Effects of early-life exposure to Western diet and voluntary exercise on adult activity levels, exercise physiology, and associated traits in selectively bred High Runner mice.

Exercise behavior is under partial genetic control, but it is also affected by numerous environmental factors, potentially including early-life experiences whose effects persist into adulthood. We studied genetic and early-life environmental effects on wheel-running behavior in a mouse model that includes four replicate high runner (HR) lines selectively bred for increased voluntary wheel running as young adults and four non-selected control (C) lines. In a full factorial design, mice from each line were granted wheel access or not and administered either standard or Western diet (WD) from weaning (3 weeks old) to 6 weeks of age (sexual maturity). In addition to acute effects, after a washout period of 8 weeks (∼6 human years) in which all mice had standard diet and no wheel access, we found both beneficial and detrimental effects of these early-life exposures. During the first week of treatments, WD increased distance run by 29% in C mice and 48% in HR mice (significant Diet × Linetype interaction), but diet effects disappeared by the third week. Across the three weeks of juvenile treatment, WD significantly increased fat mass (with lean mass as a covariate). Tested as adults, early-life exercise increased wheel running of C mice but not HR mice in the first week. Early-life exercise also reduced adult anxiety-like behavior and increased adult fasted blood glucose levels, triceps surae mass, subdermal fat pad mass, and brain mass, but decreased heart ventricle mass. Using fat mass as a covariate, early-life exercise treatment increased adult leptin concentration. In contrast, early-life WD increased adult wheel running of HR mice but not C mice. Early-life WD also increased adult lean mass and adult preference for Western diet in all groups. Surprisingly, early-life treatment had no significant effect on adult body fat or maximal aerobic capacity (VO2max). No previous study has tested for combined or interactive effects of early-life WD and exercise. Our results demonstrate that both factors can have long-lasting effects on adult voluntary exercise and related phenotypes, and that these effects are modulated by genetic background. Overall, the long-lasting effects of early-life exercise were more pervasive than those of WD, suggesting critical opportunities for health intervention in childhood habits, as well as possible threats from modern challenges. These results may be relevant for understanding potential effects of activity reductions and dietary changes associated with the obesity epidemic and COVID-19 pandemic.

Pathway-Based Reduction of Repeat Head Computed Tomography for Patients With Complicated Mild Traumatic Brain Injury: Implementation and Outcomes.

BACKGROUND: Routine follow-up head imaging in complicated mild traumatic brain injury (cmTBI) patients has not been shown to alter treatment, improve outcomes, or identify patients in need of neurosurgical intervention. We developed a follow-up head computed tomography (CT) triage algorithm for cmTBI patients to decrease the number of routine follow-up head CT scans obtained in this population. OBJECTIVE: To report our experience with protocol implications and patient outcome. METHODS: Data on all cmTBI patients presenting from July 1, 2018 to June 31, 2019, to our level 1, tertiary, academic medical center were collected prospectively and analyzed retrospectively. Descriptive analysis was performed. RESULTS: Of the 178 patients enrolled, 52 (29%) received a follow-up head CT. A total of 27 patients (15%) were scanned because of initial presentation and triaged to the group to receive a routine follow-up head CT. A total of 151 patients (85%) were triaged to the group without routine follow-up head CT scan. Protocol adherence was 89% with 17 violations. CONCLUSION: Utilizing this protocol, we were able to safely decrease the use of routine follow-up head CT scans in cmTBI patients by 71% without any missed injuries or delayed surgery. Adoption of the protocol was high among all services managing TBI patients.

Chest computed tomography imaging utility for radiographically occult rib fractures in elderly fall-injured patients.

BACKGROUND: Previous studies demonstrate an association between rib fractures and morbidity and mortality in trauma. This relationship in low-mechanism injuries, such as ground-level fall, is less clearly defined. Furthermore, computed tomography (CT) has increased sensitivity for rib fractures compared with chest x-ray (CXR); its utility in elderly fall patients is unknown. We sought to determine whether CT-diagnosed rib fractures in elderly fall patients with a normal CXR were associated with increased in-hospital resource utilization or mortality. METHODS: Retrospective analysis of emergency department patients presenting over a 3-year period. INCLUSION CRITERIA: age, 65 years or older; chief complaint, including mechanical fall; and both CXR and CT obtained. We quantified rib fractures on CXR and CT and reported operating characteristics for both. Outcomes of interest included hospital admission/length of stay (LOS), intensive care unit (ICU) admission/LOS, endotracheal intubation, tube thoracostomy, locoregional anesthesia, pneumonia, in-hospital mortality. RESULTS: We identified 330 patients, mean age was 84 years (±SD, 9.4 years); 269 (82%) of 330 were admitted. There were 96 (29%) patients with CT-diagnosed rib fracture, 56 (17%) by CT only. Compared with CT, CXR had a sensitivity of 40% (95% confidence interval, 30-50%) and specificity of 99% (95% confidence interval, 97-100%) for rib fracture. A median of two additional radiographically occult rib fractures were identified on CT. Despite an increased hospital admission rate (91% vs. 78%) p = 0.02, there was no difference between patients with and without radiographically occult (CT+ CXR-) rib fracture(s) for: median LOS (4; interquartile range (IQR) 2-7 vs 4, IQR 2-8); p = 0.92), ICU admission (28% vs. 27%) p = 0.62, median ICU LOS (2, IQR 1-8 vs 3, IQR 1-5) p = 0.54, or in-hospital mortality (10.3% vs. 7.3%) p = 0.45. CONCLUSION: Among elderly fall patients, CT-identified rib fractures were associated with increased hospital admissions. However, there was no difference in procedural interventions, ICU admission, hospital/ICU LOS or mortality for patients with and without radiographically occult fractures. LEVEL OF EVIDENCE: Diagnostic, level III.

Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior.

Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 µg/mL corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO2max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO2max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were "negative" from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant.

Maternal exposure to Western diet affects adult body composition and voluntary wheel running in a genotype-specific manner in mice.

Some human diseases, including obesity, Type II diabetes, and numerous cancers, are thought to be influenced by environments experienced in early life, including in utero. Maternal diet during the perinatal period may be especially important for adult offspring energy balance, potentially affecting both body composition and physical activity. This effect may be mediated by the genetic background of individuals, including, for example, potential "protective" mechanisms for individuals with inherently high levels of physical activity or high basal metabolic rates. To examine some of the genetic and environmental factors that influence adult activity levels, we used an ongoing selection experiment with 4 replicate lines of mice bred for high voluntary wheel running (HR) and 4 replicate, non-selected control lines (C). Dams (half HR and half C) were fed a "Western" diet (WD, high in fat and sucrose) or a standard diet (SD) from 2weeks prior to mating until their pups could feed on solid food (14days of age). We analyzed dam and litter characteristics from birth to weaning, and offspring mass and physical activity into adulthood. One male offspring from each litter received additional metabolic and behavioral tests. Maternal WD caused pups to eat solid food significantly earlier for C litters, but not for HR litters (interaction of maternal environment and genotype). With dam mass as a covariate, mean pup mass was increased by maternal WD but litter size was unaffected. HR dams had larger litters and tended to have smaller pups than C dams. Home-cage activity of juvenile focal males was increased by maternal WD. Juvenile lean mass, fat mass, and fat percent were also increased by maternal WD, but food consumption (with body mass as a covariate) was unaffected (measured only for focal males). Behavior in an elevated plus maze, often used to indicate anxiety, was unaffected by maternal WD. Maximal aerobic capacity (VO2max) was also unaffected by maternal WD, but HR had higher VO2max than C mice. Adult lean, fat, and total body masses were significantly increased by maternal WD, with greater increase for fat than for lean mass. Overall, no aspect of adult wheel running (total distance, duration, average running speed, maximum speed) or home-cage activity was statistically affected by maternal WD. However, analysis of the 8 individual lines revealed that maternal WD significantly increased wheel running in one of the 4 HR lines. On average, all groups lost fat mass after 6days of voluntary wheel running, but the absolute amount lost was greater for mice with maternal WD resulting in no effect of maternal WD on absolute or % body fat after wheel access. All groups gained lean and total body mass during wheel access, regardless of maternal WD or linetype. Measured after wheel access, circulating leptin, adiponectin, and corticosterone concentrations were unaffected by maternal WD and did not differ between HR and C mice. With body mass as a covariate, heart ventricle mass was increased by maternal WD in both HR and C mice, but fat pads, liver, spleen, and brain masses were unaffected. As found previously, HR mice had larger brains than C mice. Body mass of grand-offspring was unaffected by grand-maternal WD, but grand-offspring wheel running was significantly increased for one HR line and decreased for another HR line by grand-maternal WD. In summary, maternal Western diet had long-lasting and general effects on offspring adult morphology, but effects on adult behavior were limited and contingent on sex and genetic background.

Bedside sonography for the diagnosis of esophageal food impaction.

BACKGROUND: Esophageal foreign body (EFB) and impaction are common gastrointestinal emergencies. Detection with standard imaging can be challenging. Computed tomography is a commonly used non-invasive imaging modality, but is not 100% sensitive and not always feasible. Sensitivity of plain film x-ray varies widely and the addition of a barium swallow can obscure evaluation by subsequent esophagogastroduodenoscopy (EGD). Use of emergency ultrasound (EUS) for detection of EFB in adults has not been previously studied. OBJECTIVE: To evaluate the role of EUS in detection of EFB and to characterize sonographic findings. METHODS: A case control series of five patients with clinical suspicion of EFB underwent EUS, and findings were compared to five healthy controls. Patients were evaluated for persistent air-fluid levels after swallowing, esophageal dilatation, and visualization of EFB. RESULTS: All patients with suspected EFB had esophageal dilatation (17.5mm vs 9.3mm in healthy controls; p=0.0011) and persistent air-fluid levels after swallowing. EFB was visualized on EUS in 60% of patients. All patients had EFB confirmed on EGD except one, who vomited a significant food bolus during EUS and prior to EGD. CONCLUSION: In patients with suspected EFB, point-of-care ultrasound may identify those with impaction. Suggestive findings include cervical esophageal dilatation and persistent intraluminal air-fluid levels after swallowing. EUS is a rapid, convenient test with the potential to expedite definitive management while decreasing cost and radiation exposure in this patient population.

Acute Nontraumatic Back Pain: Risk Stratification, Emergency Department Management, and Review of Serious Pathologies.

Acute back pain is a common presenting complaint in the emergency department that leads to a great deal of resource utilization. The differential diagnosis is long and most cases are caused by benign pathology that will resolve on its own. Imaging is over-used and rarely helps. This article presents an algorithmic approach using red flags in the history and physical examination that will help physicians better identify the small of patients with serious conditions that, if untreated, will result in significant neurological damage.

Real-time optic nerve sheath diameter reduction measured with bedside ultrasound after therapeutic lumbar puncture in a patient with idiopathic intracranial hypertension.

Idiopathic intracranial hypertension (IIH), also referred to as pseudotumor cerebri, is a condition of raised intracranial pressure (ICP) with unknown etiology. Sonographic measurement of optic nerve sheath diameter (ONSD) has been shown to be a reliable, noninvasive method to characterize elevated ICP in a variety of settings. However, little is known about the immediate response of ONSD to an acute reduction in ICP after lumbar puncture. We describe a case of an emergency department patient with IIH in whom we identified real-time change in ONSD correlated with a decrease in cerebrospinal fluid pressure after a therapeutic lumbar puncture. Ocular ultrasound and ONSD measurements were performed by a trained provider using a 9- to 13-MHz linear transducer and an ultrasound machine with ocular software package and low mechanical index settings for data collection (MTurbo; SonoSite Inc, Bothell, WA). The ONSD was measured 30 minutes prior to and 30 minutes after a therapeutic lumbar puncture. Opening and closing pressures were recorded. Optic nerve sheath diameter measurements correlated with ICP as measured by opening and closing lumbar puncture pressures and showed an acute reduction in ONSD within 30 minutes after lumbar puncture. Sonographic measurement of ONSD reduction may be a novel, noninvasive and convenient way to follow acute reductions in ICP. Further investigation is necessary in order to validate this finding.