9,591 research outputs found
Foreign Students with Kenneth M. Williams, Dean of Students
No full textForeign Students with Kenneth M. Williams, Dean of Students - Japan: Hideo Osakabe, Korea: Seung Kyu Kim (John), Kenya East Africa: Bowers Ukiru, c.1960\u27shttps://digitalcommons.georgefox.edu/gfu_photos_1960_1964/1009/thumbnail.jp
Author Correction: Evaluation of skin cancer resection guide using hyper‑realistic in‑vitro phantom fabricated by 3D printing
No full textThe original version of this Article contained an error in the spelling of the author Taehun Kim which was incorrectly given as Teahun Kim. The original Article has been corrected
The role of heart rate may differ according to pathophysiological setting: from SHIFT to SIGNIFY
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Supplemental material for Non-cardioembolic stroke/transient ischaemic attack in Asians and non-Asians: A post-hoc analysis of the PERFORM study
No full textSupplemental material for Non-cardioembolic stroke/transient ischaemic attack in Asians and non-Asians: A post-hoc analysis of the PERFORM study by Takao Hoshino, Leila Sissani, Julien Labreuche, Marie-Germaine Bousser, Angel Chamorro, Marc Fisher, Ian Ford, Kim M Fox, Michael G Hennerici, Heinrich P Mattle, Peter M Rothwell, Philippe Gabriel Steg, Eric Vicaut and Pierre Amarenco in European Stroke Journal</p
Selective If inhibition:new frontiers inthe management of coronary disease
No full textTHE LAST 30 YEARS HAVE SEEN SPECTACULAR PROGRESS IN THE
management of stable coronary artery disease (CAD), with numerous
new pharmacological and interventional options becoming available.
The most recent statistics from the American Heart Association (AHA)
report a 33% reduction in rates of mortality due to CAD in the 10 years to 2004,1 which can be
largely attributed to these advances. Despite this progress, the disease remains an important
contributor to mortality and morbidity in the Western world. Indeed, the AHA statistics also place
CAD as the single largest killer of American adults, with 1 in 5 deaths being attributable to CAD.1
Clearly, there is little room for complacency in our management of stable CAD, and we need to
continue to seek original and innovative ways of saving lives in this population.
A striking demonstration of this situation came from analysis of data from patients included
in the REduction of Atherothrombosis for Continued Health (REACH) Registry in 44 countries
between 2003 and 2004.2 This 1-year, international study recruited a large subset of more than
38 000 patients with stable CAD. The majority of the REACH patients were receiving contemporary,
evidence-based, preventive drug therapy, including antiplatelet therapy, lipid-lowering agents,
and angiotensin-converting enzyme inhibitors, and about half were receiving β-blockers. Despite
this, all-cause mortality at 1 year was 2.89% and cardiovascular mortality was 1.93%. Patients
with stable CAD also had a 4.52% rate of a composite end point of cardiovascular death, myocardial
infarction (MI), and stroke. The REACH authors rightly concluded that continued efforts are
needed to improve secondary prevention and clinical outcomes.2 The implications of the REACH
data in terms of burden of disease are alarming, considering that the lifetime risk of developing
CAD for American adults aged over 40 is 49% for men and 32% for women.1 One conclusion is
that current management strategies in stable CAD are failing to reach the expectations of cardiologists
and patients alike.3
Current guidelines recommend a two-pronged management strategy for patients with stable
CAD, who require one treatment to relieve symptoms alongside another to reduce long-term morbidity
and mortality.4 Despite the progress in the field, 50% of patients remain symptomatic with
treatment, and rates of mortality are highly unsatisfactory. These shortcomings can be traced to
a number of factors. Pharmacological therapy is abound with problems of subtherapeutic dosing
and compliance. Furthermore, the optimization of treatment can be hindered by insufficient
efficacy in patients with refractory angina and by a long list of contraindications, for example,
β-blockers are contraindicated in patients with asthma, peripheral vascular disease, and severe
bradycardia, which may limit their use in those patient populations. Another factor is poor tolerability,
which may lead to treatment discontinuation and reduce the efficacy of even the most
rigorous management strategy.
Surgical intervention does not necessarily resolve these problems: intervention is not always
possible, and most revascularized patients still require antianginal treatment after the procedure.
Indeed, as the Clinical Outcomes Utilizing Revascularization and AGgressive drug Evaluation
(COURAGE) trial recently demonstrated,5 there is no benefit of percutaneous coronary interven-
E D I T O R I A L
Address for correspondence:
Prof Roberto Ferrari, Chair of
Cardiology, Arcispedale S. Anna,
University of Ferrara, Corso
Giovecca 203, 44100, Ferrara,
Italy and Fondazione Salvatore
Maugeri, IRCCS, Brescia, Italy
(e-mail [email protected])
Prof Kim Fox, Professor of
Cardiology, Royal Brompton
Hospital, London SW3 6NP, UK
(e-mail [email protected])
Medicographia.
2008;30:189-195.
Selective I
f inhibition:
new frontiers in the management
of coronary artery disease
b y R . F e r r a r i a n d K . F o x ,
I t a l y a n d U n i t e d K i n g d o m
Kim FOX, MD, FESC
Professor of Cardiology
Royal Brompton Hospital
London, UK
Roberto FERRARI, MD, PhD
Chair of Cardiology
Arcispedale S. Anna
University of Ferrara
and Fondazione Salvatore
Maugeri, IRCCS
Brescia, ITALY
tion (PCI) on top of guideline-based optimized pharmacological therapy, in terms of reduction
in risk of mortality, MI, or major cardiovascular events. This demonstrates how important it is
to raise our standards in preventive cardiology through improvement of established lifestyle and
therapeutic intervention and control of other clinical parameters, which can improve cardiovascular
risk assessment and management.
The ideal treatment for stable CAD would be one that provided both anti-ischemic and antianginal
efficacy, as well as improvement in prognosis by reducing cardiovascular events. Heart
rate (HR) is one of the clinical parameters that is most frequently assessed in daily practice. Being
the main determinant of ischemia, HR reduction is established as an important therapeutic
component of the prevention of ischemia. A strong association between elevated HR and increased
risk of all-cause mortality, cardiovascular mortality, and development of cardiovascular
disease has been shown in the general population, as well as in patients with hypertension, diabetes,
and CAD.6,7 Experimental data have demonstrated the involvement of HR in the development
of atherosclerosis with reduction in its progression after pharmacological or surgical HR
reduction. The impact of β-blockers and of some calcium blockers on mortality in post-MI patients
has been suggested to be related to reduction in resting HR. Consistent with this understanding
of the important role of HR, ivabradine, the first selective and specific If inhibitor, opens
up promising opportunities in the management of CAD
Microbially Guided Discovery and Biosynthesis of Biologically Active Natural Products
No full textThe design of small molecules that inhibit disease-relevant proteins represents a longstanding challenge of medicinal chemistry. Here, we describe an approach for encoding this challenge-the inhibition of a human drug target-into a microbial host and using it to guide the discovery and biosynthesis of targeted, biologically active natural products. This approach identified two previously unknown terpenoid inhibitors of protein tyrosine phosphatase 1B (PTP1B), an elusive therapeutic target for the treatment of diabetes and cancer. Both inhibitors appear to target an allosteric site, which confers selectivity, and can inhibit PTP1B in living cells. A screen of 24 uncharacterized terpene synthases from a pool of 4464 genes uncovered additional hits, demonstrating a scalable discovery approach, and the incorporation of different PTPs into the microbial host yielded alternative PTP-specific detection systems. Findings illustrate the potential for using microbes to discover and build natural products that exhibit precisely defined biochemical activities yet possess unanticipated structures and/or binding sites.
Author Correction: El Niño–Southern Oscillation complexity (Nature, (2018), 559, 7715, (535-545), 10.1038/s41586-018-0252-6)
No full textIn this Review, the middle initial of author Kim M. Cobb was omitted. The original Review Article has been corrected online. © 2019, The Author(s), under exclusive licence to Springer Nature Limited.11Nsciescopu
Quantitative proteome responses to oncolytic reovirus in GM-CSF- and M-CSF-differentiated bone marrow-derived cells
No full textThe efficacy of oncolytic viruses (OVs), such as reovirus, is dictated by host immune responses, including those mediated by the pro- versus anti-inflammatory macrophages. As such, a detailed understanding of the interaction between reovirus and different macrophage types is critical for therapeutic efficacy. To explore reovirus–macrophage interactions, we performed tandem mass tag (TMT)-based quantitative temporal proteomics on mouse bone marrow-derived macrophages (BMMs) generated with two cytokines, macrophage colony stimulating factor (M-CSF) and granulocytic–macrophage colony stimulating factor (GM-CSF), representing anti- and proinflammatory macrophages, respectively. We quantified 6863 proteins across five time points in duplicate, comparing M-CSF (M-BMM) and GM-CSF (GM-BMM) in response to OV. We find that GM-BMMs have lower expression of key intrinsic proteins that facilitate an antiviral immune response, express higher levels of reovirus receptor protein JAM-A, and are more susceptible to oncolytic reovirus infection compared to M-BMMs. Interestingly, although M-BMMs are less susceptible to reovirus infection and subsequent cell death, they initiate an antireovirus adaptive T cell immune response comparable to that of GM-BMMs. Taken together, these data describe distinct proteome differences between these two macrophage populations in terms of their ability to mount antiviral immune responses.Canadian Cancer Society Research InstituteCanadian Institutes of Health ResearchTerry Fox Research InstituteQEII Health Sciences Centre Foundatio
Appendix – Supplemental material for Moving From Knowledge to Action: Improving Safety and Quality of Care for Patients With Limited English Proficiency
No full textSupplemental material, Appendix for Moving From Knowledge to Action: Improving Safety and Quality of Care for Patients With Limited English Proficiency by Miriam T. Fox, Sashini K. Godage, Julia M. Kim, Carla Bossano, Sara Muñoz-Blanco, Erica Reinhardt, Linxuan Wu, Stella Karais and Lisa Ross DeCamp in Clinical Pediatrics</p
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