These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the internat...These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the international community of the compliance requirements in China.It was appreciated that the final translation must reflect the specialist understanding of those working under the Guideline whilst remaining faithful to the meaning of the original Chinese text.A three-step translation process was therefore determined.Step 1:A professional interpretation service(KL Communications,UK)was commissioned to prepare a literal translation of the Chinese text.Supportive documents were provided which explained specialist terminology.This translation was checked by two bilingual experts.Step 2:A workshop was held in Nanjing in May 2019 to which were invited experts in laboratory animal welfare and ethical use.These included international native English-speaking and Chinese-speaking delegates.The delegates worked in multilingual teams to review sections of the literal translation ahead of the workshop,and to agree an authentic interpretation during the workshop.Step 3:Following the workshop,three bilingual experts(two native Chinese speakers and one native English speaker)reviewed the entire document to ensure consistency of terminology and general accuracy.This document is thus not a“literal translation”but an“accurate interpretation”of the original text.Any challenge of work being performed under these Guidelines should rely on the Chinese text in the first place.However,this translation may be used as mitigating evidence,especially where those performing the work are non-Chinese speakers.展开更多
There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 poly...There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.展开更多
Coastal tourism holds substantial development potential.However,coastal ecosystems are affected by tourism development,which limits the supply of ecosystem services(ES).This study aims to conduct a systematic literatu...Coastal tourism holds substantial development potential.However,coastal ecosystems are affected by tourism development,which limits the supply of ecosystem services(ES).This study aims to conduct a systematic literature review on the impacts of tourism on coastal and marine ES using the Preferred Reporting Items for Systematic Reviews and Meta-alpha Methods.We initially identified 640 studies by searching titles,abstracts,and keywords.After screening,only 50 studies met the criteria for inclusion in the review.The results showed a significant increase in publications between 2011 and 2023.Most studies were conducted in Europe,Asia,and North and Central America.The most used ES classifications were MEA and CICES.Most studies concentrated on the ES supply dimension(43 studies;86%).Cultural ES(47 studies;94%)were researched more than provisioning(28 studies;56%)and regulating&maintenance(29 studies;58%)sections.Regarding cultural ES,most studies were focused on“Physical and experiential interactions with the natural environment”(34 studies;68%)and on provisioning ES on“Wild animals(terrestrial and aquatic)for nutrition,materials or energy”(18 studies;36%).Quantitative and mixed methods were the most used in the reviewed studies.Most studies identified pressures from“Tourism,urbanisation,and population increase”(27 studies;54%)and focused on“Integrative/common management strategies”(20 studies;40%).Only a few of the studies’results have been validated by external data(10 studies;20%).This study provides an overview of the most assessed marine and coastal ES,where studies are needed with more comprehensive geographic coverage.展开更多
Xenotransplantation, that is, the transplantation of cells, tissues, and organs between species, is a rapidly developing alternative to classical transplantology in human medicine. Since the first successful kidney tr...Xenotransplantation, that is, the transplantation of cells, tissues, and organs between species, is a rapidly developing alternative to classical transplantology in human medicine. Since the first successful kidney transplant in 1954, transplant medicine has made enormous progress. Until today, there are numerous patients worldwide waiting for an organ to be transplanted, and the number is still increasing, whereas the number of available organs is decreasing. One promising solution to this critical issue is the breeding of genetically modified animals as potential donors, which has gained the attention of scientists over the past two decades. Recent advancements in xenotransplantation have led to successful transfers of genetically modified pig organs into human recipients. Particularly, pig kidneys have been transplanted into living humans, demonstrating normal postsurgical function. Additionally, pig lungs functioned for 9 days in a brain-dead individual without experiencing hyperacute rejection. Furthermore, the successful xenotransplantation of pig hearts into living persons, exhibiting life-sustaining graft function, underscores significant progress toward clinically viable xenotransplants. This review provides an updated overview of the animal species and models used in xenotransplantation, with particular emphasis on the potential of transgenic pigs as donors. It discusses the process involved in producing the aforementioned animals, including the methods used to modify their genome. Particular attention is paid to immunological and genetic barriers, as well as zoonotic risks, and the possibilities and limitations of this technology. Although xenotransplantation is still in its experimental stage, it may play a crucial role in saving patients ' lives in the future.展开更多
This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square se...This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square sections)were designed and manufactured to assess the impact of casting conditions on filling length,as magnesium alloys cause severe melting and melt-mold exothermic reactions,making investment casting challenging.Combinations of traditional Mg-mold reaction mitigation techniques,such as applying a protective mold coating(Yttria)and vacuum,were examined to determine their role in the filling process.The results suggest that when induction is employed to melt reactive alloys,these methods are not always beneficial,as initially thought.Particularly at higher melt temperatures,the combination of Yttria-coated molds with low-pressure vacuum induction significantly reduce fluidity:vacuum induced melt levitation which promotes oxidation with the residual atmosphere;and Yttria-coating cracking due to thermal stress during the mold fabrication slows filling and promotes significant melt-mold reaction.This study shows that best results to investment cast thin-sections are obtained by avoiding both vacuum and protective coatings,providing a viable route for the precision manufacturing of stent biomedical devices.展开更多
Against the backdrop of a new era that commands the attention of scholars worldwide,and on a scientific research journey filled with both hope and challenges,Animal Models and Experimental Medicine(AMEM),as a beacon g...Against the backdrop of a new era that commands the attention of scholars worldwide,and on a scientific research journey filled with both hope and challenges,Animal Models and Experimental Medicine(AMEM),as a beacon guiding innovation and rigorous research in the field of animal models and experimental medicine,has once again shone brightly in 2024.With an impact factor of 3.8,a JCI and JCR Q2 ranking,and a CiteScore of 6.3,the journal has demonstrated a continuous rise in its influence and academic status.展开更多
Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachrono...Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.展开更多
Cultural ecosystem services(CES),which encompass recreational and aesthetic values,contribute to human wellbeing and yet are often underrepresented in forest management planning due to challenges in quantifying these ...Cultural ecosystem services(CES),which encompass recreational and aesthetic values,contribute to human wellbeing and yet are often underrepresented in forest management planning due to challenges in quantifying these services.This study introduces the Recreational and Aesthetic Values of Forested Landscapes(RAFL)index,a novel framework combining six measurable recreational and aesthetic components:Stewardship,Naturalness,Complexity,Visual Scale,Historicity,and Ephemera.The RAFL index was integrated into a Linear Programming(LP)Resource Capability Model(RCM)to assess trade-offs between CES and other ecosystem services,including timber production,wildfire resistance,and biodiversity.The approach was applied in a case study in Northern Portugal,comparing two forest management scenarios:Business as Usual(BAU),dominated by eucalyptus plantations,and an Alternative Scenario(ALT),focused on the conversion to native species:cork oak,chestnut,and pedunculate oak.Results revealed that the ALT scenario consistently achieved higher RAFL values,reflecting its potential to enhance CES,while also supporting higher biodiversity and wildfire resilience compared to the BAU scenario.Results highlighted further that management may maintain steady timber production and wildfire regulatory services while addressing concerns with CES.This study provides a replicable methodology for quantifying CES and integrating them into forest management frameworks,offering actionable insights for decision-makers.The findings highlight the effectiveness of the approach in designing landscape mosaics that provide CES while addressing the need to supply provisioning and regulatory ecosystem services.展开更多
Emerging infectious diseases are a major threat to biodiversity and an important public health issue.Flaviviruses are the cause of several emerging vector-borne zoonotic arboviruses whose distribution is currently inc...Emerging infectious diseases are a major threat to biodiversity and an important public health issue.Flaviviruses are the cause of several emerging vector-borne zoonotic arboviruses whose distribution is currently increasing in Europe.The evidence that West Nile virus(WNV)circulates in resident and migratory species has implications for both animal and public health and should therefore be studied in depth.USUTU(USUV),Bagaza(BAGV)and tick-borne encephalitis virus(TBEV)are other viruses that are beginning to spread more widely.An integrated surveillance program,namely in birds,is essential for reducing the risk of infection in human populations within the One Health principles.In the present study,wild birds admitted to wildlife rehabilitation centers in Portugal were sampled.Two hundred eight blood samples were assayed serologically for antibodies to flaviviruses by using a commercial ELISA kit.An over-all seroprevalence of 19.6%(95%confidence interval[CI]:13.7-26.7%)was observed.Antibodies against flaviviruses were detected in 13(35.1%)different species of wild birds.Accipitriformes(26.7%;95%CI:18.5-36.2%)and Strigi-formes(26.7%;95%CI:14.6-42.0%)were the orders with the highest seroprevalence rates recorded.There were no statistically significant differences(p=0.725)between the geographical regions(NUTSⅡ)studied,but a statistically significant difference(p=0.017)was found between sex(male:34.4%;female:4.8%).A higher seroprevalence was detected in adults(32.1%)than in juvenile birds(9.3%)(p=0.014),and age was considered a risk factor for flavivirus infection in wild birds(odds ratio 1.4;95%CI:0.5-4.0).More epidemiological studies are needed in Portugal since the actual spread of the genus Flavivirus throughout the country is unknown.展开更多
Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respira...Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respiratory compromise,and often patients present psychological ailments associated with the drastic alteration of their normal lifestyle.SCI pathophysiology derives from a massive damage to the spinal cord tissue,which is propagated展开更多
Glucose-derived carbons were prepared by hydrothermal carbonization of glucose followed by carbonization or activation to obtain carbon materials with different microporosities. These microporous carbons and carbon na...Glucose-derived carbons were prepared by hydrothermal carbonization of glucose followed by carbonization or activation to obtain carbon materials with different microporosities. These microporous carbons and carbon nanotubes(CNTs) were functionalized with melamine and/or iron(Ⅱ) phthalocyanine(FePc)following three different methodologies:(i) Functionalization with melamine via thermal treatment,(ii)incorporation of the lowest amount of FePc reported in the literature via incipient wetness impregnation followed by thermal treatment and(iii) functionalization with melamine followed by Fe Pc incorporation.The chemical and textural characterization of the prepared materials and their electrochemical assessment allowed to understand the role of microporosity in the incorporation of FePc and its effect on the oxygen reduction reaction(ORR). It was observed that FePc was preferentially incorporated inside the porous structure, especially in samples with more developed microporosity. However, functionalization with melamine modified the textural properties and the surface chemistry, favoring the incorporation of FePc on the surface. Regarding the electrochemical performance, the presence of FePc greatly enhanced the electroactivity of the microporous catalysts. An onset potential of 0.88 V and a four-electron pathway were obtained for glucose-derived carbons, whereas the limiting current densities and kinetic current densities rose by 126% and 222%, respectively, in comparison to the base sample. Notwithstanding, the highest electrochemical activity was observed for the sample prepared with CNTs, due to the synergy between the active metal centers and their highly graphitic carbon structure. The electrochemical parameters of CNTFeP csurpass the commercial Pt/C. The half-wave potential is 40 mV higher, the limiting current density increases by 17%, and a negligible production of by-products(< 1%) was observed.展开更多
AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4...AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4-year period, from January 2010 to December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography(ERCP) for suspected choledocholithiasis were included. Based on the presence or absence of predictors of choledocholithiasis(clinical ascending cholangitis, common bile duct(CBD) stones on ultrasonography(US), total bilirubin > 4 mg/d L, dilated CBD on US, total bilirubin 1.8-4 mg/d L, abnormal liver function test, age > 55 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor and risk group we used the χ2 to evaluate the statistical associations with the presence of choledocolithiasis at ERCP. Statistical analysis was performed using SPSS version 21.0. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis(P = 0.063), all other predictors of cho-ledocholitiasis(clinical ascending cholangitis, P = 0.001; CBD stones on US, P ≤ 0.001; total bilirubin > 4 mg/dL, P = 0.035; total bilirubin 1.8-4 mg/dL, P = 0.001; dilated CBD on US, P ≤ 0.001; abnormal liver function test, P = 0.012; age > 55 years, P = 0.002) showed a statistically significant association with the presence of choledocholithiasis at ERCP. Approximately four fifths of patients in the high risk group(79.8%, 154/193 patients) had confirmed choledocholithiasis on ERCP, vs 34.2%(25/73 patients) and 0(0/2 patients) in the intermediate and low risk groups, respectively. The definition of "high risk group" had a sensitivity of 86%, positive predictive value 79.8% and specificity 56.2% for the presence of choledocholithiasis at ERCP. CONCLUSION: The guidelines should be considered to optimize patients' selection for ERCP. For high risk patients specificity is still low, meaning that some patients perform ERCP unnecessarily.展开更多
Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need ...Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need of clinical intervention, several risk scores have been proposed and their use consistently recommended by international guidelines. The use of risk scoring systems in early assessment of patients suffering from UGIB may be useful to distinguish high-risks patients, who may need clinical intervention and hospitalization, from low risk patients with a lower chance of developing complications, in which management as outpatients can be considered. Although several scores have been published and validated for predicting different outcomes, the most frequently cited ones are the Rockall score and the Glasgow Blatchford score(GBS). While Rockall score, which incorporates clinical and endoscopic variables, has been validated to predict mortality, the GBS, which is based on clinical and laboratorial parameters, has been studied to predict the need of clinical intervention. Despite the advantages previously reported, their use in clinical decisions is still limited. This review describes the different risk scores used in the UGIB setting, highlights the most important research, explains why and when their use may be helpful, reflects on the problems that remain unresolved and guides future research with practical impact.展开更多
AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the dia...AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.展开更多
Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding...Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand.Despite the challenges ahead of us,cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias,which encourages efforts towards their improvement in the future.展开更多
AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cy...AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.展开更多
AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpene...AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.展开更多
Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartor...Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.展开更多
基金Astra Zeneca R&DUniversities Federation for Animal Welfare+3 种基金Royal Society for the Prevention of Cruelty to AnimalsNovo Nordisk PharmaceuticalsGovernment of the United KingdomAAALAC International。
文摘These Chinese National Guidelines(GB/T 35892-20181)were issued February 06,2018 and became effective September 01,2018.The authors recognized the urgent need for an authentic English translation to inform the international community of the compliance requirements in China.It was appreciated that the final translation must reflect the specialist understanding of those working under the Guideline whilst remaining faithful to the meaning of the original Chinese text.A three-step translation process was therefore determined.Step 1:A professional interpretation service(KL Communications,UK)was commissioned to prepare a literal translation of the Chinese text.Supportive documents were provided which explained specialist terminology.This translation was checked by two bilingual experts.Step 2:A workshop was held in Nanjing in May 2019 to which were invited experts in laboratory animal welfare and ethical use.These included international native English-speaking and Chinese-speaking delegates.The delegates worked in multilingual teams to review sections of the literal translation ahead of the workshop,and to agree an authentic interpretation during the workshop.Step 3:Following the workshop,three bilingual experts(two native Chinese speakers and one native English speaker)reviewed the entire document to ensure consistency of terminology and general accuracy.This document is thus not a“literal translation”but an“accurate interpretation”of the original text.Any challenge of work being performed under these Guidelines should rely on the Chinese text in the first place.However,this translation may be used as mitigating evidence,especially where those performing the work are non-Chinese speakers.
基金supported by funding from Parkinson Canadafunded by a scholarship from Parkinson Canadaa scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval)
文摘There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.
基金supported by the project MApping and Forecasting Ecosystem Services in Urban Areas(MAFESUR)funded by the Lithuanian Research Council(Contract:Nr.P-MIP-23-426).
文摘Coastal tourism holds substantial development potential.However,coastal ecosystems are affected by tourism development,which limits the supply of ecosystem services(ES).This study aims to conduct a systematic literature review on the impacts of tourism on coastal and marine ES using the Preferred Reporting Items for Systematic Reviews and Meta-alpha Methods.We initially identified 640 studies by searching titles,abstracts,and keywords.After screening,only 50 studies met the criteria for inclusion in the review.The results showed a significant increase in publications between 2011 and 2023.Most studies were conducted in Europe,Asia,and North and Central America.The most used ES classifications were MEA and CICES.Most studies concentrated on the ES supply dimension(43 studies;86%).Cultural ES(47 studies;94%)were researched more than provisioning(28 studies;56%)and regulating&maintenance(29 studies;58%)sections.Regarding cultural ES,most studies were focused on“Physical and experiential interactions with the natural environment”(34 studies;68%)and on provisioning ES on“Wild animals(terrestrial and aquatic)for nutrition,materials or energy”(18 studies;36%).Quantitative and mixed methods were the most used in the reviewed studies.Most studies identified pressures from“Tourism,urbanisation,and population increase”(27 studies;54%)and focused on“Integrative/common management strategies”(20 studies;40%).Only a few of the studies’results have been validated by external data(10 studies;20%).This study provides an overview of the most assessed marine and coastal ES,where studies are needed with more comprehensive geographic coverage.
基金IDUB Mobility Grant of the Nicolaus Copernicus University。
文摘Xenotransplantation, that is, the transplantation of cells, tissues, and organs between species, is a rapidly developing alternative to classical transplantology in human medicine. Since the first successful kidney transplant in 1954, transplant medicine has made enormous progress. Until today, there are numerous patients worldwide waiting for an organ to be transplanted, and the number is still increasing, whereas the number of available organs is decreasing. One promising solution to this critical issue is the breeding of genetically modified animals as potential donors, which has gained the attention of scientists over the past two decades. Recent advancements in xenotransplantation have led to successful transfers of genetically modified pig organs into human recipients. Particularly, pig kidneys have been transplanted into living humans, demonstrating normal postsurgical function. Additionally, pig lungs functioned for 9 days in a brain-dead individual without experiencing hyperacute rejection. Furthermore, the successful xenotransplantation of pig hearts into living persons, exhibiting life-sustaining graft function, underscores significant progress toward clinically viable xenotransplants. This review provides an updated overview of the animal species and models used in xenotransplantation, with particular emphasis on the potential of transgenic pigs as donors. It discusses the process involved in producing the aforementioned animals, including the methods used to modify their genome. Particular attention is paid to immunological and genetic barriers, as well as zoonotic risks, and the possibilities and limitations of this technology. Although xenotransplantation is still in its experimental stage, it may play a crucial role in saving patients ' lives in the future.
基金financed by National Funds through the Portuguese funding agency,FCT–Funda??o para a Ciência e a Tecnologia,within the strategic projects UIDB/04436/2020,UIDB/00481/2020 and LA/P/0063/2020(DOI 10.54499/LA/P/0063/2020)。
文摘This paper discusses an experimental investigation into the fluidity of AZ91D-1 wt.%Ca O magnesium melt via induction for thin-section investment casting.Plaster molds with thin spiral cavities(0.5 to 1.5 mm square sections)were designed and manufactured to assess the impact of casting conditions on filling length,as magnesium alloys cause severe melting and melt-mold exothermic reactions,making investment casting challenging.Combinations of traditional Mg-mold reaction mitigation techniques,such as applying a protective mold coating(Yttria)and vacuum,were examined to determine their role in the filling process.The results suggest that when induction is employed to melt reactive alloys,these methods are not always beneficial,as initially thought.Particularly at higher melt temperatures,the combination of Yttria-coated molds with low-pressure vacuum induction significantly reduce fluidity:vacuum induced melt levitation which promotes oxidation with the residual atmosphere;and Yttria-coating cracking due to thermal stress during the mold fabrication slows filling and promotes significant melt-mold reaction.This study shows that best results to investment cast thin-sections are obtained by avoiding both vacuum and protective coatings,providing a viable route for the precision manufacturing of stent biomedical devices.
文摘Against the backdrop of a new era that commands the attention of scholars worldwide,and on a scientific research journey filled with both hope and challenges,Animal Models and Experimental Medicine(AMEM),as a beacon guiding innovation and rigorous research in the field of animal models and experimental medicine,has once again shone brightly in 2024.With an impact factor of 3.8,a JCI and JCR Q2 ranking,and a CiteScore of 6.3,the journal has demonstrated a continuous rise in its influence and academic status.
基金Brazilian National Program of Genomics and Precision Health-Genomas Brasil,Grant/Award Number:MS-SECTICS-Decit/CNPq 16/2023São Paulo Research Foundation,Grant/Award Number:FAPESP-2021/07957-5+5 种基金Barretos Cancer Hospital,Grant/Award Number:13/2021National Oncology Care Support Program (PRONON),CNPq,Grant/Award Number:444217/2023-1Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer)Brazilian Ministry of Health (MoH)National Council for Scientific and Technological DevelopmentCNPq Productivity
文摘Background:Constitutional mismatch repair deficiency(CMMRD)is a rare disorder resulting from biallelic germline pathogenic variants in mismatch repair genes.This study described the molecular profile of two metachronous brain tumors and a patient-derived xenograft(PDX)from a Brazilian child with CMMRD.Methods:After PDX development,methylation array,whole exome sequencing,and Nano String techniques were applied to describe the genetic landscape of CMMRD.Results:A 6½-year-old girl was diagnosed with Sonic Hedgehog(SHH)-activated medulloblastoma and somatic TP53-mutant.After surgery and radiochemotherapy,she remained free of disease progression.At 10 years and 3 months,she developed a diffuse pediatric-type high-grade glioma(dp HGG).The child had a family history of cancer,and subsequent investigation revealed a biallelic germline variant on MSH6(c.3556+1G>A)with the absence of protein expression in both normal and tumor tissue.A PDX model of the dp HGG was developed.The methylation profile confirmed the diagnosis of both brain tumors and PDX,refining the classification of dp HGG,Rtk1 subtype,subclass A,with an actionable alteration on Platelet-derived growth factor receptor A(PDGFRA).Exome analysis showed high tumor mutational burden,with 3019,540,and 1049 pathogenic variants in the medulloblastoma,dp HGG,and PDX,respectively.Only the medulloblastoma exhibited microsatellite instability.The CD24,CD47,and CD276 immune checkpoints had elevated messenger RNA levels,yet no programmed death ligand 1 expression was observed in CMMRD-derived tumors.Conclusion:We report an extensive molecular profile of a CMMRD patient,and the developed PDX model can be applied to explore new therapeutic approaches for CMMRD-associated brain tumors.
基金supported by the Forest Research Centre,a research unit funded by Fundacao para a Ciencia e a Tecnologia I.P.(FCT),Portugal(UIDB/00239/2020)the Associated Laboratory TERRA(LA/P/0092/2020)+4 种基金Additional funding was provided through the Ph.D.grant awarded to Dagm Abate(UI/BD/151525/2021)by two key projects:H2020-MSCA-RISE-2020/101007950,titled“DecisionES-Decision Support for the Supply of Ecosystem Services under Global Change,”funded by the Marie Curie International Staff Exchange Scheme,H2020-LCGD-2020-3/101037419,titled“FIRE-RES-Innovative technologies and socio-ecological economic solutions for fireresilient territories in Europe,”funded by the EU Horizon 2020—Research and Innovation Framework Programmesupported by a project MODFIRE—a multiple criteria approach to integrate wildfire behavior in forest management planning with reference PCIF/MOS/0217/2017a contract from Dr.Susete Marques in the scope of Norma Transitoria—DL57/2016/CP1382/CT15a grant from Fundacao para a Ciencia e a Tecnologia(FCT),Portugal to Dr.Guerra-Hernandez(CEECIND/02576/2022).
文摘Cultural ecosystem services(CES),which encompass recreational and aesthetic values,contribute to human wellbeing and yet are often underrepresented in forest management planning due to challenges in quantifying these services.This study introduces the Recreational and Aesthetic Values of Forested Landscapes(RAFL)index,a novel framework combining six measurable recreational and aesthetic components:Stewardship,Naturalness,Complexity,Visual Scale,Historicity,and Ephemera.The RAFL index was integrated into a Linear Programming(LP)Resource Capability Model(RCM)to assess trade-offs between CES and other ecosystem services,including timber production,wildfire resistance,and biodiversity.The approach was applied in a case study in Northern Portugal,comparing two forest management scenarios:Business as Usual(BAU),dominated by eucalyptus plantations,and an Alternative Scenario(ALT),focused on the conversion to native species:cork oak,chestnut,and pedunculate oak.Results revealed that the ALT scenario consistently achieved higher RAFL values,reflecting its potential to enhance CES,while also supporting higher biodiversity and wildfire resilience compared to the BAU scenario.Results highlighted further that management may maintain steady timber production and wildfire regulatory services while addressing concerns with CES.This study provides a replicable methodology for quantifying CES and integrating them into forest management frameworks,offering actionable insights for decision-makers.The findings highlight the effectiveness of the approach in designing landscape mosaics that provide CES while addressing the need to supply provisioning and regulatory ecosystem services.
基金funded by the Portuguese Foundation for Science and Technology(FCT)sup-ported by the projects UIDB/00772/2020(https://doi.org/10.54499/UIDB/00772/2020)。
文摘Emerging infectious diseases are a major threat to biodiversity and an important public health issue.Flaviviruses are the cause of several emerging vector-borne zoonotic arboviruses whose distribution is currently increasing in Europe.The evidence that West Nile virus(WNV)circulates in resident and migratory species has implications for both animal and public health and should therefore be studied in depth.USUTU(USUV),Bagaza(BAGV)and tick-borne encephalitis virus(TBEV)are other viruses that are beginning to spread more widely.An integrated surveillance program,namely in birds,is essential for reducing the risk of infection in human populations within the One Health principles.In the present study,wild birds admitted to wildlife rehabilitation centers in Portugal were sampled.Two hundred eight blood samples were assayed serologically for antibodies to flaviviruses by using a commercial ELISA kit.An over-all seroprevalence of 19.6%(95%confidence interval[CI]:13.7-26.7%)was observed.Antibodies against flaviviruses were detected in 13(35.1%)different species of wild birds.Accipitriformes(26.7%;95%CI:18.5-36.2%)and Strigi-formes(26.7%;95%CI:14.6-42.0%)were the orders with the highest seroprevalence rates recorded.There were no statistically significant differences(p=0.725)between the geographical regions(NUTSⅡ)studied,but a statistically significant difference(p=0.017)was found between sex(male:34.4%;female:4.8%).A higher seroprevalence was detected in adults(32.1%)than in juvenile birds(9.3%)(p=0.014),and age was considered a risk factor for flavivirus infection in wild birds(odds ratio 1.4;95%CI:0.5-4.0).More epidemiological studies are needed in Portugal since the actual spread of the genus Flavivirus throughout the country is unknown.
基金the financial support from Prémios Santa Casa Neurociências-Prize Melo e Castro for Spinal Cord Injury Research (MC-04/17)Portuguese Foundation for Science and Technology [Doctoral fellowship (SFRH/BD/103075/2014) to EDG+9 种基金Post- Doctoral fellowship (SFRH/BPD/97701/2013) to NASIF Development Grant to AJSfunded by national funds through FCT under the scope of grant reference TUBITAK/0007/20143599-PPCDT Project: PTDC/DTP-FTO/5109/2014developed under the scope of the projects NORTE-01-0145FEDER-000013supported by the Northern Portugal Regional Operational Programme (NORTE 2020)under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER)funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE)by National funds, through the Foundation for Science and Technology (FCT)under the scope of the project POCI-010145-FEDER-007038
文摘Spinal cord injury(SCI)is a condition without treatment,mainly characterized by the loss of motor and sensory function below the level of injury.This is accompanied by several complications such as cardiac and respiratory compromise,and often patients present psychological ailments associated with the drastic alteration of their normal lifestyle.SCI pathophysiology derives from a massive damage to the spinal cord tissue,which is propagated
基金“UniRCell”,with the reference POCI-01-0145-FEDER-016422“AIProcMat@N2020–Advanced Industrial Processes and Materials for a Sustainable Northern Region of Portugal 2020”,with the reference NORTE-010145-FEDER-000006,supported by Norte Portugal Regional Operational Programme(NORTE 2020),under the Portugal 2020 Partnership Agreement,through the European Regional Development Fund(ERDF)+1 种基金Base Funding–UIDB/50020/2020 of the Associate Laboratory LSRE-LCM–funded by national funds through FCT/MCTES(PIDDAC)PDEQB(PD9989)。
文摘Glucose-derived carbons were prepared by hydrothermal carbonization of glucose followed by carbonization or activation to obtain carbon materials with different microporosities. These microporous carbons and carbon nanotubes(CNTs) were functionalized with melamine and/or iron(Ⅱ) phthalocyanine(FePc)following three different methodologies:(i) Functionalization with melamine via thermal treatment,(ii)incorporation of the lowest amount of FePc reported in the literature via incipient wetness impregnation followed by thermal treatment and(iii) functionalization with melamine followed by Fe Pc incorporation.The chemical and textural characterization of the prepared materials and their electrochemical assessment allowed to understand the role of microporosity in the incorporation of FePc and its effect on the oxygen reduction reaction(ORR). It was observed that FePc was preferentially incorporated inside the porous structure, especially in samples with more developed microporosity. However, functionalization with melamine modified the textural properties and the surface chemistry, favoring the incorporation of FePc on the surface. Regarding the electrochemical performance, the presence of FePc greatly enhanced the electroactivity of the microporous catalysts. An onset potential of 0.88 V and a four-electron pathway were obtained for glucose-derived carbons, whereas the limiting current densities and kinetic current densities rose by 126% and 222%, respectively, in comparison to the base sample. Notwithstanding, the highest electrochemical activity was observed for the sample prepared with CNTs, due to the synergy between the active metal centers and their highly graphitic carbon structure. The electrochemical parameters of CNTFeP csurpass the commercial Pt/C. The half-wave potential is 40 mV higher, the limiting current density increases by 17%, and a negligible production of by-products(< 1%) was observed.
文摘AIM: To study the practical applicability of the American Society for Gastrointestinal Endoscopy guidelines in suspected cases of choledocholithiasis.METHODS: This was a retrospective single center study, covering a 4-year period, from January 2010 to December 2013. All patients who underwent endoscopic retrograde cholangiopancreatography(ERCP) for suspected choledocholithiasis were included. Based on the presence or absence of predictors of choledocholithiasis(clinical ascending cholangitis, common bile duct(CBD) stones on ultrasonography(US), total bilirubin > 4 mg/d L, dilated CBD on US, total bilirubin 1.8-4 mg/d L, abnormal liver function test, age > 55 years and gallstone pancreatitis), patients were stratified in low, intermediate or high risk for choledocholithiasis. For each predictor and risk group we used the χ2 to evaluate the statistical associations with the presence of choledocolithiasis at ERCP. Statistical analysis was performed using SPSS version 21.0. A P value of less than 0.05 was considered statistically significant. RESULTS: A total of 268 ERCPs were performed for suspected choledocholithiasis. Except for gallstone pancreatitis(P = 0.063), all other predictors of cho-ledocholitiasis(clinical ascending cholangitis, P = 0.001; CBD stones on US, P ≤ 0.001; total bilirubin > 4 mg/dL, P = 0.035; total bilirubin 1.8-4 mg/dL, P = 0.001; dilated CBD on US, P ≤ 0.001; abnormal liver function test, P = 0.012; age > 55 years, P = 0.002) showed a statistically significant association with the presence of choledocholithiasis at ERCP. Approximately four fifths of patients in the high risk group(79.8%, 154/193 patients) had confirmed choledocholithiasis on ERCP, vs 34.2%(25/73 patients) and 0(0/2 patients) in the intermediate and low risk groups, respectively. The definition of "high risk group" had a sensitivity of 86%, positive predictive value 79.8% and specificity 56.2% for the presence of choledocholithiasis at ERCP. CONCLUSION: The guidelines should be considered to optimize patients' selection for ERCP. For high risk patients specificity is still low, meaning that some patients perform ERCP unnecessarily.
文摘Upper gastrointestinal bleeding(UGIB) remains a significant cause of hospital admission. In order to stratify patients according to the risk of the compli-cations, such as rebleeding or death, and to predict the need of clinical intervention, several risk scores have been proposed and their use consistently recommended by international guidelines. The use of risk scoring systems in early assessment of patients suffering from UGIB may be useful to distinguish high-risks patients, who may need clinical intervention and hospitalization, from low risk patients with a lower chance of developing complications, in which management as outpatients can be considered. Although several scores have been published and validated for predicting different outcomes, the most frequently cited ones are the Rockall score and the Glasgow Blatchford score(GBS). While Rockall score, which incorporates clinical and endoscopic variables, has been validated to predict mortality, the GBS, which is based on clinical and laboratorial parameters, has been studied to predict the need of clinical intervention. Despite the advantages previously reported, their use in clinical decisions is still limited. This review describes the different risk scores used in the UGIB setting, highlights the most important research, explains why and when their use may be helpful, reflects on the problems that remain unresolved and guides future research with practical impact.
文摘AIM:To evaluate whether the use of real time viewer(RTV)and administration of domperidone to patients with delayed gastric passage of the capsule could reduce the rate of incomplete examinations(IE)and improve the diagnostic yield of small bowel capsule endoscopy(SBCE).METHODS:Prospective single center interventional study,from June 2012 to February 2013.Capsule location was systematically checked one hour after ingestion using RTV.If it remained in the stomach,the patient received 10 mg domperidone per os and the location of the capsule was rechecked after 30 min.If the capsule remained in the stomach a second dose of10 mg of domperidone was administered orally.After another 30 min the position was rechecked and if the capsule remained in the stomach,it was passed into the duodenum by upper gastrointestinal(GI)endoscopy.The rate of IE and diagnostic yield of SBCE were compared with those of examinations performed before the use of RTV or domperidone in our Department(control group,January 2009-May 2012).RESULTS:Both groups were similar regarding age,sex,indication,inpatient status and surgical history.The control group included 307 patients,with 48(15.6%)IE.The RTV group included 82 patients,with3(3.7%)IE,P=0.003.In the control group,average gastric time was significantly longer in patients with IE than in patients with complete examination of the small bowel(77 min vs 26 min,P=0.003).In the RTV group,the capsule remained in the stomach one hour after ingestion in 14/82 patients(17.0%)vs 48/307(15.6%)in the control group,P=0.736.Domperidone did not significantly affect small bowel transit time(260min vs 297 min,P=0.229).The capsule detected positive findings in 39%of patients in the control group and 49%in the RTV group(P=0.081).CONCLUSION:The use of RTV and selective administration of domperidone to patients with delayed gastric passage of the capsule significantly reduces incomplete examinations,with no effect on small bowel transit time or diagnostic yield.
基金funded by national fundsthrough the Foundation for Science and Technology(FCT)-project UIDB/50026/2020 and UIDP/50026/2020by the National Ataxia Foundation(NAF)
文摘Spinocerebellar ataxias are heritable neurodegenerative diseases caused by a cytosine-adenine-guanine expansion,which encodes a long glutamine tract(polyglutamine)in the respective wild-type protein causing misfolding and protein aggregation.Clinical features of polyglutamine spinocerebellar ataxias include neuronal aggregation,mitochondrial dysfunction,decreased proteasomal activity,and autophagy impairment.Mutant polyglutamine protein aggregates accumulate within neurons and cause neural dysfunction and death in specific regions of the central nervous system.Spinocerebellar ataxias are mostly characterized by progressive ataxia,speech and swallowing problems,loss of coordination and gait deficits.Over the past decade,efforts have been made to ameliorate disease symptoms in patients,yet no cure is available.Previous studies have been proposing the use of stem cells as promising tools for central nervous system tissue regeneration.So far,pre-clinical trials have shown improvement in various models of neurodegenerative diseases following stem cell transplantation,including animal models of spinocerebellar ataxia types 1,2,and 3.However,contrasting results can be found in the literature,depending on the animal model,cell type,and route of administration used.Nonetheless,clinical trials using cellular implants into degenerated brain regions have already been applied,with the expectation that these cells would be able to differentiate into the specific neuronal subtypes and re-populate these regions,reconstructing the affected neural network.Meanwhile,the question of how feasible it is to continue such treatments remains unanswered,with long-lasting effects being still unknown.To establish the value of these advanced therapeutic tools,it is important to predict the actions of the transplanted cells as well as to understand which cell type can induce the best outcomes for each disease.Further studies are needed to determine the best route of administration,without neglecting the possible risks of repetitive transplantation that these approaches so far appear to demand.Despite the challenges ahead of us,cell-transplantation therapies are reported to have transient but beneficial outcomes in spinocerebellar ataxias,which encourages efforts towards their improvement in the future.
基金Supported by Sao Paulo Research Foundation(FAPESP),No.2012/15036-8National Council for Scientific and Technological Development(CNPq),No.474.776/2013-1+2 种基金the Sao Paulo Research Foundation(FAPESP,NO.2015/21464-0)for the support for English revisionthe Coordination for the Improvement of Higher Education Personnel(CAPES)for the doctoral scholarshipthe National Council for Scientific and Technological Development(CNPq,NO.310120/2015-2)for the productivity research scholarship
文摘AIM To examine the effect of Fusobacterium nucleatum(F. nucleatum) on the microenvironment of colonic neoplasms and the expression of inflammatory mediators and microRNAs(miRNAs).METHODS Levels of F. nucleatum DNA, cytokine gene mRNA(TLR2, TLR4, NFKB1, TNF, IL1 B, IL6 and IL8), and potentially interacting miRNAs(miR-21-3p, miR-22-3p, mi R-28-5p, miR-34a-5p, miR-135b-5p) were measured by quantitative polymerase chain reaction(qPCR) TaqMan? assays in DNA and/or RNA extracted from the disease and adjacent normal fresh tissues of 27 colorectal adenoma(CRA) and 43 colorectal cancer(CRC) patients. KRAS mutations were detected by direct sequencing and microsatellite instability(MSI) status by multiplex PCR. Cytoscape v3.1.1 was used to construct the postulated miRNA:mRNA interaction network.RESULTS Overabundance of F. nucleatum in neoplastic tissue compared to matched normal tissue was detected in CRA(51.8%) and more markedly in CRC(72.1%). We observed significantly greater expression of TLR4, IL1 B, IL8, and miR-135 b in CRA lesions and TLR2, IL1 B, IL6, IL8, mi R-34 a and miR-135 b in CRC tumours compared to their respective normal tissues. Only two transcripts for miR-22 and miR-28 were exclusively downregulated in CRC tumour samples. The mRNA expression of IL1 B, IL6, IL8 and miR-22 was positively correlated with F. nucleatum quantification in CRC tumours. The mRNA expression of miR-135 b and TNF was inversely correlated. The miRNA:mRNA interaction network suggested that the upregulation of miR-34 a in CRC proceeds via a TLR2/TLR4-dependent response to F. nucleatum. Finally, KRAS mutations were more frequently observed in CRC samples infected with F. nucleatum and were associated with greater expression of miR-21 in CRA, while IL8 was upregulated in MSI-high CRC.CONCLUSION Our findings indicate that F. nucleatum is a risk factor for CRC by increasing the expression of inflammatory mediators through a possible mi RNA-mediated activation of TLR2/TLR4.
文摘AIM: To evaluate mucosal healing in patients with small bowel plus colonic Crohn's disease(CD) with a single non-invasive examination, by using PillCam COLON 2.(PCC2).METHODS: Patients with non-stricturing nonpenetrating small bowel plus colonic CD in sustained corticosteroid-free remission were included. At diagnosis,patients had undergone ileocolonoscopy to identify active CD lesions, such as ulcers and erosions, and small bowel capsule endoscopy to assess the Lewis Score(LS). After ≥ 1 year of follow-up, patients underwent entire gastrointestinal tract evaluation with PCC2. The primary endpoint was assessment of CD mucosal healing, defined as no active colonic CD lesions and LS < 135.RESULTS: Twelve patients were included(7 male;mean age: 32 years), and mean follow-up was 38 mo.The majority of patients(83.3%) received immunosuppressive therapy. Three patients(25%) achieved mucosal healing in both the small bowel and the colon,while disease activity was limited to either the small bowel or the colon in 5 patients(42%). It was possible to observe the entire gastrointestinal tract in 10 of the12 patients(83%) who underwent PCC2.CONCLUSION: Only three patients in sustainedcorticosteroid-free clinical remission achieved mucosal healing in both the small bowel and the colon, highlighting the limitations of clinical assessment when stratifying disease activity, and the need for pan-enteric endoscopy to guide therapeutic modification.
基金supported by project MARBIOTECH,grant NORTE-07-0124-FEDER-000047-BPD-2013-06partially funded by project MARBIOTECH(reference NORTE-070124-FEDER-000047)+6 种基金co-financed by the North Portugal Regional Operational Programme(ON.2-O Novo Norte)the National Strategic Reference Framework(NSRF)the European Regional Development Fund(ERDF)the ERDF,through the Competitiveness and TradeExpansion Program(COMPETE)national funds provided by the Foundation for Science and Technology(FCT)project PEst-C/MARL-1A0015/2013the financial aid provided by the Master of Marine Sciences-Marine Recourses,of the Institute of Biomedical Sciences Abel Salazar,University of Porto
文摘Objective:To evaluate the in vitro anticancer activity of crude ethyl acetate extracts of the culture of four marine-derived fungi Aspergillus similanensis KUFA 0013(E1),Neosartorya paulistemis KUFC 7897(E2),Neosartorya siamensis KUFA 0017(E4) and Talaromyces trachyspermus KUFC 0021(E3) on a panel of seven human cancer cell lines.Methods:Effects on cell proliferation,induction of DNA damage and cell death were assessed by MTT and clonogenic assays,comet assay and nuclear condensation assay,respectively.Results:The proliferation of HepG2,HCTl 16 and A375 cells decreased after incubation with the extracts E2 and E4.The anti-proliterative effect was confirmed by morphologic alterations and by clonogenic assay.Both extracts also induced cell death in HepG2 and HCT116 cells.Doxorubicin was used as a positive control and showed in vitro anticancer activity.Conclusions:This study demonstrated,for the first time,that extracts of Neosartorya paulistensis and Neosartorya siamensis have selective anti-proliferative and cell death activities in HepG2,HCT16 and A375 cells.The bioactivity of these extracts suggests a potential for biotechnological applications and substantiates that both should be further considered for the elucidation of the molecular targets and signal transduction pathways involved.
