Vascular endothelial growth factor:a double-edged sword in the development of white matter lesions

As the population ages,the burden of age-related diseases becomes greater.Currently,over 55 million people suffer from dementia worldwide,with Alzheimer’s disease being the most common form.However,it is becoming clearer that underlying vascular pathology such as cerebral small vessel disease(cSVD)may be a more detrimental cause for dementia(Cuadrado-Godia et al.,2018).It is estimated that 10%-30%of the elderly population and 35%-90%of all dementia patients exhibit signs of cSVD.The term cSVD refers to pathology affecting the small vessels of the brain,which can lead to lacunar cerebral infarcts,enlarged perivascular spaces,and cortical hemorrhages(Cuadrado-Godia et al.,2018).CSVD is often associated with cognitive decline,gait problems,and dementia(Cuadrado-Godia et al.,2018).

Novel insights in phosphodiesterase 4 subtype inhibition to target neuroinflammation and stimulate remyelination

In neurodegenerative and classically demyelinating disorders such as multiple sclerosis(MS),spinal cord injury(SCI),stroke,and Charcot-Marie-Tooth disease,glial functioning is compromised and nervous tissue integrity is lost.Recently,primary neurodegenerative disorders such as Alzheimer’s disease,amyotrophic lateral sclerosis(ALS),and Parkinson’s disease(PD)are increasingly linked to impaired oligodendroglia functioning upon neurodegeneration.Due to the destructive micro-environment created by nervous tissue damage,the progressive cellular loss in these disorders,and the amitotic nature of neurons,spontaneous endogenous repair process are limited in nature.Hence,there is a medical need for efficient therapeutic strategies capable of supporting neuro-reparative processes to occur,likely supported by improved oligodendroglia cell functioning.

A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL 5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm^(2).Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm^(2)),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide“click”chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.

Artificial intelligence for characterization of diminutive colorectal polyps:A feasibility study comparing two computer-aided diagnosis systems

BACKGROUND Artificial intelligence(AI)has potential in the optical diagnosis of colorectal polyps.AIM To evaluate the feasibility of the real-time use of the computer-aided diagnosis system(CADx)AI for ColoRectal Polyps(AI4CRP)for the optical diagnosis of diminutive colorectal polyps and to compare the performance with CAD EYE^(TM)(Fujifilm,Tokyo,Japan).CADx influence on the optical diagnosis of an expert endoscopist was also investigated.METHODS AI4CRP was developed in-house and CAD EYE was proprietary software provided by Fujifilm.Both CADxsystems exploit convolutional neural networks.Colorectal polyps were characterized as benign or premalignant and histopathology was used as gold standard.AI4CRP provided an objective assessment of its characterization by presenting a calibrated confidence characterization value(range 0.0-1.0).A predefined cut-off value of 0.6 was set with values<0.6 indicating benign and values≥0.6 indicating premalignant colorectal polyps.Low confidence characterizations were defined as values 40%around the cut-off value of 0.6(<0.36 and>0.76).Self-critical AI4CRP’s diagnostic performances excluded low confidence characterizations.RESULTS AI4CRP use was feasible and performed on 30 patients with 51 colorectal polyps.Self-critical AI4CRP,excluding 14 low confidence characterizations[27.5%(14/51)],had a diagnostic accuracy of 89.2%,sensitivity of 89.7%,and specificity of 87.5%,which was higher compared to AI4CRP.CAD EYE had a 83.7%diagnostic accuracy,74.2%sensitivity,and 100.0%specificity.Diagnostic performances of the endoscopist alone(before AI)increased nonsignificantly after reviewing the CADx characterizations of both AI4CRP and CAD EYE(AI-assisted endoscopist).Diagnostic performances of the AI-assisted endoscopist were higher compared to both CADx-systems,except for specificity for which CAD EYE performed best.CONCLUSION Real-time use of AI4CRP was feasible.Objective confidence values provided by a CADx is novel and self-critical AI4CRP showed higher diagnostic performances compared to AI4CRP.

Scoping review on health-related physical fitness in patients with inflammatory bowel disease:Assessment,interventions,and future directions

BACKGROUND Reaching the Selecting Therapeutic Targets in Inflammatory Bowel Disease-II(STRIDE-II)therapeutic targets for inflammatory bowel disease(IBD)requires an interdisciplinary approach.Lifestyle interventions focusing on enhancing and preserving health-related physical fitness(HRPF)may aid in improving subjective health,decreasing disability,or even controlling inflammation.However,ambiguity remains about the status and impact of HRPF(i.e.body composition,cardiorespiratory fitness,muscular strength,muscular endurance,and flexibility)in IBD patients,hindering the development of physical activity and physical exercise training guidelines.AIM To review HRPF components in IBD patients and the impact of physical activity and physical exercise training interventions on HRPF.METHODS A systematic search in multiple databases was conducted for original studies that included patients with IBD,assessed one or more HRPF components,and/or evaluated physical activity or physical exercise training interventions.RESULTS Sixty-eight articles were included.No study examined the complete concept of HRPF,and considerable heterogeneity existed in assessment methods,with frequent use of non-validated tests.According to studies that used gold standard tests,cardiorespiratory fitness seemed to be reduced,but findings on muscular strength and endurance were inconsistent.A limited number of studies that evaluated physical activity or physical exercise training interventions reported effects on HRPF,overall showing a positive impact.CONCLUSION We performed a scoping review using a systematic and iterative approach to identify and synthesize an emerging body of literature on health-related physical fitness in patients with IBD,highlighting several research gaps and opportunities for future research.Findings of this review revealed a gap in the literature regarding the accurate assessment of HRPF in patients with IBD and highlighted important methodological limitations of studies that evaluated physical activity or physical exercise training interventions.This scoping review is a step towards performing studies and systematic reviews in the future,which was not possible at present given the heterogeneity in endpoints and designs of the available studies on this topic.Future well-designed studies are required to determine the optimal training paradigm for improving HRPF in patients with IBD before guidelines can be developed and integrated into the therapeutic strategy.

Long-term efficacy of a computer-tailored physical activity intervention for prostate and colorectal cancer patients and survivors:A randomized controlled trial

Background Physical activity(PA)can improve the physical and psychological health of prostate and colorectal cancer survivors,but PA behavior change maintenance is necessary for long-term health benefits.OncoActive is a print-and web-based intervention in which prostate and colorectal cancer patients and survivors receive automatically generated,personalized feedback aimed at integrating PA into daily life to increase and maintain PA.We evaluated the long-term outcomes of OncoActive by examining the 12-month follow-up differences between OncoActive and a control group,and we explored whether PA was maintained during a 6-month non-intervention follow-up period.Methods Prostate or colorectal cancer patients were randomly assigned to an OncoActive(n=249)or a usual care waitlist control group(n=229).OncoActive participants received PA advice and a pedometer.PA outcomes(i.e.,ActiGraph and self-report moderate-to-vigorous intensity PA(MVPA)min/week and days with≥30 min PA)and health-related outcomes(i.e.,fatigue,depression,physical functioning)were assessed at baseline,6 months,and 12 months.Differences between groups and changes over time were assessed with multilevel linear regressions for the primary outcome(ActiGraph MVPA min/week)and all additional outcomes.Results At 12 months,OncoActive participants did not perform better than control group participants at ActiGraph MVPA min/week,self-report MVPA min/week,or ActiGraph days with PA.Only self-report days with PA were significantly higher in OncoActive compared to the control group.For health-related outcomes only long-term fatigue was significantly lower in OncoActive.When exploratively examining PA within OncoActive,the previously found PA effects at the end of the intervention(6 months follow-up)were maintained at 12 months.Furthermore,all PA outcomes improved significantly from baseline to 12 months.The control group showed small but non-significant improvements from 6 months to 12 months(and from baseline to 12 months),resulting in a decline of differences between groups.Conclusion The majority of previously reported significant between-group differences at 6 months follow-up were no longer present at long-term follow-up,possibly because of natural improvement in the control group.At long-term follow-up,fatigue was significantly lower in OncoActive compared to control group participants.Computer-tailored PA advice may give participants an early start toward recovery and potentially contributes to improving long-term health.

Local digital lending development and the incidence of deprivation in Kenya

In the developing world,vulnerable communities often lack access to regular income sources to cope with unforeseen events.Recent advancements in financial technology have enabled microcredit to be delivered via digital platforms.Although digital credit may quicken remote access to consumer credit without the need for collateral,little is known about its contribution to the welfare of underserved communities.This study examines the effects of local digital lending development on deprivation and explores the implications of these effects on rural inhabitants.The results show a negative association between local digital lending development and food deprivation on one hand and health deprivation on the other.The evidence suggests that local digital lending development can reduce the probability of food and health deprivation.Furthermore,the evidence reveals that inhabitants of rural communities benefit more from digital lending development.This study recommends the decentralization of financial inclusion policies as a pathway to promote digital lending at the local level.

A perspective on causality assessment in epigenetic research on neurodegenerative disorders

Epigenetics refers to herita ble and reversible processes regulating gene expression that do not involve a change to the DNA sequence.Epigenetic modifications include DNA modifications(e.g.DNA methylation a nd hydroxymethyl at ion),histone modifications,and non-coding RNAs such as micro RNAs and long-coding RNAs(Holtzman and Gersbach.

Cost-effectiveness of patient specific vs conventional instrumentation for total knee arthroplasty:A systematic review and meta-analysis

BACKGROUND Over the past years,patient specific instrumentation(PSI)for total knee arthroplasty(TKA)has been implemented and routinely used.No clear answer has been given on its associated cost and cost-effectiveness when compared to conventional instrumentation(CI)for TKA.AIM To compare the cost and cost-effectiveness of PSI TKA compared to CI TKA.METHODS A literature search was performed in healthcare,economical healthcare,and medical databases(MEDLINE,EMBASE,CINAHL,Web of Science,Cochrane Library,EconLit).It was conducted in April 2021 and again in January 2022.Relevant literature included randomised controlled trials,retrospective studies,prospective studies,observational studies,and case control studies.All studies were assessed on methodological quality.Relevant outcomes included incremental cost-effectiveness ratio,quality-adjusted life years,total costs,imaging costs,production costs,sterilization associated costs,surgery duration costs and readmission rate costs.All eligible studies were assessed for risk of bias.Meta-analysis was performed for outcomes with sufficient data.RESULTS Thirty-two studies were included into the systematic review.Two were included in the metaanalysis.3994 PSI TKAs and 13267 CI TKAs were included in the sample size.The methodological quality of the included studies,based on Consensus on Health Economic Criteria-scores and risk of bias,ranged from average to good.PSI TKA costs less than CI TKA when considering mean operating room time and its associated costs and tray sterilization per patient case.PSI TKA costs more compared to CI TKA when considering imaging and production costs.Considering total costs per patient case,PSI TKA is more expensive in comparison to CI TKA.Meta-analysis comparing total costs for PSI TKA,and CI TKA showed a significant higher cost for PSI TKA.CONCLUSION Cost for PSI and CI TKA can differ when considering distinct aspects of their implementation.Total costs per patient case are increased for PSI TKA when compared to CI TKA.

Retinal microvascular and microstructural alterations in the diagnosis of meibomian gland dysfunction in severely obese population:a new approach

AIM:To study retinal microvascular and microstructural alterations in meibomian gland dysfunction(MGD)in severely obese population using optical coherence tomography angiography(OCTA).METHODS:Twelve MGD patients with severely obese population(PAT group;24 eyes)and 12 healthy controls(HC group;24 eyes)were recruited.OCTA images were segmented into five[superior(S),nasal(N),inferior(I),temporal(T),and central foveal(C)]or nine[inner superior(IS),outer superior(OS),inner nasal(IN),outer nasal(ON),inner inferior(II),outer inferior(OI),inner temporal(IT),outer temporal(OT),and C]subregions.The superficial vessel density(SVD),retinal thickness(RT),foveal avascular zone(FAZ)parameters,and retinal volume were measured.RESULTS:Visual acuity was significantly different between two groups(0.8±0.17 in PAT group vs 0.2±0.06 in HC group).SVD was significantly lower in PATs in N,T,OS,IN,OT,and ON.The area under the receiver operating characteristic curve(AUC)for T was 0.961[95% confidence interval(CI):0.908 to 1.000],for OS was 0.962(95%CI:0.915 to 1.000).RT was significantly lower in PATs in IS,OS,OI,OT,ON,IT,IN,and II.AUC for OT was 0.935(95%CI:0.870 to 0.999),for IS was 0.915(95%CI:0.838 to 0.992).Angiography results showed significantly lower area and perimeter of FAZ,SVD of the inner retina and both retinal volume and the average volume thickness in the PAT group.CONCLUSION:Vision may be affected in patients with MGD due to changes in retinal microvessels and microstructures.These changes detected by OCTA may be a potential marker for diagnosing MGD in severe obesity.

COVID-19 and liver injury in individuals with obesity

Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations,including liver damage commonly detected by a hepatocellular pattern from liver function tests.Liver injury is associated with a worse prognosis overall.Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities,which are also associated with nonalcoholic fatty liver disease(NAFLD).The presence of NAFLD,similarly to obesity,is associated with an unfavourable impact on the coronavirus disease 2019 outcome.Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity,systemic inflammation,ischemic or hypoxic liver damage or drug side effects.However,liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals.Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection,which embodies a second hit to the underestimated liver damage.

Activity and Selectivity of Bimetallic Catalysts Based on SBA-15 for Nitrate Reduction in Water

Nitrate from the application of nitrogen-based fertilizers in intensive agriculture is a notorious waste product, though it lacks cost-effective solutions for its removal from potential drinking water resources. Catalytic reduction appears to be a promising technique for converting nitrates to benign nitrogen gas. Mesoporous silica SBA-15 is a frequently used catalyst support that has large surface areas and highly ordered nanopores. In this work, mesoporous silica SBA-15 bimetallic catalysts for nitrate reduction were investigated. The catalyst was optimized for the selection of promoter metal (Sn and Cu), noble metal (Pd and Pt) and loading ratios of these metals at different temperatures and reduction conditions. The catalysts prepared were characterized by FT-IR, N2 physisorption, XRD, SEM, and ICP. All catalysts showed the presence of cylindrical mesoporous channels and uniform pore structures that remained even after metals loading. In the presence of a CO2 buffer, the catalysts 4Pd-1Cu/SBA-15 and 1Pt-1Cu/SBA-15 reduced at 100?C under H2 and 1Pd-1Cu/SBA-15 reduced at 200°C under H2 demonstrated very high nitrate conversion. Furthermore, the forementioned Pd catalysts had higher N2 selectivity (88% - 87%) compared to Pt catalyst (80%). Nitrate conversion by the 4Pd-1Cu/SBA-15 catalyst was significantly decreased to 81% in the absence of CO2.

Meta-analysis of CO_(2) conversion,energy efficiency,and other performance data of plasma-catalysis reactors with the open access PIONEER database

This paper brings the comparison of performances of CO_(2)conversion by plasma and plasma-assisted catalysis based on the data collected from literature in this field,organised in an open access online database.This tool is open to all users to carry out their own analyses,but also to contributors who wish to add their data to the database in order to improve the relevance of the comparisons made,and ultimately to improve the efficiency of CO_(2)conversion by plasma-catalysis.The creation of this database and database user interface is motivated by the fact that plasma-catalysis is a fast-growing field for all CO_(2)conversion processes,be it methanation,dry reforming of methane,methanolisation,or others.As a result of this rapid increase,there is a need for a set of standard procedures to rigorously compare performances of different systems.However,this is currently not possible because the fundamental mechanisms of plasma-catalysis are still too poorly understood to define these standard procedures.Fortunately however,the accumulated data within the CO_(2)plasma-catalysis community has become large enough to warrant so-called“big data”studies more familiar in the fields of medicine and the social sciences.To enable comparisons between multiple data sets and make future research more effective,this work proposes the first database on CO_(2)conversion performances by plasma-catalysis open to the whole community.This database has been initiated in the framework of a H_(2)0_(2)0 European project and is called the“PIONEER Data Base”.The database gathers a large amount of CO_(2)conversion performance data such as conversion rate,energy efficiency,and selectivity for numerous plasma sources coupled with or without a catalyst.Each data set is associated with metadata describing the gas mixture,the plasma source,the nature of the catalyst,and the form of coupling with the plasma.Beyond the database itself,a data extraction tool with direct visualisation features or advanced filtering functionalities has been developed and is available online to the public.The simple and fast visualisation of the state of the art puts new results into context,identifies literal gaps in data,and consequently points towards promising research routes.More advanced data extraction illustrates the impact that the database can have in the understanding of plasma-catalyst coupling.Lessons learned from the review of a large amount of literature during the setup of the database lead to best practice advice to increase comparability between future CO_(2)plasma-catalytic studies.Finally,the community is strongly encouraged to contribute to the database not only to increase the visibility of their data but also the relevance of the comparisons allowed by this tool.

生态创新理论研究现状与前景展望

生态创新理论是用技术创新方法来解决低碳经济问题的一种有效理论。目前国内已经有一些学者开始介绍生态创新概念、研究生态创新理论,但是目前学者对生态创新概念的认识还不够系统,对生态创新的方法研究有限,还没有形成全面、系统、公认的生态创新研究体系。基于对国外大量生态创新理论和方法文献的深入研究,总结出国外生态创新理论、方法及发展状况,并基于研究现状展望生态创新理论未来发展的方向。

针对脑卒中的ICF核心分类模板

目的通过循证和专家讨论研究法建立第一版针对脑卒中的一套综合ICF核心分类模板和与之相应的简明ICF核心分类模板。方法来自于不同国家和地区的国际专家从初步研究中搜集证据,结合这些证据进行正式的决策并最终达成共识。初步研究包括Delphi研究方法、对ICF分类的系统评价以及实证数据的收集。结果来自12个不同国家的39位专家出席会议并达成共识。专家初步研究决定在ICF分类的第二、第三和第四级水平上针对脑卒中确定一套448个类目的ICF核心分类摸板,其中193项类目属于身体功能,26项属于身体结构,165项属于活动和参与,64项属于环境因素。综合性ICF核心分类模板包括在ICF分类第二级水平上的130个类目,其中41项属于"身体功能",5项属于"身体结构",51项属于"活动和参与",33项属于"环境因素"。简明型ICF核心分类模板包括在ICF分类第二级水平上的18个类目,其中6项属于身体功能,2项属于身体结构,7项属于活动参与,以及3项属于环境因素。结论专家组通过整合研究过程中的证据,以及专家们基于ICF框架和分类的观点达成正式的共识,并确定针对"脑卒中"的ICF核心分类模板,同时界定综合型ICF核心分类模板和简要型ICF核心分类模板。

中文阅读障碍儿童的时间加工缺陷:来自知觉学习干预研究的证据

前人研究指出,阅读障碍群体具有听觉通道内的时间加工缺陷,但截止目前为止,该缺陷的非模态性、跨语言一般性、干预前景及具体机制尚不明确。本文通过综述三项在中文阅读障碍儿童中开展的听觉、视觉时间加工知觉训练,以及它们对阅读成绩的迁移效应,对时间加工技能与阅读障碍的关系,及其影响阅读发展的认知机制进行了探讨和分析,并在此基础上,提出了未来的研究构想,以充实该领域的理论建构。

Challenges in diagnosing mesenteric ischemia

Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia.

Life and death at the mucosal-luminal interface: New perspectives on human intestinal ischemia-reperfusion

Intestinal ischemia is a frequently observed phenomenon. Morbidity and mortality rates are extraordinarily high and did not improve over the past decades. This is in part attributable to limited knowledge on the pathophysiology of intestinal ischemia-reperfusion(IR) in man, the paucity in preventive and/or therapeutic options and the lack of early diagnostic markers for intestinal ischemia. To improve our knowledge and solve clinically important questions regarding intestinal IR, we developed a human experimental intestinal IR model. With this model, we were able to gain insight into the mechanisms that allow the human gut to withstand short periods of IR without the development of severe inflammatory responses. The purpose of this review is to overview the most relevant recent advances in our understanding of the pathophysiology of human intestinal IR, as well as the(potential) future clinical implications.

Improving the outcomes in gastric cancer surgery

Gastric cancer remains a significant health problem worldwide and surgery is currently the only potentially curative treatment option. Gastric cancer surgery is generally considered to be high risk surgery and fiveyear survival rates are poor,therefore a continuous strive to improve outcomes for these patients is warranted. Fortunately,in the last decades several potential advances have been introduced that intervene at various stages of the treatment process. This review provides an overview of methods implemented in pre-,intra- and postoperative stage of gastric cancer surgery to improve outcome. Better preoperative risk assessment using comorbidity index(e.g.,Charlson comorbidity index),assessment of nutritional status(e.g.,short nutritional assessment questionnaire,nutritional risk screening- 2002) and frailty assessment(Groningen frailty indicator,Edmonton frail scale,Hopkins frailty) was introduced. Also preoperative optimization of patients using prehabilitation has future potential.Implementation of fast-track or enhanced recovery after surgery programs is showing promising results,although future studies have to determine what the exact optimal strategy is.Introduction of laparoscopic surgery has shown improvement of results as well as optimization of lymph node dissection.Hyperthermic intraperitoneal chemotherapy has not shown to be beneficial in peritoneal metastatic disease thus far.Advances in postoperative care include optimal timing of oral diet,which has been shown to reduce hospital stay.In general,hospital volume,i.e.,centralization,and clinical audits might further improve the outcome in gastric cancer surgery.In conclusion,progress has been made in improving the surgical treatment of gastric cancer.However,gastric cancer treatment is high risk surgery and many areas for future research remain.

Dynamic tracking of stem cells in an acute liver failure model

AIM:To investigate a dual labeling technique,which would enable real-time monitoring of transplanted embryonic stem cell(ESC) kinetics,as well as long-term tracking.METHODS:Liver damage was induced in C57/BL6 male mice(n = 40) by acetaminophen(APAP) 300 mg/kg administered intraperitoneally.Green fluorescence protein(GFP) positive C57/BL6 mouse ESCs were stained with the near-infrared fluorescent lipophilic tracer 1,1-dioctadecyl-3,3,3,3-tetramethylindotricarbocyanine iodide(DiR) immediately before transplantationinto the spleen.Each of the animals in the cell therapy group(n = 20) received 5 × 10 6 ESCs 4 h following treatment with APAP.The control group(n = 20) received the vehicle only.The distribution and dynamics of the cells were monitored in real-time with the IVIS Lumina-2 at 30 min post transplantation,then at 3,12,24,48 and 72 h,and after one and 2 wk.Immunohistochemical examination of liver tissue was used to identify expression of GFP and albumin.Plasma alanine aminotransferase(ALT) was measured as an indication of liver damage.RESULTS:DiR-stained ESCs were easily tracked with the IVIS using the indocyanine green filter due to its high background passband with minimal background autofluorescence.The transplanted cells were confined inside the spleen at 30 min post-transplantation,gradually moved into the splenic vein,and were detectable in parts of the liver at the 3 h time-point.Within 24 h of transplantation,homing of almost 90% of cells was confirmed in the liver.On day three,however,the DiR signal started to fade out,and ex vivo IVIS imaging of different organs allowed signal detection at time-points when the signal could not be detected by in vivo imaging,and confirmed that the highest photon emission was in the liver(P < 0.0001).At 2 wk,the DiRsignal was no longer detectable in vivo ;however,immunohistochemistry analysis of constitutively-expressed GFP was used to provide an insight into the distribution of the cells.GFP +ve cells were detected in tissue sections resembling hepatocytes and were dispersed throughout the hepatic parenchyma,with the presence of a larger number of GFP +ve cells incorporated within the sinusoidal endothelial lining.Very faint albumin expression was detected in the transplanted GFP +ve cells at 72 h;however at 2 wk,few cells that were positive for GFP were also strongly positive for albumin.There was a significant improvement in serum levels of ALT,albumin and bilirubin in both groups at 2 wk when compared with the 72 h time-point.In the cell therapy group,serum ALT was significantly(P = 0.016) lower and albumin(P = 0.009) was significantly higher when compared with the control group at the 2 wk time-point;however there was no difference in mortality between the two groups.CONCLUSION:Dual labeling is an easy to use and cheap method for longitudinal monitoring of distribution,survival and engraftment of transplanted cells,and could be used for cell therapy models.