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Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions. Significance: We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including >5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations. This article is highlighted in the In This Issue feature, p. 2483

STUDY OBJECTIVES: There is a paucity of contemporary prevalence estimates for common sleep disorders of insomnia, obstructive sleep apnea (OSA), and restless legs syndrome. We aimed to assess the prevalence of clinically significant common sleep disorders in a middle-aged community sample. METHODS: Parents of participants in the community-based Raine Study underwent assessments between 2015 and 2017, including comprehensive questionnaires, anthropometric measures, and in-laboratory polysomnography. Clinically significant sleep disorders were defined as chronic insomnia using the Pittsburgh Sleep Symptom Questionnaire–Insomnia with duration criterion ≥ 3 months; OSA as apnea-hypopnea index ≥ 5 events/h with excessive sleepiness (Epworth Sleepiness Scale ≥ 11) or apnea-hypopnea index ≥ 15 events/h (even in the absence of symptoms); restless legs syndrome when participants endorsed the International Restless Legs Syndrome Study Group diagnostic criteria (2003) with symptoms ≥ 5 times/month involving moderate–severe distress. RESULTS: At least 1 sleep-related assessment was completed by 1,005 (female = 586, 58.3%) middle-aged (45–65 years) participants, 72.5% of eligible Raine Study parents. The respective prevalences for clinically significant disease in females and males were as follows: OSA, 24.0% (95% confidence interval [CI]: 20.5–27.7) and 47.3% (95% CI: 42.2–53.4); insomnia, 15.8% (95% CI: 13.1–19.0) and 9.3% (95% CI: 6.8–12.4); restless legs syndrome, 3.7% (95% CI: 2.4–5.4) and 2.2% (95% CI: 1.1–3.9). At least 1 sleep disorder was present in 42.9% of those with complete data on all assessments (n = 895). CONCLUSIONS: Common sleep disorders are highly prevalent, to a clinically important extent, in an Australian community sample of middle-aged adults. Contemporary OSA prevalence is notably higher than previously reported and further work is needed to determine the communal impact of OSA. CITATION: McArdle N, Reynolds AC, Hillman D, et al. Prevalence of common sleep disorders in a middle-aged community sample. J Clin Sleep Med. 2022;18(6):1503–1514.

STUDY OBJECTIVES: Most studies on diet and sleep apnea focus on calorie restriction. Here we investigate potential associations between dietary quality (Healthy Eating Index [HEI], Dietary Inflammatory Index [DII]) and overall healthy lifestyle with sleep apnea risk. METHODS: National Health and Nutrition Examination Survey data (waves 2005–2008 and 2015–2018; n = 14,210) were used to determine HEI, DII, and their quintiles, with the fifth quintile indicating highest adherence to each dietary construct. A healthy lifestyle score was determined using diet, smoking, alcohol intake, and physical activity level. The STOP-BANG questionnaire was used to define sleep apnea risk. Generalized linear regression models with binomial family and logit link were used to investigate potential associations. The models were adjusted for socioeconomic status, lifestyle factors, and chronic conditions. RESULTS: The prevalence of high sleep apnea risk was 25.1%. Higher DII was positively associated with sleep apnea (odds ratio(Quintile 5 vs Quintile 1) = 1.55; 95% confidence interval, 1.24–1.94; P for trend < .001), whereas higher HEI was associated with reduced sleep apnea risk (odds ratio(Quintile 5 vs Quintile 1) = 0.72; 95% confidence interval, 0.59–0.88; P for trend = .007). Higher healthy lifestyle score was also associated with decreased odds of sleep apnea (P for trend < .001). There was a significant interaction between healthy lifestyle and sex with sleep apnea risk (P for interaction = .049) whereby females with higher healthy lifestyle scores had a lower risk of sleep apnea compared to males. CONCLUSIONS: Higher-quality and anti-inflammatory diets and a healthier overall lifestyle are associated with lower sleep apnea risk. These findings underline the importance of strategies to improve overall diet quality and promote healthy behavior, not just calorie restriction, to reduce sleep apnea risk. CITATION: Melaku YA, Reynolds AC, Appleton S, et al. High-quality and anti-inflammatory diets and a healthy lifestyle are associated with lower sleep apnea risk. J Clin Sleep Med. 2022;18(6):1667–1679.

Background: Physical activity (PA) and sleep duration have established associations with health outcomes individually but tend to co-occur and may be better targeted jointly. This study aimed to describe the cross-sectional prevalence, trends, and population characteristic correlates of activity-sleep patterns in a population-representative sample of US adults from the National Health Interview Survey (2004–2018). Methods: Participants (N = 359,019) self-reported aerobic and muscle-strengthening activity and sleep duration. They were categorized as “meeting both”/“meeting PA only”/“meeting sleep only”/“meeting neither” of the 2018 US PA guidelines and age-based sleep duration recommendations. Trends in activity-sleep patterns were analyzed using weighted multinomial logistic regression, and correlates were identified using weighted binary Poisson regressions, with P ≤ .001 considered significant. Results: “Meet sleep only” was most prevalent (46.4%) by 2018, followed by “meet neither” (30.3%), “meet both” (15.6%), and “meet PA only” (7.7%). Many significant sociodemographic, biological, and health-behavior correlates of the activity-sleep groups were identified, and the direction and magnitude of these associations differed between groups. Conclusions: Public health campaigns should emphasize the importance of both sufficient PA and sleep; target women and older adults, current smokers, and those with lower education and poorer physical and mental health; and consider specific barriers experienced by minority ethnic groups.

Response rates for mail surveys of dentists and other health care providers have declined appreciably over the past several decades. The objective of this study was to update evidence about the impact use of incentives and different mail strategies on response rates in a mail survey of dentists.We randomized private practice dentists in Iowa (N = 1267) into six study groups to test the effects of incentives and mail strategy on response rate. Survey incentives included either a $2 bill or a customized pen/stylus; a control group with no incentive was included. Mail strategies included bulk mail or first-class stamps.The overall survey response rate was 43%. A $2 bill incentive was associated with significantly higher likelihood of returning a survey compared to the control group with no incentive (48% response rate vs. 40%, respectively). A non-monetary incentive was not significantly associated with likelihood of response. Use of first-class stamps compared to bulk mail did not significantly affect response rate.This study demonstrated the effectiveness of a $2 incentive to increase response rate in a mail survey of dentists. Given the background trend of declining survey participation rates, researchers should consider use of monetary incentives and explore new strategies to increase participation among dentists and other health care providers.

his is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed. This is the sixth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. This summary addresses the most recently published resuscitation evidence reviewed by International Liaison Committee on Resuscitation Task Force science experts. Topics covered by systematic reviews include cardiopulmonary resuscitation during transport; approach to resuscitation after drowning; passive ventilation; minimizing pauses during cardiopulmonary resuscitation; temperature management after cardiac arrest; use of diagnostic point-of-care ultrasound during cardiac arrest; use of vasopressin and corticosteroids during cardiac arrest; coronary angiography after cardiac arrest; public-access defibrillation devices for children; pediatric early warning systems; maintaining normal temperature immediately after birth; suctioning of amniotic fluid at birth; tactile stimulation for resuscitation immediately after birth; use of continuous positive airway pressure for respiratory distress at term birth; respiratory and heart rate monitoring in the delivery room; supraglottic airway use in neonates; prearrest prediction of in-hospital cardiac arrest mortality; basic life support training for likely rescuers of high-risk populations; effect of resuscitation team training; blended learning for life support training; training and recertification for resuscitation instructors; and recovery position for maintenance of breathing and prevention of cardiac arrest. Members from 6 task forces have assessed, discussed, and debated the quality of the evidence using Grading of Recommendations Assessment, Development, and Evaluation criteria and generated consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections, and priority knowledge gaps for future research are listed.

Context Mutations in type I collagen or collagen-related proteins cause osteogenesis imperfecta (OI). Energy expenditure and body composition in OI could reflect reduced mobility or intrinsic defects in osteoblast differentiation increasing adipocyte development. Objective This study compares adiposity and resting energy expenditure (REE) in OI and healthy controls (HC), for OI genotype- and Type-associated differences. Methods We studied 90 participants, 30 with OI (11 COL1A1 Gly, 8 COL1A2 Gly, 4 COL1A1 non-Gly, 1 COL1A2 non-Gly, 6 non-COL; 8 Type III, 16 Type IV, 4 Type VI, 1 Type VII, 1 Type XIV) and 60 HC with sociodemographic characteristics/BMI/BMIz similar to the OI group. Participants underwent dual-energy x-ray absorptiometry to determine lean mass and fat mass percentage (FM%) and REE. FM% and REE were compared, adjusting for covariates, to examine the relationship of OI genotypes and phenotypic Types. Results FM% did not differ significantly in all patients with OI vs HC (OI: 36.6% ± 1.9%; HC: 32.7% ± 1.2%; P = 0.088). FM% was, however, greater than HC for those with non-COL variants (P = 0.016). FM% did not differ from HC among OI Types (P values > 0.05). Overall, covariate-adjusted REE did not differ significantly between OI and HC (OI: 1376.5 ± 44.7 kcal/d; HC: 1377.0 ± 96 kcal/d; P = 0.345). However, those with non-COL variants (P = 0.016) and Type VI OI (P = 0.04) had significantly lower REE than HC. Conclusion Overall, patients with OI did not significantly differ in either extra-marrow adiposity or REE from BMI-similar HC. However, reduced REE among those with non-COL variants may contribute to greater adiposity.

There is substantial regional variation in out-of-hospital cardiac arrest (OHCA) survival. We investigated whether regional emergency medical services (EMS) intra-arrest transport (IAT) practices are associated with patient outcomes.We performed a secondary analysis of a multi-center North American clinical trial dataset, which enrolled EMS-treated adult OHCA cases from 49 regional population-based clusters. The exposure of interest was regional-level intra-arrest transport (IAT), calculated as the proportion of cases in each cluster transported to hospital prior to return of spontaneous circulation, examined as quartiles and as a continuous variable. Multilevel mixed-effects logistic regression modeling estimated the association between regional IAT with survival to hospital discharge and favorable neurologic status (modified Rankin Scale ≤ 3) at hospital discharge.Of 26,148 subjects (median age 68 years; 36% female; 23% shockable initial rhythm) 2424 (9.3%), survived to hospital discharge and 1993 (7.6%) had favourable neurological outcomes. Across regional clusters, IAT ranged from 0.84% to 75% (quartiles6.2%, 6.2-19.6%, 19.6-30.4%, and ≥30.4%). For each quartile, 13.3%, 7.9%, 7.4%, and 4.8% survived, and 10.4%, 7.8%, 7.4%, and 4.8% had favourable neurological status. Regional IAT (per 10% change) was associated with decreased probability of survival (AOR 0.86, 95% CI 0.82-0.91) and favorable neurological outcome (AOR 0.80, 95% CI 0.76-0.85).Treatment within a region that utilizes IAT less frequently was associated with improved clinical outcomes at hospital discharge. These findings may account for some of the known regional variation in OHCA outcomes.

Due to the unpredictable nature of working time arrangements, on-call workers experience regular disruption to sleep, particularly if woken by calls. Sleep disruption can impact long term physical and mental health, next day performance, and importantly, performance immediately after waking. To reduce the impact of performance impairments upon waking (i.e., reducing sleep inertia), research has investigated strategies to promote alertness (e.g., bright light, caffeine, and exercise). This review puts forth on-call workers who are likely to return to sleep after a call, it is also important to consider the impact of these sleep inertia countermeasures on subsequent sleep. Future research should build on the preliminary evidence base for sleep inertia countermeasures by examining the impact on subsequent sleep. This research is key for both supporting alertness and performance during a call ("switching on") and for allowing the on-call worker to return to sleep after a call ("switching off").

Acute cardiorespiratory breathlessness accounts for one in eight of all emergency hospitalizations. Early, noninvasive diagnostic testing is a clinical priority that allows rapid triage and treatment. Here, we sought to find and replicate diagnostic breath volatile organic compound (VOC) biomarkers of acute cardiorespiratory disease and understand breath metabolite network enrichment in acute disease, with a view to gaining mechanistic insight of breath biochemical derangements. We collected and analyzed exhaled breath samples from 277 participants presenting acute cardiorespiratory exacerbations and aged-matched healthy volunteers. Topological data analysis phenotypes differentiated acute disease from health and acute cardiorespiratory exacerbation subtypes (acute heart failure, acute asthma, acute chronic obstructive pulmonary disease, and community-acquired pneumonia). A multibiomarker score (101 breath biomarkers) demonstrated good diagnostic sensitivity and specificity (≥80%) in both discovery and replication sets and was associated with all-cause mortality at 2 years. In addition, VOC biomarker scores differentiated metabolic subgroups of cardiorespiratory exacerbation. Louvain clustering of VOCs coupled with metabolite enrichment and similarity assessment revealed highly specific enrichment patterns in all acute disease subgroups, for example, selective enrichment of correlated C5-7 hydrocarbons and C3-5 carbonyls in heart failure and selective depletion of correlated aldehydes in acute asthma. This study identified breath VOCs that differentiate acute cardiorespiratory exacerbations and associated subtypes and metabolic clusters of disease-associated VOCs.

Recent data suggest that interactions between systems involved in higher order knowledge and associative learning drive responses during value-based learning. However, it is unknown how these systems impact subjective responses, such as pain. We tested how instructions and reversal learning influence pain and pain-evoked brain activation. Healthy volunteers (n=40) were either instructed about contingencies between cues and aversive outcomes or learned through experience in a paradigm where contingencies reversed three times. We measured predictive cue effects on pain and heat-evoked brain responses using functional magnetic resonance imaging. Predictive cues dynamically modulated pain perception as contingencies changed, regardless of whether participants received contingency instructions. Heat-evoked responses in the insula, anterior cingulate, and other regions updated as contingencies changed, and responses in the prefrontal cortex mediated dynamic cue effects on pain, whereas responses in the brainstem’s rostroventral medulla (RVM) were shaped by initial contingencies throughout the task. Quantitative modeling revealed that expected value was shaped purely by instructions in the Instructed Group, whereas expected value updated dynamically in the Uninstructed Group as a function of error-based learning. These differences were accompanied by dissociations in the neural correlates of value-based learning in the rostral anterior cingulate, thalamus, and posterior insula, among other regions. These results show how predictions dynamically impact subjective pain. Moreover, imaging data delineate three types of networks involved in pain generation and value-based learning: those that respond to initial contingencies, those that update dynamically during feedback-driven learning as contingencies change, and those that are sensitive to instruction. Together, these findings provide multiple points of entry for therapies designs to impact pain.

Trichothiodystrophy (TTD) is a rare, autosomal recessive, multisystem disorder of DNA repair and transcription with developmental delay and abnormalities in brain, eye, skin, nervous, and musculoskeletal systems. We followed a cohort of 37 patients with TTD at the National Institutes of Health (NIH) from 2001 to 2019 with a median age at last observation of 12 years (range 2-36). Some children with TTD developed rapidly debilitating hip degeneration (DHD): a distinctive pattern of hip pain, inability to walk, and avascular necrosis on imaging. Ten (27%) of the 37 patients had DHD at median age 8 years (range 5-12), followed by onset of imaging findings at median age 9 years (range 5-13). All 10 had mutations in the ERCC2/XPD gene. In 7 of the 10 affected patients, DHD rapidly became bilateral. DHD was associated with coxa valga, central osteosclerosis with peripheral osteopenia of the skeleton, and contractures/tightness of the lower limbs. Except for one patient, surgical interventions were generally not effective at preventing DHD. Four patients with DHD died at a median age of 11 years (range 9-15). TTD patients with ERCC2/XPD gene mutations have a high risk of musculoskeletal abnormalities and DHD leading to poor outcomes. Monitoring by history, physical examination, imaging, and by physical medicine and rehabilitation specialists may be warranted.

To determine the incidence of peri-intubation cardiac arrest through analysis of a multi-center Emergency Department (ED) airway registry and to report associated clinical characteristics.This is a secondary analysis of prospectively collected data (National Emergency Airway Registry) comprising ED endotracheal intubations (ETIs) of subjects14 years old from 2016 to 2018. We excluded those with cardiac arrest prior to intubation. The primary outcome was peri-intubation cardiac arrest. Multivariable logistic regression generated adjusted odds ratios (aOR) of variables associated with this outcome, controlling for clinical features, difficult airway characteristics, and ETI modality.Of 15,776 subjects who met selection criteria, 157 (1.0%, 95% CI 0.9-1.2%) experienced peri-intubation cardiac arrest. Pre-intubation systolic blood pressure100 mm Hg (aOR 6.2, 95% CI 2.5-8.5), pre-intubation oxygen saturation90% (aOR 3.1, 95% CI 2.0-4.8), and clinician-reported need for immediate intubation without time for full preparation (aOR 1.8, 95% CI, 1.2-2.7) were associated with higher likelihood of peri-intubation cardiac arrest. The association between pre-intubation shock and cardiac arrest persisted in additional modeling stratified by ETI indication, induction agent, and oxygenation status.Peri-intubation cardiac arrest for patients undergoing ETI in the ED is rare. Higher likelihood of arrest occurs in patients with pre-intubation shock or hypoxemia. Prospective trials are necessary to determine whether a protocol to optimize pre-intubation haemodynamics and oxygenation mitigates the risk of peri-intubation cardiac arrest.

Remineralisation of demineralised enamel subsurface lesions can be enhanced by pretreatment of the lesions with base (NaOH). The aim of this study was to test the effect of intralesion pH modulation on remineralisation of demineralised enamel subsurface lesions by casein phosphopeptide-stabilised amorphous calcium fluoride phosphate (CPP-ACFP) in vitro. Two remineralisation models were utilised, the first involving 60-min cyclic pH modulation for 105 h and the second involved short-term cyclic pH modulation (12-min cycle, 240 min total duration) compared with the equivalent time of continuous treatment (200 min total duration). The intralesion pH modulation was achieved by cyclic exposure to a pH 12.9 NaOH solution and a CPP-ACFP remineralisation solution at pH 5.5. Percent remineralisation was assessed using transverse microradiography with data statistically analysed using a 2-sample Student t test. For the first model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (43.8 ± 6.9%) than the control group (28.2 ± 5.8%) cycled with water. For the second model, the intralesion pH modulation group had significantly (p < 0.001) higher remineralisation (23.1 ± 3.4%) than the group with continuous equivalent CPP-ACFP treatment time (1.9 ± 1.3%). In both models, intralesion pH modulation significantly accelerated remineralisation, and this was attributed to the effect pH modulation had on the diffusion gradients of ions/ion pairs and the degree of saturation with respect to apatite phases within the lesion fluid.

Introduction Maintenance of cardiac function is required for successful outcome after out-of-hospital cardiac arrest (OHCA). Cardiac function can be augmented using a mechanical circulatory support (MCS) device, most commonly an intra-aortic balloon pump (IABP) or Impella®. Objective Our objective is to assess whether the use of a MCS is associated with improved survival in patients resuscitated from OHCA in Michigan. Methods We matched cardiac arrest cases during 2014–2017 from the Cardiac Arrest Registry to Enhance Survival (CARES) in Michigan and the Michigan Inpatient Database (MIDB) using probabilistic linkage. Multilevel logistic regression tested the association between MCS and the primary outcome of survival to hospital discharge. Results A total of 3790 CARES cases were matched with the MIDB and 1131 (29.8%) survived to hospital discharge. A small number were treated with MCS, an IABP (n = 183) or Impella® (n = 50). IABP use was associated with an improved outcome (unadjusted OR = 2.16, 95%CI [1.59, 2.93]), while use of Impella® approached significance (OR = 1.72, 95% CI [0.96, 3.06]). Use of MCS was associated with improved outcome (unadjusted OR = 2.07, 95% CI [1.55, 2.77]). In a multivariable model, MCS use was no longer independently associated with improved outcome (ORadj = 0.95, 95% CI [0.69, 1.31]). In the subset of subjects with cardiogenic shock (N = 725), MCS was associated with improved survival in univariate (unadjusted OR = 1.84, 95% CI [1.24, 2.73]) but not multi-variable modeling (ORadj = 1.14, 95% CI [0.74, 1.77]). Conclusion Use of MCS was infrequent in patients resuscitated from OHCA and was not independently associated with improvement in post arrest survival after adjusting for covariates.

Background Paramedics are routinely exposed to shift work. Existing research shows that shift work exposure is associated with adverse mental and physical health outcomes. However, the current understanding of the impact of commencing shift work in a paramedic role on health is limited. This can be addressed by recruiting new paramedics before they commence shift work, and conducting regular follow-ups of potential biological, psychological and social changes. The present study aimed to examine changes in biological, psychological and social factors relative to pre-shift work baseline in a cohort of paramedics commencing intern employment with an Australian ambulance service. Method and analysis This observational, mixed-methods, longitudinal study aims to recruit 40 interns from one Australian ambulance service. Data collection will occur at baseline (standard day schedule for initial training), and subsequently at three months, six months, nine months and twelve months, to measure biological, psychological and social changes relative to baseline measurements. Changes in cardiometabolic markers (cholesterol, triglycerides, fasting glucose), microbiome (self-collected stool samples), sleep and physical activity (actigraphy) will be measured. Interns will also complete a battery of self-report questionnaires, sleep diaries and qualitative interviews to explore various psychological and social variables over time. Statistical analyses will be conducted using mixed effects regression, specifying a random effect of subject on the intercept, allowing participants to vary according to individual baseline levels, as well as tracking progress over time, appropriately accounting for serial correlation. Qualitative study components will be analysed via coding and thematic analysis procedures. Discussion The present study protocol is a comprehensive outline of the observational study planned. The study will allow for greater knowledge of any changes in biological, psychological and social factors during a 12-month transition to shift work. The findings from the proposed study will have implications for the development of strategies to support early-career shift workers.

Context The skeletal phenotype of patients with MEN2B has been described but fracture risk in these patients has not yet been evaluated. Objective This work aims to better delineate fracture risk in patients with multiple endocrine neoplasia type 2B (MEN2B). Methods This case series with chart review was conducted at the National Institutes of Health, Pediatric Oncology Branch. A total of 48 patients with MEN2B were identified, with an age range of 5 to 36 years, median of 19; 24 of 48 (50%) patients were female. Medical records, demographic information, available imaging, and laboratory results were reviewed. History up to age 19 was included in the statistical analyses. Results Of the 48 patients with MEN2B, 20 patients experienced at least one fracture. The majority (n = 18) experienced their first fracture at or before age 19. The observed frequency of fracture occurrence throughout childhood (0-19 years) was 38%, with very little difference between males and females. This frequency is higher than the 9.47 to 36.1 fractures per 1000 persons per year that has been reported in healthy pediatric cohorts in the United States. Less common sites of fracture including vertebral compression fracture and pelvic fractures were observed in patients with MEN2B. Conclusion In this group of patients with MEN2B, there was an increased overall risk of fracture compared to general pediatric cohorts in the United States. Less common sites of fracture were also observed. This suggests a possible effect of an activating RET mutation on bone physiology and warrants further investigation.

Shift work disorder (SWD) is a circadian rhythm sleep-wake disorder, defined by symptoms of insomnia and excessive levels of sleepiness resulting from work that occurs during non-standard hours. Sleep problems are common in shift workers, yet our understanding of help seeking behaviours for sleep in shift workers is limited. The primary aim of this study was to examine the help seeking behaviours of Australian workers who meet criteria for SWD. Of the 448 (46% of sample

Antibiotic-resistant bacteria are a severe threat to human health. The World Health Organization's Global Antimicrobial Surveillance System has revealed widespread occurrence of antibiotic resistance among half a million patients across 22 countries, with Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae being the most common resistant species. Antimicrobial nanoparticles are emerging as a promising alternative to antibiotics in the fight against antimicrobial resistance. In this work, selenium nanoparticles coated with the antimicrobial polypeptide, e-poly-l-lysine, (Se NP-e-PL) were synthesized and their antibacterial activity and cytotoxicity were investigated. Se NP-e-PL exhibited significantly greater antibacterial activity against all eight bacterial species tested, including Gram-positive, Gram-negative, and drug-resistant strains, than their individual components, Se NP and e-PL. The nanoparticles showed no toxicity toward human dermal fibroblasts at the minimum inhibitory concentrations, demonstrating a therapeutic window. Furthermore, unlike the conventional antibiotic kanamycin, Se NP-e-PL did not readily induce resistance in E. coli or S. aureus. Specifically, S. aureus began to develop resistance to kanamycin from ∼44 generations, whereas it took ∼132 generations for resistance to develop to Se NP-e-PL. Startlingly, E. coli was not able to develop resistance to the nanoparticles over ∼300 generations. These results indicate that the multifunctional approach of combining Se NP with e-PL to form Se NP-e-PL is a highly efficacious new strategy with wide-spectrum antibacterial activity, low cytotoxicity, and significant delays in development of resistance.

Porphyromonas gingivalis is a Gram-negative anaerobic pathogen found in subgingival plaque associated with progressive periodontitis. Proteins associated with the outer membrane (OM) of Gram-negative pathogens are particularly important for understanding virulence and for developing vaccines. The aim of this study was to establish a reliable list of outer membrane associated proteins (Omps) for this organism. Starting with a list of 99 experimentally determined Omps, several bioinformatics tools were used to predict a further 52 proteins, leading to a predicted OM proteome of 151 proteins. The tools used included databases of protein families, prediction of OM β-barrels and structural homology. The list includes 33 T9SS cargo proteins, 43 lipoproteins and 66 OM β-barrel proteins with some overlap between categories. The proteins are discussed both in these structural categories as well as their various functions in OM biogenesis, nutrient acquisition, protein secretion, adhesion and efflux. Proteins that were previously shown to be part of large complexes are highlighted and cross reference is provided to a previous major study of protein localization in P. gingivalis. Finally, proteins were also scored according to their level of conservation within the Bacteroidales taxon. Low scores were shown to correlate with virulence factors and may be predictive of novel virulence factors.

Aim Periodontitis has been associated with other systemic diseases with underlying inflammation responsible for the shared link. This study evaluated longitudinal variation in peripheral T helper cells in periodontitis patients undergoing management over 1 year. Materials and methods Periodontal parameters and peripheral blood mononuclear cells (PBMCs) were collected from 54 periodontitis patients at baseline, and 3-, 6- and 12-months post-treatment and 40 healthy controls. IFN-γ+ , IL-4+ , IL-17+ and Foxp3+ and their double-positive expression were identified in CD4+ and TCRαβ+ cells using flow cytometry. PBMCs were incubated with P. gingivalis, and IFN-γ, IL-4, IL-17 and IL-10 in cell supernatant were measured by ELISA. Cells and cytokines were also assessed based on clinical response to treatment where good ( 20%) treatment outcome (TxO) groups had probing depths of ≥5 mm at study conclusion. Results IFN-γ+ cells were lower at baseline, and 3- and 6-months compared to health, whereas Foxp3+ cells were increased at 12-months compared to all preceding timepoints and health. The good TxO group showed treatment-related variation in IFN-γ+ and Foxp3+ cells, whereas the poor TxO group did not. IFN-γ and IL-17 cytokine expression in cell supernatants was significantly lower at baseline compared to health, and IFN-γ and IL-10 showed treatment-related decrease. Conclusion This study suggests that IFN-γ+ and Foxp3+ cells may have a role in the systemic compartment in periodontitis. Periodontal management has local and systemic effects, and thus, assessment and management of periodontitis should form an integral part of overall systemic health.

This2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendationsfor advanced life support includes updates on multiple advanced life support topics addressed with 3 different types of reviews. Topics were prioritized on the basis of both recent interest within the resuscitation community and the amount of new evidence available since any previous review. Systematic reviews addressed higher-priority topics, and included double-sequential defibrillation, intravenous versus intraosseous route for drug administration during cardiac arrest, point-of-care echocardiography for intra-arrest prognostication, cardiac arrest caused by pulmonary embolism, postresuscitation oxygenation and ventilation, prophylactic antibiotics after resuscitation, postresuscitation seizure prophylaxis and treatment, and neuroprognostication. New or updated treatment recommendations on these topics are presented. Scoping reviews were conducted for anticipatory charging and monitoring of physiological parameters during cardiopulmonary resuscitation. Topics for which systematic reviews and new Consensuses on Science With Treatment Recommendations were completed since 2015 are also summarized here. All remaining topics reviewed were addressed with evidence updates to identify any new evidence and to help determine which topics should be the highest priority for systematic reviews in the next 1 to 2 years.

Introduction Congenital nephrotic syndrome (CNS) is an ultra-rare disease associated with a pro-thrombotic state and venous thromboembolisms (VTE). There is very limited evidence evaluating thromboprophylaxis in patients with CNS. This study aimed to determine the doses and duration of treatment required to achieve adequate thromboprophylaxis in patients with CNS. Methods From 2005 to 2018 children in Scotland with a confirmed genetic or histological diagnosis of CNS were included if commenced on thromboprophylaxis. The primary study endpoint was stable drug monitoring. Secondary outcomes included VTE or significant haemorrhage. Results Eight patients were included; all initially were commenced on low-molecular weight heparin (enoxaparin). Four patients maintained therapeutic anti-Factor Xa levels (time 3–26 weeks, dose 3.2–5.07 mg/kg/day), and one patient developed a thrombosis (Anti-Factor Xa: 0.27 IU/ml). Four patients were subsequently treated with warfarin. Two patients maintained therapeutic INRs (time 6–11 weeks, dose 0.22–0.25 mg/kg/day), and one patient had two bleeding events (Bleed 1: INR 6, Bleed 2: INR 5.5). Conclusions Achieving thromboprophylaxis in CNS is challenging. Similar numbers of patients achieved stable anticoagulation on warfarin and enoxaparin. Enoxaparin dosing was nearly double the recommended starting doses for secondary thromboprophylaxis. Bleeding events were all associated with supra-therapeutic anticoagulation.

Mitochondrial-derived peptides (MDPs) are small bioactive peptides encoded by short open-reading frames (sORF) in mitochondrial DNA that do not necessarily have traditional hallmarks of protein-coding genes. To date, eight MDPs have been identified, all of which have been shown to have various cyto- or metaboloprotective properties. The 12S ribosomal RNA ( MT-RNR1) gene harbors the sequence for MOTS-c, whereas the other seven MDPs [humanin and small humanin-like peptides (SHLP) 1–6] are encoded by the 16S ribosomal RNA gene. Here, we review the evidence that endogenous MDPs are sensitive to changes in metabolism, showing that metabolic conditions like obesity, diabetes, and aging are associated with lower circulating MDPs, whereas in humans muscle MDP expression is upregulated in response to stress that perturbs the mitochondria like exercise, some mtDNA mutation-associated diseases, and healthy aging, which potentially suggests a tissue-specific response aimed at restoring cellular or mitochondrial homeostasis. Consistent with this, treatment of rodents with humanin, MOTS-c, and SHLP2 can enhance insulin sensitivity and offer protection against a range of age-associated metabolic disorders. Furthermore, assessing how mtDNA variants alter the functions of MDPs is beginning to provide evidence that MDPs are metabolic signal transducers in humans. Taken together, MDPs appear to form an important aspect of a retrograde signaling network that communicates mitochondrial status with the wider cell and to distal tissues to modulate adaptative responses to metabolic stress. It remains to be fully determined whether the metaboloprotective properties of MDPs can be harnessed into therapies for metabolic disease.

Purpose of review Point-of-care ultrasound (POCUS) is commonly used during cardiac arrest to screen for potential causes and to inform termination of resuscitation. However, unique biases and limitations in diagnostic and prognostic test accuracy studies lead to potential for misinterpretation. The present review highlights recent evidence regarding POCUS in cardiac arrest, guides the incorporation of POCUS into clinical management, and outlines how to improve the certainty of evidence. Recent findings Multiple frameworks organize and direct POCUS during cardiac arrest. Although many are proofs of concept, several have been prospectively evaluated. Indirect evidence from undifferentiated shock suggests that POCUS offers better specificity than sensitivity as a diagnostic aid. The prognostic accuracy of POCUS during cardiac arrest to predict subsequent clinical outcomes is better characterized, but subject to unique biases and confounding. Low certainty direct evidence suggests that POCUS offers better specificity than sensitivity as a prognostic aid. Summary POCUS findings might indicate a particular diagnosis or encourage the continuation of resuscitation, but absence of the same is not sufficient in isolation to exclude a particular diagnosis or cease resuscitation. Until the evidence to support POCUS during cardiac arrest is more certain, it is best characterized as a diagnostic and prognostic adjunct.

Emergency responders often credit 'adrenaline' (i.e. sympathetic activity) as the reason they respond quickly upon waking, unimpaired by sleep inertia. Movement upon waking may promote sympathetic activity in this population. This pilot study (n = 4 healthy males) tested the effects of a 30 s exercise bout (maximal sprint) upon waking during the night (02:00 h) on sympathetic activity and sleep inertia. When compared to sedentary conditions, exercise reduced subjective sleepiness levels and elicited a temporary increase in sympathetic activity, measured by plasma noradrenaline levels. These findings provide preliminary support for exercise as a potential sleep inertia countermeasure.

Results from epidemiological and prospective studies indicate a close association between periodontitis and diabetes. However the mechanisms by which periodontal pathogens influence the development of prediabetes/diabetes are not clear. We previously reported that oral administration of a periodontal pathogen, Porphyromonas gingivalis (Pg) to WT mice results in insulin resistance, hyperinsulinemia, and glucose intolerance and that Pg translocates to the pancreas. In the current study, we determined the specific localization of Pg in relation to mouse and human pancreatic α- and β-cells using 3-D confocal and immunofluorescence microscopy and orthogonal analyses. Pg/gingipain is intra- or peri-nuclearly localized primarily in β-cells in experimental mice and also in human post-mortem pancreatic samples. We also identified bihormonal cells in experimental mice as well as human pancreatic samples. A low percentage of bihormonal cells has intracellular Pg in both humans and experimental mice. Our data show that the number of Pg translocated to the pancreas correlates with the number of bihormonal cells in both mice and humans. Our findings suggest that Pg/gingipain translocates to pancreas, particularly β-cells in both humans and mice, and this is strongly associated with emergence of bihormonal cells.

Objective: On-call work is becoming increasingly common in response to service demands. This study had two aims; 1) describe the demographic profile of on-call workers in Australia, and 2) establis...

Porphyromonas gingivalis is an anaerobic, gram-negative human oral pathogen highly associated with chronic periodontitis. P. gingivalis utilizes the type IX secretion system (T9SS) to transport many of its virulence factors including the gingipains to the cell surface. The T9SS is comprised of at least 16 proteins and the involvement of these 16 proteins in the T9SS has been verified by creating gene deletion mutants in P. gingivalis. These T9SS mutants are regularly utilized to understand how these proteins function together to allow the secretion of the T9SS substrates. We performed label-free quantitative proteomic analysis on the T9SS protein mutants in P. gingivalis to understand the relative abundance of each T9SS component in different mutants. The T9SS components were reduced in abundance in the porK, porL, porM, porN, sov and porT mutants, whereas they were increased in the porE, porU, porV, porZ and porQ mutants. Sov and PorW appear to be the lowest in abundance and PorV the highest amongst all the T9SS components in P. gingivalis wild-type strain. These results are consistent with the proposed role of Sov as the translocation pore in the outer membrane and PorV as the shuttle protein that transports the T9SS substrates between sub-complexes. Together, the label-free quantitative proteomics analyses showed that different T9SS mutants have vastly different abundances of the T9SS components. This knowledge will greatly assist in interpreting the phenotype of the T9SS mutants as well as selecting the right mutant for exploring the role of an individual component.

Objectives Oral health plays an important role in the general well-being of older adults, yet older adults experience unique barriers to dental care. In the United States, almost two-thirds of older adults are dentally uninsured - a reflection of the exclusion of dental benefits from Medicare. The aim of this study was to investigate potential predictors of having a dentist among older adults receiving services funded through the Iowa Department on Aging (IDA). Methods This was a cross-sectional analysis on a convenience sample (n = 2692) of adults age 65+ who completed a required survey to determine eligibility to receive services from the IDA. Data from questionnaires completed between March and December 2017 were used to generate multivariable logistic regression models that identified predictors of having a dentist. The dependent variable, having a dentist, was gathered by self-report in the survey. Explanatory variables eligible for inclusion in the models included demographic and geographic factors, indicators of access to dental care, and factors related to activities of daily living. Results Fewer than half (46.2%) of the respondents reported having a dentist. In the final regression model, individuals with dental insurance were more than twice as likely to have a dentist than those without insurance. Conversely, individuals with a tooth/mouth problem and who need help with housekeeping and with transportation were significantly less likely to have a dentist than their counterparts. Conclusions These results align with known insurance-related barriers and identify certain activities of daily living that might influence older adults' ability to access care. The finding that individuals with oral health problems were less likely to have a dentist underscores the need to reduce barriers to care for this population.

Our cells operate based on two distinct genomes that are enclosed in the nucleus and mitochondria. The mitochondrial genome presumably originates from endosymbiotic bacteria. With time, a large portion of the original genes in the bacterial genome is considered to have been lost or transferred to the nuclear genome, leaving a reduced 16.5 Kb circular mitochondrial DNA (mtDNA). Traditionally only 37 genes, including 13 proteins, were thought to be encoded within mtDNA, its genetic repertoire is expanding with the identification of mitochondrial-derived peptides (MDPs). The biology of aging has been largely unveiled to be regulated by genes that are encoded in the nuclear genome, whereas the mitochondrial genome remained more cryptic. However, recent studies position mitochondria and mtDNA as an important counterpart to the nuclear genome, whereby the two organelles constantly regulate each other. Thus, the genomic network that regulates lifespan and/ or healthspan is likely constituted by two unique, yet co-evolved, genomes. Here, we will discuss aspects of mitochondrial biology, especially mitochondrial communication that may add substantial momentum to aging research by accounting for both mitonuclear genomes to more comprehensively and inclusively map the genetic and molecular networks that govern aging and age-related diseases.

Non-standard working hours are associated with negative health outcomes. However, little is known about the early years of exposure to non-standard work hours, or whether workers new to these work schedules perceive their work as impacting their health. This limits our ability to develop meaningful intervention strategies for transitioning into non-standard work hour schedules. This exploratory study investigated whether recent Australian graduates in various non-standard workhour schedules perceive that their work schedule negatively impacts their health. The responses of 120 graduates within four years of completing their tertiary qualification collected from an online survey were analysed. Graduates were asked whether they perceived their work arrangements as impacting their health. Significantly more of those who were engaged in non-standard work schedules or worked beyond contracted hours perceived their working arrangements as having an impact on their health. This study highlights the importance of studying workers’ perceptions of the impact of work hours on health, particularly when workers may be experiencing good global health but be at risk for negative health outcomes in future.

Porphyromonas gingivalis is an important human pathogen and also a model organism for the Bacteroidetes phylum. O-glycosylation has been reported in this phylum with findings that include the O-glycosylation motif, the structure of the O-glycans in a few species, and an extensive O-glycoproteome analysis in Tannerella forsythia. However, O-glycosylation has not yet been confirmed in P. gingivalis. We therefore used glycoproteomics approaches including partial deglycosylation with trifluoromethanesulfonic acid as well as both HILIC and FAIMS based glycopeptide enrichment strategies leading to the identification of 257 putative glycosylation sites in 145 glycoproteins. The sequence of the major O-glycan was elucidated to be HexNAc-HexNAc(P-Gro-[Ac]0-2)-dHex-Hex-HexA-Hex(dHex). Western blot analyses of mutants lacking the glycosyltransferases PGN_1134 and PGN_1135 demonstrated their involvement in the biosynthesis of the glycan while mass spectrometry analysis of the truncated O-glycans suggested that PGN_1134 and PGN_1135 transfer the two HexNAc sugars. Interestingly, a strong bias against the O-glycosylation of abundant proteins exposed to the cell surface such as abundant T9SS cargo proteins, surface lipoproteins, and outer membrane β-barrel proteins was observed. In contrast, the great majority of proteins associated with the inner membrane or periplasm were glycosylated irrespective of their abundance. The P. gingivalis O-glycosylation system may therefore function to establish the desired physicochemical properties of the periplasm. IMPORTANCE Porphyromonas gingivalis is an oral pathogen primarily associated with severe periodontal disease and further associated with rheumatoid arthritis, dementia, cardiovascular disease, and certain cancers. Protein glycosylation can be important for a variety of reasons including protein function, solubility, protease resistance, and thermodynamic stability. This study has for the first time demonstrated the presence of O-linked glycosylation in this organism by determining the basic structure of the O-glycans and identifying 257 glycosylation sites in 145 proteins. It was found that most proteins exposed to the periplasm were O-glycosylated; however, the abundant surface exposed proteins were not. The O-glycans consisted of seven monosaccharides and a glycerol phosphate with 0–2 acetyl groups. These glycans are likely to have a stabilizing role to the proteins that bear them and must be taken into account when the proteins are produced in heterologous organisms.

Little is known regarding the long-term effects of antiretroviral (ARV) exposure on body composition for people living with HIV (PLWH) since early childhood. This study explores changes in body fat distribution in relation to ARV exposure.We conducted a prospective study of adults with perinatal HIV (n = 70) using dual-energy X-ray absorptiometry and standard anthropometrics. Trunk to limb fat ratio and waist to hip ratio were compared cross-sectionally to 47 matched controls. Furthermore, changes in body composition and ARV exposure were evaluated longitudinally in a subset of 40 PLWH with a median follow-up of 7 years.Cross-sectional comparisons of PLWH with controls revealed significantly higher waist to hip ratio, trunk to limb fat ratio, HOMA-IR, and triglycerides, whereas BMI did not differ. Among PLWH with longitudinal follow-up, the prevalence of overweight increased from 27.5% to 52.5% and obesity from 12.5% to 25%; waist to hip and trunk to limb fat ratios also increased (P0.0001). Changes in waist to hip ratio were positively correlated with longer exposure during follow-up to darunavir (r = 0.36; P = 0.02), whereas increases in trunk to limb fat ratio were positively correlated with longer exposure to stavudine (r = 0.39; P = 0.01) and didanosine (r = 0.39; P = 0.01) but inversely associated with emtricitabine (r = -0.33; P = 0.04). Increases in waist to hip ratio were correlated with increases in triglyceride levels (r = 0.35; P = 0.03).This study presents strong evidence for persistent and worsening central adiposity in young adults with lifelong HIV and extensive ARV exposure. As this cohort ages, continued evaluation of the body composition and metabolic impact of lifelong ARV therapy is warranted to optimize long-term health.

Madsen et al . question the reliability of calibrated radiocarbon ages associated with human footprints discovered recently in White Sands National Park, New Mexico, USA. On the basis of the geologic, hydrologic, stratigraphic, and chronologic evidence, we maintain that the ages are robust and conclude that the footprints date to between ~23,000 and 21,000 years ago. Madsen et al . ( 1 ) question the veracity of calibrated radiocarbon ages used to constrain the antiquity of human trackways discovered recently at White Sands National Park (WHSA) Locality 2, New Mexico, USA ( 2 ). The ages were derived from seeds of the aquatic plant Ruppia cirrhosa , which they suggest may suffer from hard-water (or reservoir) effects, making them too old, potentially by thousands of years. We were well aware of this possibility, investigated it, and presented several lines of evidence that argued against such a problem. Here we respond to each of their four primary points.

The human oral microbiome is becoming recognized as playing roles in health and disease well beyond the oral cavity over the lifetime of the individual. The oral microbiome is hypothesized to result from specific colonization events followed by a reproducible and ordered development of complex bacterial communities. Colonization events, proliferation, succession and subsequent community development are dependent on a range of host and environmental factors, most notably the neonate diet. It is now becoming apparent that early childhood and prenatal influences can have long term effects on the development of human oral microbiomes. In this review, the temporal development of the infant human oral microbiome is examined, with the effects of prenatal and postnatal influences and the roles of specific bacteria. Dietary and environmental factors, especially breastfeeding, have a significant influence on the development of the infant oral microbiome. The evidence available regarding the roles and functions of early colonizing bacteria is still limited, and gaps in knowledge where further research is needed to elucidate these specific roles in relation to health and disease still exist.

Mental health conditions confer considerable global disease burden in young adults, who are also the highest demographic to work shifts, and of whom 20% meet criteria for a sleep disorder. We aimed to establish the relationship between the combined effect of shift work and sleep disorders, and mental health. The Raine Study is the only longitudinal, population-based birth cohort in the world with gold-standard, Level 1 measurement of sleep (polysomnography, PSG) collected in early adulthood. Participants (aged 22y) underwent in-laboratory PSG and completed detailed sleep questionnaires. Multivariable adjusted robust linear regression models were conducted to explore associations with anxiety (GAD7) and depression (PHQ9), adjusted for sex, health comorbidities, and work hours/week. Data were from 660 employed young adults (27.3% shift workers). At least one clinically significant sleep disorder was present in 18% of shift workers (day, evening and night shifts) and 21% of non-shift workers (p = 0.51); 80% were undiagnosed. Scores for anxiety and depression were not different between shift and non-shift workers (p = 0.29 and p = 0.82); but were higher in those with a sleep disorder than those without (Md(IQR) anxiety: 7.0(4.0–10.0) vs 4.0(1.0–6.0)), and depression: (9.0(5.0–13.0) vs 4.0(2.0–6.0)). Considering evening and night shift workers only (i.e. excluding day shift workers) revealed an interaction between shift work and sleep disorder status for anxiety (p = 0.021), but not depression (p = 0.96), with anxiety scores being highest in those shift workers with a sleep disorder (Md(IQR) 8.5(4.0–12.2). We have shown that clinical sleep disorders are common in young workers and are largely undiagnosed. Measures of mental health do not appear be different between shift and non-shift workers. These findings indicate that the identification and treatment of clinical sleep disorders should be prioritised for young workers as these sleep disorders, rather than shift work per se, are associated with poorer mental health. These negative mental health effects appear to be greatest in those who work evening and/or night shift and have a sleep disorder.

Background Most guidelines recommend both pelvic packing (PP) and angioembolization for hemodynamically unstable pelvic fractures, however their sequence varies. Some argue to use PP first because orthopaedic surgeons are more available than interventional radiologists; however, there is no data confirming this. Methods This cross-sectional survey of 158 trauma medical directors at US Level I trauma centers collected the availability of orthopaedic surgeons and interventional radiologists, the number of orthopaedic trauma surgeons trained to manage pelvic fractures, and priority treatment sequence for hemodynamically unstable pelvic fractures. The study objective was to compare the availability of orthopaedic surgeons to interventional radiologists and describe how the availability of orthopaedic surgeons and interventional radiologists affects the treatment sequence for hemodynamically unstable pelvic fractures. Fisher’s exact, chi-squared, and Kruskal-Wallis tests were used, alpha = 0.05. Results The response rate was 25% (40/158). Orthopaedic surgeons (86%) were on-site more often than interventional radiologists (54%), p = 0.003. Orthopaedic surgeons were faster to arrive 39% of the time, and interventional radiologists were faster to arrive 6% of the time. There was a higher proportion of participants who prioritized PP before angioembolization at centers with above the average number (> 3) of orthopaedic trauma surgeons trained to manage pelvic fractures, as among centers with equal to or below average, p = 0.02. Arrival times for orthopaedic surgeons did not significantly predict prioritization of angioembolization or PP. Conclusions Our results provide evidence that orthopaedic surgeons typically are more available than interventional radiologists but contrary to anecdotal evidence most participants used angioembolization first. Familiarity with the availability of orthopaedic surgeons and interventional radiologists may contribute to individual trauma center’s treatment sequence.

Human microbiomes are predicted to assemble in a reproducible and ordered manner yet there is limited knowledge on the development of the complex bacterial communities that constitute the oral microbiome. The oral microbiome plays major roles in many oral diseases including early childhood caries (ECC), which afflicts up to 70% of children in some countries. Saliva contains oral bacteria that are indicative of the whole oral microbiome and may have the ability to reflect the dysbiosis in supragingival plaque communities that initiates the clinical manifestations of ECC. The aim of this study was to determine the assembly of the oral microbiome during the first four years of life and compare it with the clinical development of ECC. The oral microbiomes of 134 children enrolled in a birth cohort study were determined at six ages between two months and four years-of-age and their mother’s oral microbiome was determined at a single time point. We identified and quantified 356 operational taxonomic units (OTUs) of bacteria in saliva by sequencing the V4 region of the bacterial 16S RNA genes. Bacterial alpha diversity increased from a mean of 31 OTUs in the saliva of infants at 1.9 months-of-age to 84 OTUs at 39 months-of-age. The oral microbiome showed a distinct shift in composition as the children matured. The microbiome data were compared with the clinical development of ECC in the cohort at 39, 48, and 60 months-of-age as determined by ICDAS-II assessment. Streptococcus mutans was the most discriminatory oral bacterial species between health and current disease, with an increased abundance in disease. Overall our study demonstrates an ordered temporal development of the oral microbiome, describes a limited core oral microbiome and indicates that saliva testing of infants may help predict ECC risk.

Point-of-care ultrasound (POCUS) is used in cardiac arrest patients to assess for reversible causes. We aimed to conduct a diagnostic test accuracy systematic review of intra-arrest POCUS to indicate the etiology of cardiac arrest in adults in any setting.This review is registered with PROSPERO (CRD42020205207) and reported according to PRISMA guidelines. We searched Medline, EMBASE, Web of Science, CINAHL, and Cochrane Library on October 6, 2021. Two investigators screened titles and abstracts, extracted data, and assessed risks of bias using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) template. We estimated sensitivity and specificity when feasible and evaluated the certainty of evidence with Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.Of 8,621 search results, 12 observational studies reported 26 combinations of index tests and reference standards to indicate six different etiologies of cardiac arrest. All studies had high risks of bias from subject selection, lack of blinding, reference standards susceptible to confounding, and/or differential verification. One study reported sufficient data to complete contingency tables for sensitivity and specificity of POCUS to identify myocardial infarction, cardiac tamponade, and pulmonary embolism as the etiology of cardiac arrest. Heterogeneity and risk of bias precluded meta-analysis and the certainty of evidence was uniformly very low.It is feasible to identify reversible causes of cardiac arrest with POCUS, but the current literature is heterogenous with high risks of bias, wide confidence intervals, and very low certainty of evidence, which render these data difficult to interpret.

Background Fatty acids, specifically polyunsaturated fatty acids (PUFAs) play an important role in inflammation and its resolution, however, their interaction with the epigenome is relatively unexplored. Here we investigate the relationship between circulating blood fatty acids and the DNA methylation of the cytokine encoding gene tumour necrosis factor (TNF, OMIM 191160). Methods Using a cross‐sectional study approach, we collected blood samples from adults (N=88 (30 males, 58 females); 18–74 years old) for DNA methylation pyrosequencing analysis at four sites in TNF exon 1 and gas‐chromatography mass‐spectrometry analysis of the fatty acid profile of dried blood spots (DBS). Results Methylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender‐specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated with TNF methylation, as was the saturated fatty acid (SFA) Stearic Acid; in contrast, mono‐unsaturated fatty acids (MUFAs) had a negative association. In the females, omega‐6 PUFA γ‐Linolenic acid (GLA) was negatively correlated with TNF methylation; Adrenic acid and Eicosadienoic Acid were positively correlated with TNF methylation. Conclusion These results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions., Methylation levels of TNF exon 1 are significantly correlated with specific fatty acids in a gender‐specific manner. In the males the PUFAs Docosahexaenoic Acid (DHA) and Arachidonic Acid (AA) were positively associated. In females, omega‐6 PUFA γ‐Linolenic acid (GLA) was negatively correlated with TNF methylation. These results suggest that one way that fatty acids interact with the inflammation is through altered methylation profiles of cytokine genes; thus, providing potential therapeutic targets for nutritional and health interventions.

Research related to the paramedic workforce is increasing, particularly given the associations with physical and mental health outcomes. However, it is clear that the evidence base to support future paramedic workforce initiatives lacks longitudinal data in cohorts of paramedics. We identify gaps in the epidemiological evidence base for this workforce, and provide insight into the role that prospective cohorts can, and should, play in future research in the paramedic workforce in order to identify health and safety changes over time, and the associations with job requirements, particularly shift work.

Background On-call research and guidance materials typically focus on ‘traditional’ on-call work (e.g., emergency services, healthcare). However, given the increasing prevalence of non-standard employment arrangements (e.g., gig work and casualisation), it is likely that a proportion of individuals who describe themselves as being on-call are not included in current on-call literature. This study therefore aimed to describe the current sociodemographic and work characteristics of Australian on-call workers. Methods A survey of 2044 adults assessed sociodemographic and work arrangements. Of this population, 1057 individuals were workforce participants, who were asked to provide information regarding any on-call work they performed over the last three months, occupation type, weekly work hours, and the presence or absence of non-standard work conditions. Results Of respondents who were working, 45.5% reported working at least one day on-call in the previous month. There was a high prevalence of on-call work in younger respondents (63.1% of participants aged 18–24 years), and those who worked multiple jobs and more weekly work hours. Additionally, high prevalence rates of on-call work were reported by machinery operators, drivers, community and personal service workers, sales workers, and high-level managers. Conclusions These data suggest that on-call work is more prevalent than previously recorded and is likely to refer to a broad set of employment arrangements. Current classification systems may therefore be inadequate for population-level research. A taxonomy for the classification of on-call work is proposed, incorporating traditional on-call work, gig economy work, relief, or unscheduled work, and out of hours work.

IntroductionThe functional consequences of the bacterial gut microbiome for child health are not well understood. Characteristics of the early child gut microbiome may influence the course of enteric infections, and enteric infections may change the composition of the gut microbiome, all of which may have long-term implications for child growth and development.Methods and analysisWe are conducting a community-based birth cohort study to examine interactions between gut microbiome conditions and enteric infections, and how environmental conditions affect the development of the gut microbiome. We will follow 360 newborns from 3 sites along a rural–urban gradient in northern coastal Ecuador, characterising enteric infections and gut microbial communities in the children every 3 to 6 months over their first 2 years of life. We will use longitudinal regression models to assess the correlation between environmental conditions and gut microbiome diversity and presence of specific taxa, controlling for factors that are known to be associated with the gut microbiome, such as diet. From 6 to 12 months of age, we will collect weekly stool samples to compare microbiome conditions in diarrhoea stools versus stools from healthy children prior to, during and after acute enteric infections, using principal-coordinate analysis and other multivariate statistical methods.Ethics and disseminationEthics approvals have been obtained from Emory University and the Universidad San Francisco de Quito institutional review boards. The findings will be disseminated through conference presentations and peer-reviewed journals.

While a large body of literature documents the impairing effect of anxiety on cognition, performing a demanding task was shown to be effective in reducing anxiety. Here we explored the mechanisms of this anxiolytic effect by examining how a pharmacological challenge designed to improve attentional processes influences the interplay between the neural networks engaged during anxiety and cognition. Using a double-blind between-subject design, we pharmacologically manipulated working memory (WM) using a single oral dose of 20 mg methylphenidate (MPH, cognitive enhancer) or placebo. Fifty healthy adults (25/drug group) performed two runs of a WM N-back task in a 3 T magnetic resonance imaging scanner. This task comprised a low (1-Back) and high (3-Back) WM load, which were performed in two contexts, safety or threat of shocks (induced-anxiety). Analyses revealed that (1) WM accuracy was overall improved by MPH and (2) MPH (vs. placebo) strengthened the engagement of regions within the fronto-parietal control network (FPCN) and reduced the default mode network (DMN) deactivation. These MPH effects predominated in the most difficult context, i.e., threat condition, first run (novelty of the task), and 3-Back task. The facilitation of neural activation can be interpreted as an expansion of cognitive resources, which could foster both the representation and integration of anxiety-provoking stimuli as well as the top–down regulatory processes to protect against the detrimental effect of anxiety. This mechanism might establish an optimal balance between FPCN (cognitive processing) and DMN (emotion regulation) recruitment.

The few studies assessing the relationship between mental health and a multidimensional measure of sleep have been conducted in samples of almost exclusively women. In the present study, we therefore assessed associations of multidimensional sleep health with mental well-being in Australian adults. A cross-sectional, national online survey of sleep health was conducted in 2019 in 2,044 community dwelling adults aged 18-90 years. Composite scores of self-reported healthy sleep were based on Ru-SATED (R-SATED) dimensions of satisfaction, alertness, timing, efficiency and duration scored 0 (never/rarely), 1 (sometimes) or 2 (usually/always), and regularity (social jet lag) was scored 0 (≥1 hr) or 1 (