New Insights Into Accelerometer-Measured Habitual Physical Activity and Sedentary Time During Early Recovery in Pediatric Concussion.

PURPOSE: Concussion management is shifting away from a rest-is-best approach, as data now suggest that exercise-is-medicine for this mild brain injury. Despite this, we have limited data on habitual physical activity following concussion. Therefore, our objective was to quantify accelerometer-measured physical activity and sedentary time in children with concussion (within the first month of injury) and healthy controls. We hypothesized that children with concussion would be less active than their healthy peers. METHODS: We performed a secondary analysis of prospectively collected accelerometer data. Our sample included children with concussion (n = 60, 31 females) and historical controls (n = 60) matched for age, sex, and season of accelerometer wear. RESULTS: Children with concussion were significantly more sedentary than controls (mean difference [MD], 38.3 min/d, P = .006), and spent less time performing light physical activity (MD, -19.5 min/d, P = .008), moderate physical activity (MD, -9.8 min/d, P < .001), and vigorous physical activity (MD, -12.0 min/d, P < .001); these differences were observed from 8:00 AM to 9:00 PM. Sex-specific analyses identified that girls with concussion were less active and more sedentary than both boys with concussion (P = .010) and healthy girls (P < .010). CONCLUSION: There is an activity deficit observed within the first month of pediatric concussion. Physical activity guidelines should address this while considering sex effects.

Emergent dynamics in an astrocyte-neuronal network coupledvianitric oxide.

In the brain, both neurons and glial cells work in conjunction with each other during information processing. Stimulation of neurons can induce calcium oscillations in astrocytes which in turn can affect neuronal calcium dynamics. The 'glissandi' effect is one such phenomenon, associated with a decrease in infraslow fluctuations, in which synchronized calcium oscillations propagate as a wave in hundreds of astrocytes. Nitric oxide molecules released from the astrocytes contribute to synaptic functions based on the underlying astrocyte-neuron interaction network. In this study, by defining an astrocyte-neuronal (A-N) calcium unit as an integrated circuit of one neuron and one astrocyte, we developed a minimal model of neuronal stimulus-dependent and NO-mediated emergence of calcium waves in astrocytes. Incorporating inter-unit communicationviaNO molecules, a coupled network of 1000 such A-N calcium units is developed in which multiple stable regimes were found to emerge in astrocytes. We examined the ranges of neuronal stimulus strength and the coupling strength between A-N calcium units that give rise to such dynamical behaviors. We also report that there exists a range of coupling strength, wherein units not receiving stimulus also start showing oscillations and become synchronized. Our results support the hypothesis that glissandi-like phenomena exhibiting synchronized calcium oscillations in astrocytes help in efficient synaptic transmission by reducing the energy demand of the process.

A multiscale modeling framework to study the interdependence of brain, behavior, and pandemic.

A major constraint of the behavioral epidemiological models is the assumption that human behavior is static; however, it is highly dynamic, especially in uncertain circumstances during a pandemic. To incorporate the dynamicity of human nature in the existing epidemiological models, we propose a population-wide multi-time-scale theoretical framework that assimilates neuronal plasticity as the basis of altering human emotions and behavior. For that, variable connection weights between different brain regions and their firing frequencies are coupled with a compartmental susceptible-infected-recovered model to incorporate the intrinsic dynamicity in the contact transmission rate ( ß ). As an illustration, a model of fear conditioning in conjunction with awareness campaigns is developed and simulated. Results indicate that in the presence of fear conditioning, there exists an optimum duration of daily broadcast time during which awareness campaigns are most effective in mitigating the pandemic. Further, global sensitivity analysis using the Morris method highlighted that the learning rate and firing frequency of the unconditioned circuit are crucial regulators in modulating the emergent pandemic waves. The present study makes a case for incorporating neuronal dynamics as a basis of behavioral immune response and has further implications in designing awareness campaigns.

Genetic analysis of colorectal carcinoma using high throughput single nucleotide polymorphism genotyping technique within the population of Jammu and Kashmir.

BACKGROUND: SNP genotyping has become increasingly more common place to understand the genetic basis of complex diseases like cancer. SNP-genotyping through MassARRAY™ is a cost-effective method to quantitatively analyse the variation of gene expression in multiple samples, making it a potential tool to identify the underlying causes of colorectal carcinogenesis. METHODS: In the present study, SNP genotyping was carried out using Agena MassARRAY™, which is a cost-effective, robust, and sensitive method to analyse multiple SNPs simultaneously. We analysed 7 genes in 492 samples (100 cases and 392 controls) associated with CRC within the population of Jammu and Kashmir. These SNPs were selected based on their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with colorectal cancer within the J&K population.7 SNPs with a call rate of 90% were selected for the study. Out of these, five SNPs rs2234593, rs1799966, rs2229080, rs8034191, rs1042522 were found to be significantly associated with the current study under the allelic model with an Odds Ratio OR = 2.981(1.731-5.136 at 95% CI); p value = 4.81E-05 for rs2234593,OR = 1.685(1.073-2.647 at 95% CI);; p value = 0.02292 for rs1799966, OR = 1.5 (1.1-2.3 at 95% CI), p value = 0.02 for rs2229080, OR = 1.699(1.035-2.791 at 95% CI); p value = 0.03521 for rs8034191, OR = 20.07 (11.26-35.75); p value = 1.84E-34 for rs1042522 respectively. CONCLUSION: This is the first study to find the relation of Genetic variants with the colorectal cancer within the studied population using high throughput MassARRAY™ technology. It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Evaluation of 17 genetic variants in association with leukemia in the north Indian population using MassARRAY Sequenom.

Leukemia is a heterogeneous disorder, characterized by elevated proliferation of white blood cells. In this study, we explored the association of 17 genetic variants with leukemia patients in the Jammu and Kashmir region of north India. The variants were genotyped by using a high-throughput Agena MassARRAY platform in 758 individuals (166 cases and 592 controls). Of the 17 single-nucleotide polymorphisms (SNPs) studied, five SNPs were showing significant association with the high risk of leukemia in the north Indian population, which includes rs10069690 of telomere reverse transcriptase (TERT) with OR = 0.34 (95% CI, 0.20-0.58; p = .0008), rs2972392 (​​​PSCA) with OR 1.86 (95% CI, 1.04-3.81; p = .035), rs4986764 (BRIP1) with OR 1.34 (95% CI, 1.00-1.80; p = .04), rs6990097 (TNKS) with OR 1.81 (95% CI, 1.2-2.6; p = .001) and rs12190287 (TCF21) with OR 2.87 (95% CI, 1.72-4.7; p = .0001) by allelic association using Plink and analyzed by SPSS. This is the first study to explore these variants with leukemia in the studied population.

Exercise Trials in Pediatric Brain Tumor: A Systematic Review of Randomized Studies.

In pediatric brain tumor patients, treatment advances have increased survival rates to nearly 70%, while consequently shifting the burden of disease to long-term management. Exercise has demonstrated potential in improving multiple health impairments secondary to brain tumor treatment. However, these effects have not been consolidated through review. Therefore, we performed a systematic review of 6 health sciences databases (Medline, Embase, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Central Database). Two reviewers screened studies against predefined inclusion criteria, namely that the study must: (i) be pediatric-specific; (ii) examine the effects of an exercise intervention; and (iii) employ a randomized or quasi-randomized trial design. The same 2 reviewers performed data extraction and analyses. From a pool of 4442, 5 articles-based on 2 independent trials-were included in our review (N=41). Exercise interventions were primarily aerobic, but included balance or muscle building components. Exercise had a positive effect on volumetric or diffusion-based neuroimaging outcomes, as well as motor performance and cardiorespiratory fitness. The effects of exercise on cognition remains unclear. Exercise did not worsen any of the outcomes studied. This review captures the state of the science, suggesting a potential role for exercise in children treated for brain tumor.

MassARRAY analysis of twelve cancer related SNPs in esophageal squamous cell carcinoma in J&K, India.

BACKGROUND: MassARRAY (Agena Bioscience™) combines competitive PCR with MALDI-TOF mass spectrometry (MS) analysis that gives highly accurate, sensitive, and high-throughput methods for the quantitative analysis of variation of gene expression in multiple samples. SNPs (Single Nucleotide Polymorphisms) have a very high potential of discovering disease-gene relationships. SNP-genotyping through MassARRAY is not only a cost-effective genotyping method but also provides a platform to validate variants observed through a high-throughput Next-generation sequencing (NGS). METHODS: In the present study, we have incorporated the use of matrix-assisted laser desorption/ionization-time of flight, mass spectrometry (MALDI-TOF) as a tool for differentiating genotypes based on the mass of variant. We have performed multiplex PCR and genotyped 12 SNPs in 758 samples (166 cases and 592 controls). The 12 studied SNPs were chosen with a rationale for their association with multiple cancers in literature. RESULTS: This is the first study to explore these SNPs with esophageal cancer within the J&K population. Out of 12 SNPs, two SNPs rs12190287 of TCF21 and rs10046 of CYP19A1 were significantly associated with esophageal cancer with Odds Ratio (OR) 1.412 (1.09-1.8 at 95% CI, p = 0.008) and 1.54 (1.21-2.072 at 95% CI, p = 0.0007) within the population of Jammu and Kashmir. CONCLUSION: We explored 12 SNPs that were found to be associated with multiple cancers in literature with esophageal cancer within the population of J&K. This is the first study to find the relation of these SNPs with ESCC within the studied population. This study explores the relation of genetic and environmental factors with the ESCC susceptibility.

MassARRAY-based single nucleotide polymorphism analysis in breast cancer of north Indian population.

BACKGROUND: Breast Cancer (BC) is associated with inherited gene mutations. High throughput genotyping of BC samples has led to the identification and characterization of biomarkers for the diagnosis of BC. The most common genetic variants studied are SNPs (Single Nucleotide Polymorphisms) that determine susceptibility to an array of diseases thus serving as a potential tool for identifying the underlying causes of breast carcinogenesis. METHODS: SNP genotyping employing the Agena MassARRAY offers a robust, sensitive, cost-effective method to assess multiple SNPs and samples simultaneously. In this present study, we analyzed 15 SNPs of 14 genes in 550 samples (150 cases and 400 controls). We identified four SNPs of genes TCF21, SLC19A1, DCC, and ERCC1 showing significant association with BC in the population under study. RESULTS: The SNPs were rs12190287 (TCF21) having OR 1.713 (1.08-2.716 at 95% CI) p-value 0.022 (dominant), rs1051266 (SLC19A1) having OR 3.461 (2.136-5.609 at 95% CI) p-value 0.000000466 (dominant), rs2229080 (DCC) having OR 0.6867 (0.5123-0.9205 at 95% CI) p-value 0.0116 (allelic) and rs2298881 (ERCC1) having OR 0.669 (0.46-0.973 at 95% CI), p-value 0.035 (additive) respectively. The in-silico analysis was further used to fortify the above findings. CONCLUSION: It is further anticipated that the variants should be evaluated in other population groups that may aid in understanding the genetic complexity and bridge the missing heritability.

Cognitive and neural effects of exercise following traumatic brain injury: A systematic review of randomized and controlled clinical trials.

Objective: Sub-maximal aerobic exercise can alleviate brain injury-related symptom burden. There is substantial data from animal studies and a growing clinical evidence base to suggest that exercise may also improve cognitive and neural outcomes following brain injury. We performed this systematic review to consolidate evidence from randomized and controlled clinical trials on the effects of exercise on cognitive and neuroimaging outcomes following brain injury in humans.Design: Systematic review.Data sources: MEDLINE, EMBASE, PsychINFO, CINAHL, SPORTDiscus, and Cochrane Central Database.Eligibility criteria for screening studies: Randomized or controlled clinical trials examining the effects of exercise on cognitive and/or neuroimaging outcomes in traumatic brain injury. No restriction was placed on age (or other demographic variables) or severity of injury.Results: Six studies (with an average sample of 42 participants) met eligibility criteria. Three studies used neuroimaging and reported exercise-related improvements as measured by either functional or diffusion-based imaging. The remainder of the trials that employed cognitive outcomes reported largely null findings.Summary/Conclusion: This review demonstrates that exercise shows promise (primarily with respect to neuroimaging outcomes) as a brain injury intervention. While the field is young and heterogeneity between studies precludes meta-analysis, this review raises important questions that need to be addressed by future trials.

Pediatric Traumatic Brain Injury and Exercise Medicine: A Narrative Review.

The multidisciplinary field of pediatric traumatic brain injury (TBI) and exercise medicine is of growing importance. There is active study into the diagnostic and therapeutic potential of exercise in pediatric TBI as well as the effects of TBI on postinjury fitness. With the evidence-based growing, a literature review can help establish the state of the science and inform future research. Therefore, the authors performed a narrative review (based on a search of 6 health sciences databases) to summarize evidence on pediatric TBI and cardiorespiratory fitness, muscular fitness and neuromotor control, and obesity. To date, studies related to cardiorespiratory fitness have centered on exercise tolerance and readiness to return to play, and indicate that protracted rest may not facilitate symptom recovery; this suggests a role for exercise in concussion management. Furthermore, strength and gait may be impaired following pediatric brain injury, and interventions designed to train these impairments may lead to their improvement. Pediatric brain injury can also lead to changes in body composition (which may be related to poorer cognitive recovery), but additional research is required to better understand such associations. This narrative review of pediatric TBI and exercise medicine can serve as a reference for researchers and clinicians alike.

Branched Chain Amino Acids (BCAAs) and Traumatic Brain Injury: A Systematic Review.

BACKGROUND: Despite the prevalence of traumatic brain injury (TBI), pharmaceutical treatment options for brain injury remain limited. However, nutritional intervention (such as with branched chain amino acids [BCAAs]) has emerged as a promising treatment option for TBI. OBJECTIVES: (1) To determine whether TBI patients have lower levels of endogenous BCAAs postinjury; and (2) to evaluate whether post-TBI BCAA supplementation improves clinical outcome. DESIGN: A systematic review of primary research articles examining the relationship between BCAAs and TBI recovery indexed in Ovid/MEDLINE, EMBASE, and PsycINFO. RESULTS: Of the 11 studies identified, 3 examined the effects of TBI on endogenous BCAA levels and consistently reported that BCAA concentrations were depressed postinjury. The remaining 8 studies examined the effects of BCAA supplementation on TBI outcome in animals (n = 3) and humans (n = 5). The animal studies (in mild-to-moderate TBI) showed that BCAAs improved post-TBI outcome. Similar results were found in human trials (conducted primarily in patients with severe TBI), with 4 of the 5 studies reporting improved outcome with BCAA supplementation. CONCLUSION: Although our review demonstrates an overall positive association between BCAAs and TBI outcome, the evidence of the efficacy of supplementation has been limited to severe TBI. To date, there is insufficient evidence to determine the benefits of BCAAs in mild TBI. Given the high frequency of mild TBI and the promise of BCAAs as an intervention in severe TBI, future research should examine the effects of BCAAs in milder brain injury.

Spinal cord injury: a review of the most-cited publications.

PURPOSE: The objective of this study was to identify and review the most-cited articles on spinal cord injury (SCI). Citation analyses showcase the relative influence of individual articles in a given field. In addition to distinguishing publications of particular quality and impact and well-developed areas of the literature, citation analyses allow for an understanding of the direction in which a field of research is headed. METHODS: A multi-disciplinary bibliographic index was used to identify the 50 SCI articles with the most lifetime citations, and the 50 SCI articles with the highest annual citation rates. Studies were categorized into one of six categories based on their primary focus: treatment, pathology/natural history, predictor of outcome, methods, epidemiology, or assessment measure. RESULTS: We report that 40.0 and 56.0 % of SCI papers with the most lifetime citations and highest annual citation rates, respectively, were systematic reviews or meta-analyses, indicating that some of the most referenced papers in SCI are not primary publications. Further, there appears to be a greater international presence in SCI research. In the highest annual citation rate cohort, 14.0 % of papers were a product of international collaboration, 50.0 % were published by outside of the United States, and the average year of publication was 2005 ± 5.4; the comparable numbers for papers that comprised the highest lifetime citation cohort were, respectively, 8.0, 28.0 %, and 1998 ± 9.2. Treatment and pathology/natural history of SCI were a common research focus in both citation cohorts, consistent with ongoing efforts to better understand and manage this injury. CONCLUSIONS: This comprehensive review provides a cross-sectional summary and bibliometric analysis of some of the most influential literature in SCI, and compliments existing systematic reviews and meta-analysis in the field by establishing which areas of the literature are growing and which have been well developed.

Traumatic Brain Injury in Spinal Cord Injury: Frequency and Risk Factors.

BACKGROUND: The frequency of traumatic brain injury (TBI) co-occurring with traumatic spinal cord injury (tSCI) is unclear despite a number of past studies; as well, limited research has examined predictors of co-morbid TBI in tSCI patients. OBJECTIVES: (1a) To summarize past literature on comorbid diagnosis of TBI in tSCI in order to reexamine the frequency of dual diagnosis in a study designed to obviate past methodological limitations; (1b) to compare dual-diagnosis frequency with vs without the inclusion of diagnostically ambiguous cases; and (2) to measure risk factors for tSCI and comorbid TBI. METHODS: Ninety-one of 135 eligible adults with tSCI, 3 to 6 months postinjury, were prospectively recruited from a tertiary inpatient tSCI rehabilitation program. TBI diagnosis was based on comprehensive, validated clinical neurological and neuroimaging measures. RESULTS: Objective 1: 39.6% of the tSCI patients sustained a concomitant TBI, but when ambiguous cases were removed from analysis, frequency rose to 58.1%. Objective 2: Motor vehicle collisions were most likely to yield a comorbid TBI diagnosis, but 31.6% of falls also resulted in TBI. Patients with cervical and thoracic injuries showed a very similar frequency of comorbid TBI. CONCLUSIONS: Varied methodological approaches, particularly the decision to include/exclude ambiguous cases, likely explain disparate past estimates of TBI in tSCI. However, even this study's lower frequency estimate, at nearly 40%, is clinically important. The prevailing assumption that dual diagnosis is less common in thoracic than cervical spine injuries was not supported. Finally, while comorbid TBI most frequently occurred in motor vehicle collisions, nearly a third of tSCIs sustained in falls resulted in comorbid TBI in our sample.

A review of the neuroprotective role of vitamin D in traumatic brain injury with implications for supplementation post-concussion.

BACKGROUND: Nutritional interventions are promising treatment adjuncts in the management of concussion. Vitamin D (VDH) supplementation has demonstrated neuroprotective properties in multiple models of acquired brain injury. OBJECTIVE: Review the neuroprotective role of VDH supplementation following traumatic brain injury (TBI). METHODS: A Medline search was conducted to review manuscripts investigating the influence of VDH status or supplementation on TBI outcomes. RESULTS: The search identified 165 studies, of which five were included. Four manuscripts studied a rodent model of TBI, while one studied a clinical sample. Vitamin D monotherapy independently reduced inflammation and neuronal injury following TBI, with a more robust effect observed in combination with progesterone (PROG). One study demonstrated VDH deficiency exacerbates post-TBI inflammatory response. One study in a clinical sample found combination therapy superior to PROG alone or placebo in improving outcomes after severe TBI. One study observed a more robust response to low-dose VDH compared to high-dose VDH when given in combination with PROG. CONCLUSION: A protective role for VDH and a vitamin D sufficient status was identified for numerous outcomes following TBI. However, VDH supplementation cannot be recommended at this time to improve outcomes following TBI.

The role of apolipoprotein E episilon (ε)-4 allele on outcome following traumatic brain injury: A systematic review.

BACKGROUND: The apolipoprotein E gene (APOE) has emerged as a candidate for prognosticating traumatic brain injury (TBI) recovery, with APOEε4 identified as a susceptibility marker for poor outcome, despite large discrepancy in its reported influence post-TBI. METHODS: A systematic review was conducted, including all primary articles investigating the role of APOEε4 on TBI outcome. A total of 65 studies were included, including 24 predominantly investigating mild (mTBI), seven moderate (modTBI) and 33 severe (sTBI); severity was not reported in one study. RESULTS: In mTBI studies, the association between APOEε4 and post-TBI outcome was concluded as non-contributory in 14 studies (58.3%), hazardous in nine (37.5%) and protective in one (4.2%). In sTBI studies, the role of APOEε4 was hazardous in 21 (63.6%), non-contributory in nine (27.3%) and protective in three (9.1%). Of the seven studies investigating dementia outcomes, four observed a hazardous association with APOEε4, while three reported no association. Six studies examined Alzheimer's dementia pathology, of which three reported a hazardous influence of APOEε4. CONCLUSIONS: The influence of APOEε4 on neuropsychological testing, functional outcome and in paediatric populations was incongruous. This review supports the majority of research indicating APOEε4 adversely influences recovery following TBI, particularly with respect to dementia-related outcomes and outcomes following sTBI.

Blood conservation in neurosurgery: erythropoietin and autologous donation.

BACKGROUND: Neurosurgery may involve significant blood loss and frequently requires allogeneic red blood cell (RBC) transfusion. Preoperative recombinant erythropoietin (EPO) may be used to improve erythroid status and recovery, and used either alone or in combination with preoperative autologous donation (PAD) it may reduce exposure to allogeneic RBC. We wished to study the use of EPO with and without PAD and the risk of RBC transfusion in neurosurgery. METHODS: Using a retrospective case-control design, 57 patients who received EPO preoperatively were matched 2:1 for age, sex, year of surgery, and International Classification of Diseases code most responsible for surgery (three were excluded because of stringent matching criteria, leaving 54 cases and 108 comparison subjects). Thirty-two cases participated in PAD. Medical and anesthetic records as well as laboratory investigations were reviewed and extracted. RESULTS: Allogeneic RBC exposure was identical for EPO cases and comparison subjects (18.5%). Concomitant PAD and EPO did not reduce allogeneic RBC exposure (21.9%), and resulted in a greater number of RBC units transfused. Last recorded hemoglobin levels suggested that autologous RBCs were not more liberally used. Patients who engaged in PAD and EPO suffered from iatrogenic anemia. A significant proportion (58.6%) of the autologous RBCs was ultimately not used and discarded. CONCLUSION: Further research is needed to determine the efficacy of EPO in neurological surgery. PAD does not appear to reduce the risk of allogeneic RBC transfusion, despite concomitant EPO. Indeed, PAD resulted in iatrogenic anemia and increased transfusion requirements. The cost-effectiveness of blood conservation efforts in neurosurgery deserves additional research.

2D-QSAR, molecular docking and MD simulation based virtual screening of the herbal molecules against Alzheimer's disorder: an approach to predict CNS activity.

Acetylcholinesterase (AChE) is one of the key enzyme targets that have been used clinically for the management of Alzheimer's Disorder (AD). Numerous reports in the literature predict and demonstrate in-vitro, and in-silico anticholinergic activity of herbal molecules, however, majority of them failed to find clinical application. To address these issues, we developed a 2D-QSAR model that could efficiently predict the AChE inhibitory activity of herbal molecules along with predicting their potential to cross the blood-brain-barrier (BBB) to exert their beneficial effects during AD. Virtual screening of the herbal molecules was performed and amentoflavone, asiaticoside, astaxanthin, bahouside, biapigenin, glycyrrhizin, hyperforin, hypericin, and tocopherol were predicted as the most promising herbal molecules for inhibiting AChE. Results were validated through molecular docking, atomistic molecular dynamics simulations and Molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) studies against human AChE (PDB ID: 4EY7). To determine whether or not these molecules can cross BBB to inhibit AChE within the central nervous system (CNS) for being beneficial for the management of AD, we determined a CNS Multi-parameter Optimization (MPO) score, which was found in the range of 1 to 3.76. Overall, the best results were observed for amentoflavone and our results demonstrated a PIC50 value of 7.377 nM, molecular docking score of -11.5 kcal/mol, and CNS MPO score of 3.76. In conclusion, we successfully developed a reliable and efficient 2D-QSAR model and predicted amentoflavone to be the most promising molecule that could inhibit human AChE enzyme within the CNS and could prove beneficial for the management of AD.Communicated by Ramaswamy H. Sarma.

The Concussion, Exercise, and Brain Networks (ConExNet) study: a cohort study aimed at understanding the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion.

BACKGROUND: Recent scientific evidence has challenged the traditional "rest-is-best" approach for concussion management. It is now thought that "exercise-is-medicine" for concussion, owing to dozens of studies which demonstrate that sub-maximal, graded aerobic exercise can reduce symptom burden and time to symptom resolution. However, the primary neuropathology of concussion is altered functional brain activity. To date, no studies have examined the effects of sub-maximal aerobic exercise on resting state functional brain activity in pediatric concussion. In addition, although exercise is now more widely prescribed following concussion, its cardiopulmonary response is not yet well understood in this population. Our study has two main goals. The first is to understand whether there are exercise-induced resting state functional brain activity differences in children with concussion vs. healthy controls. The second is to profile the physiological response to exercise and understand whether it differs between groups. METHODS: We will perform a single-center, controlled, prospective cohort study of pediatric concussion at a large, urban children's hospital and academic center. Children with sport-related concussion (aged 12-17 years) will be recruited within 4-weeks of injury by our clinical study team members. Key inclusion criteria include: medical clearance to exercise, no prior concussion or neurological history, and no implants that would preclude MRI. Age- and sex-matched healthy controls will be required to meet the same inclusion criteria and will be recruited through the community. The study will be performed over two visits separated by 24-48 h. Visit 1 involves exercise testing (following the current clinical standard for concussion) and breath-by-breath gas collection using a metabolic cart. Visit 2 involves two functional MRI (fMRI) scans interspersed by 10-minutes of treadmill walking at an intensity calibrated to Visit 1 findings. To address sub-objectives, all participants will be asked to self-report symptoms daily and wear a waist-worn tri-axial accelerometer for 28-days after Visit 2. DISCUSSION: Our study will advance the growing exercise-concussion field by helping us understand whether exercise impacts outcomes beyond symptoms in pediatric concussion. We will also be able to profile the cardiopulmonary response to exercise, which may allow for further understanding (and eventual optimization) of exercise in concussion management. TRIAL REGISTRATION: Not applicable.

Computational investigation of the impact of potential AT2R polymorphism on small molecule binding.

For more than a century, the renin-angiotensin system (RAS) has been acknowledged for playing a crucial part in the physiological control of arterial pressure, as well as sodium and fluid balance. It is now generally acknowledged that one of the receptor of RAS system i.e. angiotensin type 2 receptor (AT2R) functions as a repair system during pathophysiologic circumstances and performs a significant protective role. Efforts have been made previously to design suitable agonist and antagonist molecules to potentially modulate AT2R. One of the agonists and antagonists, named C21 and EMA401, has been studied in a number of pathological conditions. Additionally, a wide panel of single nucleotide polymorphisms (SNPs) has been reported for AT2R, which might potentially affect the efficacy of these molecules. Therefore, computational investigations have been carried out to analyze all the SNPs (1151) reported in NCBI to find potential SNPs affecting the active site of AT2R, as this domain is still unexplored. Structures of these polymorphic forms were modeled, and in silico drug interaction studies with C21 and EMA401 were carried out. The two mutants (rs868939201 and rs1042852794) that significantly affect the binding affinity as that of the wild type were subjected to molecular dynamics simulations. Our analysis of native and mutant AT2R and their complexes with C21 and EMA401 indicated that the occurrence of these mutations affects the conformation of the protein and has affected the binding of these ligand molecules. The study's findings will aid in the development of better, more versatile medications in the near future, and also in vitro and in vivo studies might be planned in accordance with recent findings.Communicated by Ramaswamy H. Sarma.

Feasibility of group telerehabilitation for individuals with chronic acquired brain injury: integrating clinical care and research.

BACKGROUND: Acquired brain injury (ABI) is a leading cause of lifelong disability, but access to treatment in the chronic stages has significant barriers. Group-based, remotely delivered neurorehabilitation reduces costs, travel barriers, and infection risk; however, its feasibility for patients with ABI is not well-established. OBJECTIVES: To investigate the feasibility of remotely group-based cognitive and mood therapies for persons with chronic ABI. METHODS: Three hundred and eighty-eight adults with chronic ABI participated in group tele-neurorehabilitation modules comprising Cognitive Behavioral Therapy, Goal Management Training®, Relaxation and Mindfulness Skills Training, and/or a novel Concussion Education & Symptom Management program. Assessments comprised quantitative metrics, surveys, as well as qualitative semi-structured interviews in a subset of participants. RESULTS: High retention, adherence, and satisfaction were observed. Facilitators of treatment included accessibility, cost-effectiveness, and convenience. Adoption of technology was high, but other people's technological interruptions were a barrier. Self-reported benefits specific to group-based format included improved mood, stress management, coping, interpersonal relationships, cognitive functioning, and present-mindedness. CONCLUSIONS: The present study examined chronic ABI patients' perceptions of telerehabilitation. Patients found remotely delivered, group-based mood, and cognitive interventions feasible with easy technology adoption. Group format was considered a benefit. Recommendations are provided to inform design of remotely delivered ABI programs.

Group-based mood and cognitive telerehabilitation is feasible for persons with chronic acquired brain injury, with high reported satisfaction.Screening for technical proficiency and providing ongoing technical support improves therapy adherence and retention.Integration of clinical care and research is feasible for delivering remote therapies to persons with brain injury.