Tubular IL-1ß Induces Salt Sensitivity in Diabetes by Activating Renal Macrophages.

BACKGROUND: Chronic renal inflammation has been widely recognized as a major promoter of several forms of high blood pressure including salt-sensitive hypertension. In diabetes, IL (interleukin)-6 induces salt sensitivity through a dysregulation of the epithelial sodium channel. However, the origin of this inflammatory process and the molecular events that culminates with an abnormal regulation of epithelial sodium channel and salt sensitivity in diabetes are largely unknown. METHODS: Both in vitro and in vivo approaches were used to investigate the molecular and cellular contributors to the renal inflammation associated with diabetic kidney disease and how these inflammatory components interact to develop salt sensitivity in db/db mice. RESULTS: Thirty-four-week-old db/db mice display significantly higher levels of IL-1ß in renal tubules compared with nondiabetic db/+ mice. Specific suppression of IL-1ß in renal tubules prevented salt sensitivity in db/db mice. A primary culture of renal tubular epithelial cells from wild-type mice releases significant levels of IL-1ß when exposed to a high glucose environment. Coculture of tubular epithelial cells and bone marrow-derived macrophages revealed that tubular epithelial cell-derived IL-1ß promotes the polarization of macrophages towards a proinflammatory phenotype resulting in IL-6 secretion. To evaluate whether macrophages are the cellular target of IL-1ß in vivo, diabetic db/db mice were transplanted with the bone marrow of IL-1R1 (IL-1 receptor type 1) knockout mice. db/db mice harboring an IL-1 receptor type 1 knockout bone marrow remained salt resistant, display lower renal inflammation and lower expression and activity of epithelial sodium channel compared with db/db transplanted with a wild-type bone marrow. CONCLUSIONS: Renal tubular epithelial cell-derived IL-1ß polarizes renal macrophages towards a proinflammatory phenotype that promotes salt sensitivity through the accumulation of renal IL-6. When tubular IL-1ß synthesis is suppressed or in db/db mice in which immune cells lack the IL-1R1, macrophage polarization is blunted resulting in no salt-sensitive hypertension.

The IFNγ-PDL1 Pathway Enhances CD8T-DCT Interaction to Promote Hypertension.

BACKGROUND: Renal T cells contribute importantly to hypertension, but the underlying mechanism is incompletely understood. We reported that CD8Ts directly stimulate distal convoluted tubule cells (DCTs) to increase NCC (sodium chloride co-transporter) expression and salt reabsorption. However, the mechanistic basis of this pathogenic pathway that promotes hypertension remains to be elucidated. METHODS: We used mouse models of DOCA+salt (DOCA) treatment and adoptive transfer of CD8+ T cells (CD8T) from hypertensive animals to normotensive animals in in vivo studies. Co-culture of mouse DCTs and CD8Ts was used as in vitro model to test the effect of CD8T activation in promoting NCC-mediated sodium retention and to identify critical molecular players contributing to the CD8T-DCT interaction. Interferon (IFNγ)-KO mice and mice receiving renal tubule-specific knockdown of PDL1 were used to verify in vitro findings. Blood pressure was continuously monitored via radio-biotelemetry, and kidney samples were saved at experimental end points for analysis. RESULTS: We identified critical molecular players and demonstrated their roles in augmenting the CD8T-DCT interaction leading to salt-sensitive hypertension. We found that activated CD8Ts exhibit enhanced interaction with DCTs via IFN-γ-induced upregulation of MHC-I and PDL1 in DCTs, thereby stimulating higher expression of NCC in DCTs to cause excessive salt retention and progressive elevation of blood pressure. Eliminating IFN-γ or renal tubule-specific knockdown of PDL1 prevented T cell homing into the kidney, thereby attenuating hypertension in 2 different mouse models. CONCLUSIONS: Our results identified the role of activated CD8Ts in contributing to increased sodium retention in DCTS through the IFNγ-PDL1 pathway. These findings provide a new mechanism for T cell involvement in the pathogenesis of hypertension and reveal novel therapeutic targets.

Improving Mechanical Circulatory Support Outcomes in Failing Bidirectional Glenn Physiology.

There remains high morbidity and mortality with mechanical circulatory support (MCS) in failing bidirectional Glenn (BDG) physiology. We performed a retrospective analysis of children with BDG physiology supported with MCS before and after 2018. Fourteen patients met inclusion criteria (median age 1.5 years, weight 9 kg). Prior to 2018 (n = 7), with variable anticoagulation and strategies including pulsatile VAD, continuous flow VAD, and extracorporeal membrane oxygenation (ECMO), 3 (43%) of patients were transplanted with a total of 536 patient-days of support (median 59 days). Major hemocompatability-related adverse event (MHRAE) rate was 63 per 100 patient-months. After 2018 (n = 7), using a staged support strategy (ECMO to pulsatile VAD) and bivalirudin anticoagulation, 5 (71%) patients were transplanted with a total of 1260 patient-days of support (median 188 days) and MHRAE rate of 24 per 100 patient-months. Despite challenging physiology, we have observed improved survival and reduced MHRAE despite longer support duration.

Harnessing nanotechnology to expand the toolbox of chemical biology.

Although nanotechnology often addresses biomedical needs, nanoscale tools can also facilitate broad biological discovery. Nanoscale delivery, imaging, biosensing, and bioreactor technologies may address unmet questions at the interface between chemistry and biology. Currently, many chemical biologists do not include nanomaterials in their toolbox, and few investigators develop nanomaterials in the context of chemical tools to answer biological questions. We reason that the two fields are ripe with opportunity for greater synergy. Nanotechnologies can expand the utility of chemical tools in the hands of chemical biologists, for example, through controlled delivery of reactive and/or toxic compounds or signal-binding events of small molecules in living systems. Conversely, chemical biologists can work with nanotechnologists to address challenging biological questions that are inaccessible to both communities. This Perspective aims to introduce the chemical biology community to nanotechnologies that may expand their methodologies while inspiring nanotechnologists to address questions relevant to chemical biology.

Contemporary outcomes of pediatric cardiac transplantation with a positive retrospective crossmatch.

BACKGROUND: A positive crossmatch (+ XM) has traditionally been associated with adverse outcomes following pediatric heart transplantation. However, more recent studies suggest that favorable intermediate-term outcomes may be achieved despite a + XM. This study's hypothesis is that children with a + XM have similar long-term survival, but higher rate of complications such as rejection, coronary allograft vasculopathy (CAV), and infection, compared to patients with a negative (-) XM. METHODS: The Pediatric Heart Transplant Society Registry (PHTS) database was queried from 2010-2021 for all patients <18 years of age with a known XM. Baseline demographics were compared between + XM and - XM groups using appropriate parametric and non-parametric group comparisons. Cox Proportional Hazards Modeling was used to identify risk factors for post-transplant graft loss, rejection, and CAV. RESULTS: Of 4599 pediatric heart transplants during the study period, XM results were available for 3914 (85%), of which 373 (9.5%) had a + XM. Univariate analysis showed lower 10-year survival for patients with + XM (HR = 1.3, p = .04). Multivariate analyses revealed no significant difference in 10-year survival in the 2 groups; however, time to first rejection (p = .0001) remained significantly shorter in the + XM group. CONCLUSIONS: Pediatric patients transplanted across a + XM experience earlier rejection; however, after multivariate adjustment, + XM is not independently associated with intermediate-term graft loss. The risk of heart transplantation against a + XM must be balanced with the ongoing risk of waitlist mortality.

Are There Differences in Opioid Prescriptions to Urban and Rural Patients by Oral and Maxillofacial Surgeons in Massachusetts From 2011 to 2021?

PURPOSE: Oral-maxillofacial surgeons (OMSs) are frequent prescribers of opioid analgesics. It remains unclear if prescription patterns differ for urban versus rural patients, given potential differences in access to and delivery of care. This study aimed to characterize urban-rural differences in opioid analgesic prescriptions to patients in Massachusetts by OMSs from 2011 to 2021. METHODS: This retrospective cohort study used the Massachusetts Prescription Monitoring Program database to identify Schedule II and III opioid prescriptions by providers with specialty of oral and maxillofacial surgery from 2011 to 2021. The primary predictor variable was patient geography (urban/rural) and secondary predictor was year (2011-2021). The primary outcome variable was milligram morphine equivalent (MME) per prescription. Secondary outcome variables were days' supply per prescription and number of prescriptions received per patient. Descriptive and linear regression statistics were performed to analyze differences in prescriptions to urban and rural patients each year and throughout the study period. RESULTS: The study data, which includes OMS opioid prescriptions (n = 1,057,412) in Massachusetts from 2011 to 2021, ranged annually between 63,678 and 116,000 prescriptions to between 58,000 and 100,000 unique patients. The cohorts each year ranged between 48 and 56% female with mean ages between 37 and 44 years. There were no differences in the mean number of patients per provider in urban and rural populations in any year. The study sample had a large majority of urban patients (>98%). MME per prescription, days' supply per prescription, and prescriptions received per patient were all generally similar between urban and rural patients each year, with the largest MME per prescription difference in 2019 (87.3 for rural to 73.9 for urban patients, P < .01). From 2011 to 2021, all patients had a steady decrease in MME per prescription (ß = -6.64, 95% confidence interval: -6.81, -6.48; R2 = 0.39) and day's supply per prescription (ß = -0.1, 95% confidence interval: -0.1, -0.09; R2 = 0.37). CONCLUSION: In Massachusetts, there were similar opioid prescribing patterns by oral and maxillofacial surgeons to urban and rural patients from 2011 to 2021. There has also been a steady decrease in the duration and total dosage of opioid prescriptions to all patients. These results are consistent with multiple statewide policies over the last several years aimed at curbing opioid overprescribing.

Kidney-Targeted Renalase Agonist Prevents Cisplatin-Induced Chronic Kidney Disease by Inhibiting Regulated Necrosis and Inflammation.

BACKGROUND: Repeated administration of cisplatin causes CKD. In previous studies, we reported that the kidney-secreted survival protein renalase (RNLS) and an agonist peptide protected mice from cisplatin-induced AKI. METHODS: To investigate whether kidney-targeted delivery of RNLS might prevent cisplatin-induced CKD in a mouse model, we achieved specific delivery of a RNLS agonist peptide (RP81) to the renal proximal tubule by encapsulating the peptide in mesoscale nanoparticles (MNPs). We used genetic deletion of RNLS, single-cell RNA sequencing analysis, and Western blotting to determine efficacy and to explore underlying mechanisms. We also measured plasma RNLS in patients with advanced head and neck squamous cell carcinoma receiving their first dose of cisplatin chemotherapy. RESULTS: In mice with CKD induced by cisplatin, we observed an approximate 60% reduction of kidney RNLS; genetic deletion of RNLS was associated with significantly more severe cisplatin-induced CKD. In this severe model of cisplatin-induced CKD, systemic administration of MNP-encapsulated RP81 (RP81-MNP) significantly reduced CKD as assessed by plasma creatinine and histology. It also decreased inflammatory cytokines in plasma and inhibited regulated necrosis in kidney. Single-cell RNA sequencing analyses revealed that RP81-MNP preserved epithelial components of the nephron and the vasculature and suppressed inflammatory macrophages and myofibroblasts. In patients receiving their first dose of cisplatin chemotherapy, plasma RNLS levels trended lower at day 14 post-treatment. CONCLUSIONS: Kidney-targeted delivery of RNLS agonist RP81-MNP protects against cisplatin-induced CKD by decreasing cell death and improving the viability of the renal proximal tubule. These findings suggest that such an approach might mitigate the development of CKD in patients receiving cisplatin cancer chemotherapy.

Pediatric heart transplant waiting times in the United States since the 2016 allocation policy change.

We describe waiting times for pediatric heart transplant (HT) candidates after the 2016 revision to the US allocation policy. The OPTN database was queried for pediatric HT candidates listed between 7/2016 and 4/2019. Of the 1789 included candidates, 65% underwent HT, 14% died/deteriorated, 8% were removed for improvement, and 13% were still waiting at the end of follow-up. Most candidates were status 1A at HT (81%). Median wait times differ substantially by listing status, blood type, and recipient weight. The likelihood of HT was lower in candidates <25 kg and in those with blood type O; The <25 kg, blood type O subgroup experiences longer wait times and higher wait list mortality. For status 1A candidates, median wait times were 108 days (≤25 kg, blood type O), 80 days (≤25 kg, non-O), 47 days (>25 kg, O), and 24 days (>25 kg, non-O). We found that centers with more selective organ acceptance practices, based on a lower median Pediatric Heart Donor Assessment Tool (PH-DAT) score for completed transplants, experience longer status 1A wait times for their listed patients. These data can be used to counsel families and to select appropriate advanced heart failure therapies to support patients to transplant.

Formulation of Lipid-Free Polymeric Mesoscale Nanoparticles Encapsulating mRNA.

INTRODUCTION: Nanoparticle-mediated gene therapy has found substantial clinical impact, primarily focused on lipid-based nanoparticles. In comparison with lipid nanoparticles, polymeric particles may have certain advantages such as increased biocompatibility and controlled release. Our prior studies have found that polymeric mesoscale nanoparticles exhibited specific targeting to the renal proximal tubules. Thus, in this study, we sought to identify formulation parameters that allow for development of polymeric mesoscale nanoparticles encapsulating functional mRNA for delivery into tubular epithelial cells. METHODS: We evaluated particle uptake in vitro prior to exploring formulation parameters related to introduction of a primary mixture of polymer in acetonitrile and hydrophilic mRNA in water. Finally, we evaluated their functionality in a renal tubular epithelial cell line. RESULTS: We found that MNPs are endocytosed within 15 min and that the mesoscale nanoparticle formulation procedure was generally robust to introduction of a primary mixture and encapsulation of mRNA. These particles exhibited substantial uptake in renal cells in vitro and rapid (< 1 h) expression of a model mCherry fluorescent protein. CONCLUSION: We anticipate these findings having potential in the delivery of specific gene therapies for renal disorders and cancer.

Addition of multiple limiting resources reduces grassland diversity.

Niche dimensionality provides a general theoretical explanation for biodiversity-more niches, defined by more limiting factors, allow for more ways that species can coexist. Because plant species compete for the same set of limiting resources, theory predicts that addition of a limiting resource eliminates potential trade-offs, reducing the number of species that can coexist. Multiple nutrient limitation of plant production is common and therefore fertilization may reduce diversity by reducing the number or dimensionality of belowground limiting factors. At the same time, nutrient addition, by increasing biomass, should ultimately shift competition from belowground nutrients towards a one-dimensional competitive trade-off for light. Here we show that plant species diversity decreased when a greater number of limiting nutrients were added across 45 grassland sites from a multi-continent experimental network. The number of added nutrients predicted diversity loss, even after controlling for effects of plant biomass, and even where biomass production was not nutrient-limited. We found that elevated resource supply reduced niche dimensionality and diversity and increased both productivity and compositional turnover. Our results point to the importance of understanding dimensionality in ecological systems that are undergoing diversity loss in response to multiple global change factors.

Physical fitness, physical activity and adiposity: associations with risk factors for cardiometabolic disease and cognitive function across adolescence.

BACKGROUND: The cross-sectional associations between physical activity, physical fitness and adiposity with risk factors for cardiometabolic disease (particularly novel ones such as inflammatory cytokines) and cognitive function across the period of adolescence are not well understood. Additionally, novel physical activity metrics that summarise activity volume and intensity in a continuous manner have not been investigated in this context. Therefore, this study investigated the cross-sectional associations between physical activity, physical fitness and adiposity with risk factors for cardiometabolic disease and cognitive function. These associations were compared between younger and older adolescents. METHODS: Seventy younger (11-12y, 35 girls) and 43 older (14-15y, 27 girls) adolescents volunteered to take part in the study. Physical fitness (multi-stage fitness test, MSFT) and adiposity (waist circumference) were determined, followed 7d later by resting blood pressure, a fasted blood sample (glucose, plasma insulin, IL6, IL10, IL15 and IL-1ß concentrations) and a cognitive function test battery. Habitual physical activity was monitored via hip-worn accelerometers over this 7-d period and the average acceleration (activity volume), and intensity gradient (intensity distribution of activity) were determined. RESULTS: Average acceleration and intensity gradient were negatively associated with mean arterial blood pressure (ß = -0.75 mmHg, p = 0.021; ß = -10 mmHg, p = 0.006, respectively), and waist circumference was positively associated with IL-6 concentration (ß = 0.03%, p = 0.026), with stronger associations observed in older adolescents. Higher physical fitness (MSFT distance) was positively associated with anti-inflammatory IL-15 concentration (ß = 0.03%, p = 0.038) and faster response times on the incongruent Stroop task (ß = -1.43 ms, p = 0.025), the one-item level of the Sternberg paradigm (ß = -0.66 ms, p = 0.026) and the simple (ß = 0.43 ms, p = 0.032) and complex (ß = -2.43 ms, p = 0.020) levels of the visual search test, but these were not moderated by age group. CONCLUSIONS: The present study highlights the important role of physical activity (both the volume and intensity distribution) and physical fitness for cardio-metabolic health. Furthermore, the present study highlights the importance of physical fitness for a variety of cognitive function domains in adolescents, irrespective of age.

Orthognathic Surgery in Older Patients: Is Age Associated With Perioperative Complications?

PURPOSE: The incidence of older patients undergoing orthognathic surgery is increasing. The purpose of this study is to evaluate the association between age and perioperative adverse outcomes in patients undergoing orthognathic surgery. METHODS: This is a retrospective cohort study of patients undergoing orthognathic surgery in the 2011 to 2019 American College of Surgeons National Surgical Quality Improvement Program databases. The primary predictor variable was age group (≥40 or <40 years). The primary outcome variable was adverse outcomes occurring within 30 days of the index operation. Descriptive, bivariate, and Firth logistic regression statistics were utilized to evaluate association between age and adverse outcomes. RESULTS: During the study period, 1,226 patients underwent an orthognathic procedure and 835 subjects were included. Of these subjects, 145 were 40 years or older (17.4%) and 690 were less than 40 years (82.6%). Subjects 40 years or older were more likely to be American Society of Anesthesiologists (ASA) classification II (P ≤ .001), ASA III (P ≤ .001), or diagnosed with obstructive sleep apnea (P ≤ .001). A total of 34 subjects experienced an adverse outcome (4.07%), though there was no significant difference in the incidence of adverse outcomes between age groups (P = .152). In bivariate analysis, hypertension on medication (P = .037), procedure type (P = .001), and segmented Le Fort I osteotomies (P = .039) were associated with adverse outcomes. After controlling for age, hypertension on medication, segmented Le Fort I osteotomies, and diagnosis of obstructive sleep apnea, isolated mandibular osteotomies were the only independent predictors of adverse outcomes (odds ratio 2.64; 95% confidence interval, 1.06 to 7.24; P = .038). Length of stay was 1.38 ± 1.43 days for the 40 years or older group compared to 1.06 ± 1.18 in the <40 group (P = .012). CONCLUSIONS: Despite higher ASA classifications, older patients did not have a significantly greater incidence of perioperative adverse outcomes including airway complications, nor was increased age associated with adverse outcomes in bivariate or multivariate analysis.

Agreement and equivalence of estimated physical activity behaviours, using ENMO- and counts-based processing methods, for wrist-worn accelerometers in adolescents.

The present study examined the agreement and equivalence between two physical activity processing methods. Data were obtained from 161 Hong-Kong adolescents (74 girls, age: 12.6 ± 1.7y). Participants wore an Actigraph GT3XBT on their non-dominant wrist for 7d. Time spent sedentary, and in light-(LPA), moderate-(MPA), vigorous-(VPA), and moderate-to-vigorous physical activity (MVPA) were calculated using different processing methods (proprietary counts and Euclidean Norm Minus One (ENMO)). Intraclass correlation coefficients (ICC) were used to examine absolute agreement (ICC2) and consistency (ICC3), and equivalence was assessed using pairwise equivalence tests. Using ENMO, sedentary time and VPA were higher, whereas all other behaviours were lower (compared to counts processing). Agreement ranged from poor (ICC2:0.42(Sedentary)) to moderate (ICC2:0.86(LPA)) and consistency ranged from moderate (ICC3:0.71(sedentary)) to good (ICC3:0.91(LPA)). Methods were not considered equivalent (all p > 0.05). Due to differences in the wear-time validation of processing methods, a sensitivity analyses (sub-sample with the same valid wear time for both methods (n = 56)), resulted in minimal change. Lack of agreement and equivalence between ENMO and counts processing methods suggests that the processing method significantly affects youth physical activity estimates.

Associations of Self-Control with Physical Activity, Physical Fitness, and Adiposity in Adolescents.

The associations between self-control and objective measures of physical activity, physical fitness, and adiposity are yet to be explored in young people; this is a gap in the literature that the present study aimed to address. The study employed a cross-sectional design. A total of 101 young people participated in the study. Participants completed the Brief Self-Control Scale as a measure of trait self-control. Free-living physical activity was assessed using an ActiGraph GT3X + triaxial accelerometer, which was worn for 7 days. Participants also completed the 15-meter version of the multistage fitness test as a measure of physical fitness. For the assessment of adiposity, three criterion measures were used: body mass index (BMI), sum of skinfolds, and waist circumference. Data were analyzed using the glm function in the open access software R. Higher levels of trait self-control were associated with higher levels of physical fitness (measured by distance run on the multistage fitness test) and lower adiposity (BMI, waist circumference, and sum of skinfolds) in adolescents. There was a tendency for a positive association between self-control and time spent in vigorous physical activity, although this did not reach statistical significance. In a combined model, self-control was also associated with both physical fitness and waist circumference, with these effects independent of each other. These findings suggest that self-control is associated with healthy behaviors and characteristics in adolescents and is thus potentially an attractive target for future interventions aimed at increasing physical activity and physical fitness and reducing adiposity in this population.

Health Help-Seeking Behaviour in Spiritual Healing Practice: Records from the Panacea Society's Healing Department, 1924-1997.

Why people seek help is a question shared by both health psychologists and scholars of spiritual healing. This overlap, however, has gone unexplored. This article shows convergence between health help-seeking behaviours in spiritual healing and secular professional health services. It does so by drawing on the archival records from the Panacea Society in Bedford, England, which began an international healing ministry by post-amassing over 120,000 correspondents from 93 different countries. Archives from the Panacea Society's Healing Department containing records of the self-reported effects of the prescribed water-taking healing ritual were used to investigate variables related to help-seeking for health problems through spiritual healing. A sample of over 10% of the available records (n = 7192) contained data from 40,627 letters written over a 73-year period from 48 different countries. In line with research from health psychology, and specifically the Health Belief Model, findings showed that those who were older, female, and receiving perceived benefits from treatment were more likely to engage in help-seeking.

Oxidative Route to Indoles via Intramolecular Amino-Hydroxylation of o-Allenyl Anilines.

A new intramolecular oxidative amino-hydroxylation of o-allenyl anilines is reported. Treatment of carbamate-protected anilines with lead(IV) carboxylates in dichloromethane at room temperature results in facile tandem C-N (allene cyclization) and C-O bond formation (carboxylate trapping) to form indole products. Detailed reaction scope, mechanistic and kinetic studies suggest a reaction pathway involving an initial Wessely dearomatization step followed by cyclization and rearomatization.

Predictors of postprandial glycaemia, insulinaemia and insulin resistance in adolescents.

Postprandial glycaemia and insulinaemia are important risk factors for type 2 diabetes. The prevalence of insulin resistance in adolescents is increasing, but it is unknown how adolescent participant characteristics such as BMI, waist circumference, fitness and maturity offset may explain responses to a standard meal. The aim of the present study was to examine how such participant characteristics affect the postprandial glycaemic and insulinaemic responses to an ecologically valid mixed meal. Data from the control trials of three separate randomised, crossover experiments were pooled, resulting in a total of 108 participants (fifty-two boys, fifty-six girls; aged 12·5 (SD 0·6) years; BMI 19·05 (SD 2·66) kg/m2). A fasting blood sample was taken for the calculation of fasting insulin resistance, using the homoeostatic model assessment of insulin resistance (HOMA-IR). Further capillary blood samples were taken before and 30, 60 and 120 min after a standardised lunch, providing 1·5 g/kg body mass of carbohydrate, for the quantification of blood glucose and plasma insulin total AUC (tAUC). Hierarchical multiple linear regression demonstrated significant predictors for plasma insulin tAUC were waist circumference, physical fitness and HOMA-IR (F(3,98) = 36·78, P < 0·001, adjusted R2 = 0·515). The variance in blood glucose tAUC was not significantly explained by the predictors used (F(7,94) = 1·44, P = 0·198). Significant predictors for HOMA-IR were BMI and maturity offset (F(2,102) = 14·06, P < 0·001, adjusted R2 = 0·021). In summary, the key findings of the study are that waist circumference, followed by physical fitness, best explained the insulinaemic response to an ecologically valid standardised meal in adolescents. This has important behavioural consequences because these variables can be modified.

A promiscuous glycosyltransferase generates poly-ß-1,4-glucan derivatives that facilitate mass spectrometry-based detection of cellulolytic enzymes.

Promiscuous activity of a glycosyltransferase was exploited to polymerise glucose from UDP-glucose via the generation of ß-1,4-glycosidic linkages. The biocatalyst was incorporated into biocatalytic cascades and chemo-enzymatic strategies to synthesise cello-oligosaccharides with tailored functionalities on a scale suitable for employment in mass spectrometry-based assays. The resulting glycan structures enabled reporting of the activity and selectivity of celluloltic enzymes.

Effect of acute football activity and physical fitness on glycaemic and insulinaemic responses in adolescents.

The present study examined the metabolic responses to an acute bout of football and the overall and moderating role of physical fitness on these responses, in adolescents. Thirty-six adolescents (16 girls, 20 boys; 12.6±0.5 y) completed two trials (60-min football and 60-min seated rest) separated by 7-d. Capillary blood samples were taken at baseline (60-min prior to exercise/rest), immediately, 30- and 60-min post-exercise and 30-, 60- and 120-min following a standardised lunch (1.5-, 2- and 3-h post-exercise), for the determination of blood glucose and plasma insulin concentrations. The median split of distance covered on the multi-stage fitness test was used to define high- and low-fit groups. Overall plasma insulin tAUC following lunch was lower in high-fit participants compared to low-fit (high-fit: 3784.2±1653.1 pmol·L-1x120min, low-fit: 6457.3±3290.7 pmol·L-1x120min; p<0.001), although there was no acute effect of the football session (p>0.05). Football reduced blood glucose concentration 1-h post-exercise compared to control (exercise: 3.8±0.6 mmol·L-1, rest: 4.6±0.8 mmol·L-1; p<0.001), but this was similar for the high- and low-fit participants (p>0.05). Blood glucose tAUC was not affected by exercise or physical fitness (p>0.05). These data emphasise the importance of physical fitness for metabolic health in adolescents, as well as the utility of football as a popular form of games-based activity for improving glucose regulation.

Online education in a hurry: Delivering pediatric graduate medical education during COVID-19.

In the setting of the coronavirus disease 2019 (COVID-19) pandemic, an emergency hospital-wide eWork policy was enacted at Boston Children's Hospital on March 16, 2020. The number of clinicians on campus was restricted to only essential personnel, guidelines limited clinical care delivery to solely non-elective patients, and strict maximums were placed on the numbers of people allowed to congregate in the same physical space. With this abrupt transition to social distancing and electronic communication, the established approach to educating graduate medical trainees became obsolete overnight. Anticipating significant impact on trainee and faculty professional and personal lives, the importance of adaptive teaching strategies was evident. This document details one approach to redesigning the clinical learning system including a description of the learners and environment, the pedagogical principles that guided the approach, and technological tools used in implementation. Additionally, available literature pertinent to this topic is explored, assessment of the work to date is presented, and suggestions are provided regarding future directions related to online graduate medical education.