Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Withdrawal time in excellent or very poor bowel preparation qualities

AIM: To evaluate association(s) between withdrawal time and polyp detection in various bowel preparation qualities. METHODS: Retrospective cohort analysis of screening colonoscopies performed between January 2005 and June 2011 for patients with average risk of colorectal cancer. Exclusion criteria included patients with a personal history of adenomatous polyps or colon cancer, prior colonic resection, significant family history of colorectal cancer, screening colonoscopy after other abnormal screening tests such as flexible sigmoidoscopy or barium enema, and screening colonoscopies during in-patient care. All procedures were performed or directly supervised by gastroenterologists. Main measurements were number of colonic segments with polyps and total number of colonic polyps.RESULTS: Multivariate analysis of 8331 colonosco-pies showed longer withdrawal time was associated with more colonic segments with polyps in good(adjusted OR = 1.16; 95%CI: 1.13-1.19), fair(OR = 1.13; 95%CI: 1.10-1.17), and poor(OR = 1.18; 95%CI: 1.11-1.26) bowel preparation qualities. A higher number of total polyps was associated with longer withdrawal time in good(OR = 1.15; 95%CI: 1.13-1.18), fair(OR = 1.13; 95%CI: 1.10-1.16), and poor(OR = 1.20; 95%CI: 1.13-1.29) bowel preparation qualities. Longer withdrawal time was not associated with more colonic segments with polyps or greater number of colonic polyps in bowel preparations with excellent(OR = 1.07, 95%CI: 0.99-1.26; OR = 1.11, 95%CI: 0.99-1.24, respectively) and very poor(OR = 1.02, 95%CI: 0.99-1.12; OR = 1.05, 95%CI: 0.99-1.10, respectively) qualities.CONCLUSION: Longer withdrawal time is not associated with higher polyp number detected in colonoscopies with excellent or very poor bowel preparation quality.

A Production Inventory Model with Shortages, Fuzzy Preparation Time and Variable Production and Demand

A production inventory model is formulated for a single item. Here, demand varies with the on-hand inventory level and production price. Shortages are allowed and fully backlogged. The time gap between the decision and actual commencement of production is termed as “preparation time” and is assumed to be crisp/imprecise in nature. The set-up cost depends on preparation time. The fuzzy preparation time is reduced to a crisp interval preparation time using nearest interval approximation and following the interval arithmetic, the reduced problem is converted to a multi-objective optimization problem. Mathematical analysis has been made for single objective crisp model (Model-I). Numerical illustration have been made for both crisp (Model-I) and fuzzy (Model-II) models. Model-I is solved by generalized reduced gradient technique and multi-objective model (Model-II) by Global Criteria Method. Sensitivity analyses have been made for some parameters of Model-I.

Comparing the Efficiency of Manual and Electronic Tender Document Preparation: Cost and Time Context

In Bangladesh, both manual and e-GP system is used to perform public procurement. Before tender publication, tender documents have to be prepared by the Procurement Entities (PEs). The problem is that the manual tendering system involves more cost and time in preparing tender documents. The study’s purpose is to compare now the efficiency of tender document preparation in the manual system with the e-GP system. This study tests the cost and time involved in tender document preparation, both manual and e-procurement tenders. Sample data was collected from the 11 RHD zones. Structured survey questionnaires were used to collect primary data from the PE officers of RHD. A hypothesis test was performed using the model of independent samples t-test. The test results indicated that e-Procurement tender document preparation costs and time were less than manual tendering. Academicians, researchers, PE officers, and policymakers will benefit from the study’s conclusions.

Achieving the best bowel preparation for colonoscopy

Bowel preparation is a core issue in colonoscopy,as it is closely related to the quality of the procedure.Patients often find that bowel preparation is the most unpleasant part of the examination.It is widely accepted that the quality of cleansing must be excellent to facilitate detecting neoplastic lesions.In spite of its importance and potential implications,until recently,bowel preparation has not been the subject of much study.The most commonly used agents are high-volume polyethylene glycol(PEG)electrolyte solution and sodium phosphate.There has been some confusion,even in published meta-analyses,regarding which of the two agents provides better cleansing.It is clear now that both PEG and sodium phosphate are effectivewhen administered with proper timing.Consequently,the timing of administration is recognized as one of the central factors to the quality of cleansing.The bowel preparation agent should be administered,at least in part,a few hours in advance of the colonoscopy.Several low volume agents are available,and either new or modified schedules with PEG that usually improve tolerance.Certain adjuvants can also be used to reduce the volume of PEG,or to improve the efficacy of other agents.Other factors apart from the choice of agent can improve the quality of bowel cleansing.For instance,the effect of diet before colonoscopy has not been completely clarified,but an exclusively liquid diet is probably not required,and a low-fiber diet may be preferable because it improves patient satisfaction and the quality of the procedure.Some patients,such as diabetics and persons with heart or kidney disease,require modified procedures and certain precautions.Bowel preparation for pediatric patients is also reviewed here.In such cases,PEG remains the most commonly used agent.As detecting neoplasia is not the main objective with these patients,less intensive preparation may suffice.Special considerations must be made for patients with inflammatory bowel disease,including safety and diagnostic issues,so that the most adequate agent is chosen.Identifying neoplasia is one of the main objectives of colonoscopy with these patients,and the target lesions are often almost invisible with white light endoscopy.Therefore excellent quality preparation is required to find these lesions and to apply advanced methods such as chromoendoscopy.Bowel preparation for patients with lower gastrointestinal bleeding represents a challenge,and the strategies available are also reviewed here.

Prospective evaluation of small bowel preparation with bisacodyl and sodium phosphate for capsule endoscopy

AIM： To determine the effect of Prepacol, a combination of sodium phosphate and bisacodyl, on transit and quality of capsule endoscopy （CE）. METHODS： Fivety two consecutive patients were included in this prospective study. CE was performed following a 12 h fasting period. Twenty six patients were randomized for additional preparation with Prepacol. The quality of CE was assessed separately for the proximal and the distal small bowel by 3 experienced endoscopists on the basis of a graduation which was initially developed with 20 previous CE. RESULTS： Preparation with Prepacol accelerated small bowel transit time （262 ± 55 rain vs 287 ± 97 min）, but had no effect on the quality of CE. Visibility was significantly reduced in the distal compared to the proximal small bowel. CONCLUSION： The significantly reduced visibility of CE in the distal small bowel allocates the need for a good preparation. Since Prepacol has no beneficial effect on CE the modality of preparation and the ideal time of application remains unclear. Further standardized examinations are necessary to identify sufficient preparation procedures and to determine the impact of the volume of the preparation solution.

Efficiency of bowel preparation for capsule endoscopy examination:A meta-analysis

Good preparation before endoscopic procedures is essential for successful visualization. The small bowel is difficult to evaluate because of its length and complex configuration. A meta-analysis was conducted of studies comparing small bowel visualization by capsule endoscopy with and without preparation. Medical data bases were searched for all studies investigating the preparation for capsule endoscopy of the small bowel up to July 31, 2007. Studies that scored bowel cleanness and measured gastric and small bowel transit time and rate of cecum visualization were included. The primary endpoint was the quality of bowel visualization. The secondary endpoints were transit times and proportion of examinations that demonstrated the cecum, with and without preparation. Meta-analysis was performed with StatDirect Statistical software, version 2.6.1 (http:// statsdirect.com). Eight studies met the inclusion criteria. Bowel visualization was scored as "good" in 78% of the examinations performed with preparation and 49% performed without (P < 0.0001). There were no significant differences in transit times or in the proportion of examinations that demonstrated the cecum with and without preparation. Capsule endoscopy preparation improves the quality of small bowel visualization, but has no effect on transit times, or demonstration of the cecum.

Protective effects of kidney-tonifying Chinese herbal preparation on substantia nigra neurons in a mouse model of Parkinson's disease

The Chinese herbs Herba Epimedii, Fructus Ligustri Lucidi and Rhizoma Polygonati were injected into Parkinson＇s disease mice established via intraperitoneal injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine hydrochloride. The selective monoamine oxidase B inhibitor selegiline was used as a positive control drug. After successive administration for 4 weeks, Herba Epimedii could downregulate the expression of caspase-3 and increase the brain-derived neurotrophic factor level, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson＇s disease mouse models. Rhizoma Polygonaticould downregulate the expression of caspase-3 and FasL, and increase neural growth factor and brain-derived neurotrophic factor levels. Fructus Ligustn Lucidi could downregulate caspase-3 expression. Rhizoma Polygonati and Fructus Ligustn Lucidi did not produce obvious effects on tyrosine hydroxylase activity. Herba Epimedii and Fructus Ligustri Lucidi yielded similar effects on apoptosis-promoting factors to those elicited by selegiline. Herba Epimedii and Rhizoma Polygonati significantly increased the levels of neurotrophic factors compared with selegiline. Herba Epimedii significantly increased tyrosine hydroxylase activity compared with selegiline. It is indicated that the kidney-tonifying Chinese herbal preparation can downregulate the expression of apoptosis-promoting factors, increase neurotrophic factors levels in the substantia nigra and striatum, as well as increase tyrosine hydroxylase activity in the substantia nigra of Parkinson＇s disease mouse models, thereby exerting a stronger or similar neuroprotective effects compared with selegiline.

Emerging space for non-polyethene-glycol bowel preparations in inflammatory bowel disease-related colonoscopy:Veering toward better adherence and palatability

Patients with inflammatory bowel diseases(IBDs)require repeated endoscopic evaluations over time by colonoscopy to weigh disease activity but also for different and additional indications(e.g.,evaluation of postoperative recurrence,colorectal cancer surveillance).Colonoscopy,however,requires adequate bowel preparation to be of quality.The latter is achieved as long as the patient takes a certain amount of product to have a number of bowel movements suitable to clean the colon and allow optimal visualization of the mucosa during endoscopy.However,significant guidelines recommend preparations for patients with IBD not excelling in palatability.This recommendation originates from the fact that most of the studies conducted on bowel preparations in patients with IBD have been done with isosmolar preparations based on polyethylene glycol(PEG),for which,therefore,more safety data exist.As a result,the low-volume non-PEG preparations(e.g.,magnesium citrate plus picosulphate,oral sulphate solutions)have been set aside for the whole range of warnings to be heeded because of their hyperosmolarity.New studies,however,are emerging,leaning in overall for a paradigm shift in this matter.Indeed,such non-PEG preparations seem to show a particularly encouraging and engaging safety profile when considering their broad potential for tolerability and patient preference.Indeed,such evidence is insufficient to indicate such preparations in all patients with IBD but may pave the way for those with remission or well-controlled disease.This article summarizes the central studies conducted in IBD settings using non-PEG preparations by discussing their results.

Quality of bowel preparation in patients with inflammatory bowel disease undergoing colonoscopy:What factors to consider?

An adequate bowel preparation in patients with inflammatory bowel disease(IBD)is a prerequisite for successful colonoscopy for screening,diagnosis,and surveillance.Several bowel preparation formulations are available,both high-and low-volume based on polyethylene glycol.Generally,low-volume formulations are also based on several compounds such as magnesium citrate preparations with sodium picosulphate,oral sulphate solution,and oral sodium phosphatebased solutions.Targeted studies on the quality of bowel preparation prior to colonoscopy in the IBD population are still required,with current evidence from existing studies being inconclusive.New frontiers are also moving towards the use of alternatives to anterograde ones,using preparations based on retrograde colonic lavage.

Preparation and Inhibitory Effects of 20(S)-Ginsenoside Rh_2 on Hep-A-22 Cells

A modified method of preparing 20（S）-ginsenoside Rh2（G-Rh2） and the inhibitory effect of 20（S）-ginsenoside Rh2 on Hep-A-22 cells were investigated. The total saponins and strong alkali were dissolved in glycerol at the atmospheric pressure, and the degradation was performed at a high temperature. After G-Rh2 had been isolated and purified, MTT（methyl thiazolyl tetrazolium） assay was applied to evaluating the effect of 20（S）-ginsenoside Rh2 on the cells viability and morphological changes were observed. It was shown that 20（S）-ginsenoside Rh2 can reduce Hep-A-22 cells viability in dose-dependent manner and the cells took on cell shrinkage, membrane blebbing, chromosomal condensations, especially under the higher concentrations of it. In conclusion, 20（S）-ginsenoside Rh2 can be prepared effectively that not only decreases viability but also induces the apoptosis of Hep-A-22 cells.

In-situ measurement of the dissolved S^(2-) in seafloor diffuse flow system: sensor preparation and calibration

The preparation approach and calibration result of an improved type of ion selective electrode （ISE）, which is used to measure the total dissolved S^2-, are introduced in this paper. The improved Ag/Ag2S electrode uses silver wire as the substrate, which is surrounded by electric polymer containing superfine silver powder. After the stabilization of the epoxy-resin, Ag2S layer was formed by chemical reaction with 0.2 mol/L （NH4）2S solution for 5 min. With Ag/AgC1 as reference electrode, the Ag/Ag2S electrode can be used to measure dissolved S^2-. The correlation between the measured potentials and the logarithm of dissolved S^2- is found to be linear, within range of the concentration of dissolved S^2- from 10^-2-10-7 mol/L. The slope of the regression line between measured potential and logarithm of dissolved S^2- is about -27.7, which agrees well with the theoretical Nernst value -29.6. Furthermore, the performance of the improved Ag/Ag2S electrode, such as the response time, sensitivity and stability, greatly outweighs the conventional Ag/Ag2S electrode.

Bandgap engineering of hierarchical network-like SnIn4S8 microspheres through preparation temperature for excellent photocatalytic performance and high stability

The effect of synthesis temperature and reaction time on the visible-light photocatalytic activity of hierarchical network-like SnIn4S8 microspheres was investigated by the low-temperature co-precipitation strategy. The preparation temperature and reaction time have great influence on the photocatalytic activity of SnIn4S8, and the optimal preparation temperature and reaction time are 70℃ and 3 h, respectively.The SnIn4S8 shows good reusability and high stability with no observable decrease of photocatalytic activity in five consecutive cycles.

Preparation of Single Crystals of Co_xZn_(1-x)S and Co_xZn_(1-x)Se—New Materials of Dilute Magnetic Semiconductors

In this paper, we report the growth of single crystals of Co_x Zn_(1-x)S and Co_x Zn_(1-x)Se (0<x<0.3) by the method of chemical transport, using iodine as a transport agent. The light green color of single crystal Co_xZn_(1-x)S as well as the light brown color of Co_xZn_(1-x)Se become deep with an increase in x. The compositions of the single crystals were nearly stoichiometric. The transfer rate decreases with an increase of the x value. The growth rate was related to the temperature difference. The large temperature difference speed up the growth rate, but the size of crystal obtained was small. In general, the optimal temperature difference was 15℃. From X-ray diffraction measurements, the structures of crystals Co_xZn_(1-x)S and Co_xZn_(1-x)Se (0<x<0.1) were identified to be zinc blende structure similar to that of ZnS and ZnSe.

“Buyi Ganshen”,a traditional Chinese medicine treatment,combined with dopa preparation for Parkinson’s disease therapy:a meta-analysis of randomized controlled trials

Traditional Chinese medicine Buyi Ganshen therapy combined with dopa preparation in the therapy of Parkinson’s disease could enhance the clinical safety and efficacy compared with dopa preparation along.The exact mechanism of how Buyi Ganshen works combined with dopa preparation still unknown and the enrolled articles quality was relatively inadequate,yet it could provide the reference in the clinical application and further studies.Background:To research the influence of“Buyi Ganshen”,a traditional Chinese medicine that commonly used in“Tonifying the Liver and the Kidney”,added dopa preparation for the therapy of Parkinson’s disease.Methods:This meta-analysis examined existing literature by searching 7 electronic databases(CNKI,WanFang,EMBASE,PubMed,Medline,the Cochrane Library,and the VIP database)from inception to December 2019.Randomized controlled trials evaluating the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease were identified.The main results were clinical efficacy,UPDRS I(mental score),total unified Parkinson’s disease ratingscale score,UPDRS III(motor score),UPDRS II(activities of daily life),and UPDRS IV(complications of treatment).The subordinate results were the SPOCA-AUT scores,traditional Chinese medicine syndromes and other adverse reactions.The Review Manager 5.3 software was used to calculate the pooled estimate effect.The outcomes were showed as relative ratio with 95%confidence interval.The fixed or random model was elected based on the level of homogeneity among researches.The I2 was used to detected heterogeneity.The quality of the researches was also assessed.Results:The meta-analysis include 2,241 individuals from a total of 30 studies.These data suggested that the therapy of Parkinson’s disease with the combination of“Buyi Ganshen”and dopa preparation were more effective compared to dopa preparation alone.Conclusion:“Buyi Ganshen”combined with dopa preparation exists,in some degree,to enhance clinical safety and effectiveness in the cure of Parkinson’s disease,compared with dopa preparation along.As most of the studies included were with low quality,this conclusion must be considered with caution.Thus,more multi-center,high-quality,prospective randomized controlled trials with large enough sample sizes are required to further illuminate the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease.

Preparation of an imaging agent for cerebral muscarinic acetylcholine receptor, (R,S)(131)~I-QNB

The method to synthesize a high affinity muscarinic receptor antagonist (R,S)I-QNB[(R)-(-)-1-azabicyclo [2,2,2]oct-3-yl-(S)-(+)-α-hydroxy-α-(4-[127I]iodophenyl)-α-phenyl acetate] from 4-nitrobenzophenone with improvement compared to literatures was reported in this article. IR, MS and 1HNMR characterized the final product. (R,S)131I-QNB was prepared using Cu(I) assisted iodine exchange labeling, and showed by TLC that the radiolabeling yield(RLY) was over 80%, and radiochemical purity(RCP) was over 95%. Stability of the labeled compound was also determined. It was found that (R,S)131I-QNB dried by nitrogen blowing can stay at 4-10℃ for a week without change of RCP.

In-situ preparation of Cu-BTC modified with organic amines for H_(2)S removal under ambient conditions

Amine modification is an effective strategy to improve the H_(2)S removal performance of Cu-BTC.In order to avoid the problem of pore blockage after amine modification in post synthesis impregnation,herein a series of Cu-BTC modified with organic amine adsorbents were prepared via an in-situ one-pot method and the H_(2)S removal performance under ambient conditions was tested.It is found that the introduced organic amines,depending on the types of amine selected,have a significant influence on the growth of Cu-BTC and its textural properties.The H_(2)S removal performance on the as-prepared materials suggested that the amine modified samples remarkably improved the H_(2)S removal capacities with an order of BA-Cu-BTC>TEA-Cu-BTC>TEOA-Cu-BTC>Cu-BTC.Besides the enlarged surface area and the increased mesopores volumes,BA has the advantages of smaller steric hindrance and-NH_(2)groups,among which the former increased the accessibility of Cu active sites while the latter acted as additional active sites for H_(2)S capturing,thus affording BA-Cu-BTC highest breakthrough capacity of 77.3 mg S/g.Overall,this study elaborates the effect of organic amines in-situ modification on the Cu-BTC structure and desulfurization.

Real-Time Information System of Power Plant Based on B/S Computing Mode

This paper introduces the system structure and work principle of the upgraded real time information system in Wangting Power Plant, and then expounds the realization way and function features of this system on B/S computing mode. The results of field application show the new system has good capability, reliability and expandability.

NEURAL NETWORK SMITH PREDICTIVE CONTROL FOR TELEROBOTS WITH TIME DELAY

A neural network Smith predictive control strategy is proposed to deal with inpu t and feedback time delays in telerobot systems. The delay time is assumed to b e invariant and unknown. The proposed control structure consists of a slave syst em and a master controller. In the slave system, a recurrent neural network (RNN ) with on-line weight tuning algorithm is employed to approximate the dynamics of the time-delay-free nonlinear plant, which is used to linearize the slave s ystem. The master controller is a Smith predictor for the linearized slave syste m, which provides prediction and maintains the desirable tracking performance. S tability propriety is guaranteed based on the Lyapunov method. A simulation of a two-link robotic manipulator is provided to illustrate the effectiveness of th e proposed control strategy.

FUZZY ROBUST H_∞ CONTROL OF UNCERTAIN NONLINEAR SYSTEM WITH TIME-DEALY

This paper addresses the problem of the fuzzy H ∞state feedback control for a class of uncertain nonlinear systems with time delay. The Takagi Sugeno (T S) mo del with time delay and parameter uncertainties is adopted for modeling of nonlinear system. The systematic design procedure for the fuzzy robust controller based on linear matrix inequality (LMI) is given. Some sufficient conditions are derived for the existence of fuzzy H ∞ state feedback controllers such that the closed loop system is asymptotically stable and the effect of the disturbance input on controlled output is reduced to a prescribed level. An example is given to demonstrate the effectiveness of the proposed method.