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STUDY OBJECTIVES: To examine whether cognitive behavioral treatments for insomnia (CBT-I) and pain (CBT-P) lead to neural activation changes in response to pain in fibromyalgia. METHODS: Thirty-two patients with fibromyalgia (mean age = 55.9, standard deviation = 12.2) underwent an experimental pain protocol during functional magnetic resonance imaging and completed 14-day diaries assessing total wake time, total sleep time, and pain intensity before and after CBT-I, CBT-P, or waitlist control. Random effects analysis of covariance identified regions with significant group (CBT-I, CBT-P, waitlist control) by time (baseline, post-treatment) interactions in blood oxygen level–dependent response to pain. Linear regressions using residualized change scores examined how changes in total wake time, total sleep time, and pain intensity were related to activation (blood oxygen level–dependent) changes. RESULTS: Twelve regions exhibited small to moderate effects with significant interactions Ps < .00; right hemisphere: inferior frontal, middle occipital, and superior temporal gyri, insula, lentiform nucleus; left hemisphere: angular, superior temporal, midfrontal, inferior occipital, midtemporal, and inferior frontal gyri. Blood oxygen level–dependent response to pain decreased in 8 regions following CBT-I, and in 3 regions following CBT-P (CBT-I effects > CBT-P). Blood oxygen level–dependent response also increased in 3 regions following CBT-P and in 6 regions following waitlist control. Improved total wake time and/or total sleep time, not pain intensity, predicted decreased blood oxygen level–dependence in 7 regions (Ps < .05), accounting for 18%–47% of the variance. CONCLUSIONS: CBT-I prompted greater decreases in neural activation in response to pain across more regions associated with pain and sleep processing than CBT-P. Reported sleep improvements may underlie those decreases. Future research examining the longer-term impact of CBT-I and improved sleep on central pain and sleep mechanisms is warranted. CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Title: Sleep and Pain Interventions in Fibromyalgia (SPIN); Identifier: NCT02001077; URL: https://clinicaltrials.gov/ct2/show/NCT02001077 CITATION: McCrae CS, Craggs JG, Curtis AF, et al. Neural activation changes in response to pain following cognitive behavioral therapy for patients with comorbid fibromyalgia and insomnia: a pilot study. J Clin Sleep Med. 2022;18(1):203–215.

Appropriate control of impurities from all sources is critically important during the development of a pharmaceutical product. One class of impurity that has gained considerable attention over the ...

Objective To describe and compare the characteristics of ectopic pregnancies (EPs) in the year prior to vs during the coronavirus disease 2019 (COVID‐19) pandemic. Methods This was a retrospective analysis of women diagnosed with an EP on transvaginal sonography conducted at a center in London, UK, providing early‐pregnancy assessment, between 1 January 2019 and 31 December 2020. Women were identified via the Astraia ultrasound reporting system using coded and non‐coded outcomes of EP or pregnancy outside the uterine cavity. Data related to predefined outcomes were collected using Astraia and Cerner electronic reporting systems. Main outcome measures included clinical, ultrasound and biochemical features of EP, in addition to reported complications and management. Results There were 22 683 consultations over the 2‐year period. Following consultation, a similar number and proportion of EPs were diagnosed in 2019 (141/12 657 (1%)) and 2020 (134/10 026 (1%)). Both cohorts were comparable in age, ethnicity, weight and method of conception. Gestational age at the first transvaginal sonography scan and at diagnosis were similar, and no difference in location, size or morphology of EP was found between the two cohorts. Serum human chorionic gonadotropin (hCG) levels at the time of EP diagnosis were higher in 2020 than in 2019 (1005 IU/L vs 665 IU/L; P = 0.03). The proportions of women according to type of final EP management were similar, but the rate of failed first‐line management was higher during vs before the pandemic (16% vs 6%; P = 0.01). The rates of blood detected in the pelvis (hemoperitoneum) on ultrasound (23% vs 26%; P = 0.58) and of ruptured EP confirmed surgically (9% vs 3%; P = 0.07) were similar in 2019 vs 2020. Conclusions No difference was observed in the location, size, morphology or gestational age at the first ultrasound examination or at diagnosis of EP between women diagnosed before vs during the COVID‐19 pandemic. Complication rates and final management strategy were also unchanged. However, hCG levels and the failure rate of first‐line conservative management measures were higher during the pandemic. Our findings suggest that women continued to access appropriate care for EP during the COVID‐19 pandemic, with no evidence of diagnostic delay or an increase in adverse outcome in our population. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Background Evidence supports an inverse relationship between weight status and motor competence, but most work utilizes body mass index as the proxy for weight status. Body mass index fails to account for essential components of body composition, which may be critical for motor performance. The purpose of this investigation was to examine the relationship between fundamental motor skills competency and body composition (i.e., fat mass, fat percentage, and fatfree mass) as measured by bio-electrical impedance analysis and body mass index in children. Methods Two hundred forty-four children from the Southeastern portion of the United States participated in this project (6.05 ± 2.01 years, 53.3% male). Fundamental motor skills were measured using the Test of Gross Motor Development – 2nd edition and body composition was assessed with the Tanita SC-331S Body Composition Analyzer (bio-electrical impedance analysis). Body mass index was calculated using CDC normative growth charts. Results Bio-electrical impedance analysis measures accounted for 23.1%, F(3, 241) = 24.10, p p = .086 variance in locomotor and object control subscales, respectively; body mass index accounted for 8.4% (locomotor) and 0.1% (object control) variance. For the Test of Gross Motor Development -2nd edition total score, bio-electrical impedance analysis measures accounted for 24.4% F(3, 241) = 25.90, p p p Conclusions Different components of body composition (i.e., fat free mass) were associated with different aspects of fundamental motor skills competency. Excess body fat may be a morphological constraint to proficient locomotor performance when transporting the body through space. In contrast, body composition did not significantly predict object manipulation performance. More work is needed to understand the causality and directionality of this relationship; however, bio-electrical impedance analysis accounts for more variance in fundamental motor skills performance than body mass index in a field-based setting.

Case: We discuss a patient with a penetrating knife wound to the chest who lost pulses from cardiac tamponade. Prehospital ultrasound was able to quickly identify the tamponade and a pericardiocentesis was performed using a Simplified Pneumothorax Emergency Air Release (SPEARTM) Needle (North American Rescue, LLC, USA) with subsequent return of spontaneous circulation. Discussion: Penetrating chest trauma carries significant morbidity and mortality. In traumatic cardiac arrest due to a penetrating mechanism, it is paramount that the patient be transported to a trauma center as quickly as possible. Prehospital pericardiocentesis is a potential life-saving intervention.

Magnetospheric accretion models predict that matter from protoplanetary disks accretes onto the star via funnel flows which follow the stellar field lines and shock on the stellar surface leaving a hot spot with a density gradient. Previous work has inferred different densities in the hot spot, but has not been sensitive to the radial density distribution. Attempts have been made to measure this with X-ray observations, but X-ray emission only traces a fraction of the hot spot and also coronal emission. Here we report periodic ultraviolet and optical light curves of the accreting star GM Aur that display a time lag of about 1 day between their peaks. The periodicity arises as the source of the ultraviolet and optical emission moves into and out of view as it rotates along with the star. The time-lag indicates a difference in the spatial distribution of ultraviolet and optical brightness over the stellar surface. Within the framework of the magnetospheric accretion model, this indicates a radial density gradient in a hot spot on the stellar surface since different density parts of the hot spot are expected to emit radiation at different wavelengths. These results are the first observational confirmation of the magnetospheric accretion model's prediction of a density gradient in the hot spot and demonstrate the insights gained from focusing on the wavelengths where the bulk of the accretion energy can be observed., published in Nature; open access link: https://www.nature.com/articles/s41586-021-03751-5

Objective: The purpose of this study was to examine the associations between acute daily stress dimensions (frequency, sum) and food intake in adolescents with overweight/obesity, and to explore th...

Cyberbullying among youth is an emerging public health concern that has a wide array of deleterious outcomes. The current meta-analytic review synthesized school-based cyberbullying prevention prog...

Fibromyalgia is a chronic widespread pain syndrome associated with hypersensitivity to nociceptive stimuli. This increased sensitivity of FM patients has been associated with central sensitization of dorsal horn neurons. Increasing evidence, however, suggests that the mechanisms of FM hypersensitivity not only affect pain but include light, smell, and sound. We hypothesized that supraspinal augmentation of sensory input including sound represent a hallmark of FM. We tested 23 FM patients and 28 healthy controls (HC) for sensory augmentation of nociceptive and non-nociceptive sensations: For assessment of nociceptive augmentation we used sensitivity adjusted mechanical and heat ramp & hold stimuli and for assessment of sound augmentation, we applied wideband noise stimuli using a random-staircase design. Quantitative sensory testing demonstrated increased heat and mechanical pain sensitivity in FM participants (P < .001). The sound pressures needed to report mild, moderate, and intense sound levels were significantly lower in FM compared to HC (P < .001), consistent with auditory augmentation. FM patients are not only augmenting noxious sensations but also sound, suggesting that FM augmentation mechanisms are not only operant in the spinal cord but also in the brain. Whether the central nervous system mechanisms for auditory and nociceptive augmentation are similar, needs to be determined in future studies. PERSPECTIVE: This study presents QST evidence that the hypersensitivity of FM patients is not limited to painful stimuli but also to innocuous stimuli like sound. Our results suggest that abnormal brain mechanisms may be responsible for the increased sensitivity of FM patients.

Conflicting results exist about the relationship between bariatric surgery and fracture risk. Also, prediction of who is at increased risk of fracture after bariatric surgery is not currently available. Hence, we used a combination of a self-controlled case series (SCCS) study to establish the association between bariatric surgery and fracture, and develop a prediction model for postoperative fracture risk estimation using a cohort study. Patients from UK Primary care records from the Clinical Practice Research Datalink GOLD linked to Hospital Episode Statistics undergoing bariatric surgery with body mass index (BMI) ≥30 kg/m2 between 1997 and 2018 were included in the cohort. Those sustaining one or more fractures in the 5 years before or after surgery were included in the SCCS. Fractures were considered in three categories: (i) any except skull and digits (primary outcome); (ii) major (hip, vertebrae, wrist/forearm, and humerus); and (iii) peripheral (forearm and lower leg). Of 5487 participants, 252 (4.6%) experienced 272 fractures (of which 80 were major and 135 peripheral) and were included in the SCCS analyses. Major fracture risk increased after surgery, incidence rate ratios (IRRs) and 95% confidence intervals (CIs): 2.77 (95% CI, 1.34-5.75) and 3.78 (95% CI, 1.42-10.08) at ≤3 years and 3.1 to 5 years postsurgery when compared to 5 years prior to surgery, respectively. Any fracture risk was higher only in the 2.1 to 5 years following surgery (IRR 1.73; 95% CI, 1.08-2.77) when compared to 5 years prior to surgery. No excess risk of peripheral fracture after surgery was identified. A prediction tool for major fracture was developed using 5487 participants included in the cohort study. It was also internally validated (area under the receiver-operating characteristic curve [AUC ROC] 0.70) with use of anxiolytics/sedatives/hypnotics and female as major predictors. Hence, major fractures are nearly threefold more likely after bariatric surgery. A simple prediction tool with five variables identifies high risk patients for major fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Repeated drug use can change dopamine function in ways that promote the development and persistence of addiction. But in what direction? By one view, drug use blunts dopamine neurotransmission, producing a hypodopaminergic state that fosters further drug use to overcome a dopamine deficiency. Another view is that drug use enhances dopamine neurotransmission, producing a sensitized, hyperdopaminergic reaction to drugs and drug cues. According to this second view, continued drug use is motivated by sensitization of drug ‘wanting’. Here we discuss recent evidence supporting the latter view, both from preclinical studies using intermittent cocaine self-administration procedures that mimic human patterns of use, and related human neuroimaging studies. These studies have implications for modeling addiction in the laboratory, and for treatment.

Insomnia is an adverse cancer outcome impacting mood, pain, quality of life, and mortality in cancer patients. Cognitive Behavioral Therapy (CBT) is an evidence-based treatment for diverse psychophysiological disorders, including pain and insomnia. Primarily studied in breast cancer, there is limited research on CBT within gynecology oncology. This study examined CBT effects on subjective and behavioral sleep outcomes: Sleep Efficiency (SE), Sleep Quality (SQ), Total Wake Time (TWT), Sleep Onset Latency (SOL), and Wake After Sleep Onset (WASO). Thirty-five women with insomnia status/post-surgery for gynecologic cancer were randomized to CBT for insomnia and pain (CBTi.p., N=18) or Psychoeducation (N=17). Sleep was assessed via sleep diaries and wrist-worn actigraphy at baseline (T1), post-intervention (T2), and two-month follow-up (T3). Intent-to-treat analyses utilizing mixed linear modeling examined longitudinal group differences on sleep controlling for age and advanced cancer. All participants demonstrated improved (1) subjective SE (0.5, p

Homophobic name-calling and sexual violence are prevalent among US high school students and have been associated with a host of negative consequences including anxiety, depression, and substance use disorders, especially among sexual and gender minority youth. Although homophobic name-calling and sexual violence are linked to common risk and protective factors, most prior studies have failed to include gender and sexual minority groups. The present study used path analyses to explore the associations between eight protective factors and the outcomes of homophobic name-calling perpetration, homophobic name-calling victimization, sexual violence perpetration, and sexual violence victimization. The sample included LGB (n = 938), transgender (n = 140), and heterosexual (n = 3,744) high school students in Colorado, USA (N = 4,822). Protective factors included: (1) family support; (2) peer support; (3) friendships with trusted adults; (4) participating in healthy activities; (5) helping others; (6) spirituality; (7) access to counseling; and (8) access to medical services. For homophobic name-calling perpetration and victimization, significant negative associations emerged across different groups for the protective factors of family support, peer support, helping others, spirituality, counseling, and medical access. For sexual violence perpetration and victimization, significant negative associations emerged across different groups for the protective factors family support, peer support, and counseling access. Findings suggest that prevention and intervention efforts to address gender-based harassment should focus on building protective, supportive environments across the schools, families, and communities.

This study compared preschoolers’ fundamental motor skills (FMS) on the Test of Gross Motor Development 2nd and 3rd editions (TGMD-2 and TGMD-3) before (pretest) and after (posttest) a motor skill intervention. This study also compared FMS changes (TGMD raw and percentile scores for total score, and locomotor and object control/ball subscales) across the intervention when FMS were measured using the two editions. Sixty-four preschoolers ( Mage = 4.4, SD = 0.44 years) completed the TGMD-2 and TGMD-3 before and after a motor skill intervention. We determined the level of agreement between assessments using intra-class correlations (ICC), Lin’s Concordance Correlation Coefficient, and Bland-Altman plots. Overall, our results support an acceptable relative agreement between the TGMD-2 and TGMD-3 for raw scores, but there were variable strengths of agreement (by subscales) for percentile scores. Both assessments supported the efficacy of the intervention. This consistent demonstration of efficacy but varied strength of agreement suggests that the TGMD-2 and TGMD-3 are similar but not interchangeable.

Objective To review obstetric personnel absences at a hospital during the initial peak of coronavirus disease 2019 (COVID-19) infection risk in New York City from March 25 to April 21, 2020. Study Design This retrospective study evaluated absences at Morgan Stanley Children's Hospital. Clinical absences for (1) Columbia University ultrasonographers, (2) inpatient nurses, (3) labor and delivery operating room (OR) technicians, (4) inpatient obstetric nurse assistants, and (5) attending physicians providing inpatient obstetric services were analyzed. Causes of absences were analyzed and classified as illness, vacation and holidays, leave, and other causes. Categorical variables were compared with the chi-square test or Fisher's exact test. Results For nurses, absences accounted for 1,052 nursing workdays in 2020 (17.2% of all workdays) compared with 670 (11.1%) workdays in 2019 (p Conclusion COVID-19 outbreak surge planning represents a major operational issue for medical specialties such as critical care due to increased clinical volume. Findings from this analysis suggest it is prudent to devise backup staffing plans. Key Points

Bias-based aggression at school in the form of homophobic name-calling is quite prevalent among early adolescents. Homophobic name-calling is associated with low academic performance, higher risky sexual behaviors, and substance abuse, among other adverse outcomes. This longitudinal study examined risk and protective factors across multiple domains of the social ecology (individual, peer, family, school and community) and levels of analysis (within- and between-person) associated with homophobic name-calling perpetration and victimization. Students from four middle schools in the U.S. Midwest ( N = 1,655; [Formula: see text] age = 12.75; range = 10–16 years) were surveyed four times (Spring/Fall 2008, Spring/Fall 2009). For homophobic name-calling perpetration, significant risk factors included impulsivity, social dominance, traditional masculinity, family violence, and neighborhood violence; while empathy, peer support, school belonging, and adult support were significant protective factors. For homophobic name-calling victimization, significant risk factors included empathy (between-person), impulsivity, traditional masculinity, family violence, and neighborhood violence, while empathy (within-person), parental monitoring, peer support, school belonging, and adult support were significant protective factors.

The average age of individuals in the United States and worldwide is steadily increasing, resulting in an increase in the number of older, terminally ill adults who may seek counseling for end-of-life decisions. Euthanasia is one such end-of-life option that is emerging in the United States. Physician-assisted dying, currently the only legal form of active euthanasia in eight states and the District of Columbia, is a relatively new and often misunderstood end-of-life option. Although arguments continue about this issue, the American Mental Health Counselors Association has developed ethical codes to guide mental health counselors working with terminally ill clients making end-of-life decisions. The core moral and ethical principles of autonomy, beneficence, nonmaleficence, justice, fidelity, and veracity provide guidance for helping terminally ill clients explore end-of-life options that could include physician-assisted dying when it is a legally viable option. Additional recommendations are made for increasing intellectual and emotional competence regarding euthanasia.

In insects, odorant receptors facilitate olfactory communication and require the functionality of the highly conserved co-receptor gene orco. Genome editing studies in a few species of ants and moths have revealed that orco can also have a neurodevelopmental function, in addition to its canonical role in adult olfaction, discovered first in Drosophila melanogaster. To extend this analysis, we determined whether orco mutations also affect the development of the adult brain of the honey bee Apis mellifera, an important model system for social behavior and chemical communication. We used CRISPR/Cas9 to knock out orco and examined anatomical and molecular consequences. To increase efficiency, we coupled embryo microinjection with a laboratory egg collection and in vitro rearing system. This new workflow advances genomic engineering technologies in honey bees by overcoming restrictions associated with field studies. We used Sanger sequencing to quickly select individuals with complete orco knockout for neuroanatomical analyses and later validated and described the mutations with amplicon sequencing. Mutant bees had significantly fewer glomeruli, smaller total volume of all the glomeruli, and higher mean individual glomerulus volume in the antennal lobe compared to wild-type controls. RNA-Sequencing revealed that orco knockout also caused differential expression of hundreds of genes in the antenna, including genes related to neural development and genes encoding odorant receptors. The expression of other types of chemoreceptor genes was generally unaffected, reflecting specificity of CRISPR activity in this study. These results suggest that neurodevelopmental effects of orco are related to specific insect life histories.

The daily challenges resulting from all types of school violence-such as physical aggression, bullying, peer victimization, and general threats-have the potential to affect, longitudinally, students' mental health, school performance, and involvement in criminal or delinquent acts. Across primary and secondary studies, however, variation in how and how much school violence relates to these outcomes, has persisted. The purpose of this systematic review and meta-analysis, therefore, was to clarify this uncertainty by synthesizing the longitudinal relations. We conducted exhaustive searching procedures, implemented rigorous screening and coding processes, and estimated an underused effect size, the partial correlation from multiple regression models, before estimating a random-effects meta-analysis using robust variance estimation. We meta-analyzed 114 independent studies, totaling 765 effect sizes across 95,618 individual participants. The results of the overall analyses found a statistically significant longitudinal relation between school violence, in any role, and the aggregated outcome variables (rp = .06). Given that this effect size inherently controls for multiple potential confounding covariates, we consider the relation's magnitude clinically meaningful. We end by discussing ways practitioners and researchers may use these analyses when implementing prevention programming and how the field of meta-analysis should more frequently utilize the partial correlation. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Epistaxis is a routine complaint in Emergency Medicine and presents most commonly in adults and children and its incidence increases with age. It is rare in infants and neonates. We discuss a case of epistaxis in a four-month-old male who presented to a critical access hospital. What initially appeared to be routine brisk epistaxis was later discovered to be a large, complex, epiglottic hemangioma. The patient was stabilized using topical tranexamic acid, nasal packing with ketamine sedation, and sent to a tertiary care center for definitive management. He required advanced airway management in the OR for definitive airway management for airway-obstructing hemangioma excision.

PURPOSE To evaluate the effectiveness of Wayne State University School of Medicine's (WSUSOM's) 50-year premedical postbaccalaureate program (PBP)-the first and oldest in the United States-in achieving its goals, as measured by medical school matriculation and graduation, primary care specialization, and current practice location. METHOD A retrospective study of a complete comparative dataset of 9,856 WSUSOM MD graduates (1979-2017) was performed in July-August 2018. This included 539 graduates who were admitted to the PBP between 1969 and 2012. Data collected included PBP students' sociodemographics, postgraduate specialization, residence location at time of admission to the PBP, and current medicine practice location. Health professional shortage areas (HPSAs) and medically underserved areas/populations (MUA/Ps) were determined for residence at admission to the PBP and current medicine practice location. RESULTS Of the 539 PBP students, 463/539 (85.9%) successfully completed the PBP and matriculated to WSUSOM. Of those, 401/463 (86.6%) obtained an MD, and of those, 233/401 (58.1%) were female and 277/401 (69.1%) were African American. Average investment per PBP student was approximately $52,000 and for an MD graduate was approximately $77,000. The majority of PBP MD graduates with current practice information resided in HPSAs or MUA/Ps at admission to PBP (204/283, 72.1%) and were currently practicing in HPSAs or MUA/Ps (232/283, 82.0%), and 139/283 (49.1%) became primary care physicians (PCPs). Comparison of WSUSOM PBP and non-PBP MD graduates showed PBP physicians become PCPs and practice in HPSAs or MUA/Ps at higher rates than non-PBP physicians (P < .001). CONCLUSIONS The PBP was successful in graduating a large proportion of physicians from socioeconomically disadvantaged and diverse backgrounds, who practice as PCPs and who practice in HPSAs and MUA/Ps, thereby accomplishing the PBP's goals of helping to address the broad health care needs of all people in the United States.

BackgroundKetamine’s potent and rapid antidepressant properties have shown great promise to treat severe forms of major depressive disorder (MDD). A recently hypothesized antidepressant mechanism of action of ketamine is the inhibition of N-methyl-D-aspartate receptor–dependent bursting activity of the habenula (Hb), a small brain structure that modulates reward and affective states.MethodsResting-state functional magnetic resonance imaging was conducted in 35 patients with MDD at baseline and 24 hours following treatment with i.v. ketamine. A seed-to-voxel functional connectivity (FC) analysis was performed with the Hb as a seed-of-interest. Pre-post changes in FC and the associations between changes in FC of the Hb and depressive symptom severity were examined.ResultsA reduction in Montgomery–Åsberg Depression Rating Scale scores from baseline to 24 hours after ketamine infusion was associated with increased FC between the right Hb and a cluster in the right frontal pole (t = 4.65, P = .03, false discovery rate [FDR]-corrected). A reduction in Quick Inventory of Depressive Symptomatology-Self Report score following ketamine was associated with increased FC between the right Hb and clusters in the right occipital pole (t = 5.18, P ConclusionsThese preliminary results suggest that the Hb might be involved in ketamine’s antidepressant action in patients with MDD, although these findings are limited by the lack of a control group.

Background Pain and substance use are frequently comorbid and have been shown to exert bidirectional effects. Self-medication of pain and distress via substance use is common and can be understood via negative reinforcement, ultimately strengthening the pathway between pain to substance use over time. As such, a testable model of the potentially modifiable candidate mechanisms that underlie the pain to substance use pathway is needed. Purpose This review proposes a testable model of pain as an antecedent to substance use to guide future research and inform clinical practice. Methods An integrative review of current evidence regarding pain, substance use, and associated risk factors (i.e., negative affect, pain-related attitudes, negative urgency, and substance use outcome expectancies) was conducted. Results The Catastrophizing, Anxiety, Negative Urgency, and Expectancy (CANUE) model highlights modifiable risk factors for self-medicating pain with substance use, including increased negative affect and maladaptive pain-related attitudes (i.e., pain catastrophizing, pain anxiety, and fear of pain), negative urgency, and substance-related outcome expectancies for pain relief and enhanced pain coping. Conclusions Targeted behavioral and psychological interventions that address these factors may facilitate more adaptive pain-coping responses, thereby reducing the impacts of pain on substance use. Systematic research is needed to evaluate the validity and clinical utility of this model.

Author(s): Chitre, Apurva S; Polesskaya, Oksana; Holl, Katie; Gao, Jianjun; Cheng, Riyan; Bimschleger, Hannah; Garcia Martinez, Angel; George, Tony; Gileta, Alexander F; Han, Wenyan; Horvath, Aidan; Hughson, Alesa; Ishiwari, Keita; King, Christopher P; Lamparelli, Alexander; Versaggi, Cassandra L; Martin, Connor; St Pierre, Celine L; Tripi, Jordan A; Wang, Tengfei; Chen, Hao; Flagel, Shelly B; Meyer, Paul; Richards, Jerry; Robinson, Terry E; Palmer, Abraham A; Solberg Woods, Leah C | Abstract: ObjectiveObesity is influenced by genetic and environmental factors. Despite the success of human genome-wide association studies, the specific genes that confer obesity remain largely unknown. The objective of this study was to use outbred rats to identify the genetic loci underlying obesity and related morphometric and metabolic traits.MethodsThis study measured obesity-relevant traits, including body weight, body length, BMI, fasting glucose, and retroperitoneal, epididymal, and parametrial fat pad weight in 3,173 male and female adult N/NIH heterogeneous stock (HS) rats across three institutions, providing data for the largest rat genome-wide association study to date. Genetic loci were identified using a linear mixed model to account for the complex family relationships of the HS and using covariates to account for differences among the three phenotyping centers.ResultsThis study identified 32 independent loci, several of which contained only a single gene (e.g., Epha5, Nrg1, Klhl14) or obvious candidate genes (e.g., Adcy3, Prlhr). There were strong phenotypic and genetic correlations among obesity-related traits, and there was extensive pleiotropy at individual loci.ConclusionsThis study demonstrates the utility of HS rats for investigating the genetics of obesity-related traits across institutions and identify several candidate genes for future functional testing.

In Part I of this series I, we looked back at the 20thcentury and re-examined the history of Motor Development research described in Clark & Whitall’s 1989 paper “What is Motor Development? The Lessons of History”. We now move to the 21stcentury, where the trajectories of developmental research have evolved in focus, branched in scope, and diverged into three new areas. These have progressed to be independent research areas, co-existing in time. We posit that the research focus on Dynamical Systems at the end of the 20thcentury has evolved into a Developmental Systems approach in the 21stcentury. Additionally, the focus on brain imaging and the neural basis of movement have resulted in a new approach, which we entitled Developmental Motor Neuroscience. Finally, as the world-wide obesity epidemic identified in the 1990s threatened to become a public health crisis, researchers in the field responded by examining the role of motor development in physical activity and health-related outcomes; we refer to this research area as the Developmental Health approach. The glue that holds these research areas together is their focus on movement behavior as it changes across the lifespan.

Sports-related concussions (SRC) are traumatic brain injuries induced as the result of a biomechanical force to the body that temporarily impair neurological functions. Not all traumatic impacts reach the threshold necessary to produce concussive symptoms; however, the culmination of these events is known as a subconcussive impact (SCI). Athletes who have been diagnosed with a SRC or those who accumulate multiple SCI have exhibited structural damage to the brain, impairments to learning and memory, and an increase in depressive symptoms. This area is rapidly evolving, and current clinical definitions of injury, diagnosis, and treatment of SRC and SCI are reviewed. In tandem, there is also growing research examining the role of nutrition in brain injuries, focusing primarily on n-3 polyunsaturated fatty acids (PUFA). The potential role of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing inflammation and promoting recovery following brain injury are also reviewed. Overall, advancements in the evaluation of SRC and SCI coupled with n-3 PUFA supplementation show promise in the management of brain injuries, leading to better long-term health outcomes for athletes. Novelty SRC have garnered widespread attention due to the growing body of reported prevalence in youth and professional sports. Current definitions and protocol(s) for diagnosing SRC and SCI have improved, but still require further evaluation. n-3, EPA and DHA, reduce inflammation and promote recovery following brain injuries in experimental models.

Objectives To evaluate the safety and feasibility of physical rehabilitation and active mobilization in patients requiring continuous renal replacement therapy in the ICU. Data sources Medline, CINAHL, PubMed, Pedro, and Cochrane Library were used to extract articles focused on physical activity and mobility in this population. Study selection Research articles were included in this review if 1) included adult patients greater than or equal to 18 years old requiring continuous renal replacement therapy located in the ICU; 2) described physical rehabilitation, active mobilization, or physical activity deliverables; 3) reported data on patient safety and/or feasibility. The primary outcome was safety, defined as number of adverse events per total number of sessions. Data extraction Five-hundred seven articles were evaluated based on title and abstract with reviewers selecting 46 to assess by full text. Fifteen observational studies were included for final analysis with seven studies focused solely on physical activity in patients requiring continuous renal replacement therapy. Data synthesis Four-hundred thirty-seven adult ICU patients requiring continuous renal replacement therapy participated in some form of physical rehabilitation, physical activity, or active mobilization. Two major adverse events (hypotension event requiring vasopressor and continuous renal replacement therapy tube disconnection, pooled occurrence rate 0.24%) and 13 minor adverse events (pooled occurrence rate 1.55%) were reported during a total of 840 individual mobility or activity sessions. Intervention fidelity was limited by a low prevalence of higher mobility with only 15.5% of incidences occurring at or above level 5 of ICU Mobility Scale (transfer to chair, marching in place or ambulation away from bed, 122/715 reports). Feasibility in the provision of these interventions and/or continuous renal replacement therapy-specific deliverables was inconsistently reported. Conclusions Early rehabilitation and mobilization, specifically activity in and near the hospital bed, appears safe and mostly feasible in ICU patients requiring continuous renal replacement therapy. A cautious interpretation of these data is necessary due to limited aggregate quality of included studies, heterogeneous reporting, and overall low achieved levels of mobility potentially precluding the occurrence or detection of adverse events.

BACKGROUND. Interventions are needed to teach fundamental motor skills (FMS) to preschoolers. There is a need to design more practical and effective interventions that can be successfully implemented by non-motor experts and fit within the existing gross motor opportunities such as outdoor free play at the preschool. The purpose of this study was to evaluate the feasibility and efficacy of a non-motor expert FMS intervention that was implemented during outdoor free play, Motor skills At Playtime (MAP). METHODS. Participants were preschoolers from two Head Start Centers (N = 46; M(age) = 4.7 ± 0.46 years; 41% boys) and were divided into a MAP (n = 30) or control (outdoor free play; n = 16) group. Children completed either a 1350-minute MAP intervention or control condition (outdoor free play) from January to April of 2018. FMS were assessed before and after each program. using both the Test of Gross Motor Development-3(rd) Edition (Ulrich, 2019) and skill outcome measures (running speed, hopping speed, jump distance, throwing speed, kicking speed, and catching percentage). Intervention implementation feasibility was measures through daily fidelity checks. Fidelity was evaluated as the percentage of intervention sessions that included all explicit intervention criteria. FMS data were analyzed using linear mixed modeling. Models were fit with fixed effects of time and treatment, covariates of sex and height, and a random intercept for each individual. RESULTS. The non-motor expert was feasibly able to implement MAP with high fidelity (> 93%). There was a significant treatment effect for MAP on process and product locomotor FMS (p< 0.05), and a trend for a treatment effect for MAP on total process FMS (p = 0.07). CONCLUSION. Results support that MAP was successfully implemented by a non-motor expert and led to improvements in children’s FMS, especially locomotor FMS.

For social animals, the genotypes of group members affect the social environment, and thus individual behavior, often indirectly. We used genome-wide association studies (GWAS) to determine the influence of individual vs. group genotypes on aggression in honey bees. Aggression in honey bees arises from the coordinated actions of colony members, primarily nonreproductive "soldier" bees, and thus, experiences evolutionary selection at the colony level. Here, we show that individual behavior is influenced by colony environment, which in turn, is shaped by allele frequency within colonies. Using a population with a range of aggression, we sequenced individual whole genomes and looked for genotype-behavior associations within colonies in a common environment. There were no significant correlations between individual aggression and specific alleles. By contrast, we found strong correlations between colony aggression and the frequencies of specific alleles within colonies, despite a small number of colonies. Associations at the colony level were highly significant and were very similar among both soldiers and foragers, but they covaried with one another. One strongly significant association peak, containing an ortholog of the Drosophila sensory gene dpr4 on linkage group (chromosome) 7, showed strong signals of both selection and admixture during the evolution of gentleness in a honey bee population. We thus found links between colony genetics and group behavior and also, molecular evidence for group-level selection, acting at the colony level. We conclude that group genetics dominates individual genetics in determining the fatal decision of honey bees to sting.

Due to the use of improvised explosive devices, blast exposure and mild traumatic brain injury (mTBI) have become hallmark injuries of the Iraq and Afghanistan wars. Although the mechanisms of the effects of blast on human neurobiology remain active areas of investigation, research suggests that the cerebrovasculature may be particularly vulnerable to blast via molecular processes that impact cerebral blood flow. Given that recent work suggests that blast exposure, even without a subsequent TBI, may have negative consequences on brain structure and function, the current study sought to further understand the effects of blast exposure on perfusion. One hundred and eighty military personnel underwent pseudo-continuous arterial spin labeling (pCASL) imaging and completed diagnostic and clinical interviews. Whole-brain analyses revealed that with an increasing number of total blast exposures, there was significantly increased perfusion in the right middle/superior frontal gyri, supramarginal gyrus, lateral occipital cortex, and posterior cingulate cortex as well as bilateral anterior cingulate cortex, insulae, middle/superior temporal gyri and occipital poles. Examination of other neurotrauma and clinical variables such as close-range blast exposures, mTBI, and PTSD yielded no significant effects. These results raise the possibility that perfusion may be an important neural marker of brain health in blast exposure.

To investigate late retinal findings and complications of eyes with a history of retinopathy of prematurity (ROP) that did not meet treatment criteria and did not receive treatment during infancy.Retrospective, nonconsecutive, noncomparative, multicenter case series.Three hundred sixty-three eyes of 186 patients.Data were requested from multiple providers on premature patients with a history of ROP and no treatment during infancy who demonstrated late retinal findings or complications and included age, gender, gestational age and weight, zone and stage at infancy, visual acuity, current retina vascularization status, vitreous character, presence of peripheral retinal findings such as lattice retinal tears and detachments (RDs), retinoschisis, and fluorescein findings.Rate of RDs and factors conferring a higher risk of RDs.The average age was 34.5 years (range, 7-76 years), average gestational age was 26.6 weeks (range, 23-34 weeks), and average birth weight was 875 g (range, 425-1590 g). Findings included lattice in 196 eyes (54.0%), atrophic holes in 126 eyes (34.7%), retinal tears in 111 eyes (30.6%), RDs in 140 eyes (38.6 %), tractional retinoschisis in 44 eyes (11.9%), and visible vitreous condensation ridge-like interface in 112 eyes (30.5%). Fluorescein angiography (FA) was performed in 113 eyes, of which 59 eyes (52.2%) showed leakage and 16 eyes (14.2%) showed neovascularization. Incomplete vascularization posterior to zone 3 was common (71.6% of eyes). Retinal detachments were more likely in patients with a gestational age of 29 weeks or less (P0.05) and in eyes with furthest vascularization to posterior zone 2 eyes compared with zone 3 eyes (P = 0.009).Eyes with ROP not meeting the treatment threshold during infancy showed various late retinal findings and complications, of which RDs were the most concerning. Complications were seen in all age groups, including patients born after the Early Treatment for Retinopathy of Prematurity Study. Contributing factors to RDs included atrophic holes within peripheral avascular retina, visible vitreous condensation ridge-like interface with residual traction, and premature vitreous syneresis. We recommend regular examinations and consideration of ultra-widefield FA examinations. Prospective studies are needed to explore the frequency of complications and benefit of prophylactic treatment and if eyes treated with anti-vascular endothelial growth factor therapy are at risk of similar findings and complications.

Background: Children in rural geographies are not universally able to access pediatric-trained palliative or hospice providers. Objective: Determine whether telehealth inclusion of a familiar pedia...

RATIONALE: With repeated administration the psychomotor activating effects of drugs such as cocaine or amphetamine can change in very different ways – showing sensitization or tolerance – depending on whether they are administered more or less intermittently. This behavioral plasticity is thought to reflect, at least in part, changes in dopamine (DA) neurotransmission, and therefore, may provide insights into the development of substance use disorders. Indeed, the most widely used preclinical model of cocaine addiction, which involves Long Access (LgA) self-administration procedures, is reported to produce tolerance to cocaine’s psychomotor activating effects and effects on DA activity. In contrast, Intermittent Access (IntA) cocaine self-administration is more effective than LgA in producing addiction-like behavior, but sensitizes DA neurotransmission. There is, however, very little information concerning the effects of IntA experience on the psychomotor activating effects of cocaine. OBJECTIVE: To determine whether IntA experience produces psychomotor sensitization with similar characteristics to that produced by the intermittent, noncontingent administration of cocaine. RESULTS: IntA to cocaine did indeed produce psychomotor sensitization that (1) was greater after a long (30 days) vs short (1 day) period of withdrawal; (2) was greater in females than males; and (3) resulted in cross-sensitization to another psychomotor stimulant drug, amphetamine. CONCLUSION: The tolerance sometimes associated with LgA cocaine self-administration has been cited in support of the idea that, in addiction, drug-seeking and –taking is motivated to overcome a DA deficiency and associated anhedonia. In contrast, the neurobehavioral sensitization associated with IntA cocaine self-administration favors an incentive-sensitization view.

Quantitative sensory testing (QST) is used to systematically interrogate normal responding and alterations of nervous system function, including pain-related central sensitization (CS). However, up to now, QST of CS in human subjects has been mostly focused on temporal summation of second pain (TSSP), has been difficult to perform, and has been associated with low reliability. In contrast, slow ramp & hold (RH) procedures are simpler tests of temporal summation and easier to perform. We examined the usefulness of RH procedures as reliable generators of CS using 2 validated QST procedures: decay of pain aftersensations and wind-down. Twenty-seven pain-free subjects (74% female) were enrolled into the study. Trains of sensitivity-adjusted TSSP or RH heat stimuli were applied to the hands of participants to achieve moderate temporal pain summation (50 Numerical Rating Scale [NRS] [0-100]). Fifteen-second aftersensations and 30-second wind-down related to TSSP or RH were used for CS comparisons. Reliability of all test procedures was tested over 24 hours. Use of sensitivity-adjusted TSSP and RH heat stimuli resulted in average pain ratings of 48.2 and 49.6 NRS, respectively. Aftersensations or wind-down decay were not significantly different after either TSSP or RH, (all P > .05), indicating that each procedure achieved similar levels of short-term CS. Sensitivity-adjusted RH stimuli were well tolerated and resulted in reliable pain increases of ∼50 NRS. The magnitude of short-term CS, determined by aftersensations and wind-down was similar after sensitivity-adjusted TSSP and RH stimuli (P > .05), suggesting that pain facilitation of healthy participants and likely chronic pain patients can not only be tested with TSSP but also with RH procedures. PERSPECTIVE: This article examines the ability of RH procedures to generate similar central sensitivity augmentation than TSSP. The results suggest that RH is similarly well suited as TSSP to explore central pain mechanisms in healthy subjects and most likely also in chronic pain patients.

BACKGROUND Traditional pain interventions limit fluctuations in pain sensation, which may paradoxically impair endogenous pain modulatory systems (EPMS). However, controlled exposures to clinically relevant pain (e.g. delayed onset muscle soreness [DOMS]) may build capacity in the EPMS. Emerging evidence suggests that regional signal variability (RSV) may be an important indicator of efficiency and modulatory capacity within brain regions. This study sought to determine the role of RSV in both susceptibility to and trainability of pain response following repeated DOMS inductions. METHODS Baseline and follow-up resting-state fMRI was performed on 12 healthy volunteers ~40 days apart. Between scanning visits, participants received four weekly DOMS inductions in alternating elbow flexors and were supplied seven days of post-induction pain ratings. Voxel-wise standard deviation of signal intensity was calculated to measure RSV. Associations among DOMS-related pain and RSV were assessed with regression. Relationships among baseline and change measurements were probed (i.e. susceptibility to DOMS; trainability following multiple inductions). RESULTS Significant association between baseline RSV in left middle frontal gyrus (MFG) and right cerebellum and reductions in DOMS-related pain unpleasantness were detected. Furthermore, increases in RSV were associated with reduced DOMS pain intensity (left lingual gyrus, right MTG, left MTG, left precuneus) and unpleasantness (left MTG, right SFG). DISCUSSION Findings suggest that RSV may be an indicator of EPMS resilience and responsivity to training, as well as an indicator that is responsive to training. Involved regions underlie cognitive, affective and representation processes. Results further clarify the potential role of RSV as an indicator of pain modulation and resilience. SIGNIFICANCE Regional signal variability may be an important indicator of endogenous pain modulatory system responsivity to training following repeated bouts of clinically relevant pain and may in fact be responsive to training itself.

Background Context Peripheral differences often do not adequately account for variation in reports of pain intensity in people with musculoskeletal pain. Purpose Here we sought to determine the extent to which structural differences in the brain (grey matter density) of pain free individuals might relate to subsequent pain (or lack thereof) after standardized peripheral muscle injury (ie, micro trauma from high intensity exercise). Study Design This was an observational laboratory-based study that was a secondary analysis from a larger trial. Methods Participants completed baseline testing (functional MRI and quantitative pain testing) followed by high intensity trunk exercise to induce delayed onset muscle soreness in the erector spinae. Forty-eight hours later, back pain intensity ratings were collected and all participants were re-imaged. Grey matter density was determined using voxel-based morphometry. The “asymptomatic” group (no reports of any pain within 48 hours after induction) to a ‘pain’ group (rating of pain at rest and movement pf>20 on a 101-point numeric rating scale). Results Our results revealed several large clusters where, compared to participants with pain, asymptomatic participants had significant greater grey matter density. These brain regions included left medial frontal gyrus, left middle occipital gyrus, left middle temporal gyrus, left inferior frontal gyrus, and right superior frontal gyrus. Conclusions Lower grey matter density in brain regions previously linked to discriminative, emotional, and cognitive aspects of cortical processing are associated with reporting musculoskeletal pain after a standardized peripheral muscle injury. Clinical Significance Cortical gray matter density of people without any pain may influence response to a standardized high intensity exercise protocol. This finding adds further support to the relevance of central factors in explaining the tremendous individual variability in pain report following acute musculoskeletal injury.

ObjectiveCountries in sub-Saharan Africa suffer the highest rates of child mortality worldwide. Urban areas tend to have lower mortality than rural areas, but these comparisons likely mask large within-city inequalities. We aimed to estimate rates of under-five mortality (U5M) at the neighbourhood level for Ghana’s Greater Accra Metropolitan Area (GAMA) and measure the extent of intraurban inequalities.MethodsWe accessed data on >700 000 women aged 25–49 years living in GAMA using the most recent Ghana census (2010). We summarised counts of child births and deaths by five-year age group of women and neighbourhood (n=406) and applied indirect demographic methods to convert the summaries to yearly probabilities of death before age five years. We fitted a Bayesian spatiotemporal model to the neighbourhood U5M probabilities to obtain estimates for the year 2010 and examined their correlations with indicators of neighbourhood living and socioeconomic conditions.ResultsU5M varied almost five-fold across neighbourhoods in GAMA in 2010, ranging from 28 (95% credible interval (CrI) 8 to 63) to 138 (95% CrI 111 to 167) deaths per 1000 live births. U5M was highest in neighbourhoods of the central urban core and industrial areas, with an average of 95 deaths per 1000 live births across these neighbourhoods. Peri-urban neighbourhoods performed better, on average, but rates varied more across neighbourhoods compared with neighbourhoods in the central urban areas. U5M was negatively correlated with multiple indicators of improved living and socioeconomic conditions among peri-urban neighbourhoods. Among urban neighbourhoods, correlations with these factors were weaker or, in some cases, reversed, including with median household consumption and women’s schooling.ConclusionReducing child mortality in high-burden urban neighbourhoods in GAMA, where a substantial portion of the urban population resides, should be prioritised as part of continued efforts to meet the Sustainable Development Goal national target of less than 25 deaths per 1000 live births.

Background & aims Methionine adenosyltransferase 1A (MAT1A) is responsible for S-adenosylmethionine (SAMe) biosynthesis in the liver. Mice lacking Mat1a have hepatic SAMe depletion, develop non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC) spontaneously. Several kinases are activated in Mat1a knockout (KO) mice livers. However, the phosphos-proteome has not been characterized and whether they contribute to liver pathology is largely unknown. Our study aimed to fill this gap. Approach & results We performed phospho-proteomics in Mat1a KO mice livers with and without SAMe treatment to identify SAMe-dependent changes that may contribute to liver pathology. Our studies used Mat1a KO mice at different ages treated with and without SAMe, cell lines, in vitro translation and kinase assays, and human liver specimens. We found the most striking change was hyperphosphorylation and increased content of La-Related Protein 1 (LARP1), which in the unphosphorylated form negatively regulates translation of 5'-terminal oligopyrimidine (TOP)-containing mRNAs. Consistently, multiple TOP proteins are induced in the KO livers. The translation of TOP mRNAs RPS3 and RPL18 was enhanced by LARP1 overexpression in liver cancer cells. We identified LARP1-T449 as a novel, SAMe-sensitive phospho-site of cyclin-dependent kinase 2 (CDK2). Knocking down CDK2 lowered LARP1 phosphorylation and prevented LARP1 overexpression mediated increase in translation. LARP1-T449 phosphorylation induced global translation, cell growth, migration, invasion, and expression of oncogenic TOP-ribosomal proteins in HCC cells. LARP1 expression is increased in human NASH and HCC. Conclusion Our results reveal a novel SAMe-sensitive mechanism of LARP1 phosphorylation that may be involved in the progression of NASH to HCC.

Deintensification therapy for human papillomavirus-related oropharyngeal squamous cell carcinoma (HPV(+) OPSCC) is under active investigation. An adaptive treatment approach based on molecular stratification could identify high-risk patients predisposed to recurrence and better select for appropriate treatment regimens. Collectively, 40 HPV(+) OPSCC FFPE samples (20 disease-free, 20 recurrent) were surveyed using mass spectrometry-based proteomic analysis via data-independent acquisition to obtain fold change and false discovery differences. Ten-year overall survival was 100.0 and 27.7% for HPV(+) disease-free and recurrent cohorts, respectively. Of 1414 quantified proteins, 77 demonstrated significant differential expression. Top enriched functional pathways included those involved in programmed cell death (73 proteins, p = 7.43 × 10-30), apoptosis (73 proteins, p = 5.56 × 10-9), β-catenin independent WNT signaling (47 proteins, p = 1.45 × 10-15), and Rho GTPase signaling (69 proteins, p = 1.09 × 10-5). PFN1 (p = 1.0 × 10-3), RAD23B (p = 2.9 × 10-4), LDHB (p = 1.0 × 10-3), and HINT1 (p = 3.8 × 10-3) pathways were significantly downregulated in the recurrent cohort. On functional validation via immunohistochemistry (IHC) staining, 46.9% (PFN1), 71.9% (RAD23B), 59.4% (LDHB), and 84.4% (HINT1) of cases were corroborated with mass spectrometry findings. Development of a multilateral molecular signature incorporating these targets may characterize high-risk disease, predict treatment response, and augment current management paradigms in head and neck cancer.

Concussions and mild traumatic brain injury (m-TBI) have been identified as a consequential public health concern because of their potential to cause considerable impairments in physical, cognitive, behavioral, and social functions. Given their prominent structural and functional roles in the brain, n-3 polyunsaturated fatty acids (PUFA) have been identified as a potentially viable prophylactic agent that may ameliorate the deleterious effects of m-TBI on brain function. The purpose of the present pilot study was to investigate the effect of n-3 PUFA on neurologic function using a weight drop injury (WDI) model. Fat-1 mice, capable of synthesizing n-3 PUFA endogenously from n-6 PUFA, and their wild-type (WT) counterparts, were subjected to a mild low-impact WDI on the closed cranium, and recovery was evaluated using the neurological severity score (NSS) to assess the motor and neurobehavioral outcomes. In comparison to the WT mice, the fat-1 mice had a significantly (p ≤ 0.05) lower NSS at all time points post-WDI, and significantly greater neurological restoration measured as the time to first movement. Overall, these findings demonstrate the protective effect of n-3 PUFA against mild brain injury.

Many countries in sub-Saharan Africa have experienced lower COVID-19 caseloads and fewer deaths than countries in other regions worldwide. Under-reporting of cases and a younger population could partly account for these differences, but pre-existing immunity to coronaviruses is another potential factor. Blood samples from Sierra Leonean Lassa fever and Ebola survivors and their contacts collected before the first reported COVID-19 cases were assessed using enzyme-linked immunosorbent assays for the presence of antibodies binding to proteins of coronaviruses that infect humans. Results were compared to COVID-19 subjects and healthy blood donors from the United States. Prior to the pandemic, Sierra Leoneans had more frequent exposures than Americans to coronaviruses with epitopes that cross-react with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), SARS-CoV, and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). The percentage of Sierra Leoneans with antibodies reacting to seasonal coronaviruses was also higher than for American blood donors. Serological responses to coronaviruses by Sierra Leoneans did not differ by age or sex. Approximately a quarter of Sierra Leonian pre-pandemic blood samples had neutralizing antibodies against SARS-CoV-2 pseudovirus, while about a third neutralized MERS-CoV pseudovirus. Prior exposures to coronaviruses that induce cross-protective immunity may contribute to reduced COVID-19 cases and deaths in Sierra Leone.

Objectives Better indicators from affordable, sustainable data sources are needed to monitor population burden of musculoskeletal conditions. We propose five indicators of musculoskeletal health and assessed if routinely available primary care electronic health records (EHR) can estimate population levels in musculoskeletal consulters. Methods We collected validated patient-reported measures of pain experience, function and health status through a local survey of adults (≥35 years) presenting to English general practices over 12 months for low back pain, shoulder pain, osteoarthritis and other regional musculoskeletal disorders. Using EHR data we derived and validated models for estimating population levels of five self-reported indicators: prevalence of high impact chronic pain, overall musculoskeletal health (based on Musculoskeletal Health Questionnaire), quality of life (based on EuroQoL health utility measure), and prevalence of moderate-to-severe low back pain and moderate-to-severe shoulder pain. We applied models to a national EHR database (Clinical Practice Research Datalink) to obtain national estimates of each indicator for three successive years. Results The optimal models included recorded demographics, deprivation, consultation frequency, analgesic and antidepressant prescriptions, and multimorbidity. Applying models to national EHR, we estimated that 31.9% of adults (≥35 years) presenting with non-inflammatory musculoskeletal disorders in England in 2016/17 experienced high impact chronic pain. Estimated population health levels were worse in women, older aged and those in the most deprived neighbourhoods, and changed little over 3 years. Conclusion National and subnational estimates for a range of subjective indicators of non-inflammatory musculoskeletal health conditions can be obtained using information from routine electronic health records.

Mechanical ventilation is a potentially life-saving therapy for patients with acute lung injury, but the ventilator itself may cause lung injury. Ventilator-induced lung injury (VILI) is sometimes an unfortunate consequence of mechanical ventilation. It is not clear however how best to minimize VILI through adjustment of various parameters including tidal volume, plateau pressure, driving pressure, and positive end expiratory pressure (PEEP). No single parameter provides a clear indication for onset of lung injury attributable exclusively to the ventilator. There is currently interest in quantifying how static and dynamic parameters contribute to VILI. One concept that has emerged is the consideration of the amount of energy transferred from the ventilator to the respiratory system per unit time, which can be quantified as mechanical power. This review article reports on recent literature in this emerging field and future roles for mechanical power assessments in prospective studies.

BACKGROUND AND AIM: Socioeconomic and spatial patterning of personal exposure to air pollution have not been well documented in rural Chinese settings where household solid fuel use is still a majo...

It has been recognized that an integration of neuronal and genetic mechanisms supports brain function, regulates behaviour, and underpins response to environmental or disease stimuli. Several different technologies are available for imaging and studying neuronal activity in living brains, such as functional magnetic resonance imaging (fMRI), and have been translated to humans. However, the tools available to measure gene expression are destructive. Here we present a method, called epigenetic MRI (eMRI), that overcomes this limitation. eMRI achieves for the first time direct and noninvasive imaging of DNA methylation, a major gene expression regulator, in intact brains. eMRI exploits the methionine metabolic pathways that are responsible for DNA methylation to label the methyl-cytosine in brain genomic DNA through carbon-13 enriched diets. It then uses a novel carbon-13 magnetic resonance spectroscopic imaging (13C-MRSI) method to map the spatial distribution of labeled DNA. We demonstrated successful 13C labeling of brain DNA through diet using mass spectrometry, and robust and specific detection of labeled DNA using 13C-MRSI. We used eMRI and a biomedical piglet model to produce the first DNA methylation map of an intact brain hemisphere. With both noninvasive labeling and imaging, we expect eMRI to be readily translated to humans and thus enable many new investigations into the epigenetic basis of brain function, behavior, and disease.

Whole apples are a source of pectin and polyphenols, both of which show potential to modulate postprandial lipaemia (PPL). The present study aimed to explore the effects of whole apple consumption on PPL, as a risk factor for CVD, in generally healthy but overweight and obese adults. A randomised, crossover acute meal trial was conducted with seventeen women and nine men (mean BMI of 34·1 (sem 0·2) kg/m2). Blood samples were collected for 6 h after participants consumed an oral fat tolerance test meal that provided 1 g fat/kg body weight and 1500 mg acetaminophen per meal for estimating gastric emptying, with and without three whole raw Gala apples (approximately 200 g). Plasma TAG (with peak postprandial concentration as the primary outcome), apoB48, chylomicron-rich fraction particle size and fatty acid composition, glucose, insulin and acetaminophen were analysed. Differences between with and without apples were identified by ANCOVA. Apple consumption did not alter postprandial TAG response, chylomicron properties, glucose or acetaminophen (P > 0·05), but did lead to a higher apoB48 peak concentration and exaggerated insulin between 20 and 180 min (P < 0·05). Overall, as a complex food matrix, apples did not modulate postprandial TAG when consumed with a high-fat meal in overweight and obese adults, but did stimulate insulin secretion, potentially contributing to an increased TAG-rich lipoprotein production.