Lawrence E. Murr is Mr.J Mrs. Macintosh Murehison Professor and Chairman of the Department of Metallurgical and Materials Engineering and Ph.D. Program Director in the Materials Research Technology Institute at The Un...Lawrence E. Murr is Mr.J Mrs. Macintosh Murehison Professor and Chairman of the Department of Metallurgical and Materials Engineering and Ph.D. Program Director in the Materials Research Technology Institute at The University of Texas at El Paso. Dr. Murr received his B.Sc. in physical science from Albright College, and his B.S.E.E. in electronics, his M.S. in engineering mechanics, and his Ph.D. in solidstate science, all from the Pennsylvania State University. Dr. Murr has published 20 books, over 750 scientific and technical articles in a wide range of research areas in materials science and engineering, environmental science and engineering, manufacturing science and engineering （especially rapid prototype/layered manufacturing）,展开更多
Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the...Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the transformation of normal colonic mucosa into invasive cancer.CRC is one of the most prevalent and incident cancers worldwide,as well as one of the most deadly.Approximately 1235108 people are diagnosed annually with CRC,and 609051 die from CRC annually.The World Health Organization estimates an increase of77%in the number of newly diagnosed cases of CRCand an increase of 80%in deaths from CRC by 2030.The incidence of CRC can benefit from different strategies depending on its stage:health promotion through health education campaigns(when the disease is not yet present),the implementation of screening programs(for detection of the disease in its early stages),and the development of nearly personalized treatments according to both patient characteristics(age,sex)and the cancer itself(gene expression).Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application,not all strategies meet the criteria required for screening tests in population programs;the three most accepted tests are the fecal occult blood test(FOBT),colonoscopy and sigmoidoscopy.FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe.Due to its non-invasive nature and low cost,it is one of the most accepted techniques by population.CRC is a very heterogeneous disease,and with a few exceptions(APC,p53,KRAS),most of the genes involved in CRC are observed in a small percentage of cases.The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy.In recent years,the use of DNA,RNA and protein markers in different biological samples 展开更多
Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival o...Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.展开更多
To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases ri...To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.展开更多
Echocardiography is the most common diagnostic method for assessing atrial function but the technique has some limitations. Traditionally, assessment of left atrial function has been performed by measuring volumes wit...Echocardiography is the most common diagnostic method for assessing atrial function but the technique has some limitations. Traditionally, assessment of left atrial function has been performed by measuring volumes with 2D echocardiography. Additionally, it can be assessed with transmitral Doppler and pulmonary vein Doppler. Recently, an alternative method has been incorporated, namely, measurement of myocardial deformation with color tissue Doppler-derived strain. However, this method has several limitations, such as suboptimal reproducibility, angle-dependence, signal artifacts and the fact that it only measures regional strain and does not obtain information about the curved portion of the atrial roof. To overcome these limitations in the quantification of atrial function, the use of speckle tracking echocardiography (STE) strain has been proposed. This technique is not derived from Doppler but rather from 2D echocardiography; it is angle-independent and allows one to measure global as well as regional atrial strain. In this editorial, we describe the physical and pathophysiological concepts of STE and underline the clinical usefulness of this new technique.展开更多
AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into h...AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS： BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS： BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thyl decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors （C/EBPβ and HNF4α）, as demonstrated by adenoviral expression vectors.CONCLUSION： Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.展开更多
Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considera...Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.展开更多
MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, t...MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.展开更多
Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options...Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.展开更多
The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix...The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary展开更多
AIM: To evaluate the treatment of pediatric functional chronic intestinal constipation (FCIC) with a probiotic goat yogurt. METHODS: A crossover double-blind formula-controlled trial was carried out on 59 students (ag...AIM: To evaluate the treatment of pediatric functional chronic intestinal constipation (FCIC) with a probiotic goat yogurt. METHODS: A crossover double-blind formula-controlled trial was carried out on 59 students (age range: 5-15 years) of a public school in Belo Horizonte, MG, Brazil, presenting a FCIC diagnostic, according to Roma Ⅲ criteria. The students were randomized in two groups to receive a goat yogurt supplemented with 109 colony forming unit/mL Bifidobacterium longum (B.longum) (probiotic) daily or only the yogurt for a period of 5 wk (formula). Afterwards, the groups were intercrossed for another 5 wk. Defecation frequency, stool consistency and abdominal and defecation pain were assessed.RESULTS: Both treatment groups demonstrated improvement in defecation frequency compared to baseline. However, the group treated with probiotic showed most signif icant improvement in the f irst phase of the study. An inversion was observed after crossing over, resulting in a reduction in stool frequency when this group was treated by formula. Probiotic and formula improved stool consistency in the f irst phase of treatment, but the improvement obtained with probiotic was significantly higher (P = 0.03). In the second phase of treatment, the group initially treated with probiotic showed worseningstool consistency when using formula. However, the difference was not signif icant. A signif icant improvement in abdominal pain and defecation pain was observed with both probiotic and formula in the first phase of treatment, but again the improvement was more signif icant for the group treated with B. longum during phase I (P < 0.05). When all data of the crossover study were analyzed, significant differences were observed between probiotic yogurt and yogurt only for defecation frequency (P = 0.012), defecation pain (P = 0.046) and abdominal pain (P = 0.015).展开更多
Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed...Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies(alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.展开更多
AIM To report the results of the International Nosocomial Infection Control Consortium(INICC) study conducted in Quito, Ecuador.METHODS A device-associated healthcare-acquired infection(DAHAI) prospective surveillance...AIM To report the results of the International Nosocomial Infection Control Consortium(INICC) study conducted in Quito, Ecuador.METHODS A device-associated healthcare-acquired infection(DAHAI) prospective surveillance study conducted from October 2013 to January 2015 in 2 adult intensive care units(ICUs) from 2 hospitals using the United States Centers for Disease Control/National Healthcare Safety Network(CDC/NHSN) definitions and INICC methods. RESULTS We followed 776 ICU patients for 4818 bed-days. The central line-associated bloodstream infection(CLABSI) rate was 6.5 per 1000 central line(CL)-days, the ventilator-associated pneumonia(VAP) rate was 44.3 per 1000 mechanical ventilator(MV)-days, and the catheterassociated urinary tract infection(CAUTI) rate was 5.7 per 1000 urinary catheter(UC)-days. CLABSI and CAUTI rates in our ICUs were similar to INICC rates [4.9(CLABSI) and 5.3(CAUTI)] and higher than NHSN rates [0.8(CLABSI) and 1.3(CAUTI)]- although device use ratios for CL and UC were higher than INICC and CDC/NSHN's ratios. By contrast, despite the VAP rate was higher than INICC(16.5) and NHSN's rates(1.1), MV DUR was lower in our ICUs. Resistance of A. baumannii to imipenem and meropenem was 75.0%, and of Pseudomonas aeruginosa to ciprofloxacin and piperacillin-tazobactam was higher than 72.7%, all them higher than CDC/NHSN rates. Excess length of stay was 7.4 d for patients with CLABSI, 4.8 for patients with VAP and 9.2 for patients CAUTI. Excess crude mortality in ICUs was 30.9% for CLABSI, 14.5% for VAP and 17.6% for CAUTI. CONCLUSION DA-HAI rates in our ICUs from Ecuador are higher than United States CDC/NSHN rates and similar to INICC international rates.展开更多
BACKGROUND Prospective study of 200 patients with hepatocellular carcinoma(HCC)that underwent liver transplant(LT)after drug-eluting beads transarterial chemoembolization(DEB-TACE)for downstaging versus bridging.Overa...BACKGROUND Prospective study of 200 patients with hepatocellular carcinoma(HCC)that underwent liver transplant(LT)after drug-eluting beads transarterial chemoembolization(DEB-TACE)for downstaging versus bridging.Overall survival and tumor recurrence rates were calculated,eligibility for LT,time on the waiting list and radiological response were compared.After TACE,only patients within Milan Criteria(MC)were transplanted.More patients underwent LT in bridging group.Five-year post-transplant overall survival,recurrence-free survival has no difference between the groups.Complete response was observed more frequently in bridging group.Patients in DS group can achieve posttransplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.AIM To determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODS Prospective cohort study of 200 patients included from April 2011 through June 2014.Bridging group included patients within MC.Downstaging group(out of MC)was divided in 5 subgroups(G1 to G5).Total tumor diameter was≤8 cm for G1,2,3,4(n=42)and was>8 cm for G5(n=22).Downstaging(n=64)and bridging(n=136)populations were not significantly different.Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method.Additionally,eligibility for LT,time on the waiting list until LT and radiological response were compared.RESULTS After TACE,only patients within MC were transplanted.More patients underwent LT in bridging group 65.9%(P=0.001).Downstaging population presented:higher number of nodules 2.81(P=0.001);larger total tumor diameter 8.09(P=0.001);multifocal HCC 78%(P=0.001);more post-transplantation recurrence 25%(P=0.02).Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT(P=0.005).Median time on the waiting list was significantly longer in downstaging group 10.6 mo(P=0.028).Five-year posttransplant overall survival was 73.5%in downstaging and 72.3%展开更多
Chimeric antigen receptor T cell(CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors(CAR).The CAR-T cell is an effector...Chimeric antigen receptor T cell(CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors(CAR).The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies,including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.展开更多
K＋ uptake in the high-affinity range of concentrations and its components have been widely studied. In Arabidposis thaliana, the AtHAK5 transporter and the AtAKT1 channel have been shown to be the main transport prot...K＋ uptake in the high-affinity range of concentrations and its components have been widely studied. In Arabidposis thaliana, the AtHAK5 transporter and the AtAKT1 channel have been shown to be the main transport proteins involved in this process. Here, we study the role of these two systems under two important stress conditions： low K＋ supply or the presence of salinity. T-DNA insertion lines disrupting AtHAK5 and A tAKT1 are employed for long-term experi- ments that allow physiological characterization of the mutant lines. We found that AtHAK5 is required for K＋ absorption necessary to sustain plant growth at low K＋ in the absence as well as in the presence of salinity. Salinity greatly reduced AtHAK5 transcript levels and promoted AtAKTl-mediated K＋ efflux, resulting in an important impairment of K＋ nutrition. Although having a limited capacity, AtHAK5 plays a major role for K＋ acquisition from low K＋ concentrations in the presence of salinity.展开更多
基金supported in part by Mr. and Mrs.MacIntosh Murshison Endowments at the University of Texas at El Paso and Lockheed Martin Aeronautics
文摘Lawrence E. Murr is Mr.J Mrs. Macintosh Murehison Professor and Chairman of the Department of Metallurgical and Materials Engineering and Ph.D. Program Director in the Materials Research Technology Institute at The University of Texas at El Paso. Dr. Murr received his B.Sc. in physical science from Albright College, and his B.S.E.E. in electronics, his M.S. in engineering mechanics, and his Ph.D. in solidstate science, all from the Pennsylvania State University. Dr. Murr has published 20 books, over 750 scientific and technical articles in a wide range of research areas in materials science and engineering, environmental science and engineering, manufacturing science and engineering （especially rapid prototype/layered manufacturing）,
基金Supported by Partially funded by the Carlos Ⅲ Health Institute No.PI11/01593
文摘Colorectal cancer(CRC)is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors.CRC develops through a gradual accumulation of genetic and epigenetic changes,leading to the transformation of normal colonic mucosa into invasive cancer.CRC is one of the most prevalent and incident cancers worldwide,as well as one of the most deadly.Approximately 1235108 people are diagnosed annually with CRC,and 609051 die from CRC annually.The World Health Organization estimates an increase of77%in the number of newly diagnosed cases of CRCand an increase of 80%in deaths from CRC by 2030.The incidence of CRC can benefit from different strategies depending on its stage:health promotion through health education campaigns(when the disease is not yet present),the implementation of screening programs(for detection of the disease in its early stages),and the development of nearly personalized treatments according to both patient characteristics(age,sex)and the cancer itself(gene expression).Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application,not all strategies meet the criteria required for screening tests in population programs;the three most accepted tests are the fecal occult blood test(FOBT),colonoscopy and sigmoidoscopy.FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe.Due to its non-invasive nature and low cost,it is one of the most accepted techniques by population.CRC is a very heterogeneous disease,and with a few exceptions(APC,p53,KRAS),most of the genes involved in CRC are observed in a small percentage of cases.The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy.In recent years,the use of DNA,RNA and protein markers in different biological samples
文摘Uterine cervical cancer is the second most common gynecological malignancy. It is estimated that over 35% of tumors are diagnosed at locally advanced disease, stage ⅠB2-ⅡB with an estimated 5-year overall survival of 60%. During the last decades, the initial treatment for these women has been debated and largely varies through different countries. Thus, radical concurrent chemoradiation is the standard of care in United Sated and Canada, and neoadjuvant chemotherapy followed by radical surgery is the first line of treatment in some institutions of Europe, Asia and Latin America. Until today, there is no evidence of which strategy is better over the other. This article describe the evidence as well as the advantages and disadvantages of the main strategies of treatment for women affected by uterine cervical cancer stage ⅠB2-ⅡB.
文摘To achieve good metabolic control in diabetes and keep long term, a combination of changes in lifestyle and pharmacological treatment is necessary. Achieving near-normal glycated hemoglobin significantly, decreases risk of macrovascular and microvascular complications. At present there are different treatments, both oral and injectable, available for the treatment of type 2 diabetes mellitus(T2DM). Treatment algorithms designed to reduce the development or progression of the complications of diabetes emphasizes the need for good glycaemic control. The aim of this review is to perform an update on the benefits and limitations of different drugs, both current and future, for the treatment of T2 DM. Initial intervention should focus on lifestyle changes. Moreover, changes in lifestyle have proven to be beneficial, but for many patients is a complication keep long term. Physicians should be familiar with the different types of existing drugs for the treatment of diabetes and select the most effective, safe and better tolerated by patients. Metformin remains the first choice of treatment for most patients. Other alternative or second-line treatment options should be individualized depending on the characteristics of each patient. This article reviews the treatments available for patients with T2 DM, with an emphasis on agents introduced within the last decade.
文摘Echocardiography is the most common diagnostic method for assessing atrial function but the technique has some limitations. Traditionally, assessment of left atrial function has been performed by measuring volumes with 2D echocardiography. Additionally, it can be assessed with transmitral Doppler and pulmonary vein Doppler. Recently, an alternative method has been incorporated, namely, measurement of myocardial deformation with color tissue Doppler-derived strain. However, this method has several limitations, such as suboptimal reproducibility, angle-dependence, signal artifacts and the fact that it only measures regional strain and does not obtain information about the curved portion of the atrial roof. To overcome these limitations in the quantification of atrial function, the use of speckle tracking echocardiography (STE) strain has been proposed. This technique is not derived from Doppler but rather from 2D echocardiography; it is angle-independent and allows one to measure global as well as regional atrial strain. In this editorial, we describe the physical and pathophysiological concepts of STE and underline the clinical usefulness of this new technique.
基金Supported by the ALIVE Foundation, the FIS from Instituto de Salud Carlos III, Spain, No. 03/0339, and the European Commission, No. LSHB-CT-2004-504761
文摘AIM： To investigate and compare the hepatogenic transdifferentiation of adipose tissue-derived stem cells （ADSC） and bone marrow-derived mesenchymal stem cells （BMSC） in vitro. Transdifferentiation of BMSC into hepatic cells in vivo has been described. Adipose tissue represents an accessible source of ADSC, with similar characteristics to BMSC. METHODS： BMSCs were obtained from patients undergoing total hip arthroplasty and ADSC from human adipose tissue obtained from lipectomy. Cells were grown in medium containing 15% human serum. Cultures were serum deprived for 2 d before cultivating under similar pro-hepatogenic conditions to those of liver development using a 2-step protocol with sequential addition of growth factors, cytokines and hormones. Hepatic differentiation was RT-PCR-assessed and liver-marker genes were immunohistochemically analysed.RESULTS： BMSC and ADSC exhibited a fibroblastic morphology that changed to a polygonal shape when cells differentiated. Expression of stem cell marker Thyl decreased in differentiated ADSC and BMSC. However, the expression of the hepatic markers, albumin and CYPs increased to a similar extent in differentiated BMSC and ADSC. Hepatic gene activation could be attributed to increased liver-enriched transcription factors （C/EBPβ and HNF4α）, as demonstrated by adenoviral expression vectors.CONCLUSION： Mesenchymal stem cells can be induced to hepatogenic transdifferentiation in vitro. ADSCs have a similar hepatogenic differentiation potential to BMSC, but a longer culture period and higher proliferation capacity. Therefore, adipose tissue may be an ideal source of large amounts of autologous stem cells, and may become an alternative for hepatocyte regeneration, liver cell transplantation or preclinical drug testing.
文摘Diabetes mellitus is a chronic condition that occurs when the body cannot produce enough or effectively use of insulin.Compared with individuals without diabetes,patients with type 2 diabetes mellitus have a considerably higher risk of cardiovascular morbidity and mortality,and are disproportionately affected by cardiovascular disease.Most of this excess risk is it associated with an augmented prevalence of well-known risk factors such as hypertension,dyslipidaemia and obesity in these patients.However the improved cardiovascular disease in type 2 diabetes mellitus patients can not be attributed solely to the higher prevalence of traditional risk factors.Therefore other non-traditional risk factors may be important in people with type 2 diabetes mellitus.Cardiovascular disease is increased in type 2 diabetes mellitus subjects due to a complex combination of various traditional and non-traditional risk factors that have an important role to play in the beginning and the evolution of atherosclerosis over its long natural history from endothelial function to clinical events.Many of these risk factors could be common history for both di-abetes mellitus and cardiovascular disease,reinforcing the postulate that both disorders come independently from"common soil".The objective of this review is to highlight the weight of traditional and non-traditional risk factors for cardiovascular disease in the setting of type 2 diabetes mellitus and discuss their position in the pathogenesis of the excess cardiovascular disease mortality and morbidity in these patients.
文摘MicroRNAs （miRNAs） are essential for regulating cell differentiation and maintaining the pluripotent state of stem cells. Although dysregulation of specific miRNAs has been associated with certain types of cancer, to date no evidence has linked miRNA expression in embryonic and tumor tissues. We assessed the expression of mature miRNAs in human embryonic colon tissue, and in colorectal cancer and paired normal colon tissue. Overlapping miRNA expression was detected between embryonic colonic mucosa and colorectal cancer. We have found that the miR-17-92 cluster and its target, E2F1, exhibit a similar pattern of expression in human colon development and colonic carcinogenesis, regulating cell proliferation in both cases. In situ hybridization confirmed the high level of expression of miR-17-5p in the crypt progenitor compartment. We conclude that miRNA pathways play a major role in both embryonic development and neoplastic transformation of the colonic epithelium.
基金the MINECO Retos,No.SAF2016-78711 and SAF2017-87919REXOHEP-CM,No.S2017/BMD-3727+8 种基金the AMMF Cholangiocarcinoma Charity,No.2018/117the COST Action,No.CA17112Ramón y Cajal,No.RYC-2014-15242 and No.RYC-2015-17438grant of ERAB,No.EA 14/18Gilead Liver Research Scholar 2018,No.44/2018Ministerio de Sanidad,Servicios Sociales e Igualdad,No.2017I065the UCM group “Lymphocyte Immunobiology”,No.920631(imas12-associated,Ref.IBL-6)German Research Foundation(SFB/TRR57/P04 and DFG NE 2128/2-1)Interdisciplinary Center for Clinical Research from the Faculty of Medicine at RWTH Aachen University(IZKF/E8-2)
文摘Alcoholic liver disease(ALD) is a major cause of acute and chronic liver injury. Extensive evidence has been accumulated on the pathological process of ALD during the past decades. However, effective treatment options for ALD are very limited due to the lack of suitable in vivo models that recapitulate the full spectrum of ALD. Experimental animal models of ALD, particularly rodents, have been used extensively to mimic human ALD. An ideal animal model should recapitulate all aspects of the ALD process, including significant steatosis, hepatic neutrophil infiltration, and liver injury. A better strategy against ALD depends on clear diagnostic biomarkers, accurate predictor(s) of its progression and new therapeutic approaches to modulate stop or even reverse the disease. Numerous models employing rodent animals have been established in the last decades to investigate the effects of acute and chronic alcohol exposure on the initiation and progression of ALD. Although significant progress has been made in gaining better knowledge on the mechanisms and pathology of ALD, many features of ALD are unknown, and require further investigation, ideally with improved animal models that more effectively mimic human ALD. Although differences in the degree and stages of alcoholic liver injury inevitably exist between animal models and human ALD, the acquisition and translational relevance will be greatly enhanced with the development of new and improved animal models of ALD.
文摘The rupture of gastric varices results in variceal hemorrhage, which is one the most lethal complications of cirrhosis. Endoscopic therapies for varices aim to reduce variceal wall tension by obliteration of the varix. The two principal methods available for esophageal varices are endoscopic sclerotherapy (EST) and band ligation (EBL). The advantages of EST are that it is cheap and easy to use, and the injection catheter fits through the working channel of a diagnostic gastroscope. Endoscopic variceal ligation obliterates varices by causing mechanical strangulation with rubber bands. The following review aims to describe the utility of EBL and EST in different situations, such as acute bleeding, primary and secondary
基金Supported by Grants from Conselho Nacional de Desenvolvi-mento Cientifico e TecnológicoFundaco de Amparo à Pesquisa do Estado de Minas Gerais
文摘AIM: To evaluate the treatment of pediatric functional chronic intestinal constipation (FCIC) with a probiotic goat yogurt. METHODS: A crossover double-blind formula-controlled trial was carried out on 59 students (age range: 5-15 years) of a public school in Belo Horizonte, MG, Brazil, presenting a FCIC diagnostic, according to Roma Ⅲ criteria. The students were randomized in two groups to receive a goat yogurt supplemented with 109 colony forming unit/mL Bifidobacterium longum (B.longum) (probiotic) daily or only the yogurt for a period of 5 wk (formula). Afterwards, the groups were intercrossed for another 5 wk. Defecation frequency, stool consistency and abdominal and defecation pain were assessed.RESULTS: Both treatment groups demonstrated improvement in defecation frequency compared to baseline. However, the group treated with probiotic showed most signif icant improvement in the f irst phase of the study. An inversion was observed after crossing over, resulting in a reduction in stool frequency when this group was treated by formula. Probiotic and formula improved stool consistency in the f irst phase of treatment, but the improvement obtained with probiotic was significantly higher (P = 0.03). In the second phase of treatment, the group initially treated with probiotic showed worseningstool consistency when using formula. However, the difference was not signif icant. A signif icant improvement in abdominal pain and defecation pain was observed with both probiotic and formula in the first phase of treatment, but again the improvement was more signif icant for the group treated with B. longum during phase I (P < 0.05). When all data of the crossover study were analyzed, significant differences were observed between probiotic yogurt and yogurt only for defecation frequency (P = 0.012), defecation pain (P = 0.046) and abdominal pain (P = 0.015).
文摘Hepatocellular carcinoma(HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and locoregional therapies(alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.
文摘AIM To report the results of the International Nosocomial Infection Control Consortium(INICC) study conducted in Quito, Ecuador.METHODS A device-associated healthcare-acquired infection(DAHAI) prospective surveillance study conducted from October 2013 to January 2015 in 2 adult intensive care units(ICUs) from 2 hospitals using the United States Centers for Disease Control/National Healthcare Safety Network(CDC/NHSN) definitions and INICC methods. RESULTS We followed 776 ICU patients for 4818 bed-days. The central line-associated bloodstream infection(CLABSI) rate was 6.5 per 1000 central line(CL)-days, the ventilator-associated pneumonia(VAP) rate was 44.3 per 1000 mechanical ventilator(MV)-days, and the catheterassociated urinary tract infection(CAUTI) rate was 5.7 per 1000 urinary catheter(UC)-days. CLABSI and CAUTI rates in our ICUs were similar to INICC rates [4.9(CLABSI) and 5.3(CAUTI)] and higher than NHSN rates [0.8(CLABSI) and 1.3(CAUTI)]- although device use ratios for CL and UC were higher than INICC and CDC/NSHN's ratios. By contrast, despite the VAP rate was higher than INICC(16.5) and NHSN's rates(1.1), MV DUR was lower in our ICUs. Resistance of A. baumannii to imipenem and meropenem was 75.0%, and of Pseudomonas aeruginosa to ciprofloxacin and piperacillin-tazobactam was higher than 72.7%, all them higher than CDC/NHSN rates. Excess length of stay was 7.4 d for patients with CLABSI, 4.8 for patients with VAP and 9.2 for patients CAUTI. Excess crude mortality in ICUs was 30.9% for CLABSI, 14.5% for VAP and 17.6% for CAUTI. CONCLUSION DA-HAI rates in our ICUs from Ecuador are higher than United States CDC/NSHN rates and similar to INICC international rates.
文摘BACKGROUND Prospective study of 200 patients with hepatocellular carcinoma(HCC)that underwent liver transplant(LT)after drug-eluting beads transarterial chemoembolization(DEB-TACE)for downstaging versus bridging.Overall survival and tumor recurrence rates were calculated,eligibility for LT,time on the waiting list and radiological response were compared.After TACE,only patients within Milan Criteria(MC)were transplanted.More patients underwent LT in bridging group.Five-year post-transplant overall survival,recurrence-free survival has no difference between the groups.Complete response was observed more frequently in bridging group.Patients in DS group can achieve posttransplant survival and HCC recurrence-free probability,at five years,just like patients within MC in patients undergoing DEB-TACE.AIM To determine long-term outcomes of patients with HCC that underwent LT after DEB-TACE for downstaging vs bridging.METHODS Prospective cohort study of 200 patients included from April 2011 through June 2014.Bridging group included patients within MC.Downstaging group(out of MC)was divided in 5 subgroups(G1 to G5).Total tumor diameter was≤8 cm for G1,2,3,4(n=42)and was>8 cm for G5(n=22).Downstaging(n=64)and bridging(n=136)populations were not significantly different.Overall survival and tumor recurrence rates were calculated by the Kaplan-Meier method.Additionally,eligibility for LT,time on the waiting list until LT and radiological response were compared.RESULTS After TACE,only patients within MC were transplanted.More patients underwent LT in bridging group 65.9%(P=0.001).Downstaging population presented:higher number of nodules 2.81(P=0.001);larger total tumor diameter 8.09(P=0.001);multifocal HCC 78%(P=0.001);more post-transplantation recurrence 25%(P=0.02).Patients with maximal tumor diameter up to 7.05 cm were more likely to receive LT(P=0.005).Median time on the waiting list was significantly longer in downstaging group 10.6 mo(P=0.028).Five-year posttransplant overall survival was 73.5%in downstaging and 72.3%
基金supported by grants from the National Natural Science Foundation of China (Nos. 31670880 and 31370868)the Guangdong Natural Science Fund for Distinguished Young Scholars (No. 2016A030306004)+2 种基金Guangdong Special Support Program for Youth Science and Technology Innovation Talents (No. 2015TQ01R473)Guangzhou Pearl River New Star Program (No. 201610010064)Guangdong Innovative Research Team Program (No. 2011Y035)
文摘Chimeric antigen receptor T cell(CAR-T cell) therapy is a novel adoptive immunotherapy where T lymphocytes are engineered with synthetic receptors known as chimeric antigen receptors(CAR).The CAR-T cell is an effector T cell that recognizes and eliminates specific cancer cells, independent of major histocompatibility complex molecules. The whole procedure of CAR-T cell production is not well understood. The CAR-T cell has been used predominantly in the treatment of hematological malignancies,including acute lymphoblastic leukemia, chronic lymphocytic leukemia, lymphoma, and multiple myeloma. Solid tumors including melanoma, breast cancer and sarcoma offer great promise in CAR-T cell research and development. CD19 CAR-T cell is most commonly used, and other targets, including CD20, CD30, CD38 and CD138 are being studied. Although this novel therapy is promising, there are several disadvantages. In this review we discuss the applications of CAR-T cells in different hematological malignancies, and pave a way for future improvement on the effectiveness and persistence of these adoptive cell therapies.
文摘K＋ uptake in the high-affinity range of concentrations and its components have been widely studied. In Arabidposis thaliana, the AtHAK5 transporter and the AtAKT1 channel have been shown to be the main transport proteins involved in this process. Here, we study the role of these two systems under two important stress conditions： low K＋ supply or the presence of salinity. T-DNA insertion lines disrupting AtHAK5 and A tAKT1 are employed for long-term experi- ments that allow physiological characterization of the mutant lines. We found that AtHAK5 is required for K＋ absorption necessary to sustain plant growth at low K＋ in the absence as well as in the presence of salinity. Salinity greatly reduced AtHAK5 transcript levels and promoted AtAKTl-mediated K＋ efflux, resulting in an important impairment of K＋ nutrition. Although having a limited capacity, AtHAK5 plays a major role for K＋ acquisition from low K＋ concentrations in the presence of salinity.
