Coupled objective function to study the role of abdominal muscle forces in lifting using the kinematics-driven model

To circumvent the existing shortcoming of optimisation algorithms in trunk biomechanical models, both agonist and antagonist trunk muscle stresses to different powers are introduced in a novel objective function to evaluate the role of abdominal muscles in trunk stability and spine compression. This coupled objective function is introduced in our kinematics-driven finite element model to estimate muscle forces and to identify the role of abdominal muscles in upright standing while lifting symmetrically a weight at different heights. Predictive equations for the compression and buckling forces are developed. Results are also compared with the conventional objective function that neglects abdominal muscle forces. An overall optimal solution involving smaller spinal compression but higher trunk stability is automatically attained when choosing muscle stress powers at and around 3. Results highlight the internal oblique muscle as the most efficient abdominal muscle during the tasks investigated. The estimated relative forces in abdominal muscles are found to be in good agreement with the respective ratios of recorded electromyography activities.     

Bacterial contamination of amniotic membrane in a tissue bank from Iran

Human Amniotic Membrane (AM) transplantation can promote tissue healing and reduce inflammation, tissue scarring and neovascularization. Homa Peyvand Tamin (HPT) tissue bank has focused on manufacturing human cell and tissue based products including AM. The purpose of this study is to evaluate and identify bacterial contamination of AMs that is produced by HPT for several ophthalmic applications. From July 2006 to April 2011, 122 placentas from cesarean sections were retrieved by HPT after obtaining informed consent from the donors. Besides testing donor’s blood sample for viral markers, microbiological evaluation was performed pre and post processing. During tissue processing, decontamination was performed by an antibiotic cocktail including; Gentamicin, Ceftriaxone and Cloxacillin. Of 271 cesarean section AM donors who were screened as potential donors, 122 were accepted for processing and assessed for microbiological contamination. Donors’ age were between 21 and 41 years (Mean = 27.61 ± 0.24). More than 92 % of mothers were in their first or second gravidity with full term pregnancies. The most prevalent organisms were Staphylococci species (72.53 %). After processing, contamination rates markedly decreased by 84.62 % (p value = 0.013). According to our results, most of bacterial contaminations were related to donation process and the contamination pattern suggests procurement team as a source. Therefore we recommend that regular training programs should be implemented by tissue banks for procurement staff. These programs should focus on improved donor screening and proper aseptic technique for tissue retrieval. We also suggest that tissue banks should periodically check the rate and types of tissue contaminations. These data help them to find system faults and to update processing methods.     

Carbohydrate-conjugate heterobimetallic complexes: synthesis, DNA binding studies, artificial nuclease activity and in vitro cytotoxicity

New carbohydrate-conjugated heterobimetallic complexes [C(32)H(62)N(10)O(8)NiSn(2)Cl(4)]Cl(2)(1) and [C(32)H(62)N(10)O(8)CuSn(2)Cl(4)]Cl(2) (2) were synthesized and characterized by spectroscopic (IR, (1)H, (13)C, and (119)Sn NMR, EPR, UV-vis, ESI-MS) and analytical methods. The interaction studies of 2 with CT DNA were studied by using various biophysical techniques, which showed high binding affinity of 2 toward CT DNA. The extent of interaction was further confirmed by the interaction of 2 with the nucleotides viz.; 5'-AMP, 5'-CMP, 5'-GMP, and 5'-TMP, by absorption titration. (1)H, (31)P, (119)Sn NMR spectroscopy further validated the interaction mode of 2 with 5'-GMP. The electrophoresis pattern observed for 2 with supercoiled pBR322 DNA, exhibited significantly good nuclease activity following oxidative pathway. The preferential selectivity of 2 toward the major groove was observed on interaction of 2 with pBR322 DNA, in the presence of standard groove binders viz.; DAPI and methyl green. Additionally, in vitro antitumor activity of 2 was evaluated on a panel of human cancer cell lines, exhibiting remarkable cytotoxicity activity against Colo205 (colon) and MCF7 (breast) cell lines with GI(50) values <10 μg/mL.     

Cost-effectiveness of homograft heart valve replacement surgery: an introductory study

The clinical effectiveness of heart valve replacement surgery has been well documented. Mechanical and homograft valves are used routinely for replacement of damaged heart valves. Homograft valves are produced in our country but we import the mechanical valves. To our knowledge the cost-effectiveness of homograft valve has not been assessed. The objective of the present study was to compare the cost-effectiveness of homograft valve replacement with mechanical valve replacement surgery. Our samples were selected from 200 patients that underwent homograft and mechanical heart valve replacement surgery in Imam-Khomeini hospital (2000–2005). In each group we enrolled 30 patients. Quality of life was measured using the SF-36 questionnaire and utility was measured in quality-adjusted life years (QALYs). For each group we calculated the price of heart valve and hospitalization charges. Finally the cost-effectiveness of each treatment modalities were summarized as costs per QALYs gained. Forty male and twenty female participated in the study. The mean score of quality of life was 66.06 (SD = 9.22) in homograft group and 57.85 (SD = 11.30) in mechanical group (P < 0.05). The mean QALYs gained in homograft group was 0.67 more than mechanical group. The incremental cost-effectiveness ratio (ICER) revealed a cost savings of 1,067 US$ for each QALY gained in homograft group. Despite limitation of this introductory study, we concluded that homograft valve replacement was more effective and less expensive than mechanical valve. These findings can encourage healthcare managers and policy makers to support the production of homograft valves and allocate more recourse for developing such activities.     

Relative efficiency of abdominal muscles in spine stability

Using an iterative kinematics-driven nonlinear finite element model, relative efficiency of individual abdominal muscles in spinal stability in upright standing posture was investigated. Effect of load height on stability and muscle activities was also computed under different coactivity levels in abdominal muscles. The internal oblique was the most efficient muscle (compared with the external oblique and rectus abdominus) in providing stability while generating smaller spinal loads with lower fatigue rate of muscles. As the weight was held higher, stability deteriorated requiring additional flexor-extensor activities. The stabilising efficacy of abdominal muscles diminished at higher activities. The difference in critical loads in frontal and sagittal planes computed in the absence of abdominal coactivity disappeared under prescribed coactivities suggesting an optimal system in stability. The central nervous system may settle for a less stable spine in favour of lowering the risk of injury. Findings could help introduce stability criterion in optimisation models.     

A comparative study of two trunk biomechanical models under symmetric and asymmetric loadings

Despite recent advances in modeling of the human spine, simplifying assumptions are still required to tackle complexities. Such assumptions need to be scrutinized to assess their likely impacts on predictions. A comprehensive comparison of muscle forces and spinal loads estimated by a single-joint (L5–S1) optimisation-assisted EMG-driven (EMGAO) and a multi-joint Kinematics-driven (KD) model of the spine under symmetric (symmetric trunk flexion from neutral upright to maximum forward flexion) and asymmetric (holding a load at various heights in the right hand) activities is carried out. Regardless of the task simulated, the KD model predicted greater activities in extensor muscles as compared to the EMGAO model. Such differences in the symmetric tasks was due mainly to the distinct approaches to resolve the redundancy while in the asymmetric tasks they were due also to the different methods used to estimate joint moments. Shear and compression forces were generally higher in the KD model. Differences in predictions between these modeling approaches varied depending on the task simulated and the joint considered in the single-joint EMGAO model. The EMGAO model should incorporate a multi-joint strategy to satisfy equilibrium at different levels while the KD model should benefit from recorded EMG activities of the antagonistic muscles to supplement input measured kinematics.     

Establishing a cGMP pancreatic islet processing facility: the first experience in Iran

It has been predicted that one of the greatest increase in prevalence of diabetes will happen in the Middle East bear in the next decades. The aim of standard therapeutic strategies for diabetes is better control of complications. In contrast, some new strategies like cell and gene therapy have aimed to cure the disease. In recent years, significant progress has occurred in beta-cell replacement therapies with a progressive improvement of short-term and long term outcomes. In year 2005, considering the impact of the disease in Iran and the promising results of the Edmonton protocol, the funding for establishing a current Good Manufacturing Practice (cGMP) islet processing facility by Endocrinology and Metabolism Research Center was approved by Tehran University of Medical Sciences. Several islet isolations were performed following establishment of cGMP facility and recruitment of all required equipments for process validation and experimental purpose. Finally the first successful clinical islet isolation and transplantation was performed in September 2010. In spite of a high cost of the procedure it is considered beneficial and may prevent long term complications and the costs associated with secondary cares. In this article we will briefly describe our experience in setting up a cGMP islet processing facility which can provide valuable information for regional countries interested to establish similar facilities.     

The implementation of tissue banking experiences for setting up a cGMP cell manufacturing facility

Cell manufacturing for clinical applications is a unique form of biologics manufacturing that relies on maintenance of stringent work practices designed to ensure product consistency and prevent contamination by microorganisms or by another patient's cells. More extensive, prolonged laboratory processes involve greater risk of complications and possibly adverse events for the recipient, and so the need for control is correspondingly greater. To minimize the associate risks of cell manufacturing adhering to international quality standards is critical. Current good tissue practice (cGTP) and current good manufacturing practice (cGMP) are examples of general standards that draw a baseline for cell manufacturing facilities. In recent years, stem cell researches have found great public interest in Iran and different cell therapy projects have been started in country. In this review we described the role of our tissue banking experiences in establishing a new cGMP cell manufacturing facility. The authors concluded that, tissue banks and tissue banking experts can broaden their roles from preparing tissue grafts to manufacturing cell and tissue engineered products for translational researches and phase I clinical trials. Also they can collaborate with cell processing laboratories to develop SOPs, implement quality management system, and design cGMP facilities.     

Epstein Barr virus inhibits the stimulatory effect of TLR7/8 and TLR9 agonists but not CD40 ligand in human B lymphocytes

Viruses and other microorganisms express specific pathogen‐associated molecular patterns that are recognized by cell surface or endosome‐associated Toll‐like receptors (TLR). There are many examples of viruses that have developed strategies to modulate TLR signaling through the use of viral or cellular molecules. Epstein–Barr virus (EBV) has recently been found to display a complex interaction with TLR. The aim of this study was to asses the effect of EBV infection on proliferative capacity of TLR7/8 and 9 agonist and CD40 ligand (CD40L) in normal B lymphocytes. Our results demonstrate that EBV induces a significant inhibition in proliferative response to TLR7/8 (P < 0.004) and TLR9 (P < 0.000) agonists but not to CD40L stimulation in enriched human normal B lymphocytes. Similar inhibitory effect was also observed in B lymphocytes prestimulated with the TLR agonists, implying that the suppressive effect is not due to downregulation of TLR protein expression by EBV. EBV infection did not induce apoptosis and did not downregulate TLR7/8 mRNA expression in B lymphocytes. Our results suggest that EBV might be able to evade the immune system by modulation of the TLR signaling pathway.     

A mechanistic approach for the DNA binding of chiral enantiomeric L- and D-tryptophan-derived metal complexes of 1,2-DACH: cleavage and antitumor activity

A new chiral series of potential antitumor metal-based complexes 1-3(a and b) of L- and D-tryptophan have been synthesized and thoroughly characterized. Both enantiomers of 1-3 bind DNA noncovalently via phosphate interaction with slight preference of metal center for covalent coordination to nucleobases. The K(b) values of L-enantiomer, however, possess higher propensity for DNA binding in comparison with the D-enantiomeric analogs. The relative trend in K(b) values is as follows: 2(a) > 2(b) > 3(a) > 1(a) > 3(b) > 1(b). These observations together with the findings of circular dichoric and fluorescence studies reveal maximal potential of L-enantiomeric form of copper complex to bind DNA, thereby exerting its therapeutic effect. The complex 2a exhibits a remarkable DNA cleavage activity with pBR322DNA in the presence of different activators such as H(2) O(2) , ascorbic acid, 3-mercaptopropionic acid, and glutathione, suggesting the involvement of active oxygen species for the DNA scission. In vitro anticancer activity of complexes 1-3(a) were screened against 14 different human carcinoma cell lines of different histological origin, and the results reveal that 2a shows significant antitumor activity in comparison with both 1a and 3a and is particularly selective for MIAPACA2 (pancreatic cancer cell line).