In Silico Design of Fusion Toxin DT389GCSF and a Comparative Study.

BACKGROUND: Chemotherapy and radiotherapy have negative effects on normal tissues and they are very expensive and lengthy treatments. These disadvantages have recently attracted researchers to the new methods that specifically affect cancerous tissues and have lower damage to normal tissues. One of these methods is the use of intelligent recombinant fusion toxin. The fusion toxin DTGCSF, which consists of linked Diphtheria Toxin (DT) and Granulocyte Colony Stimulate Factor (GCSF), was first studied by Chadwick et al. in 1993 where HATPL linker provided the linking sequence between GCSF and the 486 amino acid sequences of DT. METHODS: In this study, the fusion toxin DT389GCSF is evaluated for functional structure in silico. With the idea of the commercial fusion toxin of Ontak, the DT in this fusion protein is designed incomplete for 389 amino acids and is linked to the beginning of the GCSF cytokine via the SG4SM linker (DT389GCSF). The affinity of the DT389GCSF as a ligand with GCSF-R as receptor was compared with DT486GCSF as a ligand with GCSF-R as receptor. Both DT486GCSF and its receptor GCSF-R have been modeled by Easy Modeler2 software. Our fusion protein (DT389GCSF) and GCSF-R are modeled through Modeller software; all of the structures were confirmed by server MDWEB and VMD software. Then, the interaction studies between two proteins are done using protein-protein docking (HADDOCK 2.2 web server) for both the fusion protein in this study and DT486GCSF. RESULTS: The HADDOCK results demonstrate that the interaction of DT389GCSF with GCSF-R is very different and has a more powerful interaction than DT486GCSF with GCSF-R. CONCLUSION: HADDOCK web server is operative tools for evaluation of protein-protein interactions, therefore, in silico study of DT389GCSF will help with studying the function and the structure of these molecules. Moreover, DT389GCSF may have important new therapeutic applications.

Embryo Cryopreservation Following In-Vitro Maturation for Fertility Preservation in a Woman with Mullerian Adenosarcoma: A Case Report.

In-vitro maturation (IVM) of the immature oocytes recovered from the surgically removed ovarian tissue has been considered as a process for fertility preservation in patients with cancer. Fertility preservation for a woman with Mullerian adenocarcinoma. A 37-year-old woman with Mullerian adenocarcinoma was a candidate for ovarian resection. The immature oocytes were retrieved after ovarian resection from a 37-year-old woman with Mullerian adenocarcinoma. The oocytes underwent IVM and were fertilized using intracytoplasmic sperm injection (ICSI). Two healthy embryos were cryopreserved for future use. The immature oocytes from the ovarian tissue can be matured with IVM for generation of embryos after ICSI. The embryos can be vitrified using routine methods for fertility preservation in young women with cancer.

Aerobic exercise improves lung function in children with intellectual disability: a randomised trial.

QUESTION: In children with intellectual disability, is lung function lower than in healthy peers and does it improve with exercise? DESIGN: Randomised trial with intention-to-treat analysis and assessor blinding. PARTICIPANTS: Forty-four 12-year old children with Down syndrome or other intellectual disability with an average IQ of 42 (SD 8). INTERVENTION: The experimental group performed aerobic exercise for 30 minutes, five days per week, for eight weeks. The exercise was supervised walking, running, and cycling, with a target of moderate intensity. The control group continued usual activities and performed no specific exercise. OUTCOME MEASURES: Lung function as FEV1 and FVC in litres was measured with spirometry at baseline and after the intervention at eight weeks. Prior to the baseline measures, all participants underwent familiarisation of spirometry for one week. RESULTS: At baseline, FEV1 of the children with intellectual disability was a mean of 87% (95% CI 83 to 91) and FVC was 94% (95% CI 91 to 97) of predicted normal values. After intervention, FEV(1) had increased by 160 ml (95% CI 30 to 290) and FVC by 330 ml (95% CI 200 to 460) more in the experimental group than the control group. CONCLUSION: An 8-week program of aerobic exercise improves lung function in children with intellectual disability significantly. TRIAL REGISTRATION: ACTRN12609000365268.

Electrical simulation in addition to passive stretch has a small effect on spasticity and contracture in children with cerebral palsy: a randomised within-participant controlled trial.

QUESTION: Does electrical stimulation in addition to passive stretching reduce spasticity and contracture more than passive stretching alone in children with cerebral palsy? DESIGN: Randomised within-participant controlled trial with concealed allocation, assessor blinding, and intention-to-treat analysis. PARTICIPANTS: Eleven (one dropout) children with cerebral palsy and bilateral knee flexor spasticity aged 13 years (SD 1). INTERVENTION: One leg in each participant received the experimental intervention for four weeks which consisted of 30 min of electrical stimulation of the quadriceps 3 times per week and passive stretching of the hamstrings 5 times per week. The other leg received the control intervention for four weeks which consisted of passive stretching of the hamstrings 5 times per week. OUTCOME MEASURES: Spasticity of the hamstrings was measured using the modified Ashworth scale. Contracture was measured as maximum passive knee extension using goniometry. RESULTS: The mean difference in decrease in the modified Ashworth score due to the addition of electrical stimulation to the stretching regimen was 0.8 points (95% CI 0.1 to 1.5). The mean difference in increase in passive knee extension due to the addition of electrical stimulation to the stretching regimen was 4 degrees (95% CI 0 to 7). CONCLUSION: Electrical stimulation combined with passive stretching is marginally more effective than passive stretching alone for spastic limbs of children with cerebral palsy.

Intracytoplasmic injection using spermatids and subsequent pregnancies: round versus elongated spermatids.

The purpose of this clinical trial study was to report the outcome of intracytoplasmic injection of round (RS) and elongated (ES) spermatids retrieved from the testis of nonobstructive men. Seven and three cycles using RS and ES injections were performed, respectively. Only one cycle utilizing the late stage of ES (Sd2) resulted in an on-going pregnancy. The remarkable low success rate following RS microinjection was established in this study.