Process of estimating the material properties of human heel pad sub-layers using inverse finite element analysis and some model applications

The human heel pad is subject to repetitive loading and plays an important role in absorbing shocks which may cause injuries. The heel pad has a composite biological structure consistingof the fat pad and the skin. The fat pad tissue is organised into a superficial micro-chamber layer and a deep macro-chamber layer.The heel pad sub-layers have different structures and properties. Hence, to understand the contribution of each layer to the heel problem, it is essential to develop a model with discrete structure. Currently, only plantar pressure measurements are used for diagnosis and treatment of the heel problems, whereas it has been shown that high internal tissue stress is an important factor. Because of complex geometry, discrete structure and nonlinear material behaviour of the heel pad, the external force applied to the heel may result in inhomogeneous internal stress condition. Therefore, the relationship between the plantar pressure and internal stress does not seem to be simple. Since there is no equipment to allow measurement of internal stress, a detailed multi-layered FE model of the heel pad can be used as a solution to predict the internal stress.The main objective of this work was to obtain the hyperelastic and viscoelastic material properties of the subject-specific heel pad sub-layers in-vivo. For this purpose, a combined methodology of finite element modeling and experimentation was developed. An anatomically detailed 3D FE model of the human heel area was developed using MR images of the right foot of a female subject. A combined ultrasound and indentation systemwas used to apply series of slow and rapid compression tests on the same foot. The forcestrain responses of the heel pad and its sub-layers were used as input to the FE model to estimate properties of the heel pad sub-layers using inverse FEA. The hyperelastic and viscoelastic FE models were then implemented to investigate the effectsof experimental and geometrical factors on the heel pad responses. The model was also used to assess the robustness of the hyperelastic FE model when predicting the behaviour of other heels with different geometries. Finally, this model was used with Taguchi method to evaluatethe effect of footwear design factors on the compressive stress in the heel pad tissue. There were some key limitations in this study. For example, the properties of the heel pad sub-layers were estimated only for a specific heel pad. Also, whilst it is preferred to use xviiiautomatic segmentation and solid modeling to improve repeatability of some FE processes, some parts of the modeling process were performed manually

Estimating the material properties of heel pad sub-layers using inverse finite element analysis

Detailed information about the biomechanical behaviour of plantar heel pad tissue contributes to our understanding of load transfer when the foot impacts the ground. The objective of this work was to obtain the hyperelastic and viscoelastic material properties of heel pad sub-layers (skin, micro-chamber and macro-chamber layers) in-vivo. An anatomically detailed 3D Finite Element model of the human heel was used to derive the sub-layer material properties. A combined ultrasound imaging and motorised platform system was used to compress heel pad and to create input data for the Finite Element model. The force-strain responses of the heel pad and its sub-layers under slow compression (5mm/s) and rapid loading-hold-unloading cycles (225mm/s), were measured and hyperelastic and viscoelastic properties of the three heel pad sub-layers were estimated by the model. The loaded (under ~315N) thickness of the heel pad was measured from MR images and used for hyperelastic model validation. The capability of the model to predict peak plantar pressure was used for further validation. Experimental responses of the heel pad under different dynamic loading scenarios (loading-hold-unloading cycles at 141mm/s and sinusoidal loading with maximum velocity of 300mm/s) were used to validate the viscoelastic model. Good agreement was achieved between the predicted and experimental results for both hyperelastic (<6.4% unloaded thickness, 4.4% maximum peak plantar pressure) and viscoelastic (Root Mean Square errors for loading and unloading periods <14.7%, 5.8% maximum force) simulations. This paper provides the first definition of material properties for heel pad sub-layers by using in-vivo experimental force-strain data and an anatomically detailed 3D Finite Element model of the heel

Salford postgraduate annual research conference (SPARC) 2012 proceedings

These proceedings bring together a selection of papers from the 2012 Salford Postgraduate Annual Research Conference (SPARC). They reflect the breadth and diversity of research interests showcased at the conference, at which over 130 researchers from Salford, the North West and other UK universities presented their work. 21 papers are collated here from the humanities, arts, social sciences, health, engineering, environment and life sciences, built environment and business

Presentation of DNA Methyltransferase 3 Beta Mutation with Immune Deficiency and Dilation of Aorta and Esophagus

Background: Immunodeficiency, Centromeric region instability, and Facial anomalies syndrome (ICF) is a rare autosomal recessive disorder with Centromeric instability as a hallmark. Method: In this case report, we describe an Iranian 6-year-old male who was diagnosed with ICF syndrome. He had a history of recurrent infections, hydrocephalus report in pregnancy, failure to thrive, facial anomalies, global developmental delay, and umbilical hernia. Results: The investigation showed esophageal dilatation in barium swallow, ascending aortic dilatation in echocardiography and cutis laxa in skin biopsy. In laboratory data, impaired antibody function was observed. Finally, to find the probable causative genetic variant, a whole exome sequencing was performed. The data analysis using bioinformatics tools revealed c.1592G>A mutation in the exon 15 of DNMT3B. With respect to the diagnosis of ICF syndrome, our patient was treated with intravenous immunoglobulin (IVIG). Conclusion: It is necessary to perform periodic neurologic and ophthalmologic examinations. Echocardiography must be done annually. In addition, the possibility of HSCT should be evaluate

Primary antibody deficiency in a tertiary referral hospital: A 30-year experiment

Background: Primary antibody deficiency (PAD) is the most common group of primary immunodeficiency disorders (PID), with a broad spectrum of clinical features ranging from severe and recurrent infections to asymptomatic disease. Objectives: The current study was performed to evaluate and compare demographic and clinical data in the most common types of PAD. Materials and Methods: We performed a retrospective review of the medical records of all PAD patients with a confirmed diagnosis of common variable immunodeficiency (CVID), hyper IgM syndrome (HIgM), selective IgA deficiency (SIgAD), and X-linked agammaglobulinemia (XLA) who were diagnosed during the last 30 years at the Children�s Medical Center, Tehran, Iran. Results: A total number of 280 cases of PAD (125 CVID, 32 HIgM, 63 SIgAD, and 60 XLA) were enrolled in the study. The median (range) age at the onset of disease in CVID, HIgM, SIgAD, and XLA was 2 (0-46), 0.91 (0-9), 1 (0-26), and 1 (0-10) years, respectively. Gastrointestinal infections were more prevalent in CVID patients, as were central nervous system infections in XLA patients. Autoimmune complications were more prevalent in HIgM patients, malignancies in CVID patients, and allergies in SIgAD patients. The mortality rate for CVID, HIgM, and XLA was 27.2, 28.1, and 25, respectively. No deaths were reported in SIgAD patients. Conclusions: SIgAD patients had the best prognosis. While all PAD patients should be monitored for infectious complications, special attention should be paid to the finding of malignancy and autoimmune disorders in CVID and HIgM patients, respectively. © 2015 Esmon Publicidad

Primary immunodeficiency disorders in Iran: Update and new insights from the third report of the national registry

Background: Primary immunodeficiency disorders (PID) are a group of heterogeneous disorders mainly characterized by severe and recurrent infections and increased susceptibility to malignancies, lymphoproliferative and autoimmune conditions. National registries of PID disorders provide epidemiological data and increase the awareness of medical personnel as well as health care providers. Methods: This study presents the demographic data and clinical manifestations of Iranian PID patients who were diagnosed from March 2006 till the March of 2013 and were registered in Iranian PID Registry (IPIDR) after its second report of 2006. Results: A total number of 731 new PID patients (455 male and 276 female) from 14 medical centers were enrolled in the current study. Predominantly antibody deficiencies were the most common subcategory of PID (32.3 %) and were followed by combined immunodeficiencies (22.3 %), congenital defects of phagocyte number, function, or both (17.4 %), well-defined syndromes with immunodeficiency (17.2 %), autoinflammatory disorders (5.2 %), diseases of immune dysregulation (2.6 %), defects in innate immunity (1.6 %), and complement deficiencies (1.4 %). Severe combined immunodeficiency was the most common disorder (21.1 %). Other prevalent disorders were common variable immunodeficiency (14.9 %), hyper IgE syndrome (7.7 %), and selective IgA deficiency (7.5 %). Conclusions: Registration of Iranian PID patients increased the awareness of medical community of Iran and developed diagnostic and therapeutic techniques across more parts of the country. Further efforts must be taken by increasing the coverage of IPIDR via electronically registration and gradual referral system in order to provide better estimation of PID in Iran and reduce the number of undiagnosed cases. © 2014 Springer Science+Business Media

Consensus Middle East and North Africa Registry on Inborn Errors of Immunity

Background: Inborn errors of immunity (IEIs) are a heterogeneous group of genetic defects of immunity, which cause high rates of morbidity and mortality mainly among children due to infectious and non-infectious complications. The IEI burden has been critically underestimated in countries from middle- and low-income regions and the majority of patients with IEI in these regions lack a molecular diagnosis. Methods: We analyzed the clinical, immunologic, and genetic data of IEI patients from 22 countries in the Middle East and North Africa (MENA) region. The data was collected from national registries and diverse databases such as the Asian Pacific Society for Immunodeficiencies (APSID) registry, African Society for Immunodeficiencies (ASID) registry, Jeffrey Modell Foundation (JMF) registry, J Project centers, and International Consortium on Immune Deficiency (ICID) centers. Results: We identified 17,120 patients with IEI, among which females represented 39.4%. Parental consanguinity was present in 60.5% of cases and 27.3% of the patients were from families with a confirmed previous family history of IEI. The median age of patients at the onset of disease was 36 months and the median delay in diagnosis was 41 months. The rate of registered IEI patients ranges between 0.02 and 7.58 per 100,000 population, and the lowest rates were in countries with the highest rates of disability-adjusted life years (DALY) and death rates for children. Predominantly antibody deficiencies were the most frequent IEI entities diagnosed in 41.2% of the cohort. Among 5871 patients genetically evaluated, the diagnostic yield was 83% with the majority (65.2%) having autosomal recessive defects. The mortality rate was the highest in patients with non-syndromic combined immunodeficiency (51.7%, median age: 3.5 years) and particularly in patients with mutations in specific genes associated with this phenotype (RFXANK, RAG1, and IL2RG). Conclusions: This comprehensive registry highlights the importance of a detailed investigation of IEI patients in the MENA region. The high yield of genetic diagnosis of IEI in this region has important implications for prevention, prognosis, treatment, and resource allocation

Impact of SARS-CoV-2 Pandemic on Patients with Primary Immunodeficiency

Although it is estimated that COVID-19 life-threatening conditions may be diagnosed in less than 1:1000 infected individuals below the age of 50, but the real impact of this pandemic on pediatric patients with different types of primary immunodeficiency (PID) is not elucidated. The current prospective study on a national registry of PID patients showed that with only 1.23 folds higher incidence of infections, these patients present a 10-folds higher mortality rate compared to population mainly in patients with combined immunodeficiency and immune dysregulation. Therefore, further management modalities against COVID-19 should be considered to improve the survival rate in these two PID entities using hematopoietic stem cell transplantation and immunomodulatory agents. © 2020, The Author(s)

Monogenic Primary Immunodeficiency Disorder Associated with Common Variable Immunodeficiency and Autoimmunity

Background: Common variable immunodeficiency (CVID) is the most frequent primary immunodeficiency disorder mainly characterized by recurrent bacterial infections besides other immunological defects including loss of or dysfunction of B cells and decreased immunoglobulin levels. In this study, our aim is to evaluate clinical, immunological, and molecular data of patients with a primary clinical diagnosis of CVID and autoimmune phenotype with a confirmed genetic diagnosis. Methods: Among 297 patients with CVID, who were registered in the Iranian Primary Immunodeficiency Registry at Children's Medical Center Hospital in Iran, 83 patients have been genetically examined and 27 patients with autoimmunity and confirmed genetic mutations were selected for analysis. Whole-exome sequencing and confirmatory Sanger sequencing methods were used for the study population. A questionnaire was retrospectively filled for all patients to evaluate demographic, laboratory, clinical, and genetic data. Results: In the 27 studied patients, 11 different genetic defects were identified, and the most common mutated gene was LRBA, reported in 17 (63.0) patients. Two patients (7.7) showed autoimmune complications as the first presentation of immunodeficiency. Eleven patients (40.7) developed one type of autoimmunity, and 16 patients (59.3) progressed to poly-autoimmunity. Most of the patients with mono-autoimmunity (n = 9, 90.0) primarily developed infectious complications, while in patients with poly-autoimmunity, the most common first presentation was enteropathy (n = 6, 37.6). In 13 patients (61.9), the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency. The most frequent autoimmune manifestations were hematologic (40.7), gastrointestinal (48.1), rheumatologic (25.9), and dermatologic (22.2) disorders. Patients with poly-autoimmunity had lower regulatory T cells than patients with mono-autoimmunity. Conclusion: In our cohort, the diagnosis of autoimmune disorders preceded the diagnosis of primary immunodeficiency in most patients. This association highlights the fact that patients referring with autoimmune manifestations should be evaluated for humoral immunity. © 2020 Georg Thieme Verlag. All rights reserved