Combination of Prox1/NeuroD1 Transcription Factor Overexpression Boosts Generation of Dentate Gyrus Granule Neurons from Pluripotent Stem Cells

ESCs haben die Fähigkeit unbegrenzter Selbsterneuerung und Pluripotenz. Es sind vielversprechende Werkzeuge, die von der Grundlagenforschung in der Entwicklungsbiologie bis zu zukünftigen therapeutischen Ansätze reichen. Nach der Etablierung grundlegender Techniken für die Kultivierung und neuronalen Differenzierung der ESC war das Hauptanliegen dieser Arbeit die Differenzierung in spezifische Neuronen des Telencephalons. Und zwar bestand unser Ziel darin, die Differenzierung der ESCs auf die Körnerzellen des Gyrus dentatus auszurichten. Bislang wurden zwei wichtige Arbeiten über die Hippocampus-Induktion von ES- und IPS-Zellen publiziert (Yu, Di Giorgio et al. 2014) (Sakaguchi, Kadoshima et al. 2015). Beide Methoden basieren auf der Rolle der Wachstumsfaktoren in Bezug auf die Hippocampus-Entwicklung. Zu Beginn der Arbeit wurden sowohl die Online-Plattformen GenePaint und Allen Brain Atlas als auch frühere Studien bezüglich zellulärer Lokalisation von Wachstums- und Transkriptions-Faktoren studiert. Daraus ergab sich die Fragestellung, welche der Wachstumsfaktor- Kombinationen einen größeren Einfluss auf die Differenzierung der Körnerzellen des Gyrus dentatus aus mESCs haben. Der Wachstumsfaktor-Cocktail mit DKK1 zeigte eine ausgeprägtere Induktion der neuronalen Progenitor-Zellen im Telencephalon. Zudem bewirkte dieser eine stärkere Generierung von Kolonien hochangereicherter Gyrus dentatus-Zellen. Diese zeigen Ähnlichkeit mit Progenitor-Zellen und exprimieren die Gyrus dentatus-Marker Prox1, Neurod1 und Emx1. Im nächsten Teil wurde die Rolle der Transkriptionsfaktoren Emx2, Prox1 und NeuroD1 im Hinblick auf Produktion und Induktion von Körnerzellen des Gyrus dentatus jeweils separat untersucht. Eine hohe Expression von Emx2 unterdrückt die Differenzierung von telencephalen neuronalen Progenitor-Zellen in Körnerzellen. Eine Überexprimierung von NeuroD1 und Prox1 hingegen führen zu einer starken Hochregulierung hippocampaler Progenitor–Marker. Die stärkste Differenzierung in Körnerzellen wurde mit einer kombinierten Überexpression von PROX1 und NEUROD1 erreicht. Morphologische Beobachtungen zeigen deutlich einen signifikanten Anstieg der Neurogenese. Dies zeigt sich ebenfalls im Vergleich zu anderen Gruppen. Der Vergleich zwischen den Differenzierungs-Effekten von Wachstums- und Transkriptionsfaktoren zeigt, dass die Wachstumsfaktoren eine stärkere Induktion von Neuro-Progenitorzellen als Transkriptionsfaktoren herbeiführen. Im Gegensatz dazu führen die Transkriptionsfaktoren, und insbesondere die Kombination von Prox1 und Neurod1, zu einer Ausbildung des neuronalen Phänotyps der Zellen. Aus all diesen Beobachtungen ergibt sich Folgendes: Die Kombination von zentralen Transkriptionsfaktoren des Gyrus dentatus beeinflussen hauptsächlich die Differenzierung in Körnerzellen in vitro. Weiter zeigte sich, dass ein Gyrus dentatus spezifischer Wachstumsfaktor-Cocktail und Transkriptionsfaktoren zu einer effektiveren Differenzierung der Granula Neurone des Gyrus dentatus führen

Lipid measures for prediction of incident cardiovascular disease in diabetic and non-diabetic adults: results of the 8.6 years follow-up of a population based cohort study

<p>Abstract</p> <p>Background</p> <p>Diabetes is a strong risk factor for cardiovascular disease (CVD).The relative role of various lipid measures in determining CVD risk in diabetic patients is still a subject of debate. We aimed to compare performance of different lipid measures as predictors of CVD using discrimination and fitting characteristics in individuals with and without diabetes mellitus from a Middle East Caucasian population.</p> <p>Methods</p> <p>The study population consisted of 1021 diabetic (men = 413, women = 608) and 5310 non-diabetic (men = 2317, women = 2993) subjects, aged ≥ 30 years, free of CVD at baseline. The adjusted hazard ratios (HRs) for CVD were calculated for a 1 standard deviation (SD) change in total cholesterol (TC), log-transformed triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using Cox proportional regression analysis. Incident CVD was ascertained over a median of 8.6 years of follow-up.</p> <p>Results</p> <p>A total of 189 (men = 91, women = 98) and 263(men = 169, women = 94) CVD events occurred, in diabetic and non-diabetic population, respectively. The risk factor adjusted HRs to predict CVD, except for HDL-C, TG and TG/HDL-C, were significant for all lipid measures in diabetic males and were 1.39, 1.45, 1.36 and 1.16 for TC, LDL-C, non- HDL-C and TC/HDL-C respectively. In diabetic women, using multivariate analysis, only TC/HDL-C had significant risk [adjusted HR1.31(1.10-1.57)].Among non-diabetic men, all lipid measures, except for TG, were independent predictors for CVD however; a 1 SD increase in HDL-C significantly decreased the risk of CVD [adjusted HR 0.83(0.70-0.97)].In non-diabetic women, TC, LDL-C, non-HDL-C and TG were independent predictors.</p> <p>There was no difference in the discriminatory power of different lipid measures to predict incident CVD in the risk factor adjusted models, in either sex of diabetic and non-diabetic population.</p> <p>Conclusion</p> <p>Our data according to important test performance characteristics provided evidence based support for WHO recommendation that along with other CVD risk factors serum TC vs. LDL-C, non-HDL-C and TC/HDL-C is a reasonable lipid measure to predict incident CVD among diabetic men. Importantly, HDL-C did not have a protective effect for incident CVD among diabetic population; given that the HDL-C had a protective effect only among non- diabetic men.</p

The Impacts of Sustainable Residential Interior Space on Inhabitant’s Emotions

Focusing on inhabitant’s climate comfort causes the neglect of personal and aesthetic factors that have effects on emotions and psychological comfort. Blindly adhering to sustainable design principles regardless of the basic architectural design parameters cause similar interior spaces in today’s housing of Iran. Interior space form is one the main design factors that has some effects on inhabitant’s emotions. It is a correlation research to study inhabitant’s emotions towards sustainable interior space by focusing on interior form. It illustrates that form can consider as an influential factor in creating and improving sustainable conditions according to inhabitant’s emotions.© 2016. The Authors. Published for AMER ABRA by e-International Publishing House, Ltd., UK. Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians) and cE-Bs (Centre for Environment-Behaviour Studies, Faculty of Architecture, Planning &amp; Surveying, Universiti Teknologi MARA, Malaysia.Keywords: Sustainable interior design; emotion; shape; PA

Ethnobotanical study of medicinal plants of Boyer Ahmad and Dena regions in Kohgiluyeh and Boyer Ahmad province, Iran

Background and aims: The current paper aimed to collect and document the information about medicinal plants of Boyer Ahmad and Dena regions and their applications by indigenous inhabitants. Methods: The field surveys were carried out from March 2015 to September 2016 under supervision of local people. Collected plant specimens were identified to species level using Flora of Iran and Flora Iranica. Subsequently, information including scientific names, local names, parts used, method of preparation, medicinal effects, growth forms, and chorotypes for 71 species were recorded. Results: Medicinal plants belonged to 62 genera and 29 families. Apiaceae (14.08%) and Lamiaceae (14.08%) had the most number of species among other families. Based on Raunkier method, hemicryptophytes with 42.25% is the highest growth form and the most common chorotype was Irano-Turanian type (70.42%). The most used parts are aerial parts (40/85%),‎ and the most common mode of preparation was infusion (24%). The results of this study indicate that local people in Boyer Ahmad and Dena regions have used all collected plants for medicinal, food and sanitary purposes and their knowledge about identification of plants and their habitats, medicinal and edible properties is extensive. Conclusions: Native knowledge leads to obtaining valuable information including medicinal properties of plants, usable parts, time of growth, best time for harvesting and areas which have growing potential. Therefore, it is vital to investigate the native knowledge about medicinal plants in various regions of Iran

Comparison of peritonsillar infiltration effects of ketamine and tramadol on post tonsillectomy pain: a double-blinded randomized placebo-controlled clinical trial

Aim To assess the effect of peritonsillar infiltration of ketamine and tramadol on post tonsillectomy pain and compare the side effects. Methods The double-blind randomized clinical trial was performed on 126 patients aged 5-12 years who had been scheduled for elective tonsillectomy. The patients were randomly divided into 3 groups to receive either ketamine, tramadol, or placebo. They had American Society of Anesthesiologists physical status class I and II. All patients underwent the same method of anesthesia and surgical procedure. The three groups did not differ according to their age, sex, and duration of anesthesia and surgery. Post operative pain was evaluated using CHEOPS score. Other parameters such as the time to the first request for analgesic, hemodynamic elements, sedation score, nausea, vomiting, and hallucination were also assessed during 12 hours after surgery. Results Tramadol group had significantly lower pain scores (P = 0.005), significantly longer time to the first request for analgesic (P = 0.001), significantly shorter time to the beginning of liquid regimen (P = 0.001), and lower hemodynamic parameters such as blood pressure (P = 0.001) and heart rate (P = 0.001) than other two groups. Ketamine group had significantly greater presence of hallucinations and negative behavior than tramadol and placebo groups. The groups did not differ significantly in the presence of nausea and vomiting. Conclusion Preoperative peritonsillar infiltration of tramadol can decrease post-tonsillectomy pain, analgesic consumption, and the time to recovery without significant side effects

Evaluation of the Levels of Evidence in Three Clinical Chapters in Five Editions of the Textbook Pathways of the Pulp

Introduction: The levels of evidence (LOE) of dental education texts is critical from the educational point of view. The present study aimed to evaluate the levels of evidence of references used in three clinical chapters in the textbook Pathways of the Pulp. Material &amp; Method: The references of three clinical chapters in the text book Pathways of the Pulp were assessed in five of its editions. The levels of evidence were ranked according to study type and the Oxford scale from 0 to 5. The chi-square test was used to compare the level of evidence between different editions of the "Retreatment," "Trauma," and "Surgery" chapters. Results: A total of 3656 references were reviewed and analyzed from the "Trauma" (928 references), "Re-treatment" (1906 references), and "Surgery" (822 references) chapters in the 1998, 2002, 2006, 2011, and 2016 editions. The percentage of the LOE 0 (no evidence) was high (&gt;60%) in all three chapters in all editions (P&lt;0.001). The levels of evidence had the same distribution in all editions (P=0.871). The LOE of the "Re-treatment" (P=0.044) and "Surgery" (P&lt;0.001) chapters changed in some editions. Conclusion: The majority of references in the three clinical chapters of the book are low-level evidence. Encouragement policies for researchers to conduct studies with high LOE are necessary

Lipid ratios and appropriate cut off values for prediction of diabetes: a cohort of Iranian men and women

<p>Abstract</p> <p>Background</p> <p>Dyslipidemia is a risk factor for incident type 2 diabetes; however, no study has specifically assessed the lipid ratios (i.e. total cholesterol (TC)/high density lipoprotein cholesterol (HDL-C) and triglyceride (TG)/HDL-C) as predictors of diabetes. We aimed to compare the independent association between the different lipid measures with incident diabetes over a median follow up of 6.4 years in Iranian men and women.</p> <p>Method</p> <p>The study population consisted of 5201 non diabetic (men = 2173, women = 3028) subjects, aged ≥20 years. The risk factor adjusted odds ratios (ORs) for diabetes were calculated for every 1 standard deviation (SD) change in TC, log-transformed TG, HDL-C, non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C using multivariate logistic regression analysis. Receiver operator characteristic (ROC) curve analysis was used to define the points of the maximum sum of sensitivity and specificity (MAXss) of each lipid measure as a predictor of diabetes.</p> <p>Result</p> <p>We found 366 (146 men and 220 women) new diabetes cases during follow-up. The risk-factor-adjusted ORs for a 1 SD increase in TG, TC/HDL-C and TG/HDL-C were 1.23, 1.27 and 1.25 in men; the corresponding risks in females were 1.36, 1.14, 1.39 respectively (all p < 0.05, except TC/HDL-C in females which was marginally significant, p = 0.07). A 1 SD increase of HDL-C only in women decreased the risk of diabetes by 25% [0.75(0.64-0.89)]. In both genders, there was no difference in the discriminatory power of different lipid measures to predict incident diabetes in the risk factor adjusted models (ROC ≈ 82%). TG cutoff values of 1.98 and 1.66 mmol/l; TG/HDL-C cutoff values of 4.7 and 3.7, in men and women, respectively, TC/HDL-C cutoff value of 5.3 in both genders and HDL-C cutoff value of 1.18 mmol/l in women yielded the MAXss for defining the incidence of diabetes.</p> <p>Conclusion</p> <p>TC/HDL-C and TG/HDL-C showed similar performance for diabetes prediction in men population however; among women TG/HDL-C highlighted higher risk than did TC/HDL-C, although there was no difference in discriminatory power. Importantly, HDL-C had a protective effect for incident diabetes only among women.</p

Diallel Analysis of Yield and It’s related Traits in Sunflower (Helianthus annuus L.) under Well-watered and Water-stressed Conditions

Drought stress is one of the factors which influence sunflower production. Hence, breeding for tolerance to drought stress has become a major focus. In this paper, combining ability, gene action and genetic analysis of several characteristics were studied for five sunflower inbred lines and their ten hybrids (fifteen genotypes). The materials were evaluated in two separate experiments using a Randomized Complete Block Design (RCBD) with three replications in well-watered and waterstressed states and in field condition. Data were analyzed by Griffing’s diallel analysis model 1 (fixed effects) and method 2 (parents and crosses). Combined analysis of experiments revealed significant differences among genotypes for all studied traits. Combining ability analysis revealed that in well-watered conditions, general and specific combining abilities (GCA and SCA) effects were significant for all studied traits except for the leaf number. In water-stressed condition, GCA and SCA effects were significant for all studied traits except for the head and stem diameter. The Griffing diallel analysis showed that the genotype LR4 could be considered as the best combiner with the highest GCA effect for seed yield per plant, number of filled seed, stem diameter and head diameter in the sunflower breeding programs. In both water treatment conditions the cross ‘RHA266xLR4’ showed the highest positive SCA effects and the highest mean value for seed yield per plant

Investigating the Mediating Role of Distress Tolerance in the Relationship between Early Maladaptive Schemas and Psychiatric Symptoms among Addicts

Background: This study aimed to determine the mediating role of distress tolerance in the relationship between early maladaptive schemas and psychiatric symptoms among addicts. Methods: The statistical population of this study consists of addicts referring to addiction treatment clinics in Zanjan city, Iran. Using the multi-stage cluster sampling method, 150 participants were selected as a sample and completed the questionnaires. Early maladaptive schema questionnaire-short form, symptom checklist-25 (SCL-25), and the distress tolerance scale were completed by participants. Results: The findings of this study indicate a negative and significant relationship between early maladaptive schemas and distress tolerance among addicts. Also, there is a positive and significant relationship between early maladaptive schemas and psychiatric symptoms among addicts. It can be said that there is a significant negative relationship between distress tolerance and psychiatric symptoms in addicts. Conclusions: The final results of this study show that in the relationship between early maladaptive schemas and psychiatric symptoms among addicts in Zanjan city, distress tolerance plays a mediating role and the model has a goodness of fit. Keywords: Distress tolerance, Early maladaptive schemas, Psychiatric symptoms, Addicts

Investigating the Mediating Role of Distress Tolerance in the Relationship between Early Maladaptive Schemas and Psychiatric Symptoms among Addicts

Background: This study aimed to determine the mediating role of distress tolerance in the relationship between early maladaptive schemas and psychiatric symptoms among addicts. Methods: The statistical population of this study consists of addicts referring to addiction treatment clinics in Zanjan city, Iran. Using the multi-stage cluster sampling method, 150 participants were selected as a sample and completed the questionnaires. Early maladaptive schema questionnaire-short form, symptom checklist-25 (SCL-25), and the distress tolerance scale were completed by participants. Results: The findings of this study indicate a negative and significant relationship between early maladaptive schemas and distress tolerance among addicts. Also, there is a positive and significant relationship between early maladaptive schemas and psychiatric symptoms among addicts. It can be said that there is a significant negative relationship between distress tolerance and psychiatric symptoms in addicts. Conclusions: The final results of this study show that in the relationship between early maladaptive schemas and psychiatric symptoms among addicts in Zanjan city, distress tolerance plays a mediating role and the model has a goodness of fit. Keywords: Distress tolerance, Early maladaptive schemas, Psychiatric symptoms, Addicts