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Dust particles from high latitudes have a potentially large local, regional, and global significance to climate and the environment as short-lived climate forcers, air pollutants, and nutrient sources. Identifying the locations of local dust sources and their emission, transport, and deposition processes is important for understanding the multiple impacts of high-latitude dust (HLD) on the Earth's systems. Here, we identify, describe, and quantify the source intensity (SI) values, which show the potential of soil surfaces for dust emission scaled to values 0 to 1 concerning globally best productive sources, using the Global Sand and Dust Storms Source Base Map (G-SDS-SBM). This includes 64 HLD sources in our collection for the northern (Alaska, Canada, Denmark, Greenland, Iceland, Svalbard, Sweden, and Russia) and southern (Antarctica and Patagonia) high latitudes. Activity from most of these HLD sources shows seasonal character. It is estimated that high-latitude land areas with higher (SI ≥0.5), very high (SI ≥0.7), and the highest potential (SI ≥0.9) for dust emission cover >1 670 000 km2, >560 000 km2, and >240 000 km2, respectively. In the Arctic HLD region (≥60∘ N), land area with SI ≥0.5 is 5.5 % (1 035 059 km2), area with SI ≥0.7 is 2.3 % (440 804 km2), and area with SI ≥0.9 is 1.1 % (208 701 km2). Minimum SI values in the northern HLD region are about 3 orders of magnitude smaller, indicating that the dust sources of this region greatly depend on weather conditions. Our spatial dust source distribution analysis modeling results showed evidence supporting a northern HLD belt, defined as the area north of 50∘ N, with a “transitional HLD-source area” extending at latitudes 50–58∘ N in Eurasia and 50–55∘ N in Canada and a “cold HLD-source area” including areas north of 60∘ N in Eurasia and north of 58∘ N in Canada, with currently “no dust source” area between the HLD and low-latitude dust (LLD) dust belt, except for British Columbia. Using the global atmospheric transport model SILAM, we estimated that 1.0 % of the global dust emission originated from the high-latitude regions. About 57 % of the dust deposition in snow- and ice-covered Arctic regions was from HLD sources. In the southern HLD region, soil surface conditions are favorable for dust emission during the whole year. Climate change can cause a decrease in the duration of snow cover, retreat of glaciers, and an increase in drought, heatwave intensity, and frequency, leading to the increasing frequency of topsoil conditions favorable for dust emission, which increases the probability of dust storms. Our study provides a step forward to improve the representation of HLD in models and to monitor, quantify, and assess the environmental and climate significance of HLD.

Nurses are the largest group of healthcare workers in Africa. By adequately equipping nurses to identify, intervene and care for emergency conditions, emergency healthcare systems can be strengthened. To address this need, a nursing working group was formed within the African Federation for Emergency Medicine (AFEM). The aim of this international emergency nursing group was to develop a guiding document to help improve emergency nursing skills within Africa. Using this guiding document, a group of Tanzanian clinical nurse trainers was selected to develop a context specific short course. They used this guiding document as a foundation to improve skill development. The pilot course was well received and has since expanded to training in five regions within the United Republic of Tanzania. The clinical nurse trainers leading the course, are supported by a mentorship programme with competent educators within a global emergency nursing infrastructure. This course, a combination of local knowledge, formal mentorship programs, and international nursing support, demonstrates that investing in the improvement of emergency nursing skills can have high impact results with low-cost. This will ultimately improve emergency care on the continent.

Abstract Infectious disease is the result of interactions between host and pathogen and can depend on genetic variations in both. We conduct a genome-to-genome study of paired human and Mycobacterium tuberculosis genomes from a cohort of 1556 tuberculosis patients in Lima, Peru. We identify an association between a human intronic variant (rs3130660, OR = 10.06, 95%CI: 4.87 − 20.77, P = 7.92 × 10−8) in the FLOT1 gene and a subclavaluee of Mtb Lineage 2. In a human macrophage infection model, we observe hosts with the rs3130660-A allele exhibited stronger interferon gene signatures. The interacting strains have altered redox states due to a thioredoxin reductase mutation. We investigate this association in a 2020 cohort of 699 patients recruited during the COVID-19 pandemic. While the prevalence of the interacting strain almost doubled between 2010 and 2020, its infection is not associated with rs3130660 in this recent cohort. These findings suggest a complex interplay among host, pathogen, and environmental factors in tuberculosis dynamics.

Abstract Background Assessment of eating disorders (ED) in youth relies heavily on self-report, yet persistent lack of recognition of the presence and/or seriousness of symptoms can be intrinsic to ED. This study examines the psychometric properties of a semi-structured interview, the parent version of the Eating Disorder Examination (PEDE), developed to systematically assess caregiver report of symptoms. Methods A multi-site, clinical sample of youth (N = 522; age range: 12 to 18 years) seeking treatment for anorexia nervosa (AN) and subsyndromal AN were assessed using the Eating Disorder Examination (EDE) for youth and the PEDE for collateral caregiver report. Results Internal consistencies of the four PEDE subscales were on par with established ranges for the EDE. Significant medium-sized correlations and poor to moderate levels of agreement were found between the corresponding subscales on each measure. For the PEDE, confirmatory factor analysis of the EDE four-factor model provided a poor fit; an exploratory factor analysis indicated that a 3-factor model better fits the PEDE. Conclusions Findings suggest that the PEDE has psychometric properties on par with the original EDE. The addition of the caregiver perspective may provide incremental information that can aid in the assessment of AN in youth. Future research is warranted to establish psychometric properties of the PEDE in broader transdiagnostic ED samples.

Summary: Background: Post-tuberculosis (TB) sequelae present a significant challenge in the management of TB survivors, often leading to persistent health issues even after successful treatment. Identifying risk factors associated with post-TB sequelae is important for improving outcomes and quality of life of TB survivors. This systematic review and meta-analysis aims to identify risk factors associated with long-term physical sequelae among TB survivors. Methods: We systematically searched Medline, Embase, PROQUEST, and Scopus for studies on long-term physical sequelae among TB survivors up to December 12, 2023. The primary outcome of interest was to quantify risk factors of long-term physical sequelae (i.e., respiratory, hepatic, hearing, neurological, visual, renal, and musculoskeletal sequelae). We included all forms of TB patients who experienced long-term physical sequelae. We used narrative synthesis for risk factors reported once and random-effect meta-analysis for primary outcomes with two or more studies. Findings were presented with odds ratios (OR) and 95% confidence intervals (CI). Publication bias was assessed using funnel plots and Egger regression, and heterogeneity was examined with a Galbraith radial plot. The protocol was registered on Prospero (CRD42021250909). Findings: A total of 73 articles from 28 countries representing 31,553 TB-treated patients were included in the narrative synthesis, with 64 of these studies included in the meta-analysis. Risk factors associated with post-TB lung sequelae include older age (OR = 1.62, 95% CI: 1.07–2.47), previous TB treatment history (OR = 3.43, 95% CI: 2.37–4.97), smoking (OR = 1.41, 95% CI: 1.09–1.83), alcohol consumption (OR = 1.84, 95% CI: 1.04–3.25), smear-positive pulmonary TB diagnosis (OR = 3.11, 95% CI: 1.77–6.44), and the presence of radiographic evidence of pulmonary lesions at the commencement of treatment (OR = 2.04, 95% CI: 1.07–3.87). Risk factors associated with post-TB liver injury included pre-existing hepatitis (OR = 2.41, 95% CI: 1.16–6.08), previous TB treatment (OR = 2.64, 95% CI: 1.22–6.67), hypo-albuminemia (OR = 2.10, 95% CI: 1.53–2.88), HIV co-infection (OR = 2.72, 95% CI: 1.66–4.46), and CD4 count

Brillouin spectroscopy has become an important tool for mapping the mechanical properties of biological samples. Recently, stimulated Brillouin scattering (SBS) measurements have emerged in this field as a promising technology for lower noise and higher speed measurements. However, further improvements are fundamentally limited by constraints on the optical power level that can be used in biological samples, which effectively caps the gain and signal-to-noise ratio (SNR) of SBS biological measurements. This limitation is compounded by practical limits on the optical probe power due to detector saturation thresholds. As a result, SBS-based measurements in biological samples have provided minimal improvements (in noise and imaging speed) compared with spontaneous Brillouin microscopy, despite the potential advantages of the nonlinear scattering process. Here, we consider how a SBS spectrometer can circumvent this fundamental trade-off in the low-gain regime by leveraging the polarization dependence of the SBS interaction to effectively filter the signal from the background light via the polarization pulling effect. We present an analytic model of the polarization pulling detection scheme and describe the trade-space unique to Brillouin microscopy applications. We show that an optimized receiver design could provide >25× improvement in SNR compared to a standard SBS receiver in most typical experimental conditions. We then experimentally validate this model using optical fiber as a simplified test bed. With our experimental parameters, we find that the polarization pulling scheme provides 100× higher SNR than a standard SBS receiver, enabling 100× faster measurements in the low-gain regime. Finally, we discuss the potential for this proposed spectrometer design to benefit low-gain spectroscopy applications such as Brillouin microscopy by enabling pixel dwell times as short as 10 μs.

The World Health Organization’s end TB strategy promotes the use of symptom and chest radiograph screening for tuberculosis (TB) disease. However, asymptomatic early states of TB beyond latent TB infection and active disease can go unrecognized using current screening criteria. We conducted a longitudinal cohort study enrolling household contacts initially free of TB disease and followed them for the occurrence of incident TB over 1 year. Among 1,747 screened contacts, 27 (52%) of the 52 persons in whom TB subsequently developed during follow-up had a baseline abnormal radiograph. Of contacts without TB symptoms, persons with an abnormal radiograph were at higher risk for subsequent TB than persons with an unremarkable radiograph (adjusted hazard ratio 15.62 [95% CI 7.74–31.54]). In young adults, we found a strong linear relationship between radiograph severity and time to TB diagnosis. Our findings suggest chest radiograph screening can extend to detecting early TB states, thereby enabling timely intervention.

Abstract Natural killer (NK) cells destroy tissue that have been opsonized with antibodies. Strategies to generate or identify cells with increased potency are expected to enhance NK cell-based immunotherapies. We previously generated NK cells with increased antibody-dependent cell mediated cytotoxicity (ADCC) following treatment with kifunensine, an inhibitor targeting mannosidases early in the N-glycan processing pathway. Kifunensine treatment also increased the antibody-binding affinity of Fc γ receptor IIIa/CD16a. Here we demonstrate that inhibiting NK cell N-glycan processing increased ADCC. We reduced N-glycan processing with the CRIPSR-CAS9 knockdown of MGAT1, another early-stage N-glycan processing enzyme, and showed that these cells likewise increased antibody binding affinity and ADCC. These experiments led to the observation that NK cells with diminished N-glycan processing capability also revealed a clear phenotype in flow cytometry experiments using the B73.1 and 3G8 antibodies binding two distinct CD16a epitopes. We evaluated this “affinity profiling” approach using primary NK cells and identified a distinct shift and differentiated populations by flow cytometry that correlated with increased ADCC.

Objectives: Approximately 40% of tuberculosis (TB) cases remain undiagnosed globally. Lower lung field TB (LLF TB) presents atypically and is often misidentified as other lung diseases, leading to diagnostic delays in resource-limited settings. It may contribute to increased TB transmission and mortality. We aimed to identify microbiological determinants of LLF TB and evaluate treatment responses to optimize care. Methods: We conducted an observational cohort study in Lima, Peru, enrolling adults with microbiologically confirmed pulmonary TB (PTB) diagnosed by GeneXpert MTB/RIF assay or sputum culture. Mycobacterium tuberculosis (MTB) lineage was determined using whole-genome sequencing. Due to the delayed chest radiograph changes in LLF TB compared to non-LLF TB, we measured changes in the St. George's Respiratory Questionnaire (SGRQ) score at 2-month treatment mark and evaluated World Health Organization-specified final treatment outcomes. We used logistic regression to evaluate the associations between LLF TB and microbiological determinants and treatment outcomes. We used linear regression to assess whether the change in SGRQ scores over the first 2 months of treatment varied by LLF TB status. Results: Among 1316 PTB patients, 84 (6%) had LLF TB. Compared to non-LLF TB patients, LLF TB patients were more likely to be smear-negative (adjusted odds ratio [aOR] [95% CI] = 2.04 [1.28-3.23], P = 0.002) and to be infected with Lineage 2 (aOR [95% CI] = 1.95 [95% CI: 1.07-3.41; P = 0.024]). People with LLF TB had less improvement in SGRQ scores after 2 months of treatment (adjusted score difference [95% CI] = –6.29 [–10.99 to –1.59], P = 0.009), while they experienced better final outcomes compared to non-LLF TB patients, though this difference did not reach statistical significance (aOR = 0.43 [95% CI: 0.13-1.05], P = 0.103). Conclusion: Patients with LLF TB are more likely than those with upper lung lesions to be sputum-negative on conventional tests, to be infected with Lineage 2, and to show less clinical improvement after treatment.

Abstract The widespread adoption of machine learning and other matrix intensive computing algorithms has renewed interest in analog optical computing, which has the potential to perform large-scale matrix multiplications with superior energy scaling and lower latency than digital electronics. However, most optical techniques rely on spatial multiplexing, requiring a large number of modulators and detectors, and are typically restricted to performing a single kernel convolution operation per layer. Here, we introduce a fiber-optic computing architecture based on temporal multiplexing and distributed feedback that performs multiple convolutions on the input data in a single layer. Using Rayleigh backscattering in standard single mode fiber, we show that this technique can efficiently apply a series of random nonlinear projections to the input data, facilitating a variety of computing tasks. The approach enables efficient energy scaling with orders of magnitude lower power consumption than GPUs, while maintaining low latency and high data-throughput.

Abstract Introduction Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin‐sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin—a by‐product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward‐related processes, may provide critical insights into reward circuit function in AN. Methods This study will incorporate neuromelanin‐sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight‐restored AN (N = 30), and age‐matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin‐sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. Conclusion This study will be among the first to interrogate midbrain neuromelanin in AN—a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

Abstract Developed barrier systems (barrier islands and spits) are lowering and narrowing with sea‐level rise (SLR) such that habitation will eventually become infeasible or prohibitively expensive for most communities in its current form. Before reaching this state, choices will be made to modify the natural and built environment to reduce relatively short‐term risk. These choices will likely vary substantially even along the same developed barrier system as these landscapes are rarely uniformly managed alongshore. Building on the results from a companion paper, here we use a new modeling framework to investigate the complexities in barrier system dynamics that emerge as a function of alongshore variability in management strategies, accelerations in SLR, and changes in storm intensity and frequency. Model results suggest that when connected through alongshore sediment transport, barriers with alongshore variable management strategies—here, the construction of dunes and wide beaches to protect either roadways or communities—evolve differently than they would in the absence of alongshore connections. Shoreline stabilization by communities in one location influences neighboring areas managed solely for roadways, inducing long‐term system‐wide lags in shoreline retreat. Conversely, when barrier segments managed for roadways are allowed to overwash, this induces shoreline curvature system‐wide, thus enhancing erosion on nearby stabilized segments. Feedbacks between dunes, storms, overwash flux, and alongshore sediment transport also affect outcomes of climate adaptation measures. In the case of partial, early abandonment of roadway management, we find that system‐wide transitions to less vulnerable landscape states are possible, even under accelerated SLR and increased storminess.

Abstract Many barrier islands and spits (collectively, “barriers”) throughout the world are highly developed. As low‐lying, sandy coastal landforms, barrier systems are naturally reshaped by processes associated with storms and sea‐level rise (SLR). The resulting landscape changes threaten development, and in response, humans employ defensive measures that physically modify barrier geometry to reduce relatively short‐term risk. These measures include the construction of large dunes, emplacement of beach nourishment, and removal of washover. Simulations conducted using a new coupled modeling framework show that, over decades to centuries, measures to protect roadways and communities alter the physical characteristics of barrier systems in ways that ultimately limit their habitability. We find that the pathway toward uninhabitability (via roadway drowning or community narrowing) and future system states (drowning or rebound) depends largely on dune management—because building dunes blocks overwash delivery to the barrier interior—and on initial conditions (barrier elevation and width). In the model, barriers can become lower and narrower with SLR to the point of drowning. The timing and occurrence of barrier drowning depends on randomness in the timing and intensity of storms and dune recovery processes. We find that under a constant rate of SLR, negative feedbacks involving storms can allow barriers that do not drown to rebound toward steady‐state geometries within decades after management practices cease.

BackgroundTo date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials.AimTo elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life.MethodsThis was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers.ResultsOverall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and

Summary: Background: Tuberculosis (TB) remains a global public health challenge, causing substantial mortality and morbidity. While TB treatment has made significant progress, it often leaves survivors with post-TB sequelae, resulting in long-term health issues. Current healthcare systems and guidelines lack comprehensive strategies to address post-TB sequelae, primarily due to insufficient evidence. This systematic review and meta-analysis aimed to identify effective interventions for preventing post-TB sequelae. Methods: A systematic search was conducted across four databases including PubMed, SCOPUS, Web of Science, and Cochrane Central Register of Controlled Trials from inception to September 22, 2023. Eligible studies reported interventions designed to prevent post-TB sequelae were included. A random effect meta-analysis was conducted where applicable, and heterogeneity between studies was evaluated visually using forest plots and quantitatively using an index of heterogeneity (I2). This study is registered with PROSPERO (CRD42023464392). Findings: From the 2525 unique records screened, 25 studies involving 10,592 participants were included. Different interventions were evaluated for different outcomes. However, only a few interventions were effective in preventing post-TB sequelae. Rehabilitation programs significantly improved lung function (Hedges's g = 0.21; 95% confidence interval (CI): 0.03, 0.39) and prevented neurological sequelae (relative risk (RR) = 0.10; 95% CI: 0.02, 0.42). Comprehensive interventions and cognitive-behavioural therapy significantly reduced the risk of mental health disorders among TB survivors (Hedges's g = −1.89; 95% CI: −3.77, −0.01). In contrast, interventions targeting post-TB liver sequelae, such as vitamin A and vitamin D supplementation and hepatoprotective agents, did not show significant reductions in sequelae (RR = 0.90; 95% CI: 0.52, 1.57). Moreover, adjunctive therapies did not show a significant effect in preventing post-TB neurological sequelae (RR = 0.62, 95% CI: 0.31, 1.24). Interpretation: Rehabilitation programs prevented post-TB lung, neurologic and mental health sequelae, while adjuvant therapies and other interventions require further investigation. Funding: Healy Medical Research Raine Foundation, Curtin School of Population Health and the Australian National Health and Medical Research Council.

Abstract Background Binge-eating disorder (BED) is the most common eating disorder phenotype and is linked to several negative health outcomes. Yet, little is known about the social epidemiology of BED, particularly in early adolescence. The objective of this study was to examine the associations between sociodemographic characteristics and BED and binge-eating behaviors in a large, national cohort of 10–14-year-old adolescents in the United States (U.S.) Methods We conducted a cross-sectional analysis of two-year follow-up data from the Adolescent Brain Cognitive Development (ABCD) Study (2018 − 2020) that included 10,197 early adolescents (10 − 14 years, mean 12 years) in the U.S. Multivariable logistic regression models were used to assess the associations between sociodemographic characteristics and BED and binge-eating behaviors, defined based on the Kiddie Schedule for Affective Disorders and Schizophrenia. Results In this early adolescent sample (48.8% female, 54.0% White, 19.8% Latino/Hispanic, 16.1% Black, 5.4% Asian, 3.2% Native American, 1.5% Other), the prevalence of BED and binge-eating behaviors were 1.0% and 6.3%, respectively. Identifying as gay or bisexual (compared to heterosexual; adjusted odds ratio [AOR]: 2.25, 95% CI 1.01–5.01) and having a household income of less than $75,000 (AOR: 2.05, 95% CI: 1.21–3.46) were associated with greater odds of BED. Being male (AOR: 1.28, 95% CI: 1.06–1.55), of Native American (AOR: 1.60, 95% CI: 1.01–2.55) descent, having a household income less than $75,000 (AOR: 1.34, 95% CI: 1.08–1.65), or identifying as gay or bisexual (AOR for ‘Yes’ Response: 1.95, 95% CI: 1.31–2.91 and AOR for ‘Maybe’ Response: 1.81, 95% CI: 1.19–2.76) were all associated with higher odds of binge-eating behaviors. Conclusion Several sociodemographic variables showed significant associations with binge-eating behaviors, which can inform targeted screening, prevention, and education campaigns for BED among early adolescents.

Abstract Background Although the Eating Disorder Examination-Questionnaire (EDE-Q) is one of the most widely used self-report assessments of eating disorder symptoms, evidence indicates potential limitations with its original factor structure and associated psychometric properties in a variety of populations, including sexual minority populations. The aims of the current investigation were to explore several previously published EDE-Q factor structures and to examine internal consistency and measurement invariance of the best-fitting EDE-Q model in a large community sample of cisgender gay men and cisgender lesbian women. Methods Data were drawn from 1624 adults (1060 cisgender gay men, 564 cisgender lesbian women) who participated in The PRIDE Study, a large-scale longitudinal cohort study of sexual and gender minorities from the United States. A series of confirmatory factor analyses (CFAs) were conducted to explore the fit of eight proposed EDE-Q models; internal consistency (Cronbach’s alphas, Omega coefficients) and measurement invariance (multi-group CFA) were subsequently evaluated. Results A brief seven-item, three-factor (dietary restraint, shape/weight overvaluation, body dissatisfaction) model of the EDE-Q from Grilo et al. (Obes Surg. 23:657–662, 2013), consistently evidenced the best fit across cisgender gay men and lesbian women. The internal consistencies of the three subscales were adequate in both groups, and measurement invariance across the groups was supported. Conclusions Taken together, these findings support the use of the seven-item, three-factor version of the EDE-Q for assessing eating disorder symptomatology in cisgender gay men and lesbian women. Future studies can confirm the current findings in focused examinations of the seven-item, three-factor EDE-Q in diverse sexual minority samples across race, ethnicity, socioeconomic status, and age ranges.

Abstract The glycosylation on the spike (S) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19, modulates the viral infection by altering conformational dynamics, receptor interaction and host immune responses. Several variants of concern (VOCs) of SARS-CoV-2 have evolved during the pandemic, and crucial mutations on the S protein of the virus have led to increased transmissibility and immune escape. In this study, we compare the site-specific glycosylation and overall glycomic profiles of the wild type Wuhan-Hu-1 strain (WT) S protein and five VOCs of SARS-CoV-2: Alpha, Beta, Gamma, Delta and Omicron. Interestingly, both N- and O-glycosylation sites on the S protein are highly conserved among the spike mutant variants, particularly at the sites on the receptor-binding domain (RBD). The conservation of glycosylation sites is noteworthy, as over 2 million SARS-CoV-2 S protein sequences have been reported with various amino acid mutations. Our detailed profiling of the glycosylation at each of the individual sites of the S protein across the variants revealed intriguing possible association of glycosylation pattern on the variants and their previously reported infectivity. While the sites are conserved, we observed changes in the N- and O-glycosylation profile across the variants. The newly emerged variants, which showed higher resistance to neutralizing antibodies and vaccines, displayed a decrease in the overall abundance of complex-type glycans with both fucosylation and sialylation and an increase in the oligomannose-type glycans across the sites. Among the variants, the glycosylation sites with significant changes in glycan profile were observed at both the N-terminal domain and RBD of S protein, with Omicron showing the highest deviation. The increase in oligomannose-type happens sequentially from Alpha through Delta. Interestingly, Omicron does not contain more oligomannose-type glycans compared to Delta but does contain more compared to the WT and other VOCs. O-glycosylation at the RBD showed lower occupancy in the VOCs in comparison to the WT. Our study on the sites and pattern of glycosylation on the SARS-CoV-2 S proteins across the VOCs may help to understand how the virus evolved to trick the host immune system. Our study also highlights how the SARS-CoV-2 virus has conserved both N- and O- glycosylation sites on the S protein of the most successful variants even after undergoing extensive mutations, suggesting a correlation between infectivity/ transmissibility and glycosylation.

Abstract Strong light-matter interactions in localized nano-emitters placed near metallic mirrors have been widely reported via spectroscopic studies in the optical far-field. Here, we report a near-field nano-spectroscopic study of localized nanoscale emitters on a flat Au substrate. Using quasi 2-dimensional CdSe/CdxZn1-xS nanoplatelets, we observe directional propagation on the Au substrate of surface plasmon polaritons launched from the excitons of the nanoplatelets as wave-like fringe patterns in the near-field photoluminescence maps. These fringe patterns were confirmed via extensive electromagnetic wave simulations to be standing-waves formed between the tip and the edge-up assembled nano-emitters on the substrate plane. We further report that both light confinement and in-plane emission can be engineered by tuning the surrounding dielectric environment of the nanoplatelets. Our results lead to renewed understanding of in-plane, near-field electromagnetic signal transduction from the localized nano-emitters with profound implications in nano and quantum photonics as well as resonant optoelectronics.

Abstract Background National opioid-related overdose fatalities totaled 650,000 from 1999 to 2021. Some of the highest rates occurred in New Hampshire, where 40% of the population lives rurally. Medications for opioid use disorder (MOUD; methadone, buprenorphine, and naltrexone) have demonstrated effectiveness in reducing opioid overdose and mortality. Methadone access barriers disproportionally impact rural areas and naltrexone uptake has been limited. Buprenorphine availability has increased and relaxed regulations reduces barriers in general medical settings common in rural areas. Barriers to prescribing buprenorphine include lack of confidence, inadequate training, and lack of access to experts. To address these barriers, learning collaboratives have trained clinics on best-practice performance data collection to inform quality improvement (QI). This project sought to explore the feasibility of training clinics to collect performance data and initiate QI alongside clinics’ participation in a Project ECHO virtual collaborative for buprenorphine providers. Methods Eighteen New Hampshire clinics participating in a Project ECHO were offered a supplemental project exploring the feasibility of performance data collection to inform QI targeting increased alignment with best practice. Feasibility was assessed descriptively, through each clinic’s participation in training sessions, data collection, and QI initiatives. An end-of-project survey was conducted to understand clinic staff perceptions of how useful and acceptable they found the program. Results Five of the eighteen health care clinics that participated in the Project ECHO joined the training project, four of which served rural communities in New Hampshire. All five clinics met the criteria for engagement, as each clinic attended at least one training session, submitted at least one month of performance data, and completed at least one QI initiative. Survey results showed that while clinic staff perceived the training and data collection to be useful, there were several barriers to collecting the data, including lack of staff time, and difficulty standardizing documentation within the clinic electronic health record. Conclusions Results suggest that training clinics to monitor their performance and base QI initiatives on data has potential to impact clinical best practice. While data collection was inconsistent, clinics completed several data-informed QI initiatives, indicating that smaller scale data collection might be more attainable.

Abstract Frequency shifting loops, consisting of a fiber optic ring cavity, a frequency modulator, and an amplifier to compensate for loss, enable high-speed frequency scanning with precise and easily controlled frequency steps. This platform is particularly attractive for applications in spectroscopy and optical ranging. However, amplified spontaneous emission noise accumulates due to the repeated amplification of light circulating in the cavity, limiting the frequency scanning range of existing frequency shifting loops (FSLs). Here, we introduce a cascaded approach which addresses this basic limitation. By cascading multiple FSLs in series with different frequency shifts we are able to dramatically increase the accessible scanning range. We present modeling showing the potential for this approach to enable scanning over ranges up to 1 THz—a tenfold increase compared with the state-of-the-art. Experimentally, we constructed a pair of cascaded FSLs capable of scanning a 200 GHz range with 100 MHz steps in 10 ms and used this platform to perform absorption spectroscopy measurements of an H13C14N cell. By increasing the operating bandwidth of FSLs, the cascaded approach introduced in this work could enable new applications requiring precise and high-speed frequency scanning.

Plain English summary Adverse childhood experiences (ACEs) are common among adolescents and a significant public health concern given their associations with various health outcomes later in life. The current study examined the associations between ACEs and binge-eating disorder (BED) among early adolescents using a large, national sample in the United States. Participants with three or more ACEs had nearly nine times higher odds of developing BED at two-year follow-up. Of the different types of ACEs, household mental illness, household violence, and having a criminal household member were most strongly associated with BED. Screening for ACEs when evaluating adolescents for BED should be considered, and clinicians should provide trauma-informed care for adolescents with BED.

Abstract Background Loss of control eating (LOC-E) in youth predicts the later development of full-syndrome binge-eating disorder (BED), and therefore, could be a relevant target for prevention treatments. To develop these treatments, it is important to understand the underlying disease processes and mechanisms. Based on the putative role of neurocognitive impairments in the pathogenesis of LOC-E, treatments that modulate these neurocognitive factors warrant further exploration. For instance, stimulants are an effective treatment for impulsivity in youth with attention deficit/hyperactivity disorder (ADHD) and have been shown to improve symptoms of BED in adults. Notably, stimulants have not been examined as a treatment for LOC-E in youth. To explore this gap, we aim to measure change in LOC-E episodes and secondary outcomes in youth with comorbid ADHD and LOC-E who are being started on stimulants. Methods We will collect prospective observational data on forty 8-to-13-year-old youth diagnosed with comorbid ADHD and LOC-E who are initiating a stimulant for ADHD. Prior to stimulant initiation, participants will complete baseline measures including LOC-E episode frequency in the last 3 months (primary outcome), and secondary outcomes including disordered eating cognitions, emotions and behaviors, ADHD symptom severity, parental LOC-E, impulsivity and reward sensitivity, and anxiety/mood severity. Outcome measurements will be gathered again at 3-months after initiating the stimulant. Within-patient standardized effect sizes with 95% confidence intervals will be calculated from baseline to 3-month follow-up for all outcomes. Discussion Many individuals with LOC-E or binge eating do not fully remit over the course of psychotherapy. Whereas psychotherapy may address psychological and sociocultural domains associated with LOC-E, some individuals with neurocognitive impairments (e.g., ADHD) and neurobiological deficits (e.g., low intrasynaptic dopamine or norepinephrine) may benefit from adjunctive treatment that targets those factors. This will be the first study to provide pilot data for future studies that could examine both the effect of stimulants on LOC-E in youth and underlying mechanisms. Trial registration Trial registration number: NCT05592119

Nanoplatelets can be used as anisotropic building blocks for constructing novel optoelectronic materials. Here, Wang et al. show a route of assembling nanoplatelets with controllable positional and orientational order in three dimensions facilitated by the surface tension of drying emulsion droplets.

Summary: Mammalian cells can die by apoptosis or by one of several non-apoptotic mechanisms, such as ferroptosis. Here, we present a protocol to distinguish ferroptosis from other cell death mechanisms in cultured cells. We describe steps for seeding cells, administering mechanism-specific cell death inducers and inhibitors, and measuring cell death and viability. We then detail the use of molecular markers to verify mechanisms of cell death. This protocol can be used to identify and distinguish ferroptosis in 2D and 3D cultures.For complete details on the use and execution of this protocol, please refer to Ko, et al. (2019),1 Magtanong, et al. (2022),2 and Armenta, et al. (2022).3 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

We introduce a spectrometer design that uses Brillouin lasing to perform broadband spectral compression. This approach enables the entire C-band (optical frequencies covering 4 THz, or 25 nm) to be compressed into a 230 MHz wide RF spectrum—allowing a 4 THz wide optical spectrum to be monitored continuously using a standard analog-to-digital converter. This technique is based on the linear dependence of the Brillouin frequency shift on optical wavelength. To use this dependence for spectral analysis, we couple the input optical spectrum into a fiber ring cavity where it acts as an optical pump, exciting a frequency-shifted Brillouin lasing spectrum. The Brillouin lasing spectrum is then referenced to a copy of the original optical spectrum using heterodyne detection, converting the Brillouin frequency shift associated with each lasing mode to the RF domain. The narrow linewidth of the lasing modes enables a precise measurement of individual lines with an uncertainty of 28 MHz (0.2 pm) across a 4 THz band at an update rate of 200 Hz. This simple approach, constructed using standard fiber-coupled telecom components, provides an efficient method for high-resolution, broadband spectral analysis.

Background: Mathematical modeling of infectious diseases is an important decision-making tool for outbreak control. However, in Africa, limited expertise reduces the use and impact of these tools on policy. Therefore, there is a need to build capacity in Africa for the use of mathematical modeling to inform policy. Here we describe our experience implementing a mathematical modeling training program for public health professionals in East Africa. Methods: We used a deliverable-driven and learning-by-doing model to introduce trainees to the mathematical modeling of infectious diseases. The training comprised two two-week in-person sessions and a practicum where trainees received intensive mentorship. Trainees evaluated the content and structure of the course at the end of each week, and this feedback informed the strategy for subsequent weeks. Findings: Out of 875 applications from 38 countries, we selected ten trainees from three countries – Rwanda (6), Kenya (2), and Uganda (2) – with guidance from an advisory committee. Nine trainees were based at government institutions and one at an academic organization. Participants gained skills in developing models to answer questions of interest and critically appraising modeling studies. At the end of the training, trainees prepared policy briefs summarizing their modeling study findings. These were presented at a dissemination event to policymakers, researchers, and program managers. All trainees indicated they would recommend the course to colleagues and rated the quality of the training with a median score of 9/10. Conclusions: Mathematical modeling training programs for public health professionals in Africa can be an effective tool for research capacity building and policy support to mitigate infectious disease burden and forecast resources. Overall, the course was successful, owing to a combination of factors, including institutional support, trainees’ commitment, intensive mentorship, a diverse trainee pool, and regular evaluations.

Eating disorders are a group of psychiatric conditions that involve pathological relationships between patients and food. The most prolific of these disorders are anorexia nervosa, bulimia nervosa, and binge eating disorder. The current standard of care involves psychotherapy, pharmacotherapy, and the management of comorbid conditions, with nutritional rehabilitation reserved for severe cases of anorexia nervosa. Unfortunately, many patients often fail to respond, leaving a concerning treatment gap between the current and requisite treatments for eating disorders. To better understand the neurobiology underlying these eating disorders, investigations have been undertaken to characterize the activity of various neural networks, primarily those activated during tasks of executive inhibition, reward processing, and self-reference. Various neuromodulatory techniques have been proposed to stimulate these networks with the goal of improving patients’ BMI and mental health. The aim of this review is to compile a comprehensive summarization of the current literature regarding the underlying neural connectivity of anorexia nervosa, bulimia nervosa, and binge eating disorder as well as the numerous neuromodulatory modalities that have been investigated. Importantly, we aimed to summarize the most significant clinical trials to date as well as to provide an updated assessment of the role of deep brain stimulation, summarizing numerous recently published clinical studies that have greatly contributed to the literature. In this review, we found therapeutic evidence for transcranial magnetic stimulation and transcranial direct current stimulation in treating individuals suffering from anorexia nervosa, bulimia nervosa, and binge eating disorder. We also found significant evidence for the role of deep brain stimulation, particularly as an escalatory therapy option for the those who failed standard therapy. Finally, we hope to provide promising directions for future clinical investigations.

Abstract Background “Cheat meals”, described as brief eating episodes that depart from established dietary practices to consume prohibited foods, represent a novel and increasingly common eating behavior with particular salience in adolescence and young adulthood. However, knowledge gaps remain regarding the frequency and characterization of foods and calories consumed during cheat meals, and their associations with eating disorder behaviors and psychopathology. Thus, the aims of this study were to delineate engagement in cheat meals among a large, national sample of Canadian adolescents and young adults. Methods Participants (N = 2,717) were from the Canadian Study of Adolescent Health Behaviors. Frequencies of engagement in cheat meals, and associated foods and calories consumed, in the past 12 months and 30 days were determined. The associations between engagement in cheat meals and eating disorder behaviors and psychopathology were determined using modified Poisson regression analyses. Results Engagement in cheat meals in the past 12 months was highest among men (60.9%) compared to women (53.7%) and transgender/gender non-conforming (TGNC; 52.5%) participants. Cheat meals consisting between 1,000 and 1,499 cal were those most frequently reported among all participants. Mean number of cheat meals in the past 12 months was equivalent to > 1 per week, which was similar to engagement in the past 30 days. Finally, engagement in cheat meals in the past 12 months and 30 days was associated with patterns of eating disorder behaviors and psychopathology among all participants, including binge-eating-related behaviors. Conclusions This study further characterized and extended knowledge of cheat meal engagement across genders, aligning with prior research by demonstrating that engagement is associated with greater eating disorder psychopathology. Plain english summary Findings from this study add to the growing characterization of the novel behavioral phenomenon of cheat meals. Specifically, over half of adolescents and young adults across all 13 provinces and territories in Canada reported engaging in > 1 cal dense cheat meal per week, over the past 12 months. Despite the normalization and promotion of cheat meal engagement among the general public and unique fitness communities, engagement in this behavior is linked to greater eating disorder behaviors and psychopathology, including binge-eating episodes. Our findings emphasize the need for further research, public awareness, and clinical interventions aimed at addressing this potentially harmful eating behavior.

BackgroundPrenatal education encourages healthy behavioral choices and reduces rates of adverse birth outcomes. The use of mobile health (mHealth) technologies during pregnancy is increasing and changing how pregnant people acquire prenatal education. SmartMom is an evidence-based prenatal education SMS text messaging program that overcomes barriers to prenatal class attendance, including rural or remote location, cost, stigma among participants, lack of instructors, and cessation of classes during the COVID-19 pandemic. ObjectiveWe sought to explore perceived information needs and preferences for the content and structure of prenatal education mHealth programs among persons enrolled in or eligible to enroll in SmartMom. MethodsThis was a qualitative focus group study conducted as part of a development and usability study of the SmartMom program. Participants were older than 19 years of age, Canadian residents, fluent in English, and either currently pregnant or pregnant within the last year. We asked open-ended questions about information-seeking behaviors during pregnancy, the nature of the information that participants were seeking, how they wanted to receive information, and if SmartMom was meeting these needs. Focus groups took place via videoconference technology (Zoom) between August and December 2020. We used reflexive thematic analysis to identify themes that emerged from the data and the constant comparison method to compare initial coding to emerging themes. ResultsWe conducted 6 semistructured focus groups with 16 participants. All participants reported living with a partner and owning a cell phone. The majority (n=13, 81%) used at least 1 app for prenatal education. Our analysis revealed that “having reliable information is the most important thing” (theme 1); pregnant people value inclusive, local, and strength-based information (theme 2); and SMS text messages are a simple, easy, and timely modality (“It was nice to have that [information] fed to you”; theme 3). Participants perceived that SmartMom SMS text messages met their needs for prenatal education and were more convenient than using apps. SmartMom’s opt-in supplemental message streams, which allowed users to tailor the program to their needs, were viewed favorably. Participants also identified that prenatal education programs were not meeting the needs of diverse populations, such as Indigenous people and LGBTQIA2S+ (lesbian, gay, bisexual, transgender, queer and/or questioning, intersex, asexual, Two-Spirit plus) communities. ConclusionsThe shift toward digital prenatal education, accelerated by the COVID-19 pandemic, has resulted in a plethora of web- or mobile technology–based programs, but few of these have been evaluated. Participants in our focus groups revealed concerns about the reliability and comprehensiveness of digital resources for prenatal education. The SmartMom SMS text messaging program was viewed as being evidence-based, providing comprehensive content without searching, and permitting tailoring to individual needs through opt-in message streams. Prenatal education must also meet the needs of diverse populations.

The corporeal practice of ballet training, comprised of visual and aural input along with kinesthetic awareness and sensation, serves to transmit and reify a specific form of embodied knowledge. Passed from generation to generation and body to body, from at least mid-19th century Europe to its current global representations, systems of ballet training and modes of ballet performance have moved through history and geography continually enacting and reenacting a legacy of repertoire rife with collective/cultural memory and meaning. Ballet training methodologies and choreography have evolved significantly, yet well-established vocabulary, syllabi, curricula, and repertoire continue. Given the continually evolving yet perennial nature of ballet, theories from the field of performance studies provide an interesting lens through which we might examine classical ballet and its repertoire. This article contributes to the existing academic literature by framing ballet as a living culture – an ever-evolving, self-perpetuating, way of life - rather than as a purely historical or aesthetic topic. By engaging with performance studies theorists to explore notions of culture, tradition, ritual, orature, and repertoire, this article encourages further investigation of ballet through a variety of lenses.

Abstract Background Several unsuccessful attempts have been made to reach a cross-disciplinary consensus on issues fundamental to the field of eating disorders in the United States (U.S.). In January 2020, 25 prominent clinicians, academicians, researchers, persons with lived experience, and thought leaders in the U.S. eating disorders community gathered at the Legacy of Hope Summit to try again. This paper articulates the points on which they reached a consensus. It also: (1) outlines strategies for implementing those recommendations; (2) identifies likely obstacles to their implementation; and (3) charts a course for successfully navigating and overcoming those challenges. Methods Iterative and consensual processes were employed throughout the Summit and the development of this manuscript. Results The conclusion of the Summit culminated in several consensus points, including: (1) Eating disorder outcomes and prevention efforts can be improved by implementing creative health education initiatives that focus on societal perceptions, early detection, and timely, effective intervention; (2) Such initiatives should be geared toward parents/guardians, families, other caretakers, and frontline healthcare providers in order to maximize impact; (3) Those afflicted with eating disorders, their loved ones, and the eating disorders community as a whole would benefit from greater accessibility to affordable, quality care, as well as greater transparency and accountability on the part of in-hospital, residential, and outpatient health care providers with respect to their qualifications, methodologies, and standardized outcomes; (4) Those with lived experience with eating disorders, their loved ones, health care providers, and the eating disorders community as a whole, also would benefit from the establishment and maintenance of treatment program accreditation, professional credentialing, and treatment type and levels of care guidelines; and (5) The establishment and implementation of effective, empirically/evidence-based standards of care requires research across a diverse range of populations, adequate private and government funding, and the free exchange of ideas and information among all who share a commitment to understanding, treating, and, ultimately, markedly diminishing the negative impact of eating disorders. Conclusions Widespread uptake and implementation of these recommendations has the potential to unify and advance the eating disorders field and ultimately improve the lives of those affected. Plain English summary A cross-disciplinary group of eating disorder professionals, thought leaders, and persons with lived experience have come together and reached a consensus on issues that are fundamental to the battle against the life-threatening and life-altering illnesses that are eating spectrum disorders. Those issues include: (1) the need for early detection, intervention, prevention, and evidenced-based standards of care; (2) the critical need to make specialized care more accessible and affordable to all those in need; (3) the importance of developing uniform, evidenced-based standards of care; (4) the need for funding and conducting eating spectrum disorder research; and (5) the indispensability of advocacy, education, and legislation where these illnesses are concerned. During the consensus process, the authors also arrived at strategies for implementing their recommendations, identified likely obstacles to their implementation, and charted a course for successfully navigating and overcoming those challenges. Above all else, the authors demonstrated that consensus in the field of eating spectrum disorders is possible and achievable and, in doing so, lit a torch of hope that is certain to light the path forward for years to come.

Abstract We present a comprehensive analysis of a frequency multiplexed phase-measuring φ-OTDR sensor platform. The system uses a train of frequency-shifted pulses to increase the average power injected into the fiber and provide a diversity of uncorrelated Rayleigh backscattering measurements. Through a combination of simulations, numerical analysis, and experimental measurements, we show that this approach not only enables lower noise and mitigates interference fading, but also improves the sensor linearity. We investigate the sensor dependence on the length of the pulse train and characterize the sensor performance as a function of range, demonstrating operation from 1 to 50 km. Despite its relative simplicity, this platform enables state-of-the-art performance, including low crosstalk, high linearity, and a minimum detectable strain of only 0.6 p $$\varepsilon /\sqrt{\text{Hz}}$$ ε / Hz in a 10 km fiber with 10 m spatial resolution and a bandwidth of 5 kHz.

Abstract Anorexia nervosa (AN) is a difficult to treat, pernicious psychiatric disorder that has been linked to decision-making abnormalities. We examined the structural characteristics of habitual and goal-directed decision-making circuits and their connecting white matter tracts in 32 AN and 43 healthy controls across two independent data sets of adults and adolescents as an explanatory sub-study. Total bilateral premotor/supplementary motor area-putamen tracts in the habit circuit had a significantly higher volume in adults with AN, relative to controls. Positive correlations were found between both the number of tracts and white matter volume (WMV) in the habit circuit, and the severity of ritualistic/compulsive behaviors in adults and adolescents with AN. Moreover, we found a significant influence of the habit circuit WMV on AN ritualistic/compulsive symptom severity, depending on the preoccupations symptom severity levels. These findings suggest that AN is associated with white matter plasticity alterations in the habit circuit. The association between characteristics of habit circuit white matter tracts and AN behavioral symptoms provides support for a circuit based neurobiological model of AN, and identifies the habit circuit as a focus for further investigation to aid in development of novel and more effective treatments based on brain-behavior relationships.

Plain English summary Transgender people have a gender identity or expression that differs from what is typically associated with the sex assigned to them at birth. Gender-expansive refers to gender identities that do not fit within the binary (woman/man) gender system. We asked gender-expansive people, transgender men, and transgender women in The PRIDE Study to fill out a widely used survey about muscle dysmorphia, a condition in which a person worries they are not muscular enough. The results showed that transgender men had the highest muscle dysmorphia symptoms, followed by gender-expansive people, then transgender women. These findings can help clinicians and researchers in interpreting a survey assessing muscle dysmorphia in gender-expansive people, transgender men, and transgender women. Characterizing muscle dysmorphia symptoms in these populations is an important step to improve mental wellness among transgender and gender-expansive people.

Plain english summary Fasting has recently garnered public attention given its purported benefits, including weight loss and improved physical functioning. To date, little research has been conducted to determine the prevalence of this behavior among college students, as well as what demographic characteristics, substance use behaviors, and mental health symptoms are associated with this behavior. Results from a sample of over 8000 college students from four survey years of the Healthy Minds Study show that fasting is common among college men and women and has increased in prevalence from 2016 to 2020. Fasting is associated with indicators of poor mental health including depression, anxiety, eating disorder symptoms, suicidal ideation, and non-suicidal self-injury (e.g., cutting, burning), among both college men and women. Fasting is associated with substance use behaviors, including marijuana use and other illicit drug use (e.g., cocaine, ecstasy), among college women. These results highlight the adverse correlates of this common weight loss and compensatory behavior among college students.

Abstract Background Spinal fusion surgery is associated with severe acute postsurgical pain and high rates of chronic postsurgical pain in adolescents. Psychological distress, sleep disturbance, and low pain self-efficacy predict higher acute pain and likelihood of developing chronic postsurgical pain. Interventions targeting baseline psychosocial risk factors have potential to interrupt a negative trajectory of continued pain and poor health-related quality of life (HRQL) over time but have not yet been developed and evaluated. This randomized controlled trial will test effectiveness of a digital peri-operative cognitive-behavioral intervention (SurgeryPalTM) vs. education-control delivered to adolescents and their parents to improve acute and chronic pain and health outcomes in adolescents undergoing spine surgery. Methods Adolescents 12–18 years of age undergoing spinal fusion for idiopathic conditions, and their parent, will be recruited from pediatric centers across the USA, for a target complete sample of 400 dyads. Adolescents will be randomized into 4 study arms using a factorial design to SurgeryPalTM or education control during 2 phases of treatment: (1) pre-operative phase (one-month before surgery) and (2) post-operative phase (1 month after surgery). Acute pain severity and interference (primary acute outcomes) and opioid use will be assessed daily for 14 days following hospital discharge. Chronic pain severity and interference (primary acute outcomes), as well as HRQL, parent and adolescent distress, sleep quality, and opioid use/misuse (secondary outcomes), will be assessed at 3 months and 6 months post-surgery. Discussion Demonstration of effectiveness and understanding optimal timing of perioperative intervention will enable implementation of this scalable psychosocial intervention into perioperative care. Ultimately, the goal is to improve pain outcomes and reduce reliance on opioids in adolescents after spine surgery. Trial registration NCT04637802 ClinicalTrials.gov. Registered on November 20, 2020

Abstract Background Representing the pathological extreme pursuit of muscularity, muscle dysmorphia (MD) is characterized by a pervasive belief or fear around insufficient muscularity and an elevated drive for muscularity. Despite evidence of elevated body image-related concerns among sexual minority populations, little is known about the degree of muscle dysmorphia (MD) symptoms among sexual minorities, particularly based on Muscle Dysmorphic Disorder Inventory (MDDI) scores. The objective of this study was to examine the nature and severity of MD symptoms in cisgender sexual minority men and women and provide community norms of the MDDI for these populations. Methods Data from participants in The PRIDE Study, an existing study of health outcomes in sexual and gender minority people from the United States, were examined. Participants included cisgender gay men (N = 1090), cisgender bisexual plus (bisexual, pansexual, and/or polysexual) men (N = 100), cisgender lesbian women (N = 563), and cisgender bisexual plus women (N = 507). We calculated means, standard deviations (SD), and percentiles for the MDDI total and subscale scores for cisgender sexual minority men and women. We compared MDDI scores by sexual orientation using linear regression models, both unadjusted and adjusted for sociodemographics. Results Overall, the sample was 85.2% White, 3.0% Asian or Pacific Islander, 2.0% Black, 0.5% Native American, 3.9% multiracial, and 6.6% Hispanic/Latino/a. The mean age was 38.6 (SD = 14.3) and 69.4% had a college degree or higher. Means (SD) for the MDDI total score were 27.4 (7.7) for cisgender gay men, 26.4 (6.4) for cisgender bisexual plus men, 24.3 (6.1) for cisgender lesbian women, and 24.6 (5.5) for cisgender bisexual plus women. There were no significant differences in MDDI scores between cisgender gay and bisexual plus men, or between cisgender lesbian women and bisexual plus women in unadjusted or adjusted models. Conclusions These normative data provide insights into the experience of MD symptoms among cisgender sexual minority men and women and can aid researchers and clinicians in the evaluation of MD symptoms and interpretation of MDDI scores in sexual minority populations.

3D real-space analysis of thick nanoparticle crystals is non-trivial. Here, the authors demonstrate the structural analysis of a bulk-like Laves phase by imaging an off-stoichiometric binary mixture of hard-sphere-like nanoparticles in spherical confinement by electron tomography, enabling defect analysis on the single-particle level.

Abstract The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the “handle region peptide” from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.

Abstract Background Tissue engineered and regenerative approaches for treating tendon injuries are challenged by the limited information on the cellular signaling pathways driving tenogenic differentiation of stem cells. Members of the transforming growth factor (TGF) β family, particularly TGFβ2, play a role in tenogenesis, which may proceed via Smad-mediated signaling. However, recent evidence suggests some aspects of tenogenesis may be independent of Smad signaling, and other pathways potentially involved in tenogenesis are understudied. Here, we examined the role of Akt/mTORC1/P70S6K signaling in early TGFβ2-induced tenogenesis of mesenchymal stem cells (MSCs) and evaluated TGFβ2-induced tenogenic differentiation when Smad3 is inhibited. Methods Mouse MSCs were treated with TGFβ2 to induce tenogenesis, and Akt or Smad3 signaling was chemically inhibited using the Akt inhibitor, MK-2206, or the Smad3 inhibitor, SIS3. Effects of TGFβ2 alone and in combination with these inhibitors on the activation of Akt signaling and its downstream targets mTOR and P70S6K were quantified using western blot analysis, and cell morphology was assessed using confocal microscopy. Levels of the tendon marker protein, tenomodulin, were also assessed. Results TGFβ2 alone activated Akt signaling during early tenogenic induction. Chemically inhibiting Akt prevented increases in tenomodulin and attenuated tenogenic morphology of the MSCs in response to TGFβ2. Chemically inhibiting Smad3 did not prevent tenogenesis, but appeared to accelerate it. MSCs treated with both TGFβ2 and SIS3 produced significantly higher levels of tenomodulin at 7 days and morphology appeared tenogenic, with localized cell alignment and elongation. Finally, inhibiting Smad3 did not appear to impact Akt signaling, suggesting that Akt may allow TGFβ2-induced tenogenesis to proceed during disruption of Smad3 signaling. Conclusions These findings show that Akt signaling plays a role in TGFβ2-induced tenogenesis and that tenogenesis of MSCs can be initiated by TGFβ2 during disruption of Smad3 signaling. These findings provide new insights into the signaling pathways that regulate tenogenic induction in stem cells.

Abstract The cell wall of Mycobacterium tuberculosis is composed of diverse glycolipids which potentially interact with the human immune system. To overcome difficulties in obtaining pure compounds from bacterial extracts, we recently synthesized three forms of mycobacterial diacyltrehalose (DAT) that differ in their fatty acid composition, DAT1, DAT2, and DAT3. To study the potential recognition of DATs by human T cells, we treated the lipid-binding antigen presenting molecule CD1b with synthetic DATs and looked for T cells that bound the complex. DAT1- and DAT2-treated CD1b tetramers were recognized by T cells, but DAT3-treated CD1b tetramers were not. A T cell line derived using CD1b-DAT2 tetramers showed that there is no cross-reactivity between DATs in an IFN-γ release assay, suggesting that the chemical structure of the fatty acid at the 3-position determines recognition by T cells. In contrast with the lack of recognition of DAT3 by human T cells, DAT3, but not DAT1 or DAT2, activates Mincle. Thus, we show that the mycobacterial lipid DAT can be both an antigen for T cells and an agonist for the innate Mincle receptor, and that small chemical differences determine recognition by different parts of the immune system.