AIMTo evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition.METHODSTwenty healthy I...AIMTo evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition.METHODSTwenty healthy Italian volunteers, eight males and twelve females, participated in the study. Ten subjects took a sachet containing 4 × 10<sup>9</sup> colony-forming units (CFU) of Bifidobacterium longum BB536 and 10<sup>9</sup> CFU of Lactobacillus rhamnosus HN001, 30 min before breakfast (pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast (post-prandial administration). The ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine.RESULTSImmediately after 1-mo of probiotic administration, B. longum BB536 and L. rhamnosus HN001 load was increased in the majority of subjects in both pre-prandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in Firmicutes abundance was detected immediately after 1-mo of B. longum BB536 and L. rhamnosus HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of Proteobacteria abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of Blautia producta, Blautia wexlerae and Haemophilus ducrey was observed, together with a reduction of Holdemania filiformis, Escherichia vulneris, Gemmiger formicilis and Streptococcus sinensis abundance. In addition, during follow-up period we observed a further reduction in Escherichia vulneris and Gemmiger formicilis, together with a decrease in Roseburia faecis and Ruminococcus gnavus abundance. Conversely, the abundance of Akkermansia muciniphila was increased if compared to samples collected at the beginning of the experimental time courseCONCLUSIONB. longum BB536 and L. rhamnosus HN001 showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. Further studies are needed to better understand the specific mechanisms involved in gut microbiota modulation.展开更多
Surgical resection has been the mainstay of treatment of pharyngoesophageal(Zenker) diverticula over the past century. Developments in minimally invasive surgery and new endoscopic devices have led to a paradigm chang...Surgical resection has been the mainstay of treatment of pharyngoesophageal(Zenker) diverticula over the past century. Developments in minimally invasive surgery and new endoscopic devices have led to a paradigm change. The concept of dividing the septum between the esophagus and the pouch rather than resecting the pouch itself has been revisited during the last three decades and new technologies have been investigated to make the transoral operation safe and effective. The internal pharyngoesophageal myotomy accomplishedthrough the transoral stapling approach has been shown to effectively relieve outflow obstruction and restore physiological bolus transit in patients with medium size diverticula. Transoral techniques, either through a rigid device or by flexible endoscopy, are gaining popularity over the open surgical approach due the low morbidity, the fast recovery time and the fact that the procedure can be safely repeated. We provide an analysis of the the current status of minimally invasive endoscopic management of Zenker diverticulum.展开更多
AIM: To investigate long-term results and quality of life after transoral stapling of Zenker diverticulum.METHODS: The data of all patients admitted to our institution for the surgical treatment of Zenker diverticulum...AIM: To investigate long-term results and quality of life after transoral stapling of Zenker diverticulum.METHODS: The data of all patients admitted to our institution for the surgical treatment of Zenker diverticulum were entered into a prospective database. Demographics, symptoms, intraoperative and post-operative data, morbidity, time to oral feeding, and length of hospital stay were recorded. All patients underwent upper gastrointestinal endoscopy and a barium swallow study to measure the length of the diverticulum from the apex of the septum to the bottom of the pouch. Transoral stapling was performed using a Weerda diverticuloscope under general anesthesia. Over time, the technique was modified by applying traction sutures to ease engagement of the common septum inside the stapler jaws. Perioperative variables, symptoms, long-term outcome, and quality of life were analyzed. The operation was considered successful if the patient reported complete remission(grade 1) or marked improvement(grade 2) of dysphagia, regurgitation, and respiratory symptoms. Statistical analysis was performed using Statistical Package for Social Science(SPSS, Version 15, SPSS, Inc., Chicago, IL).RESULTS: Between 2001 and 2013, the transoral approach was successfully completed in 100 patients with a median age of 75 years. Patients with a larger(≥3 cm) diverticulum were older than those with a smaller pouch(P < 0.038). Complications occurred in 4% of the patients but there was no mortality. A statistically significant improvement of dysphagia and regurgitation scores(P < 0.001) was recorded over a median followup of 63 mo. Similarly, a significant decrease in the median number of pneumonia episodes per year(P < 0.001) was recorded after surgery. The overall longterm success rate of the procedure was 76%. The success rate of the operation was greater in patients of 70 years of age or older compared to younger individuals(P = 0.038). Use of traction sutures on the septum was associated with an improved success rate compared with the standard procedure(P = 0.04). All items of the health related quality of life questionnaire were significantly higher compared to baseline(P < 0.05).CONCLUSION: Transoral stapling is safe and effective. The operation significantly improves patients' quality of life. It appears that elderly patients with large diverticula significantly benefit from the procedure and that the modified surgical technique including traction sutures can further improve the success rate.展开更多
Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronav...Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronavirus disease,important points still remain to be clarified in this respect.Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID.However,one of the existing gaps that requires further investigation concerns a possible rela-tionship between gut candidiasis and long COVID.While recent studies also suggest an interplay between the occurrence of these two conditions,it is not yet fully clear how this may happen,as well as the specifics regarding the possible pathophysiological mechanisms involved.In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID,a better understanding of the clinical presentation,pathophysiology and clinical management of such a relationship should be essential and useful for both,additional advances towards more targeted research and appropriate case management.Knowing more about the signs,symptoms,and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population.In light of this and the need for better outcomes,here we review and discuss the content on different aspects of long COVID,including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis,as well as suggest propositions for future related research.INTRODUCTION Long coronavirus disease(COVID)is a condition characterized by the emergence of new symptoms or the persistence of existing symptoms for at least two months,three months after the initial infection[1].Although such a condition has initially been extensively studied,there are still many contradictions between the findings and methodologies of different related research articles[2,3].Within this context and since the middle of the COVID-19 pandemic,important studies have been published in the literature reporting the occurrence of fungal infections among COVID-19 patients[4,5],including mucormycosis,and oral candidiasis[6].On the other hand,evidence on a possible relationship between gut candidiasis and long COVID is still recent[7].Indeed,a marked gastrointestinal(GI)fungal dysbiosis together with perturbation of the lung-gut axis has been observed in severe COVID-19 patients.This combined with neutrophilia and an exacerbated worsening of the inflammatory response,which can be implicated in the acute and chronic immunopathology of such a viral disease[7,8].Furthermore,persistent changes in the immune system may also occur,resulting in a possible relationship with the occurrence of long COVID[7].However,more targeted evidence is still scarce and the specific topic related to gut candidiasis has been the subject of little discussion.In response to this,in this article we discuss general aspects of long COVID,the inherent pathophysiology and current evidence of a potential relationship between this condition and gut candidiasis,in addition to providing recommendations for future research.ACKNOWLEDGEMENTS Tovani-Palone MR thanks the Saveetha Institute of Medical and Technical Sciences for supporting this study.展开更多
Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity oft...Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.展开更多
Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and...Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.展开更多
Hepatitis B virus(HBV)is the leading cause of liver disease and infects an estimated 240 million people worldwide.It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcrip...Hepatitis B virus(HBV)is the leading cause of liver disease and infects an estimated 240 million people worldwide.It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication.The ten genotypes(A-J)that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution.Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe(mainly represented by subgenotypes D1-3 and A2);genotypes B and C are restricted to eastern Asia and Oceania;genotype E to central and western Africa;and genotypes H and F(classified into 4 subgenotypes)to Latin America and Alaska.This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes,particularly those concerning the origin and dispersion histories of genotypes A,D,E and F and their subgenotypes.The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain.It is hypothesised that HBV evolutionary rates are time dependent,and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.展开更多
BACKGROUND Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials(RCT).However,most RCTs do not provide data about clinical outcomes including ...BACKGROUND Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials(RCT).However,most RCTs do not provide data about clinical outcomes including lesions detection rate.Moreover,real-life comparisons are lacking.AIM To compare efficacy(both in terms of adequate bowel preparation and detection of colorectal lesions)and tolerability of a high-volume(HV:4 L polyethylene glycol,PEG)and a low-volume(LV:2 L PEG plus bisacodyl)bowel preparation in a real-life setting.METHODS Consecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016.Patients could choose either LV or HV preparation,with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures.Adequate bowel preparation according to Boston Bowel Preparation Scale(BBPS),clinical outcomes including polyp detection rate(PDR),adenoma detection rate(ADR),advanced adenoma detection rate(AADR),sessile/serrated lesion detection rate(SDR)and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed.RESULTS Total 2040 patients were enrolled and 1815(mean age 60.6 years,50.2%men)finally included.LV was chosen by 52%of patients(50.8%of men,54.9%of women).Split-dose schedule was more common with HV(44.7%vs 38.2%,P=0.005).High-definition scopes were used in 33.4%of patients,without difference in the two groups(P=0.605).HV and LV preparations showed similar adequate bowel preparation rates(89.2%vs 86.6%,P=0.098),also considering the two different schedules(HV split-dose 93.8%vs LV split-dose 93.6%,P=1;HV daybefore 85.5%vs LV day-before 82.3%,P=0.182).Mean global BBPS score was higher for HV preparations(7.1±1.7 vs 6.8±1.6,P<0.001).After adjustment for sex,age and indications for colonoscopy,HV preparation resulted higher in PDR[Odds ratio(OR)1.32,95%CI:1.07-1.63,P=0.011]and ADR(OR 1.29,95%CI 1.02–1.63,P=0.038)and comparable to LV in AADR(OR 1.51,95%CI 0.97-2.35,P=0.069),SDR and cancer detection rate.The use of standard-definition colonoscopes was associated to lower PDR(adjusted OR 1.59,95%CI:1.22-2.08,P<0.001),ADR(adjusted OR 1.71,95%CI:1.26–2.30,P<0.001)and AADR(adjusted OR 1.97,95%CI:1.09-3.56,P=0.025)in patients receiving LV preparation.Mean Visual Analogue Scale tolerability scored equally(7,P=0.627)but a≥75%dose intake was more frequent with LV(94.6%vs 92.1%,P=0.003).CONCLUSION In a real-life setting,PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation.However,with higher PDR and ADR,HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy,especially when colonoscopy is performed with standard resolution imaging.展开更多
AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-pro...AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin.Reconstituted human vaginal epithelium was exposed to a specific spermidinesupramolecular complex,i.e.,spermidine-hyaluronan(HA)50,and cell proliferation was determined by Ki-67immunohistochemical detection.Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.RESULTS:The effect of spermidine and spermidinesupramolecular complexes was first tested in skin fi-broblasts.Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition,whereas 30%stimulation over basal levels was detected at mol/L and nmol/L levels.Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers,such as HA,alginate,and polymaleate,were then tested at variable spermidine concentrations and a fixed polymer level(0.1%w/v).Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency(up to 80%)at sub-mol/L levels.Similar results were obtained with spermidine-(-cyclodextrin),another type of spermidine-supramolecular complex.Moreover,the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation.Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA,thus supporting its safety.CONCLUSION:Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects.Safety data on reconstituted human vaginal epithelium suggested that assessing spermidinesupramolecular complex efficacy in atrophic disorders is justified.展开更多
Purpose This study used downhill running as a model to investigate the repeated bout effect(RBE)on neuromuscular performance,running biomechanics,and metabolic cost of running.Methods Ten healthy recreational male run...Purpose This study used downhill running as a model to investigate the repeated bout effect(RBE)on neuromuscular performance,running biomechanics,and metabolic cost of running.Methods Ten healthy recreational male runners performed two 30-min bouts of downhill running(DR1 and DR2)at a-20%slope and 2.8 m/s 3 weeks apart.Neuromuscular fatigue,level running biomechanics during slow and fast running,and running economy parameters were recorded immediately before and after the downhill bouts,and at 24 h,48 h,72 h,96 h,and 168 h thereafter(i.e.,follow-up days).Results An RBE was confirmed by attenuated muscle soreness and serum creatine kinase rise after DR2 compared to DR1.An RBE was also observed in maximum voluntary contraction(MVC)force loss and voluntary activation where DR2 resulted in attenuated MVC force loss and voluntary activation immediately after the run and during follow-up days.The downhill running protocol significantly influenced level running biomechanics;an RBE was observed in which center of mass excursion and,therefore,lower-extremity compliance were greater during follow-up days after DR1 compared to DR2.The observed changes in level running biomechanics did not influence the energy cost of running.Conclusion This study demonstrated evidence of adaptation in neural drive as well as biomechanical changes with the RBE after DR.The higher neural drive resulted in attenuated MVC force loss after the second bout.It can be concluded that the RBE after downhill running manifests as changes to global and central fatigue parameters and running biomechanics without substantially altering the energy cost of running.展开更多
The musculoskeletal system involves multiple tissues which are constantly exposed to being exposed to various biological and mechanical stimuli.As such,isolating and studying a particular system from a complex human c...The musculoskeletal system involves multiple tissues which are constantly exposed to being exposed to various biological and mechanical stimuli.As such,isolating and studying a particular system from a complex human clinical environment is not always a realistic expectation.On top of that,recruitment limitations,in addition to the nature of orthopaedic interventions and their associated cost,sometimes preclude consideration of human trials to answer a clinical question.Therefore,in this mini review,we sought to rationalize the rapid evolution of biomedical research at a basic scientific level and explain why the perception of orthopaedic conditions has fundamentally changed over the last decades.In more detail,we highlight that the number of orthopaedic in vitro publications has soared since 1990.Last but not least,we elaborated on the minimum requirements for conducting a scientifically sound infection-related laboratory experiment to offer valuable information to clinical practitioners.We also explained the rationale behind implementing molecular biology techniques,ex vivo experiments,and artificial intelligence in this type of laboratory research.展开更多
Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advanceme...Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efficacy is lacking.The aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median sternotomy.Methods:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane Library.We included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median sternotomy.Studies were selected based on predefined inclusion criteria with-out publication year,design,or origin restrictions.Results:Six studies met the inclusion criteria,involving a total offive RCTs and one review.These studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment satisfaction.Most studies reported significant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and elasticity.Adverse events were generally mild and transient.Conclusions:Laser therapy offers a beneficial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median sternotomy.However,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this therapy.This review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.展开更多
Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis.The pathogenesis of IBD is not completely unraveled,IBD are multi-fa...Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis.The pathogenesis of IBD is not completely unraveled,IBD are multi-factorial diseases with reported alterations in the gut microbiota,activation of different immune cell types,changes in the vascular endothelium,and alterations in the tight junctions’structure of the colonic epithelial cells.Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens.It is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of IBD.Sometimes a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful biomarkers.Although some non-invasive biomarkers have been described,none can be considered as the“gold standard”for IBD diagnosis,disease activity and therapy outcome.For these reason new studies have proposed an“IBD signature”,which consists in a panel of biomarkers used to assess IBD.The above described approach characterizes“omics”and in this review we will focus on proteomics.展开更多
AIM: To analyze the effect of three-dimensional (3D)-arrangement on the expression of epithelial-to-mesenchymal transition markers in pancreatic adenocarcinoma (PDAC) cells.METHODS: HPAF-II, HPAC, and PL45 PDAC cells ...AIM: To analyze the effect of three-dimensional (3D)-arrangement on the expression of epithelial-to-mesenchymal transition markers in pancreatic adenocarcinoma (PDAC) cells.METHODS: HPAF-II, HPAC, and PL45 PDAC cells were cultured in either 2D-monolayers or 3D-spheroids. Ultrastructure was analyzed by transmission electron microscopy. The expression of E-cadherin, β-catenin, N-cadherin, collagen type I (COL-I), vimentin, α-smooth muscle actin (αSMA), and podoplanin was assayed by confocal microscopy in cells cultured on 12-mm diameter round coverslips and in 3D-spheroids. Gene expression for E-cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 was quantified by real-time PCR. E-cadherin protein level and its electrophoretic pattern were studied by Western blot in cell lysates obtained from cells grown in 2D-monolayers and 3D-spheroids.RESULTS: The E-cadherin/β-catenin complex was expressed in a similar way in plasma membrane cell boundaries in both 2D-monolayers and 3D-spheroids. E-cadherin increased in lysates obtained from 3D-spheroids, while cleavage fragments were more evident in 2D-monolayers. N-cadherin expression was observed in very few PDAC cells grown in 2D-monolayers, but was more evident in 3D-spheroids. Some cells expressing COL-I were observed in 3D-spheroids. Podoplanin, expressed in collectively migrating cells, and αSMA were similarly expressed in both experimental conditions. The concomitant maintenance of the E-cadherin/β-catenin complex at cell boundaries supports the hypothesis of a collective migration for these cells, which is consistent with podoplanin expression.CONCLUSION: We show that a 3D-cell culture model could provide deeper insight into understanding the biology of PDAC and allow for the detection of marked differences in the phenotype of PDAC cells grown in 3D-spheroids.展开更多
BACKGROUND Although the impact of microbial infections on orthopedic clinical outcomes is well recognized,the influence of viral infections on the musculoskeletal system might have been underestimated.AIM To systemati...BACKGROUND Although the impact of microbial infections on orthopedic clinical outcomes is well recognized,the influence of viral infections on the musculoskeletal system might have been underestimated.AIM To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.METHODS We searched MEDLINE,Cochrane Central Register of Controlled Trials(CENTRAL),the Reference Citation Analysis(RCA),and Scopus for completed studies published before January 30,2021,to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries.Quality assessment was performed using SYRCLE's risk of bias tool for animal studies,Moga score for case series,Wylde score for registry studies,and Newcastle-Ottawa Scale for case-control studies.RESULTS Six human and four animal studies were eligible for inclusion in the qualitative synthesis.Hepatitis C virus was implicated in several peri-and post-operative complications in patients without cirrhosis after major orthopedic surgery.Herpes virus may affect the integrity of lumbar discs,whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.CONCLUSION Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis.Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms.Therefore,based on our literature search,the proposed clinical and pathogenetic classification scheme is as follows:(1)Viral infections of bone or joint;(2)Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues;and(3)Viral infection as a risk factor for post-surgical bacterial infection.展开更多
Colonoscopy represents the most widespread and effective tool for the prevention and treatment of early stage preneoplastic and neoplastic lesions in the panorama of cancer screening.In the world there are different a...Colonoscopy represents the most widespread and effective tool for the prevention and treatment of early stage preneoplastic and neoplastic lesions in the panorama of cancer screening.In the world there are different approaches to the topic of colorectal cancer prevention and screening:different starting ages(45-50 years);different initial screening tools such as fecal occult blood with immunohistochemical or immune-enzymatic tests;recto-sigmoidoscopy;and colonoscopy.The key aspects of this scenario are composed of a proper bowel preparation that ensures a valid diagnostic examination,experienced endoscopist in detection of preneoplastic and early neoplastic lesions and open-minded to upcoming artificial intelligence-aided examination,knowledge in the field of resection of these lesions(from cold-snaring,through endoscopic mucosal resection and endoscopic submucosal dissection,up to advanced tools),and management of complications.展开更多
As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi,generic names of many groups should be reconsidered.Members of the ECMM/...As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi,generic names of many groups should be reconsidered.Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria,Scedosporium and allied taxa.The generic names Parascedosporium,Lomentospora,Petriella,Petriellopsis,and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy,annellidic conidia.Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species,some name changes are proposed.Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S.desertorum,respectively.Scedosporium prolificans is renamed as Lomentospora prolificans.展开更多
Aim:Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world.Tissue-engineering products offer a lower extremity salvage strategy when healing does not pro...Aim:Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world.Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care.New allogeneic sheets are available for the management of diabetic leg and foot ulcers.Methods:The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus.Results:Between 21 and 70 days after cellular therapy,6 out of 16 lesions were completely healed,reducing the wound dimension by 70%and improving the wound bed score by 52%.Conclusion:The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.展开更多
文摘AIMTo evaluate the ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize the intestinal environment of healthy subjects and modify the gut microbiota composition.METHODSTwenty healthy Italian volunteers, eight males and twelve females, participated in the study. Ten subjects took a sachet containing 4 × 10<sup>9</sup> colony-forming units (CFU) of Bifidobacterium longum BB536 and 10<sup>9</sup> CFU of Lactobacillus rhamnosus HN001, 30 min before breakfast (pre-prandial administration), while ten subjects took a sachet of probiotic product 30 min after breakfast (post-prandial administration). The ability of Lactobacillus rhamnosus HN001 and Bifidobacterium longum BB536 to colonize human gut microbiota was assessed by means of quantitative real-time PCR, while changes in gut microbiota composition were detected by using Ion Torrent Personal Genome Machine.RESULTSImmediately after 1-mo of probiotic administration, B. longum BB536 and L. rhamnosus HN001 load was increased in the majority of subjects in both pre-prandial and post-prandial groups. This increase was found also 1 mo after the end of probiotic oral intake in both groups, if compared to samples collected before probiotic consumption. At phyla level a significant decrease in Firmicutes abundance was detected immediately after 1-mo of B. longum BB536 and L. rhamnosus HN001 oral intake. This reduction persisted up to 1 mo after the end of probiotic oral intake together with a significant decrease of Proteobacteria abundance if compared to samples collected before probiotic administration. Whereas, at species level, a higher abundance of Blautia producta, Blautia wexlerae and Haemophilus ducrey was observed, together with a reduction of Holdemania filiformis, Escherichia vulneris, Gemmiger formicilis and Streptococcus sinensis abundance. In addition, during follow-up period we observed a further reduction in Escherichia vulneris and Gemmiger formicilis, together with a decrease in Roseburia faecis and Ruminococcus gnavus abundance. Conversely, the abundance of Akkermansia muciniphila was increased if compared to samples collected at the beginning of the experimental time courseCONCLUSIONB. longum BB536 and L. rhamnosus HN001 showed the ability to modulate the gut microbiota composition, leading to a significant reduction of potentially harmful bacteria and an increase of beneficial ones. Further studies are needed to better understand the specific mechanisms involved in gut microbiota modulation.
文摘Surgical resection has been the mainstay of treatment of pharyngoesophageal(Zenker) diverticula over the past century. Developments in minimally invasive surgery and new endoscopic devices have led to a paradigm change. The concept of dividing the septum between the esophagus and the pouch rather than resecting the pouch itself has been revisited during the last three decades and new technologies have been investigated to make the transoral operation safe and effective. The internal pharyngoesophageal myotomy accomplishedthrough the transoral stapling approach has been shown to effectively relieve outflow obstruction and restore physiological bolus transit in patients with medium size diverticula. Transoral techniques, either through a rigid device or by flexible endoscopy, are gaining popularity over the open surgical approach due the low morbidity, the fast recovery time and the fact that the procedure can be safely repeated. We provide an analysis of the the current status of minimally invasive endoscopic management of Zenker diverticulum.
文摘AIM: To investigate long-term results and quality of life after transoral stapling of Zenker diverticulum.METHODS: The data of all patients admitted to our institution for the surgical treatment of Zenker diverticulum were entered into a prospective database. Demographics, symptoms, intraoperative and post-operative data, morbidity, time to oral feeding, and length of hospital stay were recorded. All patients underwent upper gastrointestinal endoscopy and a barium swallow study to measure the length of the diverticulum from the apex of the septum to the bottom of the pouch. Transoral stapling was performed using a Weerda diverticuloscope under general anesthesia. Over time, the technique was modified by applying traction sutures to ease engagement of the common septum inside the stapler jaws. Perioperative variables, symptoms, long-term outcome, and quality of life were analyzed. The operation was considered successful if the patient reported complete remission(grade 1) or marked improvement(grade 2) of dysphagia, regurgitation, and respiratory symptoms. Statistical analysis was performed using Statistical Package for Social Science(SPSS, Version 15, SPSS, Inc., Chicago, IL).RESULTS: Between 2001 and 2013, the transoral approach was successfully completed in 100 patients with a median age of 75 years. Patients with a larger(≥3 cm) diverticulum were older than those with a smaller pouch(P < 0.038). Complications occurred in 4% of the patients but there was no mortality. A statistically significant improvement of dysphagia and regurgitation scores(P < 0.001) was recorded over a median followup of 63 mo. Similarly, a significant decrease in the median number of pneumonia episodes per year(P < 0.001) was recorded after surgery. The overall longterm success rate of the procedure was 76%. The success rate of the operation was greater in patients of 70 years of age or older compared to younger individuals(P = 0.038). Use of traction sutures on the septum was associated with an improved success rate compared with the standard procedure(P = 0.04). All items of the health related quality of life questionnaire were significantly higher compared to baseline(P < 0.05).CONCLUSION: Transoral stapling is safe and effective. The operation significantly improves patients' quality of life. It appears that elderly patients with large diverticula significantly benefit from the procedure and that the modified surgical technique including traction sutures can further improve the success rate.
文摘Since the beginning of the coronavirus disease(COVID)2019 pandemic,thou-sands of articles on the topic have been published,and although there is a growing trend of research on another associated condition,long coronavirus disease,important points still remain to be clarified in this respect.Robust evidence has suggested a relevant link between new clinical discoveries and molecular mechanisms that could be associated with the manifestations of different signs and symptoms involving cases of long COVID.However,one of the existing gaps that requires further investigation concerns a possible rela-tionship between gut candidiasis and long COVID.While recent studies also suggest an interplay between the occurrence of these two conditions,it is not yet fully clear how this may happen,as well as the specifics regarding the possible pathophysiological mechanisms involved.In this connection and with the advent of a potential strengthening of the body of evidence supporting the hypothesis of a link between gut candidiasis and long COVID,a better understanding of the clinical presentation,pathophysiology and clinical management of such a relationship should be essential and useful for both,additional advances towards more targeted research and appropriate case management.Knowing more about the signs,symptoms,and complications associated with cases of long COVID is essential in order to more effectively mitigate the related burden and provide a higher quality of care and life for the affected population.In light of this and the need for better outcomes,here we review and discuss the content on different aspects of long COVID,including its pathophysiology and the existing evidence of a potential relationship between such a condition and gut candidiasis,as well as suggest propositions for future related research.INTRODUCTION Long coronavirus disease(COVID)is a condition characterized by the emergence of new symptoms or the persistence of existing symptoms for at least two months,three months after the initial infection[1].Although such a condition has initially been extensively studied,there are still many contradictions between the findings and methodologies of different related research articles[2,3].Within this context and since the middle of the COVID-19 pandemic,important studies have been published in the literature reporting the occurrence of fungal infections among COVID-19 patients[4,5],including mucormycosis,and oral candidiasis[6].On the other hand,evidence on a possible relationship between gut candidiasis and long COVID is still recent[7].Indeed,a marked gastrointestinal(GI)fungal dysbiosis together with perturbation of the lung-gut axis has been observed in severe COVID-19 patients.This combined with neutrophilia and an exacerbated worsening of the inflammatory response,which can be implicated in the acute and chronic immunopathology of such a viral disease[7,8].Furthermore,persistent changes in the immune system may also occur,resulting in a possible relationship with the occurrence of long COVID[7].However,more targeted evidence is still scarce and the specific topic related to gut candidiasis has been the subject of little discussion.In response to this,in this article we discuss general aspects of long COVID,the inherent pathophysiology and current evidence of a potential relationship between this condition and gut candidiasis,in addition to providing recommendations for future research.ACKNOWLEDGEMENTS Tovani-Palone MR thanks the Saveetha Institute of Medical and Technical Sciences for supporting this study.
文摘Distinction between Crohn's disease of the colonrectum and ulcerative colitis or inflammatory bowel disease(IBD) type unclassified can be of pivotal importance for a tailored clinical management,as each entity often involves specific therapeutic strategies and prognosis.Nonetheless,no gold standard is available and the uncertainty of diagnosis may frequently lead to misclassification or repeated examinations.Hence,we have performed a literature search to address the problem of differential diagnosis in IBD colitis,revised current and emerging diagnostic tools and refined disease classification strategies.Nowadays,the differential diagnosis is an untangled issue,and the proper diagnosis cannot be reached in up to 10% of patients presenting with IBD colitis.This topic is receiving emerging attention,as medical therapies,surgical approaches and leading prognostic outcomes require more and more disease-specific strategies in IBD patients.The optimization of standard diagnostic approaches based on clinical features,biomarkers,radiology,endoscopy and histopathology appears to provide only marginal benefits.Conversely,emerging diagnostic techniques in the field of gastrointestinal endoscopy,molecular pathology,genetics,epigenetics,metabolomics and proteomics have already shown promising results.Novel advanced endoscopic imaging techniques and biomarkers can shed new light for the differential diagnosis of IBD,better reflecting diverse disease behaviors based on specific pathogenic pathways.
文摘Metabolic syndrome is a cluster of several clinical conditions characterized by insulin-resistance and high cardiovascular risk. Non-alcoholic fatty liver disease is the liver expression of the metabolic syndrome, and insulin resistance can be a frequent comorbidity in several chronic liver diseases, in particular hepatitis C virus infection and/or cirrhosis. Several studies have demonstrated that insulin action is not only relevant for glucose control, but also for vascular homeostasis. Insulin regulates nitric oxide production, which mediates to a large degree the vasodilating, antiinflammatory and antithrombotic properties of a healthy endothelium, guaranteeing organ perfusion. The effects of insulin on the liver microvasculature and the effects of IR on sinusoidal endothelial cells have been studied in animal models of non-alcoholic fatty liver disease. The hypotheses derived from these studies and the potential translation of these results into humans are critically discussed in this review.
文摘Hepatitis B virus(HBV)is the leading cause of liver disease and infects an estimated 240 million people worldwide.It is characterised by a high degree of genetic heterogeneity because of the use of a reverse transcriptase during viral replication.The ten genotypes(A-J)that have been described so far further segregate into a number of subgenotypes which have distinct ethno-geographic distribution.Genotypes A and D are ubiquitous and the most prevalent genotypes in Europe(mainly represented by subgenotypes D1-3 and A2);genotypes B and C are restricted to eastern Asia and Oceania;genotype E to central and western Africa;and genotypes H and F(classified into 4 subgenotypes)to Latin America and Alaska.This review summarises the data obtained by studying the global phylodynamics and phylogeography of HBV genotypes,particularly those concerning the origin and dispersion histories of genotypes A,D,E and F and their subgenotypes.The lack of any consensus concerning the HBV substitution rate and the conflicting data obtained using different calibration approaches make the time of origin and divergence of the various genotypes and subgenotypes largely uncertain.It is hypothesised that HBV evolutionary rates are time dependent,and that the changes depend on the main transmission routes of the genotypes and the dynamics of the infected populations.
文摘BACKGROUND Low-volume preparations for colonoscopy have shown similar efficacy compared to high-volume ones in randomized controlled trials(RCT).However,most RCTs do not provide data about clinical outcomes including lesions detection rate.Moreover,real-life comparisons are lacking.AIM To compare efficacy(both in terms of adequate bowel preparation and detection of colorectal lesions)and tolerability of a high-volume(HV:4 L polyethylene glycol,PEG)and a low-volume(LV:2 L PEG plus bisacodyl)bowel preparation in a real-life setting.METHODS Consecutive outpatients referred for colonoscopy were prospectively enrolled between 1 December 2014 and 31 December 2016.Patients could choose either LV or HV preparation,with a day-before schedule for morning colonoscopies and a split-dose for afternoon procedures.Adequate bowel preparation according to Boston Bowel Preparation Scale(BBPS),clinical outcomes including polyp detection rate(PDR),adenoma detection rate(ADR),advanced adenoma detection rate(AADR),sessile/serrated lesion detection rate(SDR)and cancer detection rate and self-reported tolerability of HV and LV were blindly assessed.RESULTS Total 2040 patients were enrolled and 1815(mean age 60.6 years,50.2%men)finally included.LV was chosen by 52%of patients(50.8%of men,54.9%of women).Split-dose schedule was more common with HV(44.7%vs 38.2%,P=0.005).High-definition scopes were used in 33.4%of patients,without difference in the two groups(P=0.605).HV and LV preparations showed similar adequate bowel preparation rates(89.2%vs 86.6%,P=0.098),also considering the two different schedules(HV split-dose 93.8%vs LV split-dose 93.6%,P=1;HV daybefore 85.5%vs LV day-before 82.3%,P=0.182).Mean global BBPS score was higher for HV preparations(7.1±1.7 vs 6.8±1.6,P<0.001).After adjustment for sex,age and indications for colonoscopy,HV preparation resulted higher in PDR[Odds ratio(OR)1.32,95%CI:1.07-1.63,P=0.011]and ADR(OR 1.29,95%CI 1.02–1.63,P=0.038)and comparable to LV in AADR(OR 1.51,95%CI 0.97-2.35,P=0.069),SDR and cancer detection rate.The use of standard-definition colonoscopes was associated to lower PDR(adjusted OR 1.59,95%CI:1.22-2.08,P<0.001),ADR(adjusted OR 1.71,95%CI:1.26–2.30,P<0.001)and AADR(adjusted OR 1.97,95%CI:1.09-3.56,P=0.025)in patients receiving LV preparation.Mean Visual Analogue Scale tolerability scored equally(7,P=0.627)but a≥75%dose intake was more frequent with LV(94.6%vs 92.1%,P=0.003).CONCLUSION In a real-life setting,PEG-based low-volume preparation with bisacodyl showed similar efficacy and tolerability compared to standard HV preparation.However,with higher PDR and ADR,HV should still be considered as the reference standard for clinical trials and the preferred option in screening colonoscopy,especially when colonoscopy is performed with standard resolution imaging.
基金Supported by Grants from the Italian Ministry of Education
文摘AIM:To test the growth-promoting activity of the polyamine spermidine bound to various polymeric compounds in supramolecular complexes.METHODS:A thiazolyl blue cell viability assay was used to determine the growth-promoting potency of spermidine-supramolecular complexes in a human skin fibroblast cell line exposed to spermidine and different spermidine-supramolecular complexes that were obtained by combining spermidine and polyanionic polymers or cyclodextrin.Reconstituted human vaginal epithelium was exposed to a specific spermidinesupramolecular complex,i.e.,spermidine-hyaluronan(HA)50,and cell proliferation was determined by Ki-67immunohistochemical detection.Transepithelial electrical resistance and histological analysis were also performed on reconstituted human vaginal epithelium to assess tissue integrity.RESULTS:The effect of spermidine and spermidinesupramolecular complexes was first tested in skin fi-broblasts.Spermidine displayed a reverse dose-related mode of activity with mmol/L growth inhibition,whereas 30%stimulation over basal levels was detected at mol/L and nmol/L levels.Novel spermidine-supramolecular complexes that formed between spermidine and polyanionic polymers,such as HA,alginate,and polymaleate,were then tested at variable spermidine concentrations and a fixed polymer level(0.1%w/v).Spermidine-supramolecular complexes stimulated the cell growth rate throughout the entire concentration range with maximal potency(up to 80%)at sub-mol/L levels.Similar results were obtained with spermidine-(-cyclodextrin),another type of spermidine-supramolecular complex.Moreover,the increased expression of Ki-67 in the reconstituted human vaginal epithelium exposed to spermidine-HA 50 showed that the mode of action behind the spermidine-supramolecular complexes was increased cell proliferation.Functional and morphological assessments of reconstituted human vaginal epithelium integrity did not show significant alterations after exposure to spermidine-HA,thus supporting its safety.CONCLUSION:Spermidine found in spermidine-supramolecular complexes displayed potentiated regenerative effects.Safety data on reconstituted human vaginal epithelium suggested that assessing spermidinesupramolecular complex efficacy in atrophic disorders is justified.
基金We thank the dedicated group of participants for their time and effort.We would also like to thank Michael Baggaley,Michael Esposito,Colin Lavigne,Stacy Lobos,Dr.Rogerio N.Soares,and Dr.Saied Jalal Aboodarda for their help with data collection.
文摘Purpose This study used downhill running as a model to investigate the repeated bout effect(RBE)on neuromuscular performance,running biomechanics,and metabolic cost of running.Methods Ten healthy recreational male runners performed two 30-min bouts of downhill running(DR1 and DR2)at a-20%slope and 2.8 m/s 3 weeks apart.Neuromuscular fatigue,level running biomechanics during slow and fast running,and running economy parameters were recorded immediately before and after the downhill bouts,and at 24 h,48 h,72 h,96 h,and 168 h thereafter(i.e.,follow-up days).Results An RBE was confirmed by attenuated muscle soreness and serum creatine kinase rise after DR2 compared to DR1.An RBE was also observed in maximum voluntary contraction(MVC)force loss and voluntary activation where DR2 resulted in attenuated MVC force loss and voluntary activation immediately after the run and during follow-up days.The downhill running protocol significantly influenced level running biomechanics;an RBE was observed in which center of mass excursion and,therefore,lower-extremity compliance were greater during follow-up days after DR1 compared to DR2.The observed changes in level running biomechanics did not influence the energy cost of running.Conclusion This study demonstrated evidence of adaptation in neural drive as well as biomechanical changes with the RBE after DR.The higher neural drive resulted in attenuated MVC force loss after the second bout.It can be concluded that the RBE after downhill running manifests as changes to global and central fatigue parameters and running biomechanics without substantially altering the energy cost of running.
文摘The musculoskeletal system involves multiple tissues which are constantly exposed to being exposed to various biological and mechanical stimuli.As such,isolating and studying a particular system from a complex human clinical environment is not always a realistic expectation.On top of that,recruitment limitations,in addition to the nature of orthopaedic interventions and their associated cost,sometimes preclude consideration of human trials to answer a clinical question.Therefore,in this mini review,we sought to rationalize the rapid evolution of biomedical research at a basic scientific level and explain why the perception of orthopaedic conditions has fundamentally changed over the last decades.In more detail,we highlight that the number of orthopaedic in vitro publications has soared since 1990.Last but not least,we elaborated on the minimum requirements for conducting a scientifically sound infection-related laboratory experiment to offer valuable information to clinical practitioners.We also explained the rationale behind implementing molecular biology techniques,ex vivo experiments,and artificial intelligence in this type of laboratory research.
文摘Background:Hypertrophic scars and keloids,common complications following median sternotomy for cardiac surgery,significantly impact patient quality of life due to their aesthetic and symptomatic burden.Recent advancements in laser therapy have made it a prominent option for managing these complex scars,yet a com-prehensive understanding of its efficacy is lacking.The aim of this scoping review is to explore the effects of laser therapy in managing hypertrophic scars and keloids after median sternotomy.Methods:This scoping review ana-lyzed studies up to February 2024 from databases including PubMed,EMBASE,CINAHL,Scopus,Web of Science,and the Cochrane Library.We included any study that assessed laser therapy’s effects on hypertrophic scars and keloids following median sternotomy.Studies were selected based on predefined inclusion criteria with-out publication year,design,or origin restrictions.Results:Six studies met the inclusion criteria,involving a total offive RCTs and one review.These studies primarily tested 585 and 595-nm pulsed dye laser(PDL)treatments,focusing on scar appearance,patient symptoms,and treatment satisfaction.Most studies reported significant improvements in scar height reduction and patient symptom relief after treatment,with mixed results for scar erythema and elasticity.Adverse events were generally mild and transient.Conclusions:Laser therapy offers a beneficial approach for improving the appearance and symptoms of hypertrophic scars and keloids post-median sternotomy.However,further research is necessary to optimize treatment parameters and explore the long-term psychosocial impacts of this therapy.This review highlights the need for more comprehensive studies to establish standardized treatment protocols and evaluate their effectiveness.
基金Supported by Italy’s Ministero Italiano della Salute(Italian Ministry of Health Grant)No.GR-2016-02364736
文摘Inflammatory bowel diseases(IBD)are chronic and relapsing inflammatory conditions of the gut that include Crohn's disease and ulcerative colitis.The pathogenesis of IBD is not completely unraveled,IBD are multi-factorial diseases with reported alterations in the gut microbiota,activation of different immune cell types,changes in the vascular endothelium,and alterations in the tight junctions’structure of the colonic epithelial cells.Proteomics represents a useful tool to enhance our biological understanding and to discover biomarkers in blood and intestinal specimens.It is expected to provide reproducible and quantitative data that can support clinical assessments and help clinicians in the diagnosis and treatment of IBD.Sometimes a differential diagnosis of Crohn's disease and ulcerative colitis and the prediction of treatment response can be deducted by finding meaningful biomarkers.Although some non-invasive biomarkers have been described,none can be considered as the“gold standard”for IBD diagnosis,disease activity and therapy outcome.For these reason new studies have proposed an“IBD signature”,which consists in a panel of biomarkers used to assess IBD.The above described approach characterizes“omics”and in this review we will focus on proteomics.
基金Supported by the University of Milan(Project B grant) and core support grant from the Wellcome Trust and MRC to the Wellcome Trust-Medical Research Council Cambridge Stem Cell Institute
文摘AIM: To analyze the effect of three-dimensional (3D)-arrangement on the expression of epithelial-to-mesenchymal transition markers in pancreatic adenocarcinoma (PDAC) cells.METHODS: HPAF-II, HPAC, and PL45 PDAC cells were cultured in either 2D-monolayers or 3D-spheroids. Ultrastructure was analyzed by transmission electron microscopy. The expression of E-cadherin, β-catenin, N-cadherin, collagen type I (COL-I), vimentin, α-smooth muscle actin (αSMA), and podoplanin was assayed by confocal microscopy in cells cultured on 12-mm diameter round coverslips and in 3D-spheroids. Gene expression for E-cadherin, Snail, Slug, Twist, Zeb1, and Zeb2 was quantified by real-time PCR. E-cadherin protein level and its electrophoretic pattern were studied by Western blot in cell lysates obtained from cells grown in 2D-monolayers and 3D-spheroids.RESULTS: The E-cadherin/β-catenin complex was expressed in a similar way in plasma membrane cell boundaries in both 2D-monolayers and 3D-spheroids. E-cadherin increased in lysates obtained from 3D-spheroids, while cleavage fragments were more evident in 2D-monolayers. N-cadherin expression was observed in very few PDAC cells grown in 2D-monolayers, but was more evident in 3D-spheroids. Some cells expressing COL-I were observed in 3D-spheroids. Podoplanin, expressed in collectively migrating cells, and αSMA were similarly expressed in both experimental conditions. The concomitant maintenance of the E-cadherin/β-catenin complex at cell boundaries supports the hypothesis of a collective migration for these cells, which is consistent with podoplanin expression.CONCLUSION: We show that a 3D-cell culture model could provide deeper insight into understanding the biology of PDAC and allow for the detection of marked differences in the phenotype of PDAC cells grown in 3D-spheroids.
文摘BACKGROUND Although the impact of microbial infections on orthopedic clinical outcomes is well recognized,the influence of viral infections on the musculoskeletal system might have been underestimated.AIM To systematically review the available evidence on risk factors and musculoskeletal manifestations following viral infections and to propose a pertinent classification scheme.METHODS We searched MEDLINE,Cochrane Central Register of Controlled Trials(CENTRAL),the Reference Citation Analysis(RCA),and Scopus for completed studies published before January 30,2021,to evaluate risk factors and bone and joint manifestations of viral infection in animal models and patient registries.Quality assessment was performed using SYRCLE's risk of bias tool for animal studies,Moga score for case series,Wylde score for registry studies,and Newcastle-Ottawa Scale for case-control studies.RESULTS Six human and four animal studies were eligible for inclusion in the qualitative synthesis.Hepatitis C virus was implicated in several peri-and post-operative complications in patients without cirrhosis after major orthopedic surgery.Herpes virus may affect the integrity of lumbar discs,whereas Ross River and Chikungunya viruses provoke viral arthritis and bone loss.CONCLUSION Evidence of moderate strength suggested that viruses can cause moderate to severe arthritis and osteitis.Risk factors such as pre-existing rheumatologic disease contributed to higher disease severity and duration of symptoms.Therefore,based on our literature search,the proposed clinical and pathogenetic classification scheme is as follows:(1)Viral infections of bone or joint;(2)Active bone and joint inflammatory diseases secondary to viral infections in other organs or tissues;and(3)Viral infection as a risk factor for post-surgical bacterial infection.
文摘Colonoscopy represents the most widespread and effective tool for the prevention and treatment of early stage preneoplastic and neoplastic lesions in the panorama of cancer screening.In the world there are different approaches to the topic of colorectal cancer prevention and screening:different starting ages(45-50 years);different initial screening tools such as fecal occult blood with immunohistochemical or immune-enzymatic tests;recto-sigmoidoscopy;and colonoscopy.The key aspects of this scenario are composed of a proper bowel preparation that ensures a valid diagnostic examination,experienced endoscopist in detection of preneoplastic and early neoplastic lesions and open-minded to upcoming artificial intelligence-aided examination,knowledge in the field of resection of these lesions(from cold-snaring,through endoscopic mucosal resection and endoscopic submucosal dissection,up to advanced tools),and management of complications.
文摘As a result of fundamental changes in the International Code of Nomenclature on the use of separate names for sexual and asexual stages of fungi,generic names of many groups should be reconsidered.Members of the ECMM/ISHAM working group on Pseudallescheria/Scedosporium infections herein advocate a novel nomenclature for genera and species in Pseudallescheria,Scedosporium and allied taxa.The generic names Parascedosporium,Lomentospora,Petriella,Petriellopsis,and Scedosporium are proposed for a lineage within Microascaceae with mostly Scedosporium anamorphs producing slimy,annellidic conidia.Considering that Scedosporium has priority over Pseudallescheria and that Scedosporium prolificans is phylogenetically distinct from the other Scedosporium species,some name changes are proposed.Pseudallescheria minutispora and Petriellidium desertorum are renamed as Scedosporium minutisporum and S.desertorum,respectively.Scedosporium prolificans is renamed as Lomentospora prolificans.
文摘Aim:Diabetic foot ulcers are the most common cause of nontraumatic lower extremity amputations in the industrialized world.Tissue-engineering products offer a lower extremity salvage strategy when healing does not proceed according to the standard of care.New allogeneic sheets are available for the management of diabetic leg and foot ulcers.Methods:The endpoints of this case series study regard preliminary outcomes of the application of allogeneic keratinocytes composed of benzyl ester of hyaluronic acid to 16 diabetic foot and leg ulcers in 11 patients with type 2 diabetes mellitus.Results:Between 21 and 70 days after cellular therapy,6 out of 16 lesions were completely healed,reducing the wound dimension by 70%and improving the wound bed score by 52%.Conclusion:The clinical results of the new allogeneic sheets indicate that allogeneic keratinocytes may represent an effective and safe therapy for diabetic foot and leg ulcers in the multidisciplinary approach to this diabetes-related complication.