tbuckley/cabot-search huggingface dataset:
Delta-24 Increases the Expression and Activity of Topoisomerase I and Enhances the Antiglioma Effect of Irinotecan
Authors: Candelaria Gomez-Manzano, Marta M. Alonso, W.K. Alfred Yung, Frank McCormick, David T. Curiel, Frederick F. Lang, Hong Jiang, B. Nebiyou Bekele, Xian Zhou, Ramon Alemany, Juan Fueyo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: In this study, we sought to determine whether Delta-24 could sensitize glioma cells to the topoisomerase I inhibitor irinotecan (CPT-11) and to identify the mechanisms underlying this enhanced anticancer effect. Experimental Design: We used human glioblastoma cell lines for the in vitro studies. The expression of topoisomerase I was determined in Western blot analyses, and topoisomerase I activity was determined by measuring the relaxation of a supercoiled DNA. The cell cycle distribution of cells was determined by flow cytometry analysis of the cellular DNA content. Cell viability was quantified by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tissue culture infection dose assays were used to quantitate adenovirus replication. For the in vivo studies, athymic mice received intracranial/intratumoral injections of Delta-24 in combination with CPT-11, after which animal survival was monitored. Results: Delta-24 infection caused human glioma cells to accumulate in the S phase and induced the expression and activity of topoisomerase I as shown by Western blot and in vitro enzymatic activity assays. Further, we showed that the sequential administration of Delta-24 and CPT-11 to human glioma cell cultures potentiated the CPT-11-mediated anticancer effect in vitro without modifying the replicative phenotype of the oncolytic adenovirus. In vivo experiments showed that the single intratumoral administration of Delta-24 to intracranially implanted human glioma xenografts followed by the systemic administration of CPT-11 resulted in significantly prolonged animal survival. Conclusions: The combination of Delta-24 treatment with CPT-11 showed an enhanced anticancer effect, which suggests that the interaction between adenoviral and human proteins can be exploited in rational anticancer therapies comprising replication-competent adenoviruses and conventional chemotherapeutic agents.
Primary Prevention of Cardiovascular Disease in People With Dysglycemia
Authors: Cristina Bianchi, Roberto Miccoli, Giuseppe Penno, Stefano Del Prato
Journal: Diabetes Care (2008)

Cardiovascular disease accounts for a great majority of deaths in patients with type 2 diabetes. According to the World Health Organization, the prevalence of cardiovascular disease in diabetic patients ranges from 26 to 36%. Fatality rate after myocardial infarction is greater in diabetic patients, and overall prognosis after coronary heart disease is worse. Based on these observations, it has been proposed that diabetes should be considered as a coronary heart disease risk equivalent. If that is the case, prevention of diabetes and early intervention should be pursued. This view is supported by the notion that cardiovascular risk is already increased in people with impaired glucose tolerance. Moreover, higher-than-optimum blood glucose is a major cause of cardiovascular mortality in most world regions of the world. Whether dysglycemia is a marker for a more complex metabolic condition or may directly contribute to excess cardiovascular risk is still a matter of debate. However, experimental work has shown how increased glucose level can trigger multiple mechanisms of susceptibility to atherosclerosis, and diabetes prevention trials have indicated that along with reduction of the rate of conversion toward diabetes, significant improvement in cardiovascular risk factors occurs. Moreover, in the STOP-NIDDM trial, targeting postprandial glucose was associated with reduction in new cases of hypertension, myocardial infarction, and any cardiovascular events. In conclusion, dysglycemia should be included in the list of established cardiovascular risk factors and early treatment introduced in the attempt to improve cardiovascular morbidity and mortality.
Three-Dimensional Electroanatomic Voltage Mapping Increases Accuracy of Diagnosing Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia
Authors: Domenico Corrado, Cristina Basso, Loira Leoni, Barbara Tokajuk, Barbara Bauce, Gianfranco Frigo, Giuseppe Tarantini, Massimo Napodano, Pietro Turrini, Angelo Ramondo, Luciano Daliento, Andrea Nava, Gianfranco Buja, Sabino Iliceto, Gaetano Thiene
Journal: Circulation (2005)

Three-dimensional electroanatomic voltage mapping offers the potential to identify low-voltage areas that correspond to regions of right ventricular (RV) myocardial loss and fibrofatty replacement in patients with arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D).Thirty-one consecutive patients (22 men and 9 women; mean age, 30.8+/-7 years) who fulfilled the criteria of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D diagnosis after noninvasive clinical evaluation underwent further invasive study including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175+/-23) were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal RV electroanatomic voltage mapping showing > or =1 area (mean 2.25+/-0.7) with low-voltage values (bipolar electrogram amplitude <0.5 mV), surrounded by a border zone (0.5 to 1.5 mV) that transitioned into normal myocardium (>1.5 mV). Low-voltage electrograms appeared fractionated with significantly prolonged duration and delayed activation. In 11 patients (group B; 35%), electroanatomic voltage mapping was normal, with preserved electrogram voltage (4.4+/-0.7 mV) and duration (37.2+/-0.9 ms) throughout the RV. Low-voltage areas in patients from group A corresponded to echocardiographic/angiographic RV wall motion abnormalities and were significantly associated with myocyte loss and fibrofatty replacement at EMB (P<0.0001) and familial ARVC/D (P<0.0001). Patients from group B had sporadic disease and histopathological evidence of inflammatory cardiomyopathy (P<0.0001). During the time interval from onset of symptoms to the invasive study, 11 patients (55%) with electroanatomic low-voltage regions received an implantable cardioverter/defibrillator because of life-threatening ventricular arrhythmias, whereas all but 1 patient with a normal voltage map remained stable on antiarrhythmic drug therapy (P=0.02).Three-dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing ARVC/D (1) by demonstrating low-voltage areas that were associated with fibrofatty myocardial replacement and (2) by identifying a subset of patients who fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a better arrhythmic outcome.
NHS doctors and finance staff have a negative view of each other
Authors: Adrian O’Dowd
Journal: BMJ (2007)

Doctors must be involved in financial decision making in the NHS to avoid repeating the cash disasters of recent times, England’s public spending watchdog says.

The Audit Commission has published a report calling for much better communication and working relationships between clinical and finance staff. The NHS will become more efficient and will improve services for patients only if relationships between these two groups of staff are stronger, says the report.

Failure to engage doctors and other clinical staff in managing budgets is at the heart of financial problems in the NHS, say the authors.

They interviewed staff at …
Comorbid Anxiety Disorders in Depressed Elderly Patients
Authors: Eric J. Lenze, Benoit H. Mulsant, M. Katherine Shear, Herbert C. Schulberg, Mary Amanda Dew, Amy E. Begley, Bruce G. Pollock, Charles F. Reynolds
Journal: American Journal of Psychiatry (2000)

OBJECTIVE: Anxiety disorders are common in adults with depressive disorders, but several studies have suggested a relatively low prevalence of anxiety disorders in older individuals with depression. This cross-sectional study measured current and lifetime rates and associated clinical features of anxiety disorders in depressed elderly patients. METHOD: History of anxiety disorders was assessed by using a structured diagnostic instrument in 182 depressed subjects aged 60 and older seen in primary care and psychiatric settings. Associations between comorbid anxiety disorders and baseline characteristics were measured. The modified structured instrument allowed detection of symptoms that met inclusion criteria for generalized anxiety disorder in a depressive episode. RESULTS: Thirty-five percent of older subjects with depressive disorders had at least one lifetime anxiety disorder diagnosis, and 23% had a current diagnosis. The most common current comorbid anxiety disorders were panic disorder (9.3%), specific phobias (8.8%), and social phobia (6.6%). Symptoms that met inclusion criteria for generalized anxiety disorder, measured separately, were present in 27.5% of depressed subjects. Presence of a comorbid anxiety disorder was associated with poorer social function and a higher level of somatic symptoms. Symptoms of generalized anxiety disorder were associated with a higher level of suicidality. CONCLUSIONS: Contrary to previous reports, the present study found a relatively high rate of current and lifetime anxiety disorders in elderly depressed individuals. Comorbid anxiety disorders and symptoms of generalized anxiety disorder were associated with a more severe presentation of depressive illness in elderly subjects.
Gene Therapy for Dopamine Replacement in Parkinson´s Disease
Authors: Anders Björklund, Tomas Björklund, Deniz Kirik
Journal: Science Translational Medicine (2009)

The introduction of L-dopa (L-3,4-dihydroxyphenylalanine) therapy 40 years ago was a revolution in the treatment of patients with Parkinson s disease (PD). With time, however, the shortcomings of oral L-dopa medication became apparent, in particular the appearance of troublesome side effects, expressed as involuntary movements (dyskinesias) that developed over time in many patients. A gene therapy approach, aimed at restoring dopamine synthesis in the affected brain by viral vector delivery of genes that encode the dopamine-synthesizing enzymes, may offer a solution to this problem. Now, a team of French and UK researchers reports promising results in a nonhuman primate model of PD, paving the way for clinical trials of this enzyme-replacement approach.
Cardiorespiratory Fitness and C-Reactive Protein Among a Tri-Ethnic Sample of Women
Authors: Michael J. LaMonte, J. Larry Durstine, Frank G. Yanowitz, Tobin Lim, Katrina D. DuBose, Paul Davis, Barbara E. Ainsworth
Journal: Circulation (2002)

Background — Elevated C-reactive protein (CRP) is associated with increased coronary heart disease (CHD) risk. Cardiorespiratory fitness (“fitness”) is related with lower CHD risk; however, its relationship with CRP is relatively unknown. Methods and Results — Cross-sectional associations between fitness and plasma CRP were examined among 135 African American (AA), Native American (NA), and Caucasian (CA) women (55±11 year; 28±6 kg/m 2 ). Fitness was assessed with a maximal treadmill exercise test. Plasma CRP concentrations were determined with the Dade Behring high-sensitivity immunoassay. Geometric mean CRP levels were 0.43, 0.25, and 0.23 mg/dL, and average maximal MET levels of fitness were 7.2, 9.1, and 10 METs for AA, NA, and CA, respectively. CRP decreased across tertiles of fitness ( P =0.002), increased across tertiles of BMI ( P =0.0007), and varied by race ( P =0.002). After adjustment for covariates, lower CRP ( P &lt;0.05) was observed across tertiles of fitness among NA and CA, but not AA. Among all women, after adjusting for race and covariates, the odds of high-risk CRP (&gt;0.19 mg/dL) were 0.67 (95% CI=0.19 to 2.4) among fit (&gt;6.5 METs) versus unfit women. Conclusions — The health benefits from enhanced fitness may have an antiinflammatory mechanism.
Effect of diabetes mellitus on the Time of mycobacterial clearance from sputum during the treatment of multi-drugs resistant tuberculosis
Authors: Parvaneh Baghaei, Payam Tabarsi, Majid Marjani, Afshin Moniri, Mohammad Reza Masjedi
Journal: European Respiratory Journal (2014)

Background: There is evidence that the acid-fast bacilli clearance from sputum is delayed in tuberculosis (TB) patient with diabetes mellitus (DM). The aim of study was to compare the time of sputum smear conversion and the clearance of mycobacteria from sputum during the treatment of multi-drug resistant TB with DM and without DM patients.  Methods: During 2003- 2011, 25 adult patients with MDR-TB and DM and 25 age- and sex-matched patients with MDR-TB without DM were included in the study. All patients received standardized MDR-TB treatment consisted of ofloxacin, cycloserine, amikacin, prothionamide. Time of sputum smear conversion was evaluated in both groups. The clearance of bacilli from sputum smear was compared every 15 days by using repeated measure analysis.  Results: The mean time of sputum smear conversion was 2.82±1.79 months in patients with MDR-TB and DM, and 3.06±1.76 months in patients with MDR-TB only (P=0.63). Repeated measure analysis revealed that the clearance of acid-fast bacilli from sputum in diabetic patients over time was significantly higher than non-DM patients (P=0.009)  .  Conclusion: The time of mycobacterial clearance of sputum smear in diabetic MDR-TB patients was higher than MDR-TB only.
Non-steroidal anti-inflammatory drugs, including cyclo-oxygenase-2 inhibitors, in osteoarthritic knee pain: meta-analysis of randomised placebo controlled trials
Authors: Jan Magnus Bjordal, Anne Elisabeth Ljunggren, Atle Klovning, Lars Slørdal
Journal: BMJ (2004)

<b>Although the association between acute exacerbation of interstitial lung disease and vaccination is not yet clarified, this is the first case report describing the possibility that SARS-CoV-2 vaccination may trigger acute exacerbation</b> https://bit.ly/3tpu6Cz
AMPKα2 Deletion Exacerbates Neointima Formation by Upregulating Skp2 in Vascular Smooth Muscle Cells
Authors: Ping Song, Shuangxi Wang, Chaoyong He, Shaobin Wang, Bin Liang, Benoit Viollet, Ming-Hui Zou
Journal: Circulation Research (2011)

Adenosine monophosphate-activated protein kinase (AMPK), a metabolic and redox sensor, is reported to suppress cell proliferation of nonmalignant and tumor cells. Whether AMPKα alters vascular neointima formation induced by vascular injury is unknown.The aim of this study was to determine the roles of AMPKα in the development of vascular neointima hyperplasia and to elucidate the underlying mechanisms.Vascular smooth muscle cell (VSMC) proliferation and neointimal hyperplasia were evaluated in cultured VSMCs and wire-injured mouse carotid arteries from wild-type (WT, C57BL/6J), AMPKα2(-/-), and AMPKα1(-/-) mice. Mouse VSMCs derived from aortas of AMPKα2(-/-) mice exhibited increased proliferation compared with either WT or AMPKα1(-/-) VSMCs. Further, deletion of AMPKα2 but not AMPKα1 reduced the level of p27(Kip1), a cyclin-dependent kinase inhibitor, and increased the level of S-phase kinase-associated protein 2 (Skp2), a known E3 ubiquitin ligase for p27(Kip1), through activation of p52 nuclear factor kappa B (NF-κB)-2. Moreover, either pharmacological (ie, through compound C) or genetical (ie, through AMPKα2-specific siRNA) inhibition of AMPK decreased p27(Kip1) levels but increased the abundance of Skp2 in human VSMCs. Furthermore, gene silencing of Skp2 reversed the levels of p27(Kip1) and VSMCs proliferation. Finally, neointima formation after mechanical arterial injury was increased in AMPKα2(-/-) but not AMPKα1(-/-) mice.These findings indicate that deletion of AMPKα2 through p52-Skp2-mediated ubiquitination and degradation of p27(Kip1) accentuates neointimal hyperplasia in response to wire injury.
Proteins involved in extracellular matrix dynamics are associated with respiratory syncytial virus disease severity
Authors: Annemieke Schuurhof, Louis Bont, Hennie M. Hodemaekers, Arja de Klerk, Hanneke de Groot, Regina W. Hofland, Alma C. van de Pol, Jan L.L. Kimpen, Riny Janssen
Journal: European Respiratory Journal (2012)

Severity of respiratory syncytial virus (RSV) infection ranges widely. To what extent the local immune response is involved in RSV disease pathogenesis and which markers of this response are critical in determining disease severity is still a matter of debate. The local immune response was studied in nasopharyngeal aspirates (NPAs) during RSV infection. 47 potential markers of disease severity were analysed in a screening cohort of RSV-infected infants with mild disease at home (n = 8), hospitalised infants (n = 10) and infants requiring mechanical ventilation (n = 7). Results were confirmed in a cohort of infants hospitalised for RSV infection (n = 200). Finally, genetic validation was studied in a cohort of infants hospitalised for RSV infection (n = 465) and healthy controls (n = 930). The concentration of TIMP-1 (tissue inhibitor of metalloproteinase) was higher in the NPAs of hospitalised infants compared with the NPAs of infants at home (1,199 versus 568 ng · mL(-1); p<0.0001). Similar results were found for matrix metalloproteinase (MMP)-3 (765 versus 370 pg · mL(-1); p = 0.004). MMP-3 was confirmed as a marker of disease severity in a larger cohort and MMP3 gene polymorphism rs522616 was associated with severe RSV infection (OR 0.82, p<0.05). In conclusion, extracellular matrix proteinases play an important role in the pathogenesis of RSV bronchiolitis.
Upconverting Organic Dye Doped Core-Shell Nano-Composites for Dual-Modality NIR Imaging and Photo-Thermal Therapy
Authors: Guobin Shan, Ralph Weissleder, Scott A. Hilderbrand
Journal: Theranostics (2013)

Nanotechnology approaches offer the potential for creating new optical imaging agents with unique properties that enable uses such as combined molecular imaging and photo-thermal therapy.Ideal preparations should fluoresce in the near-infrared (NIR) region to ensure maximal tissue penetration depth along with minimal scattering and light absorption.Due to their unique photophysical properties, upconverting ceramics such as NaYF 4 :Er 3+ ,Yb 3+ nanoparticles have become promising optical materials for biological imaging.In this work, the design and synthesis of NaYF 4 :Er 3+ ,Yb 3+ @SiO 2 core-shell nano-composites, which contain highly absorbing NIR carbocyanine dyes in their outer silica shell, are described.These materials combine optical emission (from the upconverting core nanoparticle) with strong NIR absorption (from the carbocyanine dyes incorporated into the shell) to enable both optical imaging and photo-thermal treatment, respectively.Ultimately, this hybrid composite nanomaterial approach imparts the ability to both visualize, via upconversion imaging, and treat, via photo-thermal heating, using two distinct optical channels.Proof-of-principle in vitro experiments are presented to demonstrate the combined imaging and photo-thermal properties of this new functional nano-composite.
Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study
Authors: A. Goy, S.H. Bernstein, B.S. Kahl, B. Djulbegovic, M.J. Robertson, S. de Vos, E. Epner, A. Krishnan, J.P. Leonard, S. Lonial, S. Nasta, O.A. O'Connor, H. Shi, A.L. Boral, R.I. Fisher
Journal: Annals of Oncology (2008)
Is community-acquired pneumonia an independent risk factor for cardiovascular disease?
Authors: A. Singanayagam, A. Singanayagam, D.H.J. Elder, J.D. Chalmers
Journal: European Respiratory Journal (2011)

Community-acquired pneumonia (CAP) is the most frequent infectious cause of death in western countries. The high mortality rate in CAP is commonly related to comorbid conditions such as cardiovascular disease. Clinical studies in both primary and secondary care settings have identified an increase in short- and long-term risk of cardiovascular events and death from vascular events following acute respiratory infections. The mechanism remains to be fully established, but it has been suggested that the inflammatory state in patients affected by CAP acts to promote platelet activation and thrombosis, and to narrow coronary arteries through vasoconstriction. Acute infections destabilise vascular endothelium and create an imbalance between myocardial oxygen supply and demand, leading to an increased risk of cardiovascular events. Acute infections have been shown to have both systemic effects and local effects on coronary vessels. These effects are mediated through both the host response to infection and, in some cases, direct effects of bacterial infection or bacterial products. In this review, we discuss the link between CAP and increased risk of cardiovascular events, drawing on existing evidence from clinical and mechanistic studies. Further studies into and increased awareness of this association is warranted to promote novel ways of protecting high-risk patients.
The evolution of human mating: Trade-offs and strategic pluralism
Authors: Steven W. Gangestad, Jeffry A. Simpson
Journal: Behavioral and Brain Sciences (2000)

During human evolutionary history, there were "trade-offs" between expending time and energy on child-rearing and mating, so both men and women evolved conditional mating strategies guided by cues signaling the circumstances. Many short-term matings might be successful for some men; others might try to find and keep a single mate, investing their effort in rearing her offspring. Recent evidence suggests that men with features signaling genetic benefits to offspring should be preferred by women as short-term mates, but there are trade-offs between a mate's genetic fitness and his willingness to help in child-rearing. It is these circumstances and the cues that signal them that underlie the variation in short- and long-term mating strategies between and within the sexes.
Independent bilateral primary bronchial carcinomas
Authors: M. R. Chaudhuri
Journal: Thorax (1971)

Independent bilateral primary bronchial carcinomas are not common. Since Beyreuther9s description in 1924, 16 well-documented cases of independent primary bronchial carcinomas of different histology have been described. From 1965 to 1970, eight cases were seen at the London Chest Hospital. In order to make the diagnosis of a second primary bronchial carcinoma, each tumour should be malignant and neither should be a metastasis from the other. To meet this last criterion, the histopathological features of the two tumours must be different. Many cases have been described in the literature as double primary bronchial carcinomas where the second primary had the same histological features as the first.