Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation a...Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.展开更多
In the last few years,preclinical and clinical studies identified the ventral tegmental area(VTA)as one of the first brain regions to be affected in the prodromal phase of Alzheimer's disease(AD).The VTA is a deep...In the last few years,preclinical and clinical studies identified the ventral tegmental area(VTA)as one of the first brain regions to be affected in the prodromal phase of Alzheimer's disease(AD).The VTA is a deep midbrain nucleus rich in dopaminergic neurons that innervates and releases dopamine(DA)in several cortical and subcortical brain regions.DA plays a crucial role in the modulation of both cognitive and noncognitive functions and failure of its release underlies both cognitive and neuropsychiatric symptoms in patients with AD.展开更多
Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer (CRC) initiation and progression. Recent genome-wide data have confirmed that in CRC this path...Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer (CRC) initiation and progression. Recent genome-wide data have confirmed that in CRC this pathway is one of the most frequently modified by genetic or epigenetic alterations affecting almost 90% of Wnt/β-catenin gene members. A major challenge is thus learning how the corrupted coordination of this pathway is tied to other signalings to enhance cell growth. Peroxisome proliferator activated receptor γ (PPARγ) is emerging as a growth-limiting and differentiation-promoting factor. In tumorigenesis it exerts a tumor suppressor role and is potentially linked with the Wnt/β-catenin pathway. Based on these results, the identification of new selective PPARγ modulators with inhibitory effects on the Wnt/β-catenin pathway is becoming an interesting perspective. Should, in fact, these molecules display such properties, new research avenues would be opened aimed at developing new molecular targeted drugs. Herein, we review the basic principles and present new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ signaling. Furthermore, we discuss the advances in our understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PPARγ agonists endowed with Wnt/β-catenin inhibitory effects to be used as therapeutic and/or preventive agents.展开更多
According to Barcelona Clinic Liver Cancer recommendations,intermediate stage hepatocellular carcinomas(stage B)are excluded from liver resection and are referred to palliative treatment.Moreover,Child-Pugh B patients...According to Barcelona Clinic Liver Cancer recommendations,intermediate stage hepatocellular carcinomas(stage B)are excluded from liver resection and are referred to palliative treatment.Moreover,Child-Pugh B patients are not usually candidates for liver resection.However,many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection,maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function.Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification,and this treatment gives good results in the setting of multinodular,large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis.In this review we explore this controversial topic,and we show through the literature analysis how liver resection may improve the short-and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients.However,other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.展开更多
Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic ...Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.展开更多
The estimate of seismic site effects by experimental approaches is based on different assumptions aimed at simplifying the complex actual site conditions and related uncertainties.However,the reliability of the result...The estimate of seismic site effects by experimental approaches is based on different assumptions aimed at simplifying the complex actual site conditions and related uncertainties.However,the reliability of the results can increase if the experimental data is focused on quite strong seismic sequences and the on-site acquisition of a large number of signals is deemed strategic for the assessment of the expected phenomena.Based on these considerations,the ground motion at the Red Zone sector of Amatrice hill,violently struck by the 2016-2017 Central Italy seismic sequence,was analyzed via an observational approach.A large set of weak motions(moment magnitude Mw 2.5-3.9)was analyzed in this study by means of standard(SSR)and horizontal to vertical(HVSR)spectral ratio techniques.The results from the experimental analysis of the site effects by using weak motion and noise signals show a significant amplification at the top of Amatrice hill with a remarkable polarization of the motion and changes in spectral shapes according to the topographic setting of the relief.展开更多
Artificial intelligence(AI)is defined as the theory and development of computer systems able to perform tasks normally requiring human intelligence,such as visual perception,speech recognition,and decision-making.Mach...Artificial intelligence(AI)is defined as the theory and development of computer systems able to perform tasks normally requiring human intelligence,such as visual perception,speech recognition,and decision-making.Machine learning and deep learning(DL)are subfields of AI that are able to learn from experience in order to complete tasks.AI and its subfields,in particular DL,have been applied in numerous fields of medicine,especially in the cure of cancer.Computer vision(CV)system has improved diagnostic accuracy both in histopathology analyses and radiology.In surgery,CV has been used to design navigation system and robotic-assisted surgical tools that increased the safety and efficiency of oncological surgery by minimizing human error.By learning the basis of AI,surgeons can take part in this revolution to optimize surgical care of oncologic disease.展开更多
文摘Irritable bowel syndrome with diarrhea is a very frequent clinical condition characterized by disabling intestinal symptoms.This disease presents with daily abdominal pain for at least 3 months related to defecation and associated with a change in the frequency of bowel movements and the shape of the stool.International surveys about this disease report a global prevalence of about 1.5%.A new amino acid based electrolyte solution has recently been commercialized for oral rehydration in diarrhea.It is composed of water,electrolytes,and five selected amino acids that function as sodium co-transporters without containing glucose.In recent years,some studies explored the effectiveness of the amino acid based electrolyte beverage in oncologic patients with gastrointestinal mucositis,reporting good results.Recently,a prospective study to evaluate the clinical impact of the amino acid based medical beverage was conducted in patients with diarrhea predominant irritable bowel syndrome.The research was based on a real-life methodology minimizing the disruption of the routine care.One hundred patients suffering from irritable bowel syndrome with diarrhea drank a solution based on selected amino acids twice a day for 2 wk.Each enrolled patient completed the study and showed a significant response rate with regard to stool consistency and pain reduction.Based on this data,we can hypothesize that the amino acid based oral rehydration solution could be a valid tool in the treatment of patients affected by irritable bowel syndrome with diarrhea.It is certainly necessary to plan highquality clinical trials comparing glucose based oral solutions and amino acid based solutions in patients with persisting diarrhea.Probably in the near future all oral rehydration solutions will contain amino acids.
基金an under-40grant from the ltalian Association for Alzheimer's Research[AIRALTZH-AGYR2021]by the Strategic University Projects-Young Researcher Independence[YRG2021]from the University Campus Bio-Medico(Rome,Italy)(to LLB)+4 种基金a PhD fellowship by Fondazione Melchiorri(IT)and by the Strategic University Projects-Young Researcher Independence[YRG2021]from the University Campus Bio-Medico(Rome,Italy)(to ES)the American Alzheimer's Association[AARG-18-566270AARG-21-851219]by the Italian Ministry of Health[Research Grant:RF-2018-12365527]by Fondazione Roma(Rome,Italy)(to MDA)。
文摘In the last few years,preclinical and clinical studies identified the ventral tegmental area(VTA)as one of the first brain regions to be affected in the prodromal phase of Alzheimer's disease(AD).The VTA is a deep midbrain nucleus rich in dopaminergic neurons that innervates and releases dopamine(DA)in several cortical and subcortical brain regions.DA plays a crucial role in the modulation of both cognitive and noncognitive functions and failure of its release underlies both cognitive and neuropsychiatric symptoms in patients with AD.
基金Supported by Ministero dell’Istruzione,Università e Ricerca,MIUR-PRIN 2010-2011,No.prot.2010W7YRLZ_003
文摘Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer (CRC) initiation and progression. Recent genome-wide data have confirmed that in CRC this pathway is one of the most frequently modified by genetic or epigenetic alterations affecting almost 90% of Wnt/β-catenin gene members. A major challenge is thus learning how the corrupted coordination of this pathway is tied to other signalings to enhance cell growth. Peroxisome proliferator activated receptor γ (PPARγ) is emerging as a growth-limiting and differentiation-promoting factor. In tumorigenesis it exerts a tumor suppressor role and is potentially linked with the Wnt/β-catenin pathway. Based on these results, the identification of new selective PPARγ modulators with inhibitory effects on the Wnt/β-catenin pathway is becoming an interesting perspective. Should, in fact, these molecules display such properties, new research avenues would be opened aimed at developing new molecular targeted drugs. Herein, we review the basic principles and present new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ signaling. Furthermore, we discuss the advances in our understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PPARγ agonists endowed with Wnt/β-catenin inhibitory effects to be used as therapeutic and/or preventive agents.
文摘According to Barcelona Clinic Liver Cancer recommendations,intermediate stage hepatocellular carcinomas(stage B)are excluded from liver resection and are referred to palliative treatment.Moreover,Child-Pugh B patients are not usually candidates for liver resection.However,many hepatobiliary centers in the world manage patients with intermediate stage hepatocellular carcinoma or Child-Pugh B cirrhosis with liver resection,maintaining that hepatic resection is not contraindicated in selected patients with non–early-stage hepatocellular carcinoma and without normal liver function.Several studies demonstrate that resection provides the best survival benefit for selected patients in very early/early and even in intermediate stages of Barcelona Clinic Liver Cancer classification,and this treatment gives good results in the setting of multinodular,large tumors in patients with portal hypertension and/or Child-Pugh B cirrhosis.In this review we explore this controversial topic,and we show through the literature analysis how liver resection may improve the short-and long-term survival rate of carefully selected Barcelona Clinic Liver Cancer B and Child-Pugh B hepatocellular carcinoma patients.However,other large clinical studies are needed to clarify which patients with intermediate stage hepatocellular carcinoma are most likely to benefit from liver resection.
文摘Pancreatic cancer(PDAC) is an aggressive and chemoresistant disease, representing the fourth cause of cancer related deaths in western countries. Majority of patients have unresectable, locally advanced or metastatic disease at time of diagnosis and the 5-year survival rate in these conditions is extremely low. For more than a decade gemcitabine has been the cornerstone of metastatic PDAC treatment, although survival benefit was very poor. PDAC cells are surrounded by an intense desmoplastic reaction that may create a barrier to the drugs penetration within the tumor. Recently PDAC stroma has been addressed as a potential therapeutic target. Nano albumin bound(Nab)-paclitaxel is an innovative molecule depleting tumor stroma, through interaction between albumin and secreted protein acidic and rich in cysteine. Addition of nab-paclitaxel to gemcitabine has showed activity and efficacy in metastatic PDAC first-line treatment improving survival and overall response rate vs gemcitabine alone in the MPACT phase Ⅲ study. This combination represents one of the standards of care in advanced PDAC therapy and is suitable to a broader spectrum of patients compared to other schedules. Nab-paclitaxel is under investigation as a backbone of chemotherapy in novel combinations with target agents or immunotherapy in locally advanced or metastatic PDAC. In this article, we provide an updated and critical overview about the role of nab-paclitaxel in PDAC treatment based on the latest advances in preclinical and clinical research. Furthermore, we focus on the use of nab-paclitaxel within the context of metastatic PDAC treatment landscape and we discuss about future implications in the light of current clinical ongoing trials.
文摘The estimate of seismic site effects by experimental approaches is based on different assumptions aimed at simplifying the complex actual site conditions and related uncertainties.However,the reliability of the results can increase if the experimental data is focused on quite strong seismic sequences and the on-site acquisition of a large number of signals is deemed strategic for the assessment of the expected phenomena.Based on these considerations,the ground motion at the Red Zone sector of Amatrice hill,violently struck by the 2016-2017 Central Italy seismic sequence,was analyzed via an observational approach.A large set of weak motions(moment magnitude Mw 2.5-3.9)was analyzed in this study by means of standard(SSR)and horizontal to vertical(HVSR)spectral ratio techniques.The results from the experimental analysis of the site effects by using weak motion and noise signals show a significant amplification at the top of Amatrice hill with a remarkable polarization of the motion and changes in spectral shapes according to the topographic setting of the relief.
文摘Artificial intelligence(AI)is defined as the theory and development of computer systems able to perform tasks normally requiring human intelligence,such as visual perception,speech recognition,and decision-making.Machine learning and deep learning(DL)are subfields of AI that are able to learn from experience in order to complete tasks.AI and its subfields,in particular DL,have been applied in numerous fields of medicine,especially in the cure of cancer.Computer vision(CV)system has improved diagnostic accuracy both in histopathology analyses and radiology.In surgery,CV has been used to design navigation system and robotic-assisted surgical tools that increased the safety and efficiency of oncological surgery by minimizing human error.By learning the basis of AI,surgeons can take part in this revolution to optimize surgical care of oncologic disease.
