tbuckley/cabot-search huggingface dataset:
Periodontal diseases and adverse pregnancy outcomes: Mechanisms
Authors: Elena Figuero, Yiping W. Han, Yasushi Furuichi
Journal: Periodontology 2000 (2020)

Abstract Adverse pregnancy outcomes ( APO s) have been defined as (a) pre‐term birth, when there is a delivery before 37 completed weeks (&lt;259 days); (b) pre‐eclampsia, which is a multisystem disorder of pregnancy characterized by maternal hypertension and proteinuria after the 20th gestational week; (c) low and very low birthweight, depending on whether the weight of the baby is less of 2500 g or &lt;1500 g and (d) the spontaneous death of the fetus with &lt;20 weeks (miscarriage) or between 20 and 36 weeks (stillbirth). In 2012, during the Consensus Report from the Joint EFP / AAP workshop on periodontitis and systematic diseases the role of periodontal diseases on APO s was reviewed. Some years later, this evidence has grown, and an update on the literature regarding the mechanisms related to this potential association ( APO s and periodontal diseases) needs to be presented. The two major pathways (direct and indirect) already accepted in 2012 are still valid nowadays. Most evidence published in the last 5 years deals with a strong and solid evidence coming from the direct pathway while there is as scarce new evidence regarding indirect pathway. In this direct pathway, the haematological dissemination of oral microorganisms and their products, would later induce an inflammatory/Immune response in the foetal‐placental unit. The most plausible route for this direct pathway is the hematogenous transmission through dental bacteremia, although not many new studies dealing with bacteremia has been performed lately.
KLF6-SV1 accelerates prostate cancer progression and metastasis
Authors: Goutham Narla, Analisa DiFeo, Yolanda Fernandez, Saravana Dhanasekaran, Fei Huang, Jaya Sangodkar, Eldad Hod, Devin Leake, Scott Friedman, Simon Hall, Arul Chinnaiyan, William Gerald, Mark Rubin, John Martignetti
Journal: Cancer Research (2008)

349  The molecular mechanisms underlying the transition from localized tumour to disseminated, hormone refractory prostate cancer (PCa) remain largely unknown. Here we demonstrate that increased tumor expression of KLF6-SV1, a splice variant of the KLF6 tumor suppressor gene, predicts a markedly poorer survival and disease recurrence profile in men following prostatectomy. As would be expected, KLF6-SV1 levels are specifically upregulated in hormone refractory, metastatic PCa. In two complementary mouse models, in vivo and ex vivo bioluminescent imaging of KLF6-SV1 overexpressing tumor cells demonstrated more rapid and frequent  and increased dissemination to lymph nodes, bone, and brain, whereas increased KLF6-SV1 expression did not impact localized tumor growth. In accord with its role as a prosurvival protein, KLF6-SV1 inhibition using RNA interference induced spontaneous apoptosis in cell culture and suppressed tumor growth in vivo. Together, these findings demonstrate that KLF6-SV1 expression levels, in tumors at the time of diagnosis or in genetically engineered cells, can define the metastatic behaviour of prostate cancer and that this metastasis promoter gene may thus represent a novel therapeutic target.
The Disproportionate Burden of COVID-19 for Immigrants in the Bronx, New York
Authors: Jonathan Ross, Chanelle M. Diaz, Joanna L. Starrels
Journal: JAMA Internal Medicine (2020)

Parsa Erfani, BA; Nishant Uppal, BS; Caroline H. Lee, BA; Ranit Mishori, MD, MHS; Katherine R. Peeler, MD
The multifaceted long-term effects of the COVID-19 pandemic on urology
Authors: Alessandro Morlacco, Giovanni Motterle, Filiberto Zattoni
Journal: Nature Reviews Urology (2020)

The COVID-19 pandemic has resulted in immediate effects on urological practice, in particular the vast reduction in elective surgeries. These changes are likely to have long-term effects for both patients and for urologists, which will persist even after the pandemic resolves. The many facets of COVID-19's effects on urology remain to be seen, but they might also offer opportunities to reassess and improve patient management in urology and beyond.
Pharmacokinetic study of the phase III, randomized, double-blind, multicenter trial of paclitaxel (Pac) and carboplatin (C) combined with erlotinib (E) or placebo in patients with advanced non-small cell lung cancer(NSCLC)
Authors: H. T. Tran, R. Zinner, G. R. Blumenschein, Y. W. Oh, V. A. Papadimitrakopoulou, E. S. Kim, C. Lu, M. Malik, B. Lum, R. S. Herbst
Journal: Journal of Clinical Oncology (2004)

2050 Background: Erlotinib is a novel, oral EGFR-TKI that has demonstrated activity as a single agent in pts with advanced NSCLC. Preclinical studies have shown additive efficacy when E was combined with cytotoxic agents including taxanes and platinums. Both Pac and E utilize CYP3A4 as a metabolic pathway. Thus, a potential drug-drug interaction may occur with E and/or Pac. Methods: 1059 previously untreated pts with advanced NSCLC were enrolled and randomized to receive either E or placebo in combination with Pac 200 mg/m2 IV/3hrs + C AUC=6 mg/ml*min. To determine possible drug-drug interaction with this combination, a subset of 24 (12 E, 12 placebo) pts were enrolled onto an intensive PK sampling group (IPK) at a single site. All IPK patients received E 100 mg/day. Analyses were completed using validated analytical methodologies. Non-compartmental modeling was utilized to estimate PK parameters. Results: 21/24 pts with complete blood sampling were included in the final IPK analysis. Mean (n=9) AUCs for erlotinib and OSI-420/413 metabolite were 29997 ng/ml and 3020 ng/ml; respectively. Mean (SD) PK parameters for Pac and C are summarized in the table below: Conclusions: Overall, no alteration in the disposition of carboplatin AUC0-inf (p=0.756) and paclitaxel AUC0-inf (p=0.80) in erlotinib-treated pts when compared to placebo-treated pts was observed. Population PK analysis is currently on going to assess if erlotinib PK is affected by the presence of paclitaxel and carboplatin. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genentech, Inc. Amgen; Aventis Genentech, Inc.
Effect of aerobic exercise training on asthma in adults: a systematic review and meta-analysis
Authors: Erik Soeren Halvard Hansen, Anders Pitzner-Fabricius, Louise Lindhardt Toennesen, Hanne Kruuse Rasmusen, Morten Hostrup, Ylva Hellsten, Vibeke Backer, Marius Henriksen
Journal: European Respiratory Journal (2020)

Objective To evaluate the effect of aerobic exercise training on asthma control, lung function and airway inflammation in adults with asthma. Design Systematic review and meta-analysis. Methods Randomised controlled trials investigating the effect of ≥8 weeks of aerobic exercise training on outcomes for asthma control, lung function and airway inflammation in adults with asthma were eligible for study. MEDLINE, Embase, CINAHL, PEDro and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to April 3, 2019. Risk of bias was assessed using the Cochrane Risk of Bias Tool. Results We included 11 studies with a total of 543 adults with asthma. Participants' mean (range) age was 36.5 (22–54) years; 74.8% of participants were female and the mean (range) body mass index was 27.6 (23.2–38.1) kg·m −2 . Interventions had a median (range) duration of 12 (8–12) weeks and included walking, jogging, spinning, treadmill running and other unspecified exercise training programmes. Exercise training improved asthma control with a standard mean difference (SMD) of −0.48 (−0.81–−0.16). Lung function slightly increased with an SMD of −0.36 (−0.72–0.00) in favour of exercise training. Exercise training had no apparent effect on markers of airway inflammation (SMD −0.03 (−0.41–0.36)). Conclusions In adults with asthma, aerobic exercise training has potential to improve asthma control and lung function, but not airway inflammation.
Tumor immunity in mice reconstituted with BM cells engineered to express single chain T cell receptor specific for the tumor antigen MUC1.
Authors: Nehad M. Alajez, Olivera J. Finn
Journal: Cancer Research (2004)

2465   MUC1 glycoprotein is overexpressed on the surface of a variety of epithelial tumors and has been under investigation as a target for immunotherapy. Cytotoxic lymphocyte clones were generated from breast and pancreatic cancer patients that recognized MUC1 on the surface of tumor cells in a TCR-mediated MHC-unrestricted manner. The purpose of this study was to explore the potential to use MHC-unrestricted MUC1-specific TCR gene transfer for cancer immunotherapy. The T cell receptor (TCR) α and β chains were cloned from one MHC-unrestricted CTL clone (MA). Various chimeric TCRs were constructed and expressed on the surface of a variety of cell lines in vitro. TCR-deficient T cell line Jurkat, JRT3.5, transfected with the TCR α and β chains from MA CTL fluxed calcium in response to stimulation with a MUC1+ human tumor, HPAF. BWZ murine thymoma cells transfected with a scTCR (consisting of the TCR extracellular domain and the CD3 ζ signaling domain) were triggered to secret IL-2 in response to stimulation with MUC1+ tumor cells. These results confirmed specificity and functionality of the cloned receptors. The tumor recognition and rejection function of one of the constructs, the scTCR, was tested in vivo in SCID mice reconstituted with BM cells transduced with scTCR-MFG retroviral vector and challenged with HPAF tumor cells. Tumor growth in mice with scTCR-transduced BM cells was significantly slower than that seen in the control group. FACS analysis showed that BM cells transduced with scTCR-MFG retroviral vector differentiated in vivo into multiple immune lineages including granulocytes, monocytes and NK cells that express the scTCR. Human MUC1 Tg. mice reconstituted with BM cells transduced with the MUC1-specific TCR did not show any signs of autoimmunity, cellular infiltration or destruction of MUC1-expressing tissues. Transduction of BM with tumor-specific TCR represents a potentially efficacious gene therapy/immunotherapy approach. MUC1-specific MHC-unrestricted TCR will make this treatment applicable to all cancer patients with MUC1+ tumors, regardless of their HLA type.
Patient perspective: Gordon Sturmey and Matt Wiltshire
Authors: Gordon Sturmey, Matt Wiltshire
Journal: BMJ (2020)

Having both been long stay patients in an intensive care unit (ICU) in the 2000s, we understand the importance of physical and psychological rehabilitation after discharge.

We were some of the lucky few that could attend a follow-up clinic (run by the Royal Berkshire Hospital),1 which in the long term improved our quality of life as well as, we believe, reducing our chances of …
Dolutegravir versus efavirenz in women starting HIV therapy in late pregnancy (DolPHIN-2): an open-label, randomised controlled trial
Authors: Kenneth Kintu, Thokozile R Malaba, Jesca Nakibuka, Christiana Papamichael, Angela Colbers, Kelly Byrne, Kay Seden, Eva Maria Hodel, Tao Chen, Adelline Twimukye, Josaphat Byamugisha, Helen Reynolds, Victoria Watson, David Burger, Duolao Wang, Catriona Waitt, Miriam Taegtmeyer, Catherine Orrell, Mohammed Lamorde, Landon Myer, Saye Khoo
Journal: The Lancet HIV (2020)
Nonoliguric Acute Renal Failure
Authors: Robert J. Anderson, Stuart L. Linas, Arnold S. Berns, William L. Henrich, Thomas R. Miller, Patricia A. Gabow, Robert W. Schrier
Journal: New England Journal of Medicine (1977)

To delineate the clinical spectrum of nonoliguric renal failure, we studied prospectively 92 patients with acute renal failure, 54 of whom were nonoliguric throughout their periods of azotemia. Although the causes of nonoliguric renal failure varied, nephrotoxic failure occurred more frequently in nonoliguric than in oliguric subjects (P<0.01). As compared to oliguric patients, those without oliguria had significantly lower urinary sodium concentrations (P<0.05) and fractional excretions of sodium (P<0.02), had a shorter hospital stay (P<0.01), had fewer septic episodes, neurologic abnormalities, gastrointestinal bleeding and acidemia, required dialysis less frequently (P<0.001) and had a lower mortality rate (26 per cent in nonoliguric vs. 50 per cent in oliguric patients — P<0.05). Nonoliguric renal failure occurs more often than is generally recognized and causes less morbidity and mortality than oliguric acute renal failure. (N Engl J Med 296:1134–1138, 1977
Shared Intentionality, joint commitment, and directed obligation
Authors: Margaret Gilbert
Journal: Behavioral and Brain Sciences (2020)

Abstract Tomasello frequently refers to joint commitment, but does not fully characterize it. In earlier publications, I have offered a detailed account of joint commitment, tying it to a sense that the parties form a “we,” and arguing that it grounds directed obligations and rights. Here I outline my understanding of joint commitment and its normative impact.
Role of MPR as an Early Signal for Efficacy in Neoadjuvant Studies
Authors: Collin M. Blakely, Caroline E. McCoach
Journal: Clinical Cancer Research (2020)

Overall survival and disease-free survival have been the gold standard primary endpoints for neoadjuvant clinical trials. Major pathologic response is a clinically proven surrogate of efficacy and when used as the primary endpoint, can allow for more efficient evaluation of drugs in the neoadjuvant setting.See related article by Cascone et al., p. 3525.
Human herpesvirus 8 K1-derived peptides disrupt the inhibitory Fas-K1 complex and restore Fas receptor-mediated apoptosis
Authors: Shu Wang, Zuzana Berkova, Suizhao Wang, Hoyoung Maeng, Soung-Chul Cha, Felipe Samaniego
Journal: Cancer Research (2008)

2667  Background: Human herpesvirus 8 (HHV-8) infection is associated with the development of primary effusion lymphoma, Kaposi sarcoma, and multicentric Castleman disease. The K1 gene of HHV-8 is expressed in tumor cells as a transmembrane protein with an immunoglobulin-like domain in its ectodomain and an immunoreceptor tyrosine-based activation motif (ITAM). We demonstrated that K1 protein activates nuclear factor-kappa B (NF-κB), and K1 expression in transgenic mice stimulated accumulation of lymphatic cells and development of lymphoma. How K1 blocks apoptosis and induces hyperplasia and lymphomas is not known. We hypothesized that K1 contributes to lymphoma development partly by suppressing apoptosis, and that this suppression combined with its NF-κB activation produces lymphoma.  Results: We found that K1 binds to Fas and in turn, inhibits Fas-mediated apoptosis. We mapped the region that K1 uses to bind to Fas as an immunoglobulin (Ig) chain-like domain by expressing deletion mutants of K1. Overexpression of an Ig domain-containing protein CD79b competed with K1-Fas binding in a dose-dependent manner. Two 20-amino acid peptides (N251, N253) representing the Ig domain of K1 competed with K1-Fas binding in immunoprecipitation/immunoblotting analysis. The N251 and N253 peptides (100 μM) enhanced anti-Fas antibody (CH-11, 50 ng/mL)-induced apoptosis of BJAB lymphoma cells that expressed K1 but that of vector-transfected BJAB cells. Ig-deleted K1 (K1dIg)-transfected mice were not protected (0/6), and K1-transfected mice were protected (7/10, P
Dexamethasone inhibits early regenerative response of rat liver after cold preservation and transplantation
Authors: F Debonera
Journal: Hepatology (2003)

Regeneration is crucial for the recovery of hepatic mass following liver transplantation. Glucocorticoids, immunosuppressive and antiinflammatory agents commonly used in transplantation, are known to inhibit the expression of specific cytokines and growth factors. Some of these proteins, namely tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), play a critical role in the initiation of liver regeneration. Following cold preservation and reperfusion of the transplanted liver, the normal recovery process is marked by increased expression of TNF-α and IL-6, followed by activation of cytokine-responsive transcription factors and progression of the cell cycle resulting in hepatocyte proliferation. We hypothesized that glucocorticoids may influence the repair mechanisms initiated after extended cold preservation and transplantation. Using a rat orthotopic liver transplant model, recipient animals were treated with dexamethasone at the time of transplantation of liver grafts with prolonged cold storage (16 hours). Treatment with dexamethasone suppressed and delayed the expression of TNF-α and IL-6 compared with animals receiving no treatment and attenuated downstream nuclear factor κB (NF-κB), signal transduction and activator of transcription 3 (STAT3), and activation protein 1 (AP-1) activation. This suppression was accompanied by poor cell-cycle progression, delayed cyclin D1 nuclear transposition, and impaired hepatocyte proliferation by BrdU uptake. Histologically, the liver grafts in treated animals demonstrated more injury than controls, which appeared to be necrosis, rather than apoptosis. In conclusion, these data provide evidence that the administration of glucocorticoids at the time of transplantation inhibits the initiation of the regenerative process and may have a deleterious effect on the recovery of liver grafts requiring significant regeneration. This may be particularly relevant for transplantation of partial liver grafts in the living donor setting. (Hepatology 2003;38:1563-1572.)
Covid-19: Campaigner calls for national guidance to stop DNR orders being made without discussion with patients and families
Authors: Clare Dyer
Journal: BMJ (2020)

The daughter of a man who successfully fought to establish that patients have a right to be consulted on cardiopulmonary resuscitation (CPR) has launched a High Court challenge against Matt Hancock, the health and social care secretary for England.

Kate Masters has written a letter before action to Hancock after news reports suggested that blanket bans on CPR were being imposed during the covid-19 pandemic.

In the letter, she called on Hancock to give an emergency direction to all healthcare professionals providing that “do not attempt cardiopulmonary resuscitation” (DNACPR) orders must not be imposed unless the patient or family have been …
Polycythemia Associated with a Hemoglobinopathy.
Authors: Samuel Charache
Journal: Annals of Internal Medicine (1966)

s1 May 1966Polycythemia Associated with a Hemoglobinopathy.Samuel Charache, M.D., David J. Weatherall, M.D., John B. Clegg, Ph.D.Samuel Charache, M.D.Search for more papers by this author, David J. Weatherall, M.D.Search for more papers by this author, John B. Clegg, Ph.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-64-5-1165_1 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptPolycythemia was encountered in a family heterozygous for an abnormal hemoglobin with an unusual affinity for oxygen. The propositus was an 81-year-old man with a hematocrit reading of 58%. In three generations of his family, carriers of the abnormal hemoglobin had significantly higher hematocrit readings than did normal individuals. The red cells of heterozygotes were normal in appearance, and the white cells and platelets appeared normal on blood smears. The abnormal hemoglobin comprised 28 to 35% of hemolysates from affected individuals. At pH 8.6 it migrated between hemoglobins A and I. The amino acid substitution was localized to amino acid... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Baltimore, Maryland, Liverpool, England, and Cambridge, PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1966Volume 64, Issue 5Page: 1165-1165KeywordsAmino acidsCellsHematocritHemoglobinHemoglobinopathiesOxygenPlateletsPolycythemiaWhite blood cells Issue Published: 1 May 1966 PDF DownloadLoading ...
Histopathological and Immunophenotypic Changes of Pancreatic Neuroendocrine Tumors after Neoadjuvant Peptide Receptor Radionuclide Therapy (PRRT)
Authors: Marco Schiavo Lena, Stefano Partelli, Paola Castelli, Valentina Andreasi, Chanel Elisha Smart, Eleonora Pisa, Mirco Bartolomei, Emilio Bertani, Giuseppe Zamboni, Massimo Falconi, Claudio Doglioni
Journal: Endocrine Pathology (2020)
Plasma exchange for Guillain-Barre syndrome.
Authors: R A Hughes
Journal: BMJ (1985)

of indexes and cross references and the potential for use in research.With modern case files the importance of indexes was equally true but here the use of microfilm was to be taken into account.Finally, for the future, it was suggested that a standardised summary sheet for each patient could be retained permanently in hard copy or microfilm.At the end of the day it was generally agreed that more specific information was needed about how much survives and where.A survey could be initiated by the Public Record Office and the Contemporary Medical Archives Centre of the Wellcome Institute for the History of Medicine, which are already conducting a pilot scheme on hospital records in record offices.Hospital administrators need to have a clearer understanding of the arrangements for hospital records, and the proposed revised guidelines updating HM(61)73 might go some way to help them.A possible reduction of the closure period to 75 years (many government records previously closed for 100 years have now had their closure period reduced to 75 years) would also remove one important disincentive to historical research use.Finally, a working party will be set up to look more closely at the issues of microfilming, selection and sampling, and how best to continue the debate and translate words into action.
PATHOGENESIS OF THE HEPATORENAL SYNDROME
Authors: E W Davidson, M J Dunn
Journal: Annual Review of Medicine (1987)

This review examines current understanding about the patient with moderately advanced cirrhosis of the liver and his or her transition to hepatorenal syndrome (HRS). Special emphasis is given to three areas of ongoing research. Atrial natriuretic factor's role in the pathogenesis of salt and water retention is examined, as well as its role in determining volume status in these patients. The current literature regarding prostaglandins (PGs) is reviewed, with emphasis on how vasodilatory PGs appear first to help maintain homeostasis in advanced cirrhosis and how vasoconstrictor thromboxane may then be involved in the transition to HRS. Finally, new findings regarding the liver hormone glomerulopressin are examined, and how deficient release of this may lead to the decrease in glomerular filtration rate seen in HRS.
Abstract 10208: Impact of Impaired Right Ventricular Strain on Prognosis in Heart Failure With Preserved Ejection Fraction
Authors: Sibille Lejeune, Clotilde Roy, Alisson F Slimani, Agnes A Pasquet, David Vancraeynest, Christophe Beauloye, Jean-Louis Vanoverschelde, Bernhard L Gerber, Anne Catherine Pouleur
Journal: Circulation (2019)

Introduction: Right ventricle strain has emerged as an accurate tool for RV function assessment and is associated with poor prognosis in HFrEF. However, its impact in HFpEF remains unclear. We soug...