Characterizing the effects of muscle-specific GSK3α/ß reduction on murine muscle contractility and metabolism in female mice.

Dysregulation of skeletal muscle morphology and metabolism is associated with chronic diseases such as obesity and type 2 diabetes. The enzyme glycogen synthase kinase 3 (GSK3) is highly involved in skeletal muscle physiology and metabolism, acting as a negative regulator of muscle size, strength, adaptive thermogenesis, and glucose homeostasis. Correspondingly, we have shown that partial knockdown (∼40%) of GSK3 specifically in skeletal muscle increases lean mass, reduces fat mass, and activates muscle-based adaptive thermogenesis via sarco(endo)plasmic reticulum Ca2+ (SERCA) uncoupling in male mice. However, the effects of GSK3 knockdown in female mice have yet to be investigated. Here, we examined the effects of muscle-specific GSK3 knockdown on body composition, muscle size and strength, and whole body metabolism in female C57BL/6J mice. Our results show that GSK3 content is higher in the female soleus versus the male soleus; however, there were no differences in the extensor digitorum longus (EDL). Furthermore, muscle-specific GSK3 knockdown did not alter body composition in female mice, nor did it alter daily energy expenditure, glucose/insulin tolerance, mitochondrial respiration, or the expression of the SERCA uncouplers sarcolipin and neuronatin. We also did not find any differences in soleus muscle size, strength, or fatigue resistance. In the EDL, we found that an increase in absolute and specific force production, but there were no differences in fatigability. Therefore, our study highlights sex differences in the response to genetic reduction of gsk3, with most of the effects previously observed in male mice being absent in females.NEW & NOTEWORTHY Here we show that partial GSK3 knockdown has minimal effects on whole body metabolism and muscle contractility in female mice. This is partly inconsistent with previous results found in male mice, which reveal a potential influence of biological sex.

Infant Modified Constraint-Induced Movement Therapy Paired With Neuromuscular Electrical Stimulation: A Feasibility Study.

PURPOSE: To determine the feasibility of modified constraint-induced movement therapy (mCIMT) paired with neuromuscular electrical stimulation (NMES) for infants with asymmetrical hand function (AHF). METHODS: Five infants received an experimental ABA design: (A1) 3 weeks of our Standard AHF Care, (B) 3 weeks mCIMT-NMES, and (A2) 3 weeks of our Standard AHF Care. Parents tracked key data in a daily log, and infants were assessed 4 times using the Hand Assessment for Infants and Peabody Developmental Motor Scale-2. RESULTS: There was a high level of participant enrollment, visit frequency adherence, and compliance with the treatment protocol. No adverse events were reported. Mean Hand Assessment for Infants Both Hands measure scores changed more after mCIMT-NMES than after our Standard AHF Care. CONCLUSIONS: mCIMT-NMES is a feasible early intervention for infants with AHF at risk for unilateral cerebral palsy. A future study in a larger sample should examine the efficacy of mCIMT-NMES in this population.

Low-dose lithium supplementation promotes adipose tissue browning and sarco(endo)plasmic reticulum Ca2+ ATPase uncoupling in muscle.

Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) uncoupling in skeletal muscle and mitochondrial uncoupling via uncoupling protein 1 (UCP1) in brown/beige adipose tissue are two mechanisms implicated in energy expenditure. Here, we investigated the effects of glycogen synthase kinase 3 (GSK3) inhibition via lithium chloride (LiCl) treatment on SERCA uncoupling in skeletal muscle and UCP1 expression in adipose. C2C12 and 3T3-L1 cells treated with LiCl had increased SERCA uncoupling and UCP1 protein levels, respectively, ultimately raising cellular respiration; however, this was only observed when LiCl treatment occurred throughout differentiation. In vivo, LiCl treatment (10 mg/kg/day) increased food intake in chow-fed diet and high-fat diet (HFD; 60% kcal)-fed male mice without increasing body mass-a result attributed to elevated daily energy expenditure. In soleus muscle, we determined that LiCl treatment promoted SERCA uncoupling via increased expression of SERCA uncouplers, sarcolipin and/or neuronatin, under chow-fed and HFD-fed conditions. We attribute these effects to the GSK3 inhibition observed with LiCl treatment as partial muscle-specific GSK3 knockdown produced similar effects. In adipose, LiCl treatment inhibited GSK3 in inguinal white adipose tissue (iWAT) but not in brown adipose tissue under chow-fed conditions, which led to an increase in UCP1 in iWAT and a beiging-like effect with a multilocular phenotype. We did not observe this beiging-like effect and increase in UCP1 in mice fed a HFD, as LiCl could not overcome the ensuing overactivation of GSK3. Nonetheless, our study establishes novel regulatory links between GSK3 and SERCA uncoupling in muscle and GSK3 and UCP1 and beiging in iWAT.

Memory impairment in the D2.mdx mouse model of Duchenne muscular dystrophy is prevented by the adiponectin receptor agonist ALY688.

NEW FINDINGS: What is the central question of this study? Can adiponectin receptor agonism improve recognition memory in a mouse model of Duchenne muscular dystrophy? What is the main finding and its importance? Short-term treatment with the new adiponectin receptor agonist ALY688 improves recognition memory in D2.mdx mice. This finding suggests that further investigation into adiponectin receptor agonism is warranted, given that there remains an unmet need for clinical approaches to treat this cognitive dysfunction in people with Duchenne muscular dystrophy. ABSTRACT: Memory impairments have been well documented in people with Duchenne muscular dystrophy (DMD). However, the underlying mechanisms are poorly understood, and there is an unmet need to develop new therapies to treat this condition. Using a novel object recognition test, we show that recognition memory impairments in D2.mdx mice are completely prevented by daily treatment with the new adiponectin receptor agonist ALY688 from day 7 to 28 of age. In comparison to age-matched wild-type mice, untreated D2.mdx mice demonstrated lower hippocampal mitochondrial respiration (carbohydrate substrate), greater serum interleukin-6 cytokine content and greater hippocampal total tau and Raptor protein contents. Each of these measures was partly or fully preserved after treatment with ALY688. Collectively, these results indicate that adiponectin receptor agonism improves recognition memory in young D2.mdx mice.

Declining Rates of Legg-Calvé-Perthes Surgery in the United States: National Trends Using the Kids' Inpatient Database and Pediatric Health Information System.

BACKGROUND: In 2004 and 2008 two large prospective, multicenter studies were published which resulted in improved understanding of operative indications for the treatment of Legg-Calvé-Perthes disease (LCPD) based on patient age, disease severity, and resultant radiographic outcomes. The primary aim of this study is to evaluate the trends in surgical management of LCPD in the United States prior, and subsequent to, the publication of these landmark studies. METHODS: Cross-sectional retrospective analysis of US pediatric hospitalizations for the surgical management of LCPD was conducted using the Kids' Inpatient Database from 2000 to 2016. Patients 12 years of age and younger were included who had a primary admission diagnosis of LCPD and a LCPD-related procedure during the hospitalization. Data was subsequently weighted to produce national-level estimates and variables pertaining to patient age group, procedure, demographics, and hospital characteristics were analyzed. In a post hoc analysis, the results of the Kids' Inpatient Database were also corroborated with the Pediatric Health Information System database. RESULTS: A weighted sample of 2786 LCPD surgical admissions met inclusion and exclusion criteria; 11.2% of surgical admissions were patients below 6 years of age, 35.9% were 6 to 8 years of age, and 52.9% were above 8 years of age. There was a significant decrease in admissions for surgical management of LCPD in all age groups over time, however there was no appreciable change in the proportion of LCPD surgical admissions performed among the above 8 to below 12, above 6 to below 8, or below 6 years age groups. Femoral osteotomy remained the most common surgical procedure, while other osteotomy types, including pelvic and unspecified osteotomies involving the hip, decreased over time ( P <0.001). CONCLUSIONS: There is a decreasing rate of hospital admissions for LCPD surgery since 2000, perhaps indicating a decline in incidence of disease. Furthermore, despite evidence supporting LCPD surgical outcomes related to patient age, there has been no change in the proportion of patients undergoing surgery by age group over time. LEVEL OF EVIDENCE: Level III-retrospective study.

Postexercise serum from humans influences the biological tug of war of APP processing in human neuronal cells.

Neurodegenerative diseases such as Alzheimer's disease (AD) are becoming more prevalent in our aging society. One specific neuropathological hallmark of this disease is the accumulation of amyloid-ß (Aß) peptides, which aggregate to form extraneuronal plaques. Increased Aß peptides are often observed well before symptoms of AD develop, highlighting the importance of targeting Aß-producing pathways early on in disease progression. Evidence indicates that exercise has the capacity to reduce Aß peptide production in the brain; however, the mechanisms remain unknown. Exercise-induced signaling mediators could be the driving force behind some of the beneficial effects observed in the brain with exercise. The purpose of this study was to examine if postexercise serum and the factors it contains can alter neuronal amyloid precursor protein (APP) processing. Human SH-SY5Y neuronal cells were differentiated with retinoic acid for 5 days and treated with 10% pre- or postexercise serum from humans for 30 min. Cells were collected for analysis of acute (30 min; n = 6) or adaptive (24 h posttreatment; n = 6) responses. There were no statistical differences in a disintegrin and metalloproteinase 10 (ADAM10) and ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) mRNA or protein expression with postexercise serum treatment at either time point. However, there was an increase in the ratio of soluble amyloid precursor protein α (sAPPα) to soluble amyloid precursor protein ß (sAPPß) protein content (P = 0.05) after 30 min of postexercise serum treatment. In addition, 30 min of postexercise serum treatment increased ADAM10 (P = 0.01) and BACE1 (P = 0.02) activity. These findings suggest that postexercise serum modulates important enzymes involved in APP processing, potentially pushing the cascade toward the nonamyloidogenic arm.

Regionalization of Isolated Pediatric Femur Fracture Treatment: Recent Trends Observed Using the Kids' Inpatient Database.

BACKGROUND: Isolated pediatric femur fractures have historically been treated at local hospitals. Pediatric referral patterns have changed in recent years, diverting patients to high volume centers. The purpose of this investigation was to assess the treatment location of isolated pediatric femur fractures and concomitant trends in length of stay and cost of treatment. METHODS: A cross-sectional analysis of surgical admissions for femoral shaft fracture was performed using the 2000 to 2012 Kids' Inpatient Database. The primary outcome was hospital location and teaching status. Secondary outcomes included the length of stay and mean hospital charges. Polytrauma patients were excluded. Data were weighted within each study year to produce national estimates. RESULTS: A total of 35,205 pediatric femoral fracture cases met the inclusion criteria. There was a significant shift in the treatment location over time. In 2000, 60.1% of fractures were treated at urban, teaching hospitals increasing to 81.8% in 2012 (P<0.001). Mean length of stay for all hospitals decreased from 2.59 to 1.91 days (P<0.001). Inflation-adjusted total charges increased during the study from $9499 in 2000 to $25,499 in 2012 per episode of treatment (P<0.001). Total charges per hospitalization were ∼$8000 greater at urban, teaching hospitals in 2012. CONCLUSIONS: Treatment of isolated pediatric femoral fractures is regionalizing to urban, teaching hospitals. Length of stay has decreased across all institutions. However, the cost of treatment is significantly greater at urban institutions relative to rural hospitals. This trend does not consider patient outcomes but the observed pattern appears to have financial implications. LEVEL OF EVIDENCE: Level III-case series, database study.

Hippotherapy in Rehabilitation Care for Children With Neurological Impairments and Developmental Delays: A Case Series.

PURPOSE: This report assesses functional mobility in children with neurological impairments and documented gross motor delays, before and after receiving either hippotherapy or standard outpatient physical therapy (PT). SUMMARY OF KEY POINTS: This is a case-series report using data previously collected for a discontinued randomized controlled trial, in which participants received hippotherapy or standard outpatient clinic PT for a 12-week treatment period. Results demonstrated both subjective and objective functional mobility improvements after treatment in participants receiving hippotherapy and standard outpatient PT, as determined by the Peabody Developmental Motor Scales-2, the Pediatric Evaluation of Disability Inventory, and the Goal Attainment Scaling. STATEMENT OF CONCLUSION AND RECOMMENDATIONS FOR CLINICAL PRACTICE:: When compared with standard outpatient PT, hippotherapy appears to be a viable treatment strategy for children aged 2 to 5 years with neurological impairments and gross motor delays, but additional research in this area is needed to validate findings.

Hybrid long-range hyperbolic phonon polariton waveguide using hexagonal boron nitride for mid-infrared subwavelength confinement.

Long propagation waveguides are critical for any photonic-on-chip applications. There has been an extensive investigation in using plasmon polaritons for near-infrared and optical networks, however, for mid- to long-wave IR applications phonon polaritons are required given that plasmonic polaritonic effects are negligible. In recent years, extensive research has been conducted on hexagonal boron nitride (h-BN), which has shown h-BN to have naturally occurring subwavelength, volumetrically confined hyperbolic phonon polaritons (HPhPs). This work presents numerical results for both long- and short-range phononic volumetric polariton modes in a slab of h-BN. A hybrid long-range phononic waveguide consisting of two identical dielectric cylinder wires symmetrically placed on each side of the h-BN slab is coupled to the long-range HPhP mode. Based on analytical coupled-mode theory and computational finite element analysis, we have investigated the modal characteristics of the hybrid long-range phonon polaritonic waveguide. Due to the strong coupling between the high index cylindrical-waveguide mode and the HPhPs in the h-BN thin film, subwavelength confinement can be achieved (modal area ranging from  10-2λo2 to  10-1λo2) while enabling long propagation distances (7λ0-370λ0).

Nationally Representative Readmission Factors Associated with Endovascular versus Open Repair of Abdominal Aortic Aneurysm.

BACKGROUND: Hospital readmissions are tied to financial penalties and thus significantly influence health-care policy. Many current studies on readmissions lack national representation by not tracking readmissions across hospitals. The recently released Nationwide Readmission Database is one of the most comprehensive national sources of readmission data available, making it an invaluable resource to understand this critically important health policy issue. METHODS: The Nationwide Readmission Database for 2013 and 2014 was queried for adult patients with abdominal aortic aneurysm (441.4) undergoing endovascular (39.71) or open (38.44) repair. Outcomes examined were overall/initial admission mortality and overall/30-day readmissions. Multivariate logistic regression for these outcomes was also performed on multiple readmission factors. RESULTS: Fifty-three thousand four hundred seventeen patients underwent abdominal aortic aneurysm repair (47,431 endovascular aortic repair [EVAR] versus 5,986 open surgical repair [OSR]). Significant differences were found for EVAR versus OSR on overall readmissions, initial admission cost, readmission costs, length of stay, days to readmission, and overall/initial admission mortality. Multivariate logistic regression analysis found that length of stay > 30, Charlson Comorbidity Index > 1, discharge disposition, and female sex were all significant predictors of 30-day readmission. Repair type was significantly associated with 30-day readmissions; however, it was not a significant factor for overall readmissions. CONCLUSION: There are significant differences in costs, prognosis, and readmission rates for EVAR versus OSR. Given that these differences are being used to create "acceptable" readmission rates, disbursement quotas among hospitals, and subsequent penalties for providers outside the expected rates, it is only prudent to obtain the most accurate information to guide those policies. LEVEL OF EVIDENCE: Care management/epidemiological, level IV.

DICER1-related Sertoli-Leydig cell tumor and gynandroblastoma: Clinical and genetic findings from the International Ovarian and Testicular Stromal Tumor Registry.

BACKGROUND: Ovarian sex cord-stromal tumors (OSCST) include juvenile granulosa cell tumors (JGCT), Sertoli-Leydig cell tumor (SLCT) and gynandroblastoma (GAB) among others. These ovarian sex cord-stromal tumors as well as other tumors including pleuropulmonary blastoma (PPB) may be associated with DICER1 mutations. We sought to describe the clinical and genetic findings from the first 107 individuals enrolled in the International Ovarian and Testicular Stromal Tumor Registry. METHODS: Medical and family history were obtained for individuals consecutively enrolled in the International Ovarian and Testicular Stromal Tumor Registry. Pathology was centrally reviewed. DICER1 sequencing was performed on blood and tumor tissue. RESULTS: Of the 107 participants, 49 had SLCT, 25 had JGCT and 5 had GAB. Nearly all (36/37) SLCTs and 4/4 GAB tested had a DICER1 mutation in an RNase IIIb domain hotspot; approximately half of these individuals had a predisposing germline DICER1 mutation. Metachronous SLCTs were seen in 3 individuals with germline DICER1 mutations. Other DICER1-associated conditions were seen in 19% of patients with SLCT or GAB. Three children of women with SLCT were diagnosed with PPB based on genetic testing and clinical screening during the course of this study. All were diagnosed with PPB in its earliest and most curable form (Type I), were treated with surgery alone, and are alive without evidence of disease. CONCLUSIONS: Recognition of the distinct genetic basis for a group of these tumors improves precise classification in difficult cases and promotes mutation-based screening and early detection.

Acceptability, Adaptation, and Clinical Outcomes of Acupuncture Provided in the Emergency Department: A Retrospective Pilot Study.

Objective: To evaluate acceptability and clinical outcomes of acupuncture on patient-reported pain and anxiety in an emergency department (ED). Design: Observational, retrospective pilot study. Setting: Abbott Northwestern Hospital ED, Minneapolis, MN. Methods: Retrospective data was used to identify patients receiving acupuncture in addition to standard medical care in the ED between 11/1/13 and 12/31/14. Feasibility was measured by quantifying the utilization of acupuncture in a novel setting and performing limited tests of its efficacy. Patient-reported pain and anxiety scores were collected by the acupuncturist using an 11-point (0-10) numeric rating scale before (pre) and immediately after (post) acupuncture. Efficacy outcomes were change in pain and anxiety scores. Results: During the study period, 436 patients were referred for acupuncture, 279 of whom were approached by the acupuncturist during their ED visit. Consent for acupuncture was obtained from 89% (248/279). A total of 182 patients, who had a pre-pain score >0 and non-missing anxiety scores, were included in analyses. Of the 52% (94/182) who did not have analgesics before or during the acupuncture session, the average decrease of 2.37 points (95% CI: 1.92, 2.83) was not different (p > 0.05) than the mean decrease of 2.68 points for those receiving analgesics (95% CI 2.21, 3.15). The average pre-anxiety score was 4.73 points (SD = 3.43) and the mean decrease was 2.27 points (95% CI: 1.89, 2.66). Conclusions: Results from this observational trial indicate that acupuncture was acceptable and effective for pain and anxiety reduction, in conjunction with standard medical care. These results will inform future randomized trials.

Acupuncture provides short-term pain relief for patients in a total joint replacement program.

OBJECTIVE: Given the risks of opioid medications, nonpharmacological strategies should be considered for total joint replacement patients. We investigated acupuncture as an adjunct therapy for postsurgical pain management in a total joint replacement program by examining which total hip and knee replacement patients elected to receive acupuncture and the effect of acupuncture on short-term pain. DESIGN: A total joint replacement program using fast-track physiotherapy offered elective postsurgical acupuncture to all patients, at no additional cost, as an adjunct therapy to opioids for pain management. SETTING: The Joint Replacement Center at Abbott Northwestern Hospital, a 630-bed teaching and specialty hospital in Minneapolis, Minnesota from 2010 to 2012. SUBJECTS: Our sample included 2,500 admissions of total hip (THR) and total knee replacement (TKR) patients. METHODS: Self-reported pain was assessed before and after acupuncture using a 0-10 scale and categorized as none/mild (0-4) and moderate/severe pain (5-10). RESULTS: Seventy-five percent of admissions included acupuncture. Women (Odds Ratio: 1.48, 95% Confidence Interval (CI): 1.22, 1.81) had higher odds of receiving acupuncture compared to men, and nonwhite patients (Odds Ratio: 0.55, 95% CI: 0.39, 0.78) had lower odds of receiving acupuncture compared to white patients. Average short-term pain reduction was 1.91 points (95% CI: 1.83, 1.99), a 45% reduction from the mean prepain score. Forty-one percent of patients reported moderate/severe pain prior to receiving acupuncture, while only 15% indicated moderate/severe pain after acupuncture. CONCLUSIONS: Acupuncture may be a viable adjunct to pharmacological approaches for pain management after THR or TKR.

The effectiveness of integrative medicine interventions on pain and anxiety in cardiovascular inpatients: a practice-based research evaluation.

BACKGROUND: Pain and anxiety occurring from cardiovascular disease are associated with long-term health risks. Integrative medicine (IM) therapies reduce pain and anxiety in small samples of hospitalized cardiovascular patients within randomized controlled trials; however, practice-based effectiveness research has been limited. The goal of the study is to evaluate the effectiveness of IM interventions (i.e., bodywork, mind-body and energy therapies, and traditional Chinese medicine) on pain and anxiety measures across a cardiovascular population. METHODS: Retrospective data obtained from medical records identified patients with a cardiovascular ICD-9 code admitted to a large Midwestern hospital between 7/1/2009 and 12/31/2012. Outcomes were changes in patient-reported pain and anxiety, rated before and after IM treatments based on a numeric scale (0-10). RESULTS: Of 57,295 hospital cardiovascular admissions, 6,589 (11.5%) included IM. After receiving IM therapy, patients averaged a 46.5% (p-value < 0.001) decrease in pain and a 54.8% (p-value < 0.001) decrease in anxiety. There was no difference between treatment modalities on pain reduction; however, mind-body and energy therapies (p-value < 0.01), traditional Chinese medicine (p-value < 0.05), and combination therapies (p-value < 0.01) were more effective at reducing anxiety than bodywork therapies. Each additional year of age reduced the odds of receiving any IM therapy by two percent (OR: 0.98, p-value < 0.01) and females had 96% (OR: 1.96, p-value < 0.01) higher odds of receiving any IM therapy compared to males. CONCLUSIONS: Cardiovascular inpatients reported statistically significant decreases in pain and anxiety following care with adjunctive IM interventions. This study underscores the potential for future practice-based research to investigate the best approach for incorporating these therapies into an acute care setting such that IM therapies are most appropriately provided to patient populations.

Reduction of Antibiotic-Associated Conditions After Tympanostomy Tube Placement in Children.

OBJECTIVE: Tympanostomy tube placement has been shown to decrease systemic antibiotics usage in patients with recurrent acute otitis media. Systemic antibiotics in children are associated with an increase in antibiotic-associated conditions (asthma, allergic rhinitis, food allergy, atopic dermatitis, celiac disease, overweight/obesity, attention-deficit hyperactivity disorder [ADHD], autism, learning disability, and Clostridium difficile colonization) later in life. The objective of this study is to estimate whether tympanostomy tube placement is associated with a reduction in antibiotic-associated conditions in children with recurrent acute otitis media (RAOM). METHODS: A retrospective cohort review of electronic medical records from 1991 to 2011 at a large pediatric hospital system was performed identifying 27,584 patients under 18 years old with RAOM, defined by 3 or more episodes of AOM. Antibiotic-associated conditions were defined using ICD-9 and ICD-10 codes. RESULTS: The enrollment population was largely composed of White patients (28.9%), Black patients (30.1%), and Hispanic/Latino patients (16.4%). The number of systemic antibiotics prescribed per encounter was significantly lower in children who pursued tympanostomy tubes (0.14 antibiotics per encounter) versus those who did not (0.23 antibiotics per encounter) (p < 0.001). Patients with RAOM who received tympanostomy tubes were less likely to have diagnoses of overweight/obesity (OR. 0.62 [0.55, 0.68]; p < 0.001), asthma (OR 0.8 [0.74, 0.87]; p < 0.001), allergic rhinitis (OR 0.72 [0.65, 0.81]; p < 0.001), and atopic dermatitis (0.78 [0.71, 0.86]; p < 0.001). CONCLUSIONS AND RELEVANCE: Tympanostomy tube placement is associated with less systemic antibiotic administration and a decreased incidence of overweight/obesity, asthma, allergic rhinitis, and atopic dermatitis in children diagnosed with RAOM. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Nightmare on CIL Street: A Simulation Series to Increase Confidence and Skill in Responding to Clinical Emergencies.

Background: The Central Texas Veterans Health Care System (CTVHCS) in Temple, a 189-bed teaching hospital, recently opened its Center for Innovation and Learning for simulation-based learning. CTVHCS built a rapid response simulation curriculum to improve preparedness for internal medicine residents, medical students, and physician assistant students that exploits newly developed medical education technology. Observations: The Center for Innovation and Learning curriculum was created based on the most common rapid response calls received over the previous 3 years. Cardiac, respiratory, and neurological simulations were implemented. Learners approach each scenario as if they were on night service alone without specialist help. Learners must identify tachyarrhythmia, impending respiratory failure, and a patient with encephalopathy requiring transfer. Conclusions: Sixteen learners were surveyed before the simulation and after addressing each educational objective was completed and showed improvement. Educating trainees on rapid response scenarios by using a simulation curriculum provides many benefits. Trainees reported improvement in addressing cardiac, respiratory, and neurological rapid response scenarios after experiencing the simulation.

Acute interleukin-6 modulates key enzymes involved in prefrontal cortex and hippocampal amyloid precursor protein processing.

Exercise has been shown to be beneficial for individuals with Alzheimer's disease (AD). In rodent models of AD, exercise decreases the amyloidogenic processing of the amyloid precursor protein (APP). Although it remains unclear as to how exercise is promoting this shift away from pathological APP processing, there is emerging evidence that exercise-induced factors released from peripheral tissues may facilitate these alterations in brain APP processing. Interleukin-6 (IL-6) is released from multiple organs into peripheral circulation during exercise and is among the most characterized exerkines. The purpose of this study is to examine whether acute IL-6 can modulate key enzymes responsible for APP processing, namely, a disintegrin and metalloproteinase 10 (ADAM10) and ß-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which initiate the nonamyloidogenic and amyloidogenic cascades, respectively. Male 10-wk-old C57BL/6J mice underwent acute treadmill exercise bout or were injected with either IL-6 or a PBS control 15 min prior to tissue collection. ADAM10 and BACE1 enzyme activity, mRNA, and protein expression, as well as downstream markers of both cascades, including soluble APPα (sAPPα) and soluble APPß (sAPPß), were examined. Exercise increased circulating IL-6 and brain IL-6 signaling (pSTAT3 and Socs3 mRNA). This occurred alongside a reduction in BACE1 activity and an increase in ADAM10 activity. IL-6 injection reduced BACE1 activity and increased sAPPα protein content in the prefrontal cortex. In the hippocampus, IL-6 injection decreased BACE1 activity and sAPPß protein content. Our results show that acute IL-6 injection increases markers of the nonamyloidogenic cascade and decreases markers of the amyloidogenic cascade in the cortex and hippocampus of the brain.NEW & NOTEWORTHY It is becoming evident that exercise modulates APP processing and can reduce amyloid-beta (Aß) peptide production. Our data help to explain this phenomenon by highlighting IL-6 as an exercise-induced factor that lowers pathological APP processing. These results also highlight brain regional differences in response to acute IL-6.