tbuckley/cabot-search huggingface dataset:
Meta-analysis of Functional Magnetic Resonance Imaging Studies of Inhibition and Attention in Attention-deficit/Hyperactivity Disorder
Authors: Heledd Hart, Joaquim Radua, Tomohiro Nakao, David Mataix-Cols, Katya Rubia
Journal: JAMA Psychiatry (2012)

<h3>Context</h3>Functional magnetic resonance imaging studies in attention-deficit/hyperactivity disorder (ADHD) revealed fronto-striato-parietal dysfunctions during tasks of inhibition and attention. However, it is unclear whether task-dissociated dysfunctions exist and to what extent they may be influenced by age and by long-term stimulant medication use.<h3>Objective</h3>To conduct a meta-analysis of functional magnetic resonance imaging studies in ADHD during inhibition and attention tasks, exploring age and long-term stimulant medication use effects.<h3>Data Sources</h3>PubMed, ScienceDirect, Web of Knowledge, Google Scholar, and Scopus databases were searched up to May 2012 for meta-analyses. Meta-regression methods explored age and long-term stimulant medication use effects.<h3>Study Selection</h3>Twenty-one data sets were included for inhibition (287 patients with ADHD and 320 control subjects), and 13 data sets were included for attention (171 patients with ADHD and 178 control subjects).<h3>Data Extraction</h3>Peak coordinates of clusters of significant group differences, as well as demographic, clinical, and methodological variables, were extracted for each study or were obtained from the authors.<h3>Data Synthesis</h3>Patients with ADHD relative to controls showed reduced activation for inhibition in the right inferior frontal cortex, supplementary motor area, and anterior cingulate cortex, as well as striato-thalamic areas, and showed reduced activation for attention in the right dorsolateral prefrontal cortex, posterior basal ganglia, and thalamic and parietal regions. Furthermore, the meta-regression analysis for the attention domain showed that long-term stimulant medication use was associated with more similar right caudate activation relative to controls. Age effects could be analyzed only for the inhibition meta-analysis, showing that the supplementary motor area and basal ganglia were underactivated solely in children with ADHD relative to controls, while the inferior frontal cortex and thalamus were underactivated solely in adults with ADHD relative to controls.<h3>Conclusions</h3>Patients with ADHD have consistent functional abnormalities in 2 distinct domain-dissociated right hemispheric fronto-basal ganglia networks, including the inferior frontal cortex, supplementary motor area, and anterior cingulate cortex for inhibition and dorsolateral prefrontal cortex, parietal, and cerebellar areas for attention. Furthermore, preliminary evidence suggests that long-term stimulant medication use may be associated with more normal activation in right caudate during the attention domain.
Valproic Acid Attenuates Proteinuria and Kidney Injury
Authors: Katrien Van Beneden, Caroline Geers, Marina Pauwels, Inge Mannaerts, Dierik Verbeelen, Leo A. van Grunsven, Christiane Van den Branden
Journal: Journal of the American Society of Nephrology (2011)

Inhibitors of histone deacetylase (HDAC) have anti-inflammatory and antifibrotic effects in several organs and tissues, but their effect on the progression of renal disease is unknown. Here, we studied the effect of valproic acid in adriamycin-induced nephropathy in mice. Administration of valproic acid before kidney injury prevented the development of proteinuria and the onset of glomerulosclerosis. Even after postponing treatment until the peak of adriamycin-induced proteinuria, valproic acid rapidly decreased the quantity of proteinuria and attenuated the progression of renal disease. Valproic acid abrogated the decrease in glomerular acetylation observed during adriamycin-induced nephropathy. Furthermore, valproic acid attenuated the significant upregulation of profibrotic and proinflammatory genes, the deposition of collagen, and the infiltration of macrophages into the kidney. Valproic acid decreased glomerular apoptosis and proliferation induced by adriamycin. Ultrastructural studies further supported the protective effect of valproic acid on podocytes in this model. Taken together, these data suggest that HDACs contribute to the pathogenesis of renal disease and that HDAC inhibitors may have therapeutic potential in CKD.
A SIMPLE DIETETIC TREATMENT IN DIABETES MELLITUS
Authors: R. T. Williamson
Journal: BMJ (1917)

nmarked susceptibility to tlhrombosis.-One man whose veins were easy to puncture lhad a local thrombus atter eachi injection.Soft thromnbi sometimues form during tlhe injection, and it is thien danigerous to proceed.One first signi of local tllhromtbosis in such a case is hiindrance to tlhe ijoNv fromn the needle.GENERAL OBSERVATIONS.1. Thle general tonie atid appearance of the patient iliij)rove so miialkedelv after one, or two illjections of sal- varsati, and the primiary sore so soon disappears, that thle practitioier nmay be persuaded by tlle patient to stop treatnient.We lhave seen several cases in whichl tlhis lhas occuLred, witli the result thiat a very early relapse has taken place.Care sliounid be taken to continiue the treat.ilient until all clinical signs have disappearedand the blood reaction is negative.2. The speed wvtli wlhich primiiary sores, secondary rashles, and condyltomata disappear is wortlhy of note; two ol thlree injections will usixally remove all ouward signs.3. Thje effect of salvarsanl is il6t so speedy in cases in wlichi the niucous.xuembranes of the imIoutih and tonsil are affected, nor in glossitis, and thley do not usually heal.until the blood has got to a negative phase.
Inhibition of Epidermal Growth Factor Receptor Signaling Protects Human Malignant Glioma Cells from Hypoxia-Induced Cell Death
Authors: Joachim P. Steinbach, Andrea Klumpp, Hartwig Wolburg, Michael Weller
Journal: Cancer Research (2004)

Epidermal growth factor receptor (EGFR) signaling has become an important target for drug development because EGFR signaling enhances tumor cell proliferation, migration, and invasion and inhibits apoptosis. However, the results of clinical trials using EGFR inhibitors in patients with solid tumors have been disappointing. Here, we report a protective effect of the EGFR inhibitors AG1478 and PD153035 against cell death induced by acute hypoxia, which contrasts with their proapoptotic effects under normoxia. Under hypoxic conditions, both agents reduced glucose consumption, delayed ATP depletion, and preserved the mitochondrial membrane potential. Exposure either to hypoxia or the EGFR inhibitors under normoxic conditions resulted in the dephosphorylation of ribosomal protein S6, a player in the energy and nutrient-sensing pathway governed by mammalian target-of-rapamycin (mTOR). Combined inhibition of phosphatidylinositol 3'-kinase (PI3K) and extracellular signal-regulated kinase-1/2 (ERK1/2) mimicked the protective effects of EGFR inhibition on hypoxia-induced cell death and protein S6 dephosphorylation. These results caution that therapies targeting EGFR signaling pathways can protect tumor cells from acute hypoxia.
Pervasive Media Violence
Authors: C. Schooler, J. A. Flora
Journal: Annual Review of Public Health (1996)

In this review, we focus our discussion on studies examining effects on children and young adults. We believe that the current epidemic of youth violence in the United States justifies a focus on this vulnerable segment of society. We consider media effects on individual children’s behaviors, such as imitating aggressive acts. In addition, we examine how the media influence young people’s perceptions of norms regarding interpersonal relationships. Next, we assess mass media effects on societal beliefs, or what children and adolescents think the “real world” is like. We suggest these media influences are cumulative and mutually reinforcing, and discuss the implications of repeated exposure to prominent and prevalent violent media messages. Finally, we catalog multiple intervention possibilities ranging from education to regulation. From a public health perspective, therefore, we evaluate the effects that pervasive media messages depicting violence have on young people and present multiple strategies to promote more healthful outcomes.
Therapeutic efficacy and safety of TRAIL-producing human adipose tissue-derived mesenchymal stem cells against experimental brainstem glioma
Authors: S. A. Choi, S.-K. Hwang, K.-C. Wang, B.-K. Cho, J. H. Phi, J. Y. Lee, H. W. Jung, D.-H. Lee, S.-K. Kim
Journal: Neuro-Oncology (2010)

Mesenchymal stem cells (MSCs) have an extensive migratory capacity for gliomas, which is comparable to that of neural stem cells. Among the various types of MSCs, human adipose tissue-derived MSCs (hAT-MSC) emerge as one of the most attractive vehicles for gene therapy because of their high throughput, lack of ethical concerns, and availability and ease of isolation. We evaluated the therapeutic potential and safety of genetically engineered hAT-MSCs encoding the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) against brainstem gliomas. Human AT-MSCs were isolated from human fat tissue, characterized, and transfected with TRAIL using nucleofector. The therapeutic potential of TRAIL-producing hAT-MSCs (hAT-MSC.TRAIL) was confirmed using in vitro and in vivo studies. The final fate of injected hAT-MSCs was traced in long-survival animals. The characterization of hAT-MSCs revealed the expression of MSC-specific cell-type markers and their differentiation potential into mesenchymal lineage. Short-term outcomes included a 56.3% reduction of tumor volume (P < .001) with increased apoptosis (3.03-fold, P < .05) in animals treated with hAT-MSC.TRAIL compared with the control groups. Long-term outcomes included a significant survival benefit in the hAT-MSC.TRAIL-treated group (26 days of median survival in the control group vs 84 days in the hAT-MSC.TRAIL-treated group, P < .0001), without any evidence of mesenchymal differentiation in vivo. Our study demonstrated the therapeutic efficacy and safety of nonvirally engineered hAT-MSCs against brainstem gliomas and showed the possibility of stem-cell-based targeted gene therapy for clinical application.
Systematic Review: Surveillance Systems for Early Detection of Bioterrorism-Related Diseases
Authors: Dena M. Bravata, Kathryn M. McDonald, Wendy M. Smith, Chara Rydzak, Herbert Szeto, David L. Buckeridge, Corinna Haberland, Douglas K. Owens
Journal: Annals of Internal Medicine (2004)

Background: Given the threat of bioterrorism and the increasing availability of electronic data for surveillance, surveillance systems for the early detection of illnesses and syndromes potentially related to bioterrorism have proliferated. Purpose: To critically evaluate the potential utility of existing surveillance systems for illnesses and syndromes related to bioterrorism. Data Sources: Databases of peer-reviewed articles (for example, MEDLINE for articles published from January 1985 to April 2002) and Web sites of relevant government and nongovernment agencies. Study Selection: Reports that described or evaluated systems for collecting, analyzing, or presenting surveillance data for bioterrorism-related illnesses or syndromes. Data Extraction: From each included article, the authors abstracted information about the type of surveillance data collected; method of collection, analysis, and presentation of surveillance data; and outcomes of evaluations of the system. Data Synthesis: 17 510 article citations and 8088 government and nongovernmental Web sites were reviewed. From these, the authors included 115 systems that collect various surveillance reports, including 9 syndromic surveillance systems, 20 systems collecting bioterrorism detector data, 13 systems collecting influenza-related data, and 23 systems collecting laboratory and antimicrobial resistance data. Only the systems collecting syndromic surveillance data and detection system data were designed, at least in part, for bioterrorism preparedness applications. Syndromic surveillance systems have been deployed for both event-based and continuous bioterrorism surveillance. Few surveillance systems have been comprehensively evaluated. Only 3 systems have had both sensitivity and specificity evaluated. Limitations: Data from some existing surveillance systems (particularly those developed by the military) may not be publicly available. Conclusions: Few surveillance systems have been specifically designed for collecting and analyzing data for the early detection of a bioterrorist event. Because current evaluations of surveillance systems for detecting bioterrorism and emerging infections are insufficient to characterize the timeliness or sensitivity and specificity, clinical and public health decision making based on these systems may be compromised.
Transepidermmal water vapour loss is not increased during and following dithranol irritation
Authors: E. SNATER, E.A.A.J. JANSSEN, P.G.M. VALK, P.C.M. KERKHOF
Journal: British Journal of Dermatology (2010)

Dithranol is established as a very successful treatment for psoriasis. Its main disadvantages are irritation and staining at sites of application. The aim of the present study was to elucidate further the mechanism of dithranol‐induced irritation, in particular to what extent this is related to an impairment of the skin barrier.
Primary Tumor Levels of Tissue Inhibitor of Metalloproteinases-1 Are Predictive of Resistance to Chemotherapy in Patients with Metastatic Breast Cancer
Authors: Anne-Sofie Schrohl, Marion E. Meijer-van Gelder, Mads N. Holten-Andersen, Ib Jarle Christensen, Maxime P. Look, Henning T. Mouridsen, Nils Brünner, John A. Foekens
Journal: Clinical Cancer Research (2006)

Only about 50% of metastatic breast cancer patients benefit from cytotoxic chemotherapy. Today, no validated markers exist for prediction of chemotherapy sensitivity/resistance in this patient group. Tissue inhibitor of metalloproteinases-1 (TIMP-1) has been shown to protect against apoptosis, and the purpose of the present study was to test the hypothesis that tumors expressing high levels of TIMP-1 are protected against apoptosis-inducing agents and thus less sensitive to apoptosis-inducing chemotherapeutic drugs.We investigated the association between primary tumor expression levels of TIMP-1 protein and objective response to first-line chemotherapy in 173 patients with metastatic breast cancer.When analyzed as a continuous log-transformed variable, increasing TIMP-1 levels were significantly associated with lack of response to cyclophosphamide/methotrexate/5-fluorouracil and anthracycline-based chemotherapy (P = 0.01; odds ratio, 2.0; 95% confidence interval, 1.1-3.3). In a multivariate model, including lymph node status, steroid hormone receptor status, menopausal status, dominant metastases site, type of chemotherapy, and disease-free interval, TIMP-1 was significantly associated with resistance to treatment (P = 0.03; odds ratio, 1.7; 95% confidence interval, 1.1-3.3).In the present exploratory study, we showed that elevated tumor tissue TIMP-1 levels were significantly associated with a poor response to chemotherapy. By using TIMP-1, we identified a group of patients with metastatic breast cancer, which hardly respond to the most frequently used chemotherapy regimes (i.e., cyclophosphamide/methotrexate/5-fluorouracil and anthracyclines).
Hepatitis B vaccine: Should we give it a shot?
Authors: Chris J. Dickinson, Alan Olson
Journal: Hepatology (1993)

Objective: To determine clinical and economic consequences of alternative vaccination strategies for preventing hepatitis B virus infection (HBV). Methods: Decision analysis was used to evaluate costs, outcomes, and cost-effectiveness of three HBV management strategies (“no vaccination,” “universal vaccination,” and “screen and vaccinate”) in four populations (newborns, 10-year-old adolescents, a high-risk adult population, and the general adult U.S. population). Information on HBV incidence and prevalence, clinical course, and management of acute illness and chronic sequelae was obtained from the literature and a panel of experts. Actual payments (costs) were obtained from Blue Cross/Blue Shield and local pharmacies. Incremental cost-effectiveness was calculated from the perspective of the payer of medical care and subjected to sensitivity analysis. Results: Vaccination (with or without screening) prevents more disease at somewhat increased cost than no vaccination for the neonatal, adolescent, and adult populations. Vaccination (with or without screening) is a dominant strategy in adult high-risk populations (lower cost and greater benefit than no vaccination). Optimal cost-effectiveness, with nonmonetary benefits not discounted, results if all pregnant women are screened for active HBV infection, and HBV vaccine and hepatitis B immune globulin are administered to babies born to mothers with positive screening tests. Then HBV vaccine is administered to all children at age 10 and again 10 years later (incremental cost-per-year-of-life-saved relative to the “no vaccination” strategy is $375). A strategy of universal newborn vaccination alone leads to an incremental cost-per-year-of-life saved of $3332. If adolescents are vaccinated at age 10, incremental cost-per-year-of-life saved is $13,938; for the general adult population, the incremental cost-per-year-of-life saved of universal vaccination is $54,524. Discounting benefits will increase cost-per-year-of-life saved 7 to 12 times for all strategies. Conclusions: HBV vaccine is most cost-effective when a strategy of screening newborns is combined with routine administration to 10-year-old children. The means to achieve substantial improvements in the health of the public in a cost-effective fashion are now available and should be pursued aggressively.
Simple Clinical Test for the Diagnosis of Early Pregnancy
Authors: G. D. Matthew
Journal: BMJ (1956)

The history of one identical case, and another somewhat similar case recorded previously by other authors, are summarized, and theories of causation are discussed particularly in relation to the analogous auriculo- temporal syndrome.The aetiology is somewhat uncertain, but the phenomenon would seem to be due to a reflex definitely related to the chorda tympani and abnormal regeneration of nerve fibres.It is suggested that the symptomcomplex be termed " the chorda tympani syndrome."I am indebted to Dr. E. A. Carmichael for his advice and for the photographs, which were taken at the National Hospital, Queen Square; to the librarian of the Royal Society of Medicine; to Mr. D. S. Hawke
Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C
Authors: Emmanuel A. Tsochatzis, Catriona Crossan, Louise Longworth, Kurinchi Gurusamy, Manolo Rodriguez-Peralvarez, Konstantinos Mantzoukis, Julia O'Brien, Evangelos Thalassinos, Vassilios Papastergiou, Anna Noel-Storr, Brian Davidson, Andrew K. Burroughs
Journal: Hepatology (2014)

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries.
AN ELECTROPHORETIC STUDY OF NEPHROTIC SERA AND URINE
Authors: L. G. Longsworth, D. A. MacInnes
Journal: The Journal of Experimental Medicine (1940)

The electrophoretic patterns of the sera and urine of two cases of lipoid nephrosis have been obtained and have been compared with a typical pattern of normal serum. The patterns of the pathological sera deviated widely from the normal, indicating relatively low albumin and high globulin content. The comparison of the patterns of nephrotic sera cleared by centrifugation and by ether extraction shows that a large portion of the ß globulin consisted of a labile lipo-protein. The pattern of the nephrotic urine proteins resembled that of normal serum, with, however, significant differences.
Muscle Wasting in Cancer Cachexia: Clinical Implications, Diagnosis, and Emerging Treatment Strategies
Authors: Shontelle Dodson, Vickie E. Baracos, Aminah Jatoi, William J. Evans, David Cella, James T. Dalton, Mitchell S. Steiner
Journal: Annual Review of Medicine (2010)

Cancer cachexia is a complex metabolic condition characterized by loss of skeletal muscle. Common clinical manifestations include muscle wasting, anemia, reduced caloric intake, and altered immune function, which contribute to increased disability, fatigue, diminished quality of life, and reduced survival. The prevalence of cachexia and the impact of this disorder on the patient and family underscore the need for effective management strategies. Dietary supplementation and appetite stimulation alone are inadequate to reverse the underlying metabolic abnormalities of cancer cachexia and have limited long-term impact on patient quality of life and survival. Therapies that can increase muscle mass and physical performance may be a promising option; however, there are currently no drugs approved for the prevention or treatment of cancer cachexia. Several agents are in clinical development, including anabolic agents, such as selective androgen receptor modulators and drugs targeting inflammatory cytokines that promote skeletal muscle catabolism.