGISTRATION NUMBER: NCT01500551.

Cumulative lifetime stressor exposure impairs stimulus-response but not contextual learning.

Greater exposure to stressors over the life course is believed to promote striatum-dependent over hippocampus-dependent learning and memory processes under stressful conditions. However, little research in this context has actually assessed lifetime stressor exposure and, moreover, it remains unknown whether greater cumulative lifetime stressor exposure exerts comparable effects on striatum-dependent learning and hippocampus-dependent learning in non-stressful contexts. To investigate this issue, we used the Stress and Adversity Inventory for Adults (Adult STRAIN) and Multicued Search Task to investigate the relation between cumulative lifetime stressor exposure and striatum-dependent stimulus-response learning and hippocampus-dependent contextual learning under non-stressful conditions among healthcare professionals (N = 205; 157 females, 48 males; Age: M = 34.23, SD 9.3, range 20-59 years). Individuals with moderate, but not low, cumulative lifetime stressor exposure exhibited impaired learning for stimulus-response associations. In contrast, learning for context associations was unrelated to participants' lifetime stressor exposure profiles. These results thus provide first evidence that cumulative lifetime stressor exposure may have negative consequences on human striatum-dependent stimulus-response learning under non-stressful environmental conditions.

Genome-scale clustered regularly interspaced short palindromic repeats screen identifies nucleotide metabolism as an actionable therapeutic vulnerability in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied ribonucleic acid (RNA)-seq and genome-scale loss-offunction clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations. Atm-/-nu-/-lymphomas, which phenotypically resemble either activated B-cell-like or germinal center Bcell-like DLBCL, harbor a complex karyotype, and are characterized by MYC pathway activation. In Atm-/-nu-/-lymphomas, we discovered nucleotide biosynthesis as a MYCdependent cellular vulnerability that can be targeted through the synergistic nucleotidedepleting actions of mycophenolate mofetil (MMF) and the WEE1 inhibitor, adavosertib (AZD1775). The latter is mediated through a synthetically lethal interaction between RRM2 suppression and MYC dysregulation that results in replication stress overload in Atm-/-nu-/-lymphoma cells. Validation in cell line models of human DLBCL confirmed the broad applicability of nucleotide depletion as a therapeutic strategy for MYC-driven DLBCL independent of ATM mutation status. Our findings extend current understanding of lymphomagenic mechanisms underpinning ATM loss and highlight nucleotide metabolism as a targetable therapeutic vulnerability in MYC-driven DLBCL.

S100 proteins as potential predictive biomarkers of abatacept response in polyarticular juvenile idiopathic arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of conditions that can cause marked disability and diminished quality of life. Data on predictors of clinical response are insufficient to guide selection of the appropriate biologic agent for individual patients. This study aimed to investigate the propensity of S100A8/9 and S100A12 as predictive biomarkers of abatacept response in polyarticular-course juvenile idiopathic arthritis (pJIA). METHODS: Data from a phase 3 trial (NCT01844518) of subcutaneous abatacept in patients with active pJIA (n = 219) were used in this exploratory analysis. Association between biomarker levels at baseline and improvements in JIA-American College of Rheumatology (ACR) criteria responses or baseline disease activity (measured by Juvenile Arthritis Disease Activity Score in 27 joints using C-reactive protein [JADAS27-CRP]) were assessed. Biomarker level changes from baseline to month 4 were assessed for disease outcome prediction up to 21 months. RESULTS: At baseline, 158 patients had available biomarker samples. Lower baseline S100A8/9 levels (≤ 3295 ng/mL) were associated with greater odds of achieving JIA-ACR90 (odds ratio [OR]: 2.54 [95% confidence interval (CI): 1.25-5.18]), JIA-ACR100 (OR: 3.72 [95% CI: 1.48-9.37]), JIA-ACR inactive disease (ID; OR: 4.25 [95% CI: 2.03-8.92]), JADAS27-CRP ID (OR: 2.34 [95% CI: 1.02-5.39]) at month 4, and JIA-ACR ID (OR: 3.01 [95% CI: 1.57-5.78]) at month 16. Lower baseline S100A12 levels (≤ 176 ng/mL) were associated with greater odds of achieving JIA-ACR90 (OR: 2.52 [95% CI: 1.23-5.13]), JIA-ACR100 (OR: 3.68 [95% CI: 1.46-9.28]), JIA-ACR ID (OR: 3.66 [95% CI: 1.76-7.61]), JIA-ACR90 (OR: 2.03 [95% CI: 1.07-3.87]), JIA-ACR100 (OR: 2.14 [95% CI: 1.10-4.17]), and JIA-ACR ID (OR: 4.22 [95% CI: 2.15-8.29]) at month 16. From baseline to month 4, decreases in S100A8/9 and S100A12 generally exceeded 50% among JIA-ACR90/100/ID responders. CONCLUSION: Lower baseline levels of S100A8/9 and S100A12 proteins predicted better response to abatacept treatment than higher levels and may serve as early predictive biomarkers in pJIA. Decreases in these biomarker levels may also predict longer-term response to abatacept in pJIA.

Neural activity and connectivity are related to food preference changes induced by food go/no-go training.

Simply withholding a response while viewing an appetizing food, over the course of many presentations (i.e., during food go/no-go training) can modify individuals' food preferences-which could, in turn, promote healthier eating behaviors. However, the neural mechanisms underlying this food go/no-go training-induced change in food preferences are still relatively unclear. We addressed this issue in the present functional magnetic resonance imaging (fMRI) study. To this end, we administered a novel passive viewing task before and after food go/no-go training to 91 participants in the scanner. Participants' food preferences were measured with a binary food choice task. At the behavioral level, we found the expected training effect on food preferences: Participants preferred go over no-go foods following training. At the neural level, we found that changes in food preferences were associated with training-related go vs. no-go differences in activity and functional connectivity, such as less activity in the anterior cingulate cortex and superior frontal gyrus but greater functional connectivity between the superior frontal gyrus and middle occipital gyrus. Critically, Dynamic causal modeling showed that this preference change effect was largely driven by top-down influence from the superior frontal gyrus to the middle occipital gyrus. Together, these findings suggest a neural mechanism of the food go/no-go training effect-namely, that the food-viewing-related interplay between prefrontal regions and visual regions might be related to the food preference change following food go/no-go training.

Abundant hydrocarbons in the disk around a very-low-mass star.

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

Can the cross-education of strength attenuate the impact of detraining after a period of strength training? A quasi-randomized trial.

PURPOSE: Unilateral strength training may attenuate the decline in muscle strength and size in homologous, contralateral muscles. This study aimed to determine whether the cross-education of strength could specifically attenuate the effects of detraining immediately after a short (prehabilitation-type) period of strength training. METHODS: Twenty-six strength-trained participants were assigned to either four weeks of unilateral strength training of the stronger arm (UNI) or detraining (Detrain). Motor evoked potential (MEP) and cortical silent period (cSP) responses, muscle cross-sectional area (CSAFlexor; peripheral quantitative computed tomography) and maximal strength, rate of force development (RFD) and muscle activation (EMG) were examined in both elbow flexors before and after the intervention period. RESULTS: In UNI, one-repetition maximum (1-RM) strength improved in both the trained (∆ = 2.0 ± 0.9 kg) and non-trained (∆ = 0.8 ± 0.9 kg) arms despite cessation of training of the weaker arm, whereas 1-RM strength was unchanged in Detrain. Maximal voluntary isometric contraction, isokinetic peak torque, and RFD did not change in either group. No neural changes were detected in UNI, but cSP increased in Detrain (∆ = 0.010 ± 0.015 s). CSAFlexor increased in the trained arm (∆ = 51 ± 43 mm2) but decreased in the non-trained arm (∆ = -53 ± 50 mm2) in UNI. CSAFlexor decreased in both arms in Detrain and at a similar rate to the non-trained arm in UNI. CONCLUSION: UNI attenuated the effects of detraining in the weaker arm as shown by the improvement in 1-RM strength. However, the cross-education of strength did not attenuate the decline in muscle size in the contralateral arm.

Evidence for response inhibition as a control process distinct from the common executive function: A two-study factor analysis.

The dominant model of executive functions, which has held for over two decades, contends that various aspects of seemingly disparate forms of inhibitory control-for example, inhibiting a prepotent response, or inhibiting irrelevant thoughts and distractions-are in fact manifestations of a single latent executive function. Recent work, however, has cast doubt on this dominant model, as certain conditions can dissociate performance on tasks thought to index inhibitory control. Moreover, issues related to task reliability and latent estimation of inhibition processes have prompted questions about whether the structure of inhibitory control can even be reliably estimated at a latent level. We addressed these issues in two studies of healthy young adults (Study 1 N = 154, Study 2, N = 279), examining seven then 12 different tasks taken by prior research to assess inhibitory control. Contrary to the dominant model of executive functions, we found that, at a latent level, inhibitory control was best fit by a replicable two-factor solution, with response inhibition as a distinct executive function. Further, our data suggested that prior work on executive functions may not have observed a response inhibition factor due to task selections (i.e., including either one of two specific tasks was critical to identifying a separate response inhibition factor). Therefore, contrary to the current primary theoretical model of executive functions, these results suggest that response inhibition is, in fact, a distinct control process from the control process underpinning other forms of inhibition, which has important implications for designing interventions and assessing outcomes related to inhibitory control. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A mismatch between early and recent life stress predicts better response inhibition, but not cognitive inhibition.

A growing body of work has found that a mismatch between early and recent life stress, more than a cumulative influence of stress, contributes to detrimental stress-related health outcomes. To date, however, no work has examined how such a mismatch might relate to stress-related cognitive outcomes. We addressed this gap in the current study by assessing participants' (N = 154, Mage = 18.7, 104 female) early and recent life stress using the same inventory, and subsequently assessing their inhibitory control in a hybrid stop-signal/flanker task. Surprisingly, we found that a greater degree of stressor mismatch was associated with better response inhibition (i.e. smaller stop-signal reaction time) across a number of analytic approaches. Cognitive inhibition (i.e. the flanker interference effect) was not associated with stressor mismatch. These results thus show that a greater degree of mismatch between early and recent life stress is related to response inhibition in the same way as acute stress affects response inhibition, suggesting that response inhibition may be an important cognitive process for navigating both acute stress and general environmental conditions that do not match the conditions in which expected stress occurrence was established.

Dysphagia in COVID-19 Patients on Extracorporeal Membrane Oxygenation.

Patients on extracorporeal membrane oxygenation (ECMO) are infrequently nourished via oral feeding due to aspiration risks. Patients with COVID-19 and on ECMO represent a subpopulation that has additional factors that may affect their swallow function. This study aimed to describe the swallow function and ability to maintain oral feeding in patients with COVID-19 while on ECMO. A retrospective study of patients with COVID-19 who started veno-venous ECMO at the beginning of the COVID-19 pandemic (March 2020 and August 2020) was conducted at a tertiary care hospital. Clinical swallow evaluations and videofluoroscopic swallow studies (VFSS) were analyzed using standardized measurement scales. Pearson's correlation coefficient (r) identified relationships between ECMO and swallowing function at different time points. 19 patients were included; all underwent clinical swallow evaluation and 4 underwent VFSS while on ECMO. Mean age was 43.2 years (standard deviation: 9.2), mean duration of ECMO was 65.7 days (58.7), and mean duration of intubation was 14.4 days (8.6). All patients were able to undergo swallow function evaluation, regain swallow function, and resume oral feeding while cannulated. Duration of ECMO and time to feeding tube removal was positively correlated (r = 0.747, p < 0.001) with patients demonstrating less functional swallowing independence and requiring a more modified diet upon oral diet initiation. Clinical swallow evaluation and videofluoroscopic swallowing evaluation are possible for COVID-19 patients actively on ECMO. Patient swallow function can improve, and oral diet can be achieved while on ECMO, demonstrating benefit of SLP surveillance and swallowing assessment prior to ECMO decannulation.

New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.

INTRODUCTION: Systemic juvenile idiopathic arthritis (sJIA) is a severe inflammatory condition with onset in childhood. It is sporadic, but elements of its stereotypical innate immune responses are likely genetically encoded by both common variants with small effect sizes and rare variants with larger effects. AREAS COVERED: Genomic investigations have defined the unique genetic architecture of sJIA. Identification of the class II HLA locus as the strongest sJIA risk factor for the first time brought attention to T lymphocytes and adaptive immune mechanisms in sJIA. The importance of the human leukocyte antigen (HLA) locus was reinforced by recognition that HLA-DRB1*15 alleles are strongly associated with development of drug reactions and sJIA-associated lung disease (sJIA-LD). At the IL1RN locus, genetic variation relates to both risk of sJIA and may also predict non-response to anakinra. Finally, rare genetic variants may have critical roles in disease complications, such as homozygous LACC1 mutations in families with an sJIA-like illness, and hemophagocytic lymphohistiocytosis (HLH) gene variants in some children with macrophage activation syndrome (MAS). EXPERT OPINION: Genetic and genomic analysis of sJIA holds great promise for both basic discovery of the course and complications of sJIA, and may help guide personalized medicine and therapeutic decision-making.

Methods of measurement for pneumothorax in pediatric patients: a systematic review.

Accurate measurement of pneumothorax (PTX) size is necessary to guide clinical decision making; however, there is no consensus as to which method should be used in pediatric patients. This systematic review seeks to identify and evaluate the methods used to measure PTX size with CXR in pediatric patients. A systematic review of the literature through 2021 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was conducted using the following databases: Ovid/MEDLINE, Scopus, Cochrane Database of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar. Original research articles that included pediatric patients (< 18 years old) and outlined the PTX measurement method were included. 45 studies were identified and grouped by method (Kircher and Swartzel, Rhea, Light, Collins, Other) and societal guideline used. The most used method was Collins (n = 16; 35.6%). Only four (8.9%) studies compared validated methods. All found the Collins method to be accurate. Seven (15.6%) studies used a standard classification guideline and 3 (6.7%) compared guidelines and found significant disagreement between them. Pediatric-specific measurement guidelines for PTX are needed to establish consistency and uniformity in both research and clinical practice. Until there is a better method, the Collins method is preferred.