BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, ...BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.展开更多
Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people wi...Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of “hepatitis B virus AND liver transplantation”. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.展开更多
BACKGROUND: Bilio-intestinal drainage is routinely per- formed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of ...BACKGROUND: Bilio-intestinal drainage is routinely per- formed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of an isolated jejunal segment (CDJI). This method offers the benefit of potential endoscopic control and intervention during fol- low-up. Critics of CDJI assume a higher rate of postopera- tive cholangitis compared to the Roux-en-Y construction. METHODS: Seventy-six patients with malignant tumors (n = 56) or benign strictures and choledochal cysts (n =20) were treated between 1989 and 2002 by cholangio-duodenal interposition of an isolated jejunal segment (measuring 15- 25 cm) after central bile duct resection. In 22 patients endoscopic control was first performed postoperatively dur- ing hospitalization. In 12 patients bilio-intestinal anastomo- sis could be inspected endoscopically. In the remaining patients the anastomosis could not be visualized endoscopi- cally because of kinking of the jejunal segment, but in all patients it could be evaluated by endoscopic retrograde cholangiography (ERC). RESULTS: During follow-up, 25 (33%) patients died from extrahepatic tumor recurrence. Three patients receiving CDJI after severe iatrogenic bile duct injury developed anas- tomotic strictures. Two of these patients were treated by endoscopic pigtail drainage, and one was treated by percu- taneous drainage. Two patients who had received CDJI af- ter choledochal cyst resection developed cholestasis post- operatively because of sludge formation (1 patient) and an intrahepatic concrement (1), which could be solved endo- scopically. One patient after resection of a Klatskin tumor developed an anastomotic stricture which could not be vi- sualized endoscopically, making percutaneous drainage necessary. The rate of postoperative cholangitis after CDJI in our patients was comparable to that after the Roux-en-Y reconstruction.CONCLUSION: Interposition of an isolated jejunal seg- ment for reconstruction after bile duct resection should be performed in patients with a high risk of postoperative ste- nosis. To benefit endoscopic follow-up the jejunal segment should be shorter than 20 cm.展开更多
Background:The COVID-19 pandemic and governments’attempts to contain it are negatively affecting young children’s health and development in ways we are only beginning to understand and measure.Responses to the pande...Background:The COVID-19 pandemic and governments’attempts to contain it are negatively affecting young children’s health and development in ways we are only beginning to understand and measure.Responses to the pandemic are driven largely by confining children and families to their homes.This study aims to assess the levels of and associated socioeconomic disparities in household preparedness for protecting young children under the age of five from being exposed to communicable diseases,such as COVID-19,in low-and middle-income countries(LMICs).Methods:Using data from nationally representative household surveys in 56 LMICs since 2016,we estimated the percentages of young children under the age of five living in households prepared for communicable diseases(e.g.,COVID-19)and associated residential and wealth disparities at the country-and aggregate-level.Preparedness was defined on the basis of space for quarantine,adequacy of toilet facilities and hand hygiene,mass media exposure at least once a week,and phone ownership.Disparities within countries were measured as the absolute gap in two domains—household wealth and residential area-and compared across regions and country income groups.Results:The final data set included 766,313 children under age five.On average,19.4%of young children in the 56 countries lived in households prepared for COVID-19,ranging from 0.6%in Ethiopia in 2016 to 70.9%in Tunisia in 2018.In close to 90%of countries(50),fewer than 50%of young children lived in prepared households.Young children in rural areas or in the poorest households were less likely to live in prepared households than their counterparts.Conclusions:A large portion of young children under the age of five in LMICs were living in households that did not meet all preparedness guidelines for preventing COVID-19 and caring for patients at home.This study highlights the need to ensure all families in LMICs have the means to prevent the spread of the pandemic or other communicable illnesses to young children during pandemics.展开更多
Correction to:Global Health Research and Policy(2022)7:18 https://doi.org/10.1186/s41256-022-00254-2 Following publication of the original article[1],the authors reported that one reference number needs to be correcte...Correction to:Global Health Research and Policy(2022)7:18 https://doi.org/10.1186/s41256-022-00254-2 Following publication of the original article[1],the authors reported that one reference number needs to be corrected,and the captions listed in the Supplementary Information section need to be updated.The original article[1]has been corrected.展开更多
Abstract Despite important gains in human rights, persons with disabilities -- and in particular women and girls with disabilities -- continue to experience significant inequalities in the areas of sexual, reproductiv...Abstract Despite important gains in human rights, persons with disabilities -- and in particular women and girls with disabilities -- continue to experience significant inequalities in the areas of sexual, reproductive, and parenting rights. Persons with disabilities are sterilized at alarming rates; have decreased access to reproductive health care services and information; and experience denial of parenthood. Precipitating these inequities are substantial and instantiated stereotypes of persons with disabilities as either asexual or unable to engage in sexual or reproductive activities, and as incapable of performing parental duties. The article begins with an overview of sexual, reproductive, and parenting rights regarding persons with disabilities. Because most formal adjudications of these related rights have centered on the issue of sterilization, the article analyzes commonly presented rationales used to justify these procedures over time and across jurisdictions. Next, the article examines the Convention on the Rights of Persons with Disabilities and the attendant obligations of States Parties regarding rights to personal integrity, access to reproductive health care services and information, parenting, and the exercise of legal capacity. Finally, the article highlights fundamental and complex issues requiring future research and consideration.展开更多
文摘BACKGROUND: Cancer of the pancreas is the fourth leading cause of cancer death in industrialized countries. In malignancy, actively proliferating cells may be effectively targeted and killed by anti-cancer therapies, but stem cells may survive and support re-growth of the tumor. Thus, new strategies for the treatment of cancer clearly will also have to target cancer stem cells. The goal of the present study was to determine whether pancreatic carcinoma cell growth may be driven by a subpopulation of cancer stem cells. Because previous data implicated ABCG2 and CD133 as stem cell markers in hematopoietic and neural stem/progenitor cells, we analyzed the expression of these two proteins in pancreatic carcinoma cell lines. METHODS: Five established pancreatic adenocarcinoma cell lines were analyzed. Total RNA was isolated and real- time RT-PCR was performed to determine the expression of ABCG2 and CD133. Surface expression of ABCG2 and CD133 was analyzed by flow cytometric analysis. RESULTS: All pancreatic carcinoma cell lines tested expressed significantly higher levels of ABCG2 than non-malignant fibroblasts or two other malignant non- pancreatic cell lines, i.e., SaOS2 osteosarcoma and SKOV3 ovarian cancer. Elevated CD133 expression was found in two out of five pancreatic carcinoma cell lines tested. Using flow cytometric analysis we confirmed surface expression of ABCG2 in all five lines. Yet, CD133 surface expression was detectable in the two cell lines, A818-6 and PancTu1, which exhibited higher mRNA levels.CONCLUSIONS: Two stem cell markers, ABCG2 and CD133 are expressed in pancreatic carcinoma cell lines. ABCG2 and/or CD133 positive cells may represent subpopulation of putative cancer stem cells also in this malignancy. Because cancer stem cells are thought to be responsible for tumor initiation and its recurrence after an initial response to chemotherapy, they may be a very promising target for new drug developments.
基金Supported by A grant(No.R15 HL 117199)contract No.U01 DK 065201 from the United States National Institutes of Health(to Bonkovsky HL)+1 种基金institutional funds from Carolinas HealthCare System(to Sendi H)Beth Israel Deaconess Medi-cal Center(to Ghaziani T)
文摘Hepatitis B virus (HBV) continues to be a major cause of morbidity and mortality worldwide. It is estimated that about 350 million people throughout the world are chronically infected with HBV. Some of these people will develop hepatic cirrhosis with decompensation and/or hepatocellular carcinoma. For such patients, liver transplantation may be the only hope for cure or real improvement in quality and quantity of life. Formerly, due to rapidity of recurrence of HBV infection after liver transplantation, usually rapidly progressive, liver transplantation was considered to be contraindicated. This changed dramatically following the demonstration that hepatitis B immune globulin (HBIG), could prevent recurrent HBV infection. HBIG has been the standard of care for the past two decades or so. Recently, with the advent of highly active inhibitors of the ribose nucleic acid polymerase of HBV (entecavir, tenofovir), there has been growing evidence that HBIG needs to be given for shorter lengths of time; indeed, it may no longer be necessary at all. In this review, we describe genetic variants of HBV and past, present, and future prophylaxis of HBV infection during and after liver transplantation. We have reviewed the extant medical literature on the subject of infection with the HBV, placing particular emphasis upon the prevention and treatment of recurrent HBV during and after liver transplantation. For the review, we searched PubMed for all papers on the subject of “hepatitis B virus AND liver transplantation”. We describe some of the more clinically relevant and important genetic variations in the HBV. We also describe current practices at our medical centers, provide a summary and analysis of comparative costs for alternative strategies for prevention of recurrent HBV, and pose important still unanswered questions that are in need of answers during the next decade or two. We conclude that it is now rational and cost-effective to decrease and, perhaps, cease altogether, the routine use of HBIG during and following liver transplantation for HBV infection. Here we propose an individualized prophylaxis regimen, based on an integrated approach and risk-assessment.
文摘BACKGROUND: Bilio-intestinal drainage is routinely per- formed by Roux-en-Y reconstruction after resection of the central bile duct. Alternatively reconstruction can be achieved by cholangio-duodenal interposition of an isolated jejunal segment (CDJI). This method offers the benefit of potential endoscopic control and intervention during fol- low-up. Critics of CDJI assume a higher rate of postopera- tive cholangitis compared to the Roux-en-Y construction. METHODS: Seventy-six patients with malignant tumors (n = 56) or benign strictures and choledochal cysts (n =20) were treated between 1989 and 2002 by cholangio-duodenal interposition of an isolated jejunal segment (measuring 15- 25 cm) after central bile duct resection. In 22 patients endoscopic control was first performed postoperatively dur- ing hospitalization. In 12 patients bilio-intestinal anastomo- sis could be inspected endoscopically. In the remaining patients the anastomosis could not be visualized endoscopi- cally because of kinking of the jejunal segment, but in all patients it could be evaluated by endoscopic retrograde cholangiography (ERC). RESULTS: During follow-up, 25 (33%) patients died from extrahepatic tumor recurrence. Three patients receiving CDJI after severe iatrogenic bile duct injury developed anas- tomotic strictures. Two of these patients were treated by endoscopic pigtail drainage, and one was treated by percu- taneous drainage. Two patients who had received CDJI af- ter choledochal cyst resection developed cholestasis post- operatively because of sludge formation (1 patient) and an intrahepatic concrement (1), which could be solved endo- scopically. One patient after resection of a Klatskin tumor developed an anastomotic stricture which could not be vi- sualized endoscopically, making percutaneous drainage necessary. The rate of postoperative cholangitis after CDJI in our patients was comparable to that after the Roux-en-Y reconstruction.CONCLUSION: Interposition of an isolated jejunal seg- ment for reconstruction after bile duct resection should be performed in patients with a high risk of postoperative ste- nosis. To benefit endoscopic follow-up the jejunal segment should be shorter than 20 cm.
基金UKRI Collective Fund Award(Grant Ref:ES/T003936/1)to the University of Oxford,UKRI ESRC GCRF,Harnessing the power of global data to support young children’s learning and development:Analyses,dissemination and implementation。
文摘Background:The COVID-19 pandemic and governments’attempts to contain it are negatively affecting young children’s health and development in ways we are only beginning to understand and measure.Responses to the pandemic are driven largely by confining children and families to their homes.This study aims to assess the levels of and associated socioeconomic disparities in household preparedness for protecting young children under the age of five from being exposed to communicable diseases,such as COVID-19,in low-and middle-income countries(LMICs).Methods:Using data from nationally representative household surveys in 56 LMICs since 2016,we estimated the percentages of young children under the age of five living in households prepared for communicable diseases(e.g.,COVID-19)and associated residential and wealth disparities at the country-and aggregate-level.Preparedness was defined on the basis of space for quarantine,adequacy of toilet facilities and hand hygiene,mass media exposure at least once a week,and phone ownership.Disparities within countries were measured as the absolute gap in two domains—household wealth and residential area-and compared across regions and country income groups.Results:The final data set included 766,313 children under age five.On average,19.4%of young children in the 56 countries lived in households prepared for COVID-19,ranging from 0.6%in Ethiopia in 2016 to 70.9%in Tunisia in 2018.In close to 90%of countries(50),fewer than 50%of young children lived in prepared households.Young children in rural areas or in the poorest households were less likely to live in prepared households than their counterparts.Conclusions:A large portion of young children under the age of five in LMICs were living in households that did not meet all preparedness guidelines for preventing COVID-19 and caring for patients at home.This study highlights the need to ensure all families in LMICs have the means to prevent the spread of the pandemic or other communicable illnesses to young children during pandemics.
文摘Correction to:Global Health Research and Policy(2022)7:18 https://doi.org/10.1186/s41256-022-00254-2 Following publication of the original article[1],the authors reported that one reference number needs to be corrected,and the captions listed in the Supplementary Information section need to be updated.The original article[1]has been corrected.
文摘Abstract Despite important gains in human rights, persons with disabilities -- and in particular women and girls with disabilities -- continue to experience significant inequalities in the areas of sexual, reproductive, and parenting rights. Persons with disabilities are sterilized at alarming rates; have decreased access to reproductive health care services and information; and experience denial of parenthood. Precipitating these inequities are substantial and instantiated stereotypes of persons with disabilities as either asexual or unable to engage in sexual or reproductive activities, and as incapable of performing parental duties. The article begins with an overview of sexual, reproductive, and parenting rights regarding persons with disabilities. Because most formal adjudications of these related rights have centered on the issue of sterilization, the article analyzes commonly presented rationales used to justify these procedures over time and across jurisdictions. Next, the article examines the Convention on the Rights of Persons with Disabilities and the attendant obligations of States Parties regarding rights to personal integrity, access to reproductive health care services and information, parenting, and the exercise of legal capacity. Finally, the article highlights fundamental and complex issues requiring future research and consideration.
