tbuckley/cabot-search huggingface dataset:
D<scp>IETARY</scp> F<scp>LAVONOIDS</scp>: Bioavailability, Metabolic Effects, and Safety
Authors: Julie A. Ross, Christine M. Kasum
Journal: Annual Review of Nutrition (2002)

▪ Abstract Flavonoids comprise the most common group of plant polyphenols and provide much of the flavor and color to fruits and vegetables. More than 5000 different flavonoids have been described. The six major subclasses of flavonoids include the flavones (e.g., apigenin, luteolin), flavonols (e.g., quercetin, myricetin), flavanones (e.g., naringenin, hesperidin), catechins or flavanols (e.g., epicatechin, gallocatechin), anthocyanidins (e.g., cyanidin, pelargonidin), and isoflavones (e.g., genistein, daidzein). Most of the flavonoids present in plants are attached to sugars (glycosides), although occasionally they are found as aglycones. Interest in the possible health benefits of flavonoids has increased owing to their potent antioxidant and free-radical scavenging activities observed in vitro. There is growing evidence from human feeding studies that the absorption and bioavailability of specific flavonoids is much higher than originally believed. However, epidemiologic studies exploring the role of flavonoids in human health have been inconclusive. Some studies support a protective effect of flavonoid consumption in cardiovascular disease and cancer, other studies demonstrate no effect, and a few studies suggest potential harm. Because there are many biological activities attributed to the flavonoids, some of which could be beneficial or detrimental depending on specific circumstances, further studies in both the laboratory and with populations are warranted.
Auer rod positive dysmyelopoietic syndrome
Authors: Daniel J. Weisdorf, Martin M. Oken, Gerhard J. Johnson, Robert E. Rydell
Journal: American Journal of Hematology (1981)

Twenty-five patients with refractory anemia with excess blasts (RAEB) were studied. Five of these patients showed Auer rods in their myeloblasts, but met other criteria for RAEB. Median survival of the Auer rod-positive group was 14 months (range 2-27) from diagnosis with survival of 7 months after Auer rods were first observed. Median survival for the Auer rod-negative group was 12 months. Two patients developed overt acute leukemia, both from the Auer rod-negative group. The clinical course of Auer rod-positive RAEB, like that of Auer rod-negative RAEB, was one of progressive bone marrow failure complicated by infection, serious bleeding and the development of absolute transfusion requirement. These findings suggest that Auer rod-positive RAEB is a morphologic variant dysmyelopoietic syndrome that may pursue a similar clinical course to Auer rod-negative disease. Formulation of a separate treatment approach for those RAEB patients who possess Auer rods would appear ill advised.
Prevalence and risk factors for pulmonary artery systolic hypertension among sickle cell disease patients in Nigeria
Authors: Zakari Y. Aliyu, Victor Gordeuk, Vandana Sachdev, Aliyu Babadoko, Aisha I. Mamman, Peter Akpanpe, Ester Attah, Yusuf Suleiman, Nurudeen Aliyu, Jamilu Yusuf, Laurel Mendelsohn, Gregory J. Kato, Mark T. Gladwin
Journal: American Journal of Hematology (2008)

Abstract Pulmonary artery systolic hypertension is common and associated with increased mortality among adult sickle cell disease (SCD) patients in the United States. Although the prevalence of SCD is highest in sub‐Saharan Africa, the frequency of pulmonary artery systolic hypertension and the risk factors for the development of pulmonary hypertension have not been reported from Africa. We studied 208 hydroxyurea naïve Nigerian SCD patients at steady state and 94 healthy controls. Pulmonary artery systolic hypertension was defined prospectively as tricuspid regurgitant jet velocity ≥2.5 m/sec. Results were compared with a previously published US prospective SCD cohort. Only 7% of Nigerians compared with 46% of US adults with SCD were &gt;35 years. Tricuspid regurgitant jet velocity was ≥2.5 m/sec in 25% of Nigerian SCD patients. Higher jet velocity was associated with greater serum globulin ( P = 0.002), blood urea nitrogen ( P = 0.019) and lactate dehydrogenase concentrations ( P = 0.026) and with inability to walk &gt;300 m in 6 min ( P = 0.042). Compared with the US cohort, Nigerian patients had more hemolysis as indicated by lower hemoglobin and higher lactate dehydrogenase concentrations ( P ≤ 0.003). Pulmonary hypertension is common among Nigerian SCD patients. The public health implication of this finding is significant considering the potential number of individuals at risk for this complication. Better understanding of the long term outcome of pulmonary hypertension and causes of death in SCD and the institution of preventive measures are major public health challenges for Africa. The inclusion of African sites in sickle cell pulmonary hypertension clinical trials should be encouraged. Am. J. Hematol., 2008. © 2008 Wiley‐Liss, Inc.
For and against: Should steroids be the first line treatment for asthma? For Against
Authors: G. Strube
Journal: BMJ (2000)

# Should steroids be the first line treatment for asthma? {#article-title-2}

Step one of the current British asthma guidelines recommends that inhaled short acting β2 agonists should be used as required. Some clinicians, including George Strube, a general practitioner from Crawley, believe that this step is unnecessary and that steroids should be introduced earlier. Michael Rudolph, a consultant physician from Ealing Hospital, defends the guidelines.

# For {#article-title-3}

Evidence for the inflammatory basis of asthma comes from bronchial biopsies, which show inflammation of the mucosa even in patients with mild intermittent asthma.1 Mucosal oedema and excess mucus production cause reduction in the lumen and obstruction to airflow. Bronchospasm occurs as the natural ‘foreign body’ response to irritation caused by inflammation, the bronchi become hyperactive and the airflow is further reduced. Persistent inflammation may lead to structural changes in the airways, with reduction in lung function and irreversible airways obstruction.2

Steroids are the most effective anti-inflammatory drugs available. They reduce mucosal oedema and bronchial hyperreactivity thus relieving acute symptoms and preventing structural damage to the lungs. It is therefore best to give them as soon as the diagnosis of asthma has been confirmed.

β Agonists are effective bronchodilators but they have no anti-inflammatory activity and so although they offer temporary clinical improvement the underlying inflammation persists. When their effect wears off there is a return of bronchial hyperreactivity and bronchoconstriction, which may even be increased.3 If this is countered with further doses of bronchodilator a pattern of dependence can be established with regular use aggravating the asthma it is intended to control. This may even occur in patients already taking steroids, and the dose required for control may need to be increased. Regular use of bronchodilators should therefore be avoided and should be kept in reserve for breakthrough wheezing.

Trials comparing the effect of inhaled steroids with β agonists showed that …
All-Cause Mortality in Randomized Trials of Cancer Screening
Authors: William C. Black, David A. Haggstrom, H. Gilbert Welch
Journal: JNCI Journal of the National Cancer Institute (2002)

The most widely accepted end point in randomized cancer screening trials is disease-specific mortality. The validity of this end point, however, rests on the assumption that cause of death can be determined accurately. An alternative end point is all-cause mortality, which depends only on the accurate ascertainment of deaths and when they occur. We compared disease-specific and all-cause mortality in published randomized cancer-screening trials to indirectly assess the validity of the disease-specific mortality end point.We examined all 12 published randomized trials of cancer screening for which both end points were available (seven of mammography, three of fecal occult blood detection, and two of chest x-ray screening for lung cancer). For each randomized trial, we subtracted disease-specific mortality observed in the screened group from that observed in the control group and all-cause mortality in the screened group from that in the control group. We then compared the differences in these two mortality measures.In five of the 12 trials, differences in the two mortality rates went in opposite directions, suggesting opposite effects of screening. In four of these five trials, disease-specific mortality was lower in the screened group than in the control group, whereas all-cause mortality was the same or higher. In two of the remaining seven trials, the mortality rate differences were in the same direction but their magnitudes were inconsistent; i.e., the difference in all-cause mortality exceeded the disease-specific mortality in the control group. Thus, results of seven of the 12 trials were inconsistent in their direction or magnitude.Major inconsistencies were identified in disease-specific and all-cause mortality end points in randomized cancer screening trials. Because all-cause mortality is not affected by bias in classifying the cause of death, it should be examined when interpreting the results of randomized cancer-screening trials.
Police find no evidence of forgery by accused paediatricians
Authors: C. Dyer
Journal: BMJ (2002)

<h3>Abstract</h3> Identifying protein environments at the virus-host cell interface can improve our understanding of viral entry and pathogenesis. SARS-CoV-2, the virus behind the ongoing COVID-19 pandemic, uses the cell surface ACE2 protein as a major receptor, but the contribution of other cellular proteins in the entry process is unknown. To probe the microenvironment of SARS-CoV-2 Spike-ACE2 protein interactomes on human cells, we developed a photocatalyst-based viral-host protein microenvironment mapping platform (ViraMap) employing iridium photocatalysts conjugated to Spike for visible-light driven proximity labelling on host cells. Application of ViraMap on ACE2-expressing cells captured ACE2, the established co-receptor NRP1, as well as other proteins implicated in host cell entry and immunomodulation. We further investigated these enriched proteins via loss-of-function and over-expression in pseudotype and authentic infection models and observed that the Ig receptor PTGFRN and tyrosine kinase ligand EFNB1 can serve as SARS-CoV-2 entry factors. Our results highlight additional host targets that participate infection and showcase ViraMap for interrogating virus-host cell surface interactomes.
Affirmative-action for the brainstem in the neuroscience of consciousness: The zeitgeist of the brainstem as a “dumb arousal” system
Authors: Douglas F. Watt
Journal: Behavioral and Brain Sciences (2007)

Merker offers a remarkable statement about the neural integration essential to conscious states provided by the mesodiencephalon. The model for triangular interaction between action selection, target selection, and emotion is heuristic. Unfortunately, there is little interest (relatively speaking) in neuroscience in the mesodiencephalon, and attention is currently heavily directed to the telencephalon. This suggests that there may be less real momentum than commonly assumed towards the Holy Grail of neuroscience, a scientific theory of mind, despite the major upsurge in interest.
<i>KRAS</i> Mutations As an Independent Prognostic Factor in Patients With Advanced Colorectal Cancer Treated With Cetuximab
Authors: Astrid Lièvre, Jean-Baptiste Bachet, Valérie Boige, Anne Cayre, Delphine Le Corre, Emmanuel Buc, Marc Ychou, Olivier Bouché, Bruno Landi, Christophe Louvet, Thierry André, Fréderic Bibeau, Marie-Danièle Diebold, Philippe Rougier, Michel Ducreux, Gorana Tomasic, Jean-François Emile, Frédérique Penault-Llorca, Pierre Laurent-Puig
Journal: Journal of Clinical Oncology (2008)

Cetuximab is efficient in advanced colorectal cancer (CRC). We previously showed that KRAS mutations were associated with resistance to cetuximab in 30 CRC patients. The aim of this study was to validate, in an independent larger series of 89 patients, the prognostic value of KRAS mutations on response to cetuximab and survival.Eighty-nine metastatic CRC patients treated with cetuximab after treatment failure with irinotecan-based chemotherapy were analyzed for KRAS mutation by allelic discrimination on tumor DNA. The association between KRAS mutations and tumor response, skin toxicity, progression-free survival (PFS) and overall survival (OS) was analyzed.A KRAS mutation was present in 27% of the patients and was associated with resistance to cetuximab (0% v 40% of responders among the 24 mutated and 65 nonmutated patients, respectively; P < .001) and a poorer survival (median PFS: 10.1 v 31.4 weeks in patients without mutation; P = .0001; median OS: 10.1 v 14.3 months in patients without mutation; P = .026). When we pooled these 89 patients with patients from our previous study, the multivariate analysis showed that KRAS status was an independent prognostic factor associated with OS and PFS, whereas skin toxicity was only associated with OS. In a combined analysis, median OS times of patients with two, one, or no favorable prognostic factors (severe skin toxicity and no KRAS mutation) was of 15.6, 10.7, and 5.6 months, respectively.These results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic CRC patients treated with cetuximab.
Incidence of glioma in a northwestern region of England, 2006-2010
Authors: E. A. J. Sehmer, G. J. Hall, D. C. Greenberg, C. O'Hara, S. C. Wallingford, K. A. Wright, A. C. Green
Journal: Neuro-Oncology (2014)

Gliomas are important because they affect disproportionately high numbers of people of working age and have a poor prognosis. Neurosurgeons were concerned about a possible recent cluster of glioma cases in a northwestern region in England. All patients aged 18–89 years in Lancashire and South Cumbria with a histologically confirmed glioma diagnosed at the Royal Preston Hospital between January 1, 2006, and December 31, 2010, were ascertained. Clinical information was extracted from hospital records. Completeness of case referral to Royal Preston Hospital was checked against the National Cancer Registry and National Brain Tumour Registry records for the same period. For a comprehensive assessment of regional incidence, age-standardized incidence rates of all gliomas diagnosed in adults (aged 15 years and older) in the study area were then compared with those for the North West region and England as a whole. Rates for the North West region in defined small area-units ("Middle Super Output Areas") were also investigated to assess any small-area variation in the region during the decade to 2010. There were 435 glioma patients from Lancashire and South Cumbria diagnosed at the Royal Preston Hospital between 2006 and 2010, with case ascertainment verified to be complete by the National Cancer Registration Service. The age-standardized incidence rate of gliomas in the study area was 7.10 per 100 000 in 2006–2010, which was minimally different from the rate for all cancer networks in England over the 10 years from 2001. Small-area analysis confirmed lack of major variation in glioma rates in the North West region of England. Glioma incidence rates in England have remained stable by region and over time during the last decade.
Alcohol abuse and the risk of pancreatic cancer
Authors: W Ye, J Lagergren, E Weiderpass, O Nyren, H-O Adami, A Ekbom
Journal: Gut (2002)

<b>Background:</b> Although most epidemiological studies do not support a role for alcohol in the aetiology of pancreatic cancer, an increased risk among heavy drinkers cannot be excluded. <b>Methods:</b> In a retrospective cohort based on the Swedish Inpatient Register, we analysed the risk of pancreatic cancer among patients admitted to hospital for alcoholism (n=178 688), alcoholic chronic pancreatitis (n=3500), non-alcoholic chronic pancreatitis (n=4952), alcoholic liver cirrhosis (n=13 553), or non-alcoholic liver cirrhosis (n=7057) from 1965 to 1994. Follow up through to 1995 was accomplished by linkage to nationwide registers. Standardised incidence ratios (SIRs) express the relative risks by taking the general Swedish population as reference. To minimise the possible influence of selection bias, we excluded the first year observations. <b>Results:</b> Alcoholics had only a modest 40% excess risk of pancreatic cancer (SIR 1.4, 95% confidence interval (CI) 1.2–1.5). Overrepresented smokers among alcoholics might confound a true SIR of unity among alcoholics to approximately 1.4. SIR among alcoholic chronic pancreatitis patients (2.2, 95% CI 0.9–4.5) was considerably lower than that among non-alcoholic chronic pancreatitis patients (8.7, 95% CI 6.8–10.9), and decreased with increasing duration of follow up in both groups, indicating that most of the excess might be explained by reversed causation from undiagnosed cancers. Among patients with alcoholic liver cirrhosis, the increased risk of pancreatic cancer was also moderate (SIR 1.9, 95% CI 1.3–2.8) while no significant excess risk was found among non-alcoholic liver cirrhosis patients (SIR 1.2, 95% CI 0.6–2.2). <b>Conclusions:</b> The excess risk for pancreatic cancer among alcoholics is small and could conceivably be attributed to confounding by smoking.
Redistribution of canalicular cell membrane enzyme in hepatocytes following their isolation and during early cell culture
Authors: R Gratzl, R Lassacher, A Majcen, J Graf
Journal: Hepatology (1997)

in this study, although it may not have been immediately tis C in which there were no changes in albumin, bilirubin, or prothrombin time during deterioration of APC amongst apparent from studying the group data in Figs. 2 and3.The statement by Dr. Fabbri et al. that the variability between patients who had relapsed after a short-term response.We therefore continue to assert that monitoring of liver function these groups can be explained by differences in environmental factors is not an appropriate conclusion because we ex-using a sensitive test may be of value in charting the natural history of chronic hepatitis C. cluded patients from the study who were exposed to environmental factors, like drug ingestion, that would have a major
Variable phenotypic expression of mutations in genes of the immune system
Authors: R. H. Buckley
Journal: Journal of Clinical Investigation (2005)

Discovery of mutated genes that cause various types of primary immunodeficiencies has significantly advanced our understanding of the pathogenesis of these diseases and of the functions of normal gene products. However, it is becoming abundantly clear that the phenotypic presentation of mutations in a given gene can be quite different, depending upon the location and type of mutation but also probably upon other genetic factors and environmental influences. In this issue of the JCI, de Villartay et al. describe a third phenotype for mutations in recombination activating gene 1 (RAG1), in addition to the already known phenotypes of SCID and Omenn syndrome.
Receptor for Advanced Glycation End Products on Human Synovial Fibroblasts
Authors: Fan Fan Hou, Jian Ping Jiang, Jun Qi Guo, Guo Bao Wang, Xun Zhang, David M. Stern, Ann Marie Schmidt, William F. Owen
Journal: Journal of the American Society of Nephrology (2002)

ABSTRACT. An important component of amyloid fibrils in dialysis-related amyloidosis (DRA) is β 2 -microglobulin (β 2 m) modified with advanced glycation end products (AGE). The amyloid deposits are located principally in joint structures, with adjacent chronic inflammatory reaction characterized by monocyte infiltration. This study examined the interaction of AGE-β 2 m with human synovial fibroblasts and investigated the proinflammatory effects of that interaction. It was demonstrated that human synovial fibroblasts constitutively expressed the receptor for AGE (RAGE). RAGE expression was detected mainly in synovial intima and was upregulated in DRA synovium. 125 I-AGE-β 2 m bound to immobilized human synovial fibroblasts in a specific, dose-dependent manner ( K d of approximately 138.0 nM), and binding was inhibited by anti-RAGE IgG. Incubation of human synovial fibroblasts with AGE-β 2 m induced degradation of this AGE-modified protein, as well as increased monocyte chemoattractant protein-1 (MCP-1) mRNA and protein expression. The amount of MCP-1 produced by AGE-β 2 m-stimulated human synovial fibroblasts was sufficient to induce the chemotaxis of monocytes. MCP-1 synthesis resulted from engagement of RAGE, because the increase in MCP-1 synthesis was attenuated by preincubation of human synovial fibroblasts with anti-RAGE IgG. These data provide evidence of RAGE-mediated perturbation of human synoviocytes, which may be involved in the pathogenesis of inflammatory processes associated with DRA.
Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients
Authors: R Cervera, R Serrano, G J Pons-Estel, L Ceberio-Hualde, Y Shoenfeld, E de Ramón, V Buonaiuto, S Jacobsen, M M Zeher, T Tarr, A Tincani, M Taglietti, G Theodossiades, E Nomikou, M Galeazzi, F Bellisai, P L Meroni, R H W M Derksen, P G D de Groot, M Baleva, M Mosca, S Bombardieri, F Houssiau, J-C Gris, I Quéré, E Hachulla, C Vasconcelos, A Fernández-Nebro, M Haro, Z Amoura, M Miyara, M Tektonidou, G Espinosa, M L Bertolaccini, M A Khamashta
Journal: Annals of the Rheumatic Diseases (2014)

To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later.In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10 years.53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10 years was 90.7%.Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.
Far-Fetched Benefit of Inflammation
Authors: Daniel I. Simon, Vincent J. Pompili
Journal: Circulation (2007)

ecent observations suggest that circulating stem cells contribute to neointimal formation.For example, DNA in situ hybridization for the human Y chromosome in sex-mismatched heart transplantions has detected up to 2.6% to 16% of human coronary artery smooth muscle cells of host origin. 1 This process likely contributes not only to transplant vasculopathy but also to neointimal thickening in atherosclerosis and restenosis. 2 Yet, the factors that modulate this process are unknown.