Mutations in Epigenetic Modifiers in Myeloid Malignancies and the Prospect of Novel Epigenetic-Targeted Therapy

In the recent years, the discovery of a series of mutations in patients with myeloid malignancies has provided insight into the pathogenesis of myelodysplastic syndromes (MDSs), myeloproliferative neoplasms (MPNs), and acute myeloid leukemia (AML). Among these alterations have been mutations in genes, such as IDH1/2, TET2, DNMT3A, and EZH2, which appear to affect DNA and/or histone lysine methylation. Large clinical correlative studies are beginning to decipher the clinical importance, prevalence, and potential prognostic significance of these mutations. Additionally, burgeoning insight into the role of epigenetics in the pathogenesis of myeloid malignancies has prompted increased interest in development of novel therapies which target DNA and histone posttranslational modifications. DNA demethylating agents have been demonstrated to be clinically active in a subset of patients with MDS and AML and are used extensively. However, newer, more specific agents which alter DNA and histone modification are under preclinical study and development and are likely to expand our therapeutic options for these diseases in the near future. Here, we review the current understanding of the clinical importance of these newly discovered mutations in AML and MDS patients. We also discuss exciting developments in DNA methyltransferase inhibitor strategies and the prospect of novel histone lysine methyltransferase inhibitors

The value of visual inspections for emergency management of bridges under seismic hazard

One of the major problems in the aftermath of an earthquake is the management of the emergency inspection operations. Traffic restriction, including limited emergency operations or bridge closure due to safety concerns, may be issued to keep an appropriate level of safety. Visual inspections may be conducted to provide useful information on the damage state of the bridge and support the decision of imposing traffic restriction up to the complete closure of the bridge, or for allowing the immediate use of safe bridges after the event. The cost related to the inspection shall be at least balanced by the uncertainty reduction provided by the inspection data and the benefit is higher when the costs associated with taking a wrong management decision are high, but may be negligible if this is not the case. Practical tools and methods to forecast this benefit before collecting the information exist in classical decision theory, but are seldom applied by engineers. In this paper a framework based on the concept of Value of Information (VoI) from the pre-posterior Bayesian decision analysis is adopted and applied to the case study of a two span reinforced concrete bridge

The Role of Urban Morphology Design on Enhancing Physical Activities and Public Health

Along with environmental pollutions, urban planning has been connected to public health. The research indicates that the quality of built environments plays an important role in reducing mental disorders and overall health. The structure and shape of the city are considered as one of the factors influencing happiness and health in urban communities and the type of the daily activities of citizens. The aim of this study was to promote physical activity in the main structure of the city via urban design in a way that the main form and morphology of the city can encourage citizens to move around and have physical activity within the city. Functional, physical, cultural- social, and perceptual-visual features are regarded as the most important and effective criteria in increasing physical activities in urban spaces based on literature review. The environmental quality of urban spaces and their role in the physical activities of citizens in urban spaces were assessed by using the questionnaire tool and analytical network process (ANP) of structural equation modeling. Further, the space syntax method was utilized to evaluate the role of the spatial integration of urban spaces on improving physical activities. Based on the results, the consideration of functional diversity, spatial flexibility and integration, security, and the aesthetic and visual quality of urban spaces plays an important role in improving the physical health of citizens in urban spaces. Further, more physical activities, including motivation for walking and consequently, the sense of public health and happiness, were observed in the streets having higher linkage and space syntax indexes with their surrounding texture

A molecular dynamics study on the wettability property of modified hydrophilic quartz (001) surface with hydrophobic nanoparticles

In this study, molecular dynamics simulation was used to investigate the modification of quartz surface with adsorption of polystyrene and graphene nanoparticles. The simulations were performed on the super-hydrophilic quartz (001) surface. Polystyrene nanoparticles in three different percentages of surface coverage (5, 7, and 10) and one, two, four, and six layers’ graphene nano-sheets were created and adsorbed on the quartz surface. Then, contact angle, dipole moments, and intermolecular and intermolecular interactions between different nano-particles, quartz surface as a super hydrophilic substrate, and water molecules in the nano droplets were measured as the indicators of surface wettability. Analysis of the simulation results showed that the net and uncovered surface of quartz tolerates a high and asymmetric distribution of partial charge, causing a severe surface stress and intense hydrophilic behavior of the mineral surface. However, with the adsorption of polystyrene and graphene nanoparticles, the wettability behavior of the surface was changed to hydrophobic. Besides, changes in the surface energy due to nanoparticle adsorption, led to extensive changes in the dipole moment arrangement of water molecules on the quartz surface

Effect of Vitamin C on Serum Cortisol after Etomidate Induction of Anesthesia

Objectives: Etomidate is suitable for induction of anesthesia, especially in elderly patients and patients who have cardiovascular compromise. Vitamin C has been introduced as a treatment option to decrease Etomidate induced adrenal insufficiency but its actual effect is still controversial. Objective is to determine the effect of Vitamin C on reduction of serum cortisol after etomidate induction of anesthesia. Methods: In a randomized clinical trial, 40 patients of ASA class I & II, aged between 25 to 70 years old, candidate for elective laparatomy were selected. One hour before induction of surgery, 1 gram of intravenous Vitamin C were administered to the patients in Vitamin C group. Two blood samples were obtained 5 minutes before induction and then another sample 4 hours after induction with etomidate after surgery. All samples were measured for serum free cortisol, ACTH, and C-reactive protein (CRP). Results: There were no significant differences between duration of surgery, preoperative and post-operative blood pressure and heart rate in two groups (p>0.05). Serum cortisol was significantly declined in control group from 16.2±6.3 μg/dl in preoperative to 8.5±4.2 in postop (p=0.0005), but not in Vitamin C group from 17.5±5.6 in preop to 16.8±6.4 in postop (p=0.75). ACTH levels increased non-significantly from preop to postop period in both Vitamin C (pre: 52.1±15 vs. post: 56.4±18 pg/ml) (p=0.48) and in control group (pre:50.5±16 vs. post:56.2±20). Conclusion: Etomidate could significantly decrease postoperative serum free cortisol and induce adrenocortical suppression and CRP increase. This effect could be reversed by using Vitamin C premedication to maintain serum cortisol at preoperative level

Učinak intervalnog treninga, aerobnog treninga i treninga otpornosti te konzumiranog dodatka spiruline na razine UCP-1, TRPV1 i HOMA-IR u bijelom masnom tkivu štakora sa šećernom bolesti.

The purpose of this study was to investigate the effect of high-intensity interval, aerobic, and resistance training, and spirulina supplement consumption on the levels of Uncoupling Protein-1 (UCP1), Transient Receptor Potential Vanilloid (TRPV1) and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) in the white adipose tissue of diabetic rats. A total of 42 male rats with diabetes type II were randomly assigned into seven groups as follows: aerobic training (n=6), resistance training (n=6), interval training (n=6), aerobic training combined with supplementation (n=6), resistance training combined with supplementation (n=6), interval training combined with supplementation (n=6) and control (n=6) groups. The training groups carried out the training (8 weeks/5 days) on a rodent treadmill and ladder. The paired sample t-test and one-way ANOVA were employed for data analysis. The three kinds of training, with and without supplementation, significantly reduced mass, glucose, insulin, and insulin resistance. In the three supplementation-combined training groups the difference on the HOMA-IR index was significant; however, the decline was larger in the resistance training with supplementation group. The concentration of UCP-1 and TRPV1 proteins significantly increased in all training groups, with and without supplementation. Nonetheless, the significant increase in the UCP-1 levels in the interval training with supplementation group was more than in the other groups. Furthermore, the TRPV1 protein levels were higher in the resistance training with supplementation group. Eight weeks of training, with and without Spirulina supplementation, reduced insulin resistance and gave rise to significant changes in UCP-1 and TPRV1 concentrations.Svrha istraživanja bila je utvrditi učinak treninga s intervalom visokog intenziteta, anaerobnog treninga, treninga otpornosti i konzumiranja dodatka spiruline na razine nevezanog proteina-1 (UCP1), vaniloidnog potencijalnog prijelaznog receptora (TRPV1) te na procjenu homeostatskog modela za rezistenciju na inzulin (HOMA-IR) u bijelom masnom tkivu štakora sa šećernom bolesti. Ukupno 42 muška štakora sa šećernom bolesti tipa II nasumično su raspoređena u sedam skupina kako slijedi: aerobni trening (n = 6), trening otpornosti (n = 6), intervalni trening (n = 6), aerobni trening kombiniran s dodatkom spiruline (n = 6), trening otpornosti kombiniran s dodatkom spiruline (n = 6), intervalni trening kombiniran s dodatkom spirulina (n = 6) i kontrolna skupina (n = 6). Trening (8 tjedana/5 dana) je proveden na pomičnoj traci i ljestvama za glodavce. Za analizu podataka korišteni su t-test za parne uzorke i jednosmjerna ANOVA. Tri vrste treninga, sa i bez dodataka spiruline, znakovito su smanjile masu, glukozu, inzulin i rezistenciju na inzulin. U tri skupine s kombiniranim treningom i dodatkom spiruline razlika u indeksu HOMA-IR bila je znakovita, međutim pad je bio veći u skupini treninga otpornosti s dodatkom spiruline. Koncentracija proteina UCP-1 i TRPV1 znakovito se povećala u svim skupinama s treningom, sa i bez dodataka spiruline. Pri tome, povećanje razina UCP-1 u skupini koja je imala trening s intervalnom visokog intenziteta i dodatak spiruline bilo je znakovito više nego u drugim skupinama. Nadalje, razine proteina u TRPV1 bile su više u skupini s treningom otpornosti i dodatkom spiruline. Osam tjedana treninga, sa i bez dodatka spiruline, smanjilo je inzulinsku rezistenciju i dovelo do znakovitih promjena u koncentracijama UCP-1 i TPRV1

Effects of contrast administration on cardiac MRI volumetric, flow and pulse wave velocity quantification using manual and software-based analysis.

OBJECTIVE: The aim of the current study was to determine the effects of gadolinium contrast agent on right (RV) and left ventricular (LV) volumetric, aortic flow and pulse wave velocity (PWV) quantification using manual, semi-automatic and fully automatic analysis techniques. METHODS: 61 participants free from known cardiovascular disease were recruited. Cardiac MR was performed on a 3 T scanner. A balanced steady-state free precession stack was acquired of the ventricles with phase contrast imaging of the aorta performed pre- and post-administration of 10 ml 0.5 mmol ml-1 gadoterate meglumine. The images were analysed manually, and using a semi-automated and a fully automated technique. RESULTS: 54 completed the study. Gadolinium-based contrast administration significantly increase the signal-to-noise ratio (pre: 830 ± 398 vs post: 1028 ± 540, p = 0.003) with no significant change in contrast-to-noise ratio (pre: 583 ± 302 vs post: 559 ± 346, p = 0.54). On LV analysis, post-contrast analysis yielded significantly higher end systolic volume (54 ± 20 vs 57 ± 18 ml, p = 0.04), and lower ejection fraction (59 ± 9 vs 57 ± 8%, p = 0.023). On RV analysis, gadolinium contrast resulted in no significant differences. Similar results were seen using the semi-automated and fully-automated techniques but with a larger magnitude of difference. Conversely, using both manual and software analysis aortic flow and PWV quantification proved robust to the effects of contrast agent producing only small non-significant differences. CONCLUSION: Gadolinium contrast administration significantly alters LV endocardial contour detection with this effect amplified when using semi-automated analysis techniques. In comparison, RV and PWV analysis is robust to these effects. Advances in knowledge: Contrast administration alters LV quantification but not flow analysis. However, these differences are small

Methane emission: strategies to reduce global warming in relation to animal husbandry units with emphasis on ruminants

Concerns about global warming and greenhouse gases have increased the interest of governments and the public sector to find solutions. To reduce the effects of global warming caused by greenhouse gases, especially methane, it is necessary to change animal production systems and adopt new strategic approaches. The reduction of enteric methane in livestock is a long-standing problem regarding the energy efficiency of consumed feed. In this review, the sources of production, dissemination, and introduction of accepted scientific and practical solutions in order to reduce methane gas in breeding and production units of dairy cows have been investigated. To carry out this research, a thorough search was conducted in articles published in valid databases between 1967 and 2022. A total of 213 articles were reviewed, and after screening, 159 were included in the study and analyzed using a PRISMA flow diagram. In general, low livestock efficiency, low-quality feed, a shortage of knowledge, and inadequate investment are the main causes of emission of these gases in poor or developing countries. On the other hand, developing countries may not always have access to the same methods that are utilized in industrialized countries to minimize the production of methane and other greenhouse gases like nitrous oxide. According to their conditions, developing countries should use the available tools to reduce methane production and emission, considering the costs, local knowledge, feasibility, and local laws. In future, there will be a greater need for interdisciplinary research to look for sustainable and acceptable methods for reducing methane emissions and other greenhouse gases from animal husbandry units, especially dairy cows. To change the population of rumen methanogens, as the main producers of methane, strategies such as feeding management, addition of inhibitors and vaccination are suggested. Also, there is a need for more applied research for reducing methane emissions