Analyzing Strain in the Ovine Anterior Cruciate Ligament

Osteoarthritis (OA) is the most common joint disorder affecting adults. Relating the mechanics and biology of the knee joint is crucial to understanding the development and progression OA. A key aim of such studies is to determine the structure/function relationship and failure thresholds of the joint tissues, in-vivo. The Anterior Cruciate Ligament (ACL) is of great interest as it is one of the most commonly injured ligaments linked with premature OA. Previous ACL studies have been unable to determine the stresses within the structure, due to absence of reliable methods of measuring the cross-sectional area of the loaded part of the ligament. Purpose: This study aims to evaluate the normal in-vivo stresses within the ACL, by developing a suitable method to measure the loaded area of the ACL. Methods: Ovine stifle joints were used due to morphological and biochemical proximity to human knee joints. Measurements of in-vivo loadings within the ACL were obtained using an instrumented spatial linkage and robotic test system. Two techniques to measure the area of the loaded ACL will be explored: 3D Virtual Reconstruction (3DVR) and Magnetic Resonance Imaging (MRI). 3DVR: The non-loaded part of the ACL was removed. A cloud of points was measured along the surface of the remaining (loaded) part of the ligament and processed to create a 3DVR of the ACL. MRI: Tests (proton density and T2 mapping) will be run on the 9.4T MR to compare structural differences between a loaded and relaxed ligament. Results: 3DVR method produced only a partial surface reconstruction due to the relatively large size of the probe in comparison to the ligament and femorotibial joint space. Differences between loaded and unloaded MRI images will be assessed using a special jig allowing sequential tensioning of the ligament. Conclusions: It was concluded that the partial 3DVR was insufficient to determine the loaded cross- sectional areas along the ligament accurately. The MRI results will be available for examination shortly

Estimation of the Thyroid Secondary Cancer Risk on the Patient of Standard Breast External Beam Radiotherapy

Background: The purpose of this study was to estimate the secondary cancer risk of thyroid in standard radiotherapy methods which are commonly used for breast cancer patients. Methods: A total of 64 breast cancer patients (their age range was around 50 years old) who referred to Seyed-Al-Shohada hospital (Isfahan, Iran) were included in this study. The radiotherapy of the mentioned patients was performed using 6-MV photon beams. Dose measurements were also done using thermoluminescent dosimeters. Calculation of the risk of developing secondary cancer in thyroid was done using the Biological Effects of Ionizing Radiation Committee VII and recommended quantity of the International Radiation Protection Commission, excess relative risk. Results: The mean radiation dose to thyroid for the tangential beams, tangential field with supraclavicular (SC) field, and also a tangential field with SC field in modified radical mastectomy (MRM) were 0.883 ± 0.472, 1.512 ± 0.365, and 1.587 ± 0.37, respectively. The risk of developing secondary thyroid cancer over a period of 5 years after breast cancer therapy in the tangential, tangential with a SC field, and also tangential beam with SC field in MRM were 9.974 ± 4.318, 17.891 ± 0.365, and 18.783 ± 4.384, respectively. The mean of the measured thyroid doses in patients treated with tangent fields was significantly lower than the patients under the irradiation of the tangent fields with SC field (P < 0.001). Conclusions: Using radiation protection equipment is suggested for breast cancer patients who treated with the studied radiotherapy methods

Differential MicroRNA Expression Levels in Cutaneous Acute Graft-versus Host Disease

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for numerous haematological malignancies. However, acute graft-versus-host disease (aGvHD) is a major complication affecting 40-70% of all transplant patients, whereby the earliest and most frequent presentation is in the skin. MicroRNAs play a role in varied biological process and have been reported as potential biomarkers for aGvHD. More recently, microRNAs have received added attention as circulatory biomarkers that can be detected in biofluids. In the present study we performed global microRNA expression profiling using a discovery cohort of diagnostic cutaneous aGvHD biopsies (n=5, stage 1-3) and healthy volunteers (n=4), in order to identify a signature list of microRNAs that could be used as diagnostic biomarkers for cutaneous aGvHD. Candidate microRNAs (n=8) were then further investigated in a validation cohort of post-HSCT skin biopsies (n=17) for their association with aGvHD. Expression of miR-34a-5p (p<0.001), miR-34a-3p (p=0.013), miR-503-5p (p=0.021) and let-7c-5p (p=0.037) was elevated in cutaneous aGvHD and significantly associated with survival outcome (miR-34a-3p ROC AUC=0.93, p=0.003, Log Rank p=0.004; miR-503-5p ROC AUC=0.83 p=0.021, Log Rank p=0.003). There was no association with relapse. A statistical interaction between miR-34a-3p and miR-503-5p (p=0.016) was diagnostic for aGvHD. Expression levels of the miR-34a-5p protein target p53 were assessed in the epidermis of the skin, and an inverse correlation was identified (r2=0.44, p=0.039). Expression of the validated candidate microRNAs was also assessed at day 28 post-HSCT in the sera of transplant recipients, in order to investigate their potential as circulatory microRNA biomarkers. Expression of miR-503-5p (p=0.001), miR-34a-5p (p=0.005) and miR-34a-3p (p=0.004) were significantly elevated in the sera of patients who developed aGvHD vs. no-aGvHD (n=30) and miR-503-5p was associated with overall survival (ROC AUC=0.80, p=0.04, Log Rank p=0.041). In conclusion, this investigation reports that microRNA expression levels in clinical skin biopsies, obtained at the time of cutaneous aGvHD onset, show potential as diagnostic biomarkers for aGvHD and as predictive biomarkers for overall survival. Additionally, the same microRNAs can be detected in the circulation and show predictive association with post-HSCT outcomes

Design of a generally applicable abdominal shield for reducing fetal dose during radiotherapy of common malignancies in pregnant patients

Background: In most cancer cases, the treatment choice for a pregnant patient is radiotherapy. In these patients, the abdomen is usually not exposed; therefore fetus exposure is due to peripheral dose (PD). The purpose of this study was to estimate the fetal dose (the maximum PD in each pregnancy stage) for modalities available and to fabricate and evaluate a generally applicable fetal shield. Materials and Methods: PD values were measured for brain, breast and mediastinum irradiation in a whole body anthropomorphic phantom using a NE 2571 ionization chamber. An external shield was then designed to reduce the fetal dose to the standard dose limit, 5 mSv. Results: The range of PD values as a function of distance from the field&apos;s edge were as follows 1) 9.4-259 cGy for Mantel field; 2) 6.5-95 cGy for chest wall irradiation with 10 MeV electrons, 3) 8.5-52.5 cGy for tangential field with Co-60 and 4) 4.8-7.8 cGy for brain radiotherapy with 9 MV photon. PD values for the same setups using the fetal shield were as follows: 1) 1.4-22 cGy, 2) 0.5-4 cGy, 3) 1.5-5 cGy and 4) under 1 cGy. Conclusions: The measured PD data sets can be used to estimate fetal dose for specific treatment setups and pregnancy stages. The use of external shield designed in this research reduced the fetal dose effectively to under the threshold (a 70-90% reduction), except for the final stages of pregnancy in Hodgkin&apos;s patients. Iran. J. Radiat. Res., 2012; 10(3-4): 151-15

Expression and characterization of a novel recombinant cytotoxin II from Naja naja oxiana venom: A potential treatment for breast cancer

Breast cancer (BC) is among the leading causes of mortality from cancer in women. Many of the available anticancer drugs have various side effects. Therefore, researchers are seeking novel anticancer agents particularly from natural compounds and in this regard, snake venom is still one of the main sources of drug discovery. Previous studies showed potential anticancer effects of Cytotoxin II (CTII) from Naja naja oxiana against the different types of cancers. In this study, a pET-SUMO-CTII vector was transformed into SHuffle® T7 Express, an Escherichia coli strain, for recombinant protein expression (rCTII) and the cytotoxic effects of this protein was assessed in MCF-7 cells. The flow cytometry assay was applied to measure the apoptosis and cell cycle. Also, mRNA levels of the Bax, Bcl2, P53, caspase-3, caspase-8, caspase-9, caspase-10, matrix metalloproteinases (MMP)-3, and MMP-9 were analyzed by quantitative real-time PCR to determine the underlying cellular pathways affected by rCTII. The results of this study showed that treatment with 4 μg mL−1 of rCTII enhanced apoptosis through the intrinsic and extrinsic pathways. Also, the increase of the cells' proportion in the sub-G1 phase as well as a reduction in S phase was observed. In addition, the expression of MMP-3 and MMP-9 was decreased in the treated group in comparison to the control group that may contribute to the reduced migratory ability of tumor cells. These experimental results indicate that rCTII has anti-proliferative potential, and so this protein could be a potential drug for BC therapy in combination with other drugs

Revisiting fetal dose during radiation therapy: evaluating treatment techniques and a custom shield

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135233/1/acm20001i.pd

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

Targeted Gene Panel Sequencing for Early-onset Inflammatory Bowel Disease and Chronic Diarrhea

Background: In contrast to adult-onset inflammatory bowel disease (IBD), where many genetic loci have been shown to be involved in complex disease etiology, early-onset IBD (eoIBD) and associated syndromes can sometimes present as monogenic conditions. As a result, the clinical phenotype and ideal disease management in these patients often differ from those in adult-onset IBD. However, due to high costs and the complexity of data analysis, high-throughput screening for genetic causes has not yet become a standard part of the diagnostic work-up of eoIBD patients. Methods: We selected 28 genes of interest associated with monogenic IBD and performed targeted panel sequencing in 71 patients diagnosed with eoIBD or early-onset chronic diarrhea to detect causative variants. We compared these results to whole-exome sequencing (WES) data available for 25 of these patients. Results: Target coverage was significantly higher in the targeted gene panel approach compared with WES, whereas the cost of the panel was considerably lower (approximately 25% of WES). Disease-causing variants affecting protein function were identified in 5 patients (7%), located in genes of the IL10 signaling pathway (3), WAS (1), and DKC1 (1). The functional effects of 8 candidate variants in 5 additional patients (7%) are under further investigation. WES did not identify additional causative mutations in 25 patients. Conclusions: Targeted gene panel sequencing is a fast and effective screening method for monogenic causes of eoIBD that should be routinely established in national referral centers.info:eu-repo/semantics/publishedVersio

Risk factors for asthmatic children requiring hospitalization

Asthma is one of the most common chronic illnesses in childhood with an increased rate of hospitalization. In order to detemine the considerable factors for hospitalization of asthmatic children in our patients, we carried out a retrospective study of children with asthma who were admitted to children Medical center affiliated to Tehran University of Medical Sciences over a 3 year period ( 1993-1995). In this study 100 admitted asthmatic children were evaluated including 58 males and 42 females . The mean age of patients at the time of study was 19 months (6 months- 12 years). Fifty – three out of 100 patients (53%) were admitted in intensive care unit (ICU). 26 out of 53 patients admitted to ICU, required tracheal intubation and mechanical ventilation. Among the 100 admitted patients, 78 patients had respiratory infection before hospitalization, 60 had history of emergency room visit for asthma in 48 hours prior to hospitalization and 23 patients were steroid dependent. Family of 90 patients had little formal education about asthma. We conclude that most asthma exacerbations are provoked by respiratory infections, and proper family education is essential for improving outcome of asthma managemen