An RNA degradation machine sculpted by Ro autoantigen and noncoding RNA.

Many bacteria contain an ortholog of the Ro autoantigen, a ring-shaped protein that binds noncoding RNAs (ncRNAs) called Y RNAs. In the only studied bacterium, Deinococcus radiodurans, the Ro ortholog Rsr functions in heat-stress-induced ribosomal RNA (rRNA) maturation and starvation-induced rRNA decay. However, the mechanism by which this conserved protein and its associated ncRNAs act has been obscure. We report that Rsr and the exoribonuclease polynucleotide phosphorylase (PNPase) form an RNA degradation machine that is scaffolded by Y RNA. Single-particle electron microscopy, followed by docking of atomic models into the reconstruction, suggests that Rsr channels single-stranded RNA into the PNPase cavity. Biochemical assays reveal that Rsr and Y RNA adapt PNPase for effective degradation of structured RNAs. A Ro ortholog and ncRNA also associate with PNPase in Salmonella Typhimurium. Our studies identify another ribonucleoprotein machine and demonstrate that ncRNA, by tethering a protein cofactor, can alter the substrate specificity of an enzyme.

Population genomics and geographic dispersal in Chagas disease vectors: Landscape drivers and evidence of possible adaptation to the domestic setting.

Accurate prediction of vectors dispersal, as well as identification of adaptations that allow blood-feeding vectors to thrive in built environments, are a basis for effective disease control. Here we adopted a landscape genomics approach to assay gene flow, possible local adaptation, and drivers of population structure in Rhodnius ecuadoriensis, an important vector of Chagas disease. We used a reduced-representation sequencing technique (2b-RADseq) to obtain 2,552 SNP markers across 272 R. ecuadoriensis samples from 25 collection sites in southern Ecuador. Evidence of high and directional gene flow between seven wild and domestic population pairs across our study site indicates insecticide-based control will be hindered by repeated re-infestation of houses from the forest. Preliminary genome scans across multiple population pairs revealed shared outlier loci potentially consistent with local adaptation to the domestic setting, which we mapped to genes involved with embryogenesis and saliva production. Landscape genomic models showed elevation is a key barrier to R. ecuadoriensis dispersal. Together our results shed early light on the genomic adaptation in triatomine vectors and facilitate vector control by predicting that spatially-targeted, proactive interventions would be more efficacious than current, reactive approaches.

Altered Glucose Kinetics Occurs With Aging, A New Outlook on Metabolic Flexibility.

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers, along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios (RER=CO2/O2) during a 2-hour 75-gram oral glucose tolerance test (OGTT). After an 12-hour overnight fast, 28 participants, 15 young (21-35 yr.; 7 men and 8 women) and 13 older (60-80 yr.; 7 men and 6 women) received venous primed-continuous infusions of [6,6-2H]glucose, and [3-13C]lactate with a H13CO3- bolus. Following a 90-minute metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 minutes post-glucose consumption, peaked at 60 minutes, and remained elevated. As assessed by rates of appearance (Ra), disposal (Rd) and metabolic clearance (MCR) glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population following the oral glucose challenge. Lastly, there were no differences in 12-hr fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population following a glucose challenge. Further, those physiological deficits are not detected from changes in RER during an OGTT.

The effect of NK3-Saporin injection within the arcuate nucleus on puberty, the LH surge, and the response to Senktide in female sheep†.

The timing of puberty onset is reliant on increased gonadotropin-releasing hormone (GnRH). This elicits a corresponding increase in luteinizing hormone (LH) due to a lessening of sensitivity to the inhibitory actions of estradiol (E2). The mechanisms underlying the increase in GnRH release likely involve a subset of neurons within the arcuate (ARC) nucleus of the hypothalamus that contain kisspeptin, neurokinin B (NKB), and dynorphin (KNDy neurons). We aimed to determine if KNDy neurons in female sheep are critical for: timely puberty onset; the LH surge; and the response to an intravenous injection of the neurokinin-3 receptor (NK3R) agonist, senktide. Prepubertal ewes received injections aimed at the ARC containing blank-saporin (control, n = 5) or NK3-saporin (NK3-SAP, n = 6) to ablate neurons expressing NK3R. Blood samples taken 3/week for 65 days following surgery were assessed for progesterone to determine onset of puberty. Control ewes exhibited onset of puberty at 33.2 ± 3.9 days post sampling initiation, whereas 5/6 NK3-SAP treated ewes didn't display an increase in progesterone. After an artificial LH surge protocol, surge amplitude was lower in NK3-SAP ewes. Finally, ewes were treated with senktide to determine if an LH response was elicited. LH pulses were evident in both groups in the absence of injections, but the response to senktide vs saline was similar between groups. These results show that KNDy cells are necessary for timely puberty onset and for full expresson of the LH surge. The occurrence of LH pulses in NK3-SAP treated ewes may indicate a recovery from an apulsatile state.

Higher substance use is associated with low executive control neural activity and higher inflammation.

Individuals with substance use problems show lower executive control and alterations in prefrontal brain systems supporting emotion regulation and impulse control. A separate literature suggests that heightened inflammation also increases risk for substance use, in part, through targeting brain systems involved in executive control. Research on neural and inflammatory signaling in substance use, however, has occurred in parallel. Drawing on recent neuroimmune network models, we used fMRI to examine the relationships between executive control-related brain activity (as elicited by an n-back working memory task), peripheral inflammation, as quantified by inflammatory cytokines and C-reactive protein (CRP), and substance use for the past month in 93 participants [mean age = 24.4 (SD = 0.6)]. We operationalized low executive control as a neural inefficiency during the n-back task to achieve normative performance, as reflected in higher working memory-related brain activity and lower activity in the default mode network (DMN). Consistent with prediction, individuals with low executive control and high inflammation reported more substance use over the past month, controlling for behavioral performance on the n-back, sex, time between assessments, body-mass-index (BMI), and personal socioeconomic status (SES) (interaction between inflammation and working memory-related brain activity, b = 0.210, p = 0.005; interaction between inflammation and DMN, b = -0.219, p < 0.001). Findings suggest that low executive control and high inflammation may be associated with higher substance use. This has implications for understanding psychological, neural, and immunological risk for substance use problems and the development of interventions to target each of these components.

Major stress in early childhood strengthens the association between peripheral inflammatory activity and corticostriatal responsivity to reward.

BACKGROUND: Severe, chronic stress during childhood accentuates vulnerability to mental and physical health problems across the lifespan. To explain this phenomenon, the neuroimmune network hypothesis proposes that childhood stressors amplify signaling between peripheral inflammatory cells and developing brain circuits that support processing of rewards and threats. Here, we conducted a preliminary test of the basic premises of this hypothesis. METHODS: 180 adolescents (mean age = 19.1 years; 68.9 % female) with diverse racial and ethnic identities (56.1 % White; 28.3 % Hispanic; 26.1 % Asian) participated. The Childhood Trauma Interview was administered to quantify early adversity. Five inflammatory biomarkers were assayed in antecubital blood - C-reactive protein, tumor necrosis factor-a, and interleukins-6, -8, and -10 - and were averaged to form a composite score. Participants also completed a functional MRI task to measure corticostriatal responsivity to the anticipation and acquisition of monetary rewards. RESULTS: Stress exposure and corticostriatal responsivity interacted statistically to predict the inflammation composite. Among participants who experienced major stressors in the first decade of life, higher inflammatory activity covaried with lower corticostriatal responsivity during acquisition of monetary rewards. This relationship was specific to participants who experienced major stress in early childhood, implying a sensitive period for exposure, and were evident in both the orbitofrontal cortex and the ventral striatum, suggesting the broad involvement of corticostriatal regions. The findings were independent of participants' age, sex, racial and ethnic identity, family income, and depressive symptoms. CONCLUSIONS: Collectively, the results are consistent with hypotheses suggesting that major stress in childhood alters brain-immune signaling.

Multicenter Comparison of the Safety and Efficacy of Clopidogrel Versus Ticagrelor for Neuroendovascular Stents.

BACKGROUND: Dual antiplatelet therapy (DAPT) is commonly employed for neuroendovascular stenting due to the significant risk of thromboembolism. Clopidogrel and aspirin are most often selected as initial DAPTs; however, there is limited literature available to support guidance of DAPT in this setting. The objective of this study was to evaluate safety and efficacy in patients whose final regimen included either DAPT with aspirin and clopidogrel (DAPT-C) or DAPT with aspirin and ticagrelor (DAPT-T). METHODS: This was a multicenter, retrospective cohort of patients who underwent neuroendovascular stenting and received DAPT between July 1, 2017, and October 31, 2020. Study participants were allocated into groups based on discharge DAPT regimen. The primary outcome was incidence of stent thrombosis at 3-6 months on DAPT-C versus DAPT-T, as defined by the presence of thrombus on imaging or new onset stroke. Secondary outcomes included major and minor bleeding and death within 3-6 months after the procedure. RESULTS: Five hundred and seventy patients were screened across 12 sites. Of those, 486 were included (DAPT-C n = 360, DAPT-T n = 126). There was no difference in the primary outcome of stent thrombosis between the DAPT-C and DAPT-T groups (8% vs. 8%, p = 0.97) and no difference in any of the secondary safety outcomes. CONCLUSIONS: Using DAPT-C or DAPT-T regimens in a broad population of neuroendovascular stenting procedures appears to have similar safety and efficacy profiles. Further prospective evaluation is warranted to streamline the practice of DAPT selection and monitoring to determine the impact on clinical outcomes.

Corridor-based approach with spatial cross-validation reveals scale-dependent effects of geographic distance, human footprint and canopy cover on grizzly bear genetic connectivity.

Understanding how human infrastructure and other landscape attributes affect genetic differentiation in animals is an important step for identifying and maintaining dispersal corridors for these species. We built upon recent advances in the field of landscape genetics by using an individual-based and multiscale approach to predict landscape-level genetic connectivity for grizzly bears (Ursus arctos) across ~100,000 km2 in Canada's southern Rocky Mountains. We used a genetic dataset with 1156 unique individuals genotyped at nine microsatellite loci to identify landscape characteristics that influence grizzly bear gene flow at multiple spatial scales and map predicted genetic connectivity through a matrix of rugged terrain, large protected areas, highways and a growing human footprint. Our corridor-based modelling approach used a machine learning algorithm that objectively parameterized landscape resistance, incorporated spatial cross validation and variable selection and explicitly accounted for isolation by distance. This approach avoided overfitting, discarded variables that did not improve model performance across withheld test datasets and spatial predictive capacity compared to random cross-validation. We found that across all spatial scales, geographic distance explained more variation in genetic differentiation in grizzly bears than landscape variables. Human footprint inhibited connectivity across all spatial scales, while open canopies inhibited connectivity at the broadest spatial scale. Our results highlight the negative effect of human footprint on genetic connectivity, provide strong evidence for using spatial cross-validation in landscape genetics analyses and show that multiscale analyses provide additional information on how landscape variables affect genetic differentiation.

The complex interactions between nutrition, immunity and infection in insects.

Insects are the most diverse animal group on the planet. Their success is reflected by the diversity of habitats in which they live. However, these habitats have undergone great changes in recent decades; understanding how these changes affect insect health and fitness is an important challenge for insect conservation. In this Review, we focus on the research that links the nutritional environment with infection and immune status in insects. We first discuss the research from the field of nutritional immunology, and we then investigate how factors such as intracellular and extracellular symbionts, sociality and transgenerational effects may interact with the connection between nutrition and immunity. We show that the interactions between nutrition and resistance can be highly specific to insect species and/or infection type - this is almost certainly due to the diversity of insect social interactions and life cycles, and the varied environments in which insects live. Hence, these connections cannot be easily generalised across insects. We finally suggest that other environmental aspects - such as the use of agrochemicals and climatic factors - might also influence the interaction between nutrition and resistance, and highlight how research on these is essential.

Evolutionary potential mitigates extinction risk under climate change in the endangered southwestern willow flycatcher.

The complexity of global anthropogenic change makes forecasting species responses and planning effective conservation actions challenging. Additionally, important components of a species' adaptive capacity, such as evolutionary potential, are often not included in quantitative risk assessments due to lack of data. While genomic proxies for evolutionary potential in at-risk species are increasingly available, they have not yet been included in extinction risk assessments at a species-wide scale. In this study, we used an individual-based, spatially explicit, dynamic eco-evolutionary simulation model to evaluate the extinction risk of an endangered desert songbird, the southwestern willow flycatcher (Empidonax traillii extimus), in response to climate change. Using data from long-term demographic and habitat studies in conjunction with genome-wide ecological genomics research, we parameterized simulations that include 418 sites across the breeding range, genomic data from 225 individuals, and climate change forecasts spanning 3 generalized circulation models and 3 emissions scenarios. We evaluated how evolutionary potential, and the lack of it, impacted population trajectories in response to climate change. We then investigated the compounding impact of drought and warming temperatures on extinction risk through the mechanism of increased nest failure. Finally, we evaluated how rapid action to reverse greenhouse gas emissions would influence population responses and species extinction risk. Our results illustrate the value of incorporating evolutionary, demographic, and dispersal processes in a spatially explicit framework to more comprehensively evaluate the extinction risk of threatened and endangered species and conservation actions to promote their recovery.

Value of Routine Troponin Measurement in Open Abdominal Aortic Aneurysm Repair.

BACKGROUND: Cardiovascular complications are a major cause of morbidity and mortality in the postoperative period after major vascular surgery. Depending on the study population, up to 25% of patients have troponin elevation after noncardiac surgery, yet many do not meet the diagnosis of myocardial infarction (MI). Although outcomes of routine troponin elevation in patients undergoing mixed major vascular surgery have been evaluated, this has not been studied exclusively in elective, open abdominal aortic aneurysm repair (oAAA), especially regarding perioperative and overall mortality. METHODS: We conducted a single-center, retrospective review of routine troponin surveillance for consecutive, oAAA from 2014 to 2019. A total of 319 patients were identified and analyzed for management patterns and interventions. The cohort was stratified into groups for comparison based on those in whom troponin was routinely checked (RC) as part of a care strategy during the study period, not routinely checked (NRC), elevated troponin (ET) >0.001 ng/mL, and not elevated. The median follow-up was 21.5 ± 23.8 months. Groups were compared on demographic data, cardiac comorbidities, 30-day and 3-year outcomes for MI and death using two-sample t-tests, Wilcoxon rank sum tests, Pearson chi-square tests, and Fisher exact tests when appropriate. RESULTS: Troponin was measured in 83.7% (267/319) of patients who underwent elective oAAA repair. Routine troponin checks were obtained in 79.9% (255/319) of patients. ET was identified in 16.5% of those with RC (42/255) and 4.7% of those with NRC (3/64). Of patients with ET, 37.8% (17/45) had a cardiology consultation, 4.4% (2/45) had a percutaneous coronary intervention (PCI), and 4.4% (2/45) had another cardiac intervention. All 4 patients undergoing PCI or other cardiac intervention had received routine troponin checks. Patients with ET were older (71.2 vs. 68.6; P = 0.04), more likely to receive intraoperative blood products (P = 0.003), had longer operative times (P = 0.011), higher length of stay (9 vs. 7 days; P < 0.01), and higher 30-day MI rate (3 vs. 0; P = 0.04). They had neither longer aortic clamp times nor worse preoperative cardiac function, and the proximal clamp position during oAAA repair did not impact troponin detection. Additionally, 3-year overall mortality was increased in patients who had ET but there was not a significant difference in 3-year mortality between groups receiving routine troponin checks versus not. CONCLUSIONS: ET, identified after elective oAAA repair, was associated with a higher risk of 30-day MI and lower overall survival. However, it was not demonstrated that routine assessment of troponin levels postoperatively leads to decreased 3-year mortality in this setting.

PHASE 2 RANDOMIZED STUDY (ORION-1) OF A NOVEL, BIODEGRADABLE DEXAMETHASONE IMPLANT (AR-1105) FOR THE TREATMENT OF MACULAR EDEMA DUE TO CENTRAL OR BRANCH RETINAL VEIN OCCLUSION.

PURPOSE: AR-1105 is a novel biodegradable sustained-release dexamethasone implant designed to deliver 6-month durability. This Phase 2 study evaluated two AR-1105 formulations with different release profiles in patients with macular edema due to retinal vein occlusion. METHODS: Patients received a single intravitreal injection with 340 µg dexamethasone. In the initial phase, five patients received clinical formulation (CF) 1. In the randomized phase, 44 patients were randomized 1:1 to CF1 or CF2. The follow-up was 6 months. Patients had vision loss due to macular edema diagnosed ≥9 (central retinal vein occlusion) or ≥12 months (branch retinal vein occlusion) before screening, and could be treatment-naive or -experienced (if received prior steroids, must have demonstrated response). RESULTS: Both formulations improved vision and reduced retinal thickening from baseline across all visits. At Month 6, mean changes in best-corrected visual acuity were +4.3 and +8.0 letters, and mean changes in central subfield thickness were -93 µm and -211 µm in CF1 and CF2 randomized patients, respectively. Most common adverse events were reduced visual acuity, worsening macular edema, conjunctival hemorrhage, and increased intraocular pressure. No patients required surgery or laser for intraocular pressure control. CONCLUSION: Both formulations were well tolerated and demonstrated clinically meaningful and sustained improvements in vision and retinal thickening in patients with retinal vein occlusion with longstanding edema.

Serum per- and polyfluoroalkyl substance concentrations in four municipal US fire departments.

BACKGROUND: Firefighters have occupational and environmental exposures to per- and polyfluoroalkyl substances (PFAS). The goal of this study was to compare serum PFAS concentrations across multiple United States fire departments to National Health and Nutrition Examination Survey (NHANES) participants. METHODS: Nine serum PFAS were compared in 290 firefighters from four municipal fire departments (coded A-D) and three NHANES participants matched to each firefighter on sex, ethnicity, age, and PFAS collection year. Only Departments A and C had sufficient women study participants (25 and six, respectively) to compare with NHANES. RESULTS: In male firefighters compared with NHANES, geometric mean perfluorohexane sulfonate (PFHxS) was elevated in Departments A-C, sum of branched perfluoromethylheptane sulfonate isomers (Sm-PFOS) was elevated in all four departments, linear perfluorooctane sulfonate (n-PFOS) was elevated in Departments B and C, linear perfluorooctanoate (n-PFOA) was elevated in Departments B-D, and perfluorononanoate (PFNA) was elevated in Departments B-D, but lower in A. In male firefighters compared with NHANES, perfluoroundecanoate (PFUnDA) was more frequently detected in Departments B and D, and 2-(N-methyl-perfluorooctane sulfonamido) acetate (MeFOSAA) was less frequently detected in Departments B-D. In female firefighters compared with NHANES, PFHxS and Sm-PFOS concentrations were elevated in Departments A and C. Other PFAS concentrations were elevated and/or reduced in only one department or not significantly different from NHANES in any department. CONCLUSIONS: Serum PFHxS, Sm-PFOS, n-PFOS, n-PFOA, and PFNA concentrations were increased in at least two of four fire departments in comparison to NHANES.

A Novel Approach to Clustering Accelerometer Data for Application in Passive Predictions of Changes in Depression Severity.

The treatment of mood disorders, which can become a lifelong process, varies widely in efficacy between individuals. Most options to monitor mood rely on subjective self-reports and clinical visits, which can be burdensome and may not portray an accurate representation of what the individual is experiencing. A passive method to monitor mood could be a useful tool for those with these disorders. Some previously proposed models utilized sensors from smartphones and wearables, such as the accelerometer. This study examined a novel approach of processing accelerometer data collected from smartphones only while participants of the open-science branch of the BiAffect study were typing. The data were modeled by von Mises-Fisher distributions and weighted networks to identify clusters relating to different typing positions unique for each participant. Longitudinal features were derived from the clustered data and used in machine learning models to predict clinically relevant changes in depression from clinical and typing measures. Model accuracy was approximately 95%, with 97% area under the ROC curve (AUC). The accelerometer features outperformed the vast majority of clinical and typing features, which suggested that this new approach to analyzing accelerometer data could contribute towards unobtrusive detection of changes in depression severity without the need for clinical input.

Underfeeding Alters Brain Tissue Synthesis Rate in a Rat Brain Injury Model.

Brain injuries (BI) are highly disruptive, often having long lasting effects. Inadequate standard of care (SOC) energy support in the hospital leads to dietary energy deficiencies in BI patients. However, it is unclear how underfeeding (UF) affects protein synthesis post-BI. Therefore, in a rat model, we addressed the issue of UF on the protein fractional synthesis rate (fSR) post-BI. Compared to ad libitum (AL)-fed animals, we found that UF decreased protein synthesis in hind-limb skeletal muscle and cortical mitochondrial and structural proteins (p ≤ 0.05). BI significantly increased protein synthesis in the left and right cortices (p ≤ 0.05), but suppressed protein synthesis in the cerebellum (p ≤ 0.05) as compared to non-injured sham animals. Compared to underfeeding alone, UF in conjunction with BI (UF+BI) caused increased protein synthesis rates in mitochondrial, cytosolic, and whole-tissue proteins of the cortical brain regions. The increased rates of protein synthesis found in the UF+BI group were mitigated by AL feeding, demonstrating that caloric adequacy alleviates the effects of BI on protein dynamics in cortical and cerebellar brain regions. This research provides evidence that underfeeding has a negative impact on brain healing post-BI and that protein reserves in uninjured tissues are mobilized to support cortical tissue repair following BI.

More Physical Activity Is Correlated With Reduction in Kinesiophobia for Adolescents With Persistent Symptoms After Concussion.

CONTEXT: The relationship between physical activity (PA) and fear of pain with movement (ie, kinesiophobia) during concussion recovery is unknown. Kinesiophobia may limit PA, while PA after concussion may reduce kinesiophobia. Our purpose was to examine the correlation between PA and self-reported kinesiophobia during concussion recovery for adolescents with and without persistent symptoms. DESIGN: Prospective cohort study of children ages 10-18 years within 14 days of concussion. METHODS: Participants rated kinesiophobia using the Tampa Scale of Kinesiophobia (TSK) at initial (≤14 d postconcussion) and return to play (RTP) assessments, and wore activity monitors between assessments. Our primary outcome was TSK score change from initial to RTP assessments. We grouped participants based on whether they experienced persistent symptoms (symptoms ≥28 days) or not (symptoms <28 days) and calculated correlation coefficients (Pearson r for normally distributed and Spearman rho for nonnormally distributed variables) between PA variables and TSK change scores. RESULTS: Among the 41 participants enrolled, 44% developed persistent symptoms (n = 18; age = 14.5 [2.0] y; 50% female; symptom duration = 57.3 [6.2] d; RTP = 66.8 [6.4] d) and 56% did not (n = 23; age = 14.9 [1.8] y; 48% female; symptom duration = 15.2 [1.5] d; RTP = 21.7 [1.9] d). For the persistent symptoms group, greater TSK change scores (mean = -2.5 [5.7] point change) were significantly and moderately correlated with higher daily step count (r = -.60, P = .008) and exercise frequency (r = -.63, P = .005), but were not correlated with exercise duration (ρ = -.12, P = .65). Among the no persistent symptoms group, TSK change scores (mean = -6.0 [5.0] point change) were not correlated with step count (r = -.18, P = .41) or exercise duration (ρ = .10, P = .67), and the correlation with frequency was low and not significant (r = -.34, P = .12). CONCLUSIONS: Regular PA during concussion recovery, regardless of duration or intensity, may help reduce kinesiophobia for those experiencing persistent symptoms.

Early Moderate to Vigorous Physical Activity After Concussion Is Associated With Faster Symptom Resolution Time.

CONTEXT: Early physical activity (PA) after concussion may promote symptom resolution. Prior studies have investigated exercise frequency/duration, yet precise PA intensity or volume required for optimal recovery requires further investigation. moderate to vigorous physical activity (MVPA) is beneficial for physical health. We investigated whether sedentary time, light activity time, MVPA time, or activity frequency in the weeks following concussion are associated with time to symptom resolution among adolescents. DESIGN: Prospective cohort study. METHODS: Adolescents 10-18 years of age were tested ≤14 days of concussion and followed until symptom resolution. At the initial visit, participants rated symptom severity and were provided wrist-worn activity trackers to monitor PA for the following week. PA behavior was categorized each day based on heart rate: sedentary (resting), light PA (50%-69% age-predicted max heart rate), and MVPA (70%-100% age-predicted max heart rate). Symptom resolution was defined as the date when participants reported cessation of concussion-like symptoms. Patients were not given specific PA instructions, though some may have received instructions from their physician. RESULTS: Fifty-four participants were included in the study (54% female; mean age = 15.0 [1.8] y; initially assessed 7.5 [3.2] d after concussion). Female athletes recorded more sedentary time (900 [46] vs 738 [185] min/d; P = .01; Cohen d = 0.72), and less time in light PA (194.7 [64.5] vs 224 [55] min/d; P = .08; Cohen d = 0.48) and MVPA (23 [17] vs 38 [31] min/d; P = .04; Cohen d = 0.58) than male athletes. After adjusting for sedentary time, hours per day with >250 steps, sex, and initial symptom severity, more MVPA time was associated with faster symptom resolution time (hazard ratio = 1.016; 95% confidence interval, 1.001-1.032; P = .04). CONCLUSION: Our findings offer preliminary insight into how varying PA intensities affect concussion recovery, as MVPA may be a higher intensity than what is typically prescribed in concussion care.

SalterHarris fractures in paediatric skiers and snowboarders.

The incidence of paediatric fractures among winter sport athletes is not adequately studied. Our objective was to categorize fractures that occurred in paediatric skiers and snowboarders at a single ski resort. X-rays of 756 skiers/snowboarders aged 3-17 diagnosed with a fracture were categorized using the Salter-Harris (SH) classification. SH fractures were seen in 158 (21%) patients, with 123 (77%) being Type II. There were no significant differences between patients with a SH fracture and patients with a non-SH fracture for age, sex, snowboarding or skiing, mechanism of injury, terrain or the resort conditions on the day of injury. The most common mechanism of injury was falling onto snow while collisions resulted in more severe injuries. Compared to fractures without growth plate involvement, a higher proportion of SH fractures were seen in the humerus, radius, fibula and thumb; a lower proportion of SH fractures were observed at the tibia and clavicle.

Guardianship Before and Following Hospitalization.

When ethics committees are consulted about patients who have or need court-appointed guardians, they lack empirical evidence about several common issues, including the relationship between guardianship and prolonged, potentially medically unnecessary hospitalizations for patients. To provide information about this issue, we conducted quantitative and qualitative analyses using a retrospective cohort from Veterans Healthcare Administration. To examine the relationship between guardianship appointment and hospital length of stay, we first compared 116 persons hospitalized prior to guardianship appointment to a comparison group (n = 348) 3:1 matched for age, diagnosis, date of admission, and comorbidity. We then compared 91 persons hospitalized in the year following guardianship appointment to a second matched comparison group (n = 273). Mean length of stay was 30.75 days (SD = 46.70) amongst those admitted prior to guardianship, which was higher than the comparison group (M = 7.74, SD = 9.71, F = 20.75, p < .001). Length of stay was lower following guardianship appointment (11.65, SD = 12.02, t = 15.16, p < .001); while higher than the comparison group (M = 7.60, SD = 8.46), differences were not associated with guardianship status. In a separate analysis involving 35 individuals who were hospitalized both prior to and following guardianship, length of stay was longer in the year prior (M = 23.00, SD = 37.55) versus after guardianship (M = 10.37, SD = 10.89, F = 4.35, p = .045). In qualitative analyses, four themes associated with lengths of stay exceeding 45 days prior to guardianship appointment were: administrative issues, family conflict, neuropsychiatric comorbidity, and medical complications. Our results suggest that persons who are admitted to hospitals, and subsequently require a guardian, experience extended lengths of stay for multiple complex reasons. Once a guardian has been appointed, however, differences in hospital lengths of stay between patients with and without guardians are reduced.

Lactate in contemporary biology: a phoenix risen.

After a century, it's time to turn the page on understanding of lactate metabolism and appreciate that lactate shuttling is an important component of intermediary metabolism in vivo. Cell-cell and intracellular lactate shuttles fulfil purposes of energy substrate production and distribution, as well as cell signalling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. Moreover, the presence of lactate shuttling as part of postprandial glucose disposal and satiety signalling has been recognized. Mitochondrial respiration creates the physiological sink for lactate disposal in vivo. Repeated lactate exposure from regular exercise results in adaptive processes such as mitochondrial biogenesis and other healthful circulatory and neurological characteristics such as improved physical work capacity, metabolic flexibility, learning, and memory. The importance of lactate and lactate shuttling in healthful living is further emphasized when lactate signalling and shuttling are dysregulated as occurs in particular illnesses and injuries. Like a phoenix, lactate has risen to major importance in 21st century biology.