tbuckley/cabot-search huggingface dataset:
Multifunctional Iron Oxide Nanoparticles for Diagnostics, Therapy and Macromolecule Delivery
Authors: Swee Kuan Yen, Parasuraman Padmanabhan, Subramanian Tamil Selvan
Journal: Theranostics (2013)

In recent years, multifunctional nanoparticles (NPs) consisting of either metal (e.g.Au), or magnetic NP (e.g.iron oxide) with other fluorescent components such as quantum dots (QDs) or organic dyes have been emerging as versatile candidate systems for cancer diagnosis, therapy, and macromolecule delivery such as micro ribonucleic acid (microRNA).This review intends to highlight the recent advances in the synthesis and application of multifunctional NPs (mainly iron oxide) in theranostics, an area used to combine therapeutics and diagnostics.The recent applications of NPs in miRNA delivery are also reviewed.
Biological Markers of Acute Kidney Injury
Authors: Edward D. Siew, Lorraine B. Ware, T. Alp Ikizler
Journal: Journal of the American Society of Nephrology (2011)

An abrupt change in serum creatinine, the most common indicator of acute kidney injury (AKI), is strongly linked to poor outcomes across multiple clinical settings. Despite endless attempts to distill the magnitude and timing of a changing serum creatinine into a standardized metric, singular focus on this traditional functional marker obligates the characterization of AKI to remain, at best, retrospective and causally noninformative. The resultant inability to meaningfully segregate critical aspects of injury such as type, onset, propagation, and recovery from ongoing decrements in renal function has hindered successful translation of promising therapeutics. Over the past decade, however, the emerging field of clinical proteomics reinvigorates hope of identifying novel plasma and urine biomarkers to characterize cause and course of kidney injury. Efforts to validate these markers for use in clinical studies now show early promise but face important obstacles including interpretive difficulties inherent in using serum creatinine as a sole comparator for diagnostic performance, a need to better evaluate the incremental performance of new markers above established clinical and biochemical predictors, a relative lack of power to sufficiently examine hard clinical end points, and a potential over-reliance on use alone of receiver operating curves for assessing biomarker utility. Here, we discuss efforts to address these barriers and further ascertain the clinical value of new markers.
Practice variations in utilization of diagnostic techniques to evaluate acute aortic dissection — results from the international registry of aortic dissection (IRAD)
Authors: S. Dais, E. Isselbacher, P. Hagan, A. Evangelista, R. Fatton, T. Suzuki, J.K. Oh, U. Sechtem, J. Marcos, Y. Robles, H.-J. Deutsch, D. Gilon, D. Bhakta, D. Karavite, P. Russman, W.F. Armstrong, G.M. Deeb, C.A. Nienaber, K.A. Eagle
Journal: Journal of the American College of Cardiology (1998)
When We Became Rich
Authors: George A. Sarosi
Journal: Annals of Internal Medicine (2013)

On Being a Doctor21 May 2013When We Became RichGeorge A. Sarosi, MDGeorge A. Sarosi, MDFrom University of Minnesota, Minneapolis, Minnesota.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-158-10-201305210-00014 Audio Reading - “When We Became Rich” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "When We Became Rich," by G.A. Sarosi. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail It was a rather difficult faculty meeting. The entire time was given to the director of the faculty practice plan, who went over our tenuous financial situation, emphasizing that revenues were down and that we were not likely to get a raise or a bonus at the end of the year. In discussing the possible remedies, he suggested that we consider reducing some of the frills that we currently enjoyed, the number of fellows that the department was paying, or the educational allowance provided each faculty member. Finally, he warned us that unless we turned around the downward trend of ... Author, Article, and Disclosure InformationAffiliations: From University of Minnesota, Minneapolis, Minnesota.Corresponding Author: George A. Sarosi, MD, Minneapolis Veterans Affairs Medical Center, One Veterans Drive, Minneapolis, MN 55417; e-mail, george.[email protected]gov. PreviousarticleNextarticle Advertisement Audio Reading - “When We Became Rich” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "When We Became Rich," by G.A. Sarosi. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 21 May 2013Volume 158, Issue 10Page: 774-775KeywordsDiagnosis related groupsElectronic medical recordsHealth careLength of stayMedical educationMedicareOintmentsPatientsResidencySub-specialty care ePublished: 21 May 2013 Issue Published: 21 May 2013 Copyright & PermissionsCopyright © 2013 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Does exercise training during pregnancy influence fetal cardiovascular responses to an exercise stimulus? Insights from a randomised, controlled trial
Authors: R Barakat, J R Ruiz, G Rodríguez-Romo, R Montejo-Rodríguez, A Lucia
Journal: British Journal of Sports Medicine (2009)

In this study, the effects of maternal physical activity level on several fetal haemodynamic parameters such as pulsatility index of the fetal middle cerebral and umbilical arteries and cerebral-to-fetal ratio, as well as on fetal heart rate responses to one bout of moderate exercise (20 min cycle-ergometry at approximately 60% of age-predicted maximum heart rate) during the third pregnancy trimester were assessed. 26 Sedentary and 26 physically active gravidae aged 29 (3) and 30 (2) years, respectively, were studied. Maternal exercise did not have a deleterious effect on fetal haemodynamics (particularly, cerebral-to-fetal ratio remained within normal limits with exercise). Overall, maternal training status did not influence the fetal cardiovascular variables studied.
New referrals, a decreasing phenomenon in 1971-94: analysis of registry data in the Netherlands
Authors: E. H Van de Lisdonk, C Van Weel
Journal: BMJ (1996)

Referrals to secondary care are an important but incompletely understood feature of general practice,1 particularly in health care systems where general practitioners are gatekeepers to secondary care. In the Netherlands from 1971 to 1994 the number of medical specialists increased by 128%, from 5909 to about 13 500, the number of general practitioners by 56%, from 4504 to 7013, and the population by 16%, from 13.3 to 15.5 million. The influence of such powerful external factors would suggest that the number of referrals should also have increased over that time. To test this hypothesis we assessed the mean referral rates in …
End-of-Life Care and Circumstances of Death in Patients Dying As a Result of Cancer in Belgium and the Netherlands: A Retrospective Comparative Study
Authors: Koen Meeussen, Lieve Van den Block, Michael A. Echteld, Nicole Boffin, Johan Bilsen, Viviane Van Casteren, Ebun Abarshi, Gé Donker, Bregje Onwuteaka-Philipsen, Luc Deliens
Journal: Journal of Clinical Oncology (2011)

Purpose To examine and compare end-of-life care in patients with cancer dying in Belgium and the Netherlands. Patients and Methods A mortality follow-back study was undertaken in 2008 via representative nationwide sentinel networks of general practitioners (GPs) in Belgium and the Netherlands. By using similar standardized procedures, GPs reported on aspects of end-of-life care and the circumstances of nonsudden death of patients with cancer in their practice. Results Of the 422 reported patients with cancer, most resided at home during the last year of life (Belgium, 91%; the Netherlands, 95%). Death occurred at home in 34% (Belgium) and 61% (the Netherlands) and in the hospital in 29% (Belgium) and 19% (the Netherlands). In the last month of life, end-of-life issues were more often discussed in the Netherlands (88%) than in Belgium (68%). In both countries, physical problems were discussed most often (Belgium, 49%; the Netherlands, 78%) and spiritual issues least often (Belgium, 20%; the Netherlands, 32%). Certain end-of-life treatment preferences were known for 43% (Belgium) and 67% (the Netherlands) of patients. In the last week of life, treatment was most often focused on palliation (Belgium, 94%; the Netherlands, 91%). Physical distress was reported in 84% (Belgium) and 76% (the Netherlands) of patients and psychological distress in 59% and 36%. Most distressing was lack of energy (Belgium, 73%; the Netherlands, 71%) and lack of appetite (Belgium, 61%; the Netherlands, 53%). Two thirds of patients were bedridden (Belgium, 67%; the Netherlands, 69%). Conclusion Although place of death and communication about end-of-life issues differ substantially, a palliative treatment goal is adopted for the vast majority of patients in both countries. However, GPs reported that the majority of patients experienced symptom distress at the end of life, which suggests important challenges remain for improving end-of-life care.
Insulin Receptor Substrate 1 Gene Variation Modifies Insulin Resistance Response to Weight-Loss Diets in a 2-Year Randomized Trial
Authors: Qibin Qi, George A. Bray, Steven R. Smith, Frank B. Hu, Frank M. Sacks, Lu Qi
Journal: Circulation (2011)

Background— Common genetic variants in the insulin receptor substrate 1 ( IRS1 ) gene have been recently associated with insulin resistance and hyperinsulinemia. We examined whether the best-associated variant modifies the long-term changes in insulin resistance and body weight in response to weight-loss diets in Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial. Methods and Results— We genotyped IRS1 rs2943641 in 738 overweight adults (61% were women) who were randomly assigned to 1 of 4 diets varying in macronutrient contents for 2 years. We assessed the progress in fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and weight loss by genotypes. At 6 months, participants with the risk-conferring CC genotype had greater decreases in insulin ( P =0.009), HOMA-IR ( P =0.015), and weight loss ( P =0.018) than those without this genotype in the highest-carbohydrate diet group whereas an opposite genotype effect on changes in insulin and HOMA-IR ( P ≤0.05) was observed in participants assigned to the lowest-carbohydrate diet group. No significant differences were observed across genotypes in the other 2 diet groups. The tests for genotype by intervention interactions were all significant ( P &lt;0.05). At 2 years, the genotype effect on changes in insulin and HOMA-IR remained significant in the highest-carbohydrate diet group ( P &lt;0.05). The highest carbohydrate diet led to a greater improvement of insulin and HOMA-IR ( P for genotype–time interaction ≤0.009) in participants with the CC genotype than those without this genotype across 2-year intervention. Conclusions— Individuals with the IRS1 rs2943641 CC genotype might obtain more benefits in weight loss and improvement of insulin resistance than those without this genotype by choosing a high-carbohydrate and low-fat diet. Clinical Trial Registration— http:www.clinicaltrials.gov . Unique identifier: NCT00072995.
Evolutionary Analysis Identifies an MX2 Haplotype Associated with Natural Resistance to HIV-1 Infection
Authors: Manuela Sironi, Mara Biasin, Rachele Cagliani, Federica Gnudi, Irma Saulle, Salomè Ibba, Giulia Filippi, Sarah Yahyaei, Claudia Tresoldi, Stefania Riva, Daria Trabattoni, Luca De Gioia, Sergio Lo Caputo, Francesco Mazzotta, Diego Forni, Chiara Pontremoli, Juan Antonio Pineda, Uberto Pozzoli, Antonio Rivero-Juarez, Antonio Caruz, Mario Clerici
Journal: Molecular Biology and Evolution (2014)

The protein product of the myxovirus resistance 2 (MX2) gene restricts HIV-1 and simian retroviruses. We demonstrate that MX2 evolved adaptively in mammals with distinct sites representing selection targets in distinct branches; selection mainly involved residues in loop 4, previously shown to carry antiviral determinants. Modeling data indicated that positively selected sites form a continuous surface on loop 4, which folds into two antiparallel α-helices protruding from the stalk domain. A population genetics–phylogenetics approach indicated that the coding region of MX2 mainly evolved under negative selection in the human lineage. Nonetheless, population genetic analyses demonstrated that natural selection operated on MX2 during the recent history of human populations: distinct selective events drove the frequency increase of two haplotypes in the populations of Asian and European ancestry. The Asian haplotype carries a susceptibility allele for melanoma; the European haplotype is tagged by rs2074560, an intronic variant. Analyses performed on three independent European cohorts of HIV-1-exposed seronegative individuals with different geographic origin and distinct exposure route showed that the ancestral (G) allele of rs2074560 protects from HIV-1 infection with a recessive effect (combined P = 1.55 × 10−4). The same allele is associated with lower in vitro HIV-1 replication and increases MX2 expression levels in response to IFN-α. Data herein exploit evolutionary information to identify a novel host determinant of HIV-1 infection susceptibility.
Large-Scale Association Study Identifies <b> <i>ICAM</i> </b> Gene Region as Breast and Prostate Cancer Susceptibility Locus
Authors: Stefan Kammerer, Richard B. Roth, Richard Reneland, George Marnellos, Carolyn R. Hoyal, Nathan J. Markward, Florian Ebner, Marion Kiechle, Ulrike Schwarz-Boeger, Lyn R. Griffiths, Christian Ulbrich, Korbinian Chrobok, Gerhard Forster, Georg M. Praetorius, Peter Meyer, Joachim Rehbock, Charles R. Cantor, Matthew R. Nelson, Andreas Braun
Journal: Cancer Research (2004)

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.
Mild Renal Insufficiency Is Associated With Angiographic Coronary Artery Disease in Women
Authors: Steven E. Reis, Marian B. Olson, Linda Fried, Virginia Reeser, Sunil Mankad, Carl J. Pepine, Richard Kerensky, C. Noel Bairey Merz, Barry L. Sharaf, George Sopko, William J. Rogers, Richard Holubkov
Journal: Circulation (2002)

Background — Mild renal insufficiency is associated with an increased risk for cardiovascular events in women with coronary artery disease (CAD). However, the relationship between mild renal insufficiency and atherosclerotic CAD in women is not known. Methods and Results — Women with chest pain who were referred for coronary angiography in the NHLBI Women’s Ischemia Syndrome Evaluation (WISE) study underwent quantitative coronary angiography, blood measurements of creatinine, lipids, and homocysteine, and assessment of CAD risk factors. Fifty-six women had mild renal insufficiency (serum creatinine 1.2 to 1.9 mg/dL), and 728 had normal renal function (creatinine &lt;1.2 mg/dL). Creatinine correlated with angiographic CAD severity score ( r =0.11, P &lt;0.004) and maximum coronary artery stenosis ( r =0.11, P &lt;0.003). Compared with women with normal renal function, those with mild renal insufficiency were more likely to have significant angiographic CAD (≥50% diameter stenosis in ≥1 coronary artery) (61% versus 37%; P &lt;0.001) and CAD in multiple vessels ( P &lt;0.001 for association) and had greater maximum percent diameter coronary stenosis (59±35% versus 38±36%; P &lt;0.001). Mild renal insufficiency was associated with significant angiographic CAD independent of age and risk factors (OR=1.9, 95%CI=1.1 to 3.5). After controlling for homocysteine in 509 women, mild renal insufficiency remained predictive of CAD (OR=3.2, 95%CI=1.4 to 7.2). Conclusions — In women with chest pain, mild renal insufficiency is an independent predictor of significant angiographic CAD. Mildly increased serum creatinine is probably a marker for unmeasured proatherogenic factors.
Diagnostic Value of Arterial Blood Gas Measurement in Suspected Pulmonary Embolism
Authors: MARC A. RODGER, MARC CARRIER, GWYNNE N. JONES, PASTEUR RASULI, FRANÇOIS RAYMOND, HELENE DJUNAEDI, PHILIP S. WELLS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Pulmonary embolism (PE) is a common and lethal yet treatable condition. Several authors have reported on the diagnostic value of combinations of arterial blood gas (ABG) and other clinical data (i.e., prediction rules), and have claimed that these combinations can be safely used to exclude PE. The purpose of this investigation was to evaluate the diagnostic value of ABG measurement and to attempt to validate the ABG prediction rules published by these various authors for the assessment of patients with suspected PE. Two hundred ninety-three consecutive patients referred for imaging to investigate suspected PE were approached to participate in the investigation. ABG and other clinical data were obtained from consenting and eligible patients before an outcome classification (PE versus non-PE) was performed. None of the ABG data or prediction rules had sufficient negative predictive value, specificity, or likelihood ratios to be useful in the management of patients with suspected PE. We conclude that ABG data alone or in combination with other clinical data are not useful in the assessment of suspected PE.
14-3-3ζ, a Novel Androgen-Responsive Gene, Is Upregulated in Prostate Cancer and Promotes Prostate Cancer Cell Proliferation and Survival
Authors: Taro Murata, Ken-ichi Takayama, Tomohiko Urano, Tetsuya Fujimura, Daisaku Ashikari, Daisuke Obinata, Kuniko Horie-Inoue, Satoru Takahashi, Yasuyoshi Ouchi, Yukio Homma, Satoshi Inoue
Journal: Clinical Cancer Research (2012)

Androgen receptor is an essential transcriptional factor that contributes to the development and progression of prostate cancer. In this study, we investigated the androgen regulation and functional analysis of 14-3-3ζ in prostate cancer.Using chromatin immunoprecipitation (ChIP) combined with DNA microarray (ChIP-chip) analysis in LNCaP cells, we identified a functional androgen receptor-binding site in the downstream region of the 14-3-3ζ gene. Androgen regulation was examined by quantitative reverse transcription PCR and Western blot analysis. Prostate cancer cells stably expressing 14-3-3ζ and siRNA knockdown were used for functional analyses. We further examined 14-3-3ζ expression in clinical samples of prostate cancer by immunohistochemistry and quantitative reverse transcription PCR.Androgen-dependent upregulation of 14-3-3ζ was validated at the mRNA and protein levels. The 14-3-3ζ gene is favorable for cancer-cell survival, as its ectopic expression in LNCaP cells contributes to cell proliferation and the acquired resistance to etoposide-induced apoptosis. 14-3-3ζ expression was associated with androgen receptor transcriptional activity and prostate-specific antigen (PSA) mRNA expression. Immunoprecipitation indicated that 14-3-3ζ was associated with androgen receptor in the nucleus. Clinicopathologic studies further support the relevance of 14-3-3ζ in prostate cancers, as its higher expression is associated with malignancy and lymph node metastasis.14-3-3ζ is a novel androgen-responsive gene that activates proliferation, cell survival, and androgen receptor transcriptional activity. 14-3-3ζ may facilitate the progression of prostate cancer.
Developmental Influences on Medically Unexplained Symptoms
Authors: C.A. Tony Buffington
Journal: Psychotherapy and Psychosomatics (2009)

&lt;i&gt;Background:&lt;/i&gt; Medically unexplained (or ‘functional’) symptoms (MUS) are physical symptoms that prompt the sufferer to seek healthcare but remain unexplained after an appropriate medical evaluation. Examples of MUS also occur in veterinary medicine. For example, domestic cats suffer a syndrome comparable to interstitial cystitis, a chronic pelvic pain syndrome of humans. &lt;i&gt;Method:&lt;/i&gt; Review of current evidence suggests the hypothesis that developmental factors may play a role in some cases of MUS. Maternal perception of a threatening environment may be transmitted to the fetus when hormones cross the placenta and affect fetal physiology, effectively ‘programming’ the fetal stress response system and associated behaviors toward enhanced vigilance. After birth, intense stress responses in the individual may result in similar vulnerability, which may be unmasked by subsequent stressors. &lt;i&gt;Results:&lt;/i&gt; Epigenetic modulation of gene expression (EMGEX) appears to play a central role in creation of this ‘survival phenotype’. The recent development of techniques to identify the presence of EMGEX provides new tools to investigate these questions, and drugs and other interventions that may reverse EMGEX are also under active investigation. &lt;i&gt;Conclusion:&lt;/i&gt; Viewing MUS from the perspective of underlying developmental influences involving EMGEX that affect function of a variety of organs based on familial (genetic and environmental) predispositions rather than from the traditional viewpoint of isolated organ-originating diseases has at least two important implications: it provides a parsimonious explanation for findings heretofore difficult to reconcile, and it opens whole new areas of investigation into causes and treatments for this class of disorders.
Is Time to First Skeletal-Related Event the Best Primary End Point in the Assessment of Bisphosphonate Efficacy in Patients With Castration-Sensitive Prostate Cancer?
Authors: Francesca Valcamonico, Fausto Petrelli, Laura Ferrari, Vittorio Ferrari, Salvatore Grisanti, Sandro Barni, Alfredo Berruti
Journal: Journal of Clinical Oncology (2014)