Search

The electrocardiogram (ECG) is a vital device to examine the electrical activities of the heart. It is useful for diagnosing cardiovascular diseases, which often manifest themselves through alterations in the ECG signals' characteristics. These alterations are primarily observed in the signals' key components: the Q, R, S, T, and P peaks. At present, cardiologists typically rely on manual inspection of ECG measurements taken in controlled environments, such as hospitals and clinics, but most cardiac conditions reveal themselves outside clinical settings, when patients freely move and exert. In this paper, we dynamically identify and extract prominent ECG features in measurements taken outside clinical settings by subjects who have no medical training. The activities we consider are typical activities cardiac patients carry out in residential and rehabilitation environments, such as sitting, climbing up and down stairs, and standing up. To achieve accurate feature extraction, we employ adaptive thresholding and localization techniques. Our approach achieves promising results, with an average% for R peak detection and 92% for Q and S peaks detection. Similarly, our approach enables the detection of T and P peaks with an average accuracy of 87% and 84%, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Despite the recent progresses in therapeutic and diagnostic methods, there is still a significantly high rate of mortality among cancer patients. One of the main reasons for the high mortality rate in cancer patients is late diagnosis, which leads to the failure of therapeutic strategies. Therefore, investigation of cancer biology can lead to the introduction of early diagnostic markers in these patients. MicroRNAs (miRNAs) play an important role in regulation of cellular processes associated with tumor progression. Due to the high stability of miRNAs in body fluids, these factors can be considered as the non-invasive tumor markers. Deregulation of miR-382 has been widely reported in different cancers. Therefore, in this review, we investigated the role of miR-382 during tumor development. It has shown that miR-382 has mainly a tumor suppressive, which inhibits the growth of tumor cells through the regulation of signaling pathways, RNA-binding proteins, and transcription factors. Therefore, miR-382 can be suggested as a diagnostic and therapeutic marker in cancer patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: Despite careful design of clinical trials, unforeseen disruptions can arise. The PICOTS (Patient population, Intervention, Comparator, Outcomes, Timepoints, Setting) framework was used to assess disruptions in pain management research imposed by coronavirus disease 2019 (COVID-19) within the Pain Management Collaboratory., Methods: Rapid qualitative methods were employed to identify trial disruptions due to COVID-19 in 11 pragmatic clinical trials of nonpharmacological approaches for pain management. The PICOTS framework was applied by investigators of 4 Collaboratory trials selected to cover 4 types of trial designs (individually randomized, stepped-wedge, cluster, sequential multiple assignment randomized trial-SMART). Interviews with the lead investigators of these trials were completed, and findings were presented/discussed on video calls over a 6-month period (March-August 2021) from which themes/lessons learned were identified and consensus reached., Results: Investigators indicated that patient populations remained generally stable. A major COVID-19 trial disruption was moving from in-person to virtual care affecting delivery of interventions/comparators and outcome assessments. The resultant mixed-mode of care delivery created issues with intervention fidelity posing analytic challenges. COVID-19 also induced ongoing/intermittent delays and other barriers to accessing primary and specialty care at some facilities, creating research capacity issues affecting delivery of experimental interventions requiring sustained, reliable participation of clinical partners. Study designs most affected by COVID-19 were stepped-wedge (intervention/comparator changing over time), cluster (increased site variability inflating intracluster correlation), and SMART (second-stage randomizations disrupted); stratified individually-randomized trials were less vulnerable because of individual-level randomization., Conclusions: PICOTS provides a framework for assessing the impact of trial disruptions in a structured manner. Given the COVID-19 experience, it is important for researchers to consider the potential impact of future trial disruptions during study planning., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hypomyelinating leukodystrophy-17 is a neurodevelopmental disorder caused by autosomal recessive mutations in the AIMP2 gene, resulting in a lack of myelin deposition during brain development, leading to variable neurological symptoms. Research on brain function in these disorders is challenging due to the lack of access to brain tissue. To overcome this problem, researchers have utilized different cell and animal models. The CRISPR-Cas9 system is considered the most optimal and effective method for genetic modification and developing cell models. We studied the efficacy of the CRISPR-Cas9 technology in inducing mutations in the AIMP2 gene in HEK293 cell lines. The study involved transfecting HEK293 cells with recombinant PX458 plasmids targeting spCas-9 and AIMP2 sgRNA. The cells were evaluated using fluorescent microscopy and enriched using serial dilution. The CRISPR/Cas9 plasmids were validated through PCR and Sanger sequencing. After serial dilution, AS-PCR, Sanger sequencing, and TIDE program analysis showed the construct successfully induces an indel mutation in HEK cells. Our findings demonstrated the great efficacy of the CRISPR system and produced a construct for inducing mutations in the AIMP2 gene, which can be utilized to edit the AIMP2 gene in nerve cells and create a cellular model of the HLD17 disease., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Physical therapy (PT) is recommended as a primary treatment for low back pain (LBP), a common and impactful musculoskeletal condition after limb loss. The purpose of this brief report is to report the duration and cost of PT care, and subsequent escalation of care events, for LBP in service members with and without limb loss., Materials and Methods: This was a retrospective cohort, descriptive study. Service members with and without limb loss (matched) who received PT for LBP at a military treatment facility from 2015 to 2017 were included. Duration of PT care, number of PT visits, and escalation of care events 1 year after PT were extracted from medical records. Escalation of care events was identified as epidural steroid injections, referrals to specialists (e.g., orthopedists, spine surgeons, and pain management), and LBP-related hospitalizations.LBP-related PT encounters were queried; duration of care, number of visits, and cost of care were quantified. Escalation of care events, including opioid prescription, epidural steroid injections, specialty referrals, and hospitalizations, were identified up to 1 year after PT care., Results: The average course of PT care for LBP was 12.9 more visits, 48.7 days longer, and $764.50 more expensive in service members with limb loss (n = 16) vs. those without limb loss (n = 48). Higher rates of opioid prescriptions and specialty referrals were observed in service members with limb loss., Conclusions: This study suggests that service members with limb loss and LBP received higher quantities and longer durations of PT than those without limb loss, yielding a nearly 4 times higher cost of PT., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Objective: The objective of this study was to examine the associations between active, passive, and manual therapy interventions with the escalation-of-care events following physical therapist care for veterans with low back pain (LBP)., Methods: A retrospective cohort study was conducted in 3618 veterans who received physical therapist care for LBP between January 1, 2015 and January 1, 2018. The Department of Veterans Affairs (VA) Corporate Data Warehouse was utilized to identify LBP-related physical therapist visits and procedures, as well as opioid prescription and non-physical therapy clinic encounters. The association between physical therapist interventions with 1-year escalation-of-care events were assessed using adjusted odds ratios from logistic regression., Results: Nearly all veterans (98%) received active interventions, but only a minority (31%) received manual therapy. In the 1-year follow-up period, the odds of receiving an opioid prescription were 30% lower for those who received manual therapy in addition to active interventions, as compared with patients who received only active interventions. Moreover, the odds of receiving primary care, specialty care, and diagnostic testing were 30% to 130% higher for patients who received electrical stimulation or more than 1 passive intervention in addition to active treatments, as compared with patients who received only active interventions., Conclusion: The use of manual therapy along with active interventions was associated with reduced prescription of opioids, while utilization of specific passive interventions such as electrical stimulation or multiple modalities in conjunction with active interventions resulted in increased escalation-of-care events., Impact: The use of active interventions, which is supported by most clinical practice guidelines, was the cornerstone of physical therapist care for veterans with LBP. However, the use of clinical practice guideline-recommended manual therapy interventions was low but associated with reduced opioid prescriptions. The use of 2 or more different passive interventions along with active interventions was common (34%) and associated with less-than-optimal escalation-of-care outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

HLD17 (Hypomyelinating Leukodystrophy 17) is an inherited white matter disorder characterized by insufficient myelin production due to biallelic loss of function mutations in the aminoacyl-tRNA synthetase complex-interacting multifunctional protein 2 (AIMP2) gene. In silico analysis of SNVs (single nucleotide variants) in the AIMP2 gene is an efficient and cost-effective method for analyzing and predicting the impact of mutations on protein function and disease pathophysiology. The study used dbSNP and Ensembl databases to obtain data on 343 nonsynonymous single nucleotide variants (nsSNVs) in the human AIMP2 gene. Six prediction algorithm tools were used to assess the effects of these nsSNVs on AIMP2's functions and structures. Results showed that 18 nsSNVs were located within functional domains, while 10 nsSNVs led to decreased protein stability. The structural and functional properties of the AIMP2 protein were investigated using databases such as Predict Protein, Mutpred2, and HOPE. ConSurf analysis provided information about conserved nsSNVs. GeneMANIA and STRING software tools were used to predict interactions between gene-gene and protein-protein, respectively. Phyre2 and I-TASSER web servers were used to predict the 3D structures of wild-type and mutant proteins. In addition, having the challenge of probable post-translational modification sites in the AIMP2, we made predictions using various bioinformatics tools. Consecuently, three minor mutations (L138Q, V161E, and I188N) and five major mutations (C23S, D121G, I122S, P128S, and W268S) were found to affect the AIMP2 protein's structure or function. Anyway, These mutations need to be further studied and confirmed through experimental investigation and GWAS studies., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Purpose: Glioblastoma (GBM) stands out as the most prevalent and aggressive intracranial tumor, notorious for its poor prognosis. The current standard-of-care for GBM patients involves surgical resection followed by radiotherapy, combined with concurrent and adjuvant chemotherapy using Temozolomide (TMZ). The effectiveness of TMZ primarily relies on the activity of O 6 -methylguanine DNA methyltransferase (MGMT), which removes alkyl adducts from the O 6 position of guanine at the DNA level, thereby counteracting the toxic effects of TMZ., Method: In this study, we employed fusions of catalytically-inactive Cas9 (dCas9) to DNA methyltransferases (dCas9-DNMT3A) to selectively downregulation MGMT transcription by inducing methylation at MGMT promoter and K-M enhancer., Result: Our findings demonstrate a significant reduction in MGMT expression, leading to intensified TMZ sensitivity in the HEK293T cell line., Conclusion: This study serves as a proof of concept for the utilization of CRISPR-based gene suppression to overcome TMZ resistance and enhance the lethal effect of TMZ in glioblastoma tumor cells., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: The aims of this project were to assess (1) the prevalence and timing of post-traumatic osteoarthritis (PTOA) after a traumatic lower limb injury, (2) the risk of PTOA based on injury type, and (3) the association of PTOA with psychological health and quality of life (QoL)., Materials and Methods: The Wounded Warrior Recovery Project (WWRP) database and the Expeditionary Medical Encounters Dataset were queried to identify service members injured during deployment. The Military Health System Data Repository was utilized to extract medical record data to identify individuals with PTOA. Data on PTSD, depression symptoms, and QoL were extracted from the WWRP., Results: Of the 2,061 WWRP participants with lower limb injuries, 124 (6%) were diagnosed with PTOA, with first PTOA diagnosis occurring 3.8 ± 3.1 years after injury. Of the injury categories identified, only fractures were associated with high odds of lower limb PTOA (adjusted odds ratio [OR] = 3.92, 95% confidence interval [CI]: 2.38, 6.44). Individuals with PTOA diagnoses reported lower QoL scores relative to those without PTOA (F(1,2057) = 14.21, B = -0.05, P < .05). Additionally, rates of PTSD and depression symptoms were high but not different between those with or without PTOA., Conclusions: Despite a low prevalence of lower limb PTOA in our study, fractures increased the risk of PTOA after deployment-related injuries. Additionally, those with PTOA reported lower QoL scores relative to those without PTOA. The findings of this study highlight the personalized needs of patients with trauma beyond just the repair of the immediate injury., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: The primary objective was to describe rates of general and pain-related psychological distress for individuals with low back pain (LBP) in the Military Health System (MHS). We identified common phenotypes defined by rates of general and pain-related psychological distress and compared phenotypes on their level of pain interference, physical function, anxiety, and depression., Methods: We created a cohort from two completed trials assessing nonpharmacological treatment for LBP in the MHS (n = 510 total). The Optimal Screening for Prediction of Referral and Outcome Yellow Flag assessment tool identified the presence of 11 different yellow flags. Latent class analysis (LCA) used yellow flag indicators to identify common psychological phenotypes. We then compared Patient-Reported Outcomes Measurement Information Systems measures of pain interference, physical function, sleep disturbance, depression, and anxiety across phenotypes., Results: LCA identified five phenotypes (percentage of the sample): low distress (32%), high distress (27%), poor pain coping and low self-efficacy (18%), low self-efficacy and acceptance (14%), and poor pain coping (10%). Highly distressed phenotypes reported higher levels of pain interference, sleep disturbance, depression, and anxiety than those with other phenotypes, whereas the low distress phenotype had significantly lower pain interference and higher physical function scores than those characterized by all other phenotypes., Conclusion: These phenotypes provide opportunities for clinicians and researchers to develop novel LBP treatment pathways tailored to patients with different profiles of psychological distress. Future work is needed to validate their predictive capabilities for clinical outcomes., (© 2024 American College of Rheumatology. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Humans continuously adapt locomotor patterns. Whether metabolic cost reduction is the primary objective or a by-product of the observed biomechanical changes during adaptation is not known. The main goal of our study is to determine if perception of task duration affects the adaptation of locomotor patterns to reduce energetic cost during split-belt walking. We tested the hypothesis that individuals who believe they will sustain a locomotor adaptation task for a prolonged time will reduce metabolic cost by adapting toward a walking pattern associated with lower mechanical work. N=14 participants walked on a split-belt treadmill for 10 minutes with knowledge of task duration (group K), while N=15 participants performed the task under the assumption that they would walk for 30 minutes (group U). Both groups walked for 10 minutes with the belts moving at 1.5 and 0.5 m/s, followed by 6 minutes of walking with both belts at 1.0 m/s. We observed a significant main effect of Time (p<0.001, observed power 1.0) and the interaction of Time×Group (p=0.004, observed power 0.84) on metabolic cost. Participants in the U group had a metabolic cost that was 12% lower during adaptation compared to the K group, which did not reduce metabolic cost during adaptation. The metabolic cost reduction observed in group U was not associated with biomechanical changes during adaptation. Our results indicate that metabolic cost reduction has a primary role in tasks that need to be sustained for a prolonged time, and this reduction is not only related to biomechanical factors.

Introduction: Running-related injuries are prevalent in the military and are often related to physical fitness test training. Non-rearfoot striking while running is known to increase the risk of Achilles tendon injuries because of the high eccentric energy absorption by the elastic components of the planarflexor muscle-tendon complex. However, there is limited evidence to suggest benefits of converting runners with Achilles tendon pain to use a rearfoot strike., Methods: This is a case series of two active-duty Service members with chronic, running-related Achilles tendon pain that utilized a natural non-rearfoot strike pattern. Both patients were trained to utilize a rearfoot strike while running through the use of real-time visual feedback from wearable sensors., Results: The trained rearfoot strike pattern was retained for over one month after the intervention, and both patients reported improvements in pain and self-reported function., Conclusions: This case series demonstrated the clinical utility of converting two non-rearfoot strike runners to a rearfoot strike pattern to decrease eccentric demands on the plantarflexors and reduce Achilles tendon pain while running., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Duchenne Muscular Dystrophy (DMD) is a progressive muscle wasting disorder caused by loss-of-function mutations in the dystrophin gene. Although the search for a definitive cure has failed to date, extensive efforts have been made to introduce effective therapeutic strategies. Gene editing technology is a great revolution in biology, having an immediate application in the generation of research models. DMD muscle cell lines are reliable sources to evaluate and optimize therapeutic strategies, in-depth study of DMD pathology, and screening the effective drugs. However, only a few immortalized muscle cell lines with DMD mutations are available. In addition, obtaining muscle cells from patients also requires an invasive muscle biopsy. Mostly DMD variants are rare, making it challenging to identify a patient with a particular mutation for a muscle biopsy. To overcome these challenges and generate myoblast cultures, we optimized a CRISPR/Cas9 gene editing approach to model the most common DMD mutations that include approximately 28.2% of patients. GAP-PCR and sequencing results show the ability of the CRISPR-Cas9 system to efficient deletion of mentioned exons. We showed producing truncated transcript due to the targeted deletion by RT-PCR and sequencing. Finally, mutation-induced disruption of dystrophin protein expression was confirmed by western blotting. All together, we successfully created four immortalized DMD muscle cell lines and showed the efficacy of the CRISPR-Cas9 system for the generation of immortalized DMD cell models with the targeted deletions., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In persons with limb loss, prosthetic devices cause skin breakdown, largely because residual limb skin (nonvolar) is not intended to bear weight such as palmoplantar (volar) skin. Before evaluation of treatment efficacy to improve skin resiliency, efforts are needed to establish normative data and assess outcome metric reliability. The purpose of this study was to use optical coherence tomography to (i) characterize volar and nonvolar skin epidermal thickness and (ii) examine the reliability of optical coherence tomography. Four orientations of optical coherence tomography images were collected on 33 volunteers (6 with limb loss) at 2 time points, and the epidermis was traced to quantify thickness by 3 evaluators. Epidermal thickness was greater ( P < .01) for volar skin (palm) (265.1 ± 50.9 μm, n = 33) than for both nonvolar locations: posterior thigh (89.8 ± 18.1 μm, n = 27) or residual limb (93.4 ± 27.4 μm, n = 6). The inter-rater intraclass correlation coefficient was high for volar skin (0.887-0.956) but low for nonvolar skin (thigh: 0.292-0.391, residual limb: 0.211-0.580). Correlation improved when comparing only 2 evaluators who used the same display technique (palm: 0.827-0.940, thigh: 0.633-0.877, residual limb: 0.213-0.952). Despite poor inter-rater agreement for nonvolar skin, perhaps due to challenges in identifying the dermal-epidermal junction, this study helps to support the utility of optical coherence tomography to distinguish volar from nonvolar skin.

Objective: The aim of this study was to explore associations between the utilization of active, passive, and manual therapy interventions for low back pain (LBP) with 1-year escalation-of-care events, including opioid prescriptions, spinal injections, specialty care visits, and hospitalizations., Methods: This was a retrospective cohort study of 4827 patients identified via the Military Health System Data Repository who received physical therapist care for LBP in 4 outpatient clinics between January 1, 2015 and January 1, 2018. One-year escalation-of-care events were evaluated based on type of physical therapist interventions (ie, active, passive, or manual therapy) received using adjusted odds ratios., Results: Most patients (89.9%) received active interventions. Patients with 10% higher proportion of visits that included at least 1 passive intervention had a 3% to 6% higher likelihood of 1-year escalation-of-care events. Similarly, with 10% higher proportion of passive to active interventions used during the course of care, there was a 5% to 11% higher likelihood of 1-year escalation-of-care events. When compared to patients who received active interventions only, the likelihood of incurring 1-year escalation-of-care events was 50% to 220% higher for those who received mechanical traction and 2 or more different passive interventions, but lower by 50% for patients who received manual therapy., Conclusion: Greater use of passive interventions for LBP was associated with elevated odds of 1-year escalation-of-care events. In addition, the use of specific passive interventions such as mechanical traction in conjunction with active interventions resulted in suboptimal escalation-of-care events, while the use of manual therapy was associated with more favorable downstream health care outcomes., Impact: Physical therapists should be judicious in the use of passive interventions for the management of LBP as they are associated with greater likelihood of receiving opioid prescriptions, spinal injections, and specialty care visits., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Persons who undergo unilateral transtibial amputation are at an increased risk of secondary musculoskeletal joint pain and degeneration, which has been linked to excessive loading rates of the intact-side limb. Tibial axial acceleration, a feasible measure of loading rates with wearable sensors, would be clinically useful to relate to joint pain in persons with unilateral transtibial amputation., Research Question: What is the relationship between peak tibial axial accelerations and intact-side joint pain in persons with unilateral transtibial amputation during walking?, Methods: Persons with unilateral transtibial amputation (n = 51) were separated into two groups based on the presence of intact-side limb pain (with pain: n = 16; without pain: n = 35). Tibial axial accelerations were measured with bilateral shank-mounted IMUs while participants completed three 10-meter walk tests. Peak tibial axial accelerations for each limb and between-limb symmetry were compared between groups using analysis of co-variance; significance was set at 0.05., Results: Between persons with vs. without intact-side limb pain, peak tibial axial accelerations were smaller on the prosthetic side (0.64 vs. 0.81 g; p = 0.04), similar on the intact side (0.82 vs. 0.79 g; p = 0.53), and more asymmetrical between sides (intact > prosthetic) (0.81 vs. 1.03 g; p = 0.01)., Significance: Symmetry in peak tibial axial acceleration can assist with identifying preferential limb loading during walking and, with future research, could serve as a useful clinical target for intact-side limb unloading strategies to help mitigate secondary musculoskeletal pain in persons with unilateral transtibial amputation., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier B.V.)

Background: Chronic rhinosinusitis (CRS), as an inflammatory airway disease, could be a risk factor for COVID-19 patients. This study aimed to investigate the frequency and severity of symptoms of COVID-19 in patients with CRS and to assess the association between the status of CRS symptoms and the quality of life (QoL) of the patients., Methods: In this observational and cross-sectional study, 207 adult CRS patients participated. The patients, who presented the symptoms of COVID-19, were examined by taking the reverse transcription-polymerase chain reaction test. A questionnaire was completed by each patient, regarding their demographic and clinical data. In addition, the GA 2 LEN and Sino-Nasal Outcome Test (SNOT-22) standard questionnaires were used to identify the comorbid allergic condition and QoL of CRS patients., Results: The frequency of patients with COVID-19 was 25 (12.1%) of which 22 were treated as outpatients, 2 of them admitted in wards and 1 at intensive care unit. The severity of hyposmia in the patients was 2 (8%) as mild, 5 (20%) moderate, and 11 (72%) as anosmia. The most common allergic and underlying comorbid diseases were allergic rhinitis (88%) and thyroid disorders (28%). Further, the average SNOT-22 score in 4 SNOT-22 domains (nasal, otologic, sleep, and emotional symptoms) was significantly decreased in CRS patients after a period of one year since the pandemic started (40.1 ± 18.0 vs. 46.3 ± 17.7; P < .0001)., Discussion: This study showed a low frequency of COVID-19 in patients with CRS and about the same rate of infection positivity in the general population; therefore, we concluded that CRS could not be considered as a risk factor for COVID-19. Interestingly, the lower average score of SNOT-22 after one year of the pandemic in the patients with CRS confirmed the necessity for performing the standard health protocols by the patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Military service members (SMs) demonstrate high rates of patellofemoral chondral defects (PFCDs) that are difficult to diagnosis and, if untreated, result in a cascade of events eventually leading to osteoarthritis. Running is an essential occupational task for SMs; however, there is little evidence regarding techniques to maintain running ability in individuals with cartilage defects. The purpose of this case series was to assess the clinical application of foot strike run retraining in patients with PFCDs. This case series included two active duty U.S. Marine Corps SMs who presented to outpatient physical therapy with PFCD, diagnosed via MRI. Both patients attended eight foot strike run retraining sessions. Running mechanics and patient-reported outcomes were recorded pre-training, post-training, and at a 1-month follow-up visit. Both patients successfully converted their strike pattern from a rearfoot to a non-rearfoot strike pattern with training and retained this strategy at 1-month follow-up. Post-intervention, both patients demonstrated increased running tolerance, and improvements in Numeric Pain Rating Scale and Lower Extremity Functional Scale scores. Biomechanical analysis showed that both patients demonstrated a 63% to 70% reduction in average and peak vertical ground reaction force loading rates post-treatment. Modification of foot strike pattern from rear to non-rearfoot strike during running for individuals with PFCD can reduce the magnitude of impact loading, which potentially limits disease progression. These findings suggest that foot strike run retraining may be a feasible strategy to reduce pain and improve function in SMs with PFCD who are required to run for occupational responsibilities., (© The Association of Military Surgeons of the United States 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rapid advancement in genome editing technologies has provided new promises for treating neoplasia, cardiovascular, neurodegenerative, and monogenic disorders. Recently, the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system has emerged as a powerful gene editing tool offering advantages, including high editing efficiency and low cost over the conventional approaches. Human pluripotent stem cells (hPSCs), with their great proliferation and differentiation potential into different cell types, have been exploited in stem cell-based therapy. The potential of hPSCs and the capabilities of CRISPR/Cas9 genome editing has been paradigm-shifting in medical genetics for over two decades. Since hPSCs are categorized as hard-to-transfect cells, there is a critical demand to develop an appropriate and effective approach for CRISPR/Cas9 delivery into these cells. This review focuses on various strategies for CRISPR/Cas9 delivery in stem cells., (© 2023. The Author(s).)

The present study aimed to elucidate the effect of 10 mg/kg Δ9-tetrahydrocannabinol (THC) on cerebellar neuronal and glial morphology, apoptosis and inflammatory gene expression using a series of histological assays including stereology, Sholl analysis, immunofluorescence and real-time qPCR in male Wistar rats. A decrease in the number of Purkinje neurons and the thickness of the granular layer in the cerebellum was reported in THC-treated rats. Increased expression of Iba-1 and arborization of microglial processes were evidence of microgliosis and morphological changes in microglia. In addition, astrogliosis and changes in astrocyte morphology were other findings associated with THC administration. THC also led to an increase in caspase-3 positive cells and a decrease in autophagy and inflammatory gene expression such as mTOR, BECN1 and LAMP2. However, there were no significant changes in the volume of molecular layers and white matter, the spatial arrangement of granular layers and white matter, or the spatial arrangement of granular layers and white matter in the cerebellum. Taken together, our data showed both neuroprotective and neurodegenerative properties of THC in the cerebellum, which require further study in the future., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Standing sway assessments can detect sensory imbalances which compromise postural control. Persons with lower limb amputation (LLA) often demonstrate impaired postural control, increasing fall risk. Here, principal features of postural sway were identified in persons with unilateral LLA using a single, commercially available wearable sensor. Sixty-one persons with LLA (n = 44 transtibial; n = 17 transfemoral) stood on a firm surface with eyes open/closed while wearing a single accelerometer mounted over the sacrum. Common parameters quantified spatiotemporal and spectral features of sway in anterior-posterior (AP) and mediolateral (ML) directions. Principal component (PC) dimensionality reduction was applied and loadings inspected to identify a reduced, non-redundant set among 14 original variables capturing 90 % variance. Six PCs described ≥ 90 % variance, with the first 3 explaining 75 %. With eyes open and closed, PC1 was loaded by variables characterizing trajectory planar size: area, jerk (i.e., sway smoothness), AP/ML RMS path distance, and AP/ML path range. With eyes open, PC2 was loaded by variables characterizing direction and spectral features: ellipse rotation, AP centroidal frequency, and ML jerk. With eyes closed, PC2 spectral loadings increased: ML centroidal frequency, ML frequency dispersion, and AP centroidal frequency. With eyes open, PC3 was loaded by ellipse rotation, jerk, ML velocity, ML centroidal frequency. With eyes closed, PC3 was loaded by ellipse rotation, ML centroidal frequency, ML frequency dispersion, and AP path velocity, characterizing off-axis error/corrections. RMS of path distance, ellipse rotation, centroidal frequency, frequency dispersion, path velocity, and jerk are a concise parameter set, derived from an accelerometer, to capture principal sway features in persons with LLA during standing balance with visual perturbations., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction: Weight gain can contribute to osteoarthritis, cardiovascular disease, low back pain, and poor health-related quality of life. Weight trajectory patterns have been described in older veterans with limb loss; however, there is limited evidence of changes in weight in younger veterans with limb loss., Materials and Methods: Service members with unilateral or bilateral lower limb amputations (LLAs) (and without an upper limb amputation) were included in this retrospective cohort analysis (n = 931). The mean postamputation baseline weight was 78.0 ± 14.1 kg. Bodyweight and sociodemographic data were extracted from clinical encounters within electronic health records. Group-based trajectory modeling assessed weight change patterns 2 years postamputation., Results: Three weight change trajectory groups were identified: 58% (542 of 931) of the cohort had stable weight, 38% (352 of 931) had weight gain (mean gain = 19.1 kg), and 4% (31 of 931) had weight loss (mean loss = 14.5 kg). Individuals with bilateral amputations were more frequently noted in the weight loss group compared with those with unilateral amputations. Individuals with LLAs because of trauma other than blasts were more frequently found in the stable weight group compared with those with amputations because of disease or a blast. Younger individuals (<20 years old) with amputations were more likely to be in the weight gain group compared with older individuals., Conclusions: More than half the cohort maintained a stable weight for two years after amputation, and more than a third experienced weight gain during the same time frame. Knowledge of underlying factors that were associated with weight gain could inform preventative strategies for young individuals with LLAs., (Published by Oxford University Press on behalf of the Association of Military Surgeons of the United States 2023. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Knee diagnoses account for more than 50% of lower extremity musculoskeletal conditions in non-deployed US Service members. However, there is limited information regarding kinesiophobia in Service members with non-operative knee diagnoses., Hypotheses: The objectives of this study were to determine the prevalence of high levels of kinesiophobia in US military Service members with knee pain across different knee diagnoses, and to determine the relationships between kinesiophobia and lower extremity function and/or specific functional limitations in Service members with knee pain. It was hypothesized Service members with knee pain would exhibit high levels of kinesiophobia across all knee diagnoses examined, and higher levels of both kinesiophobia and pain would be associated with worse self-reported function in this population. It was also hypothesized higher levels of kinesiophobia would be associated with functional activities with high knee loading., Design: Retrospective cohort study., Level of Evidence: IV., Methods: Sixty-five US Service members presenting to an outpatient physical therapy clinic were included in this study (20 females; age = 30.8 ± 7.7 years; height = 1.74 ± 0.9 m; mass = 80.7 ± 16.2 kg). Inclusion criterion was the presence of knee pain (duration = 50 ± 59 months); exclusion criterion was knee pain as a sequela of knee surgery. Data regarding demographic, pain chronicity, pain by Numeric Rating Scale (NRS), Tampa Scale of Kinesiophobia (TSK), and Lower Extremity Functional Scale (LEFS) were retrospectively obtained from patients' medical records. A high level of kinesiophobia was defined as a TSK score of greater than 37 points. Patient diagnoses included: osteoarthritis (n = 16); patellofemoral pain syndrome (n = 23); and other non-operative knee diagnoses (n = 26). Commonality analysis was utilized to determine the effects of age, height, mass, NRS, and TSK on LEFS score. Predictor values were interpreted as <1% = negligible, >1% = small; >9% = moderate, >25% = large. Additionally, exploratory item-specific analyses examined the strength of the relationships between kinesiophobia and LEFS item responses. Binary logistic regression determined if difficulty with an individual LEFS item could be predicted from either NRS or TSK score. Statistical significance was set at P < 0.05., Results: High levels of kinesiophobia were identified in 43 individuals (66%). NRS and TSK explained 19.4% and 8.6% of the unique variance in LEFS, and 38.5% and 20.5% of total variance, respectively. Age, height, and mass explained negligible to small proportions of the unique variance in LEFS. TSK and NRS were independent predictors for 13/20 individual LEFS items, with odds ratios ranging from 1.12 to 3.05 (P < 0.05)., Conclusion: The majority of US Service members in this study exhibited high levels of kinesiophobia. Kinesiophobia was significantly related to self-reported functional scores and performance on individual functional tasks in Service members with knee pain., Clinical Relevance: Treatment strategies addressing both fear of movement and pain reduction in patients with knee pain may help optimize functional outcomes., Competing Interests: Declaration of competing interest The authors certify they have no affiliations with or financial involvement in any organization or entity with a direct financial interest in the subject matter or materials discussed in the article., (Published by Elsevier Ltd.)

Introduction: The adverse influence of chronic pain on function and psychological health in the general population is well understood. However, the relationship between phantom limb pain (PLP) after limb loss with function and psychological health is less clear. The study purpose was to assess the influences of PLP presence and intensity on function and psychosocial health in individuals with lower-limb loss (LLL)., Methods: One hundred two individuals with major LLL completed a study-specific questionnaire on the presence and intensity of their PLP. The Patient-Reported Outcomes Measurement Information System -29 questionnaire was also administered., Results: Of 102 participants, 64% reported PLP, with a mean intensity of 4.8 ± 2.3 out of 10. Individuals with vs. without PLP demonstrated significantly greater sleep disturbances ( p = 0.03), whereas the differences in function, fatigue, pain interference, depressive symptoms, anxiety, or ability to participate in social roles and activities were not statistically different between groups ( p > 0.05). Of note, mean scores for many of the Patient-Reported Outcomes Measurement Information System-29 short forms among the current sample were similar to the mean of the general population, minimizing the potential clinical impact of PLP on these domains., Conclusions: Our findings indicate a lack of meaningful associations between PLP presence or intensity with function, and psychosocial health among individuals with LLL. These findings conflict with previous research suggesting an adverse relationship between PLP, function, and psychosocial health after limb loss., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

The etiology of uveitis greatly varies worldwide, whereby in industrial nations noninfectious causes occur relatively more frequently. In Germany, 44% of all cases of uveitis are due to systemic diseases. In rheumatology, uveitis or other kinds of ocular inflammation, such as scleritis or retinal vasculitis, most commonly occur in spondylarthritis, vasculitis and sarcoidosis. Vice versa, ophthalmologists often ask rheumatologists about an underlying rheumatic disease in patients with uveitis. It is of utmost importance to differentiate between the different forms of uveitis. This review article presents the associations with inflammatory rheumatic diseases as well as treatment options from the point of view of both ophthalmologists and rheumatologists., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Study Design: Retrospective cohort study INTRODUCTION: Service members who have sustained traumatic amputations are typically young and otherwise healthy. Beyond standard care, these individuals desire long, highly active, and relatively pain-free lifestyle, whether that is returning to active duty or transitioning to civilian life. Development of overuse musculoskeletal conditions could have a significant influence on quality of life for Service members with traumatic upper limb amputation., Purpose of the Study: Compare one-year incidence of overuse musculoskeletal injuries in Service members with different levels of combat-related upper limb amputation to Service members with minor combat-related upper limb injuries., Methods: Service members with deployment-related upper limb injury (N = 519), 148 major upper limb amputation (55 with amputation at or above elbow, 93 with amputation below elbow) and 371 minor upper limb injury were included in the study. Outcomes of interest clinical diagnosis codes associated with overuse conditions of the upper limb, neck and upper back, lower limb, low back pain, and all regions combined, one year before and one year after injury., Results: Overall, the one-year incidence of developing at least one musculoskeletal overuse condition after upper limb amputation was between 60% and 65%. Service members with upper limb amputations were 2.7 to 4.7 times more likely to develop an overuse upper limb condition, 3.6 to 3.8 times more likely to develop a neck and upper back condition, 2.8 to 4.4 times more likely to develop a lower limb condition, and 3.3 to 3.9 times more likely to develop low back pain as compared those who sustained minor combat-related injuries. No significant differences in the odds of developing a musculoskeletal condition was found between the above elbow and below elbow amputation groups., Conclusions: Incidence of secondary overuse conditions is elevated in Service members with upper limb amputation and warrants focused research efforts toward preventative and rehabilitative interventions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021. Published by Elsevier Inc.)

Background: Lower back pain is a debilitating condition common to individuals with lower limb amputation. It is unclear what risk factors contribute to the development of back pain. This study systematically reviewed and analyzed the available evidence regarding the clinical and biomechanical differences between individuals with amputation, with and without lower back pain., Methods: A literature search was conducted in PubMed, Web of Science, Scopus, and CINAHL databases in November 2020 and repeated in June 2021 and June 2022. Studies were included if they reported comparisons of demographic, anthropometric, biomechanical, and other clinical variables between participants with and without LBP. Study quality and potential for reporting bias were assessed. Meta-analyses were conducted to compare the two groups., Findings: Thirteen studies were included, with aggregated data from 436 participants (239 with LBP; 197 pain free). The median reporting quality score was 37.5%. The included studies enrolled participants who were predominantly male (mean = 91.4%, range = 77.8-100%) and with trauma-related amputation. Meta-analyses showed that individuals with LBP exhibited moderate (3.4 out of 10) but significantly greater pain than those without LBP. We found no between-group differences in age, height, weight, BMI, and time since amputation (p = 0.121-0.682). No significant differences in trunk/pelvic kinematics during gait were detected (p = 0.07-0.446) between the groups., Interpretation: Demographic, anthropometric, biomechanical, and simple clinical outcome variables may be insufficient for differentiating the risk of developing back pain after amputation. Investigators should be aware of the existing gender bias in sampling and methodological limitations, as well as to consider incorporating psychosocial measures when studying LBP in this clinical population., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Szu-Ping Lee and Jo Armour Smith report financial support was provided by the National Institutes of Health. Szu-Ping Lee reports a relationship with US Department of Defense that includes: consulting or advisory and funding grants. Szu-Ping Lee has patent #Method and Apparatus for Performing Timed Up-And-Go Test (#10,335,058) issued to US Patent Office., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Over the past years, several studies have also reported the adverse effects of hyperthermia on normal testicular tissues in several species including mice, rats, and humans. These deleterious impacts include temporarily drop in relative weight of testis along with a temporary partial or complete infertility. Sambucus nigra, also known as elderberry or sweet elder, is a source of bioactive compounds that has drawn growing attention for its potential beneficial effects in preventing and treating several diseases. This experimental research divided 30 mice into the following three groups: (1) control, (2) hyperthermia, and (3) hyperthermia receiving elderberry diet for 35 days. Scrotal hyperthermia was induced by water bath with 43 °C for 30 min. Then, the mice were euthanized, and their sperm samples were collected for sperm parameters analysis. Then, we took the testis samples for histopathological experimentations, immunohistochemistry against TNF-α and caspase-3 and serum testosterone, FSH and LH levels. Our outputs indicated that elderberry diet could largely improve the sperms parameters and stereological parameters, like spermatogonia, primary spermatocyte, round spermatid, and Leydig cells together with an increasing level of the serum testosterone compared to the scrotal hyperthermia induced mice. In addition, it was found that the expression of TNF-α and caspase-3 significantly decreased in the treatment groups by elderberry diet compared to the scrotal hyperthermia-induced mice. In conclusion, it could be concluded that elderberry diet may be regarded as an alternative treatment for improving the spermatogenesis process in the scrotal hyperthermia induced mice., (© 2022. Society for Reproductive Investigation.)

The etiology of uveitis greatly varies worldwide, whereby in industrial nations noninfectious causes occur relatively more frequently. In Germany, 44% of all cases of uveitis are due to systemic diseases. In rheumatology, uveitis or other kinds of ocular inflammation, such as scleritis or retinal vasculitis, most commonly occur in spondylarthritis, vasculitis and sarcoidosis. Vice versa, ophthalmologists often ask rheumatologists about an underlying rheumatic disease in patients with uveitis. It is of utmost importance to differentiate between the different forms of uveitis. This review article presents the associations with inflammatory rheumatic diseases as well as treatment options from the point of view of both ophthalmologists and rheumatologists., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

This review article presents the different forms of uveitis and their clinical manifestations. The exact type and localization of the ocular inflammation is crucial for the probability of the underlying rheumatological disease and thus for a correct differential diagnosis. In this first part, in addition to the anatomy of the eye, the different forms of uveitis including the associated nomenclature, typical symptoms, diagnostics and possible complications are presented. In a following second part ("Association of the different forms of uveitis with inflammatory rheumatic diseases and their treatment"), the associations with rheumatological and other systemic diseases are explained and highlighted from an ophthalmological and rheumatological perspective., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Introduction: Military training is associated with a high incidence of knee pain. Conversion from a rearfoot to non-rearfoot strike during running is effective at reducing knee pain in research environments. The purpose of this report was to demonstrate run retraining as a clinical intervention for service members with knee pain., Methods: Sixteen service members with running-related chronic knee pain underwent run retraining that converted foot strike from a rearfoot to a non-rearfoot strike using real-time visual feedback. The Lower Extremity Functional Scale (LEFS) and Numerical Pain Rating Scale (NPRS) for knee pain during running were assessed pretraining, at the final training session and at a 1-month follow-up. During running, foot inclination angle and vertical ground reaction force (VGRF) average loading rate were measured pretraining and at 1 month of follow-up., Results: Service members underwent 7.4±1.0 training sessions over the course of 15.8±4.6 days. LEFS improved by 8±6 points immediately after retraining, with an overall improvement of 10±6 points from pretraining to 1-month follow-up (p<0.01). NPRS improved by 2.0±0.4 points immediately after retraining, with an overall improvement of 2.0±0.4 points from pretraining to 1-month follow-up (p<0.01). Conversion to a non-rearfoot strike pattern was apparent at follow-up for all but two patients. VGRF average loading rate decreased by 56%±17% (p<0.01) from pretraining to 1-month follow-up., Conclusions: Knee pain and function improved as a result of non-rearfoot strike run retraining, which supports the clinical use of this evidence-based intervention., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

This research aimed to develop a novel composite as a low-cost adsorbent for the removal of nitrate ion from aqueous solutions. The characterization of this composite (composition of red mud with dimethyldioctadecylammonium bromide (DDAB)) was performed by XRF, XRD, FTIR, and BET analyses. The most influential variables on nitrate adsorption, including contact time, solution acidity, adsorbent amount, and temperature were studied. The maximum amount of nitrate adsorbed onto the prepared adsorbent was obtained at pH 5.5 and contact time 30 min. The heterogeneous adsorption occurred during the uptake of nitrate. The results of kinetic study revealed that intra-particle diffusion was the major limitation for nitrate adsorption rate. The values of thermodynamic parameters illustrate the non-spontaneous, associative, and exothermic adsorption process. Increasing the temperature enhances the tendency of the process to non-spontaneously. Research on fixed-bed column has been done under different initial nitrate concentrations. The adsorption capacity of nitrate was increased with an increase in the initial concentration of nitrate. The results of column data were successfully explained using the Thomas and Yoon-Nelson models., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pragmatic clinical trials (PCTs) are well-suited to address unmet healthcare needs, such as those arising from the dual public health crises of chronic pain and opioid misuse, recently exacerbated by the COVID-19 pandemic. These overlapping epidemics have complex, multifactorial etiologies, and PCTs can be used to investigate the effectiveness of integrated therapies that are currently available but underused. Yet individual pragmatic studies can be limited in their reach because of existing structural and cultural barriers to dissemination and implementation. The National Institutes of Health, Department of Defense, and Department of Veterans Affairs formed an interagency research partnership, the Pain Management Collaboratory. The partnership combines pragmatic trial design with collaborative tools and relationship building within a large network to advance the science and impact of nonpharmacological approaches and integrated models of care for the management of pain and common co-occurring conditions. The Pain Management Collaboratory team supports 11 large-scale, multisite PCTs in veteran and military health systems with a focus on team science with the shared aim that the "whole is greater than the sum of the parts." Herein, we describe this integrated approach and lessons learned, including incentivizing all parties; proactively offering frequent opportunities for problem-solving; engaging stakeholders during all stages of research; and navigating competing research priorities. We also articulate several specific strategies and their practical implications for advancing pain management in active clinical, "real-world," settings., (© The Association of Military Surgeons of the United States 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Lateral ankle sprains (LASs) are common injuries among military service members. Approximately 40% of individuals with an LAS progress to develop chronic ankle instability (CAI), a condition that results in substantial mechanical and neurophysiological impairment and activity limitation. Since proprioceptive and balance training improve functional outcomes and prevent secondary injury following LAS, they are recommended in clinical practice. Uneven treadmills are an innovative modality that challenge the sensorimotor system while performing an ecologically valid task simulating environments frequently encountered by service members with LAS and CAI., Objective: The aim of this study is to evaluate whether the inclusion of uneven treadmill training in standard rehabilitation can improve clinical, functional, biomechanical, and patient-reported outcomes compared with the standard of care alone in service members with LAS and CAI. The prophylactic effects of treatment on secondary injury and identification of any contributing or mediating factors that influence outcomes following treatment will also be evaluated. We hypothesize that service members receiving uneven treadmill training will demonstrate greater improvements in clinical and instrumented measures of impairment, patient-reported function, and lower risk of injury recurrence than the control group immediately post and 18 months following treatment., Methods: A multisite, parallel randomized clinical trial will be performed among service members aged 18-49 years being treated for LAS and CAI in military treatment facilities in the United States. Participants randomly assigned and allocated to receive the experimental intervention will be provided up to 12 sessions of training on an uneven terrain treadmill over a 6-week treatment course to supplement standard rehabilitation care. Treatment intensity of the rehabilitation exercises and treadmill training will be progressed on the basis of patient-perceived intensity and treatment responses. Outcome measures will include patient-reported outcomes, functional assessments, performance measures, and biomechanical measures. Investigators collecting outcome measures will be blinded to treatment allocation. Reinjury rates and patient-reported outcomes of function will be tracked over 18 months following treatment., Results: The project was funded in September 2020. Patient recruitment began in November 2021, with 3 participants enrolled as of February 2022. Dissemination of the main study findings is anticipated in 2024., Conclusions: This study will assess the impact of an innovative uneven-terrain treadmill on treatment outcomes in the rehabilitation of service members with LAS and CAI. The results of this study will be used to inform rehabilitation practices and to potentially improve functional outcomes and secondary prevention in this patient population., Trial Registration: ClinicalTrials.gov NCT04999904; https://clinicaltrials.gov/ct2/show/NCT04999904?term=NCT04999904., International Registered Report Identifier (irrid): DERR1-10.2196/38442., (©Elizabeth Russell Esposito, Shawn Farrokhi, Benjamin R Shuman, Pinata H Sessoms, Eliza Szymanek, Carrie W Hoppes, Laura Bechard, David King, John J Fraser. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 22.06.2022.)

Background: Recent international health events have led to an increased proliferation of remotely delivered health interventions. Even with the pandemic seemingly coming under control, the experiences of the past year have fueled a growth in ideas and technology for increasing the scope of remote care delivery. Unfortunately, clinicians and health systems will have difficulty with the adoption and implementation of these interventions if ongoing and future clinical trials fail to report necessary details about execution, platforms, and infrastructure related to these interventions. The purpose was to develop guidance for reporting of telehealth interventions., Methods: A working group from the US Pain Management Collaboratory developed guidance for complete reporting of telehealth interventions. The process went through 5-step process from conception to final checklist development with input for many stakeholders, to include all 11 primary investigators with trials in the Collaboratory., Results: An extension focused on unique considerations relevant to telehealth interventions was developed for the Template for the Intervention Description and Replication (TIDieR) checklist., Conclusion: The Telehealth Intervention guideline encourages use of the Template for the Intervention Description and Replication (TIDieR) checklist as a valuable tool (TIDieR-Telehealth) to improve the quality of research through a reporting guide of relevant interventions that will help maximize reproducibility and implementation., (© 2022. The Author(s).)

Introduction: Recent studies show that the paracrine immunomodulatory effects of mesenchymal stem cells (MSCs) are mediated by the secretion of interleukin-10 (IL-10), transforming growth factor-beta (TGF β), and nitric oxide (NO). The preconditioning of MSCs improves their immunomodulatory characteristics. Chitosan is a biopolymer with low toxicity and biodegradability, used as a membrane for MSCs three-dimensional culture. The present study aimed to evaluate the levels of immunomodulatory mediators of mesenchymal cells cultured on the chitosan film., Materials & Methods: MSCs were isolated from abdominal adipose tissue of BALB/c mice. Flow cytometry and differential culture medium were used to confirm the identity of isolated mesenchymal stem cells. The MSCs were divided into three groups; The first group was treated with 10 ng/mL LPS. The second group was seeded in the flasks coated with the chitosan film (3% w/v). The last group was cultured in the flasks without any preconditioning. After 72 h, IL-10, TGF-β, and NO concentrations were measured in the conditioned media. In addition, the arginase activity in mesenchymal stem cells was measured using a colorimetric method., Results: The proliferative spindle-shaped MSCs formed several three-dimensional spheroids on the chitosan film. It was shown that the level of TGF-β and IL-10 were increased significantly after treatment with LPS (P = 0.02) and spheroid formation (P = 0.01). In addition, the arginase activity was enormously augmented in spheroids compared to controls (7.13-fold increase; 1.71 ± 0.08 and 0.24 ± 0.01 respectively; P = 0.021). On the other hand, the LPS treatment but not the culture on chitosan film increased the NO level significantly (P = 0.02 and P = 0.14, respectively)., Conclusion: Using chitosan film as a three-dimensional culture strategy significantly affects the production of immunosuppressive factors by MSCs in vitro through increased secretion of TGF-β and IL-10 and arginase activity., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: Ankle sprains are common injuries within the civilian and military populations, with lingering symptoms that include pain, swelling, giving-way, and a high likelihood for recurrence. Numerous bracing systems are available to stabilize the ankle joint following sprains, with new design iterations frequently entering the market. Currently available braces generally include sleeve, lace-up, and stirrup designs. Sleeves provide mild compression and warmth but limited stability for the ankle, while lace-ups and stirrups appear to be more effective at preventing and treating lateral ankle sprains., Areas Covered: This review summarizes the use of various brace options in practice. Their major clinical benefits, and limitations are highlighted, followed by an overview of emerging concepts in brace design. Current advancements in biomechanical simulation, multifunctional material fabrication, and wearable, field-deployed devices for human injury surveillance are discussed, providing possibilities for conceiving new design concepts for next-generation smart ankle braces., Expert Opinion: Performance of the commercially available braces are limited by their current design concepts. Suggestions on future brace design include: (1) incorporating high-performance materials suitable for extreme environments, (2) leveraging modeling and simulation techniques to predict mechanical support requirements, and (3) implementing adaptive, customizable componentry material to meet the needs of each unique patient.

Background: Balance is sustained through multi-joint coordination in response to postural perturbations. Low back pain alters postural responses; however, it is unknown how coordination between the trunk and lower extremities affects center of mass control during standing balance among persons with limb loss, particularly those with back pain., Methods: Forty participants with unilateral lower limb loss (23 with back pain) stood with eyes open and closed on a firm surface, while wearing IMUs on the sternum, pelvis, and bilaterally on the thigh, shank, and foot. A state-space model with Kalman filter calculated sagittal trunk, hip, knee, and ankle joint angles. Fuzzy entropy quantified center of mass variability of sagittal angular velocity at the sacrum. Normalized cross-correlation functions identified coordination patterns (trunk-hip, trunk-knee, trunk-ankle). Multiple linear regression predicted fuzzy entropy from cross-correlation values for each pattern, with body mass and amputation level as covariates., Findings: With eyes open, trunk-lower limb joint coordination on either limb did not predict fuzzy entropy. With eyes closed, positive trunk-hip coordination on the intact limb predicted fuzzy entropy in the pain group (p = 0.02), but not the no pain group. On the prosthetic side, inverse trunk-hip coordination patterns predicted fuzzy entropy in pain group (p = 0.03) only., Interpretation: Persons with limb loss and back pain demonstrated opposing coordination strategies between the lower limbs and trunk when vision was removed, perhaps identifying a mechanism for pain recurrence. Vision is the dominant source of balance stabilization in this population, which may increase fall risk when visual feedback is compromised., (Published by Elsevier Ltd.)

Ankle sprains are the most common musculoskeletal injury in sport and military activity, despite existing prophylactic strategies. The purpose of this report was to develop a probabilistic simulation of lateral ankle sprains during single-limb drop landing, towards accelerating innovation in ankle sprain prevention. A deterministic, subject-specific musculoskeletal model was extended with automation and probabilistic distributions on sprain-related biomechanical factors. Probabilistic simulations were generated using traditional Monte Carlo techniques and the advanced mean value method, a more computationally-efficient approach. Predicted distributions of peak ankle joint rotations, velocities, and moments borne by supporting passive structures agreed favorably with the deterministic model and with reports of real sprain biomechanics. Parameter sensitivities identified that predictions were most strongly influenced by drop height, subtalar joint posture at contact, invertor/evertor co-activation, and passive ankle stiffness. The advanced mean value method predicted confidence bounds comparable to a 1000-trial Monte Carlo simulation, and required only 14 model evaluations and 4-min processing time. The extended probabilistic simulation may be useful to virtually test new prophylactic strategies for ankle sprains, and is made available for open-source use (https://simtk.org/projects/sprain-sim)., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Yoder, Petrella and Farrokhi.)

Low back pain is a prevalent military and veteran health problem and individuals injured on deployment may be at particularly high risk of pain conditions. Given that increasing numbers of active duty and veteran military personnel are seeking care in community settings, it is critical that health care providers are aware of military health issues. The current study examined the prevalence of low back pain among individuals with deployment-related injuries, compared their self-reported pain intensity and interference ratings, and assessed the relationship between low back pain, self-reported pain ratings, and quality of life. Almost half of participants had low back pain diagnoses, and individuals with low back pain reported significantly higher intensity and interference due to their pain than individuals without low back pain. Finally, the relationship between low back pain and quality of life was explained by self-reported pain indices, underscoring the importance of patient-centered metrics in pain treatment., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC part of Springer Nature.)