New Tools for Viscoelastic Spectral Analysis, with Application to the Mechanics of Cells and Collagen across Hierarchies

Viscoelastic relaxation spectra are essential for predicting and interpreting the mechanical responses of materials and structures. For biological tissues, these spectra must usually be estimated from viscoelastic relaxation tests. Interpreting viscoelastic relaxation tests is challenging because the inverse problem is expensive computationally. We present here (1) an efficient algorithm and (2) a quasi-linear model that enable rapid identification of the viscoelastic relaxation spectra of both linear and nonlinear materials. We then apply these methods to develop fundamental insight into the mechanics of collagenous and fibrotic tissues. The first algorithm, which we term the discrete spectral approach, is fast enough to yield a discrete spectrum of time constants that is sufficient to fit a measured relaxation spectrum with an accuracy insensitive to further refinement. The algorithm fits a discrete spectral generalized Maxwell (Maxwell-Wiechert) model, which is a linear viscoelastic model, to results from a stress-relaxation test. The discrete spectral approach was tested against trial data to characterize its robustness and identify its limitations and strengths. The algorithm was then applied to identify the viscoelastic response of reconstituted collagen and engineered fibrosis tissues, revealing that cells actively adapted the ECM, and that cells relax at multiple timescales, including one that is fast compared to those of the ECM. The second algorithm, which we term the discrete quasi-linear viscoelastic (DQLV) approach, is a spectral extension of the Fung quasi-linear viscoelastic (QLV) model, a standard tool for characterizing biological materials. The Fung QLV model provides excellent fits to most stress-relaxation data by imposing a simple form upon a material\u27s temporal relaxation spectrum. However, model identification is challenging because the Fung QLV model\u27s “box” shaped relaxation spectrum, predominant in biomechanics applications, because it can provide an excellent fit even when it is not a reasonable representation of a material\u27s relaxation spectrum. The DQLV model is robust, simple, and unbiased. It is able to identify ranges of time constants over which the Fung QLV model\u27s typical box spectrum provides an accurate representation of a particular material\u27s temporal relaxation spectrum, and is effective at providing a fit to this model. The DQLV spectrum also reveals when other forms or discrete time constants are more suitable than a box spectrum. After validating the approach against idealized and noisy data, we applied the methods to analyze medial collateral ligament stress-relaxation and sinusoidal excitation data and identify the strengths and weaknesses of an optimal Fung QLV fit. Taken together, the tools in this dissertation form a comprehensive approach to characterizing the mechanics of viscoelastic biological tissues, and to dissecting the micromechanical mechanisms that underlie a tissue\u27s viscoelastic responses

Development of rheumatoid arthritis during treatment of multiple sclerosis with interferon beta 1-a. Coincidence of two conditions or a complication of treatment: A case report

AbstractCoexistence of multiple sclerosis (MS) with other autoimmune diseases has been attributed to common background genetic or environmental factors. This study presents development of rheumatoid arthritis (RA) during treatment of MS. The MS was confirmed by the Mc Donald criteria and the diagnosis of RA was confirmed by the ACR/EULAR criteria. A 35years old women with 9years of MS who was receiving interferon beta 1-a (INF) for 7years and who did not respond to conventional therapy of RA over 8months developed clinical manifestations of RA. But a rapid response was observed after discontinuation of INF. These findings suggest a possible contribution of INF in the development of RA

The Role of Privatization in the Development of Public Sports Participation

Sport, and especially public sports, is very important because it increases life expectancy by promoting community health. The purpose of this study was to investigate the role of privatization in the development of participation in public sports in Alborz, Iran. This study was a mixed research (qualitative and quantitative). In the qualitative phase, the participants included 12 university faculty members and public sports administrators. In the quantitative section, 384 people were selected as a statistical sample based on Morgan table. Amiri et al.'s Privatization Questionnaire (2013) and a researcher-developed questionnaire were used to measure the research variables. Confirmatory factor analysis and structural equation modeling were used to test the research hypotheses. The results showed that privatization has a critical role in the development of participation in public sports in Alborz province. Therefore, expansion of the role and position of the private sector is one of the actions that can be taken in this field. It is suggested that sports, health and well-being officials seriously consider privatization in order to facilitate and increase the participation in public sports

Viscoelastic spectrum analysis and the identification of a fung viscoelastic material

Despite its many limitations, the Fung “quasi-linear viscoelastic” constitutive model continues to serve as a workhorse of the biomechanics community. A central challenge in applying the model is that it requires a specific form for the relaxation spectrum that is difficult to relate to easily obtained experimental spectra such as a generalized Maxwell relaxation spectrum. Here, we present a simple and general technique for obtaining a from relaxation data a viscoelastic spectrum appropriate to the Fung model. We apply the model to identify several biomaterials that are modeled reasonably by a Fung model, and many more that are not

Serum ferritin levels and bone mineral density in the elderly

Background: Iron overload influences negatively on bone mineral density (BMD) but the results of studies regarding serum ferritin (SF) and BMD are conflicting.This study aimed to determine the association of SF and BMD in the elderly. Methods: All participants of the Amirkola cohort selected between 2011-2012, aged > 60 years were classified as high or normal (<200ng/ml) SF. BMD at femoral neck and lumbar spine was determined by dual energy x-ray absorptiometry (DXA) and the results were expressed as BMD g/cm2 and BMDT-score. Multiple logistic regression analysis with calculation of odds ratio (OR) and 95% confidence interval was used to estimate the association of low BMD (LBMD) defined as BMD T-score < -1 with SF. Results: 1089 subjects (women, 44.7%) were studied. High SF was observed in 366 (33.6%) and LBMD in 874 (80.2%) subjects. The two groups of SF were similar regarding biochemical parameters and demographic characteristics except MetS, overweight /obesity and diabetes which were more prevalent in high SFgroup. BMD g/cm2 at both measurement sites was significantly higher (P=0.001 for both) and the prevalence of LBMD was significantly lower (74.1% vs 83.1%, P=0.001) in high SF group by OR= 0.60 (0.44-0.81). After adjustment for all biochemical and demographic variables, the association remained significant by adjusted OR= 0. 68 (0.49-0.94). Conclusions: These findings show a negative association between high SF and LBMD indicating a beneficial effect of high SF in the elderly. Regarding detrimental effect of iron overload on bone mass, these findings require further studies

Effect of long-term low dose prednisolone administration on bone mineral density: Relating to non-compliant women with rheumatoid arthritis

Background: Long-term treatment of rheumatoid arthritis (RA) with prednisolone (PRED) is associated with bone mineral density (BMD) loss. This study aimed to determine the status of BMD in non-compliant women who used PRED alone for RA. Methods: Non-adherent RA taking 6 months, and RA patients taking methotrexate +PRED (RA control) were compared with age-matched non-RA controls. BMD was measured by dual energy x-ray absorptiometry (DXA) method and osteoporosis (OP) was diagnosed by WHO criteria. Influence of PRED on RA bone mass, and the risk of OP in RA was assessed by comparing PRED users RA and RA control,versus non-RA controls. Results: Sixty-four PRED user RA, 39 RA controls and 111 non RA-controls, with respective mean (±SD) age of 52±11; 8, 51±11; and 52±7.5 years (P=0.91) were studied. Median duration of treatment in PRED users and RA control was 2.5 and 4 years, respectively. BMD g/cm2 at the femoral neck (FN-BMD) and lumber spine (LS-BMD) in PRED users and RA control was significantly lower than non-RA control (P=0.001). The prevalence of OP at either FN or LS in both RA groups was significantly higher than controls (P=0.001). In PRED users, the risk of OP increased by OR=4.9, P=0.001) and in RA controls by OR=1.7 (P=0.20). The risk of OP in PRED user RA was 2.89 times (P=0.014) greater than RA controls. Conclusions: These findings indicate significantly lower BMD, and higher prevalence of osteoporosis in non-compliant women with RA taking low-dose PRED alone for a median period of 2.5 years, as compared with patients taking standard treatment comprising methotrexate +PRED

Real-Time Gas Identification by Analyzing the Transient Response of Capillary-Attached Conductive Gas Sensor

In this study, the ability of the Capillary-attached conductive gas sensor (CGS) in real-time gas identification was investigated. The structure of the prototype fabricated CGS is presented. Portions were selected from the beginning of the CGS transient response including the first 11 samples to the first 100 samples. Different feature extraction and classification methods were applied on the selected portions. Validation of methods was evaluated to study the ability of an early portion of the CGS transient response in target gas (TG) identification. Experimental results proved that applying extracted features from an early part of the CGS transient response along with a classifier can distinguish short-chain alcohols from each other perfectly. Decreasing time of exposition in the interaction between target gas and sensing element improved the reliability of the sensor. Classification rate was also improved and time of identification was decreased. Moreover, the results indicated the optimum interval of the early transient response of the CGS for selecting portions to achieve the best classification rates

Correlation between systemic markers of inflammation and local synovitis in knee osteoarthritis

Background: In the elderly population joint swelling, effusion and pain indicate local synovitis and the presence of inflammation. At present, no serum marker has been shown linking to knee synovitis in KOA. With regard to serum high sensitive C-reactive protein (hsCRP) as a measure of inflammation, this study aimed to determine the association of systemic inflammation with local synovitis, as well as with pain and muscle strength in KOA. Methods: The study population was selected consecutively among patients with KOA presented to Ayatollah Rouhani Hospital Rheumatology Clinic with knee joint synovitis. The diagnosis of KOA was confirmed according to the American College of Rheumatology diagnostic criteria. Data regarding radiographic, demographic and biochemical characteristics were provided and IL-17, IL-10, TGF-&#223; and hsCRP in serum and synovial fluid (SF) were measured in all patients. Stepwse linear regression models were used to determine the correlation between SF- hsCRP as a measure of local inflammation with other systemic or local markers of inflammation. Results: A total of 40 patients (women 65) with mean age 65.6+8.9 (49-86) years, mean BMI 27.7+3.7 (22-38) kg/m2, were analyzed. SF-hsCRP was positively correlated with serum hsCRP as well as serum and SF cytokines. Knee pain was positively associated with BMI and radiographic severity and negatively with quadriceps muscle strength (QMS) (r=-0.350, p=0.029). In stepwise linear regression analysis the SF-hsCRP was positively correlated with serum hs-CRP (r=0.769, p=0.001), SF-IL-17 (r=0.428, p=0.001) and negatvely with serum IL-10 (r=-0.316, p=0.002). Conclusion: These findings indicate that systemic markers of inflammation such as serum hsCRP, and IL-17 are associated with local inflamation in KOA

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Restorative Effect of Vitamin D Deficiency on Knee Pain and Quadriceps Muscle Strength in Knee Osteoarthritis

Both vitamin D deficiency and quadriceps muscle weakness are associated with knee osteoarthritis (KOA) and pain. The aim of this study was to determine the restorative effect of vitamin D deficiency on pain and quadriceps muscle strength in knee osteoarthritis. Patients with KOA aged≥30 years, the presence of knee pain for at least one month or longer and serum 25-hydroxyvitamin (25-OHD) deficiencies were recruited in the study. Participants with KOA compatible with Kellgren-Lawrence grade 4, joint instability, and effusion, history of surgery or inflammatory arthropathies were excluded. Serum 25-OHD was assessed by ELISA method and concentrations<20 ng/ml was considered deficiency. Quadriceps muscle strength was measured by dynamometry method and intensity of knee pain by Western Ontario and McMaster University Osteoarthritis index scored by Likert scale and visual analog scale. All participants received 50.000 IU oral cholecalciferol weekly for at least two months. The influence of raising serum 25-OHD on  uadriceps muscle strength and pain was assessed by calculation of mean changes from baseline at the end of the treatment period using paired t-test. A total of 67 patients with mean age of 50±6.6 years of age were treated for 2 months. Serum 25-OHD reached to sufficient levels in all except one patient. At the end of the study period, serum 25-OHD and quadriceps muscle strength increased significantly as compared with baseline (P=0.007 and P=0.002, respectively), whereas knee pain decreased significantly based on Western Ontario and McMaster University Osteoarthritis index (P=0.001) as well as visual analogue scale scores (P=0.001).These findings indicated that correction of vitamin D deficiency in patients with KOA exerts a significant favorable effect on quadriceps muscle streng h and knee pain