A comparison of population-level exposure and equity tradeoffs across strategies to reduce fine particulate matter emissions from transportation sources in the northeastern US.

BACKGROUND: Many climate mitigation policies to reduce transportation emissions have public health benefits related to ambient air pollution. However, few health analyses consider the equity implications of alternative policies. Equity can be conceptualized in many different ways that may be relevant to communities, decision-makers, and other stakeholders. OBJECTIVES: To evaluate alternative transportation emissions reduction scenarios across the northeastern United States considering population exposure reductions and multiple equity constructs. METHODS: We developed four quantitative indicators reflecting equity constructs that aligned with stakeholder perspectives, including racial/ethnic exposure inequities, proportion of benefits in environmental justice communities, distribution of benefits among participating states, and rural/urban share of benefits. We analyzed numerous transportation emissions reduction scenarios for directly emitted fine particulate matter (primary PM2.5) covering 12 Northeast states and the District of Columbia. We used the Community Multiscale Air Quality model with the decoupled direct method to estimate the reduction in population-weighted primary PM2.5 exposure and the impact on equity for each scenario. RESULTS: Scenarios that yielded greater reductions in population-weighted primary PM2.5 exposure generally emphasized emissions reductions in urban areas or states with large urban centers, with a more than threefold difference in benefits across scenarios. The higher exposure-benefit scenarios typically also had greater reductions in racial/ethnic exposure inequities but led to higher between-state or rural/urban inequality. Scenarios that targeted uniform percentage emission reductions from light or heavy-duty trucks best addressed rural/urban inequalities but led to the smallest reductions in racial/ethnic inequity. CONCLUSION: There are intrinsic tradeoffs among equity constructs, where focusing resources on distributing benefits across states or between urban and rural populations could come at the expense of less reduction in racial/ethnic exposure inequities or in environmental justice communities. Future health benefits analyses should incorporate multiple equity indicators that reflect different stakeholder perspectives and articulate the underlying constructs and tradeoffs.

Healthcare workers' experiences protecting themselves and their families during the COVID-19 pandemic in 2020-2021.

We characterized experiences and strategies used by frontline healthcare workers to prevent severe-acute-respiratory-syndrome-related coronavirus transmission at work and to household members during the coronavirus disease pandemic. Alongside an online questionnaire (n = 234), remote semi-structured interviews (n = 23: 15 clinicians, 8 non-clinicians) were conducted in 2021. Mitigation challenges and facilitators were identified from data to represent experiences as a process considering the before, during, and after work shifts. Journey mapping was utilized to visually describe how healthcare workers experienced the stages of the work environment, leaving work, commuting home, and the home environment, and strategies implemented to stay safe. Major facilitators included the uptake of coronavirus disease vaccines and testing, information regarding virus transmission, and adequate personal protective equipment. The most critical challenges identified included a lack of designated areas for end-of-day disinfection, changing rooms, showers, and lockers in the leaving work stage. Psychosocial and environmental factors must be considered in future hospital pandemic preparations.

Functional Composite Spacer (Antibiotic Cement around a Hemiarthroplasty) for the Treatment of Shoulder Infections: Minimum 5-Year Outcomes.

BACKGROUND: Periprosthetic infections remain a challenging complication following shoulder arthroplasty and an ideal treatment protocol has yet to be established. Two-stage revision is a common approach. Historically, the first stage entails placement of an all-cement antibiotic spacer. While prior studies have reported on cement spacers as definitive management, persistent pain and inadequate function often lead many to later request a second stage procedure. The functional composite spacer consists of a humeral hemiarthroplasty implant with antibiotic cement coated around the stem alone to preserve the metallic humeral head-glenoid articulation. Functional composite spacers have demonstrated improvements in function and motion with high patient satisfaction at 25 months, but longer-term follow-up is needed to better understand the role it may play in the management of shoulder infections. The purpose of this study is to evaluate outcomes at a minimum of 5 years in patients who initially planned to undergo two-stage revision but elected to retain the functional spacer. METHODS: A retrospective review of a single institution's shoulder surgery repository from 2007 to 2018 identified 30 patients who underwent placement of a composite spacer. Overall, 5 patients underwent second stage reimplantation and 12 patients did not have 5-year follow-up (6 lost to follow-up and 6 deceased). A total 13 patients were included who maintained a functional composite spacer and had minimum 5-year follow-up. Patient-reported outcome measures (ASES, SST, SANE, VAS F and VAS P), satisfaction, range of motion, and radiographic estimation of glenoid wear were evaluated. RESULTS: Two of 13 patients (15%) required additional surgery: one secondary closure for early superficial wound dehiscence and one revision spacer for pain. There were no re-infections. At most recent follow-up patient satisfaction was high and significant improvements were noted for ASES (45.4; p<0.001), SST (5.3; p=0.003), SANE (47.3; p=0.002), VAS F (4.9; p=0.004), and VAS P (-4.4; p=0.007) as well as range of motion including abduction (39.2˚; p=0.005) and elevation (65.9˚; p=0.005). There was no significant change in humeral head medialization (p=0.11). CONCLUSIONS: Patients who do not undergo an early revision and retain a functional composite spacer maintain good function and range of motion with minimal pain at mid-term follow-up.

A novel approach to the epidemiology of people living with spinal cord injuries in France based on an original algorithm from public health insurance data.

INTRODUCTION: French Public Health Insurance gathers health, demographic and economic data based on codes from the 10th version of the international classification of diseases (ICD-10), specific nomenclature for each health-care (medical or surgical) procedures, medical expenses and justifications for full coverage of medical care. We aimed to build an algorithm that could identify the French population of people living with spinal cord injury (SCI) relying on public health insurance metadata. MATERIAL AND METHODS: The SNDS (in French, Système National des Données de Santé) was searched for the time-period 2012-2019, looking for: full-coverage motives, ICD-10 codes, and health-therapeutic procedures specific of our population of interest. We built a step-by-step algorithm that identified i)including codes, ii)excluding codes, iii)codes needing confirmation. A group of 3 physicians recognized as experts in this field contributed with data scientists to the selection of pertinent codes and their association. Including codes were ALD-20 (full-coverage 'paraplegia', in French, Affection de Longue Durée), G114 (spastic paraplegia), Q05.x (spina bifida), spinal cord trauma (S14.x; S24.x), vascular myelopathy (G951), degenerative myelopathies (M47.x). Autoimmune, other disabling neurological diseases with a specific ICD code, and oncologic patients were excluded. Neurological symptoms (G82.x) needed confirmation. We identified 6 categories of SCI regarding their etiology, based on ICD-10 code combinations (congenital, genetic, tumoral, traumatic, acquired and symptomatic) Finally antibiotics consumption and hospitalizations of persons identified as SCI were compared to a control sample from overall population (with a 1:5 ratio). RESULTS: Among almost 245 000 persons with putative SCI, we identified 133 849 living individuals with SCI aged>16 (55.8% men, age 57 yo [44;70]) by 2019. Confirmed traumatic SCI were 21 459 (67% were men, age 53 yo [39;67]), acquired non-traumatic were the most frequent (n=62 561, 46.7%). SCI consumed 1.5 to 3-times more antibiotics and were 4-fold more hospitalized than controls. Also, when hospitalized, they remained twice longer in rehabilitation facilities and 3-times longer in acute care. CONCLUSION: Using multiple code entries, our algorithm allowed an exhaustive identification of the French adult SCI population, with an updated epidemiology. This innovative method opens the field for large-scale studies regarding medical history of persons living with SCI by the prism of medical expenses and habits.

Improvement in Sleep Disturbance Following Arthroscopic Rotator Cuff Repair.

BACKGROUND: Approximately 90% of patients express concerns with sleep shortly after developing shoulder-related symptoms. Previous small cohort studies have demonstrated the impact of rotator cuff repair on sleep, but none have characterized the observed benefits. The purpose of this study is to evaluate sleep improvement after rotator cuff repair including the speed of sleep recovery, the time at which improvement plateaus, and the longer-term maintenance of improved sleep. METHODS: A retrospective review of our institution's shoulder and elbow repository identified patients who underwent primary arthroscopic rotator cuff repair from 2012 - 2021 and reported sleep disturbance preoperatively. Patients were evaluated using sleep-related questions from the Simple Shoulder Test and American Shoulder and Elbow Surgeons score. Sleep outcomes were compared from a preoperative visit to 3-month, 6-month, 12-month, and most recent follow-ups to evaluate efficacy of treatment, speed of recovery and improvement plateaus. RESULTS: Among 677 RCR patients, 95.7% (648/677) reported sleep disturbance preoperatively. A total of 474 met inclusion criteria with median follow-up of 4.1 years (IQR, 2.1-6.1). At most recent follow-up, 81.8% were able to sleep comfortably and 65.7% were able to sleep on the affected side. A plateau in the ability to sleep comfortably was seen at 6 months while no plateau was observed in the ability to sleep on the affected side. More rapid improvement in the ability to sleep comfortably occurred during the first 3 months and from 3 - 6 months for the ability to sleep on the affected side. CONCLUSION: The majority of patients with sleep disturbance who undergo RCR, report significant, rapid, and lasting improvement in the ability to sleep comfortably and the ability to sleep on the affected side.

Identification of ChatGPT-Generated Abstracts Within Shoulder and Elbow Surgery Poses a Challenge for Reviewers.

PURPOSE: To evaluate the extent to which experienced reviewers can accurately discern between AI-generated and original research abstracts published in the field of shoulder and elbow surgery and compare this to the performance of an AI-detection tool. METHODS: Twenty-five shoulder and elbow-related articles published in high-impact journals in 2023 were randomly selected. ChatGPT was prompted with only the abstract title to create an AI-generated version of each abstract. The resulting 50 abstracts were randomly distributed to and evaluated by 8 blinded peer reviewers with at least 5 years of experience. Reviewers were tasked with distinguishing between original and AI-generated text. A Likert scale assessed reviewer confidence for each interpretation and the primary reason guiding assessment of generated text was collected. AI output detector (0-100%) and plagiarism (0-100%) scores were evaluated using GPTZero. RESULTS: Reviewers correctly identified 62% of AI-generated abstracts and misclassified 38% of original abstracts as being AI-generated. GPTZero reported a significantly higher probability of AI output among generated abstracts (median 56%, IQR 51-77%) compared to original abstracts (median 10%, IQR 4-37%; p < 0.01). Generated abstracts scored significantly lower on the plagiarism detector (median 7%, IQR 5-14%) relative to original abstracts (median 82%, IQR 72-92%; p < 0.01). Correct identification of AI-generated abstracts was predominately attributed to the presence of unrealistic data/values. The primary reason for misidentifying original abstracts as AI was attributed to writing style. CONCLUSIONS: Experienced reviewers faced difficulties in distinguishing between human and AI-generated research content within shoulder and elbow surgery. The presence of unrealistic data facilitated correct identification of AI abstracts, whereas misidentification of original abstracts was often ascribed to writing style.

Development and evaluation of two educational sessions on take-home lead exposure prevention for construction workers and their families.

Take-home exposures occur when workers accidentally bring workplace contaminants home. Regular job responsibilities may expose construction workers to lead, which extends to their households via the take-home pathway. The present study aimed to develop and evaluate 2 educational sessions addressing take-home lead exposure tailored to construction workers and their families. Educational materials on take-home lead exposure and prevention strategies were designed following guidance from US government institutions and experts on construction work, lead exposure, and educational interventions. The educational materials were pilot-tested with construction workers and their family members during in-person or online sessions in English or Spanish. Changes in knowledge of take-home lead exposure were assessed through pre- and post-testing and open-ended feedback was collected from both participants and session facilitators. The study sample comprised 44 participants, including 33 workers and 11 family members. Among all participants, 81% were male, 46% were Hispanic or Latino, and the average age was 29 years. Post-test scores (µ = 93%, SD = 10%) were higher than pre-test scores (µ = 82%, SD = 19%), and younger participants (<30 years) were more likely to have a lower pre-test score compared to older participants (≥30 years). Overall, feedback from participants and facilitators was positive, indicating appropriate duration, appealing visuals, and ease of engagement through the training activities. Effective public health education for lead-exposed construction workers and their families is needed to reduce lead exposure disparities, especially among children of workers. Interventions must recognize that take-home exposures are not isolated to occupational or home environments.

Screening Strategies for Sleep-Disordered Breathing in Patients With Spinal Cord Injury in a Tertiary Care Rehabilitation Center.

BACKGROUND: Sleep-disordered breathing (SDB) is frequent in patients with spinal-cord injury (SCI). However, SDB is frequently underdiagnosed due to limited access to diagnostic testing and knowledge about the condition. Moreover, SDB heterogeneity (sleep apnea, obstructive sleep apnea or central sleep apnea and nocturnal alveolar hypoventilation) implies complex evaluation of both nocturnal respiratory effort and hypercapnia. The aim of this study was to compare different screening strategies for an SDB diagnosis in patients with SCI. METHODS: This was a retrospective analysis of data from subjects with SCI followed up in a tertiary-care rehabilitation center with a specialized sleep unit. Subjective (questionnaires) and objective data (polysomnography [PSG]), SpO2 extracted from the PSG, morning blood gases, and nocturnal transcutaneous CO2 (PtcCO2 ) were collected and analyzed. A retrospective comparison of different strategies for SDB screening was carried out. Each strategy was compared (alone and in combination) with the standard of care for sleep apnea (PSG) and nocturnal alveolar hypoventilation (PtcCO2 ) diagnosis. The performance of the usual cutoff and visual analysis was studied. RESULTS: Among 190 subjects with SCI who underwent a full night's PSG, data were available for 104 questionnaires and 162 with oximetry. Nocturnal alveolar hypoventilation was screened by PtcCO2 and blood gases in 52 subjects with SCI. Questionnaires (the modified Screening for Obstructive Sleep Apnea in Tetraplegia and the Epworth Sleepiness Scale) had poor performance for identifying sleep apnea and did not identify nocturnal alveolar hypoventilation. SpO2 (oxygen desaturation index score ≥ 13) and visual analysis of SpO2 were good at identifying sleep apnea but insufficient to identify nocturnal alveolar hypoventilation. Diurnal blood gases were poor predictors of nocturnal alveolar hypoventilation. CONCLUSIONS: Questionnaires were of limited use in subjects with SCI, but the oxygen desaturation index derived from oximetry performed well for sleep apnea screening. Both diurnal blood gases and oximetry visual analysis were insufficient for nocturnal alveolar hypoventilation screening. PtcCO2 monitoring should be mandatory and ideally combined with PSG given the heterogeneity of SDB phenotypes and associated sleep comorbidities of patients with SCI.

The expanding clinical and genetic spectrum of DYNC1H1-related disorders.

Intracellular trafficking involves an intricate machinery of motor complexes including the dynein complex to shuttle cargo for autophagolysosomal degradation. Deficiency in dynein axonemal chains as well as cytoplasmic light and intermediate chains have been linked with ciliary dyskinesia and skeletal dysplasia. The cytoplasmic dynein 1 heavy chain protein (DYNC1H1) serves as a core complex for retrograde trafficking in neuronal axons. Dominant pathogenic variants in DYNC1H1 have been previously implicated in peripheral neuromuscular disorders (NMD) and neurodevelopmental disorders (NDD). As heavy-chain dynein is ubiquitously expressed, the apparent selectivity of heavy-chain dyneinopathy for motor neuronal phenotypes remains currently unaccounted for. Here, we aimed to evaluate the full DYNC1H1-related clinical, molecular and imaging spectrum, including multisystem features and novel phenotypes presenting throughout life. We identified 47 cases from 43 families with pathogenic heterozygous variants in DYNC1H1 (aged 0-59 years) and collected phenotypic data via a comprehensive standardized survey and clinical follow-up appointments. Most patients presented with divergent and previously unrecognized neurological and multisystem features, leading to significant delays in genetic testing and establishing the correct diagnosis. Neurological phenotypes include novel autonomic features, previously rarely described behavioral disorders, movement disorders, and periventricular lesions. Sensory neuropathy was identified in nine patients (median age of onset 10.6 years), of which five were only diagnosed after the second decade of life, and three had a progressive age-dependent sensory neuropathy. Novel multisystem features included primary immunodeficiency, bilateral sensorineural hearing loss, organ anomalies, and skeletal manifestations, resembling the phenotypic spectrum of other dyneinopathies. We also identified an age-dependent biphasic disease course with developmental regression in the first decade and, following a period of stability, neurodegenerative progression after the second decade of life. Of note, we observed several cases in whom neurodegeneration appeared to be prompted by intercurrent systemic infections with double-stranded DNA viruses (Herpesviridae) or single-stranded RNA viruses (Ross-River fever, SARS-CoV-2). Moreover, the disease course appeared to be exacerbated by viral infections regardless of age and/or severity of NDD manifestations, indicating a role of dynein in anti-viral immunity and neuronal health. In summary, our findings expand the clinical, imaging, and molecular spectrum of pathogenic DYNC1H1 variants beyond motor neuropathy disorders and suggest a life-long continuum and age-related progression due to deficient intracellular trafficking. This study will facilitate early diagnosis and improve counselling and health surveillance of affected patients.

Concomitant Botulinum Toxin Injections for Neurogenic Detrusor Overactivity and Spasticity-A Retrospective Analysis of Practice and Safety.

As multiple indications for botulinum toxin injections (BTIs) can coexist for neurological patients, there are to date no description of concomitant injections (CIs) to treat both spasticity and neurogenic detrusor overactivity incontinence (NDOI) in patients with spinal cord injuries (SCIs) and multiple sclerosis (MS). We therefore identified patients followed at our institution by health data hub digging, using a specific procedure coding system in use in France, who have been treated at least once with detrusor and skeletal muscle BTIs within the same 1-month period, over the past 5 years (2017-2021). We analyzed 72 patients representing 319 CIs. Fifty (69%) were male, and the patients were mostly SCI (76%) and MS (18%) patients and were treated by a mean number of CIs of 4.4 ± 3.6 [1-14]. The mean cumulative dose was 442.1 ± 98.8 U, and 95% of CIs were performed within a 72 h timeframe. Among all CIs, five patients had symptoms evocative of distant spread but only one had a confirmed pathological jitter in single-fiber EMG. Eleven discontinued CIs for surgical alternatives: enterocystoplasty (five), tenotomy (three), intrathecal baclofen (two) and neurotomy (one). Concomitant BTIs for treating both spasticity and NDOI at the same time appeared safe when performed within a short delay and in compliance with actual knowledge for maximum doses.

Variations in the Anatomic Morphology of the Scapular Spine and Implications on Fracture After Reverse Shoulder Arthroplasty.

INTRODUCTION: This study evaluates the role of anatomic scapular morphology in acromion and scapular spine fracture (SSAF) risk after reverse shoulder arthroplasty (RSA). METHODS: Twelve scapular measurements were captured based on pilot study data, including scapular width measurements at the acromion (Z1), middle of the scapular spine (Z2), and medial to the first major angulation (Z3). Measurements were applied to 3D-CT scans from patients who sustained SSAF after RSA (SSAF group) and compared with those who did not (control group). Measurements were done by four investigators, and the intraclass correlation coefficient was calculated. Regression analysis determined trends in fracture incidence. RESULTS: One hundred forty-nine patients from two separate surgeons (J.L., A.M.) were matched by age and surgical indication of whom 51 sustained SSAF after reverse shoulder arthroplasty. Average ages for the SSAF and control cohorts were 78.6 and 72.1 years, respectively. Among the SSAF group, 15 were Levy type I, 26 Levy type II, and 10 Levy type 3 fractures. The intraclass correlation coefficient of Z1, Z2, and Z3 measurements was excellent (0.92, 0.92, and 0.94, respectively). Zone 1 and 3 measurements for the control group were 18.6 ± 3.7 mm and 3.2 ± 1.0 mm, respectively, compared with 22.5 ± 5.9 mm and 2.0 ± 0.70 mm in the SSAF group, respectively. The fracture group trended toward larger Z1 and smaller Z3 measurements. The average scapular spine proportion (SSP), Z1/Z3, was significantly greater in the control 6.20 ± 1.80 versus (12.60 ± 6.30; P < 0.05). Regression analysis showed a scapular spine proportion of ≤5 was associated with a fracture risk <5%, whereas an SSP of 9.2 correlated with a 50% fracture risk. DISCUSSION: Patients with a thicker acromions (Z1) and thinner medial scapular spines (Z3) have increased fracture risk. Understanding anatomic scapular morphology may allow for better identification of high-risk patients preoperatively.

Correlation Between Patient-Reported and Clinician-Measured Shoulder Range of Motion in Patients Undergoing Shoulder Surgery.

INTRODUCTION: There has been increasing interest in remote measures of patients' health, both in the clinical and research settings. This study sought to evaluate correlations between patient-reported and clinician-measured (CM) shoulder range of motion (ROM). METHODS: ROM measures including elevation, abduction, and internal rotation were recorded by a patient-reported picture-based survey and clinician measurement during each patient visit. A total of 13,842 visits over a 16-year period met inclusion criteria. Spearman correlation was performed to determine the correlation between patient-reported and CM elevation, abduction, and internal rotation. A subgroup analysis was conducted to evaluate motion in patients who underwent arthroplasty and arthroscopy. RESULTS: Patients were 52.4% male with a median age of 67 years (range, 18 to 96). PR and CM shoulder ROM were gathered at 13,842 patient visits. Strong correlations between PR and CM elevation (r = 0.70) and internal rotation (r = 0.66) were found, as well as a moderate correlation between PR and CM abduction (r = 0.59). Strong correlations were found between all three PR and CM measures of motion in the arthroplasty subgroup (elevation r = 0.74, abduction r = 0.63, and internal rotation r = 0.64). CONCLUSIONS: There is a strong correlation between patient-reported and CM shoulder elevation and internal rotation, as well as a moderate correlation between PR and CM abduction. This allows for a method of assessing patient motion without requiring an in-person visit. LEVEL OF EVIDENCE: Level III Retrospective Cohort Study.

Neural alignment during outgroup intervention predicts future change of affect towards outgroup.

While social psychology studies have shown that paradoxical thinking intervention has a moderating effect on negative attitudes toward members from rival social groups (i.e. outgroup), the neural underpinnings of the intervention have not been studied. Here, we investigate this by examining neural alignment across individuals at different phases during the intervention regarding Covid-19 vaccine-supporters' attitudes against vaccine-opposers. We raise two questions: Whether neural alignment varies during the intervention, and whether it predicts a change in outgroup attitudes measured via a survey 2 days after the intervention and compared to baseline. We test the neural alignment using magnetoencephalography-recorded neural oscillations and multiset canonical correlation analysis. We find a build-up of neural alignment which emerges at the final phase of the paradoxical thinking intervention in the precuneus-a hub of mentalizing; there was no such effect in the control conditions. In parallel, we find a behavioral build-up of dissent to the interventional stimuli. These neural and behavioral patterns predict a prosocial future change in affect and actions toward the outgroup. Together, these findings reveal a new operational pattern of mentalizing on the outgroup, which can change the way individuals may feel and behave toward members of that outgroup.

Multiple prenatal exposures and acute-care clinical encounters for asthma among children born to mothers living near a Superfund site.

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology.

Post-translational modification-centric base editor screens to assess phosphorylation site functionality in high throughput.

Signaling pathways that drive gene expression are typically depicted as having a dozen or so landmark phosphorylation and transcriptional events. In reality, thousands of dynamic post-translational modifications (PTMs) orchestrate nearly every cellular function, and we lack technologies to find causal links between these vast biochemical pathways and genetic circuits at scale. Here we describe the high-throughput, functional assessment of phosphorylation sites through the development of PTM-centric base editing coupled to phenotypic screens, directed by temporally resolved phosphoproteomics. Using T cell activation as a model, we observe hundreds of unstudied phosphorylation sites that modulate NFAT transcriptional activity. We identify the phosphorylation-mediated nuclear localization of PHLPP1, which promotes NFAT but inhibits NFκB activity. We also find that specific phosphosite mutants can alter gene expression in subtle yet distinct patterns, demonstrating the potential for fine-tuning transcriptional responses. Overall, base editor screening of PTM sites provides a powerful platform to dissect PTM function within signaling pathways.

Aircraft noise exposure and body mass index among female participants in two Nurses' Health Study prospective cohorts living around 90 airports in the United States.

OBJECTIVE: Aircraft noise exposure is linked to cardiovascular disease risk. One understudied candidate pathway is obesity. This study investigates the association between aircraft noise and obesity among female participants in two prospective Nurses' Health Study (NHS and NHSII) cohorts. METHODS: Aircraft day-night average sound levels (DNL) were estimated at participant residential addresses from modeled 1 dB (dB) noise contours above 44 dB for 90 United States (U.S.) airports in 5-year intervals 1995-2010. Biennial surveys (1994-2017) provided information on body mass index (BMI; dichotomized, categorical) and other individual characteristics. Change in BMI from age 18 (BMI18; tertiles) was also calculated. Aircraft noise exposures were dichotomized (45, 55 dB), categorized (<45, 45-54, ≥55 dB) or continuous for exposure ≥45 dB. Multivariable multinomial logistic regression using generalized estimating equations were adjusted for individual characteristics and neighborhood socioeconomic status, greenness, population density, and environmental noise. Effect modification was assessed by U.S. Census region, climate boundary, airline hub type, hearing loss, and smoking status. RESULTS: At baseline, the 74,848 female participants averaged 50.1 years old, with 83.0%, 14.8%, and 2.2% exposed to <45, 45-54, and ≥55 dB of aircraft noise, respectively. In fully adjusted models, exposure ≥55 dB was associated with 11% higher odds (95% confidence interval [95%CI]: -1%, 24%) of BMIs ≥30.0, and 15% higher odds (95%CI: 3%, 29%) of membership in the highest tertile of BMI18 (ΔBMI 6.7 to 71.6). Less-pronounced associations were observed for the 2nd tertile of BMI18 (ΔBMI 2.9 to 6.6) and BMI 25.0-29.9 as well as exposures ≥45 versus <45 dB. There was evidence of DNL-BMI trends (ptrends ≤ 0.02). Stronger associations were observed among participants living in the West, arid climate areas, and among former smokers. DISCUSSION: In two nationwide cohorts of female nurses, higher aircraft noise exposure was associated with higher BMI, adding evidence to an aircraft noise-obesity-disease pathway.

It's not you (well, it is a bit you), it's me: Self- versus social image in warm-glow giving.

Attempts by charities to motivate giving tend to focus on potential donors' altruistic tendencies. However, prior research suggests that approximately 50% of individuals are to some extent motivated by warm glow, the satisfaction received from the act of giving. The satisfaction derives from looking good to themselves (self-image) and/or to others (social image). We conduct an online experiment on MTurk participants (n = 960) with a more realistic simulation of being watched to determine the importance of self- and social image to warm-glow giving. We find evidence that suggests that social image concerns do not increase the likelihood that someone will give but they do increase the amount given; average giving is significantly higher in the treatments when feelings of being watched are stimulated. Our results suggest that charities looking to increase their donor bases might effectively do so by focusing on self-image concerns. Charities wishing to increase the amount donated might effectively do so by focusing on the social image concerns of the donor.

Generation WhatsApp: inter-brain synchrony during face-to-face and texting communication.

Texting has become one of the most prevalent ways to interact socially, particularly among youth; however, the effects of text messaging on social brain functioning are unknown. Guided by the biobehavioral synchrony frame, this pre-registered study utilized hyperscanning EEG to evaluate interbrain synchrony during face-to-face versus texting interactions. Participants included 65 mother-adolescent dyads observed during face-to-face conversation compared to texting from different rooms. Results indicate that both face-to-face and texting communication elicit significant neural synchrony compared to surrogate data, demonstrating for the first time brain-to-brain synchrony during texting. Direct comparison between the two interactions highlighted 8 fronto-temporal interbrain links that were significantly stronger in the face-to-face interaction compared to texting. Our findings suggest that partners co-create a fronto-temporal network of inter-brain connections during live social exchanges. The degree of improvement in the partners' right-frontal-right-frontal connectivity from texting to the live social interaction correlated with greater behavioral synchrony, suggesting that this well-researched neural connection may be specific to face-to-face communication. Our findings suggest that while technology-based communication allows humans to synchronize from afar, face-to-face interactions remain the superior mode of communication for interpersonal connection. We conclude by discussing the potential benefits and drawbacks of the pervasive use of texting, particularly among youth.

Expansion of the neurodevelopmental phenotype of individuals with EEF1A2 variants and genotype-phenotype study.

Translation elongation factor eEF1A2 constitutes the alpha subunit of the elongation factor-1 complex, responsible for the enzymatic binding of aminoacyl-tRNA to the ribosome. Since 2012, 21 pathogenic missense variants affecting EEF1A2 have been described in 42 individuals with a severe neurodevelopmental phenotype including epileptic encephalopathy and moderate to profound intellectual disability (ID), with neurological regression in some patients. Through international collaborative call, we collected 26 patients with EEF1A2 variants and compared them to the literature. Our cohort shows a significantly milder phenotype. 83% of the patients are walking (vs. 29% in the literature), and 84% of the patients have language skills (vs. 15%). Three of our patients do not have ID. Epilepsy is present in 63% (vs. 93%). Neurological examination shows a less severe phenotype with significantly less hypotonia (58% vs. 96%), and pyramidal signs (24% vs. 68%). Cognitive regression was noted in 4% (vs. 56% in the literature). Among individuals over 10 years, 56% disclosed neurocognitive regression, with a mean age of onset at 2 years. We describe 8 novel missense variants of EEF1A2. Modeling of the different amino-acid sites shows that the variants associated with a severe phenotype, and the majority of those associated with a moderate phenotype, cluster within the switch II region of the protein and thus may affect GTP exchange. In contrast, variants associated with milder phenotypes may impact secondary functions such as actin binding. We report the largest cohort of individuals with EEF1A2 variants thus far, allowing us to expand the phenotype spectrum and reveal genotype-phenotype correlations.