Introduction: Vaccination faces several obstacles in the fight against COVID-19, yet it has been identified as one of the most effective means of preventing new epidemics of COVID-19. The aim was to contribute to impr...Introduction: Vaccination faces several obstacles in the fight against COVID-19, yet it has been identified as one of the most effective means of preventing new epidemics of COVID-19. The aim was to contribute to improving vaccination coverage against COVID-19 in the Kindu health zone. Method: We conducted a cross-sectional descriptive study with an analytical focus, using a questionnaire that enabled us to carry out a survey from October 03 to 30, 2022. Our target study population was residents of the Kindu health zone. A total of 420 subjects participated in our study, including 42 per site. Results: The study revealed a low proportion of vaccinated subjects (38.3%) and a high proportion of non-vaccinated subjects (61.70%). Non-belief in the efficacy of vaccines (p = 0.001), infodemia (p = 0.001) and respect for ethnic norms (p = 0.001) were identified as perceived barriers to vaccination. Fear of being branded with the “666” beast badge (p = 0.004) as the perceived severity. Respondents’ perceptions of mass vaccination against COVID-19 are mixed, and their opinions and expectations of COVID-19 vaccination in the town of Kindu are divided. Conclusion: In order to increase the proportion of people vaccinated against COVID-19, it is suggested here to increase the population’s ability to detect false information through a well-structured communication and health education program.展开更多
BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highli...BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.展开更多
Dissolved organic matter(DOM)in surface waters can vary markedly in character depending on seasonal variations such as rainfall intensity,UV radiations and temperature.Changes in DOM as well as temperature and rainfal...Dissolved organic matter(DOM)in surface waters can vary markedly in character depending on seasonal variations such as rainfall intensity,UV radiations and temperature.Changes in DOM as well as temperature and rainfall intensity over the year can affect the biochemical processes occurring in bank filtration(BF).Identification and characterization of DOM in the surface water could help to optimize the water treatment and provide stable and safe drinking water.This study investigated year-long variations of DOM concentrations and compositions in a surface water of a circulated outdoor pond(research facility)connected to a BF passage.DOM was dominated by humic substances and a changing pattern of DOM in surface water was observed throughout the year.A significant increase of DOM(~38%)in surface water was noted in August compared to November.The fluorescent DOM showed that DOM in summer was enriched with the degradable fraction whilst non-degradable fraction was dominated in winter.A constant(1.7±0.1 mg/L)effluent DOM was recirculated in the system throughout the year.DOM removal through BF varied between 4%to 39%and was achieved within a few meters after infiltration and significantly correlated with influent DOM concentration(R^(2)=0.82,p<0.05).However,no significant(p>0.05)change in the removal of DOM was observed in two subsurface layers(upper and lower).This study highlights the presence of a constant non-degradable DOM in the bank filtrate,which was not affected by temperature,redox conditions and UV radiations.展开更多
Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by ...Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.展开更多
Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serio...Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.展开更多
BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication...BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.展开更多
The Gelsari and Lentini marshes, in east-central Sicily, are wetland under heavy anthropogenic pressure. This area is regularly subjected to water withdrawals and agriculture is practiced. Periodic bird census activit...The Gelsari and Lentini marshes, in east-central Sicily, are wetland under heavy anthropogenic pressure. This area is regularly subjected to water withdrawals and agriculture is practiced. Periodic bird census activities had been conducted in this area between 2016 and 2022 with collected data being supplemented with the data from a previous survey conducted between 2010 and 2016. During the censuses, numerous photographs were collected, which were later used for counts. In total, 121 surveys were carried out, with visits occurring approximately 20 times per year, covering all seasons. The data collected, both from bibliography and unpublished observations, were organised in table. 120 species and subspecies have been reported, 41 of which are in Annex I of the Birds Directive. Between 2021 and 2022, a water column measurement was taken in a central area of the Lentini marsh and compared with rainfall data in the area. It was found that water removal, occurring in both marshes in different modes, produced different effects on habitat conservation. Of the two marshes, Lentini is the one in which the existing favorable conditions in its most depressed areas, located below sea level, have allowed for the adequate conservation of the wetland. This environmental improvement having occurred with respect to the previous period has restored to the marsh its historically recognized possibility of not drying up completely during the summer period, allowing permanence of numerous birds. The obtained results suggest total elimination of agriculture and discontinuation of water withdrawals in the Lentini marsh as well as regulation of withdrawals in the Gelsari marsh.展开更多
Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle g...Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.展开更多
Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the ...Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.展开更多
In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumo...In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumors(LST).LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection.According to the Paris classification,NPTs are distinguished in slightly elevated(0-Ⅱa,less than 2.5 mm),flat(0-Ⅱb) or slightly depressed(0-Ⅱc).NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions,cell proliferation growth progresses in depth in the colonic wall,thus leading to an increased risk of submucosal invasion(SMI) even for smaller neoplasms.NPTs may be frequently missed by inexperienced endoscopists,thus a careful training and precise assessment of all suspected mucosal areas should be performed.Chromoendoscopy or,if possible,narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs,and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and,therefore,to guide the therapeutic decision.Lesions suitable to endoscopic resection are those confined to the mucosa(or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible.Endoscopic mucosal resection(EMR,piecemeal for LSTs > 20 mm,en bloc for smaller neoplasms) remains the first-line therapy for NPTs,whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR.After piecemeal EMR,follow-up colonoscopy should be performed at 3 mo to assess resection completeness.In case of en bloc resection,surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm,or in presence of villous features or high-grade dysplasia patients(regardless of the size),while less intensive surveillance(colonoscopy at 5-10 years) is needed in case of single(or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.展开更多
Water soluble organic carbon （WSOC） is considered the most mobile and reactive soil carbon source and its characterization is an important issue for soil ecology study. A biodegradability test was set up to study WS...Water soluble organic carbon （WSOC） is considered the most mobile and reactive soil carbon source and its characterization is an important issue for soil ecology study. A biodegradability test was set up to study WSOC extracted from 7 soils differently managed. WSOC was extracted from soil with water （soil/water ratio of 1：2, W/V） for 30 min, and then tested for biodegradability by a liquid state respirometric test. Result obtained confirmed the finding that WSOC biodegradability depended on the both land use and management practice. These results suggested the biodegradability test as suitable method to characterize WSOC, and provided useful information to soil fertility.展开更多
The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropa...The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation-involving the activation and proliferation of resident glial cells(astrocytes, Muller cells and microglia) and the release of a plethora of anti-and pro-inflammatory cytokines, chemokines and reactive oxygen species-has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma.展开更多
Esophageal achalasia is the most commonly diagnosed primary esophageal motor disorder and the second most common functional esophageal disorder. Current therapy of achalasia is directed toward elimination of the outfl...Esophageal achalasia is the most commonly diagnosed primary esophageal motor disorder and the second most common functional esophageal disorder. Current therapy of achalasia is directed toward elimination of the outflow resistance caused by failure of the lower esophageal sphincter to relax completely upon swallow- ing. The advent of minimally invasive surgery has nearly replaced endoscopic pneumatic dilation as the fi rst-line therapeutic approach. In this editorial, the rationale and the evidence supporting the use of laparoscopic Hel- ler myotomy combined with fundoplication as a primary treatment of achalasia are reviewed.展开更多
Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-...Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during longterm culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-re- lated transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.展开更多
文摘Introduction: Vaccination faces several obstacles in the fight against COVID-19, yet it has been identified as one of the most effective means of preventing new epidemics of COVID-19. The aim was to contribute to improving vaccination coverage against COVID-19 in the Kindu health zone. Method: We conducted a cross-sectional descriptive study with an analytical focus, using a questionnaire that enabled us to carry out a survey from October 03 to 30, 2022. Our target study population was residents of the Kindu health zone. A total of 420 subjects participated in our study, including 42 per site. Results: The study revealed a low proportion of vaccinated subjects (38.3%) and a high proportion of non-vaccinated subjects (61.70%). Non-belief in the efficacy of vaccines (p = 0.001), infodemia (p = 0.001) and respect for ethnic norms (p = 0.001) were identified as perceived barriers to vaccination. Fear of being branded with the “666” beast badge (p = 0.004) as the perceived severity. Respondents’ perceptions of mass vaccination against COVID-19 are mixed, and their opinions and expectations of COVID-19 vaccination in the town of Kindu are divided. Conclusion: In order to increase the proportion of people vaccinated against COVID-19, it is suggested here to increase the population’s ability to detect false information through a well-structured communication and health education program.
文摘BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)is a leading cause of chronic liver disease globally.Current diagnostic methods,such as liver biopsies,are invasive and have limitations,highlighting the need for non-invasive alternatives.AIM To investigate extracellular vesicles(EVs)as potential biomarkers for diagnosing and staging steatosis in patients with MASLD using machine learning(ML)and explainable artificial intelligence(XAI).METHODS In this single-center observational study,798 patients with metabolic dysfunction were enrolled.Of these,194 met the eligibility criteria,and 76 successfully completed all study procedures.Transient elastography was used for steatosis and fibrosis staging,and circulating plasma EV characteristics were analyzed through nanoparticle tracking.Twenty ML models were developed:Six to differentiate non-steatosis(S0)from steatosis(S1-S3);and fourteen to identify severe steatosis(S3).Models utilized EV features(size and concentration),clinical(advanced fibrosis and presence of type 2 diabetes mellitus),and anthropomorphic(sex,age,height,weight,body mass index)data.Their performance was assessed using receiver operating characteristic(ROC)-area under the curve(AUC),specificity,and sensitivity,while correlation and XAI analysis were also conducted.RESULTS The CatBoost C1a model achieved an ROC-AUC of 0.71/0.86(train/test)on average across ten random five-fold cross-validations,using EV features alone to distinguish S0 from S1-S3.The CatBoost C2h-21 model achieved an ROC-AUC of 0.81/1.00(train/test)on average across ten random three-fold cross-validations,using engineered features including EVs,clinical features like diabetes and advanced fibrosis,and anthropomorphic data like body mass index and weight for identifying severe steatosis(S3).Key predictors included EV mean size and concentration.Correlation,XAI,and SHapley Additive exPlanations analysis revealed non-linear feature relationships with steatosis stages.CONCLUSION The EV-based ML models demonstrated that the mean size and concentration of circulating plasma EVs constituted key predictors for distinguishing the absence of significant steatosis(S0)in patients with metabolic dysfunction,while the combination of EV,clinical,and anthropomorphic features improved the diagnostic accuracy for the identification of severe steatosis.The algorithmic approach using ML and XAI captured non-linear patterns between disease features and provided interpretable MASLD staging insights.However,further large multicenter studies,comparisons,and validation with histopathology and advanced imaging methods are needed.
基金supported by the German Academic Exchange Service (DAAD)and Higher Education Commission (HEC),Pakistan。
文摘Dissolved organic matter(DOM)in surface waters can vary markedly in character depending on seasonal variations such as rainfall intensity,UV radiations and temperature.Changes in DOM as well as temperature and rainfall intensity over the year can affect the biochemical processes occurring in bank filtration(BF).Identification and characterization of DOM in the surface water could help to optimize the water treatment and provide stable and safe drinking water.This study investigated year-long variations of DOM concentrations and compositions in a surface water of a circulated outdoor pond(research facility)connected to a BF passage.DOM was dominated by humic substances and a changing pattern of DOM in surface water was observed throughout the year.A significant increase of DOM(~38%)in surface water was noted in August compared to November.The fluorescent DOM showed that DOM in summer was enriched with the degradable fraction whilst non-degradable fraction was dominated in winter.A constant(1.7±0.1 mg/L)effluent DOM was recirculated in the system throughout the year.DOM removal through BF varied between 4%to 39%and was achieved within a few meters after infiltration and significantly correlated with influent DOM concentration(R^(2)=0.82,p<0.05).However,no significant(p>0.05)change in the removal of DOM was observed in two subsurface layers(upper and lower).This study highlights the presence of a constant non-degradable DOM in the bank filtrate,which was not affected by temperature,redox conditions and UV radiations.
文摘Chronic viral hepatitis causes an increased risk of progressive liver disease and hepatocellular carcinoma.On the wave of the World Health Organization’s goal to reduce new cases and deaths from hepatitis B and C by 2030,there is an increasing call to expand the indications for treatment of chronic hepatitis B.Currently,the main goal of treatment is to achieve a functional cure due to the inability of current drugs to completely eradicate the virus.There are still many discrepancies between available guidelines in terms of eligibility for treatment as well as an uncertainty about the appropriate treatment duration.This editorial addresses key questions about the topic and whether indications for treatment should be expanded.
基金supported by PON AIM(PON RICERCA E INNOVAZIONE 2014-2020,-AZIONE I.2.D.D.N.407 DEL 27 FEBBRAIO 2018-“ATTRACTION AND INTERNATIONAL MOBILITY”)(to GC)Zardi-Gori Foundation(research grant 2021)(to MS)+1 种基金intramural funds from the University of Cagliari(to NS)Fondazione CON IL SUD and The U.S.-Italy Fulbright Commission(to AEP).
文摘Preclinical and clinical studies indicate that psychostimulants,in addition to having abuse potential,may elicit brain dysfunctions and/or neurotoxic effects.Central toxicity induced by psychostimulants may pose serious health risks since the recreational use of these substances is on the rise among young people and adults.The present review provides an overview of recent research,conducted between 2018 and 2023,focusing on brain dysfunctions and neurotoxic effects elicited in experimental models and humans by amphetamine,cocaine,methamphetamine,3,4-methylenedioxymethamphetamine,methylphenidate,caffeine,and nicotine.Detailed elucidation of factors and mechanisms that underlie psychostimulant-induced brain dysfunction and neurotoxicity is crucial for understanding the acute and enduring noxious brain effects that may occur in individuals who use psychostimulants for recreational and/or therapeutic purposes.
文摘BACKGROUND Acute liver failure(ALF)may be the first and most dramatic presentation of Wilson’s disease(WD).ALF due to WD(WD-ALF)is difficult to distinguish from other causes of liver disease and is a clear indication for liver transplantation.There is no firm recommendation on specific and supportive medical treatment for this condition.AIM To critically evaluate the diagnostic and therapeutic management of WD-ALF patients in order to improve their survival with native liver.METHODS A retrospective analysis of patients with WD-ALF was conducted in two pediatric liver units from 2018 to 2023.RESULTS During the study period,16 children(9 males)received a diagnosis of WD and 2 of them presented with ALF.The first was successfully treated with an unconventional combination of low doses of D-penicillamine and zinc plus steroids,and survived without liver transplant.The second,exclusively treated with supportive therapy,needed a hepatotransplant to overcome ALF.CONCLUSION Successful treatment of 1 WD-ALF patient with low-dose D-penicillamine and zinc plus steroids may provide new perspectives for management of this condition,which is currently only treated with liver transplantation.
文摘The Gelsari and Lentini marshes, in east-central Sicily, are wetland under heavy anthropogenic pressure. This area is regularly subjected to water withdrawals and agriculture is practiced. Periodic bird census activities had been conducted in this area between 2016 and 2022 with collected data being supplemented with the data from a previous survey conducted between 2010 and 2016. During the censuses, numerous photographs were collected, which were later used for counts. In total, 121 surveys were carried out, with visits occurring approximately 20 times per year, covering all seasons. The data collected, both from bibliography and unpublished observations, were organised in table. 120 species and subspecies have been reported, 41 of which are in Annex I of the Birds Directive. Between 2021 and 2022, a water column measurement was taken in a central area of the Lentini marsh and compared with rainfall data in the area. It was found that water removal, occurring in both marshes in different modes, produced different effects on habitat conservation. Of the two marshes, Lentini is the one in which the existing favorable conditions in its most depressed areas, located below sea level, have allowed for the adequate conservation of the wetland. This environmental improvement having occurred with respect to the previous period has restored to the marsh its historically recognized possibility of not drying up completely during the summer period, allowing permanence of numerous birds. The obtained results suggest total elimination of agriculture and discontinuation of water withdrawals in the Lentini marsh as well as regulation of withdrawals in the Gelsari marsh.
基金supported by a Sara Borrell postdoctoral contract granted by Instituto de Salud Carlos III(CD21/00138).PLV,DB-G and AL are funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Alejandro Lucia,Grant No.PI18/00139)TP is funded by the Spanish Ministry of Economy and Competitiveness and Fondos Feder(Tomas Pinos,Grant No.PI22/00201).
文摘Background:This study aimed to determine the effect of different carbohydrate(CHO)doses on exercise capacity in patients with McArdle disease—the paradigm of“exercise intolerance”,characterized by complete muscle glycogen unavailability—and to determine whether higher exogenous glucose levels affect metabolic responses at the McArdle muscle cell(in vitro)level.Methods:Patients with McArdle disease(n=8)and healthy controls(n=9)underwent a 12-min submaximal cycling constant-load bout followed by a maximal ramp test 15 min after ingesting a non-caloric placebo.In a randomized,double-blinded,cross-over design,patients repeated the tests after consuming either 75 g or 150 g of CHO(glucose:fructose=2:1).Cardiorespiratory,biochemical,perceptual,and electromyographic(EMG)variables were assessed.Additionally,glucose uptake and lactate appearance were studied in vitro in wild-type and McArdle mouse myotubes cultured with increasing glucose concentrations(0.35,1.00,4.50,and 10.00 g/L).Results:Compared with controls,patients showed the“classical”second-wind phenomenon(after prior disproportionate tachycardia,myalgia,and excess electromyographic activity during submaximal exercise,all p<0.05)and an impaired endurance exercise capacity(-51%ventilatory threshold and55%peak power output,both p<0.001).Regardless of the CHO dose(p<0.05 for both doses compared with the placebo),CHO intake increased blood glucose and lactate levels,decreased fat oxidation rates,and attenuated the second wind in the patients.However,only the higher dose increased ventilatory threshold(+27%,p=0.010)and peak power output(+18%,p=0.007).In vitro analyses revealed no differences in lactate levels across glucose concentrations in wild-type myotubes,whereas a doseresponse effect was observed in McArdle myotubes.Conclusion:CHO intake exerts beneficial effects on exercise capacity in McArdle disease,a condition associated with total muscle glycogen unavailability.Some of these benefits are dose dependent.
文摘Inflammatory bowel diseases (IBD) are complex multifactorial disorders that include Crohn’s disease (CD) and ulcerative colitis (UC). Considering that IBD is a genetic and multifactorial disease, we screened for the distribution dynamism of IBD pathogenic genetic variants (single nucleotide polymorphisms;SNPs) and risk factors in four (4) IBD pediatric patients, by integrating both clinical exome sequencing and computational statistical approaches, aiming to categorize IBD patients in CD and UC phenotype. To this end, we first aligned genomic read sequences of these IBD patients to hg19 human genome by using bowtie 2 package. Next, we performed genetic variant calling analysis in terms of single nucleotide polymorphism (SNP) for genes covered by at least 20 read genomic sequences. Finally, we checked for biological and genomic functions of genes exhibiting statistically significant genetic variant (SNPs) by introducing Fitcon genomic parameter. Findings showed Fitcon parameter as normalizing IBD patient’s population variability, as well as inducing a relative good clustering between IBD patients in terms of CD and UC phenotypes. Genomic analysis revealed a random distribution of risk factors and as well pathogenic SNPs genetic variants in the four IBD patient’s genome, claiming to be involved in: i) Metabolic disorders, ii) Autoimmune deficiencies;iii) Crohn’s disease pathways. Integration of genomic and computational statistical analysis supported a relative genetic variability regarding IBD patient population by processing IBD pathogenic SNP genetic variants as opposite to IBD risk factor variants. Interestingly, findings clearly allowed categorizing IBD patients in CD and UC phenotypes by applying Fitcon parameter in selecting IBD pathogenic genetic variants. Considering as a whole, the study suggested the efficiency of integrating clinical exome sequencing and computational statistical tools as a right approach in discriminating IBD phenotypes as well as improving inflammatory bowel disease (IBD) molecular diagnostic process.
基金国家自然科学青年基金项目(31501851)四川大学优秀青年教师名师名校访学项目+9 种基金环保部生物多样性示范监测项目生物安全监测系统应用模拟与示范推广项目(2016YFC12000705)中国科学院国际高级访问学者项目(2011T2S04)National Geographic Society/Waitt FundFunds from the American Philosophical Societythe American Museum of Natural Historythe American Ornithologists’ Unionthe Society for the Study of Evolutionthe Paulson Institutethe Animal Behavior Society等项目
基金国家科技支撑计划资助项目(2013BAD11B03)国家重点基础研究发展计划项目(973计划)(2012CB955904)+1 种基金The University of Melbourne Early Career Research Grant Scheme 2014中央级公益性科研院所基本科研业务费专项资助项目
文摘In the last years,an increasing interest has been raised on non-polypoid colorectal tumors(NPT) and in particular on large flat neoplastic lesions beyond 10 mm tending to grow laterally,called laterally spreading tumors(LST).LSTs and large sessile polyps have a greater frequency of high-grade dysplasia and local invasiveness as compared to pedunculated lesions of the same size and usually represent a technical challenge for the endoscopist in terms of either diagnosis and resection.According to the Paris classification,NPTs are distinguished in slightly elevated(0-Ⅱa,less than 2.5 mm),flat(0-Ⅱb) or slightly depressed(0-Ⅱc).NPTs are usually flat or slightly elevated and tend to spread laterally while in case of depressed lesions,cell proliferation growth progresses in depth in the colonic wall,thus leading to an increased risk of submucosal invasion(SMI) even for smaller neoplasms.NPTs may be frequently missed by inexperienced endoscopists,thus a careful training and precise assessment of all suspected mucosal areas should be performed.Chromoendoscopy or,if possible,narrow-band imaging technique should be considered for the estimation of SMI risk of NPTs,and the characterization of pit pattern and vascular pattern may be useful to predict the risk of SMI and,therefore,to guide the therapeutic decision.Lesions suitable to endoscopic resection are those confined to the mucosa(or superficial layer of submucosa in selected cases) whereas deeper invasion makes endoscopic therapy infeasible.Endoscopic mucosal resection(EMR,piecemeal for LSTs > 20 mm,en bloc for smaller neoplasms) remains the first-line therapy for NPTs,whereas endoscopic submucosal dissection in high-volume centers or surgery should be considered for large LSTs for which en bloc resection is mandatory and cannot be achieved by means of EMR.After piecemeal EMR,follow-up colonoscopy should be performed at 3 mo to assess resection completeness.In case of en bloc resection,surveillance colonoscopy should be scheduled at 3 years for adenomatous lesions ≥ 1 cm,or in presence of villous features or high-grade dysplasia patients(regardless of the size),while less intensive surveillance(colonoscopy at 5-10 years) is needed in case of single(or two) NPT < 1 cm presenting tubular features or low-grade dysplasia at histology.
文摘Water soluble organic carbon （WSOC） is considered the most mobile and reactive soil carbon source and its characterization is an important issue for soil ecology study. A biodegradability test was set up to study WSOC extracted from 7 soils differently managed. WSOC was extracted from soil with water （soil/water ratio of 1：2, W/V） for 30 min, and then tested for biodegradability by a liquid state respirometric test. Result obtained confirmed the finding that WSOC biodegradability depended on the both land use and management practice. These results suggested the biodegradability test as suitable method to characterize WSOC, and provided useful information to soil fertility.
文摘The pathogenesis of glaucoma is still not fully clarified but a growing body of evidence suggests that neuroinflammation and immune response are part of the sequence of pathological events leading to the optic neuropathy. Indeed, inflammation-involving the activation and proliferation of resident glial cells(astrocytes, Muller cells and microglia) and the release of a plethora of anti-and pro-inflammatory cytokines, chemokines and reactive oxygen species-has been reported as common features in clinical and experimental glaucoma. In the insulted retina, as for other neuronal tissues, pathogenic and reparative aspects coexist in the inflammatory process, with extent and persistency affecting the final outcome. In view of this, therapies aimed at modulating the immune and inflammatory responses may represent a promising approach for limiting the optic nerve damage and the loss of retinal ganglion cells associated with glaucoma.
文摘Esophageal achalasia is the most commonly diagnosed primary esophageal motor disorder and the second most common functional esophageal disorder. Current therapy of achalasia is directed toward elimination of the outflow resistance caused by failure of the lower esophageal sphincter to relax completely upon swallow- ing. The advent of minimally invasive surgery has nearly replaced endoscopic pneumatic dilation as the fi rst-line therapeutic approach. In this editorial, the rationale and the evidence supporting the use of laparoscopic Hel- ler myotomy combined with fundoplication as a primary treatment of achalasia are reviewed.
基金part supported by the Department of Biomedical Sciences and Biotechnologies,Medical School,University of Catania,Italy(National Grant.PON 01_00110)
文摘Aging is the most prominent risk factor contributing to the development of neurodegenerative disorders. In the United States, over 35 million of elderly people suffer from age-related diseases. Aging impairs the self-repair ability of neuronal cells, which undergo progressive deterioration. Once initiated, this process hampers the already limited regenerative power of the central nervous system, making the search for new therapeutic strategies particularly difficult in elderly affected patients. So far, mesenchymal stem cells have proven to be a viable option to ameliorate certain aspects of neurodegeneration, as they possess high proliferative rate and differentiate in vitro into multiple lineages. However, accumulating data have demonstrated that during longterm culture, mesenchymal stem cells undergo spontaneous transformation. Transformed mesenchymal stem cells show typical features of senescence, including the progressive shortening of telomers, which results in cell loss and, as a consequence, hampered regenerative potential. These evidences, in line with those observed in mesenchymal stem cells isolated from old donors, suggest that senescence may represent a limit to mesenchymal stem cells exploitation in therapy, prompting scholars to either find alternative sources of pluripotent cells or to arrest the age-re- lated transformation. In the present review, we summarize findings from recent literature, and critically discuss some of the major hurdles encountered in the search of appropriate sources of mesenchymal stem cells, as well as benefits arising from their use in neurodegenerative diseases. Finally, we provide some insights that may aid in the development of strategies to arrest or, at least, delay the aging of mesenchymal stem cells to improve their therapeutic potential.
