tbuckley/cabot-search huggingface dataset:
Anticipating and managing postoperative delirium and cognitive decline in adults
Authors: R. D. Sanders, P. P. Pandharipande, A. J. Davidson, D. Ma, M. Maze
Journal: BMJ (2011)

The brain is vulnerable during the perioperative period in people of all ages. Neurobehavioural disturbances are common complications of perioperative care, manifesting in three distinct forms: emergence delirium, postoperative delirium, and postoperative cognitive decline. Delirium is defined by the presence of disturbed consciousness (reduced clarity of awareness of the environment with reduced ability to focus, sustain, or shift attention) and a change in cognition (such as memory deficit, disorientation, or language disturbance) or the development of a perceptual disturbance that is not better accounted for by a pre-existing, established, or evolving dementia. Emergence delirium occurs on emergence from anaesthesia and sedation, with no lucid interval, and lasts approximately 30 minutes. Postoperative delirium lasts hours or longer, with or without lucid intervals. Postoperative cognitive decline refers to a more subtle cognitive impairment noted on neuropsychological tests that typically assess attention and memory.

Postoperative delirium is the most severe of the three disorders, tantamount to an acute brain failure, and should be considered akin to other postoperative organ failures. We review delirium and long term cognitive decline associated with perioperative care in adults and discuss potential mechanisms and preventive/intervention strategies in light of recent randomised controlled trials, meta-analyses, and prospective cohort studies.

#### Sources and selection criteria

Each author had previously conducted a search of published work. In addition a formal Medline search was undertaken in March 2011 with keywords “delirium”, “hip”, and “fracture” to provide data for the figure. Studies were identified by RDS and selected based on published criteria for meta-analysis10 by Nina Frasen. Joost Witlox and Pim Van Gool analysed the data and kindly provided the figure.

Young adults seem particularly vulnerable to emergence delirium, whereas in older patients (over 60) postoperative delirium, and its subsequent sequelae, are more common. Three large cohort studies have shown that emergence delirium occurs in about 5-21% …
Oral Imatinib Mesylate (STI571/Gleevec) Improves the Efficacy of Local Intravascular Vascular Endothelial Growth Factor-C Gene Transfer in Reducing Neointimal Growth in Hypercholesterolemic Rabbits
Authors: Olli Leppänen, Juha Rutanen, Mikko O. Hiltunen, Tuomas T. Rissanen, Mikko P. Turunen, Tobias Sjöblom, Josef Brüggen, Gudrun Bäckström, Marianne Carlsson, Elisabeth Buchdunger, David Bergqvist, Kari Alitalo, Carl-Henrik Heldin, Arne Östman, Seppo Ylä-Herttuala
Journal: Circulation (2004)

Platelet-derived growth factor (PDGF) antagonists have demonstrated beneficial effects on neointima formation, but in studies using PDGF inhibitors and extended follow-up, the lesions reoccur. These findings implicate a need to combine targeting of PDGF with other strategies. Stimulation of reendothelialization by treatment with endothelial cell mitogens of the vascular endothelial growth factor (VEGF) family counteracts restenosis, but there are also concerns regarding the durability of the effect with this approach.To explore whether a combined use of PDGF antagonist and stimulation of reendothelialization confers better results than each therapy alone, we combined systemic administration of imatinib mesylate (STI571/Gleevec, 10 mg/kg(-1) per d(-1)), a tyrosine kinase inhibitor with activity against PDGF receptors, with local intravascular adenovirus-mediated VEGF-C gene transfer (1.15x10(10) pfu) in cholesterol-fed, balloon-injured rabbits. Throughout the course of the STI571 therapy, the circulating concentrations were able to suppress PDGF receptor phosphorylation. At 3 weeks, the treatment with STI571 led to a transient decrease in intralesion macrophages and to an increase in intimal smooth muscle cell apoptosis. VEGF-C application reduced neointima formation and accelerated reendothelialization. However, none of the therapies alone reduced intimal thickening at a 6-week time point, whereas the combined treatment led to a persistent reduction (55% versus control) in lesion size at this time point.Our study provides one of the first successful examples of gene therapy combined with a pharmacological treatment to modulate 2 distinct ligand-receptor signaling systems and suggests combination of local VEGF-C gene therapy with systemic inhibition of PDGF signaling as a novel principle to prevent intimal hyperplasia after vascular manipulations.
Feasibility of Energy-Autonomous Wireless Microsensors for Biomedical Applications: Powering and Communication
Authors: Farhad Goodarzy, Efstratios Stan Skafidas, Simone Gambini
Journal: IEEE Reviews in Biomedical Engineering (2014)

In this review, biomedical-related wireless miniature devices such as implantable medical devices, neural prostheses, embedded neural systems, and body area network systems are investigated and categorized. The two main subsystems of such designs, the RF subsystem and the energy source subsystem, are studied in detail. Different application classes are considered separately, focusing on their specific data rate and size characteristics. Also, the energy consumption of state-of-the-art communication practices is compared to the energy that can be generated by current energy scavenging devices, highlighting gaps and opportunities. The RF subsystem is classified, and the suitable architecture for each category of applications is highlighted. Finally, a new figure of merit suitable for wireless biomedical applications is introduced to measure the performance of these devices and assist the designer in selecting the proper system for the required application. This figure of merit can effectively fill the gap of a much required method for comparing different techniques in simulation stage before a final design is chosen for implementation.
Effect of Alterations in Vasomotor Tone on Pressure-Flow Relationships in the Totally Perfused Dog
Authors: RAYMOND C. READ, HIROSHI KUIDA, JOHN A. JOHNSON
Journal: Circulation Research (1957)

The technic of total body perfusion with a pump oxygenator system has been used to extend pressure flow studies to the circulation as a whole. The effect of alterations in vasomotor tone on both total peripheral resistance and pressure flow relationships has been investigated by surgical ablation of the central nervous system or administration of vasoactive drugs. Certain aspects of the results obtained are discussed in relation to the concept of critical closing pressures.
The Biology of Affective Disorders
Authors: Edward J. Sachar, Miron Baron
Journal: Annual Review of Neuroscience (1979)

The clinical features, genetic data, psychopharmacological studies, hormonal abnormalities, and biochemical observations all serve to define major depressive illness as an inherited neurochemical disorder affecting the hypothalamus, and probably involving monoamine pathways. While the precise nature of the defect and its mode of transmission remain obscure, the rapid development of this field in less than two decades permits optimism that major depressive illness illness will be among the first "functional" psychiatric disorders to have its chemical pathology elucidated.
Exercise is medicine: but what is the dose?
Authors: K Khan
Journal: British Journal of Sports Medicine (2011)

Lecture 19 The term ‘polypill’ was coined in a BMJ publication; researchers wondered whether a cocktail of five pills taken on a population basis could reduce cardiovascular disease by 80% (Wald 2003). Some would argue that there exists a polypill already – but the multi-system benefits of physical activity have been under-recognised. In this short presentation, I address the question ‘What is the optimum dose of physical activity for health?’ Recommended reading below.1 2
Inhibition of IκB Kinase Subunit 2 in Cutaneous T-Cell Lymphoma Down-Regulates Nuclear Factor-κB Constitutive Activation, Induces Cell Death, and Potentiates the Apoptotic Response to Antineoplastic Chemotherapeutic Agents
Authors: Aurore Sors, Francette Jean-Louis, Elodie Bégué, Laurent Parmentier, Louis Dubertret, Michel Dreano, Gilles Courtois, Hervé Bachelez, Laurence Michel
Journal: Clinical Cancer Research (2008)

Abstract Purpose: A key molecular feature of cutaneous T-cell lymphomas (CTCL) is the constitutive activation of the nuclear factor-κB (NF-κB) transcription factor. We investigated in vitro the effects on CTCL survival and chemoresistance of a specific inhibition of IκB kinase subunit 2 (IKK2). Experimental Design: Selective IKK2 inhibition was carried out by transfection of SeAx and MyLa CTCL lines with an inactive form of IKK2 and by exposing these lines and tumor cells from 10 patients with Sézary syndrome (SS) to AS602868, a new IKK2 inhibitor. The constitutive nuclear translocation of NF-κB was analyzed by electrophoretic mobility shift assay and confocal microscopy. Apoptosis was determined by Annexin V/propidium iodide–positive staining and mitochondrial transmembrane potential alterations as well as poly(ADP-ribose)polymerase cleavage. The expression of Bcl-2 family oncoproteins and survivin was studied by immunoblotting. Results: Specific IKK2 inhibition resulting from transfection or from incubation with AS602868 allowed a down-regulation of NF-κB transcriptional activity. As shown by electrophoretic mobility shift assay and apoptosis assays, AS602868 down-regulated the nuclear translocation of NF-κB and induced a potent apoptotic response in CTCL lines and in tumor cells from patients with SS while preserving the viability of both peripheral blood lymphocytes from healthy donors and of nonmalignant T cells from SS patients. Moreover, CTCL death induction by conventional antineoplastic agents etoposide and vincristine was potentiated by AS602868. Finally, AS602868-induced apoptosis of CTCL cells was associated with an up-regulation of Bax dimers and a decrease of survivin. Conclusion: These results indicate that IKK2 inhibition represents a promising strategy for the treatment of advanced stages of CTCL.
Coronary Microvascular Endothelial Cell Redox State in Left Ventricular Hypertrophy
Authors: Derek Lang, Salah I. Mosfer, Alison Shakesby, Francis Donaldson, Malcolm J. Lewis
Journal: Circulation Research (2000)

Abstract —Left ventricular hypertrophy (LVH) is associated with elevated plasma angiotensin II (Ang II) levels and endothelial dysfunction. The relationship between Ang II and endothelial dysfunction remains unknown, however, but it may involve an alteration in endothelial cell redox state. We therefore investigated the effect of Ang II on NADH/NADPH oxidase–mediated superoxide anion (O 2 − ) production by cultured guinea pig coronary microvascular endothelial cells (CMVEs) and CMVEs freshly isolated from a guinea pig, pressure-overload model of LVH. Lucigenin chemiluminescence was used to measure O 2 − production in the particulate fraction of CMVE lysates. In cultured cells, incubation with Ang II (0.1 nmol/L to 1 μmol/L for 18 hours) resulted in significant ( P &lt;0.01) increases in both NADH- and NADPH-dependent O 2 − production, with a peak effect at 1 nmol/L. The latter was significantly ( P &lt;0.01) inhibited by the AT 1 receptor antagonist losartan (1 μmol/L for 18 hours). In contrast, the O 2 − response to Ang II (0.1 nmol/L to 1 μmol/L for 18 hours) was largely unaffected by concomitant exposure to the AT 2 antagonist PD 123319 (1 μmol/L). In freshly isolated CMVEs from nonoperated animals, NADH- and NADPH-dependent O 2 − production was not different from that in sham-operated animals but was significantly ( P &lt;0.05) elevated in the aortic-banded animals. Plasma Ang II levels were significantly ( P &lt;0.001) elevated in the aortic-banded (1.25±0.12 μg/L, n=12) compared with sham-operated animals (0.63±0.06 μg/L, n=12). These data suggest that the endothelial dysfunction associated with LVH may be due, at least in part, to the Ang II–induced upregulation of NADH/NADPH oxidase-dependent O 2 − production.
THE MODE OF SPREAD OF A FRIEDLÄNDER BACILLUS-LIKE RESPIRATORY INFECTION OF MICE
Authors: Leslie T. Webster
Journal: The Journal of Experimental Medicine (1928)

A spontaneous respiratory disease of mice incited by Friedländer like bacilli has been described. The bacilli inducing the disease, while morphologically and culturally indistinguishable from the usual varieties of Friedländer bacilli, are antigenically distinct from the common type strains known. The bacilli grow better in cultures at 23 degrees C. than at 37 degrees C. The disease in mice displayed an incubation period of about 48 hours. About 50 per cent of an exposed population succumbed to septicemic and acute hemorrhagic, pneumonic processes. Among the exposed animals were some individuals which remained apparently well and carried the pathogenic bacilli in their nasal passages. The several manifestations of the spontaneous disease were reproduced by instilling small numbers of the cultured bacilli into the nasal passages. 48 hours after inoculation, certain mice had already succumbed; the deaths continued to occur, so that by the end of the 2nd week, 70-80 per cent of the animals had died. Among the survivors certain carriers of the bacilli in the nasal passages occurred; a few appeared entirely refractory to the infection. The succumbing mice showed at autopsy and by culture septicemia and diffuse pneumonic inflammation. No fluctuation in virulence could be detected in bacilli derived from mice while the disease was spreading spontaneously at the periods of epidemic rise, interepidemic interval, or postepidemic quiescence. Moreover, the bacilli cultured from the nares of apparently healthy carriers were equally pathogenic with those taken from the blood and lungs of animals succumbing quickly. No rough colony variants were cultured at any phase of the spontaneous disease, although they were readily obtainable by artificial culture. The variant strains proved stable and of low virulence. This Friedländer bacilli infection in mice takes several clinical courses, depending on variations in host reaction and not depending on bacterial variation. The particular type of infection manifested is determined by the degree of resisting power displayed by the infected animals at the moment that the infection occurred and progressed.
Impact of preventing exacerbations on deterioration of health status in COPD
Authors: S. Spencer, P.M.A. Calverley, P.S. Burge, P.W. Jones
Journal: European Respiratory Journal (2004)

Exacerbations of chronic obstuctive pulmonary disease (COPD) are associated with worse health status. The Inhaled Steroids in Obstructive Lung Disease in Europe (ISOLDE) study showed that treatment with fluticasone propionate (FP) reduced exacerbation frequency and the rate of deterioration in health status as compared with placebo. The present study analysed these data to test whether the effect of FP on health status was attributable to its effect on exacerbations. Rates of deterioration in St George's Respiratory Questionnaire (SGRQ) total score were obtained for 613 patients with moderate to severe COPD followed for a maximum of 3 yrs. Exacerbation rates were skewed and could not be normalised, therefore, patients were stratified into three exacerbation groups: none, infrequent (&lt;1.65 exacerbations·yr −1 ) and frequent (&gt;1.65 exacerbations·yr −1 ). There were 91 patients with no exacerbations, 285 with infrequent exacerbations and 235 with frequent exacerbations. Frequent exacerbations were independently associated with a worse baseline SGRQ score (p&lt;0.0001) and a more rapid rate of deterioration in health status (p=0.0003). Exacerbation frequency and rate of decline in forced expiratory volume in one second were independently related to the rate of deterioration in SGRQ score. Statistical modelling showed the beneficial effect of fluticasone propionate on deterioration in health status to be largely due to its effect on exacerbation frequency.
Screening for Adolescent Idiopathic Scoliosis
Authors: Harold C. Sox
Journal: JAMA (1993)

THE SCOLIOSIS Research Society defines scoliosis as a lateral spinal curve of 11° or greater. An estimated 500 000 adults in the United States have scoliosis.<sup>1</sup>Idiopathic scoliosis accounts for about 65% of cases of structural scoliosis<sup>2,3</sup>(curves caused by spinal column disorders vs other conditions, such as limb-length inequality), and a large proportion of these cases develop during adolescence. A lateral spinal curve of 11° or greater is present in about 2% to 3% of adolescents at the end of their growth period. Curves greater than 20° occur in less than 0.5% of adolescents.<sup>4</sup> Scoliosis can progress undetected as the size of the spinal curve increases. The progression is generally painless and produces no symptoms. Curves may be unnoticed by parents or other adults because the deviations are subtle. Health professionals may also fail to detect the disorder because an examination of the spine may not
Preventing Pandemics Via International Development: A Systems Approach
Authors: Tiffany L. Bogich, Rumi Chunara, David Scales, Emily Chan, Laura C. Pinheiro, Aleksei A. Chmura, Dennis Carroll, Peter Daszak, John S. Brownstein
Journal: PLoS Medicine (2012)

Tiffany Bogich and colleagues find that breakdown or absence of public health infrastructure is most often the driver in pandemic outbreaks, whose prevention requires mainstream development funding rather than emergency funding.
Nonablative fractional photothermolysis for facial actinic keratoses: 6-month follow-up with histologic evaluation
Authors: Tracy M. Katz, Leonard H. Goldberg, Denise Marquez, Arash Kimyai-Asadi, Kristel D. Polder, Jennifer M. Landau, Paul M. Friedman
Journal: Journal of the American Academy of Dermatology (2011)
Rapid (24-Hour) Reaccumulation of Brain Organic Osmolytes (Particularly myo-Inositol) in Azotemic Rats after Correction of Chronic Hyponatremia
Authors: Alain Soupart, Stephen Silver, Barbara Schroöeder, Richard Sterns, Guy Decaux
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. It was recently demonstrated that renal failure and exogenous urea prevent myelinolysis induced by rapid correction of experimental hyponatremia. To determine why elevated blood urea levels favorably affect brain tolerance to osmotic stress, the changes in brain solute composition that occur when chronic hyponatremia is rapidly corrected were studied in rats with or without mercuric chloride-induced renal failure. After 48 h of hyponatremia, the brains of azotemic and nonazotemic animals became depleted of sodium, potassium, and organic osmolytes. Twenty-four hours after rapid correction of hyponatremia, the brains of animals without azotemia remained depleted of organic osmolytes, with little increase in <i>myo</i>-inositol or taurine contents above those observed in animals with uncorrected hyponatremia; brain electrolytes were rapidly reaccumulated, increasing the brain sodium content to a level 17% higher than values for normonatremic control animals. In contrast, within 2 h after correction of hyponatremia, brain <i>myo</i>-inositol contents in azotemic rats returned to control levels and brain taurine levels were significantly higher than those in azotemic animals with uncorrected hyponatremia (16.5 <i>versus</i> 9 μmol/g dry weight). There was no “overshooting” of brain sodium and water contents after rapid correction in the azotemic animals. Rapid reaccumulation of brain organic osmolytes after correction of hyponatremia could explain why azotemia protects against myelinolysis.
The Migrainous Brain: What You See Is Not All You Get?
Authors: Peter J Goadsby
Journal: PLoS Medicine (2006)

Migraine is an episodic brain disorder [1] that affects about 15 percent of the population [2,3]. The disorder can be highly disabling [4], and has been estimated to be the most costly neurological disorder in the European Community, costing more than €27 billion per year [5].

Two clinical forms are commonly seen: migraine with aura and migraine without aura [6]. Aura in this context is defined as a recurrent disorder manifesting in attacks of reversible focal neurological symptoms, usually developing gradually over a period of five to 20 minutes and lasting for less than 60 minutes. These symptoms are typically visual [7], and are often described as bright jagged lines (fortification spectra) that move across the visual field, often followed by visual loss (scotoma).

The phenomenon of migraine has been known since antiquity. Now there are new data on anatomical alterations in the visual motion-processing regions. Do these new data shed light on aura, or perhaps illuminate more basic principles about the migrainous brain? Is the traditional view—that the migrainous brain is structurally normal—incorrect?
Cyclin-Dependent Kinase–Mediated Phosphorylation Plays a Critical Role in the Oncogenic Functions of PELP1
Authors: Binoj C. Nair, Sujit S. Nair, Dimple Chakravarty, Rambabu Challa, Bramanandam Manavathi, P. Renee Yew, Rakesh Kumar, Rajeshwar Rao Tekmal, Ratna K. Vadlamudi
Journal: Cancer Research (2010)

Abstract Estrogen receptor (ER) signaling plays an important role in breast cancer progression, and ER functions are influenced by coregulatory proteins. PELP1 (proline-, glutamic acid–, and leucine-rich protein 1) is a nuclear receptor coregulator that plays an important role in ER signaling. Its expression is deregulated in hormonal cancers. We identified PELP1 as a novel cyclin-dependent kinase (CDK) substrate. Using site-directed mutagenesis and in vitro kinase assays, we identified Ser477 and Ser991 of PELP1 as CDK phosphorylation sites. Using the PELP1 Ser991 phospho-specific antibody, we show that PELP1 is hyperphosphorylated during cell cycle progression. Model cells stably expressing the PELP1 mutant that lack CDK sites had defects in estradiol (E2)–mediated cell cycle progression and significantly affected PELP1-mediated oncogenic functions in vivo. Mechanistic studies showed that PELP1 modulates transcription factor E2F1 transactivation functions, that PELP1 is recruited to pRb/E2F target genes, and that PELP1 facilitates ER signaling cross talk with cell cycle machinery. We conclude that PELP1 is a novel substrate of interphase CDKs and that its phosphorylation is important for the proper function of PELP1 in modulating hormone-driven cell cycle progression and also for optimal E2F transactivation function. Because the expression of both PELP1 and CDKs is deregulated in breast tumors, CDK-PELP1 interactions will have implications in breast cancer progression. Cancer Res; 70(18); 7166–75. ©2010 AACR.