Deciphering von Hippel-Lindau (VHL/Vhl)-Associated Pancreatic Manifestations by Inactivating Vhl in Specific Pancreatic Cell Populations

The von Hippel-Lindau (VHL) syndrome is a pleomorphic familial disease characterized by the development of highly vascularized tumors, such as hemangioblastomas of the central nervous system, pheochromocytomas, renal cell carcinomas, cysts and neuroendocrine tumors of the pancreas. Up to 75% of VHL patients are affected by VHL-associated pancreatic lesions; however, very few reports in the published literature have described the cellular origins and biological roles of VHL in the pancreas. Since homozygous loss of Vhl in mice resulted in embryonic lethality, this study aimed to characterize the functional significance of VHL in the pancreas by conditionally inactivating Vhl utilizing the Cre/LoxP system. Specifically, Vhl was inactivated in different pancreatic cell populations distinguished by their roles during embryonic organ development and their endocrine lineage commitment. With Cre recombinase expression directed by a glucagon promoter in α-cells or an insulin promoter in β-cells, we showed that deletion of Vhl is dispensable for normal functions of the endocrine pancreas. In addition, deficiency of VHL protein (pVHL) in terminally differentiated α-cells or β-cells is insufficient to induce pancreatic neuroendocrine tumorigenesis. Most significantly, we presented the first mouse model of VHL-associated pancreatic disease in mice lacking pVHL utilizing Pdx1-Cre transgenic mice to inactivate Vhl in pancreatic progenitor cells. The highly vascularized microcystic adenomas and hyperplastic islets that developed in Pdx1-Cre;Vhl f/f homozygous mice exhibited clinical features similar to VHL patients. Establishment of three different, cell-specific Vhl knockouts in the pancreas have allowed us to provide evidence suggesting that VHL is functionally important for postnatal ductal and exocrine pancreas, and that VHL-associated pancreatic lesions are likely to originate from progenitor cells, not mature endocrine cells. The novel model systems reported here will provide the basis for further functional and genetic studies to define molecular mechanisms involved in VHL-associated pancreatic diseases

ACC/AHA 2002 guideline update for the management of patients with chronic stable angina - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina)

"The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or a full revision is needed. This process gives priority to areas in which major changes in text, and particularly recommendations, are merited on the basis of new understanding or evidence. Minor changes in verbiage and references are discouraged. The ACC/AHA/American College of Physicians-American Society of Internal Medicine (ACP-ASIM) Guidelines for the Management of Patients With Chronic Stable Angina, which were published in June 1999, have now been updated. The full-text guideline incorporating the updated material is available on the Internet (www.acc.orgor www.americanheart.org) in both a track-changes version showing the changes in the 1999 guideline in strike-out (deleted text) and highlighting (new text) and a “clean” version that fully incorporates all the changes. This summary article describes the 4 most important areas of change reflected in the update in a format that we hope can be read and understood as a stand-alone document. Interested readers are referred to the full-length version on the Internet to completely understand the location of these changes within the full-length guideline, as well as their proper context. The full-length guideline includes some additional changes that are not reflected in this summary article. All new references appear in bold-faced type; all original references appear in normal type. Although the primary focus of this guideline is on symptomatic patients, asymptomatic patients with known or suspected coronary disease are included in this update and are described in Section V.

ACC/AHA 2002 guideline update for the management of patients with chronic stable angina - Summary article: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina)

"The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or a full revision is needed. This process gives priority to areas in which major changes in text, and particularly recommendations, are merited on the basis of new understanding or evidence. Minor changes in verbiage and references are discouraged. The ACC/AHA/American College of Physicians–American Society of Internal Medicine (ACP-ASIM) Guidelines for the Management of Patients With Chronic Stable Angina, which were published in June 1999, have now been updated. The full-text guideline incorporating the updated material is available on the Internet (www.acc.org or www.americanheart.org) in both a track-changes version showing the changes in the 1999 guideline in strike-out (deleted text) and highlighting (new text) and a “clean” version that fully incorporates all the changes. This summary article describes the 4 most important areas of change reflected in the update in a format that we hope can be read and understood as a stand-alone document. Interested readers are referred to the full-length version on the Internet to completely understand the location of these changes within the full-length guideline, as well as their proper context. The full-length guideline includes some additional changes that are not reflected in this summary article. All new references appear in bold-faced type; all original references appear in normal type. Although the primary focus of this guideline is on symptomatic patients, asymptomatic patients with known or suspected coronary disease are included in this update and are described in Section V.

Comparing Transactional eHealth Literacy of Individuals With Cancer and Surrogate Information Seekers: Mixed Methods Study

BackgroundThe number of adults entering higher-risk age groups for receiving a cancer diagnosis is rising, with predicted numbers of cancer cases expected to increase by nearly 50% by 2050. Living with cancer puts exceptional burdens on individuals and families during treatment and survivorship, including how they navigate their relationships with one another. One role that a member of a support network may enact is that of a surrogate seeker, who seeks information in an informal capacity on behalf of others. Individuals with cancer and surrogate seekers often use the internet to learn about cancer, but differences in their skills and strategies have received little empirical attention. ObjectiveThis study aimed to examine the eHealth literacy of individuals with cancer and surrogate information seekers, including an investigation of how each group evaluates the credibility of web-based cancer information. As a secondary aim, we sought to explore the differences that exist between individuals with cancer and surrogate seekers pertaining to eHealth literacies and sociodemographic contexts. MethodsBetween October 2019 and January 2020, we conducted a web-based survey of 282 individuals with cancer (n=185) and surrogate seekers (n=97). We used hierarchical linear regression analyses to explore differences in functional, communicative, critical, and translational eHealth literacy between individuals with cancer and surrogate seekers using the Transactional eHealth Literacy Instrument. Using a convergent, parallel mixed methods design, we also conducted a thematic content analysis of an open-ended survey response to qualitatively examine how each group evaluates web-based cancer information. ResultseHealth literacy scores did not differ between individuals with cancer and surrogate seekers, even after adjusting for sociodemographic variables. Individuals with cancer and surrogate seekers consider the credibility of web-based cancer information based on its channel (eg, National Institutes of Health). However, in evaluating web-based information, surrogate seekers were more likely than individuals with cancer to consider the presence and quality of scientific references supporting the information. Individuals with cancer were more likely than surrogate seekers to cross-reference other websites and web-based sources to establish consensus. ConclusionsWeb-based cancer information accessibility and evaluation procedures differ among individuals with cancer and surrogate seekers and should be considered in future efforts to design web-based cancer education interventions. Future studies may also benefit from more stratified recruitment approaches and account for additional contextual factors to better understand the unique circumstances experienced within this population