Recent decades have seen a change in the runoff characteristics of the Suntar River in Eastern Siberia. This study attempts to attribute these changed hydrological conditions through parameterizing a hydrological model based on historical short-term observations conducted in 1957-1959 at the Suntar-Khayata research station. The Hydrograph model is applied as it has the advantage of using observed physical properties of landscapes as its parameters. The developed parametrization of the goltsy landscape (rocky-talus) is verified by comparison of the results of simulations of variable states of snow and frozen ground with observations carried out in 1957-1959. Continuous simulations of streamflow on a daily time step are conducted for the period 1957-2012 in the Suntar River (area 7680 km2, altitude 828-2794 m) with mean and median values of Nash-Sutcliff criteria reaching 0.58 and 0.67 respectively. The results of simulations have shown that the largest component of runoff (about 70%) is produced in the high-altitude area which comprises only 44% of the Suntar River basin area. The simulated streamflow reproduces the patterns of recently observed changes, including the increase in low flows, suggesting that the increase in the proportion of liquid precipitation in autumn due to air temperature rise is an important factor in driving streamflow changes in the region. The data presented are unique for the vast mountainous parts of North-Eastern Eurasia which play an important role in global climate system. The results indicate that parameterizing a hydrological model based on observations rather than blind calibration allows the model to be used in studying the response of river basins to climate change with greater confidence.

Background: C-KIT mutation and extramedullary infiltration highly occur in AML1-ETO-positive acute myeloid leukemia (AE-AML). Whether they having the same clinical significance in pediatric and adult patients remains unsure.  Procedure: Totally 75 pediatric and 98 adult patients with newly diagnosed AE-AML from 5 centers were included and analyzed. Results: The incidence of extramedullary leukemia (EML) (13.3% vs. 29.6%, P=0.008) and c-KIT mutations (12/68, 17.6% vs. 30/74, 40.5%, P=0.003) in pediatric patients were less than half compared to adult counterpart. The disease outcome including complete response (CR), disease-free survival (DFS) and overall survival (OS) was comparable between the two patient groups, when induction/consolidation regimens were taken into consideration. Based on multivariate analysis, EML was associated with a higher relapse and worse survival, and patients carrying c-KIT mutations showed a trend toward a worse prognosis. Grouping by age, the adverse effect of EML and c-KIT mutations on prognosis was only seen in adults but not children and was not affected by consolidation regimens. Conclusions: The occurrence of EML and c-KIT mutations was much less in pediatric than adult AE-AML. Both EML and c-KIT mutations adversely impacted the disease outcome in adult but not pediatric patients, suggesting the behavior of AML1-ETO fusion protein might be age-dependent.

Introduction We aimed to provide reference ranges for the right ventricular outflow tract (RVOT) diameter by cardiovascular magnetic resonance (CMR) in children and compare the measurements with two-dimensional (2D) transthoracic echocardiography (TTE). Methods We measured the RVOT diameter in 49 children with normal RVOT anatomy on balanced steady-state free precession (bSSFP) CMR images in the strict transverse and sagittal views, and on 2D TTE images in parasternal short axis (PSAX) and parasternal long-axis (PLAX) views. Results Based on 63 measurements, we obtained the following mean RVOT diameters and their reference ranges, indexed to body surface area: 15.2 mm/m2 (7.0-23.3 mm/m2) in the strict transverse view, and 14.0 mm/m2 (7.8-20.2 mm/m2) in the strict sagittal view. Pearson correlation showed a very strong correlation between the CMR strict transverse view and the 2D TTE PSAX view (r=0.84; p<0.0001), and a strong correlation between the CMR strict sagittal view and the 2D TTE PLAX view (r=0.78; p<0.0001). The Bland-Altman analysis showed poor agreement between the CMR strict transverse view and the 2D TTE PSAX view (bias -3.34 mm/m2 or -16.6%), and between the CMR strict sagittal view and the 2D TTE PLAX view (bias -3.90 mm/m2 or -19.7%). Conclusions There is strong correlation but poor agreement between the measurements of the RVOT diameter in the strict transverse and sagittal views by CMR and the similar PSAX and PLAX views by 2D TTE. The static bSSFP CMR images in the strict transverse and sagittal views can’t be used to define RVOT dilatation in children

In this article, the Cauchy problem of three-dimensional (3-D) incompressible magnetohydrodynamic system with infinite energy initial data is investigated. Via some elaborate analysis of the time evolution of both the vorticity ω=: ▽×u and the current density j=: ▽×b , the local-in-time well-posedness of mild solutions with arbitrarily large initial data in Morrey spaces is established.

Purpose and overview : The main purpose of the activity is that the student will know, how their garden can benefit not just to their class room or school but also to the entire community. The student collect data to get knowledge about the impact of their activity and use this data for community engagement. The student then plan and execute a campaign to point out needs, issues, questions they got during the activity. Time : The activity time is a part of extended learning period that keep the student to create a school garden. This time is in the following pattern: 1. 45 minutes for class period. 2. 90 minutes for preparing the required things for the activities. 3. 45 minutes for each of the activity suggested in this section. 4. An extended service learning project for 2 to 4 weeks.

We reported a rare case of iatrogenic aortic dissection caused by incorrect frozen elephant trunk (FET) deployment. A 53-year-old man underwent total arch replacement with FET for aortic arch aneurysm and concurrent PAU in the descending aorta. However, after FET deployment, aortic dissection occurred. We analyzed that the tip of FET stent had been inserted into the PAU and caused aortic dissection. We performed some salvage procedures. However, the patient died on the 1st postoperative day. Therefore, care should be taken to avoid incorrect deployment of FET when there is a large tear or ulcer lesion in the proximal descending aorta.

Backgrounds: Enormous number of possible conformations in the protein structure simulation have led molecular dynamics researchers to be frustrated until now. Some methods with defects ended their experiments into failure. This made them fail to determine the structure and function of folded protein in stable state with the lowest potential energy. This apparently exist in nature. The purpose of resolving a protein folding pathway that follows protein backbone residues torsional inertia was accomplished. Results: A new method, torsion angle modeling, was adopted focused on the rotation of dihedral angles. The potential energy was calculated by rotating torsion angles of the peptide with 8 residues. It was found that when moving in the order of torsional inertia, 8 residues swivel in sequence. Six passes were repeated to find the lowest value. Conclusion: The protein backbone torsion angle plays very important role in predicting protein structure. Actually it was thousand times faster or more than others to get the obvious pathway.

In this paper, we deal with the non-linear integro-differential equation in which we proposed a quadrature method in order to find an approximate solution. We provide an error analysis and we conclude by giving the algorithm.

The repair of thoracoabdominal aortic aneurysm (TAAA) require a range of surgical techniques and is associated with serious complications such as paraplegia, gastrointestinal complications and acute kidney injury. In this report, we present a case of successful giant TAAA repair. Repair was performed from proximal to distal by sequential aortic cross clamp-and-sew under normothermia in this case. To prevent visceral, renal and spinal cord ischemia, organ protection was supplemented with cerebrospinal fluid drainage, renal perfusion and selective visceral perfusion in this case.

Diabetes mellitus is among the chronic diseases considered emergencies. Products obtained from medicinal plants have been used for thousands of years by the population in the treatment of various diseases. The objective of this work was to evaluate the possible effects of inputs obtained from the artichoke (Cynara scolumus L.) on biochemical markers in diabetic rats. The dry extract was obtained by hydroethanolic (70% v / v) maceration. Male Wistar rats were treated with alloxan (150 mg / kg of mass dissolved in 0.9% saline) intraperitoneally. The extract (0.2g extract / kg) was given in normal and diabetic rats for 30 days. Animals from the Control and Diabetes groups received only water. Biochemical markers were determined in the serum by enzymatic colorimetric method. The chemical characterization was performed quantifying the total polyphenol content (Folin-Ciocalteau) and quantification of the total flavonoid in dry extract (1 mg / mL), by the complexation method with aluminum chloride. The evaluation of fasting blood glucose was positive, when considered that the glycemic levels from “diabetic group” was partially higher when compared with “water group”, “extract group” and “diabetic extract group”. The treatment with extract for the diabetic animals also prevented significantly the serum levels of fructosamine and presented serum levels of total cholesterol and triglycerides significantly lower than non-treated animals. However, the treatment with artichoke extract was able to control glycemic levels at short and medium term, showing an improvement in lipid profile. Key words: Artichoke. Oxidative stress. Phytochemical screening. Flavonoids. Total polyphenols.

Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding and prevention of adverse effects associated with the drugs. The objective of PV is to ensure safety of the medicines and patients by monitoring and reporting of all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2-24% of hospitalization cases are due to ADRs out of which 3.7% of patients have lethal ADRs. The reasons includes number of prescribing drugs, increased new drugs in the market, and inadequate PV system for ADRs monitoring, lack of awareness and knowledge about ADRs reporting. Serious ADRs leads to enhanced hospital stay, increased treatment cost, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is important to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1% whereas worldwide it is 5% due to lack of awareness about PV and ADR monitoring among healthcare providers and patients. Spontaneous reporting is the most commonly used PV method to report ADRs in both urban and rural areas of India. Evidences revealed that there is not any effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR thus increasing threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring and reporting of ADR in rural areas.

Pre-eclampsia usually occurs in the antenatal period after 20 weeks of gestation. However, case of postpartum preeclampsia can also occur especially within the first one week after the delivery. The diagnosis of postpartum preeclampsia can be easily missed since it is rare.

Temozolomide (TMZ) is a standard of care treatment for Glioblastoma Multiforme (GBM). We report a fatal outcome of a 55 years old female with GBM who developed persistent aplastic anemia (AA) while being treated with TMZ. This case highlights the possibility of a dose-independent and fatal AA secondary to TMZ.

Incoordination during the pharyngeal phase in severe dysphagia due to lateral medullary syndromeRunning title: Severe dysphagia due to LMS

Abstract Background: It is still unclear if and to what extent antenatal or early postnatal or infants vitamin D supplementation would affect the development of allergy diseases later in life. Methods: Randomized controlled trials about vitamin D supplementation in pregnant or healthy children from birth to five years of age to prevent allergic diseases were selected. Descriptive and quantitative information was extracted. Relative risk estimates were synthesized under a fixed or random effects model. Heterogeneity was assessed by using the I2 metric. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to asses certainty of findings. MEDLINE(PubMed), EMBASE(OVID), and The Cochrane Central Register of Controlled Trials were searched up to March 1st 2020.Eligibility criteria for selecting studies: (1) the design was an randomized controlled trial(RCT); (2) healthy pregnant or lactating females and/or healthy children from birth to five years of age;(3) vitamin D protocol was specified in the treatment group; (4) outcomes were asthma/wheeze, allergic rhinitis, eczema(atopic dermatitis), food allergy and atopic sensitization; (5) the study contained relevant data to calculate the effect size. Results: In the present systematic review and meta-analysis, the available published randomized evidence on vitamin D supplementation in pregnant or infants for preventing allergic diseases across 7 RCTs were systematically assessed. Our meta-analysis showed that non-significant trends between vitamin D supplementation in pregnant or infants and the primary prevention of allergic diseases in offspring. The Grade quality assessment for all these conclusions indicated an evidence confidence level of low. Conclusions: In terms of practice implications, the data in this review should not make patients, doctors, and public health authorities confident that vitamin D supplementation in pregnant or infants or young children can primarily prevent allergic diseases. Systematic review registration: PROSPERO (CRD42020167747)

We report a 56-year-old male with methemoglobinemia and hemolytic anemia, secondary to fava bean ingestion. Methylene blue administration worsened the hemolysis as he was G6PD deficient but not diagnosed before. We have discussed the mechanism of hemolysis in such patients and the management of such cases.

Inhibition of interleukin 6 (IL-6) signalling has been proposed as a potential cardioprotective strategy for patients with chronic kidney disease (CKD) but the direct renal effects of IL-6 inhibition are not established. A Mendelian randomization (MR) study was performed to investigate the association of genetically proxied inhibition of IL-6 signalling with estimated glomerular filtration rate (eGFR), CKD and blood urea nitrogen (BUN). Inverse variance weighted MR was used as the main analysis, with sensitivity analyses performed using simple median, weighted median and MR-Egger methods. There was no evidence for an association of genetically proxied inhibition of IL-6 signalling (scaled per unit decrease in natural log transformed C-reactive protein) with log eGFR (0.002, 95% confidence interval -0.004 – 0.008), BUN (0.088, 95% confidence interval -0.003 – 0.019) and CKD (odds ratio 1.018, 95% confidence interval 0.899 – 1.153). These findings suggest that inhibition of IL-6 signalling is unlikely to have a direct effect on renal function.

Purpose: The current research has been intended to evaluate the impacts of 6-shogaol in rodent model of ischemic-reperfusion induced- brain injury and also assessed whether 6-shogaol enhanced sevoflurane’s neuroprotective effects. Methods: Ischemic-Reperfusion (I/R) injury was induced by middle cerebral artery occlusion (MCAO) method in Sprague-Dawley rats. A separate group of animals was exposed to sevoflurane (2.5%) post-conditioning for 1 h immediately after reperfusion. 6-shogaol (25 mg or 50 mg/kg body weight) was orally administered to treatment group rats for 14 days and then subjected to I/R. Results: 6-shogaol treatment along with/without sevoflurane post-conditioning reduced the number of apoptotic cell counts, brain edema and cerebral infarct volume. The western blotting analysis revealed a significant stimulation of the PI3K/Akt/mTOR signal pathway. RT-PCR and western blotting studies revealed improved expressions of HIF-1α and HO-1were also noticed at both gene level and protein levels as determined by. I/R induced neurological deficits were also alleviated on sevoflurane post-conditioning with/without 6-shogaol treatment. Conclusion: The study’s findings reveal that pre-treatment with 6-shogoal enhanced the neuroprotective properties of sevoflurane post-conditioning, illustrating the efficacy of the compound against I/R injury. 6-Shogaol thus could be investigated further for cerebral protection following I/R.

Celecoxib or Celebrex, an NSAID (non-steroidal anti-inflammatory drug), is one of the most common medicines for treating inflammatory diseases. Recently, it has been shown that celecoxib is associated with implications in complex diseases such as Alzheimer’s disease and cancer, as well as with cardiovascular risk assessment and toxicity, suggesting that celecoxib may affect multiple unknown targets. In this project, we detected targets of celecoxib within the nervous system using a label-free TPP (Thermal Proteome Profiling) method. First, proteins of the rat hippocampus were treated with multiple drug concentrations and temperatures. Next, we separated the soluble proteins from the denatured and sedimented total protein load by ultracentrifugation. Subsequently, the soluble proteins were analyzed by nano-liquid chromatography-mass spectrometry to determine the identity of the celecoxib targeted proteins based on structural changes by thermal stability variation of targeted proteins towards higher solubility in the higher temperatures. In the analysis of the soluble protein extract at 67 centigrade, 44 proteins were uniquely detected in drug-treated samples out of all 478 identified proteins at this temperature. Rab4a, one out of these 44 proteins, has previously been reported as one of the celecoxib off-targets in the rat CNS. Furthermore, we provide more molecular details through biomedical enrichment analysis to explore the potential role of all detected proteins in the biological systems. We show that the determined proteins play a role in the signaling pathways related to neurodegenerative disease - and cancer pathways. Finally, we fill out molecular supporting evidence for using celecoxib towards the drug repurposing approach by exploring drug targets.

Background and Purpose The cyclic nucleotides cAMP and cGMP are ubiquitous second messengers participating in the regulation of several biological processes. Interference of cNMP signalling is linked to multiple diseases and thus is an important component of pharmaceutical research. The existing optogenetic toolbox in C. elegans is restricted to soluble adenylyl cyclases, the membrane-bound Blastocladiella CyclOp and hyperpolarizing rhodopsins, yet missing are membrane-bound photoactivatable adenylyl cyclases and hyperpolarizers on the basis of K+-currents. Experimental Approach For the characterization of the photoactivatable nucleotidyl cyclases, we expressed the proteins alone or in combination with cyclic-nucleotide gated channels in C. elegans muscle cells and cholinergic motor neurons. To investigate the extent of optogenetic cNMP production and the ability of the systems to de- or hyperpolarize the cells, we performed behavioural analyses (locomotion, muscle contraction) and measured the cNMP content in vitro. Key Results We implemented Catenaria CyclOp as a new tool for cGMP production, allowing fine-control of cGMP levels. As photoactivatable membrane-bound adenylyl cyclases, we established YFP::BeCyclOp(A-2x) and YFP::CaCyclOp(A-2x), enabling more specific optogenetic cAMP signalling compared to soluble ACs. For the hyperpolarization of excitable cells by K+-currents, we introduced the cAMP-gated K+-channel SthK from Spirochaeta thermophila with either bPAC or BeCyclOp(A-2x), and the Blastocladiella emersonii cGMP-gated K+-channel BeCNG1 with BeCyclOp. Conclusion and Implications We established a comprehensive suite of optogenetic tools for cNMP manipulation for the nematode, which will be useful for applications in many cell types, including sensory neurons which use mainly cGMP as second messenger, and for potent hyperpolarization using K+-ions.

Ferroptosis is a new form of programmed cell death characterized by intracellular iron-dependent accumulation of lipid peroxide and primarily associated with iron metabolism, glutathione-dependent pathway, and Coenzyme Q10-dependent pathway. Recent studies demonstrate that ferroptosis is associated with central nervous system (CNS) diseases, such as stroke, Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. This review summarizes the key regulatory mechanisms of modulation of ferroptosis and its role in CNS diseases. These updates may provide novel prospective on therapeutical agent developments against CNS diseases.

Stuttering is a childhood onset fluency disorder, intertwined with physiological, emotional and anxiety factors. The present study was designed to evaluate the recurrence of the reported mutations among three previously implicated (GNPTAB, GNPTG, NAGPA) candidate genes, in persons with stuttering (PWS) from south India. Mutation screening was performed on 64 probands on 12 specific exons, by Sanger sequencing. A total of 12 variants were identified, which included five nonsynonymous missense, five synonymous and two non coding variants. Only three unrelated probands, harbored heterozygous likely pathogenic missense variants (c.3598G>A in GNPTAB, c.802A>C in GNPTG and c.131G>C in NAGPA) resulting in an overall frequency of 4.7% and an allele frequency of 2.3% (3/128*100). Among the three likely pathogenic variants only two co-segregated (c.3598G>A in GNPTAB - STU 29 and c.802A>C in GNPTG - STU 63) with the affected status reducing the likely pathogenic allele frequency to 1.6% (2/128*100). The recurrence of pathogenic variants in our study corroborate the causative role of these genes in stuttering but still remains unknown as to how the speech dysfluency occurs even in its heterozygous condition. Keywords: Stuttering, candidate genes, GNPTAB, GNPTG, NAGPA

Abstract Stuttering is a complex speech disorder and heritability of this trait is persuasive, with multiple afflicted families showing phenotypic segregation across generations, yet no conclusive genetic etiology could be identified. Analyzing multiplex families using exome sequencing(ES) may help in identification of putative genes and scope for understanding the mutational burden for speech implicated pathways. In this study ES was performed in six individuals from two clinically well characterized, multiple affected, south Indian families (STU-65 and STU-66) showing stuttering across five generations. From ES to variant prioritization, a sequential bioinformatics approach was implemented to search for putative gene targets. In the two multiplex families studied, ES data analysis resulted in an enriched list of 14 genes (with variants) (COL4A2,COL6A3,COL6A6,ITGAX,LAMA5,ADAMTS9,CSGALNACT1, TMOD2,HTR2B,RSC1A1,TRPV2,WNK1,ARSD and SPTBN5) involved in neural functions. Additionally, a homozygous variant in NLRP11 gene and a heterozygous variant in NAGPA gene were identified in STU-65 family that needs further confirmation. Our results support the fact that stuttering is a polygenic disorder. The putative gene targets identified in our study can drive the research prospects to understand the underlying mechanisms. We hypothesize multiple and combined mechanisms to be involved in the genesis of stuttering. Keywords: Stuttering, exome sequencing, neural pathways

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