A Predictive Model for Assessment of Successful Outcome in Posterior Spinal Fusion Surgery

Background: Low back pain is a common problem in many people. Neurosurgeons recommend posterior spinal fusion (PSF) surgery as one of the therapeutic strategies to the patients with low back pain. Due to the high risk of this type of surgery and the critical importance of making the right decision, accurate prediction of the surgical outcome is one of the main concerns for the neurosurgeons.Methods: In this study, 12 types of multi-layer perceptron (MLP) networks and 66 radial basis function (RBF) networks as the types of artificial neural network methods and a logistic regression (LR) model created and compared to predict the satisfaction with PSF surgery as one of the most well-known spinal surgeries.Results: The most important clinical and radiologic features as twenty-seven factors for 480 patients (150 males, 330 females; mean age 52.32 ± 8.39 years) were considered as the model inputs that included: age, sex, type of disorder, duration of symptoms, job, walking distance without pain (WDP), walking distance without sensory (WDS) disorders, visual analog scale (VAS) scores, Japanese Orthopaedic Association (JOA) score, diabetes, smoking, knee pain (KP), pelvic pain (PP), osteoporosis, spinal deformity and etc. The indexes such as receiver operating characteristic–area under curve (ROC-AUC), positive predictive value, negative predictive value and accuracy calculated to determine the best model. Postsurgical satisfaction was 77.5% at 6 months follow-up. The patients divided into the training, testing, and validation data sets.Conclusion: The findings showed that the MLP model performed better in comparison with RBF and LR models for prediction of PSF surgery.Keywords: Posterior spinal fusion surgery (PSF); Prediction, Surgical satisfaction; Multi-layer perceptron (MLP); Logistic regression (LR) (PDF) A Predictive Model for Assessment of Successful Outcome in Posterior Spinal Fusion Surgery. Available from: https://www.researchgate.net/publication/325679954_A_Predictive_Model_for_Assessment_of_Successful_Outcome_in_Posterior_Spinal_Fusion_Surgery [accessed Jul 11 2019].Peer reviewe

Institutional health promotion standards in school of medicine at Shahid Beheshti University of Medical Sciences according to medical students' opinions in 2020

Background: Health promotion in occupational and educational environments contributes to the improvement and higher efficiency of the people affected by them. The health status of medical students as future providers of health services has great importance. This study aimed to evaluate health promotion standards in the school of medicine at Shahid Beheshti University of Medical Sciences. Methods: This cross-sectional study evaluated health promotion standards of school of medicine using a questionnaire filled out by medical students in 2020. The validity and reliability of the questionnaire were confirmed. The questionnaire measured health promotion standards in the fields of healthy nutrition, facilities for proper physical activity, providing a healthy environment for students, adequate education for health promotion and disease prevention. Analytical and statistical tests were performed using IBM SPSS 23 software. Results: Among 340 medical students participated in the study 31.8 percent were in the basic sciences grade, 26.5 percent were stagers, and 41.8 percent were interns. The mean score of all questions among different grades was 1.11 (SD=0.33), 0.97 (SD=0.43), and 0.93 (SD=0.34), respectively (on a scale of 0-3). A significant difference was reported in the comparison of "basic sciences versus stagers (PV=0.011)" and "basic sciences versus interns (PV<0.01) ". the mean score of questions overall was 1.00 (SD=0.37). Conclusion: Based on findings, health promotion in the school of medicine at Shahid Beheshti University of Medical Sciences was in the medium range, which demonstrates the need for future policies that lead to a more efficient health-promoting environment

Virus-free induction of pluripotency and subsequent excision of reprogramming factors

Reprogramming of somatic cells to pluripotency, thereby creating induced pluripotent stem (iPS) cells, promises to transform regenerative medicine. Most instances of direct reprogramming have been achieved by forced expression of defined factors using multiple viral vectors1-7. However, such iPS cells contain a large number of viral vector integrations1,8, any one of which could cause unpredictable genetic dysfunction. While c-Myc is dispensable for reprogramming9,10, complete elimination of the other exogenous factors is also desired since ectopic expression of either Oct4 or Klf4 can induce dysplasia11,12. Two transient transfection reprogramming methods have been published to address this issue13,14. However, the efficiency of either approach is extremely low, and neither has thus far been applied successfully to human cells. Here we show that non-viral transfection of a single multiprotein expression vector, which comprises the coding sequences of c-Myc​,​ Klf4​,​ Oct4 and Sox2 linked with 2A peptides, can reprogram both mouse and human fibroblasts. Moreover, the transgene can be removed once reprogramming has been achieved. iPS cells produced with this non-viral vector show robust expression of pluripotency markers, indicating a reprogrammed state confirmed functionally by in vitro differentiation assays and formation of adult chimeric mice. When the single vector reprogramming system was combined with a piggyBac transposon15,16 we succeeded in establishing reprogrammed human cell lines from embryonic fibroblasts with robust expression of pluripotency markers. This system minimizes genome modification in iPS cells and enables complete elimination of exogenous reprogramming factors, efficiently providing iPS cells that are applicable to regenerative medicine, drug screening and the establishment of disease models

<em>piggyBac</em> transposition reprograms fibroblasts to induced pluripotent stem cells

Transgenic expression of just four defined transcription factors (c-Myc, Klf4, Oct4 and Sox2) is sufficient to reprogram somatic cells to a pluripotent state. The resulting induced pluripotent stem (iPS) cells resemble embryonic stem cells in their properties and potential to differentiate into a spectrum of adult cell types. Current reprogramming strategies involve retroviral, lentiviral, adenoviral and plasmid transfection to deliver reprogramming factor transgenes. Although the latter two methods are transient and minimize the potential for insertion mutagenesis, they are currently limited by diminished reprogramming efficiencies. piggyBac (PB) transposition is host-factor independent, and has recently been demonstrated to be functional in various human and mouse cell lines. The PB transposon/transposase system requires only the inverted terminal repeats flanking a transgene and transient expression of the transposase enzyme to catalyse insertion or excision events. Here we demonstrate successful and efficient reprogramming of murine and human embryonic fibroblasts using doxycycline-inducible transcription factors delivered by PB transposition. Stable iPS cells thus generated express characteristic pluripotency markers and succeed in a series of rigorous differentiation assays. By taking advantage of the natural propensity of the PB system for seamless excision, we show that the individual PB insertions can be removed from established iPS cell lines, providing an invaluable tool for discovery. In addition, we have demonstrated the traceless removal of reprogramming factors joined with viral 2A sequences delivered by a single transposon from murine iPS lines. We anticipate that the unique properties of this virus-independent simplification of iPS cell production will accelerate this field further towards full exploration of the reprogramming process and future cell-based therapies. © 2009 Macmillan Publishers Limited. All rights reserved.Link_to_subscribed_fulltex

Role of Nestin in Mouse Development

Although nestin has served as a marker of neural stem/progenitor cells for close to twenty years, its function is still poorly understood. During development, this intermediate filament protein is expressed in many different progenitors including those of the central nervous system, heart, skeletal muscle and kidney. The adult expression of nestin is mainly restricted to the subependymal zone and dentate gyrus of the brain, the neuromuscular junction and renal podocytes. I have used two approaches of gain of function and loss of function to elucidate the role of nestin in vivo. Although I was able to generate transgenic lines in which the transgene was ubiquitously expressed at the RNA level, over-expression of nestin at the protein level was not achieved possibly due to post transcriptional regulation of this gene. My data from loss of function approach indicates that nestin-deficient mice have impaired coordination. Balance and muscle strength are not affected and there are no apparent anatomical defects. I found that nestin deficiency is compatible with normal development of the central nervous system but results in abnormal clustering of acetylcholine receptors in the neuromuscular junctions, similar to the phenotype described for deficiency of cyclin-dependent kinase 5 (Cdk5) a candidate downstream effector of nestin. In renal podocytes, where both nestin and Cdk5 are normally expressed, we found reduced branching and abnormally contoured podocyte processes. To further connect the phenotype of nestin deficiency to Cdk5, I demonstrated that nestin deficiency can rescue maintenance of acetylcholine receptor clusters in the absence of agrin, similar to Cdk5/agrin double knockouts, indicating that the observed nestin deficiency phenotypes are the consequence of aberrant Cdk5 activity.Ph

Role of Nestin in Mouse Development

Although nestin has served as a marker of neural stem/progenitor cells for close to twenty years, its function is still poorly understood. During development, this intermediate filament protein is expressed in many different progenitors including those of the central nervous system, heart, skeletal muscle and kidney. The adult expression of nestin is mainly restricted to the subependymal zone and dentate gyrus of the brain, the neuromuscular junction and renal podocytes. I have used two approaches of gain of function and loss of function to elucidate the role of nestin in vivo. Although I was able to generate transgenic lines in which the transgene was ubiquitously expressed at the RNA level, over-expression of nestin at the protein level was not achieved possibly due to post transcriptional regulation of this gene. My data from loss of function approach indicates that nestin-deficient mice have impaired coordination. Balance and muscle strength are not affected and there are no apparent anatomical defects. I found that nestin deficiency is compatible with normal development of the central nervous system but results in abnormal clustering of acetylcholine receptors in the neuromuscular junctions, similar to the phenotype described for deficiency of cyclin-dependent kinase 5 (Cdk5) a candidate downstream effector of nestin. In renal podocytes, where both nestin and Cdk5 are normally expressed, we found reduced branching and abnormally contoured podocyte processes. To further connect the phenotype of nestin deficiency to Cdk5, I demonstrated that nestin deficiency can rescue maintenance of acetylcholine receptor clusters in the absence of agrin, similar to Cdk5/agrin double knockouts, indicating that the observed nestin deficiency phenotypes are the consequence of aberrant Cdk5 activity.Ph

Characterization and Regulation of the Genes for a Novel Anthranilate 1,2-Dioxygenase from Burkholderia cepacia DBO1

Anthranilate (2-aminobenzoate) is an important intermediate in tryptophan metabolism. In order to investigate the degradation of tryptophan through anthranilate by Burkholderia cepacia, several plasposon mutations were constructed of strain DBO1 and one mutant with the plasposon insertion in the anthranilate dioxygenase (AntDO) genes was chosen for further study. The gene sequence obtained from flanking DNA of the plasposon insertion site revealed unexpected information. B. cepacia DBO1 AntDO (designated AntDO-3C) is a three-component Rieske-type [2Fe-2S] dioxygenase composed of a reductase (AndAa), a ferredoxin (AndAb), and a two-subunit oxygenase (AndAcAd). This is in contrast to the two-component (an oxygenase and a reductase) AntDO enzyme from Acinetobacter sp. strain ADP1, P. aeruginosa PAO1, and P. putida P111. AntDO from strains ADP1, PAO1, and P111 are closely related to benzoate dioxygenase, while AntDO-3C is closely related to aromatic hydrocarbon dioxygenases from Novosphingobium aromaticivorans F199 and Sphingomonas yanoikuyae B1 and 2-chlorobenzoate dioxygenase from P. aeruginosa strains 142 and JB2. Escherichia coli cells expressing the functional AntDO-3C genes transform anthranilate and salicylate (but not 2-chlorobenzoate) to catechol. The enzyme includes a novel reductase whose absence results in less efficient transformation of anthranilate by the oxygenase and ferredoxin. AndR, a possible AraC/XylS-type transcriptional regulator, was shown to positively regulate expression of the andAcAdAbAa genes. Anthranilate was the only effector (of 12 aromatic compounds tested) that was able to induce expression of the genes

Linkage Disequilibrium Mapping of Schizophrenia Susceptibility to the CAPON Region of Chromosome 1q22

Previously, we have reported linkage of markers from chromosome 1q22 to schizophrenia, a finding supported by several independent studies. We have now examined the region of strongest linkage for evidence of linkage disequilibrium (LD) in a sample of 24 Canadian familial-schizophrenia pedigrees. Analysis of 14 microsatellites and 15 single-nucleotide polymorphisms (SNPs) from the 5.4-Mb region between D1S1653 and D1S1677 produced significant evidence (nominal P<.05) of LD between schizophrenia and 2 microsatellites and 6 SNPs. All of the markers exhibiting significant LD to schizophrenia fall within the genomic extent of the gene for carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (CAPON), making it a prime positional candidate for the schizophrenia-susceptibility locus on 1q22, although initial mutation analysis of this gene has not identified any schizophrenia-associated changes within exons. Consistent with several recently identified candidate genes for schizophrenia, CAPON is involved in signal transduction in the NMDA receptor system, highlighting the potential importance of this pathway in the etiology of schizophrenia

Naphthenic Acid Mixtures from Oil Sands Process-Affected Water Enhance Differentiation of Mouse Embryonic Stem Cells and Affect Development of the Heart

Extraction of petrochemicals from the surface mining of oil sand deposits results in generation of large volumes of oil sands process-affected water (OSPW). Naphthenic acids (NA) are generally considered to be among the most toxic components of OSPW. Previous studies have shown that NAs are toxic to aquatic organisms, however knowledge of their effects on mammalian health and development is limited. In the present study, we evaluated the developmental effects of an NA extract prepared from fresh OSPW on differentiating mouse embryonic stem cells (ESC). We found that treatment of differentiating cells with the NA extract at noncytotoxic concentrations alters expression of various lineage specification markers and development of the heart. Notably, expression of cardiac specific markers such as <i>Nkx2.5</i>, <i>Gata4</i>, and<i> Mef2c</i> were significantly up-regulated. Moreover, exposure to the NA extract enhanced differentiation of embryoid bodies and resulted in the early appearance of spontaneously beating clusters. Interestingly, exposure of undifferentiated mouse ESCs to the NA extract did not change the expression level of pluripotency markers (i.e., <i>Oct4</i>, <i>Nanog</i>, and <i>Sox2</i>). Altogether, these data identify some of the molecular pathways affected by components within this NA extract during differentiation of mammalian cells

Oct4 Is Required ∼E7.5 for Proliferation in the Primitive Streak

<div><p>Oct4 is a widely recognized pluripotency factor as it maintains Embryonic Stem (ES) cells in a pluripotent state, and, <i>in vivo</i>, prevents the inner cell mass (ICM) in murine embryos from differentiating into trophectoderm. However, its function in somatic tissue after this developmental stage is not well characterized. Using a tamoxifen-inducible Cre recombinase and floxed alleles of Oct4, we investigated the effect of depleting Oct4 in mouse embryos between the pre-streak and headfold stages, ∼E6.0–E8.0, when Oct4 is found in dynamic patterns throughout the embryonic compartment of the mouse egg cylinder. We found that depletion of Oct4 ∼E7.5 resulted in a severe phenotype, comprised of craniorachischisis, random heart tube orientation, failed turning, defective somitogenesis and posterior truncation. Unlike in ES cells, depletion of the pluripotency factors Sox2 and Oct4 after E7.0 does not phenocopy, suggesting that ∼E7.5 Oct4 is required within a network that is altered relative to the pluripotency network. Oct4 is not required in extraembryonic tissue for these processes, but is required to maintain cell viability in the embryo and normal proliferation within the primitive streak. Impaired expansion of the primitive streak occurs coincident with Oct4 depletion ∼E7.5 and precedes deficient convergent extension which contributes to several aspects of the phenotype.</p></div