PIP-Seq identifies novel heterogeneous lung innate lymphocyte population activation after combustion product exposure.

Innate lymphoid cells (ILCs) are a heterogeneous population that play diverse roles in airway inflammation after exposure to allergens and infections. However, how ILCs respond after exposure to environmental toxins is not well understood. Here we show a novel method for studying the heterogeneity of rare lung ILC populations by magnetic enrichment for lung ILCs followed by particle-templated instant partition sequencing (PIP-seq). Using this method, we were able to identify novel group 1 and group 2 ILC subsets that exist after exposure to both fungal allergen and burn pit-related constituents (BPC) that include dioxin, aromatic hydrocarbon, and particulate matter. Toxin exposure in combination with fungal allergen induced activation of specific ILC1/NK and ILC2 populations as well as promoted neutrophilic lung inflammation. Oxidative stress pathways and downregulation of specific ribosomal protein genes ( Rpl41 and Rps19 ) implicated in anti-inflammatory responses were present after BPC exposure. Increased IFNγ expression and other pro-neutrophilic mediator transcripts were increased in BPC-stimulated lung innate lymphoid cells. Further, the addition of BPC induced Hspa8 (encodes HSC70) and aryl hydrocarbon transcription factor activity across multiple lung ILC subsets. Overall, using an airway disease model that develops after occupational and environmental exposures, we demonstrate an effective method to better understand heterogenous ILC subset activation.

Expansion of the phenotypic spectrum of KARS1-related disorders to include arthrogryposis multiplex congenita and summary of experiences with lysine supplementation.

There are currently multiple disorders of aminoacyl-tRNA synthetases described, including KARS1-related disorder resulting from dysfunctional lysyl-tRNA synthetases. In this report, we describe four novel KARS1 variants in three affected individuals, two of whom displayed arthrogryposis-like phenotypes, suggestive of phenotypic expansion. We also highlight subjective clinical improvement in one subject following lysine supplementation in conjunction with a protein-fortified diet, suggesting its potential as a novel treatment modality for KARS1-related disorders. This report offers additional insight into the etiology and management of KARS1-related disorders and expands our ability to provide guidance to affected individuals and their families.

Amphibian Segmentation Clock Models Suggest How Large Genome and Cell Sizes Slow Developmental Rate.

Evolutionary increases in genome size, cell volume, and nuclear volume have been observed across the tree of life, with positive correlations documented between all three traits. Developmental tempo slows as genomes, nuclei, and cells increase in size, yet the driving mechanisms are poorly understood. To bridge this gap, we use a mathematical model of the somitogenesis clock to link slowed developmental tempo with changes in intra-cellular gene expression kinetics induced by increasing genome size and nuclear volume. We adapt a well-known somitogenesis clock model to two model amphibian species that vary 10-fold in genome size: Xenopus laevis (3.1 Gb) and Ambystoma mexicanum (32 Gb). Based on simulations and backed by analytical derivations, we identify parameter changes originating from increased genome and nuclear size that slow gene expression kinetics. We simulate biological scenarios for which these parameter changes mathematically recapitulate slowed gene expression in A. mexicanum relative to X. laevis, and we consider scenarios for which additional alterations in gene product stability and chromatin packing are necessary. Results suggest that slowed degradation rates as well as changes induced by increasing nuclear volume and intron length, which remain relatively unexplored, are significant drivers of slowed developmental tempo.

The reciprocal relationship between amyloid precursor protein and mitochondrial function.

Amyloid precursor protein (APP), secretase enzymes, and amyloid beta (Aß) have been extensively studied in the context of Alzheimer's disease (AD). Despite this, the function of these proteins and their metabolism is not understood. APP, secretase enzymes, and APP processing products (Aß and C-terminal fragments) localize to endosomes, mitochondria, endoplasmic reticulum (ER), and mitochondrial/ER contact sites. Studies implicate significant relationships between APP, secretase enzyme function, APP metabolism, and mitochondrial function. Mitochondrial dysfunction is a key pathological hallmark of AD and is intricately linked to proteostasis. Here, we review studies examining potential functions of APP, secretase enzymes, and APP metabolites in the context of mitochondrial function and bioenergetics. We discuss implications and limitations of studies and highlight knowledge gaps that remain in the field.

Estimated Pulse-Wave Velocity and Magnetic Resonance Imaging Markers of Cerebral Small-Vessel Disease in the NOMAS.

BACKGROUND: Pulse-wave velocity is a measure of arterial stiffness and a risk factor for cardiovascular disease. Recently, an estimated pulse-wave velocity (ePWV) was introduced that was predictive of increased risk of cardiovascular disease. Our objective was to determine whether ePWV was associated with cerebral small-vessel disease on magnetic resonance imaging. METHODS AND RESULTS: We included 1257 participants from the NOMAS (Northern Manhattan Study). The ePWV values were calculated using a nonlinear function of age and mean arterial blood pressure. The association between ePWV and white matter hyperintensity volume was assessed. Modification by race and ethnicity was evaluated. Associations between ePWV and other cerebral small-vessel disease markers, covert brain infarcts, cerebral microbleeds, and enlarged perivascular spaces, were explored as secondary outcomes. Mean±SD age of the cohort was 64±8 years; 61% were women; 18% self-identified as non-Hispanic Black, 67% as Hispanic, and 15% as non-Hispanic White individuals. Mean±SD ePWV was 11±2 m/s in the total NOMAS population and was similar across race and ethnic groups. The ePWV was significantly associated with white matter hyperintensity volume (ß=0.23 [95% CI, 0.20-0.26]) after adjustment. Race and ethnicity modified the association between ePWV and white matter hyperintensity volume, with stronger associations in Hispanic and non-Hispanic Black individuals. Significant associations were found between ePWV and covert brain infarcts, cerebral microbleeds, and perivascular spaces after adjustment. CONCLUSIONS: The ePWV function may provide a vascular mechanism for deleterious cerebrovascular outcomes in individuals with cerebral small-vessel disease and is particularly apparent in the racial and ethnic minorities represented in the NOMAS cohort.

Steady-state, therapeutic, and helminth-induced IL-4 compromise protective CD8 T cell bystander activation.

Memory CD8 T cells (Tmem) can be activated into innate-like killers by cytokines like IL-12, IL-15, and/or IL-18; but mechanisms regulating this phenomenon (termed bystander activation) are not fully resolved. We found strain-intrinsic deficiencies in bystander activation using specific pathogen-free mice, whereby basal IL-4 signals antagonize IL-18 sensing. We show that therapeutic and helminth-induced IL-4 impairs protective bystander-mediated responses against pathogens. However, this IL-4/IL-18 axis does not completely abolish bystander activation but rather tunes the expression of direct versus indirect mediators of cytotoxicity (granzymes and interferon-γ, respectively). We show that antigen-experience overrides strain-specific deficiencies in bystander activation, leading to uniform IL-18 receptor expression and enhanced capacity for bystander activation/cytotoxicity. Our data highlight that bystander activation is not a binary process but tuned/deregulated by other cytokines that are elevated by contemporaneous infections. Further, our findings underscore the importance of antigen-experienced Tmem to dissect the contributions of bystander Tmem in health and disease.

Inflammation dynamically regulates steroid hormone metabolism and action within macrophages in rheumatoid arthritis.

RATIONALE: In inflammatory diseases such as rheumatoid arthritis (RA), steroid metabolism is a central component mediating the actions of immuno-modulatory glucocorticoids and sex steroids. However, the regulation and function of cellular steroid metabolism within key leukocyte populations such as macrophages remain poorly defined. In this study, the inflammatory regulation of global steroid metabolism was assessed in RA macrophages. METHODS: Bulk RNA-seq data from RA synovial macrophages was used to assess transcripts encoding key enzymes in steroid metabolism and signalling. Changes in metabolism were assessed in synovial fluids, correlated to measures of disease activity and functionally validated in primary macrophage cultures. RESULTS: RNA-seq revealed a unique pattern of differentially expressed genes, including changes in genes encoding the enzymes 11ß-HSD1, SRD5A1, AKR1C2 and AKR1C3. These correlated with disease activity, favouring increased glucocorticoid and androgen levels. Synovial fluid 11ß-HSD1 activity correlated with local inflammatory mediators (TNFα, IL-6, IL-17), whilst 11ß-HSD1, SRD5A1 and AKR1C3 activity correlated with systemic measures of disease and patient pain (ESR, DAS28 ESR, global disease activity). Changes in enzyme activity were evident in inflammatory activated macrophages in vitro and revealed a novel androgen activating role for 11ß-HSD1. Together, increased glucocorticoids and androgens were able to suppress inflammation in macrophages and fibroblast-like-synoviocytes. CONCLUSIONS: This study underscores the significant increase in androgen and glucocorticoid activation within inflammatory polarized macrophages of the synovium, contributing to local suppression of inflammation. The diminished profile of inactive steroid precursors in postmenopausal women may contribute to disturbances in this process, leading to increased disease incidence and severity.

Lady With the Blue Hair: An Atypical Cause of Myasthenic Crisis.

A myasthenic crisis denotes a severe exacerbation of myasthenia gravis, leading a patient to enter a life-threatening state due to progressing muscle weakness that ultimately results in respiratory failure. A crisis can require intubation, mechanical ventilation, and additional critical care to prevent further decompensation and potentially death. Numerous well-documented precipitating factors exist, such as infections, surgery, stress, and various medications. We present the case of a 43-year-old woman recently diagnosed with myasthenia gravis who has experienced two myasthenic crises since diagnosis without evident triggers such as surgery, changes in medication, or infection. Following an unremarkable initial diagnostic test and continued treatment for the crisis, we sought additional information from the patient's family member at the bedside. We were informed that two weeks prior to both times of crisis with intubation, the patient had dyed her hair blue. The common chemical component in the two different hair dyes used was methylisothiazolinone, which is suspected to have contributed to the exacerbation of the patient's myasthenia gravis. As more evidence for new precipitating factors of myasthenic crises develops, it is crucial for physicians to quickly identify signs and symptoms of a crisis so appropriate intervention can occur in a time-sensitive manner. In addition, myasthenia gravis patients should be made aware to be cautious of precipitating factors of a crisis, including but not limited to new beauty products.

A unique multi-synaptic mechanism involving acetylcholine and GABA regulates dopamine release in the nucleus accumbens through early adolescence in male rats.

Adolescence is characterized by changes in reward-related behaviors, social behaviors, and decision making. These behavioral changes are necessary for the transition into adulthood, but they also increase vulnerability to the development of a range of psychiatric disorders. Major reorganization of the dopamine system during adolescence is thought to underlie, in part, the associated behavioral changes and increased vulnerability. Here, we utilized fast scan cyclic voltammetry and microdialysis to examine differences in dopamine release as well as mechanisms that underlie differential dopamine signaling in the nucleus accumbens (NAc) core of adolescent (P28-35) and adult (P70-90) male rats. We show baseline differences between adult and adolescent stimulated dopamine release in male rats, as well as opposite effects of the a6 nicotinic acetylcholine receptor (nAChR) on modulating dopamine release. The a6-selective blocker, a-conotoxin, increased dopamine release in early adolescent rats, but decreased dopamine release in rats beginning in middle adolescence and extending through adulthood. Strikingly, blockade of GABAA and GABAB receptors revealed that this a6-mediated increase in adolescent dopamine release requires NAc GABA signaling to occur. We confirm the role of a6 nAChR and GABA in mediating this effect in vivo using microdialysis. Results herein suggest a multisynaptic mechanism potentially unique to the period of development that includes early adolescence, involving acetylcholine acting at a6-containing nAChRs to drive inhibitory GABA tone on dopamine release.

Collaboration between IL-7 and IL-15 enables adaptation of tissue-resident and circulating memory CD8+ T cells.

Interleukin-7 (IL-7) is considered a critical regulator of memory CD8+ T cell homeostasis, but this is primarily based on analysis of circulating and not tissue-resident memory (TRM) subsets. Furthermore, the cell-intrinsic requirement for IL-7 signaling during memory homeostasis has not been directly tested. Using inducible deletion, we found that Il7ra loss had only a modest effect on persistence of circulating memory and TRM subsets and that IL-7Rα was primarily required for normal basal proliferation. Loss of IL-15 signaling imposed heightened IL-7Rα dependence on memory CD8+ T cells, including TRM populations previously described as IL-15-independent. In the absence of IL-15 signaling, IL-7Rα was upregulated, and loss of IL-7Rα signaling reduced proliferation in response to IL-15, suggesting cross-regulation in memory CD8+ T cells. Thus, across subsets and tissues, IL-7 and IL-15 act in concert to support memory CD8+ T cells, conferring resilience to altered availability of either cytokine.

Prevalence of current chronic pain in Royal Canadian Mounted Police cadets.

Background: Nearly half of active duty Royal Canadian Mounted Police (RCMP) officers report experiencing current chronic pain (43%; i.e. pain lasting longer than 3 months). Most RCMP officers who report chronic pain indicate that the pain started after working as RCMP officers (91%). Baseline data on chronic pain prevalence among RCMP cadets has not been available. Aims: The current study was designed to provide cross-sectional estimates of chronic pain prevalence among RCMP cadets starting the Cadet Training Program and to assess for sociodemographic differences among participants. Methods: The RCMP Study uses a longitudinal prospective sequential experimental cohort design to create a clustered randomized trial that engages individual participants for 5.5 years. The current article provides cross-sectional associations between chronic pain prevalence and sociodemographic characteristics. Participants were RCMP cadets starting the Cadet Training Program (n = 770). Location, intensity (on a 0-10 scale and days per week experienced), and duration (number of months) of chronic pain were reported. Differences across sociodemographic characteristics were examined. Results: Few RCMP cadets reported experiencing chronic pain (10%); lower back pain was rated as the most severe in terms of intensity and duration and second most frequently reported in number of days experienced per week. Prevalence of chronic pain was lower among RCMP cadets than among RCMP officers. Conclusions: Chronic pain prevalence among active duty RCMP officers may result from or be moderated by operational duties, as well as routine aging. Future researchers could examine ways to mitigate chronic pain development during RCMP officer careers.

Contexte: Près de la moitié des agents de la Gendarmerie royale du Canada (GRC) en service actif déclarent souffrir de douleur chronique (43 %; c'est-à-dire une douleur qui dure plus de trois mois). La plupart des agents de la GRC qui déclarent souffrir de douleur chronique indiquent que la douleur a commencé après avoir travaillé comme agents de la GRC (91 %). Il n'existe pas de données de référence sur la prévalence de la douleur chronique chez les cadets de la GRC.Objectifs: La présente étude a été conçue pour fournir des estimations transversales de la prévalence de la douleur chronique chez les cadets de la GRC qui commencent le Programme de formation des cadets et évaluer les différences sociodémographiques entre les participants.Méthodes: L'étude sur la GRC utilise un devis de cohorte expérimental séquentiel prospectif longitudinal pour créer un essai randomisé en grappes impliquant des participants individuels pendant 5,5 ans. Le présent article présente des associations transversales entre la prévalence de la douleur chronique et les caractéristiques sociodémographiques. Les participants étaient des cadets de la GRC qui commençaient le Programme de formation des cadets (n = 770). Le lieu, l'intensité (sur une échelle de 0 à 10 et selon le nombre de jours par semaine où la douleur était ressentie), de même que la durée (nombre de mois) pendant laquelle la douleur chronique était ressentie, ont été déclarés.Résultats: Peu de cadets de la GRC ont déclaré souffrir de douleur chronique (10 %); la douleur lombaire a été évaluée comme la plus sévère en termes d'intensité et de durée, et la deuxième la plus fréquemment rapportée en nombre de jours par semaine. La prévalence de la douleur chronique était plus faible chez les cadets de la GRC que chez les agents de la GRC.Conclusions: La prévalence de la douleur chronique chez les agents de la GRC en service actif peut résulter des tâches opérationnelles ou être modérée par celles-ci, ainsi que par le vieillissement normal. Les futurs chercheurs pourraient examiner les moyens d'atténuer le développement de la douleur chronique au cours de la carrière des agents de la GRC.

The Study of the Epidemiology of Pediatric Hypertension Registry (SUPERHERO): Rationale and Methods.

Despite increasing prevalence of hypertension in youth and high adult cardiovascular mortality rates, the long-term consequences of youth-onset hypertension remain unknown. This is due to limitations of prior research such as small sample sizes, reliance on manual record review, and limited analytic methods that did not address major biases. The Study of the Epidemiology of Pediatric Hypertension (SUPERHERO) is a multisite retrospective Registry of youth evaluated by subspecialists for hypertension disorders. Sites obtain harmonized electronic health record data using standardized biomedical informatics scripts validated with randomized manual record review. Inclusion criteria are index visit for International Classification of Diseases Diagnostic Codes, 10th Revision (ICD-10 code)-defined hypertension disorder ≥January 1, 2015 and age <19 years. We exclude patients with ICD-10 code-defined pregnancy, kidney failure on dialysis, or kidney transplantation. Data include demographics, anthropomorphics, U.S. Census Bureau tract, histories, blood pressure, ICD-10 codes, medications, laboratory and imaging results, and ambulatory blood pressure. SUPERHERO leverages expertise in epidemiology, statistics, clinical care, and biomedical informatics to create the largest and most diverse registry of youth with newly diagnosed hypertension disorders. SUPERHERO's goals are to (i) reduce CVD burden across the life course and (ii) establish gold-standard biomedical informatics methods for youth with hypertension disorders.

The prevalence of anxiety in respiratory and sleep diseases: A systematic review and meta-analysis.

BACKGROUND: Anxiety is common in those with chronic physical health conditions and can have significant impacts on both quality of life and physical health outcomes. Despite this, there are limited studies comprehensively investigating the prevalence of anxiety in respiratory and sleep medicine settings. This systematic review and meta-analysis aims to provide insight into the global prevalence of anxiety symptoms/disorders in respiratory and sleep medicine outpatients. METHODS: PubMed, Embase, Cochrane, PsycINFO and Google Scholar databases were searched from database inception to January 23, 2023 for studies assessing the prevalence of anxiety in adult (≥16 years) respiratory and sleep medicine outpatients. Data was screened and extracted independently by two investigators. Anxiety was measured using various self-report questionnaires, structured interviews, and/or patient records. Using CMA software for the meta-analysis, a random-effects model was used for pooled estimates, and subgroup analysis was conducted on relevant models using a mixed-effects model. RESULTS: 116 studies were included, featuring 36,340 participants across 40 countries. The pooled prevalence of anxiety was 30.3 % (95%CI 27.9-32.9 %, 10,679/36,340). Subgroup analysis found a significant difference across type of condition, with pulmonary tuberculosis the highest at 43.1 % and COVID-19 outpatients the lowest at 23.4 %. No significant difference was found across anxiety types, country or age. Female sex and the use of self-report measures was associated with significantly higher anxiety estimates. CONCLUSIONS: Anxiety is a common experience amongst patients in respiratory and sleep medicine outpatient settings. Thus, it is crucial that anxiety identification and management is considered by physicians in the field. REGISTRATION: The protocol is registered in PROSPERO (CRD42021282416).

Lymphatic vessel transit seeds cytotoxic resident memory T cells in skin draining lymph nodes.

Lymphatic transport shapes the homeostatic immune repertoire of lymph nodes (LNs). LN-resident memory T cells (TRMs) play an important role in site-specific immune memory, yet how LN TRMs form de novo after viral infection remains unclear. Here, we tracked the anatomical distribution of antiviral CD8+ T cells as they seeded skin and LN TRMs using a model of vaccinia virus-induced skin infection. LN TRMs localized to the draining LNs (dLNs) of infected skin, and their formation depended on the lymphatic egress of effector CD8+ T cells from the skin, already poised for residence. Effector CD8+ T cell transit through skin was required to populate LN TRMs in dLNs, a process reinforced by antigen encounter in skin. Furthermore, LN TRMs were protective against viral rechallenge in the absence of circulating memory T cells. These data suggest that a subset of tissue-infiltrating CD8+ T cells egress from tissues during viral clearance and establish a layer of regional protection in the dLN basin.

Furthering racial liberalism in UK higher education: The populist construction of the 'free speech crisis'.

In this article we analyse the constructed 'free speech crisis' associated with higher education (HE) in the United Kingdom (UK). We examine the media discourses from 2012 to 2022 which led to the establishment of a sense of crisis around speech in universities and, ultimately, to the Freedom of Speech Act in May 2023. We undertake a critical discourse analysis focused on the constructions of universities and university students in two major right-wing broadsheet newspapers, The Times and The Telegraph, and in the right-wing magazine The Spectator. We conceptualise the 'free speech crisis' as a discursive formation which is part of broader political efforts of conservative elites to maintain hegemony in Britain. Drawing on populism theory and race critical analyses, we argue that the 'free speech crisis' is an expression of racial liberalism and a placeholder for a deeper white anxiety over the social reproduction of elites in university spaces, and thus over (cultural) hegemony in the public sphere. We understand the desire to regulate 'free' speech in HE as an effort to prevent the emergence of an elite and (counter)hegemony different to the status quo. We make contributions to two emergent and interrelating bodies of literature: firstly, the study of populism in (post)Brexit Britain, and secondly, the study of culture wars, including iterations of the 'free speech crisis' and 'the war on woke'.

Trouble with the curve: the 90-9-1 rule to measure volitional participation inequalities among Royal Canadian Mounted Police cadets during training.

Objective: The Royal Canadian Mounted Police (RCMP) Study includes longitudinal multimodal assessments of RCMP cadets from pre-training (i.e., starting the Cadet Training Program [CTP]) to post-deployment and for five years thereafter. The data allow for investigating the multidimensionality of volitional participation in digital health data collection frameworks within serial data collection platforms and the impact of participation inequalities by classifying cadets using the 90-9-1 rule. By classifying cadets as Lurkers, Contributors, and Superusers formally described by the 90-9-1 rule, where 90% of actors do not participate, 9% seldom contribute, and 1% contribute substantially allows for the assessing of relationships between participation inequalities in self-monitoring behaviors as well as whether mental health disorder symptoms at pre-training (i.e., starting the CTP) were associated with subsequent participation. Methods: Participants were asked to complete a Full Assessment prior to their training at CTP, as well as short daily surveys throughout their training. Participation frequency was described using a process where participants were rank ordered by the number of daily surveys completed and classified into one of three categories. Full assessment surveys completed prior to their training at CTP included screening tools for generalized anxiety disorder (GAD), major depressive disorder (MDD), posttraumatic stress disorder (PTSD), alcohol use disorder (AUD), and panic disorder (PD). The Kruskal-Wallis H test was used to assess differences in participation rates between mental health disorder symptom screening groups for each measure at pre-training, and Spearman's Rho was used to test for associations amongst self-reported Full Assessment screening tool responses and the number of daily surveys completed during CTP. Results: There were 18557 daily survey records collected from 772 participants. The rank-ordering of cadets by the number of daily surveys completed produced three categories in line with the 90-9-1 rule: Superusers who were the top 1% of cadets (n=8) and produced 6.4% of all recordings; Contributors who were the next 9% of cadets (n=68) and produced 49.2% of the recordings; and Lurkers who were the next 90% of cadets (n=695) and produced 44.4% of daily survey recordings. Lurkers had the largest proportion of positive screens for self-reported mental health disorders at pre-training. Conclusion: The creation of highly individualized, population-based mental health injury programs has been limited by an incomplete understanding of the causal relationships between protective factors and mental health. Disproportionate rates of disengagement from persons who screen positive for mental health disorders further compounds the difficulty in understanding the relationships between training programs and mental health. The current results suggest persons with mental health challenges may be less likely to engage in some forms of proactive mental health training. The current results also provide useful information about participation, adherence, and engagement that can be used to inform evidence-based paradigm shifts in health-related data collection in occupational populations.

Daily Eicosapentaenoic Acid Infusion in IUGR Fetal Lambs Reduced Systemic Inflammation, Increased Muscle ADRß2 Content, and Improved Myoblast Function and Muscle Growth.

Intrauterine growth-restricted (IUGR) fetuses exhibit systemic inflammation that contributes to programmed deficits in myoblast function and muscle growth. Thus, we sought to determine if targeting fetal inflammation improves muscle growth outcomes. Heat stress-induced IUGR fetal lambs were infused with eicosapentaenoic acid (IUGR+EPA; n = 9) or saline (IUGR; n = 8) for 5 days during late gestation and compared to saline-infused controls (n = 11). Circulating eicosapentaenoic acid was 42% less (p < 0.05) for IUGR fetuses but was recovered in IUGR+EPA fetuses. The infusion did not improve placental function or fetal O2 but resolved the 67% greater (p < 0.05) circulating TNFα observed in IUGR fetuses. This improved myoblast function and muscle growth, as the 23% reduction (p < 0.05) in the ex vivo differentiation of IUGR myoblasts was resolved in IUGR+EPA myoblasts. Semitendinosus, longissimus dorsi, and flexor digitorum superficialis muscles were 24-39% lighter (p < 0.05) for IUGR but not for IUGR+EPA fetuses. Elevated (p < 0.05) IL6R and reduced (p < 0.05) ß2 adrenoceptor content in IUGR muscle indicated enhanced inflammatory sensitivity and diminished ß2 adrenergic sensitivity. Although IL6R remained elevated, ß2 adrenoceptor deficits were resolved in IUGR+EPA muscle, demonstrating a unique underlying mechanism for muscle dysregulation. These findings show that fetal inflammation contributes to IUGR muscle growth deficits and thus may be an effective target for intervention.

Attitudes towards Telemedicine among Pregnant People and Parents of Toddlers in an Urban Safety-net Setting.

OBJECTIVE: To understand attitudes towards telemedicine and to further elucidate benefits, disadvantages, and visit preferences in a largely minority, urban safety-net setting. METHODS: Between 2020 and 2021, pregnant people, and parents of children younger than two years old were recruited from outpatient clinics. Interviews were conducted via phone, recorded, transcribed, and translated. Data were analyzed using content analysis. RESULTS: Seventy-four (74) individuals participated including 42 pregnant people and 32 parents. Most participants cited advantages to telemedicine including safety, convenience, improved access, and less disruption of work schedules, and wished to continue to have the telemedicine option available after the pandemic. CONCLUSIONS: Patients seeking care in safety-net settings, many of whom are working parents, noted that telemedicine improves access to care by providing an efficient and accessible option that overcomes barriers related to transportation and work schedules. Their experiences highlight the importance of continuing to offer telemedicine services.

Imaging in Lung Cancer Staging.

Lung cancer remains one of the leading causes of mortality worldwide, as well as in the United States. Clinical staging, primarily with imaging, is integral to stratify patients into groups that determine treatment options and predict survival. The eighth edition of the tumor, node, metastasis (TNM-8) staging system proposed in 2016 by the International Association for the Study of Lung Cancer remains the current standard for lung cancer staging. The system is used for all subtypes of lung cancer, including non-small cell lung cancer, small cell lung cancer, and bronchopulmonary carcinoid tumors.

Pericardial Recesses on Computed Tomography: Implications for the Pulmonologist.

The pericardium comprises a double-walled fibrous-serosal sac that encloses the heart. Reflections of the serosal layer form sinuses and recesses. With advances in multidetector computed tomography (CT) technology, pericardial recesses are frequently detected with thin-section CT. Knowledge of pericardial anatomy on imaging is crucial to avoid misinterpretation of fluid-filled pericardial sinuses and recesses as adenopathy/pericardial metastasis or aortic dissection, which can impact patient management and treatment decisions. The authors offer a comprehensive review of pericardial anatomy and its variations observed on CT, potential pitfalls in image interpretation, and implications for the pulmonologist with respect to unnecessary diagnostic procedures or interventions.