Search

Background: In recent years frequency of skin allergic diseases such as atopic dermatitis (eczema) and urticaria is reported to be high in the region. Identi?cation of reactive allergens in different areas are very important in the diagnosis and treatment of these diseases. The aim of this study was to determine frequency of common allergens in patients with skin allergies in province of Bushehr with regards to eczema and urticaria. Materials and methods: In this cross-sectional study, 234 patients with urticarial and eczema were enrolled. The participants reacted to at least one allergen with SPT. Skin prick test with standard inhaled and food was performed on patients according to the herbal geography of the area. Results: Among 837 patients referred to allergy clinic, 91 patients had eczema and 143 had urticaria. The frequency of both eczema and urticaria was significantly higher in females than in males. The most common food allergens in patients with eczema were almond (56.6%), walnut (47.7%) and soybean (46.1%). And in patients with urticaria were almond (58%), walnut (53.1%) and tomato (48.2%). Also, aeroallergens in the subjects were house dust mite (HDM) (63.7%), Russian thistle (57.7%) and Alternaria alternara (51.6%). Meanwhile, the common aeroallergens in the patients were HDM (66.4%), Russian thistle (52.4%) and date palm (51%). Conclusion: Our findings indicated that almond and walnut are important food allergens in participants with eczema and urticaria. Moreover, SPT reactivity was positive with aeroallergens such as HDM and weeds. [ABSTRACT FROM AUTHOR]

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.)

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.

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.

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.

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.)

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: 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.

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.)

Introduction: Allergic diseases could play a role of a predisposing factor for coronavirus disease 2019 (COVID-19). The aim of this study was to investigate allergic comorbidity and its association in COVID-19 patients., Methods: Demographic data, clinical manifestations, laboratory reports, and radiologic findings, together with underlying comorbidity of patients, were studies. Allergic diseases were identified by using the standard GA 2 LEN questionnaire. The severity of COVID-19 was assessed by a visual analog scale (VAS) and an intensive care unit (ICU) report., Results: Out of 400 COVID-19 patients admitted in the hospital, 158 (39.5%) presented with different allergic diseases, and a reverse association was observed between having allergic comorbidity and severity of COVID-19 infection (P = 0.005, relative risk = 0.96; 95% Confidence Interval (95% CI): 0.77-1.19). The respective frequency of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS), atopic dermatitis, chronic urticaria, and food or drug allergy was 7.3%, 16%, 1.8%, 5%, 10% and 13.3%. Significantly, only AR was reversely associated with the severity of COVID-19 (P = 0.02, relative risk = 0.45; 95% CI: 0.77-1.19). Additionally, 43% of the patients presented hypoxemia, and 93.5% had chest CT scan involvement. Interestingly, patients with allergic diseases had significantly lower hypoxemia and chest CT involvement as compared with non-allergic patients (P = 0.002 and 0.003, respectively)., Conclusion: The results of this study established that allergic diseases were not determined to be a predisposing factor for the severe acute respiratory syndrome (SARS) due to coronavirus 2 (SARS-CoV-2) infection. Significantly, AR patients developed mild clinical manifestations of COVID-19 and admitted to ICU as compared to non-AR patients., Competing Interests: There were no conflicts of interest in this study.

Introduction: Skeletal dysplasia is a common, clinically and genetically heterogeneous disorder in the human population. An increasing number of different genes are being identified causing this disorder. We used whole exome sequencing (WES) for detection of skeletal dysplasia causing mutation in a fetus affected to severe lethal skeletal dysplasia., Patient: Fetus was assessed by ultrasonography in second trimester of pregnancy. He suffers from severe rhizomelic dysplasia and also pathologic shortening of ribs. WES was applied to finding of causal mutation. Furthermore, bioinformatics analysis was performed to predict mutation impact., Results: Whole exome sequencing (WES) identified a homozygous frameshift mutation in the TMEM263 gene in a fetus with severe lethal skeletal dysplasia. Mutations of this gene have been previously identified in dwarf chickens, but this is the first report of involvement of this gene in human skeletal dysplasia. This gene plays a key role in the growth hormone signaling pathway., Conclusion: TMEM263 can be considered as a new gene responsible for skeletal dysplasia. Given the complications observed in the affected fetus, the mutation of this gene appears to produce much more intense complications than that found in chickens and is likely to play a more important role in bone development in human.

Allergic rhinitis (AR) is a prevalent disease affecting the quality of life of patients throughout the world. This study aimed to assess the prevalence of AR and its association with chronic rhinosinusitis (CRS) in the adult population living in Bushehr, southwestern part of Iran. In this population-based study, a total of 5420  individuals aged 15-65 years were selected through a multi-stage, cluster, random sampling method from which 5201 of them completed the Global Allergy and Asthma Network of Excellence (GA2LEN) questionnaire (Response rate=96.1%). The prevalence of AR, based on Allergic Rhinitis and Its Impact on Asthma (ARIA) classification (mild or moderate; intermittent or persistent) was calculated and the association of AR and CRS was evaluated using a multiple logistic regression model. The overall prevalence of AR was 28.8%, and for the intermittent and persistent AR were 25.9% (out of which 81.34% were moderate to severe) and 74.1% respectively. Moreover, the prevalence of AR was significantly higher in health workers and smokers (p=0.002 and p<0.001, respectively). Furthermore, an association was found between AR and CRS (p<0.001, aOR: 4.68, 95%CI: 4.07-5.39), and also, between the persistent AR and CRS as compared with the intermittent (p<0.001, aOR: 4.21, 95%CI: 3.40-5.22). The present study showed that the prevalence of AR in Bushehr (Southwestern part of Iran) was significantly high. In addition, the results indicated a strong association between AR and CRS, especially in individuals with moderate to severe persistent AR.

Background: Regarding the growing interest and importance of understanding the cellular changes of the cornea in diseases, a quantitative cellular characterization of the epithelium is becoming increasingly important. Towards this, the latest research offers considerable improvements in imaging of the cornea by confocal laser scanning microscopy (CLSM). This study presents a pipeline to generate normative morphological data of epithelial cell layers of healthy human corneas., Methods: 3D in vivo CLSM was performed on the eyes of volunteers (n=25) with a Heidelberg Retina Tomograph II equipped with an in-house modified version of the Rostock Cornea Module implementing two dedicated piezo actuators and a concave contact cap. Image data were acquired with nearly isotropic voxel resolution. After image registration, stacks of en-face sections were used to generate full-thickness volume data sets of the epithelium. Beyond that, an image analysis algorithm quantified en-face sections of epithelial cells regarding the depth-dependent mean of cell density, area, diameter, aggregation (Clark and Evans index of aggregation), neighbor count and polygonality., Results: Imaging and cell segmentation were successfully performed in all subjects. Thereby intermediated cells were efficiently recognized by the segmentation algorithm while efficiency for superficial and basal cells was reduced. Morphological parameters showed an increased mean cell density, decreased mean cell area and mean diameter from anterior to posterior (5,197.02 to 8,190.39 cells/mm 2 ; 160.51 to 90.29 µm 2 ; 15.9 to 12.3 µm respectively). Aggregation gradually increased from anterior to posterior ranging from 1.45 to 1.53. Average neighbor count increased from 5.50 to a maximum of 5.66 followed by a gradual decrease to 5.45 within the normalized depth from anterior to posterior. Polygonality gradually decreased ranging from 4.93 to 4.64 sides of cells. The neighbor count and polygonality parameters exhibited profound depth-dependent changes., Conclusions: This in vivo study demonstrates the successful implementation of a CLSM-based imaging pipeline for cellular characterization of the human corneal epithelium. The dedicated hardware in combination with an adapted image registration method to correct the remaining motion-induced image distortions followed by a dedicated algorithm to calculate characteristic quantities of different epithelial cell layers enabled the generation of normative data. Further significant effort is necessary to improve the algorithm for superficial and basal cell segmentation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/qims-20-1052). Dr. KAS reports grants from German Federal Ministry of Education and Research, during the conduct of the study; Dr. KS reports grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), during the conduct of the study; Dr. TS reports grants from German Federal Ministry of Education and Research, during the conduct of the study; Dr. SA reports grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), during the conduct of the study; Dr. BK reports grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), during the conduct of the study; SB reports grants from Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), during the conduct of the study. The other authors have no conflicts of interest to declare., (2021 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Background: Physical therapy (PT) is frequently used for the management of low back pain (LBP) within the US Departments of Defense (DOD) and Veterans Affairs (VA). However, variations in PT practice patterns and use of ineffective interventions lower the quality and increase the cost of care. Although adherence to the clinical practice guidelines (CPGs) can improve the outcomes and cost-effectiveness of LBP care, PT CPG adherence remains below 50%. The Resolving the Burden of Low Back Pain in Military Service Members and Veterans (RESOLVE) trial will evaluate the effectiveness of an active PT CPG implementation strategy using an education, audit, and feedback model for reducing pain, disability, medication use, and cost of LBP care within the DOD and VA health care systems., Design: The RESOLVE trial will include 3,300 to 7,260 patients with LBP across three DOD and two VA medical facilities using a stepped-wedge study design. An education, audit, and feedback model will be used to encourage physical therapists to better adhere to the PT CPG recommendations. The Oswestry Disability Index and the Defense and Veterans Pain Rating Scale will be used as primary outcomes. Secondary outcomes will include the LBP-related medication use, medical resource utilization, and biopsychosocial predictors of outcomes. Statistical analyses will be based on the intention-to-treat principle and will use linear mixed models to compare treatment conditions and examine the interactions between treatment and subgrouping status (e.g., limb loss)., Summary: The RESOLVE trial will provide a pragmatic approach to evaluate whether better adherence to PT CPGs can reduce pain, disability, medication use, and LBP care cost within the DOD and VA health care systems., (Published by Oxford University Press on behalf of the American Academy of Pain Medicine 2020.This work is written by US Government employees and is in the public domain in the US.)

Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: An award was given to Iraj Nabipour by “Novo Nordisk Pars” (The Best Innovator of Diabetes in Iran 2013). For the remaining authors none were declared., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Common variable immunodeficiency (CVID) is a primary immune deficiency disorder characterized by a failure in B cell differentiation, impaired immunoglobulin production,and defect in response to vaccines. As a result of defective B cell maturation and differentiation in CVID, the affected patients commonly present with reduced numbers of memory B cell and antibody-secreting plasma cells. B-cell lymphoma 6 protein (BCL6) and B lymphocyte induced maturation protein 1 (BLIMP1) molecules are two important transcription factors that have key roles in the maturation of B cells to plasma cells. Hence, in the current survey, we aimed to evaluate the mRNA and protein expression levels of BCL6 and BLIMP1 in B lymphocytes isolated from peripheral blood in CVID patients. We collected blood samples from 12 CVID patients and 12 healthy controls. We isolated peripheral blood mononuclear cells (PBMCs) using Ficoll density gradient separation. Then, CD19+ B cells were purified using MACS. The protein expression and transcriptional level of BCL6 and BLIMP1 were respectively measured using flow cytometry and real-time PCR. Our results showed that the BLIMP1 mRNA expression, as well as BLIMP1 protein expression, were significantly higher in CVID patients compared to control subjects (p=0.009 and p=0.007, respectively). However, we found no significant difference in mRNA and protein expression of BCL6 between patients and healthy controls. According to our findings, increased mRNA and protein expression levels of BLIMP1 could be involved in defective maturation of B cells in patients with CVID and elucidate mechanistic insights into the pathogenesis of this disorder.

Objective: This study preliminarily characterizes and compares the impact of lower limb loss and development of chronic low back pain (cLBP) on psychosocial factors, as well as the relationship between these factors and low back pain-related functional disability., Design: Cross-sectional study., Methods: Participants were adults, active duty or retired military, with traumatic lower limb loss with and without chronic low back pain. Psychosocial factors and low back pain-related functional disability were measured using common clinical self-report questionnaires. The presence of psychosocial factors was compared between those with and without cLBP using multivariate analysis of covariance (P < 0.05), and correlations determined relationships between psychosocial factors and cLBP-related functional disability., Results: There were no statistically significant differences among psychosocial factors between those with vs without cLBP (F(4, 13) = 0.81, P = 0.54, η2= 0.19). Employment status (ρ = 0.43, P = 0.02), anxiety (ρ = 0.45, P = 0.04), and kinesiophobia (ρ = 0.47, P = 0.04) were moderately associated with low back pain-related disability., Conclusions: Psychological (i.e., anxiety) and social (i.e., employment status) factors may influence how persons with traumatic lower limb loss respond to self-reported measures of low back pain-related disability. The findings suggest that the Modified Oswestry Disability Index identifies cLBP-related functional disability in the context of lower limb loss. These results support the interdependence among biological, psychological, and social factors, which should be collectively considered during the development of rehabilitative strategies to treat secondary musculoskeletal conditions within this population., (2019 American Academy of Pain Medicine. This work is written by US Government employees and is in the public domain in the US.)

Background: Asthma is recognized as a major public health concern in the world. The aim of this investigation was to evaluate the prevalence of asthma by using the Global Allergy and Asthma Network of Excellence (GA 2 LEN) questionnaire and examine its association with chronic rhinosinusitis, in the province of Bushehr, Southwestern of Iran., Methods: In a cross-sectional, population-based study, a total of 5420 invited individuals, aged 15-65, were selected through a multi-stage, stratified, cluster random sampling and from which 5201 completed the GA 2 LEN questionnaire (response rate = 95.9%). The prevalence of asthma, current, and physician-diagnosed asthma were analyzed by using sex and age groups and the association of asthma and chronic rhinosinusitis (CRS) was investigated using a multiple logistic regression model., Results: Based on the information from the GA 2 LEN questionnaire, the overall prevalence of asthma in the population under study was 10.0% (95% CI 9.2-10.8). Moreover, the prevalence of current asthma was 8.9% (95% CI 8.1-9.7). Further, the prevalence of current early, late-onset and physician-diagnosed asthma within the asthma group was 51.1% (95% CI 46.5-55.7), 48.9% (95% CI 44.3-53.5) and 3.9% (95% CI 2.1-2.5), respectively. Additionally, CRS was more frequent among the participants with asthma [(57.3%, OR = 2.3; 95% CI 2.1-2.5)], and there was a significant association between CRS and current, early and late-onset of asthma (P < 0.001; OR = 4.4, 3.2 and 6, respectively)., Conclusion: This large population study conducted in the southwestern part of Iran suggests that the prevalence of asthma is high. Moreover, the result of this study showed a strong association of asthma with CRS; also after adjusting for sex, age, educational level, and smoking., Competing Interests: Competing interestsThe authors declare that they have no competing interests.

Controlled trunk motion is crucial for balance and stability during walking. Persons with lower extremity amputation often exhibit abnormal trunk motion, yet underlying mechanisms are not well understood nor have optimal clinical interventions been established. The aim of this work was to characterize associations between altered lower extremity joint moments and altered trunk dynamics in persons with unilateral, transtibial amputation (TTA). Full-body gait data were collected from 10 persons with TTA and 10 uninjured persons walking overground (~1.4 m/s). Experimentally-measured trunk angular accelerations were decomposed into constituent accelerations caused by net joint moments throughout the body using an induced acceleration analysis. Results showed persons with TTA had similar ankle moment magnitude relative to uninjured persons (P > 0.05), but greater trunk angular acceleration induced by the prosthetic ankle which acted to lean the trunk ipsilaterally (P = 0.003). Additionally, persons with TTA had a reduced knee extensor moment relative to uninjured persons (P < 0.001), resulting in lesser sagittal and frontal induced trunk angular accelerations (P < 0.001). These data indicate kinetic compensations at joints other than the lumbar and hip contribute to altered trunk dynamics in persons with a unilateral TTA. Findings may inform development of new clinical strategies to modify problematic trunk motion.

Cardiovascular toxicity is the most common cause of fatality in the first 24 hours of poisoning with aluminium phosphide (AlP). Most often manifesting itself in cardiac dysrhythmias. The aim of this study was to evaluate the benefits of amiodarone prophylaxis against cardiac dysrhythmia in 46 patients with acute AlP poisoning. They were divided in two groups of 23: one receiving amiodarone and the other not (control). The treatment group received amiodarone prophylaxis in the initial intravenous bolus dose of 150 mg, followed by a drip of 1 mg/min for six hours and then of 0.5 mg/min for eighteen hours. Both groups were Holter-monitored for 24 hours since admission. Save for amiodarone, both groups received the same standard treatment. Amiodarone had a significant beneficial effect in reducing the frequency of ST-segment elevation and ventricular fibrillation plus atrial fibrillation (P=0.02 and P=0.01, respectively), but the groups did not differ significantly in mortality (9 vs 11 patients, respectively). The mean time between ICU admission and death (survival time) was significantly longer in the treatment group (22 vs 10 h, respectively; P=0.03). Regardless its obvious limitations, our study suggests that even though amiodarone alone did not reduce mortality, it may provide enough time for antioxidant therapy to tip the balance in favour of survival and we therefore advocate its prophylactic use within the first 24 h of AlP poisoning.

Major amputations of the lower and upper limbs are among the most life-altering and debilitating combat injuries. From 1 January 2001 through 31 October 2017, a total of 1,705 service members sustained major deployment-related lower and upper limb amputations. Lower limb amputations were far more common than upper limb amputations, with a total of 1,914 lower limb amputations, compared to 302 upper limb amputations. The greatest single-year number of amputations occurred in 2011, with a reported total of 273 service members who sustained 403 major limb amputations. The injured cohort mostly comprised non-Hispanic white male service members aged 21-29 years. Furthermore, the majority of the injured cohort included active component, mid-level or junior enlisted members of the Army or Marine Corps in combat-specific occupations. These findings reiterate and extend previous reports of the annual numbers, types, and anatomic locations of deployment-related limb amputations, along with the demographics and military characteristics of the injured cohort from the Iraq and Afghanistan conflicts.

Toll-like receptors (TLRs), a family of pattern recognition receptors expressed on many cell types of innate immunity, recognize the pathogen-associated molecular patterns of microbes. The hygiene hypothesis suggests that a reduced microbial exposure in early childhood increases the susceptibility to allergic diseases due to deviation in development of the immune system. TLRs are key roles in the right and healthy direction of adaptive immunity with the induction of T-helper 2 toward Th1 immune responses and regulatory T cells. TLR ligand CpG-ODN-based immunomodulation is independent of allergen and it mainly affects innate immune system. While, CpG-oligodeoxynucleotide-based vaccination is allergen specific and induces adaptive immune system. The use of agonists of TLR9 in two distinct strategies of immunotherapy, immunomodulation and vaccination, could be presented as the curative method for the treatment of allergic diseases.

Background: Patients with β-thalassemia major (TM) develop iron overload through increased iron absorption and transfusional therapy and it's the most important complication of TM. Thalassemia is common in coastal regions and lands with low altitudes. The aim of this study is to determine the effect of high and low altitude on serum ferritin and treatment requirement in two groups of β-thalassemia major (TM) patients., Subjects and Methods: Patients were divided into two groups, the first group (No: 50) living at sea level (in the port of Bushehr, Iran) and the second group (No: 40) living at the altitude of 2061 m (in the city of Shahrekord, Iran). All patient's clinical history, blood transfusion and laboratory tests including complete blood count and hemoglobin electrophoresis were reviewed., Results: There were no significant difference in ferritin levels, transfusion period and diabetes incidence of the two cities patients (P>0.05). Patient's cardiac function and liver condition were significantly better in patients of Bushehr (P<0.05). Patients under 20 years in Bushehr were less splenectomized in comparison with Shahrekord (P<0.05)., Conclusion: Our result showed that some of clinical manifestations of patients in low altitude such as cardiac and liver condition were better. But it did not affect ferritin level probably due to transfusion and chelating therapy. Totally patients of Bushehr had better conditions and had longer survivals.

Purpose: The main objective of the Bushehr Elderly Health Programme, in its first phase, is to investigate the prevalence of cardiovascular risk factors and their association with major adverse cardiovascular events., Participants: Between March 2013 and October 2014, a total of 3000 men and women aged ≥ 60 years, residing in Bushehr, Iran, participated in this prospective cohort study (participation rate=90.2%)., Findings to Date: Baseline data on risk factors, including demographic and socioeconomic status, smoking and medical history, were collected through a modified WHO MONICA questionnaire. Vital signs and anthropometric measures, including systolic and diastolic blood pressure, weight, height, and waist and hip circumference, were also measured. 12-lead electrocardiography and echocardiography were conducted on all participants, and total of 10 cc venous blood was taken, and sera was separated and stored at -80 °C for possible future use. Preliminary data analyses showed a noticeably higher prevalence of risk factors among older women compared to that in men., Future Plans: Risk factor assessments will be repeated every 5 years, and the participants will be followed during the study to measure the occurrence of major adverse cardiac events. Moreover, the second phase, which includes investigation of bone health and cognition in the elderly, was started in September 2015. Data are available at the Persian Gulf Biomedical Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran, for any collaboration., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Electromechanical delay (EMD) and uncertain nonlinear muscle dynamics can cause destabilizing effects and performance loss during closed-loop control of neuromuscular electrical stimulation (NMES). Linear control methods for NMES often perform poorly due to these technical challenges. A new predictor-based closed-loop controller called proportional integral derivative controller with delay compensation (PID-DC) is presented in this paper. The PID-DC controller was designed to compensate for EMDs during NMES. Further, the robust controller can be implemented despite uncertainties or in the absence of model knowledge of the nonlinear musculoskeletal dynamics. Lyapunov stability analysis was used to synthesize the new controller. The effectiveness of the new controller was validated and compared with two recently developed nonlinear NMES controllers, through a series of closed-loop control experiments on four able-bodied human subjects. Experimental results depict statistically significant improved performance with PID-DC. The new controller is shown to be robust to variations in an estimated EMD value.

Purpose: This study aimed to test the hypothesis that internal rotation of the femur increases patellofemoral joint stress in persons with patellofemoral pain (PFP)., Methods: Patella cartilage stress profiles of nine female participants with PFP were obtained during squatting using subject-specific finite element (FE) models of the patellofemoral joint (15° and 45° of knee flexion). Input parameters for the FE model included joint geometry, quadriceps muscle forces during squatting, and weight-bearing patellofemoral joint kinematics. The femur of each model was then internally rotated 5° and 10° along its long axis beyond that of the natural degree of rotation. Using a nonlinear FE solver, quasistatic loading simulations were performed to quantify patellofemoral joint stress., Results: Compared with those at the natural position of the femur, mean hydrostatic pressure and mean octahedral shear stress were significantly higher when the femur was internally rotated 5° and 10°. No significant differences in stress variables were observed when the femur was rotated from 5° to 10°. These findings were consistent across both knee flexion angles (15° and 45°)., Conclusions: The finding of elevated hydrostatic pressure and octahedral shear stress with internal rotation of the femur supports the premise that females with PFP who exhibit abnormal hip kinematics may be exposed to elevated patellofemoral joint stress.

Aeroallergens continue to have a key role in the pathogenesis of asthma and allergic diseases and have recently received increased attention in medical research throughout the world. The prevalence of aeroallergens vary in different regions, depending on the type of climate. The aim of the present study was to determine prevalence of the sensitivity to aeroallergens among patients with asthma and allergic rhinitis (AR), based on skin prick test (SPT) reactivity in the province of Bushehr, Iran. In this cross-sectional study, 743 patients were enrolled. The participants had asthma and AR and reacted to at least one allergen with SPT. Skin prick test with standard extracts including house dust mites (HDMs), animal dander, molds and pollens were performed on patients according to the herbal geography of the area. The male to female ratio and mean age of the patients were 1.03 and 27.6± 15.4 year, respectively. Out of 567 patients with AR, the common aeroallergens were HDMs (88.5%), molds (82.9%), animal dander (79.5%), weeds (77.6%), trees (75.5%) and grass pollen (71.5%). Moreover, among 176 patients with asthma, the prevalence of aeroallergens were HDMs (90.5 %), molds (80.7%), animal dander (77.5%), weeds (73.3%), trees (73.3%) and grass pollen (67.9%). The sensitivity to animal dander, Chenopodium album and Russian thistle pollens were significantly associated with the severity of AR. Moreover, sensitivity to animal dander such as cat and feather of birds, cockroach, Bermuda grass and Chenopodium album pollens were significantly associated with the severity of asthma. The results of this study revealed that HDM was the most common sensitizing aeroallergen in patients with asthma and AR. Molds and animal dander as indoor allergens were also common aeroallergens. We suggest that the hot weather and ambient humidity in the region may be the main cause of the change in the pattern of SPT reactivity.

Background: Rehabilitation plays an important role to improve the outcomes of total knee arthroplasty (TKA). Evidence about the appropriate dose of exercise to recover gait dysfunction after TKA is limited. We posed the research question: In patients during the post-acute stage after TKA, is increased dose of exercise associated with larger improvements in gait parameters such as step length and single support time?, Methods: This was a secondary analysis from two randomized studies on exercise after TKA to investigate dose-dependence of gait parameters in response to exercise. Participants were 50 years or older who underwent unilateral TKA at least two months prior. They participated in 2 months of supervised exercises followed by 4 months of a home exercise program. The primary outcome was change in gait parameters from baseline to 6 months. Participants were divided in three groups according to the dose of exercise: group 1 (light-to-moderate intensity exercise), group 2 (high intensity + functional exercise), and group 3 (high intensity + functional + balance exercise). Jonckheere-Terpstra test was used to test if the magnitude of changes in gait parameters increased from group 1 to group 3 in an ordered fashion., Results: Increased dose of exercise was associated with progressive increases in step length in the operated-limb (p=0.008) and decreases in step length in the non-operated limb (p=0.011). Increased dose of exercise was associated with ordinal decreases in loading response time (p=0.049) and increases in single-leg support time (p=0.021) on the operated- limb, but not on the non-operated-limb. Increased dose of exercise was associated with decreases in unloading time on the non-operated-limb (p=0.011) but not on the operated-limb (p=0.400)., Conclusions: Significant dose-response of exercise on gait parameters support the promotion of more intensive exercise programs that combine functional and balance training programs after TKA.

Objective: Studies determining the relationship between serum vitamin D status and childhood asthma have yielded controversial results. Findings indicated that vitamin D deficiency is associated with asthma and airway hyper responsiveness. The aim of this study was to assess the relationship between serum vitamin D status and childhood asthma., Methods: Data were obtained from 200 asthmatic children (age 3-12 years) and 200 healthy controls. Serum levels of 25(OH) vitamin D, total IgE, calcium, phosphorus, parathormone (PTH) and eosinophil count were measured in both asthmatic children and healthy controls. Also, the mean values of 25(OH) vitamin D were compared with asthma symptom severities., Findings: There was a significant decrease in the concentration of serum 25(OH) vitamin D in the asthmatic patients as compared with the controls (20.34±2.8 vs 25.39±4.1 ng/mL, 95%CI: 1.46-3.86, P=0.01). Out of total asthmatic subjects, 40 (20%) were vitamin D sufficient, 48 (24%) were insufficient, and 112 (56%) were deficient. Total IgE concentration was also significantly higher in asthmatic patients having vitamin D deficiency (132.4±20.1 IU/ml, 95%CI: 1.38-3.75, P=0.03). Comparing asthmatic patients with healthy controls, odds of having vitamin D level less than 20ng/mL was 2.47., Conclusion: Our findings suggest that vitamin D deficiency or insufficiency may be positively related to the prevalence of asthma in children.