Validating the Use of Continuous Glucose Monitors With Nondiabetic Recreational Runners.

PURPOSE: Continuous glucose monitors (CGMs) are becoming increasingly popular among endurance athletes despite unconfirmed accuracy. We assessed the concurrent validity of the FreeStyle Libre 2 worn on 2 different sites at rest, during steady-state running, and postprandial. METHODS: Thirteen nondiabetic, well-trained recreational runners (age = 40 [8] y, maximal aerobic oxygen consumption = 46.1 [6.4] mL·kg-1·min-1) wore a CGM on the upper arm and chest while treadmill running for 30, 60, and 90 minutes at intensities corresponding to 50%, 60%, and 70% of maximal aerobic oxygen consumption, respectively. Glucose was measured by manually scanning CGMs and obtaining a finger-prick capillary blood glucose sample. Mean absolute relative difference, time in range, and continuous glucose Clarke error grid analysis were used to compare paired CGM and blood glucose readings. RESULTS: Across all intensities of steady-state running, we found a mean absolute relative difference of 13.8 (10.9) for the arm and 11.4 (9.0) for the chest. The coefficient of variation exceeded 70%. Approximately 47% of arm and 50% of chest paired glucose measurements had an absolute difference ≤10%. Continuous glucose Clarke error grid analysis indicated 99.8% (arm) and 99.6% (chest) CGM data fell in clinically acceptable zones A and B. Time-in-range analysis showed reduced accuracy at lower glucose levels. However, CGMs accurately detected trends in mean glucose readings over time. CONCLUSIONS: CGMs are not valid for point glucose monitoring but appear to be valid for monitoring glucose trends during steady-state exercise. Accuracy is similar for arm and chest. Further research is needed to determine whether CGMs can detect important events such as hypoglycemia during exercise.

Meta-analysis highlight the therapeutic potential of stem cells for premature ovarian failure.

Stem cell (SC) transplantation has shown potential as a therapeutic approach for premature ovarian failure (POF). Despite this, no quantitative analysis has been conducted on the efficacy of SC therapy for POF in humans. To address this gap, the present study conducted a meta-analysis to evaluate the effectiveness of the transplantation of SC in improving ovarian function among POF patients. A systematic review in this regard by searching PubMed, ScienceDirect, clinicalTrial.gov, and Cochrane's library databases was conducted to identify relevant studies, while associated reviews were also considered. The extracted data included parameters such as estradiol (E2), follicle-stimulating hormone (FSH), follicle count (FC), ovarian weight (OW), number of pregnancies, and live birth. As per the combined effect taking the last follow-up time, the level of FSH and AMH for the SC group was lower than these were at the baseline as (SMD: 1.58, 95% CI: 0.76 to 3.92, P-value: 0.185 > 0.05, I2: 94.03%) and (SMD: 1.34, 95% CI: 0.77 to 1.92, P-value: 0.001 < 0.05, I2: 0%) respectively. While the means of E2 and OW for the SC group was higher than these were at the baseline as (SMD: -0.47, 95% CI: -0.73 to -0.21, P-value: 0.001 < 0.01, I2: 38.23%) and (SMD: -1.18, 95% CI: -2.62 to 0.26, P-value: 0.108 > 0.05, I2: 76.68%) respectively. The overall effect size measured with proportion of pregnancy and live birth at a 5% level of significance expected SC transplantation results were as (combined proportion: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.002 < 0.05, I2: 46.29%) and (SMD: 0.09, 95% CI: 0.03 to 0.15, P-value: 0.003 < 0.05, I2: 1.76%) respectively. Based on the fixed-effects model, the estimated average log odds ratio of Follicles count was 1.0234 (95% CI: 0.1252 to 1.9216). Therefore, the average outcome differed significantly from zero (P-value: 0.0255 < 0.05) due to SC transplantation. These results suggest that using SCs to restore ovarian function may be viable for treating POF. However, larger and better-quality investigations would need to be conducted in the future due to the heterogeneity of the examined studies.

Meta-analysis shows that mesenchymal stem cell therapy can be a possible treatment for diabetes.

Objective: This meta-analysis includes the systematic literature review and meta-analysis involving clinical trials to assess the efficacy and safety of mesenchymal stem cell (MSC) transplantation for treating T1DM and T2DM. Methods: We searched PubMed, ScienceDirect, Web of Science, clinicaltrials.gov, and Cochrane Library for "published" research from their inception until November 2023. Two researchers independently reviewed the studies' inclusion and exclusion criteria. Our meta-analysis included 13 studies on MSC treatment for diabetes. Results: The MSC-treated group had a significantly lower HbA1c at the last follow-up compared to the baseline (MD: 0.95, 95% CI: 0.33 to 1.57, P-value: 0.003< 0.05), their insulin requirement was significantly lower (MD: 0.19, 95% CI: 0.07 to 0.31, P-value: 0.002< 0.05), the level of FBG with MSC transplantation significantly dropped compared to baseline (MD: 1.78, 95% CI: -1.02 to 4.58, P-value: 0.212), the FPG level of the MSC-treated group was significantly lower (MD: -0.77, 95% CI: -2.36 to 0.81, P-value: 0.339 > 0.05), and the fasting C-peptide level of the MSC-treated group was slightly high (MD: -0.02, 95% CI: -0.07 to 0.02, P-value: 0.231 > 0.05). Conclusion: The transplantation of MSCs has been found to positively impact both types of diabetes mellitus without signs of apparent adverse effects.

Proceedings of the 11th Annual Deep Brain Stimulation Think Tank: pushing the forefront of neuromodulation with functional network mapping, biomarkers for adaptive DBS, bioethical dilemmas, AI-guided neuromodulation, and translational advancements.

The Deep Brain Stimulation (DBS) Think Tank XI was held on August 9-11, 2023 in Gainesville, Florida with the theme of "Pushing the Forefront of Neuromodulation". The keynote speaker was Dr. Nico Dosenbach from Washington University in St. Louis, Missouri. He presented his research recently published in Nature inn a collaboration with Dr. Evan Gordon to identify and characterize the somato-cognitive action network (SCAN), which has redefined the motor homunculus and has led to new hypotheses about the integrative networks underpinning therapeutic DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers, and researchers (from industry and academia) can freely discuss current and emerging DBS technologies, as well as logistical and ethical issues facing the field. The group estimated that globally more than 263,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: cutting-edge translational neuromodulation, cutting-edge physiology, advances in neuromodulation from Europe and Asia, neuroethical dilemmas, artificial intelligence and computational modeling, time scales in DBS for mood disorders, and advances in future neuromodulation devices.

Cone allometry and seed protection from fire are similar in serotinous and nonserotinous conifers.

Serotiny is an adaptive trait that allows certain woody plants to persist in stand-replacing fire regimes. However, the mechanisms by which serotinous cones avoid seed necrosis and nonserotinous species persist in landscapes with short fire cycles and serotinous competitors remain poorly understood. To investigate whether ovulate cone traits that enhance seed survival differ between serotinous and nonserotinous species, we examined cone traits in 24 species within Pinaceae and Cupressaceae based on physical measurements and cone heating simulations using a computational fluid dynamics model. Fire-relevant cone traits were largely similar between cone types; those that differed (e.g. density and moisture) conferred little seed survival advantage under simulated fire. The most important traits influencing seed survival were cone size and seed depth within the cone, which was found to be an allometric function of cone mass for both cone types. Thus, nonserotinous cones should not suffer significantly greater seed necrosis than serotinous cones of equal size. Closed nonserotinous cones containing mature seeds may achieve substantial regeneration after fire if they are sufficiently large relative to fire duration and temperature. To our knowledge, this is the most comprehensive study of the effects of fire-relevant cone traits on conifer regeneration supported by physics-based fire simulation.

The therapeutic effect of mesenchymal stem cells in diabetic kidney disease.

Diabetes mellitus (DM) often causes chronic kidney damage despite best medical practices. Diabetic kidney disease (DKD) arises from a complex interaction of factors within the kidney and the whole body. Targeting specific disease-causing agents using drugs has not been effective in treating DKD. However, stem cell therapies offer a promising alternative by addressing multiple disease pathways and promoting kidney regeneration. Mesenchymal stem cells (MSCs) offer great promise due to their superior accessibility ratio from adult tissues and remarkable modes of action, such as the production of paracrine anti-inflammatory and cytoprotective substances. This review critically evaluates the development of MSC treatment for DKD as it moves closer to clinical application. Results from animal models suggest that systemic MSC infusion may positively impact DKD progression. However, few registered and completed clinical trials exist, and whether the treatments are effective in humans is still being determined. Significant knowledge gaps and research opportunities exist, including establishing the ideal source, dose, and timing of MSC delivery, better understanding of in vivo mechanisms, and developing quantitative indicators to obtain a more significant therapeutic response. This paper reviews recent literature on using MSCs in preclinical and clinical trials in DKD. Potent biomarkers related to DKD are also highlighted, which may help better understand MSCs' action in this disease progression. KEY MESSAGES: Mesenchymal stem cells have anti-inflammatory and paracrine effects in diabetic kidney disease. Mesenchymal stem cells alleviate in animal models having diabetic kidney disease. Mesenchymal stem cells possess promise for the treatment of diabetic kidney disease.

Breaking point? An analysis of fatal stab wounds to the torso in Ireland between 2011 and 2018, examining the extent of rib fractures.

This study examines the pattern of rib injuries occurring in cases of fatal torso stab wounds in Ireland between 2011 and 2018. It has been suggested by previous studies that rib fractures are not commonly sustained in stab wounds to the torso. We wanted to ascertain whether this was the case, as our data suggested that rib fractures were frequent, and where a rib is fractured there is a higher chance of organ injury and death, making this an important area of study. One hundred and forty seven cases of fatal stab wounds from an eight-year period were retrospectively reviewed. Fatal stab wounds to other body areas, were excluded; leaving a total of 104 cases with stab wounds to the torso. We found that 69.2% of cases had rib injuries, a figure significantly higher than previously reported. Our data suggests that stab wounds to the torso often fracture ribs, putting the underlying organs at increased risk of injury and perhaps contributing to fatality. The amount of force needed to cause a rib fracture can be difficult to quantify and indeed from the high percentage of rib fractures sustained in our data it appears that the ribs may be fractured regardless of the amount of force used; this is borne out by the finding that self-inflicted injuries also caused rib fractures. Our study shows that other factors, such as anatomical positioning and wound depth may have a greater bearing than force in terms of whether a rib fracture is sustained.

Exercise as adjunctive therapy for systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) is a rare, chronic autoimmune inflammatory disease with a prevalence varying from 4.3 to 150 people in 100,000, or approximately five million people worldwide. Systemic manifestations frequently include internal organ involvement, a characteristic malar rash on the face, pain in joints and muscles, and profound fatigue. Exercise is purported to be beneficial for people with SLE. For this review, we focused on studies that examined all types of structured exercise as an adjunctive therapy in the management of SLE. OBJECTIVES: To evaluate the benefits and harms of structured exercise as adjunctive therapy for adults with SLE compared with usual pharmacological care, usual pharmacological care plus placebo and usual pharmacological care plus non-pharmacological care. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 30 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of exercise as an adjunct to usual pharmacological treatment in SLE compared with placebo, usual pharmacological care alone and another non-pharmacological treatment. Major outcomes were fatigue, functional capacity, disease activity, quality of life, pain, serious adverse events, and withdrawals due to any reason, including any adverse events. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our major outcomes were 1. fatigue, 2. functional capacity, 3. disease activity, 4. quality of life, 5. pain, 6. serious adverse events, and 7. withdrawals due to any reason. Our minor outcomes were 8. responder rate, 9. aerobic fitness, 10. depression, and 11. anxiety. We used GRADE to assess certainty of evidence. The primary comparison was exercise compared with placebo. MAIN RESULTS: We included 13 studies (540 participants) in this review. Studies compared exercise as an adjunct to usual pharmacological care (antimalarials, immunosuppressants, and oral glucocorticoids) with usual pharmacological care plus placebo (one study); usual pharmacological care (six studies); and another non-pharmacological treatment such as relaxation therapy (seven studies). Most studies had selection bias, and all studies had performance and detection bias. We downgraded the evidence for all comparisons because of a high risk of bias and imprecision. Exercise plus usual pharmacological care versus placebo plus usual pharmacological care Evidence from a single small study (17 participants) that compared whole body vibration exercise to whole body placebo vibration exercise (vibrations switched off) indicated that exercise may have little to no effect on fatigue, functional capacity, and pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). The study did not report disease activity, quality of life, and serious adverse events. The study measured fatigue using the self-reported Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue), scale 0 to 52; lower score means less fatigue. People who did not exercise rated their fatigue at 38 points and those who did exercise rated their fatigue at 33 points (mean difference (MD) 5 points lower, 95% confidence interval (CI) 13.29 lower to 3.29 higher). The study measured functional capacity using the self-reported 36-item Short Form health questionnaire (SF-36) Physical Function domain, scale 0 to 100; higher score means better function. People who did not exercise rated their functional capacity at 70 points and those who did exercise rated their functional capacity at 67.5 points (MD 2.5 points lower, 95% CI 23.78 lower to 18.78 higher). The study measured pain using the SF-36 Pain domain, scale 0 to 100; lower scores mean less pain. People who did not exercise rated their pain at 43 points and those who did exercise rated their pain at 34 points (MD 9 points lower, 95% CI 28.88 lower to 10.88 higher). More participants from the exercise group (3/11, 27%) withdrew from the study than the placebo group (1/10, 10%) (risk ratio (RR) 2.73, 95% CI 0.34 to 22.16). Exercise plus usual pharmacological care versus usual pharmacological care alone The addition of exercise to usual pharmacological care may have little to no effect on fatigue, functional capacity, and disease activity (low-certainty evidence). We are uncertain whether the addition of exercise improves pain (very low-certainty evidence), or results in fewer or more withdrawals (very low-certainty evidence). Serious adverse events and quality of life were not reported. Exercise plus usual care versus another non-pharmacological intervention such as receiving information about the disease or relaxation therapy Compared with education or relaxation therapy, exercise may reduce fatigue slightly (low-certainty evidence), may improve functional capacity (low-certainty evidence), probably results in little to no difference in disease activity (moderate-certainty evidence), and may result in little to no difference in pain (low-certainty evidence). We are uncertain whether exercise results in fewer or more withdrawals (very low-certainty evidence). Quality of life and serious adverse events were not reported. AUTHORS' CONCLUSIONS: Due to low- to very low-certainty evidence, we are not confident on the benefits of exercise on fatigue, functional capacity, disease activity, and pain, compared with placebo, usual care, or advice and relaxation therapy. Harms data were not well reported.

The promise of autologous and allogeneic cellular therapies in the clinical trials of autism spectrum disorder.

Autism spectrum disorder (ASD) is a consortium of developmental conditions. As scientists have not yet identified the exact underlying cause for these disorders, it is not easy to narrow down a singular therapy to propose a reliable cure. The preponderance of research suggests that stem-cell therapy improves aspects of outcome measure scales in patients with ASD; therefore, future studies should give us more confidence in the results. This overview considers the data that have emerged from the small set of published trials conducted using different approaches in stem-cell therapy for ASD, evaluates their results and proposes additional steps that could be taken if this field of endeavor is to be pursued further.

Telehealth-supervised exercise in systemic lupus erythematosus: A pilot study.

OBJECTIVES: To explore the feasibility and effectiveness of telehealth-supervised exercise for adults with Systemic lupus erythematosus (SLE). METHODS: This was a non-randomised controlled pilot trial comparing telehealth-supervised exercise (8 weeks, 2 days/week, 45 min, moderate intensity) plus usual care with usual care alone. Mixed methods were used to assess change in fatigue (FACIT-fatigue), quality of life (SF36), resting fatigue and pain (11-point scale), lower body strength (five-time sit-to-stand) and endurance (30 s sit-to-stand), upper body endurance (30 s arm curl), aerobic capacity (2 min step test), and experience (survey and interviews). Group comparison was performed statistically using a two-sample T-test or Mann-Whitney U-test. Where known, we used MCID or MCII, or assumed a change of 10%, to determine clinically meaningful change within groups over time. Interviews were analysed using reflexive thematic analysis. RESULTS: Fifteen female adults with SLE were included (control group n = 7, exercise group n = 8). Statistically significant differences between groups, in favour of the exercise intervention, were noted for SF36 domain emotional well-being (p = 0.048) and resting fatigue (p = 0.012). There were clinically meaningful improvements over time for FACIT-fatigue (+6.3 ± 8.3, MCID >5.9), SF36 domains physical role functioning (+30%), emotional role functioning (+55%), energy/fatigue (+26%), emotional well-being (+19%), social functioning (+30%), resting pain (-32%), and upper body endurance (+23%) within the exercise group. Exercise attendance was high (98%, 110/112 sessions); participants strongly agreed (n = 5/7, 71%) or agreed (n = 2/7, 29%) they would do telehealth-supervised exercise again and were satisfied with the experience. Four themes emerged: (1) ease and efficiency of exercising from home, (2) value of live exercise instruction, (3) challenges of exercising at home, and (4) continuation of telehealth-supervised exercise sessions. CONCLUSION: Key findings from this mixed-method investigation suggest that telehealth-supervised exercise was feasible for, and well-accepted by, adults with SLE and resulted in some modest health improvements. We recommend a follow-up RCT with more SLE participants.

The Therapeutic Potential of Human Umbilical Cord Derived Mesenchymal Stem Cells for the Treatment of Premature Ovarian Failure.

Premature ovarian failure (POF) affects 1% of women under 40, leading to infertility. The clinical symptoms of the POF include hypoestrogenism, lack of mature follicles, hypergonadotropinism, and amenorrhea. POF can be caused due to genetic defects, autoimmune illnesses, and environmental factors. The conventional treatment of POF remains a limited success rate. Therefore, an innovative treatment strategy like the regeneration of premature ovaries by using human umbilical cord mesenchymal stem cells (hUC-MSCs) can be a choice. To summarize all the theoretical frameworks for additional research and clinical trials, this review article highlights all the results, pros, and cons of the hUC-MSCs used to treat POF. So far, the data shows promising results regarding the treatment of POF using hUC-MSCs. Several properties like relatively low immunogenicity, multipotency, multiple origins, affordability, convenience in production, high efficacy, and donor/recipient friendliness make hUC-MSCs a good choice for treating basic POF. It has been reported that hUC-MSCs impact and enhance all stages of injured tissue regeneration by concurrently stimulating numerous pathways in a paracrine manner, which are involved in the control of ovarian fibrosis, angiogenesis, immune system modulation, and apoptosis. Furthermore, some studies demonstrated that stem cell treatment could lead to hormone-level restoration, follicular activation, and functional restoration of the ovaries. Therefore, all the results in hand regarding the use of hUC-MSCs for the treatment of POF encourage researchers for further clinical trials, which will overcome the ongoing challenges and make this treatment strategy applicable to the clinic in the near future.

MASTREE+: Time-series of plant reproductive effort from six continents.

Significant gaps remain in understanding the response of plant reproduction to environmental change. This is partly because measuring reproduction in long-lived plants requires direct observation over many years and such datasets have rarely been made publicly available. Here we introduce MASTREE+, a data set that collates reproductive time-series data from across the globe and makes these data freely available to the community. MASTREE+ includes 73,828 georeferenced observations of annual reproduction (e.g. seed and fruit counts) in perennial plant populations worldwide. These observations consist of 5971 population-level time-series from 974 species in 66 countries. The mean and median time-series length is 12.4 and 10 years respectively, and the data set includes 1122 series that extend over at least two decades (≥20 years of observations). For a subset of well-studied species, MASTREE+ includes extensive replication of time-series across geographical and climatic gradients. Here we describe the open-access data set, available as a.csv file, and we introduce an associated web-based app for data exploration. MASTREE+ will provide the basis for improved understanding of the response of long-lived plant reproduction to environmental change. Additionally, MASTREE+ will enable investigation of the ecology and evolution of reproductive strategies in perennial plants, and the role of plant reproduction as a driver of ecosystem dynamics.

Aún existen importantes vacíos en la comprensión de la respuesta reproductiva de las plantas al cambio medioambiental, en parte, porque su monitoreo en especies de plantas longevas requiere una observación directa durante muchos años, y estos conjuntos de datos rara vez han estado disponibles. Aquí presentamos a MASTREE +, una base de datos que recopila series de tiempo de la reproducción de las plantas de todo el planeta, poniendo a disposición estos datos de libre acceso para la comunidad científica. MASTREE + incluye 73.828 puntos de observación de la reproducción anual georreferenciados (ej. conteos de semillas y frutos) en poblaciones de plantas perennes en todo el mundo. Estas observaciones consisten en 5971 series temporales a nivel de población provenientes de 974 especies en 66 países. La mediana de la duración de las series de tiempo es de 10 años (media = 12.4 años) y el conjunto de datos incluye 1.122 series de al menos dos décadas (≥20 años de observaciones). Para un subconjunto de especies bien estudiadas, MASTREE +incluye un amplio conjunto de series temporales replicadas en gradientes geográficos y climáticos. Describimos el conjunto de datos de acceso abierto disponible como un archivo.csv y presentamos una aplicación web asociada para la exploración de datos. MASTREE+ proporcionará la base para mejorar la comprensión sobre la respuesta reproductiva de plantas longevas al cambio medioambiental. Además, MASTREE+ facilitará los avances en la investigación de la ecología y la evolución de las estrategias reproductivas en plantas perennes y el papel de la reproducción vegetal como determinante de la dinámica de ecosistemas.

Proceedings of the 10th annual deep brain stimulation think tank: Advances in cutting edge technologies, artificial intelligence, neuromodulation, neuroethics, interventional psychiatry, and women in neuromodulation.

The deep brain stimulation (DBS) Think Tank X was held on August 17-19, 2022 in Orlando FL. The session organizers and moderators were all women with the theme women in neuromodulation. Dr. Helen Mayberg from Mt. Sinai, NY was the keynote speaker. She discussed milestones and her experiences in developing depression DBS. The DBS Think Tank was founded in 2012 and provides an open platform where clinicians, engineers and researchers (from industry and academia) can freely discuss current and emerging DBS technologies as well as the logistical and ethical issues facing the field. The consensus among the DBS Think Tank X speakers was that DBS has continued to expand in scope however several indications have reached the "trough of disillusionment." DBS for depression was considered as "re-emerging" and approaching a slope of enlightenment. DBS for depression will soon re-enter clinical trials. The group estimated that globally more than 244,000 DBS devices have been implanted for neurological and neuropsychiatric disorders. This year's meeting was focused on advances in the following areas: neuromodulation in Europe, Asia, and Australia; cutting-edge technologies, closed loop DBS, DBS tele-health, neuroethics, lesion therapy, interventional psychiatry, and adaptive DBS.

An assessment of temporal variability in mast seeding of North American Pinaceae.

Our overall objective is to synthesize mast-seeding data on North American Pinaceae to detect characteristic features of reproduction (i.e. development cycle length, serotiny, dispersal agents), and test for patterns in temporal variation based on weather variables. We use a large dataset (n = 286 time series; mean length = 18.9 years) on crop sizes in four conifer genera (Abies, Picea, Pinus, Tsuga) collected between 1960 and 2014. Temporal variability in mast seeding (CVp) for 2 year genera (Abies, Picea, Tsuga) was higher than for Pinus (3 year), and serotinous species had lower CVp than non-serotinous species; there were no relationships of CVp with elevation or latitude. There was no difference in family-wide CVp across four tree regions of North America. Across all genera, July temperature differences between bud initiation and the prior year (ΔT) was more strongly associated with reproduction than absolute temperature. Both CVp and ΔT remained steady over time, while absolute temperature increased by 0.09°C per decade. Our use of the ΔT model included a modification for Pinus, which initiates cone primordia 2 years before seedfall, as opposed to 1 year. These findings have implications for how mast-seeding patterns may change with future increases in temperature, and the adaptive benefits of mast seeding. This article is part of the theme issue 'The ecology and evolution of synchronized seed production in plants'.

Increasing fire and the decline of fire adapted black spruce in the boreal forest.

Intensifying wildfire activity and climate change can drive rapid forest compositional shifts. In boreal North America, black spruce shapes forest flammability and depends on fire for regeneration. This relationship has helped black spruce maintain its dominance through much of the Holocene. However, with climate change and more frequent and severe fires, shifts away from black spruce dominance to broadleaf or pine species are emerging, with implications for ecosystem functions including carbon sequestration, water and energy fluxes, and wildlife habitat. Here, we predict that such reductions in black spruce after fire may already be widespread given current trends in climate and fire. To test this, we synthesize data from 1,538 field sites across boreal North America to evaluate compositional changes in tree species following 58 recent fires (1989 to 2014). While black spruce was resilient following most fires (62%), loss of resilience was common, and spruce regeneration failed completely in 18% of 1,140 black spruce sites. In contrast, postfire regeneration never failed in forests dominated by jack pine, which also possesses an aerial seed bank, or broad-leaved trees. More complete combustion of the soil organic layer, which often occurs in better-drained landscape positions and in dryer duff, promoted compositional changes throughout boreal North America. Forests in western North America, however, were more vulnerable to change due to greater long-term climate moisture deficits. While we find considerable remaining resilience in black spruce forests, predicted increases in climate moisture deficits and fire activity will erode this resilience, pushing the system toward a tipping point that has not been crossed in several thousand years.

Effect of a Scalable School-Based Intervention on Cardiorespiratory Fitness in Children: A Cluster Randomized Clinical Trial.

Importance: Cardiorespiratory fitness is an important marker of childhood health and low fitness levels are a risk factor for disease later in life. Levels of children's fitness have declined in recent decades. Whether school-based physical activity interventions can increase fitness at the population level remains unclear. Objective: To evaluate the effect of an internet-based intervention on children's cardiorespiratory fitness across a large number of schools. Design, Setting, and Participants: In this cluster randomized clinical trial, 22 government-funded elementary schools (from 137 providing consent) including 1188 students stratified from grades 3 and 4 in New South Wales, Australia, were randomized. The other schools received the intervention but were not included in the analysis. Eleven schools received the internet-based intervention and 11 received the control intervention. Recruitment and baseline testing began in 2016 and ended in 2017. Research assistants, blinded to treatment allocation, completed follow-up outcome assessments at 12 and 24 months. Data were analyzed from July to August 2020. Interventions: The internet-based intervention included standardized online learning for teachers and minimal in-person support from a project mentor (9-10 months). Main Outcomes and Measures: Multistage 20-m shuttle run test for cardiorespiratory fitness. Results: Of 1219 participants (49% girls; mean [SD] age, 8.85 [0.71] years) from 22 schools, 1188 students provided baseline primary outcome data. At 12 months, the number of 20-m shuttle runs increased by 3.32 laps (95% CI, 2.44-4.20 laps) in the intervention schools and 2.11 laps (95% CI, 1.38-2.85 laps) in the control schools (adjusted difference = 1.20 laps; 95% CI, 0.17-2.24 laps). By 24 months, the adjusted difference was 2.22 laps (95% CI, 0.89-3.55 laps). The cost per student was AUD33 (USD26). Conclusions and Relevance: In this study, a school-based intervention improved children's cardiorespiratory fitness when delivered in a large number of schools. The low cost and sustained effect over 24 months of the intervention suggests that it may have potential to be scaled at the population level. Trial Registration: http://anzctr.org.au Identifier: ACTRN12616000731493.

Acute effects of brain-responsive neurostimulation in drug-resistant partial onset epilepsy.

OBJECTIVE: Understanding the acute effects of responsive stimulation (AERS) based on intracranial EEG (iEEG) recordings in ambulatory patients with drug-resistant partial epilepsy, and correlating these with changes in clinical seizure frequency, may help clinicians more efficiently optimize responsive stimulation settings. METHODS: In patients implanted with the NeuroPace® RNS® System, acute changes in iEEG spectral power following active and sham stimulation periods were quantified and compared within individual iEEG channels. Additionally, acute stimulation-induced acute iEEG changes were compared within iEEG channels before and after patients experienced substantial reductions in clinical seizure frequency. RESULTS: Responsive stimulation resulted in a 20.7% relative decrease in spectral power in the 2-4 second window following active stimulation, compared to sham stimulation. On several detection channels, the AERS features changed when clinical outcomes improved but were relatively stable otherwise. AERS change direction associated with clinical improvement was generally consistent within detection channels. CONCLUSIONS: In this retrospective analysis, patients with drug-resistant partial epilepsy treated with direct brain-responsive neurostimulation showed an acute stimulation related reduction in iEEG spectral power that was associated with reductions in clinical seizure frequency. SIGNIFICANCE: Identifying favorable stimulation related changes in iEEG activity could help physicians to more rapidly optimize stimulation settings for each patient.

Variations in lower body stiffness during sports-specific tasks in well-trained female athletes.

The present study aimed to assess the differences in leg stiffness and the associated performance variables between athletes from various training backgrounds during tasks relevant to athletic training. Forty-seven female participants (20 nationally identified netballers, 13 high-level endurance athletes and 14 age-matched controls) completed a sprint, anticipated sidestep change of direction and unilateral repetitive hopping task to assess leg stiffness and the relationship of stiffness between the different tasks. Leg stiffness and performance variables were evaluated with a 10-camera motion analysis system and force plate, and leg stiffness was derived through the McMahon and Cheng methodology (1990). Significant differences were evident in leg stiffness, and the contributing performance variables between groups across all assessed tasks (p < 0.001-0.017). Furthermore, results indicated the control group displayed no leg stiffness relationship between the evaluated tasks, while the stiffness relationship between tasks within athletic populations reflected training-specific demands of athletes. The results of this study indicated that the athletic training background of individuals may contribute to inherent leg stiffness differences between groups. Furthermore, the stiffness relationship observed between tasks suggests practitioners should take care in the selection of task used to monitor leg stiffness from a performance or injury risk perspective.

Osteochondral Autograft Plugs versus Paste Graft: Ex Vivo Morselization Increases Chondral Matrix Production.

OBJECTIVE: Patients undergoing articular cartilage paste grafting have been shown in studies to have significant improvement in pain and function in long-term follow-ups. We hypothesized that ex vivo impacting of osteochondral autografts results in higher chondrocyte matrix production versus intact osteochondral autograft plugs. DESIGN: This institutional review board-approved study characterizes the effects of impacting osteochondral plugs harvested from the intercondylar notch of 16 patients into a paste, leaving one graft intact as a control. Cell viability/proliferation, collagen type I/II, SOX-9, and aggrecan gene expression via qRT-PCR (quantitative reverse transcription-polymerase chain reaction) were analyzed at 24 and 48 hours. Matrix production and cell morphology were evaluated using histology. RESULTS: Paste samples from patients (mean age 39.7) with moderate (19%) to severe (81%) cartilage lesions displayed 34% and 80% greater cell proliferation compared to plugs at 24 and 48 hours post processing, respectively (P = 0.015 and P = 0.021). qRT-PCR analysis yielded a significant (P = 0.000) increase of aggrecan, SOX-9, collagen type I and II at both 24 and 48 hours. Histological examination displayed cell division throughout paste samples, with accumulation of aggrecan around multiple chondrocyte lacunae. CONCLUSIONS: Paste graft preparation resulted in increased mobility of chondrocytes by matrix disruption without loss of cell viability. The impaction procedure stimulated chondrocyte proliferation resulting in a cellular response to reestablish native extracellular matrix. Analysis of gene expression supports a regenerative process of cartilage tissue formation and contradicts long-held beliefs that impaction trauma leads to immediate cell death. This mechanism of action translates into clinical benefit for patients with moderate to severe cartilage damage.

Diabetes and Humor: A Preliminary Investigation.

Diabetes can take a tremendous toll on physical and psychological health. Given the growing evidence of the benefits of humor, this study examined the association between diabetes and humor. The sample consisted of 249 participants: 72.3% with type 1 diabetes, 70.3% female, 89.5% Caucasian, and 70.9% college educated. Participants completed the Humor Styles Questionnaire (HSQ) and were compared with HSQ norms. On the affiliative humor scale, the diabetes group did not differ from the norm (P >0.05), nor did those with type 1 diabetes (P >0.05). Scores of those with type 2 diabetes were lower than the norm (P <0.05). On the self-enhancing humor scale, the diabetes group did not differ from the norm (P >0.05), nor did the subgroups with type 1 diabetes (P >0.05) or type 2 diabetes (P >0.05). The diabetes group was lower than the norm on aggressive humor (P <0.01), as were the subgroups with type 1 diabetes (P <0.01) and type 2 diabetes (P <0.05). The diabetes group was higher than the norm on self-defeating humor (P <0.01), as were the subgroups with type 1 diabetes (P <0.01) and type 2 diabetes (P <0.01). Results suggest that people with either type of diabetes are more inclined toward self-enhancing humor, are less inclined toward aggressive humor, and score higher on self-defeating humor, and those with type 1 diabetes are also inclined toward affiliative humor. Results are discussed relative to the sample being comprised of individuals with good glycemic control (mean A1C 7.06 ± 1.39%). This study offers a preliminary comparison of humor among people with diabetes versus those in a healthy norm group without diabetes.