Genotype-Phenotype Characterization of Serial Mycobacterium tuberculosis Isolates in Bedaquiline-Resistant Tuberculosis.

BACKGROUND: Emerging resistance to bedaquiline (BDQ) threatens to undermine advances in the treatment of drug-resistant tuberculosis (DRTB). Characterizing serial Mycobacterium tuberculosis (Mtb) isolates collected during BDQ-based treatment can provide insights into the etiologies of BDQ resistance in this important group of DRTB patients. METHODS: We measured mycobacteria growth indicator tube (MGIT)-based BDQ minimum inhibitory concentrations (MICs) of Mtb isolates collected from 195 individuals with no prior BDQ exposure who were receiving BDQ-based treatment for DRTB. We conducted whole-genome sequencing on serial Mtb isolates from all participants who had any isolate with a BDQ MIC >1 collected before or after starting treatment (95 total Mtb isolates from 24 participants). RESULTS: Sixteen of 24 participants had BDQ-resistant TB (MGIT MIC ≥4 µg/mL) and 8 had BDQ-intermediate infections (MGIT MIC = 2 µg/mL). Participants with pre-existing resistance outnumbered those with resistance acquired during treatment, and 8 of 24 participants had polyclonal infections. BDQ resistance was observed across multiple Mtb strain types and involved a diverse catalog of mmpR5 (Rv0678) mutations, but no mutations in atpE or pepQ. Nine pairs of participants shared genetically similar isolates separated by <5 single nucleotide polymorphisms, concerning for potential transmitted BDQ resistance. CONCLUSIONS: BDQ-resistant TB can arise via multiple, overlapping processes, including transmission of strains with pre-existing resistance. Capturing the within-host diversity of these infections could potentially improve clinical diagnosis, population-level surveillance, and molecular diagnostic test development.

Distinguishing gene flow between malaria parasite populations.

Measuring gene flow between malaria parasite populations in different geographic locations can provide strategic information for malaria control interventions. Multiple important questions pertaining to the design of such studies remain unanswered, limiting efforts to operationalize genomic surveillance tools for routine public health use. This report examines the use of population-level summaries of genetic divergence (FST) and relatedness (identity-by-descent) to distinguish levels of gene flow between malaria populations, focused on field-relevant questions about data size, sampling, and interpretability of observations from genomic surveillance studies. To do this, we use P. falciparum whole genome sequence data and simulated sequence data approximating malaria populations evolving under different current and historical epidemiological conditions. We employ mobile-phone associated mobility data to estimate parasite migration rates over different spatial scales and use this to inform our analysis. This analysis underscores the complementary nature of divergence- and relatedness-based metrics for distinguishing gene flow over different temporal and spatial scales and characterizes the data requirements for using these metrics in different contexts. Our results have implications for the design and implementation of malaria genomic surveillance studies.

Charting the sequence-activity landscape of peptide inhibitors of translation termination.

Apidaecin (Api), an unmodified 18-amino-acid-long proline-rich antibacterial peptide produced by bees, has been recently described as a specific inhibitor of translation termination. It invades the nascent peptide exit tunnel of the postrelease ribosome and traps the release factors preventing their recycling. Api binds in the exit tunnel in an extended conformation that matches the placement of a nascent polypeptide and establishes multiple contacts with ribosomal RNA (rRNA) and ribosomal proteins. Which of these interactions are critical for Api's activity is unknown. We addressed this problem by analyzing the activity of all possible single-amino-acid substitutions of the Api variants synthesized in the bacterial cell. By conditionally expressing the engineered api gene, we generated Api directly in the bacterial cytosol, thereby bypassing the need for importing the peptide from the medium. The endogenously expressed Api, as well as its N-terminally truncated mutants, retained the antibacterial properties and the mechanism of action of the native peptide. Taking advantage of the Api expression system and next-generation sequencing, we mapped in one experiment all the single-amino-acid substitutions that preserve or alleviate the on-target activity of the Api mutants. Analysis of the inactivating mutations made it possible to define the pharmacophore of Api involved in critical interactions with the ribosome, transfer RNA (tRNA), and release factors. We also identified the Api segment that tolerates a variety of amino acid substitutions; alterations in this segment could be used to improve the pharmacological properties of the antibacterial peptide.

Medical Student Debt and the US Infectious Diseases Workforce.

Student debt in the United States is at historically high levels and poses an excessive burden on medical graduates. Studies suggest that financial limitations dissuade some medical trainees from pursuing careers in infectious diseases (ID) and other cognitive specialties, despite their interest in the subject matter. Addressing student debt may have a transformative impact on ID recruitment, diversification of the ID workforce, and contributions of ID physicians to underserved public health needs. Relief of student debt also has the potential to narrow the racial wealth gap because nonwhite students are more likely to finance their postsecondary education, including medical school, with student loans, yet they have a lower earning potential following graduation. An executive order from the Biden-Harris administration announced in August 2022 presents a first step toward student debt relief, but the policy would need to be expanded in volume and scope to effectively achieve these goals.

Stabilization of Functional DNA Structures with Mild Photochemical Methods.

A significant barrier to biological applications of DNA structures is their instability to nucleases. UV-mediated thymine dimerization can crosslink and stabilize DNA nanostructures, but its effect on DNA strand hybridization fidelity and function is unclear. In this work, we first compare a number of methods for DNA irradiation with different wavelengths of light and different photosensitizers. We demonstrate that all approaches can achieve nuclease protection; however, the levels of DNA off-target crosslinking and damage vary. We then describe mild irradiation conditions intended to safeguard DNA against nuclease degradation. We demonstrate up to 25× increase in serum stability while minimizing off-target damage and maintaining functions such as hybridization efficiency, gene silencing, aptamer binding, and DNA nanostructure formation. Our methodology requires no complex instruments beyond a UV light source and no synthetic modification of the DNA itself, allowing for applications in numerous areas of nucleic acid therapy and nanotechnology.

Improvement in Multidisciplinary Provider Rounding (Surgical Rounds) in the Pediatric Cardiac ICU: An Application of Lean Methodology.

OBJECTIVES: Provider-only, combined surgical, and medical multidisciplinary rounds ("surgical rounds") are essential to achieve optimal outcomes in large pediatric cardiac ICUs. Lean methodology was applied with the aims of identifying areas of waste and nonvalue-added work within the surgical rounds process. Thereby, the goals were to improve rounding efficiency and reduce rounding duration while not sacrificing critical patient care discussion nor delaying bedside rounds or surgical start times. DESIGN: Single-center improvement science study with observational and interventional phases from February 2, 2021, to July 31, 2021. SETTING: Tertiary pediatric cardiac ICU. PARTICIPANTS: Cardiothoracic surgery and cardiac intensive care team members participating in daily "surgical" rounds. INTERVENTIONS: Implementation of technology automation, creation of work instructions, standardization of patient presentation content and order, provider training, and novel role assignment. MEASUREMENTS AND MAIN RESULTS: Sixty-one multidisciplinary rounds were observed (30 pre, 31 postintervention). During the preintervention period, identified inefficiencies included prolonged preparation time, redundant work, presentation variability and extraneous information, and frequent provider transitions. Application of targeted interventions resulted in a 26% decrease in indexed rounds duration (2.42 vs 1.8 min; p = 0.0003), 50% decrease in indexed rounds preparation time (0.53 vs 0.27 min; p < 0.0001), and 66% decrease in transition time between patients (0.09 vs 0.03 min; p < 0.0001). The number of presenting provider changes also decreased (9 vs 4; p < 0.0001). Indexed discussion duration did not change (1 vs 0.98 min; p = 0.08) nor did balancing measures (bedside rounds and surgical start times) change (8.5 vs 9 min; p = 0.89 and 38 vs 22 min; p = 0.09). CONCLUSIONS: Lean methodology can be effectively applied to multidisciplinary rounds in a joint cardiothoracic surgery/cardiac intensive care setting to decrease waste and inefficiency. Interventions resulted in decreased preparation time, transition time, presenting provider changes, total rounds duration indexed to patient census, and anecdotal improvements in provider satisfaction.

Blackfoot Words: a database of Blackfoot lexical forms.

This paper describes the structure and creation of Blackfoot Words, a new relational database of lexical forms (inflected words, stems, and morphemes) in Blackfoot (Algonquian; ISO 639-3: bla). To date, we have digitized 63,493 individual lexical forms from 30 sources, representing all four major dialects, and spanning the years 1743-2017. Version 1.1 of the database includes lexical forms from nine of these sources. This project has two aims. The first is to digitize and provide access to the lexical data in these sources, many of which are difficult to access and discover. The second is to organize the data so that connections can be made between instances of the "same" lexical form across all sources, despite variation across sources in the dialect recorded, orthographic conventions, and the depth of morpheme analysis. The database structure was developed in response to these aims. The database comprises five tables: Sources, Words, Stems, Morphemes, and Lemmas. The Sources table contains bibliographic information and commentary on the sources. The Words table contains inflected words in the source orthography. Each word is broken down into stems and morphemes which are entered into the Stems and Morphemes tables in the source orthography. The Lemmas table contains abstract versions of each stem or morpheme in a standardized orthography. Instances of the same stem or morpheme are linked to a common lemma. We expect that the database will support projects by the language community and other researchers.

Left Atrial Phasic Function via Cardiac Magnetic Resonance Imaging in Patients with Duchenne Muscular Dystrophy.

Cardiac dysfunction is a leading cause of morbidity and mortality in Duchenne muscular dystrophy (DMD). Left atrial (LA) function is a poorly understood concept in this patient population, and research suggests underlying structural changes that could affect atrial function. Cardiac magnetic resonance (CMR) imaging may provide an important non-invasive approach to evaluating LA function. This study was a single center retrospective review of consecutive CMR studies over a 1 year period comparing LA phasic function within a cohort of DMD patients, and to those with structurally and functionally normal hearts. LA strain measurements including global reservoir, conduit, boost-pump strain, and LA volumes were obtained retrospectively. Spearman correlation analyses were performed on atrial strain measurements. 107 DMD and 79 normal CMR studies were included. The DMD cohort had worse systolic function (p < 0.001), smaller indexed max LA and left ventricular (LV) volumes (p < 0.001), and greater LA emptying fraction (p < 0.001). In the DMD cohort, emptying fraction decreased with advanced patient age (p < 0.001) and diminishing systolic function (p < 0.001). DMD patients with moderate or severe LV dysfunction demonstrated lower LA emptying fraction (p = 0.002), more impaired 2-chamber LA reservoir (p = 0.003), and LA pump (p = 0.006) and conduit strain (p = 0.018). DMD patients with preserved function have lower indexed LA volumes with higher LA emptying fractions than controls. Progression of disease and age is associated with decreased LA emptying fraction with early manifestations in reservoir and conduit strain. These findings suggest that strain markers of LA compliance and early left ventricular relaxation are associated with worsening cardiomyopathy in the DMD population.

Balloon atrial septostomy versus left atrial cannulation for left heart decompression in children with dilated cardiomyopathy and myocarditis on extracorporeal membrane oxygenation: An ELSO registry analysis.

INTRODUCTION: In children with myocarditis or dilated cardiomyopathy (DCM) on extracorporeal membrane oxygenation (ECMO) for cardiogenic shock, it is often necessary to decompress the left heart to minimize distension and promote myocardial recovery. We compare outcomes in those who underwent balloon atrial septostomy (BAS) versus direct left atrial (LA) drainage for left heart decompression in this population. METHODS: Retrospective study of the Extracorporeal Life Support Organization (ELSO) multicenter registry of patients ≤ 18 years with myocarditis or DCM on ECMO who underwent LA decompression. Descriptive and univariate statistics assessed association of patient factors with decompression type. Multivariable logistic regression sought independent associations with outcomes. RESULTS: 369 pediatric ECMO runs were identified. 52% myocarditis, 48% DCM, overall survival 74%. 65% underwent BAS and 35% LA drainage. Patient demographics including age, weight, gender, race/ethnicity, diagnosis, pre-ECMO pH, mean airway pressure, and arrest status were similar. 89% in the BAS group were peripherally cannulated onto ECMO, versus 3% in the LA drainage group (p < .001). On multivariable analysis, LA drainage (OR 3.96; 95% CI, 1.47-10.711; p = .007), renal complication (OR 2.37; 95% CI, 1.41-4.01; p = .001), cardiac complication (OR 3.14; 95% CI, 1.70-5.82; p < .001), and non-white race/ethnicity (OR 1.75; 95% CI, 1.04-2.94; p = .035) were associated with greater odds of mortality. There was a trend toward more episodes of pulmonary hemorrhage in BAS (n = 17) versus LA drainage group (n = 3), p = .08. Comparing only those with central cannulation, LA drainage group was more likely to be discontinued from ECMO due to recovery (72%) versus the BAS group (48%), p = .032. CONCLUSIONS: In children with myocarditis or DCM, there was a three times greater likelihood for mortality with LA drainage versus BAS for LA decompression. When adjusted for central cannulation groups only, there was better recovery in the LA drainage group and no difference in mortality. Further prospective evaluation is warranted.

Nanoparticle Properties Influence Transendothelial Migration of Monocytes.

Nanoparticle-based delivery of therapeutics to the brain has had limited clinical impact due to challenges crossing the blood-brain barrier (BBB). Certain cells, such as monocytes, possess the ability to migrate across the BBB, making them attractive candidates for cell-based brain delivery strategies. In this work, we explore nanoparticle design parameters that impact both monocyte association and monocyte-mediated BBB transport. We use electrohydrodynamic jetting to prepare nanoparticles of varying sizes, compositions, and elasticity to address their impact on uptake by THP-1 monocytes and permeation across the BBB. An in vitro human BBB model is developed using human cerebral microvascular endothelial cells (hCMEC/D3) for the assessment of migration. We compare monocyte uptake of both polymeric and synthetic protein nanoparticles (SPNPs) of various sizes, as well as their effect on cell migration. SPNPs (human serum albumin/HSA or human transferrin/TF) are shown to promote increased monocyte-mediated transport across the BBB over polymeric nanoparticles. TF SPNPs (200 nm) associate readily, with an average uptake of 138 particles/cell. Nanoparticle loading is shown to influence the migration of THP-1 monocytes. The migration of monocytes loaded with 200 nm TF and 200 nm HSA SPNPs was 2.3-fold and 2.1-fold higher than that of an untreated control. RNA-seq analysis after TF SPNP treatment suggests that the upregulation of several migration genes may be implicated in increased monocyte migration (ex. integrin subunits α M and α L). Integrin ß 2 chain combines with either integrin subunit α M chain or integrin subunit α L chain to form macrophage antigen 1 and lymphocyte function-associated antigen 1 integrins. Both products play a pivotal role in the transendothelial migration cascade. Our findings highlight the potential of SPNPs as drug and/or gene delivery platforms for monocyte-mediated BBB transport, especially where conventional polymer nanoparticles are ineffective or otherwise not desirable.

Exploring healthcare professionals' experiences with informal family cancer caregiving.

Caring for a family member with cancer is often associated with significant cognitive, emotional, and physical demands. Although considerable research has explored informal cancer caregiver role burden, research has seldom focused on the experiences of individuals who hold the dual role of informal caregiver and healthcare professional. This qualitative study begins to explore this dual role experience. Participants (N = 12) who had at least 1 year of prior professional experience and cared for a family member with cancer were recruited conveniently from a large university-affiliated hospital in Montreal, Quebec. Individual face-to-face semi-structured interviews were conducted. Using thematic analysis, key themes were developed from verbatim transcripts: (1) salient dual role advantages, (2) significant challenges related to this role, (3) changes in professional practice as a consequence of informal caregiving, and (4) important palliative and end-of-life care access issues. Whereas professional knowledge helped advocate on behalf of patients, the dual role often came with over-solicitation from others, enhanced sense of responsibility, increased burden, and significant distress. Further study of critical ramifications linked to jointly enacting informal and professional caregiving across various health contexts should continue to inform supportive care strategies for this understudied yet increasingly prevalent segment of the caregiver population.

Pre-detection history of extensively drug-resistant tuberculosis in KwaZulu-Natal, South Africa.

Antimicrobial-resistant (AMR) infections pose a major threat to global public health. Similar to other AMR pathogens, both historical and ongoing drug-resistant tuberculosis (TB) epidemics are characterized by transmission of a limited number of predominant Mycobacterium tuberculosis (Mtb) strains. Understanding how these predominant strains achieve sustained transmission, particularly during the critical period before they are detected via clinical or public health surveillance, can inform strategies for prevention and containment. In this study, we employ whole-genome sequence (WGS) data from TB clinical isolates collected in KwaZulu-Natal, South Africa to examine the pre-detection history of a successful strain of extensively drug-resistant (XDR) TB known as LAM4/KZN, first identified in a widely reported cluster of cases in 2005. We identify marked expansion of this strain concurrent with the onset of the generalized HIV epidemic 12 y prior to 2005, localize its geographic origin to a location in northeastern KwaZulu-Natal ∼400 km away from the site of the 2005 outbreak, and use protein structural modeling to propose a mechanism for how strain-specific rpoB mutations offset fitness costs associated with rifampin resistance in LAM4/KZN. Our findings highlight the importance of HIV coinfection, high preexisting rates of drug-resistant TB, human migration, and pathoadaptive evolution in the emergence and dispersal of this critical public health threat. We propose that integrating whole-genome sequencing into routine public health surveillance can enable the early detection and local containment of AMR pathogens before they achieve widespread dispersal.

Synthesis and Activity of Triazole-Adenosine Analogs as Protein Arginine Methyltransferase 5 Inhibitors.

Protein arginine methyltransferase 5 (PRMT5) is an attractive molecular target in anticancer drug discovery due to its extensive involvement in transcriptional control, RNA processing, and other cellular pathways that are causally related to tumor initiation and progression. In recent years, various compounds have been screened or designed to target either the substrate- or cofactor-binding site of PRMT5. To expand the diversity of chemotypes for inhibitory binding to PRMT5 and other AdoMet-dependent methyltransferases, in this work, we designed a series of triazole-containing adenosine analogs aimed at targeting the cofactor-binding site of PRMT5. Triazole rings have commonly been utilized in drug discovery due to their ease of synthesis and functionalization as bioisosteres of amide bonds. Herein, we utilized the electronic properties of the triazole ring as a novel way to specifically target the cofactor-binding site of PRMT5. A total of about 30 compounds were synthesized using the modular alkyne-azide cycloaddition reaction. Biochemical tests showed that these compounds exhibited inhibitory activity of PRMT5 at varying degrees and several showed single micromolar potency, with clear selectivity for PRMT5 over PRMT1. Docking-based structural analysis showed that the triazole ring plays a key role in binding to the characteristic residue Phe327 in the active pocket of PRMT5, explaining the compounds' selectivity for this type-II enzyme. Overall, this work provides new structure-activity relationship information on the design of AdoMet analogs for selective inhibition of PRMT5. Further structural optimization work will further improve the potency of the top leads.

Coronavirus Disease 2019 (COVID-19) Diagnostic Clinical Decision Support: A Pre-Post Implementation Study of CORAL (COvid Risk cALculator).

BACKGROUND: Isolation of hospitalized persons under investigation (PUIs) for coronavirus disease 2019 (COVID-19) reduces nosocomial transmission risk. Efficient evaluation of PUIs is needed to preserve scarce healthcare resources. We describe the development, implementation, and outcomes of an inpatient diagnostic algorithm and clinical decision support system (CDSS) to evaluate PUIs. METHODS: We conducted a pre-post study of CORAL (COvid Risk cALculator), a CDSS that guides frontline clinicians through a risk-stratified COVID-19 diagnostic workup, removes transmission-based precautions when workup is complete and negative, and triages complex cases to infectious diseases (ID) physician review. Before CORAL, ID physicians reviewed all PUI records to guide workup and precautions. After CORAL, frontline clinicians evaluated PUIs directly using CORAL. We compared pre- and post-CORAL frequency of repeated severe acute respiratory syndrome coronavirus 2 nucleic acid amplification tests (NAATs), time from NAAT result to PUI status discontinuation, total duration of PUI status, and ID physician work hours, using linear and logistic regression, adjusted for COVID-19 incidence. RESULTS: Fewer PUIs underwent repeated testing after an initial negative NAAT after CORAL than before CORAL (54% vs 67%, respectively; adjusted odd ratio, 0.53 [95% confidence interval, .44-.63]; P < .01). CORAL significantly reduced average time to PUI status discontinuation (adjusted difference [standard error], -7.4 [0.8] hours per patient), total duration of PUI status (-19.5 [1.9] hours per patient), and average ID physician work-hours (-57.4 [2.0] hours per day) (all P < .01). No patients had a positive NAAT result within 7 days after discontinuation of precautions via CORAL. CONCLUSIONS: CORAL is an efficient and effective CDSS to guide frontline clinicians through the diagnostic evaluation of PUIs and safe discontinuation of precautions.

A Structural Equation Model of the Effect of Masculinity and Avoidant Coping on Gay and Bisexual Men's Sexual Risk-Taking.

This study aims to extend the scientific knowledge base on the association between masculine norm adherence and sexual risk-taking, in the context of gay and bisexual men, by examining emotional suppression, social support seeking, and avoidant coping as potential mediating pathways. A sample of 482 gay and bisexual men was recruited. Structural equation modeling was used to assess for mediation. Findings revealed that although gender role conflict and conformity to masculine norms (i.e., the two masculine norm adherence predictor variables) did not have a direct effect on sexual risk-taking, a significant indirect effect was observed for gender role conflict on sexual risk-taking via increased avoidant coping. Accordingly, gender role conflict and avoidant coping may create a unique effect on sexual risk-taking whereby the effect of gender role conflict on sexual risk-taking is not transmitted directly but only indirectly through the mediating role of avoidant coping. Future research directions are discussed.

Genomic Determination of Reproductive Mode in Facultatively Parthenogenetic Opiliones.

Sexual reproduction may pose myriad short-term costs to females. Despite these costs, sexual reproduction is near ubiquitous. Facultative parthenogenesis is theorized to mitigate some of the costs of sex, as individuals can participate in occasional sex to limit costs while obtaining many benefits. However, most theoretical models assume sexual reproduction is fixed following mating, with no possibility of clutches of mixed reproductive ontogeny. Therefore, we asked: if coercive males are present at high frequency in a population of facultative parthenogens, will their clutches be solely sexually produced, or will there be evidence of sexually and asexually-produced offspring? How will their offspring production compare to conspecifics in low-frequency male populations? We addressed our questions by collecting females and egg clutches of the facultatively parthenogenetic Opiliones species Leiobunum manubriatum and L. globosum. In L. manubriatum, females from populations with few males were not significantly more fecund than females from populations with higher male relative frequency, despite the potential release of the former from sexual conflict. We used 3 genotyping methods along with a custom set of DNA capture probes to reveal that offspring of L. manubriatum from these high male populations were primarily produced via asexual reproduction. This is surprising because sex ratios in these southern populations approach equality, increasing the probability for females to encounter mates and produce offspring sexually. We additionally found evidence for reproductive polymorphisms within populations. Rapid and accurate SNP genotyping data will continue to allow us to address broader evolutionary questions regarding the role of facultative reproductive modes in the maintenance of sex.

Ionic liquids for oral insulin delivery.

With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.

Accelerated Idioventricular Rhythm: A Rare Case of Wide-Complex Dysrhythmia in a Teenager.

BACKGROUND: Accelerated idioventricular rhythm (AIVR) is an uncommon and typically benign dysrhythmia with similarities to more malignant forms of ventricular tachycardia (VT). It is often seen in adults after myocardial infarctions, although it also arises in the newborn period, as well as in children with and without congenital heart disease. CASE REPORT: We describe a presentation of AIVR in an otherwise healthy 13-year-old girl, discovered on arrival to the pediatric emergency department in the setting of post-tonsillectomy bleeding. The case reviews the diagnostic criteria of AIVR, associated symptoms, the pathophysiologic origin of AIVR, and potential treatment strategies. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Given its morphologic similarities to life-threatening forms of VT, AIVR can be misdiagnosed in the emergency department or primary care settings. With an understanding of the dysrhythmia's unique features, emergency physicians can avoid unnecessary interventions and provide the correct diagnosis, workup, and management of AIVR for pediatric patients.

Lower-Limb Biomechanics Differ Between Sexes During Maximal Loaded Countermovement Jumps.

ABSTRACT: Fain, AC, Semore, KD, Lobb, NJ, and Brown, TN. Lower-limb biomechanics differ between sexes during maximal loaded countermovement jumps. J Strength Cond Res 35(2): 325-331, 2021-To improve military personnel's operational performance, this study determined the impact of heavy, military body-borne load on vertical jump performance. Twenty men and 17 women had lower-limb work and power quantified during a series of countermovement jumps with 4 body-borne loads (20, 25, 30, and 35 kg). For each jump, subjects stood in athletic position with feet shoulder-width apart, then squatted down and immediately performed a maximal-effort vertical jump. Subjects performed 3 successful jumps with each load. During each jump, limb and hip, knee and ankle work and power, each joint's contribution to limb work, as well as jump height and center of mass velocity were quantified. Each dependent measure was submitted to a 2-way repeated-meausres analysis of variance, with alpha level 0.05. Body-borne load reduced jump height (p = 0.001) but increased ankle work (p < 0.001). To jump higher (p < 0.001) with a greater center of mass velocity (p = 0.001), men produced more limb work (p < 0.001), hip (p = 0.001; p < 0.001), knee (p < 0.001; p < 0.001), and ankle (p < 0.001; p < 0.001) joint power and work. But, women produced a greater percentage of work at the ankle (p = 0.020) than men. Military practitioners may target different training adaptations to improve male and female personnel operational performance because lower-limb biomechanics differ between sexes during loaded vertical jumps.

Sex and Stride Impact Joint Stiffness During Loaded Running.

This study determined changes in lower limb joint stiffness when running with body-borne load, and whether they differ with stride or sex. Twenty males and 16 females had joint stiffness quantified when running (4.0 m/s) with body-borne load (20, 25, 30, and 35 kg) and 3 stride lengths (preferred or 15% longer and shorter). Lower limb joint stiffness, flexion range of motion (RoM), and peak flexion moment were submitted to a mixed-model analysis of variance. Knee and ankle stiffness increased 19% and 6% with load (P < .001, P = .049), but decreased 8% and 6% as stride lengthened (P = .004, P < .001). Decreased knee RoM (P < .001, 0.9°-2.7°) and increased knee (P = .007, up to 0.12 N.m/kg.m) and ankle (P = .013, up to 0.03 N.m/kg.m) flexion moment may stiffen joints with load. Greater knee (P < .001, 4.7°-5.4°) and ankle (P < .001, 2.6°-7.2°) flexion RoM may increase joint compliance with longer strides. Females exhibited 15% stiffer knee (P = .025) from larger reductions in knee RoM (4.3°-5.4°) with load than males (P < .004). Stiffer lower limb joints may elevate injury risk while running with load, especially for females.