tbuckley/cabot-search huggingface dataset:
The “Other” Neglected Diseases in Global Public Health: Surgical Conditions in Sub-Saharan Africa
Authors: Doruk Ozgediz, Robert Riviello
Journal: PLoS Medicine (2008)

Currently in sub-Saharan Africa, most patients with surgical problems that are routinely treatable in highincome countries never reach a health facility, or are treated at a facility with inadequate human or physical resources.These conditions lead to premature death or physical disability with a significant economic burden.Meanwhile, the last decade has seen the emergence of numerous "neglected tropical disease" (NTD) initiatives in global public health.As surgeons working with clinicians in sub-Saharan Africa, the momentum for NTDs causes us to ask: Shouldn't surgical conditions also be considered "neglected"?This article compares NTDs and surgical conditions in sub-Saharan Africa, considering their estimated burden and the cost-effectiveness of treatment, the scope of these conditions and associated global health disparities, and the effect of donor priorities on provision of surgical services.Lessons from NTD initiatives are analyzed among possible solutions to improving access to surgical services in sub-Saharan Africa. Burden and Cost-EffectivenessVariably defined [1,2], NTDs are primarily parasitic and bacterial infectious diseases-excluding the "big three" infections (HIV, tuberculosis, and malaria)-that affect the world's rural poor in low-income countries (LICs) and can be cheaply addressed [1,2].Despite their significant, primarily chronic disease burden, they are sidelined as "other diseases" in the Millennium Development Goals.Even with limited data, conservative estimates suggest that surgical conditions account for 11% of the total global burden of disease and 25 million disability-adjusted life years (DALYs) in Africa, the region with the highest concentration of surgical DALYs (38/1,000 population) [3].Meanwhile, NTDs account for 1.3% of the global burden of disease and 20 million DALYs globally, mainly in Africa [1,4].Despite a greater burden of disease, surgical conditions (except emergency obstetric care) are also not included in the Millennium Development Goals.Recent cost-effectiveness studies (Table 1) show that basic surgical care compares favorably (US$11-US$33/DALY averted) with traditional public health interventions such as vaccinations (US$5/DALY averted) [5][6][7].Basic surgical services are more cost-effective than antiretroviral therapy (US$300-US$500/DALY averted), even assuming low-cost production, high HIV prevalence, and high compliance [6].Similar to essential surgery, integrated treatment programs for NTDs are quite cost-effective, at US$2-US$9/DALY averted.[1].The cost estimates for surgery include the minimum human resources, infrastructure, and supplies necessary to provide surgical care at a first-level referral facility-the district hospital.The relative cost-effectiveness of surgical
The Knockout Mouse Project
Authors: Christopher P Austin, James F Battey, Allan Bradley, Maja Bucan, Mario Capecchi, Francis S Collins, William F Dove, Geoffrey Duyk, Susan Dymecki, Janan T Eppig, Franziska B Grieder, Nathaniel Heintz, Geoff Hicks, Thomas R Insel, Alexandra Joyner, Beverly H Koller, K C Kent Lloyd, Terry Magnuson, Mark W Moore, Andras Nagy, Jonathan D Pollock, Allen D Roses, Arthur T Sands, Brian Seed, William C Skarnes, Jay Snoddy, Philippe Soriano, David J Stewart, Francis Stewart, Bruce Stillman, Harold Varmus, Lyuba Varticovski, Inder M Verma, Thomas F Vogt, Harald von Melchner, Jan Witkowski, Richard P Woychik, Wolfgang Wurst, George D Yancopoulos, Stephen G Young, Brian Zambrowicz
Journal: Nature Genetics (2004)

Mouse knockout technology provides a powerful means of elucidating gene function in vivo, and a publicly available genome-wide collection of mouse knockouts would be significantly enabling for biomedical discovery. To date, published knockouts exist for only about 10% of mouse genes. Furthermore, many of these are limited in utility because they have not been made or phenotyped in standardized ways, and many are not freely available to researchers. It is time to harness new technologies and efficiencies of production to mount a high-throughput international effort to produce and phenotype knockouts for all mouse genes, and place these resources into the public domain.
A clinical predictor of varices and portal hypertensive gastropathy in patients with chronic liver disease
Authors: Yang Won Min, So Young Bae, Geum-Youn Gwak, Yong Han Paik, Moon Seok Choi, Joon Hyoek Lee, Seung Woon Paik, Byung Chul Yoo, Kwang Cheol Koh
Journal: Clinical and Molecular Hepatology (2012)

Background/Aims The aim of this study was to identify the parameters that could noninvasively predict the presence of esophageal/gastric varices and portal hypertensive gastropathy (PHG) in patients with chronic liver disease (CLD), and to determine the accuracy of those parameters. Methods We retrospectively analyzed 232 patients with CLD who underwent both upper endoscopy and liver CT within an interval of 3 months. The multidimensional index (M-Index) for spleen volume was obtained from the multiplication of splenic length, width, and thickness, as measured by computer tomography. Results The multivariate analysis revealed that platelet, albumin, and M-Index were independently associated with the presence of varices and PHG. We combined three independent parameters, and developed a varices and portal hypertensive gastropathy (VAP) scoring system (=[platelet count (/mm3)×albumin (g/dL)]/[M-Index (cm3)]). The area under the receiver operating characteristic curve of the VAP score was 0.850 (95% confidence interval, 0.801-0.899). The VAP cut-off value of 861 had a sensitivity of 85.3%, a positive likelihood ratio of 3.17, and a negative predictive value of 86.4%. For predicting high-risk lesions for bleeding, with a cut-off value of 861 the sensitivity was 92.0%, the positive likelihood ratio was 2.20, and the negative predictive value was 96.4%. Conclusions The VAP score can predict the presence of varices and PHG in patients with CLD and may increase the cost-benefit of screening endoscopy in the clinical practice setting. A prospective validation study is necessary in the future. Keywords: Esophageal and gastric varices; Portal hypertensive gastropathy; VAP score
Abstract LB-13: Calcitonin receptor-zonnula occludens-1 interaction is critical for calcitonin-induced destabilization of tight junctions and s prostate cancer metastasis
Authors: Girish V. Shah, Pratistha Tamrakar, Shibu Thomas, Vijaybasker Lakshmikanthan, Parash Parajuli, Seetharama Sathyanarayanajois, Suleiman Bahouth, Alan Fanning, James Anderson
Journal: Cancer Research (2011)

Abstract Most primary prostate cancers (PCs) and PC cell lines express calcitonin (CT) and/or its receptor (CTR), and their co-expression positively correlates with tumor grade of primary PCs and growth/invasiveness of PC cell lines. Activation of the CT-CTR axis in non-invasive PC cells induces an invasive phenotype. In contrast, silencing of CT-CTR axis markedly reduces the tumorigenicity and metastatic capacity. We have identified that cytoplasmic (C) tail of CTR contains a canonical class I type PSD-95, Discs-large, Zonnula Occludens-1 (PDZ)-binding motif, mutation of which does not affect its ability to bind its ligand or activate its G protein-coupled actions but abrogates CT-elicited destabilization of tight junctions or invasion. We then used CTR-C tail as a bait to identify its interactor by yeast two hybrid screening of prostate cDNA library. This revealed that CTR-C tail binds to intracellular membrane protein zonula occludens (ZO-1) through its PDZ domain. This interaction was confirmed using multiple approaches such as pull-down assays, overlay assays, co-immunoprecipitation and acceptor photobleaching FRET microscopy. The results demonstrate that CTR binds to PDZ3 domain of ZO-1 through its PDZ-binding motif. Mutation of either CTR-C PDZ-binding motif or ZO-1- PDZ3 domain abrogated actions of CT on tight junctions, invasion, orthotopic tumor growth and promotion of distant metastasis. These results for the first time demonstrate PDZ-dependent interaction between CTR and ZO-1; and that this interaction is critical for CT-CTR axis-elicited prostate cancer progression. Considering overexpression of CT-CTR axis in malignant prostate, the results suggest that prevention of this interaction may serve as a new therapeutic possibility for the treatment of advanced prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-13. doi:10.1158/1538-7445.AM2011-LB-13
The effect of treatment on plasma uroporphyrin levels in cutaneous hepatic porphyria
Authors: B.R. ALLEN, SHEENA PARKER, G.G. THOMPSON, M.R. MOORE, F.J. DARBY, J.A.A. HUNTER
Journal: British Journal of Dermatology (1975)

Seven patients undergoing treatment for cutaneous hepatic porphyria had serial measurements of their plasma uroporphyrin. In each case there was a progressive fall during treatment but even in remission the levels did not return to normal. There was a significant correlation between urinary and plasma uroporphyrin concentrations.
The Efficacy of Generic Primidone-Reply
Authors: Elaine Wyllie
Journal: JAMA (1989)

In Reply. —  We presented the events of our case honestly and completely, just as they occurred, and our report passed a critical peer review before publication. Most important, the Food and Drug Administration investigation provided no new evidence to alter the reported critical facts in the case.  The key issues in our report were that our patient had been taking Mysoline (Ayerst Laboratories, New York, NY) for 13 days before the October 1985 hospital admission, that serum primidone and phenobarbital concentrations were adequate at the time of that admission, and that serum drug concentrations dropped dramatically during hospitalization, with no other plausible cause than the switch to generic medication. These facts remained firm after the Food and Drug Administration investigation and are dated clearly in the medical record just as they were reported in our article. No relevant or important information was excluded from our published report. Eventually, after
Left Ventricular Rupture in a Patient with Coexisting Right Ventricular Infarction
Authors: Mark A. Greenberg, Bernard Gitler
Journal: New England Journal of Medicine (1983)

CARDIAC rupture, although usually an acute catastrophic event, may be subacute, so that diagnosis and surgical treatment of cardiac tamponade and the underlying myocardial tear is possible.1 2 3 The diagnosis of cardiac tamponade depends on clinical and hemodynamic evaluation. Although the clinical presentation of hypotension, distended neck veins, and pulsus paradoxus is characteristic of tamponade,4 these findings may also be present in right ventricular infarction.5 , 6 Equalization of right atrial and pulmonary capillary wedge pressures may occur in right ventricular infarction as well as cardiac tamponade, thus making differentiation difficult. In a recent series, 4 of 12 patients with right ventricular infarction . . .
The Connectivity Map Links Iron Regulatory Protein-1–Mediated Inhibition of Hypoxia-Inducible Factor-2a Translation to the Anti-inflammatory 15-deoxy-Δ12,14-Prostaglandin J2
Authors: Michael Zimmer, Justin Lamb, Benjamin L. Ebert, Mary Lynch, Christopher Neil, Emmett Schmidt, Todd R. Golub, Othon Iliopoulos
Journal: Cancer Research (2010)

Abstract Hypoxia-inducible factors 1 and 2 (HIF1 and HIF2) are heterodimeric transcription factors consisting of α regulatory subunits and a constitutively expressed β subunit. The expression of α regulatory subunits is promoted by hypoxia, cancer-associated mutations, and inflammatory cytokines. Thus, HIF1 and HIF2 provide a molecular link between cancer and inflammation. We have recently identified novel small molecules that selectively inhibit translation of the HIF2a message and thereby powerfully inhibit the expression of HIF2a target genes. We report here that Connectivity Map analysis links three of these compounds to the anti-inflammatory cytokine 15-deoxy-Δ12,14-prostaglandin J2 (PGJ2). As with our identified compounds, PGJ2 inhibits translation of the HIF2a message in a mammalian target of rapamycin–independent manner by promoting the binding of iron regulatory protein-1 (IRP1) to a noncanonical iron responsive element (IRE) embedded within the 5′-untranslated region of the HIF2a message. The IRE is necessary and sufficient for mediating the effect. Mutation of the IRE sequence, or downregulation of IRP1 expression, blocks the effect of PGJ2 on HIF2a translation. This is the first report of an endogenous natural molecule regulating HIF2a translation, and it suggests that part of the anti-inflammatory and putative antineoplastic effects of PGJ2 may be mediated through inhibition of HIF2a within tumor epithelial cells themselves and/or mesenchymal cells of the tumor microenvironment. Cancer Res; 70(8); 3071–9. ©2010 AACR.
Family History and the Risk of Sudden Cardiac Death as a Manifestation of an Acute Coronary Event
Authors: Kari S. Kaikkonen, Marja-Leena Kortelainen, Eeva Linna, Heikki V. Huikuri
Journal: Circulation (2006)

Observational studies have suggested that a parental history of sudden death increases one's risk of dying suddenly. This study tested the hypothesis that a family history of sudden cardiac death (SCD) is a risk factor for SCD caused by an acute coronary event.A retrospective case-control study included (1) consecutive victims of SCD (n=138) whose deaths were verified to be due to an acute coronary event without a history of prior myocardial infarction at medicolegal autopsy, (2) consecutive patients surviving an acute myocardial infarction (AMI; n=254), and (3) healthy control subjects (n=470). Family history of AMI and SCD among the first-degree relatives was ascertained in each study group. The incidence of SCD in the 1223 first-degree relatives of SCD victims was higher (5.2%) than that in the 2326 relatives of AMI survivors (3.3%; odds ration [OR] 1.6, 95% confidence interval [CI] 1.2 to 2.2, P<0.01) or the 3748 relatives of controls (OR 2.2; 95% CI 1.6 to 3.0, P<0.001). The history of SCD in 2 or more first-degree relatives was also higher (10.9%) among SCD victims than among AMI survivors (3.5%; OR 3.3, 95% CI 1.4 to 7.8, P<0.01) or controls (1.1%; OR 11.3, 95% CI 4.0 to 31.8, P<0.001). The family history of AMI did not differ between the SCD and AMI groups. Male gender and current smoking were the only coronary risk factors that were more prevalent among SCD victims than among AMI survivors (P<0.001 for both).Subjects with a family history of SCD have an increased risk of dying suddenly during an acute coronary event.
PTEN-Deficient Tumors Depend on AKT2 for Maintenance and Survival
Authors: Y. Rebecca Chin, Xin Yuan, Steven P. Balk, Alex Toker
Journal: Cancer Discovery (2014)

Loss of PTEN is a common event in many cancers and leads to hyperactivation of the PI3K-AKT signaling pathway. The mechanisms by which AKT isoforms mediate signaling to phenotypes associated with PTEN inactivation in cancer have not been defined. Here, we show that AKT2 is exclusively required for PTEN-deficient prostate tumor spheroid maintenance, whereas AKT1 is dispensable. shRNA silencing of AKT2 but not AKT1 promotes regression of prostate cancer xenografts. Mechanistically, we show that AKT2 silencing upregulates p21 and the proapoptotic protein BAX and downregulates the insulin-like growth factor receptor-1. We also show that p21 is an effector of AKT2 in mediating prostate tumor maintenance. Moreover, AKT2 is also exclusively required for the maintenance and survival of other PTEN-deficient solid tumors, including breast cancer and glioblastoma. These findings identify a specific function for AKT2 in mediating survival of PTEN-deficient tumors and provide a rationale for developing therapeutics targeting AKT2.Depletion of AKT2, but not AKT1, induces potent tumor regression in PTEN-deficient prostate cancer xenografts, concomitant with upregulation of p21, which may serve as a potential biomarker for screening AKT2 activity in clinical samples. The specific role of AKT2 in tumor maintenance provides a rationale for the development of isoform-specific inhibitors for patients with PTEN-deficient cancers.
Limited utility of inflammatory markers in the early detection of postoperative inflammatory complications after pancreatic resection: Cohort study and meta-analyses
Authors: Leonardo Solaini, Bambang T. Atmaja, Jennifer Watt, Prabhu Arumugam, Robert R. Hutchins, Ajit T. Abraham, Satyajit Bhattacharya, Hemant M. Kocher
Journal: International Journal of Surgery (2015)
Turning a blind eye to alternative medicine education
Authors: D. M. Marcus
Journal: BMJ (2013)

Donald M Marcus investigates how medical schools deal with the teaching of CAM

Despite little evidence for their efficacy,1 2 3 and growing information about their adverse effects,4 complementary and alternative medicine (CAM) therapies are popular. In 2007 consumers spent $24bn (£15bn; €18bn) out of pocket on self prescribed alternative treatments and products.5 The use of these therapies is driven, in large part, by the prevalence of misinformation in the media and on the internet. Academic health science centers should provide evidence based guidance to health professionals and to the public. Unfortunately, many medical and nursing schools endorse the use of CAM.

The mission of integrative medicine centers, which are present in more than 40 medical and nursing schools, is to introduce evidence based information regarding safe and effective alternative therapies into healthcare education. Although clinical trials before 2000 provided data supporting the efficacy of some alternative therapies, systematic reviews showed serious defects in their methodology that made them uninterpretable. More rigorous, independently funded trials of the past decade found no evidence for their efficacy beyond a placebo effect.1 2 3

A detailed review of curriculums created by 15 institutions that received educational grants from the National Center for Complementary and Alternative Medicine (NCCAM) showed that they failed to conform to the principles of evidence …
Abstract A59: Protein kinase CK2 regulates β-catenin association to E-cadherin and hence viability and invasion of colorectal cancer cells
Authors: Roger Yefi, Eduardo Silva, Pablo Cabello, Ignacio Niechi, Hernan Huerta, Ricardo Armisen, Cristina Fernandez, Julio C. Tapia
Journal: Cancer Research (2013)

Abstract The key factor in the canonical Wnt pathway is β-catenin which also functions in cell-cell adhesion forming a complex with E-cadherin at the cell surface. Activation of the canonical Wnt pathway is linked to the release of β-catenin from the cell surface, its cytoplasmic stabilization and nuclear import, followed by increased transcriptional activity on genes normally linked to cancer progression, such as survivin and cyclin D1. We already described that caveolin-1 is a member of this complex (termed CEB for caveolin-1/E-cadherin/β-catenin) which inhibits β-catenin transcriptional activity thereby acting as a tumor suppressor. Conversely, protein kinase CK2 is abnormally elevated in a wide variety of cancers, promoting progression by regulating oncogene and tumor suppressor proteins, but also promoting an elevated β-catenin activity. We already demonstrated that cyclooxygenase-2 (COX-2) is a target of CK2 and its metabolite, prostaglandin E2 (PGE2), is key to up-regulate cell proliferation and apoptosis resistance. However, how CK2, PGE2, and caveolin-1 participate in the mechanism of CK2-mediated colorectal cancer progression is yet unknown. In this work, we hypothesize that CK2 promotes cancer progression by augmenting COX-2 expression and subsequently PGE2 production, which disrupts the putative CEB complex in an autocrine manner, leading to the release of β-catenin and increase of its nuclear activity. This was investigated by determining the presence of CEB complex in DLD-1 colon cancer cells (IP), as well as by evaluating the effect of either PGE2 or a CK2 inhibitor (TBB) on in vitro proliferation (MTS®), apoptosis (Caspase-Glo®) and invasiveness (wound-healing and matrigel assays) of these cancer cells. Our results suggest that the CK2-dependent autocrine production of PGE2 in DLD-1 colon cancer cells promotes the dissociation of caveolin-1 from the CEB complex at the cell surface, allowing β-catenin to be apparently phosphorylated (WB anti-P-antibodies) and released to the cytosol, which increments its nuclear import and transcriptional activity on cancer-related genes. Supported by ICGEB (CRP/CHI10-01) and FONDECYT (11070116, 1120132) grants to J.C.T. Citation Format: Roger Yefi, Eduardo Silva, Pablo Cabello, Ignacio Niechi, Hernan Huerta, Ricardo Armisen, Cristina Fernandez, Julio C. Tapia. Protein kinase CK2 regulates β-catenin association to E-cadherin and hence viability and invasion of colorectal cancer cells. [abstract]. In: Proceedings of the Third AACR International Conference on Frontiers in Basic Cancer Research; Sep 18-22, 2013; National Harbor, MD. Philadelphia (PA): AACR; Cancer Res 2013;73(19 Suppl):Abstract nr A59.
Charles James Barton Anderson
Authors: R. Anderson
Journal: BMJ (2014)

As a boy, Charles James Barton Anderson lived at Aucharnie Farm near Huntly. He went to the local primary school at Forgue and then on to Huntly for his secondary education. When in Huntley he stayed in lodgings during the week, returning home at weekends, but later he commuted daily in a three wheeler car, which he shared with two of his siblings. He went on to study medicine at Aberdeen, where he developed an interest in surgery. After wartime service in the army, he obtained a surgical training post in Aberdeen, where …
Bone marrow fails to differentiate into liver epithelium during murine development and regeneration†
Authors: C. Bart Rountree, Xuli Wang, Shundi Ge, Lora Barsky, Judy Zhu, Ignacio Gonzales, Gay M. Crooks
Journal: Hepatology (2007)

Recent reports have provided conflicting conclusions regarding the role for bone marrow (BM)–derived cells in the regeneration of liver. Our aim was to investigate the potential of BM to contribute to liver epithelium using different BM transplant models designed to explore differentiation during normal liver development and regeneration after toxic injury. BM cells from transgenic green fluorescent protein (GFP) mice were injected into neonatal and adult immunodeficient and neonatal immune-competent mice. Three distinct models of liver injury were employed to test the contribution of marrow to the regeneration of hepatocytes, cholangiocytes, and oval cells in immune-deficient adult animals after neonatal transplant. Immunohistochemistry was combined with flow cytometry (FACS) and reverse transcription (RT)-PCR to increase the sensitivity and specificity of the analyses. Although GFP+ marrow-derived cells were observed in the livers of all transplanted animals, immunohistochemistry failed to demonstrate any marrow derived hepatocytes or cholangiocytes. FACS confirmed that GFP+ marrow-derived cells in the liver maintained expression of CD45, a leukocyte marker. Gene expression studies of GFP+ cells isolated by FACS failed to demonstrate expression of liver specific genes in these marrow-derived cells. Conclusion: Through highly sensitive and specific analyses, we were unable to demonstrate any evidence of transdifferentiation of BM-derived cells into epithelial hepatic tissue during the period of rapid growth in the neonatal period. Furthermore, although increased migration of hematopoietic cells to the liver occurred after toxic injury, these cells did not contribute directly to the replacement of hepatocytes, cholangiocytes, or oval cells. (HEPATOLOGY 2007;45:1250–1260.)