This article introduces briefly current status in managing type 2 diabetes (T2D) and an updated classical standardized comprehensive program which combines optimal medical treatment (OMT) with lifestyle modification, that is, intervention of RT-ABCDEFG (iRT-ABCDEFG) for control and prevention of T2D, and discusses its advantages and prospects. Here, G means goals; F means follow-up; E means examination; D means disease & risk factors control; C means changing unhealthy “environment-sleep-emotion-exercise-diet” intervention [E(e)SEEDi] lifestyle & Chinese medicine or control the source of infection & cutting genetic or spreading pathways during the COVID-19 pandemic; B means biohazard control; And A means antagonistic treatment, such as optimal anti-diabetic agents, the glucagon-like peptide-1 receptor (GLPR) agonists, the sodium-glucose cotransporter 2 (SGLT2) inhibitors, and the ultralong-acting, once-daily basal insulin. As a novel strategy for Intervention of diabetes, this program can be used as a Reverse, Right, and Routine Treatment in clinical practice. Moreover, the vital goals which include less major adverse cardiocerebrovascular events (MACCE) and diabetic complications, less medical costs, longer life expectancy, lower morbidity and mortality, and higher quality of life, will be realized by consistently practicing this program due to early diagnosis, OMT, and overall prevention. Whatever, this program is very helpful to manage or self-manage T2D and improve its outcomes since it highly links to cardiovascular disease (CVD), stroke, cancer, and other MACCEs.

Stochastic optimization algorithm and random signal nonlinear optimal filtering algorithm, as the two computing cores of high-performance intelligent calculation in intelligent control, are typical representatives of intelligent optimization algorithms in the rapidly developing scientific research and engineering application technology fields. In order to effectively improve the efficiency of information filtering and optimal quantization modeling of a class of partially observable random signals with massive characteristics in intelligent control, this paper uses stochastic optimal control theory and methods to discuss in depth the mathematical construction of this type of random signal transmission system. Two optimal control mathematical models are obtained via the optimal calculation and random optimization analysis of the allowable coding function and decoding function under this type of signal. It provides an idea mathematical processing method for improving the intelligent control and information management efficiency of the signal transmission system.

From the point of view of three famous and important techniques we will achieve new expectations for the soliton configurations to the (2+1)-dimensional generalized nonlinear Schrödinger equation (GNLSE) with four waves mixing (FWM). The suggested model describes propagation of solitons in birefringent fiber. The FWM governed effectively the performance of the resultant soliton amplitudes. The three famous methods candidates for this purpose are the extended direct algebraic method (EDAM), the extended simple equation method(ESEM) and the solitary wave ansatz method (SWAM). The three techniques are implemented successively for the suggested model successfully. Surprise expectations for solitons via these three techniques to this model which weren’t achieved previously by any other authors who used other techniques have been demonstrated.

This paper deals with an inverse problem for identification the leading coefficient function from the final state observation in a two-dimensional hyperbolic problem. Since such inverse problems are ill-posed, the study focused on finding a regularized solution. The regularized solution is obtained by using the Levenberg-Marquardt method in nonlinear least squares optimization. It has been observed with numerical tests that the obtained results are quite successful.

Introduction: Evidence-based medicine is the cornerstone of shared-decision making in healthcare today. The public deserves clear, transparent and trust-worthy information on drug efficacy. Yet today, many drugs are prescribed and used without solid evidence of efficacy. Moreover, meta-analyses are the staple to test for drug efficacy and adverse effects, but spins can lead to unconvincing conclusions. In a shared medical decision-making approach, general practitioners need drug assessment to be based on patient-important outcomes. The aim of project Rebuild the Evidence Base (REB) is to bridge the gap between the data needed in clinical practice and the data available from clinical research. Methods and Analysis: The drugs will be assessed on clinical patient important outcomes and for a population. Using the Cochrane tools, we propose to analyse for each population and outcome : 1) a meta-analysis, based on randomised controlled trials (RCTs) with low risk of bias overall ; 2) Confirmatory RCT with low risk of biais overall; 3) Heterogeneity between RCT, and 4) Publication bias assessment. Depending on the results of these analyses, evidence would be rated according to 4 levels: firm evidence, evidence, results to be confirmed (but no evidence) or lack of evidence. Conclusion: Project REB proposes a method for reading and interpreting randomized clinical trials and their meta-analysis to produce quality data for general practitioners to focus on benefit-risk assessment in the interest of patients. If this data does not exist, it could enable clinical research to better its aim.

Aims Anlotinib is a novel oral tyrosine kinase inhibitor that targets VEGFR-2, VEGFR -3, FGFR1-4, PDGFR-α, PDGFR-β, c-Kit, and Ret. This study aimed to develop a population pharmacokinetic model of anlotinib in patients with malignant tumors and identify various covariates that might affect its pharmacokinetic parameters. Methods 407 plasma concentrations from 16 patients were analyzed to establish a population pharmacokinetic model using the nonlinear mixed-effects model method. All patients were administered anlotinib (12 mg) orally, as a single drug therapy. The potential influence of demographic, hepatic, and renal function data was investigated using automated stepwise covariate model. The final model was evaluated using diagnostic goodness-of-fit plots, bootstrap, and visual predictive check methods. Results A one-compartment model with first-order absorption and elimination adequately described anlotinib pharmacokinetics. The population estimates of apparent total plasma clearance (CL/F) was 9.26 L/h (29.20% IIV), apparent volume of distribution (V/F) was 2010 L (29.20 IIV), and absorption rate constant (Ka) was 0.64 h-1 (56.70% IIV). Total cholesterol (TC) was identified as a covariate affecting CL/F, while alkaline phosphatase (ALP) was found to be statistically significant for V/F. Conclusion The population pharmacokinetic model adequately described the pharmacokinetics of anlotinib in patients with malignant tumors. TC and ALP might have a slight effect on the pharmacokinetic profile of anlotinib.

The Covid-19 Pandemic has impacted all Latin American countries, which has become worse by having fragmented health systems and deep social inequalities, it is noteworthy that public policies are formulated based on general economic principles such as the law of dynamic equilibrium, assuming that all the processes that determine the socioeconomic evolution flow smoothly and continuously, taking out of consideration the occurrence of contingencies and emergent events that force all social action levels to adjust their plans and strategies, for which it is necessary to evaluate the impacts that this pandemic has caused in Latin American countries (Argentina, Brazil, Chile, and Colombia), which allow us to know the evolution of the disease in these countries. The objectives of this article are: Provide evidence that fractional models are easily adaptable to the evolution of the virus in populations from different socioeconomic contexts; Know the behavior of the disease in the study countries from the parameters of the best approximation of the model in contrast with the real data of the infection; For the modeling, systems of differential equations will be applied and for the calculation of the optimal coefficients, the method of Markov Monte Carlo chains (MCMC) will be implemented to estimate model parameters.

Aim: This study was conducted to determine the metabolic phenotypes of newly discovered CYP2D6 genotypes. Methods: Totally, 22 volunteers were recruited in the study. The peripheral blood and urine were collected at the indicated time after orally administration of 100 mg metoprolol. After sample preparation, a validated HPLC method was employed to determine metoprolol and α-hydroxymetoprolol. Meanwhile, the blood pressure and electrocardiogram of the subjects were monitored. Results: It is demonstrated that the main pharmacokinetic parameters of analytes in CYP2D6*1/*34 were comparable to CYP2D6*1/*1. The AUC and t1/2 of CYP2D6*10/*87, CYP2D6*10/*95 and CYP2D6*97/*97 increased by 2-3 times comparing to wild-type. The urine metabolic rate of metoprolol in these genotypes were in consistence to the tendencies obtained from plasma samples. Therefore, CYP2D6*1/*34 can be assigned as normal metabolizer, while CYP2D6*10/*87, CYP2D6*10/*95 and CYP2D6*97/*97 were intermediate metabolizers. Although the blood concentration of metoprolol is correlated with genotype of CYP2D6, its blood pressure lowering effect is saturated at the maximum efficacy at 25 mmHg. In addition, the P-Q interval prolongation and heart rate lowing were not positively correlated with metoprolol blood exposure. Conclusion: Based on the PK-PD model, this study clarified the pharmacokinetic and pharmacodynamic characteristics of metoprolol with novel CYP2D6 genotypes, and provided a solid basic data for translational medicine of substrate drug.

We report the case of a 23 years old primiparous woman that was admitted for shortness of breath after seven days post partum. preliminary diagnosis of pulmonary embolism was made. Patient condition worsens and got admitted to ICU without improvement. point of care ultrasounds has completely changed the outcome .

Objective: To determine the role and significance of anatomy in the practice of obstetrics and gynaecology (O&G) and the relationship between the importance of anatomy and the acquisition of anatomical knowledge. Design: Explorative qualitative study. Setting: Belgium and the Netherlands. Population: Twelve gynaecologists and gynaecology trainees. Methods: Semi-structured Interviews including questions on the importance of anatomy in the practice of O&G. Main Outcome: Themes to understand the role of anatomy. Results: The role of anatomy in the practice of O&G lies in three areas: 1. daily activities 2. for the feeling of self-efficacy; 3. to gain a respected name as a doctor. Motivation plays a central role to which extent anatomy knowledge is actually obtained and seems to come quite late during postgraduate training or even while being already a gynaecologist. Stimulating factors for obtaining knowledge are responsibility, patient problems, new techniques and supervisors who pay attention to anatomy. Barriers are found in the feeling of insecurity and the lack of a reference. Conclusions: Although anatomical knowledge plays an important role in gynaecology practice, this importance is frequently not recognized until late in postgraduate training. This may have a negative impact on patient safety, as this late realisation can negatively affect knowledge acquisition. Trainees require reasons for action early in their curricula. Change in trainee motivations and innovations in teaching methods may optimise the process of knowledge acquisition. The overarching goal should be to educate doctors to work safely and with a high degree of self-efficacy.

Seed germination is the first and the most susceptible stage in plant’s growing phases, so could be considered as an index to evaluate the effect of newly developed materials like nanoparticles (NPs), providing useful information for researchers. Germination tests have been carried out in Petri plates, containing wet filter paper and nano-primed seeds. We had biosynthesized seven nanoparticles in our previous researches, including calcinated and non-calcinated zinc oxide, zinc, magnesium oxide, silver, copper and iron nanoparticles. The effect of these biogenic nanoparticles and their counterpart metallic salts including zinc acetate, magnesium sulphate, silver nitrate, copper sulphate and iron (III) chloride was studied on two popularly grown plants, wheat and flax, in laboratory condition to obtain preliminary information for future field experiments. Germination percentage, shoot length, root length, seedlings length, root-shoot ratio, seedling vigor index (SVI), shoot length stress tolerance index (SLSI) and root length stress tolerance index (RLSI) were calculated at 2nd and 7th days of the experiment. According to the results, the response of the plants to metal containing nanoparticles and metal salts mainly depend on type of the metal, plant species, concentration of the NP suspension or salt solution, condition of the exposure and the stage of growth.

The chief goal of this article was to do a literature review on a sensitive topic that has affected many people worldwide. COVID-19 was declared as a pandemic as it crossed all the boundaries. The effects of COVID-19 infection were seen globally, affecting every individual of the society. But here, the main intention was to study the impact of COVID-19 illness in pregnancy since pregnancy is an immune-compromised condition. The effects that had on pregnancy were preterm labor, premature birth, pre-eclampsia, and miscarriages. The other objective was to study the neonatal outcomes, which showed fetal respiratory distress syndrome, Prolonged QT.

Fusion expression is widely employed to enhance the solubility of recombinant proteins. However, removal of the fusion tag is often required due to its potential impact on the structure and activity of passenger proteins. Tobacco etch virus protease (TEV) is widely used for this purpose due to its stringent sequence recognition. In the present work, fusing to acyl carrier protein (ACP) significantly increased the yield of recombinant soluble TEV, and the ACP tag also greatly improved TEV stability. The cleavage activity of TEV was not affected by the ACP fusion tag, and ACP-TEV retained high activity, even at unfavourable pH. Moreover, ACP-TEV could be efficiently modified by co-expressed holo-ACP synthase (AcpS), leading to covalent attachment of the 4’-phosphopantetheine (4’-PP) group to ACP. The long, flexible 4’-PP (sulfhydryl group) displayed high specific reactivity with iodoacetyl groups on the solid support. Thus, TEV could be immobilised effectively and conveniently via the active holo-ACP, and immobilized TEV retained high cleavage activity after a long storage period and several cycles of reuse. As a low-cost and recyclable biocatalyst, TEV immobilised by this method holds promise for biotechnological research and development.

Liner Dextrin (LD) was prepared by waxy potato starch debranched with pullulanse, which has attracted immense interest in food, pharmaceutical and cosmetic industries as a versatile ingredient. These LD were separated on the basis of their differential solubility in aqueous/ethanol solutions of different volumetric ratios. Three LD products F-40, F-50, and F-M were obtained with average DP degree of polymerization values of 31.44, 21.84, 16.10. The results of Fourier transform infrared spectroscopy (FT-IR) analysis reveal that the reaction mainly conclude hydrogen bonding and hydrophobic interaction between LD and insulin in the process of inclusion complexes formation. X-ray diffraction (XRD) results indicate that the insulin is dispersed in the linear dextrin in an amorphous state, which proves that insulin is encapsulated in LD. The results of circular dichroism (CD) show that the changes in the secondary structure of insulin were negligible during the release from the inclusion complexes. The order of encapsulation capacity is F-M-INS> LD-INS> F-50-INS> F-40-INS. F-M-INS inclusion complexes show better effect on reducing the release of insulin in gastric juice and promote the release of insulin in intestinal juice and blood plasma than LD-INS.

Cannabidiol and its potential use by athletesVinicius S. Vaz1 PT, Anderson B. dos Santos1 PT, Priscila K. Morelhão2PhD, Sergio Tufik2 MD PhD, Monica L. Andersen2 PhD and Cynthia Gobbi1 PhD1Universidade Cesumar (UniCesumar), Maringá, Paraná, Brazil.2Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, Brazil.

Background: Growing evidence from observational studies suggests a link between Allergic [rhinitis](https://www.sciencedirect.com/topics/neuroscience/rhinitis) (AR) and psychiatric disorders; whether these associations represent causal relationships remains uncertain. Methods: We performed bi-directional two-sample mendelian randomization (MR) using summary statistics from European genome-wide association studies to examine evidence of causality, specificity and direction of association of AR with 11 different psychiatric disorders or relevant traits. MR was conducted using the inverse-variance weighted method (IVW), MR-Egger and weighted median methods. Sensitivity analyses included the MR-Egger regression and MR pleiotropy residual sum and outlier test. Results: AR from 2 different GWAS data was positively associated with bipolar disorder (OR=1.649, 95% CI: 1.077-2.526; P=0.021; OR=1.599; 95%CI 1.058-2.417; P=0.026). AR was also associated with major depressive disorder (OR=1.539; 95%CI 1.007-2.353; P=0.047). There were no significant association between AR and other 9 psychiatric disorders. Bidirectional analyses showed that bipolar disorder is negatively associated with AR (OR=0.964; 95%CI: 0.936-0.993; P=0.015). There was no evidence for potential causal schizophrenia and effects of attention deficit/hyperactivity disorder on risk of AR by MR method, but, MR pleiotropy residual outlier test suggested that attention deficit/hyperactivity disorder is negatively associated with AR after outlier correction (OR=0.976, 95%CI: 0.958-0.995, P=0.012). Conclusions: This MR study indicated that AR was a causal risk factor for bipolar disorder and major depressive disorder, but not for other psychiatric disorders. Bipolar disorder and attention deficit/hyperactivity disorder may be a protective factor for AR. Further studies could be carried out to leverage these new found insight into better clinical and experimental research in AR and psychiatric disorders.

In this study, DNA barcoding was applied to identify the exact species of fish products from Guangzhou supermarkets and sushi restaurants and to check if these products are correctly labeled. Different samples were analyzed using mitochondrial cytochrome C oxidase subunit I (COI) gene as the target. Our results showed that the CO I gene of all 139 samples examined were successfully amplified by PCR. However when sequenced, 30 samples (21.58%) were mislabeled, in which all the products labeled with “snapper” were actually the low-cost “tilapia”; 11 samples could not be identified (7.91%) and 4 samples failed (2.88%). We also found that the proper label for fish products in sushi restaurants was higher than that in supermarkets. As a simple, rapid and efficient technology, DNA barcoding can be widely used for species identification of fish products. Our work shows that regulation on the labelling of fish products in Guangzhou is needed.

Alopecia is one of the most intolerable side effects of chemotherapy for cancer. Scalp cooling is currently the only way to prevent alopecia due to chemotherapy, but the mechanisms involved in scalp cooling were unclear. The present work reveals a preliminary inhibitory mechanism of scalp cooling on paclitaxel-induced alopecia. Cold stimulation enhanced local vasoconstriction, the vascular diameter presented an oscillating attenuation. The final change rate of blood vessel dimensionless diameter was 0.32 at 22℃. This led to the reduction of chemotherapeutic drugs transported by blood flow and the reduction of drug concentration in scalp. Cooling significantly rescued REK cells with individual chemotherapy drugs, and the lower temperature, the better the protection. Cooling weakened the cytotoxicity of paclitaxel and carboplatin (TC) treatment in some extent. Cells cultured at 22°C resulted in G1 phase arrest. Paclitaxel-treated cells blocked G2 phase and induced cell apoptosis. However, when the cells were treated with paclitaxel at 22°C, the cell cycle returned to normal. The low temperature balanced the effect of paclitaxel on the cell cycle. The cells were treated at 22°C for 2h, the concentration of HSP70 was significantly higher than that of the control group, more than 3 times. Cooling reduced the number of PH3+ and Caspase-3+ cells in the hair follicle, and effectively reduced the cell apoptosis in the hair follicle. These results can be potential to provide a basis for more deeply understanding alopecia prevention with scalp cooling during chemotherapy.

Genes with sex-biased expression are thought to underlie sexually dimorphic phenotypes and are therefore subject to different selection in males and females. Many have proposed that sexual conflict leads to the evolution of sex-biased expression, which resolves conflict and allows males and females to reach separate phenotypic and fitness optima. The strong selection pressures associated with domestication may cause changes in population characteristics and mating systems, which in turn can later the direction and strength of sex-specific selection. We used to compare sex-biased expression and population genomic characteristics in wild and domestic ducks (Anas platyrhynchos). We observed changes in the intensity of sexual selection by measuring sexual size dimorphism and provide an opportunity to identify the genomic divergence affected by relaxed sexual selection. Population genetic analysis shows the extent of sex-biased genes in both sexes is positively correlated with the level of both dN/dS and nucleotide diversity. This observed pattern may mainly be due to genetic constraints rather than sexual selection. We also demonstrate a clear link between domestication and sex-biased evolutionary rate in a comparative framework. Decreased polymorphism and evolutionary rate in domestication breeds generally matched life-history phenotypes known to experience artificial selection. Taken together, our work suggests the important implications of domestication in sex-biased evolution and the roles of artificial selection and sexual selection for shaping the diversity and evolutionary rate of the genome.

Objective: The COVID-19 pandemic is an important cause of morbidity and mortality, which has had a negative impact worldwide. We aimed to contribute to the medical literature by sharing the knowledge and experience of pediatric patients who were diagnosed as having COVID-19 in a one-year period. Method: Patients aged 1 month to 18 years who were diagnosed as having COVID-19 in our clinic, between March 2020 and April 2020, from when COVID-19 was declared as a pandemic, were included in the study. Results: Four hundred sixty-seven children were included in the study. There were 34 (7.3%) patients under one year of age, 111 (23.8%) between 1-5 years, 98 (30.4%) between 5-10 years, 142 (30.4%) between 11-15 years, and 82 (17.6%) age over 15 years. Fever (88.2%), vomiting (32.4%), and diarrhea (29.4%) in patients aged under 1 year, sore throat (36.6%) in patients aged 11-15 years, and dysgeusia (11%), anosmia (14.6%), headache (18.3%), malaise (40.8%), myalgia (28%), and dyspnea (17.1%) in those aged over 15 years of age were found significantly more common compared with the other age groups. Thirty-five (7.5%) patients were asymptomatic, 365 (78.1%) had mild disease, 35 (7.5%) were moderate, 27 (5.8%) were severe, and five (1.07%) were critical. Leukocyte count, erythrocyte sedimentation rate, ferritin, and C-reactive protein values were significantly higher in hospitalized patients. Four patients died during the study period (0.8%, 4/494). Conclusion: Although COVID-19 has an asymptomatic and mild course in children, it should be kept in mind that it may have a severe course.

Anthracycline antibiotics are among the most effective antineoplastic agents. However, despite their high efficacy in the treatment of various types of cancer, their administration is limited primarily because they exhibit myocardial toxicity. This may be a limiting factor in the dosage of medications; nevertheless, drugs exhibiting this mechanism of action constitute a very important group of chemotherapeutics. One of the more widely studied antibiotics from the anthracycline group is doxorubicin. It exhibits the highest antineoplastic activity from among a number of derivative compounds. Because of the adverse effects of doxorubicin, especially cardiotoxicity, it is important to maintain control of its concentration in body fluids. The aim of the presented work is a method for rapid, simple and accurate determination of the level of doxorubicin in blood and plasma using spectrophotometric methods. The method consists in the study of the absorbance of light in the visible light range in a DOX solution with respect to a reference sample. Characteristic peaks are selected from the absorbance spectrum, and for those peaks the wavelength at which maximum absorption occurs is determined. The concentration of the analyte is determined by comparison with the calibration curve.

The response of photosynthetic CO2 assimilation to changes of illumination affects plant growth and crop productivity under natural fluctuating light conditions. However, the effects of nitrogen (N) supply on photosynthetic physiology after transition from low to high light are seldom studied. To elucidate this, we measured gas exchange and chlorophyll fluorescence under fluctuating light in tomato (Solanum lycopersicum) seedlings grown with different N conditions. After transition from low to high light, the induction speeds of net CO2 assimilation (AN), stomatal conductance (gs) and mesophyll conductance (gm) delayed with the decline in leaf N content. The times to reach 90% of maximum AN, gs and gm were negatively correlated to leaf N content. This delayed photosynthetic induction in plants grown under low N concentration was mainly caused by the slow induction response of gm rather than that of gs. Furthermore, the photosynthetic induction upon transfer from low to high light was hardly limited by photosynthetic electron flow. These results indicate that decreased leaf N content declines carbon gain under fluctuating light in tomato. Increasing the induction kinetics of gm has the potential to enhance the carbon gain of field crops grown in infertile soil.

Aims: A high baseline hepatitis B virus (HBV) load has always been listed as an exclusion criterion for programmed cell death-1 (PD-1) inhibitor-associated therapy in clinical trials, as the interaction between HBV load and anti-PD-1/PD-L1 therapy remains controversial. Methods: We performed a retrospective cohort study of unresectable HCC patients who were seropositive for HBsAg and accepted tenofovir alafenamide fumarate (TAF) therapy before anti-PD-1 in combination with an antiangiogenic treatment. Patients were divided into a low HBV DNA group (≤ 2000 IU/ml) and a high HBV DNA group (> 2000 IU/ml) according to the baseline HBV DNA levels. Tumour response and progression-free survival (PFS) were compared, and univariate and multivariate Cox analyses were performed to identify potential risk factors for PFS. The incidences of HBV reactivation and HBV-associated hepatitis were also recorded. Results: Seventy eligible patients were included: 48 in the low group and 22 in the high group. The objective response rates (ORRs), disease control rates (DCRs), and PFS did not differ significantly between the two groups (P = 0.761, 0.552, and 0.784, respectively). The results of Cox analyses revealed that the baseline HBV load did not affect PFS. Additionally, HBV reactivation occurred in only 2 patients (2.9%), and no patient experienced HBV-related hepatic impairment when given a continuous TAF treatment. Conclusions: Baseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with an antiangiogenic therapy, while PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment in patients simultaneously subjected to TAF prophylaxis.

Rapid-onset hyponatremia as well as rhabdomyolysis are rare, but potential, complications of olanzapine treatment. Hyponatremia, secondary to atypical antipsychotic use, has been reported in many case reports and is thought to be associated with a syndrome of inappropriate anti-diuretic hormone secretion (SIADH). We report a case of sudden-onset hyponatremia associated to a sever rhabdomyolysis resulting in a coma necessitating intensive care unit admission. His evolution was favorable after correction of all his metabolic disorders and Olanzapine suspension.