Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routines

BACKGROUND: N-Acetylserotonin O-methyltransferase (ASMT) is an enzyme which by converting nor-melatonin to melatonin catalyzes the final reaction in melatonin biosynthesis in tryptophan metabolism pathway. High Expression of ASMT gene is evident in PPTs. The presence of abnormally high levels of ASMT in pineal gland could serve as an indication of the existence of pineal parenchymal tumors (PPTs) in the brain (J Neuropathol Exp Neurol 65: 675–684, 2006). Different levels of melatonin are used as a trait marker for prescribing the mood disorders e.g. Seasonal affective disorder, bipolar disorder, or major depressive disorder. In addition, melatonin levels can also be used to calculate the severity of a patient’s illness at a given point in time. METHODS: Seventy three melatoninergic inhibitors were docked with acetylserotonin-O-methyltransferase in order to identify the potent inhibitor against the enzyme. The chemical nature of the protein and ligands greatly influence the performance of docking routines. Keeping this fact in view, critical evaluation of the performance of four different commonly used docking routines: AutoDock/Vina, GOLD, FlexX and FRED were performed. An evaluation criterion was based on the binding affinities/docking scores and experimental bioactivities. RESULTS AND CONCLUSION: Results indicated that both hydrogen bonding and hydrophobic interactions contributed significantly for its ligand binding and the compound selected as potent inhibitor is having minimum binding affinity, maximum GoldScore and minimum FlexX energy. The correlation value of r(2) = 0. 66 may be useful in the selection of correct docked complexes based on the energy without having prior knowledge of the active site. This may lead to further understanding of structures, their reliability and Biomolecular activity especially in connection with bipolar disorders

Open Access

Molecular docking studies for the identification of novel melatoninergic inhibitors for acetylserotonin-O-methyltransferase using different docking routine

Anesthetic recovery and hemodynamic effects of continuous thiopental infusion versus halothane for maintenance anesthesia in patients undergoing ocular surgery

Purpose: To investigate anesthesia recovery and hemodynamic status in patients under thiopental infusion or halothane maintenance anesthesia undergoing ocular surgery. Methods: Fifty-nine voluntary patients undergoing ocular surgery in Farabi hospital were allocated to one of two maintenance anesthesia groups: inhaled halothane, 0.8 to 1 per cent, (group I, n=37) and thiopental infusion, 10 to 12 mg/kg/hour, (group II, n=22). Hemodynamic parameters were recorded at the time of patient entrance to the operation room and at the 1, 2, 5, 10, 15, 20, 25, 30, 35, and 40 minutes following anesthesia. Anesthesia recovery variables were also compared between the two groups. Results: In group I, arterial blood pressure at 10 to 40 min and heart rate at 1 and 25 min after the administration of anesthetics were significantly lower when compared with group II (W-2=25.10, p=0.005). Arterial oxygen saturation was similar in the two groups over the whole points of time. The time intervals between the end of surgery and beginning of the first body movements and respiratory efforts were significantly longer in group received halothane (

Cost-Effectiveness Comparison between Ticagrelor and Clopidogrel in Acute Coronary Syndrome in Iran

Background: The present study aimed to determine the cost-effectiveness of ticagrelor compared with clopidogrel in Iranian patients with acute coronary syndrome (ACS). Methods:  A 1-year decision tree model combined with a 20-year Markov transition model was used to simulate the long-term cost and effectiveness of both ticagrelor and clopidogrel in Iran based on an Iranian payer’s perspective. Clinical efficacy data were extracted from the PLATO trial and other published studies. Costs were estimated based on local prices in public sectors.  Deterministic and probabilistic sensitivity analyses were used to test the robustness of base-case results over the uncertainties of model inputs. All calculations, analyses, and modeling were done in TreeAge 2011 and Microsoft Excel 2013. Results: Compared with clopidogrel, the treatment of Iranian ACS patients with ticagrelor for 20 years resulted in an additional cost of US$2.39 in a hypothetical cohort of 1000 patients. However, ticagrelor led to 7.2 quality-adjusted life-years (QALYs) gained per 1000 hypothetical patients. Accordingly, the estimated incremental cost-effectiveness ratio for this analysis was US$ 332.032 per 1 QALY gained. Conclusion: Ticagrelor was a cost-effective antiplatelet medicine compared with clopidogrel in Iranian patients with ACS. This could help Iran’s policymakers to allocate resources more efficiently to ACS

Response Surface Methodology for Optimization of Operational Parameters to Remove Ciprofloxacin from Contaminated Water in the Presence of a Bacterial Consortium

Ciprofloxacin (CFX) is a broad-spectrum fluoroquinolone antibiotic that is widely used to treat bacterial infections in humans and other animals. However, its unwanted occurrence in any (eco)system can affect nontarget bacterial communities, which may also impair the performance of the natural or artificially established bioremediation system. The problem could be minimized by optimization of operational parameters via modeling of multifactorial tests. To this end, we used a Box–Behnken design in response surface methodology (RSM) to generate the experimental layout for testing the effect of the CFX biodegradation for four important parameters, that is, temperature (°C), pH, inoculum size (v/v %), and CFX concentration (mg L–1). For inoculation, a consortium of three bacterial strains, namely, Acenitobacter lwofii ACRH76, Bacillus pumilus C2A1, and Mesorihizobium sp. HN3 was used to degrade 26 mg L–1 of CFX. We found maximum degradation of CFX (98.97%; initial concentration of 25 mg L–1) at 2% inoculum size, 7 pH, and 35 °C of temperature in 16 days. However, minimum degradation of CFX (48%; initial concentration of 50 mg L–1) was found at pH 6, temperature 30 °C, and inoculum size 1%. Among different tested parameters, pH appears to be the main limiting factor for CFX degradation. Independent factors attributed 89.37% of variation toward CFX degradation as revealed by the value of the determination coefficient, that is, R2 = 0.8937. These results were used to formulate a mathematical model in which the computational data strongly correlated with the experimental results. This study showcases the importance of parameter optimization via RSM for any bioremediation studies particularly for antibiotics in an economical, harmless, and eco-friendly manner.The authors are thankful to Higher Education Commission (HEC) for the grant No TTSF-77.Scopu

Association of social jetlag with gestational diabetes: Qazvin Maternal and Neonatal Metabolic Study

The association of social jetlag (SJL), as a quantitative measure of circadian misalignment, with insulin resistance and metabolic syndrome has been reported. The present study was designed to investigate the association of SJL with gestational diabetes mellitus (GDM). Pregnant women with gestational age ≤14 weeks were enrolled in this longitudinal study. The participants with pre-GDM, shift workers and those who used alarms for waking up on free days were excluded from the study. SJL as well as behavioral and psychological parameters were evaluated at enrollment. The participants were categorized based on each 1-h increment of SJL. The association of SJL with the occurrence of GDM in the late second trimester was evaluated using univariate and multivariate methods. In total, 821 pregnant women entered the study, and after omitting individuals with excluding criteria, analyses were performed on 557 participants. The frequencies of SJL < 1 h,1 ≤ SJL < 2 h and SJL ≥ 2 h were 44.7%, 37.2% and 18.1%, respectively. Average sleep duration was higher in SJL < 1 h compared with the two other groups (p < 0.001). During follow-up, 90 (16.1%) women with GDM were identified. SJL ≥ 2 h was associated with a 4.4-5.6 times higher risk of GDM in different models of adjustment (p < 0.05). Pregnant women with high SJL are at a higher risk of GDM. Further studies for evaluating the mechanisms by which SJL affects GDM are warranted

In Vitro Spermatogenesis by Three-dimensional Culture of Spermatogonial Stem Cells on Decellularized Testicular Matrix

Background: In the males, Spermatogonial Stem Cells (SSCs) contribute to the production of sex cells and fertility. In vitro SSCs culture can operate as an effective strategy for studies on spermatogenesis and male infertility treatment. Cell culture in a three-dimensional (3D) substrate, relative to a two-dimensional substrate (2D), creates better conditions for cell interaction and is closer to in vivo conditions. In the present study, in order to create a 3D matrix substrate, decellularized testicular matrix (DTM) was used to engender optimal conditions for SSCs culture and differentiation. Materials and Methods: After, testicular cells enzymatic extraction from testes of brain-dead donors, the SSCs were proliferated in a specific culture medium for four weeks, and after confirming the identity of the colonies derived from the growth of these cells, they were cultured on a layer of DTM as well as in 2D condition with a differentiated culture medium. In the Sixth week since the initiation of the differentiation culture, the expression of pre meiotic (OCT4 & PLZF), meiotic (SCP3 & BOULE) and post meiotic (CREM & Protamine-2) genes were measured in both groups. Results: The results indicated that the expression of pre meiotic, meiotic and post meiotic genes was significantly higher in the cells cultured on DTM (P <= 0.001). Conclusion: SSCs culture in DTM with the creation of ECM and similar conditions with in vivo can be regarded as a way of demonstrating spermatogenesis in vitro, which can be adopted as a treatment modality for male infertility. Keywords Author Keywords:Spermatogonial Stem Cells; Decellularization; Testicular Matrix; Proliferation; Diffetentiatio

The unfinished agenda of communicable diseases among children and adolescents before the COVID-19 pandemic, 1990-2019: a systematic analysis of the Global Burden of Disease Study 2019

BACKGROUND: Communicable disease control has long been a focus of global health policy. There have been substantial reductions in the burden and mortality of communicable diseases among children younger than 5 years, but we know less about this burden in older children and adolescents, and it is unclear whether current programmes and policies remain aligned with targets for intervention. This knowledge is especially important for policy and programmes in the context of the COVID-19 pandemic. We aimed to use the Global Burden of Disease (GBD) Study 2019 to systematically characterise the burden of communicable diseases across childhood and adolescence. METHODS: In this systematic analysis of the GBD study from 1990 to 2019, all communicable diseases and their manifestations as modelled within GBD 2019 were included, categorised as 16 subgroups of common diseases or presentations. Data were reported for absolute count, prevalence, and incidence across measures of cause-specific mortality (deaths and years of life lost), disability (years lived with disability [YLDs]), and disease burden (disability-adjusted life-years [DALYs]) for children and adolescents aged 0-24 years. Data were reported across the Socio-demographic Index (SDI) and across time (1990-2019), and for 204 countries and territories. For HIV, we reported the mortality-to-incidence ratio (MIR) as a measure of health system performance. FINDINGS: In 2019, there were 3·0 million deaths and 30·0 million years of healthy life lost to disability (as measured by YLDs), corresponding to 288·4 million DALYs from communicable diseases among children and adolescents globally (57·3% of total communicable disease burden across all ages). Over time, there has been a shift in communicable disease burden from young children to older children and adolescents (largely driven by the considerable reductions in children younger than 5 years and slower progress elsewhere), although children younger than 5 years still accounted for most of the communicable disease burden in 2019. Disease burden and mortality were predominantly in low-SDI settings, with high and high-middle SDI settings also having an appreciable burden of communicable disease morbidity (4·0 million YLDs in 2019 alone). Three cause groups (enteric infections, lower-respiratory-tract infections, and malaria) accounted for 59·8% of the global communicable disease burden in children and adolescents, with tuberculosis and HIV both emerging as important causes during adolescence. HIV was the only cause for which disease burden increased over time, particularly in children and adolescents older than 5 years, and especially in females. Excess MIRs for HIV were observed for males aged 15-19 years in low-SDI settings. INTERPRETATION: Our analysis supports continued policy focus on enteric infections and lower-respiratory-tract infections, with orientation to children younger than 5 years in settings of low socioeconomic development. However, efforts should also be targeted to other conditions, particularly HIV, given its increased burden in older children and adolescents. Older children and adolescents also experience a large burden of communicable disease, further highlighting the need for efforts to extend beyond the first 5 years of life. Our analysis also identified substantial morbidity caused by communicable diseases affecting child and adolescent health across the world. FUNDING: The Australian National Health and Medical Research Council Centre for Research Excellence for Driving Investment in Global Adolescent Health and the Bill & Melinda Gates Foundation