tbuckley/cabot-search huggingface dataset:
A Nutrient-Wide Association Study on Blood Pressure
Authors: Ioanna Tzoulaki, Chirag J. Patel, Tomonori Okamura, Queenie Chan, Ian J. Brown, Katsuyuki Miura, Hirotsugu Ueshima, Liancheng Zhao, Linda Van Horn, Martha L. Daviglus, Jeremiah Stamler, Atul J. Butte, John P.A. Ioannidis, Paul Elliott
Journal: Circulation (2012)

Background— A nutrient-wide approach may be useful to comprehensively test and validate associations between nutrients (derived from foods and supplements) and blood pressure (BP) in an unbiased manner. Methods and Results— Data from 4680 participants aged 40 to 59 years in the cross-sectional International Study of Macro/Micronutrients and Blood Pressure (INTERMAP) were stratified randomly into training and testing sets. US National Health and Nutrition Examination Survey (NHANES) four cross-sectional cohorts (1999–2000, 2001–2002, 2003–2004, 2005–2006) were used for external validation. We performed multiple linear regression analyses associating each of 82 nutrients and 3 urine electrolytes with systolic and diastolic BP in the INTERMAP training set. Significant findings were validated in the INTERMAP testing set and further in the NHANES cohorts (false discovery rate &lt;5% in training, P &lt;0.05 for internal and external validation). Among the validated nutrients, alcohol and urinary sodium-to-potassium ratio were directly associated with systolic BP, and dietary phosphorus, magnesium, iron, thiamin, folacin, and riboflavin were inversely associated with systolic BP. In addition, dietary folacin and riboflavin were inversely associated with diastolic BP. The absolute effect sizes in the validation data (NHANES) ranged from 0.97 mm Hg lower systolic BP (phosphorus) to 0.39 mm Hg lower systolic BP (thiamin) per 1-SD difference in nutrient variable. Inclusion of nutrient intake from supplements in addition to foods gave similar results for some nutrients, though it attenuated the associations of folacin, thiamin, and riboflavin intake with BP. Conclusions— We identified significant inverse associations between B vitamins and BP, relationships hitherto poorly investigated. Our analyses represent a systematic unbiased approach to the evaluation and validation of nutrient-BP associations.
No Ljungan Virus RNA in Stool Samples From the Norwegian Environmental Triggers of Type 1 Diabetes (MIDIA) Cohort Study
Authors: German Tapia, Ondrej Cinek, Trond Rasmussen, Bjørn Grinde, Kjersti S. Rønningen
Journal: Diabetes Care (2010)

OBJECTIVE Ljungan virus (LjV) has been proposed as a potential environmental factor for type 1 diabetes. The objective was to test for any association of LjV with type 1 diabetes. RESEARCH DESIGN AND METHODS A nested case-control design was used to test for any association between the development of pre-diabetic autoimmunity and presence of LjV in stool samples (n = 3,803) in the Norwegian Environmental Triggers of Type 1 Diabetes (MIDIA) study. The children followed were 27 infants who developed pre-diabetic autoimmunity during or shortly after the sampling period, 54 matched control subjects, and 94 other children. RESULTS No LjV RNA was detected. CONCLUSIONS The results indicate that LjV is rare in young children. LjV does not seem to be involved in the development of human type 1 diabetes.
Art: Demon Drink: George Cruikshank's "The Worship of Bacchus" in Focus
Authors: T. Jackson
Journal: BMJ (2001)

Tate Britain, Millbank, London SW1, until 2 December 2001

Firstly, we are told that one or two glasses of red wine a day are good for you, and then researchers claim that there are no health benefits whatsoever, even from moderate drinking. To the 19th century artist George Cruikshank it seemed quite clear: all alcohol was evil, and moderate drinking invariably led to addiction and moral, social, and financial ruin.

Cruikshank was a prolific illustrator and social satirist who produced the famous original plates for Sketches by Boz and Oliver Twist . His father, …
Sports-related extensor carpi ulnaris pathology: a review of functional anatomy, sports injury and management
Authors: Doug Campbell, Rob Campbell, Phil O'Connor, Roger Hawkes
Journal: British Journal of Sports Medicine (2013)

The extensor carpi ulnaris (ECU) muscle plays a key role not only in the active movements of wrist extension and ulnar deviation but also in providing stability to the ulnar side of the wrist. Its position relative to the other structures in the wrist changes with forearm pronation and supination. As such, it must be mobile yet stable. The ECU tendon relies on specific stabilising structures to hold it in the correct positions to perform its different functions. These structures can be injured in a variety of different athletic activities such as tennis, golf and rugby league, yet their injury and disruption is predictable when the mechanics of the ECU and the techniques of the sport are understood. The ECU tendon is also vulnerable to tendon pathologies other than instability. It lies subcutaneously and is easily palpated and visualised with diagnostic ultrasound, allowing early diagnosis and management of its specific conditions. Treatment includes rest, splintage and surgery with each modality having specific indications and recognised outcomes. This review described the functional anatomy in relevant sporting situations and explained how problems occur as well as when and how to intervene.
Efficacy and Safety of Extended-Release Venlafaxine in the Treatment of Generalized Anxiety Disorder in Children and Adolescents: Two Placebo-Controlled Trials
Authors: Moira A. Rynn, Mark A. Riddle, Paul P. Yeung, Nadia R. Kunz
Journal: American Journal of Psychiatry (2007)

Objective: The authors evaluated the efficacy, safety, and tolerability of extended-release venlafaxine in the treatment of pediatric generalized anxiety disorder. Method: Two randomized, double-blind, placebo-controlled trials were conducted at 59 sites in 2000 and 2001. Participants 6 to 17 years of age who met DSM-IV criteria for generalized anxiety disorder received a flexible dosage of extended-release venlafaxine (N=157) or placebo (N=163) for 8 weeks. The primary outcome measure was the composite score for nine delineated items from the generalized anxiety disorder section of a modified version of the Schedule for Affective Disorders and Schizophrenia for School-Age Children, and the primary efficacy variable was the baseline-to-endpoint change in this composite score. Secondary outcome measures were overall score on the nine delineated items, Pediatric Anxiety Rating Scale, Hamilton Anxiety Rating Scale, Screen for Child Anxiety Related Emotional Disorders, and the severity of illness and improvement scores from the Clinical Global Impression scale (CGI). Results: The extended-release venlafaxine group showed statistically significant improvements in the primary and secondary outcome measures in study 1 and significant improvements in some secondary outcome measures but not the primary outcome measure in study 2. In a pooled analysis, the extended-release venlafaxine group showed a significantly greater mean decrease in the primary outcome measure compared with the placebo group (–17.4 versus –12.7). The response rate as indicated by a CGI improvement score <3 was significantly greater with extended-release venlafaxine than placebo (69% versus 48%). Common adverse events were asthenia, anorexia, pain, and somnolence. Statistically significant changes in height, weight, blood pressure, pulse, and cholesterol levels were observed in the extended-release venlafaxine group. Conclusions: Extended-release venlafaxine may be an effective, well-tolerated short-term treatment for pediatric generalized anxiety disorder.
Predicting Hepatocellular Carcinoma by Detection of Aberrant Promoter Methylation in Serum DNA
Authors: Yu-Jing Zhang, Hui-Chen Wu, Jing Shen, Habibul Ahsan, Wei Yann Tsai, Hwai-I Yang, Li-Yu Wang, Shu-Yuan Chen, Chien-Jen Chen, Regina M. Santella
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Most hepatocellular carcinomas (HCC) are diagnosed at an advanced stage. Hypermethylation of CpG islands in promoter regions is now recognized as an important early event in carcinogenesis and detection of methylated DNA has been suggested as a potential biomarker for early detection of cancer. There are no studies on epigenetic changes in samples from HCC patients before diagnosis. We explored the possible diagnostic value of aberrant promoter hypermethylation of three tumor suppressor genes in serum DNA for early detection of HCC. Experimental Design: Aberrant promoter hypermethylation was investigated in DNA isolated from the serum of 50 HCC patients who provided repeated blood samples before diagnosis and 50 controls enrolled in a cancer screen program in Taiwan. Methylation-specific PCR was used to determine the methylation status of p16, p15, and ras association domain family 1A (RASSF1A). Results: Among cases, aberrant methylation was found in serum DNA 1 to 9 years before clinical HCC diagnosis. RASSF1A had the highest frequency of hypermethylation with 35 (70%) cases having at least one positive sample compared with 22 (44%) for p16 and 12 (22%) for p15. Six subjects were hypermethylation negative for all three genes. For the 50 controls, promoter hypermethylation was found in three and two subjects for RASSF1A and p16, respectively; none had methylation of p15. A receiver operating characteristic curve that included clinical risk factors (age, HBsAg status, anti–hepatitis C virus status, smoking, and alcohol status) and hypermethylation biomarkers gave an overall predictive accuracy of 89% with sensitivity and specificity 84% and 94%, respectively. Conclusions: The analysis of epigenetic changes on RASSF1A, p16, and p15 tumor suppressor genes in serum DNA may be a valuable biomarkers for early detection in populations at high risk of HCC.
Improving care of the critically ill: institutional and health-care system approaches
Authors: Derek C Angus, Nick Black
Journal: The Lancet (2004)

Institutional and health-care system approaches complement bedside strategies to improve care of the critically ill. Focusing on the USA and the UK, we discuss seven approaches: education (especially of non-clinical managers, policy-makers, and the public), organisational guidelines, performance reporting, financial and sociobehavioural incentives to health-care professionals and institutions, regulation, legal requirements, and health-care system reorganisation. No single action is likely to have sustained effect and we recommend a combination of approaches. Several recent initiatives that hold promise tie performance reporting to financial incentives. Though performance reporting has been hampered by concerns over cost and accuracy, it remains an essential component and we recommend continued effort in this area. We also recommend more public education and use of organisational guidelines, such as admission criteria and staffing levels in intensive care units. Even if these endeavours are successful, with rising demand for services and continuing pressure to control costs, optimum care of the critically ill will not be realised without a fundamental reorganisation of services. In both the USA and UK, we recommend exploration of regionalised care, akin to US state trauma systems, and greater use of physician-extenders, such as nurse practitioners, to provide enhanced access to specialist care for critical illness.
Epigenetic Downregulation of Mitogen-Activated Protein Kinase Phosphatase MKP-2 Relieves Its Growth Suppressive Activity in Glioma Cells
Authors: Anke Waha, Jörg Felsberg, Wolfgang Hartmann, Anna von dem Knesebeck, Thomas Mikeska, Stefan Joos, Marietta Wolter, Arend Koch, Pearlly S. Yan, Elmar Endl, Otmar D. Wiestler, Guido Reifenberger, Torsten Pietsch, Andreas Waha
Journal: Cancer Research (2010)

Critical tumor suppression pathways in brain tumors have yet to be fully defined. Along with mutational analyses, genome-wide epigenetic investigations may reveal novel suppressor elements. Using differential methylation hybridization, we identified a CpG-rich region of the promoter of the dual-specificity mitogen-activated protein kinase phosphatase-2 gene (DUSP4/MKP-2) that is hypermethylated in gliomas. In 83 astrocytic gliomas and 5 glioma cell lines examined, hypermethylation of the MKP-2 promoter was found to occur relatively more frequently in diffuse or anaplastic astrocytomas and secondary glioblastomas relative to primary glioblastomas. MKP-2 hypermethylation was associated with mutations in TP53 and IDH1, exclusive of EGFR amplification, and with prolonged survival of patients with primary glioblastoma. Expression analysis established that promoter hypermethylation correlated with reduced expression of MKP-2 mRNA and protein. Consistent with a regulatory role, reversing promoter hypermethylation by treating cells with 5-aza-2'-deoxycytidine increased MKP-2 mRNA levels. Furthermore, we found that glioblastoma cell growth was inhibited by overexpression of exogenous MKP-2. Our findings reveal MKP-2 as a common epigenetically silenced gene in glioma, the inactivation of which may play a significant role in glioma development.
Calcium entry via Na/Ca exchange during the action potential directly contributes to contraction of failing human ventricular myocytes
Authors: J Weisser-Thomas
Journal: Cardiovascular Research (2003)

Prolongation of the Ca2+ transient and action potential (AP) durations are two characteristic changes in myocyte physiology in the failing human heart. The hypothesis of this study is that Ca2+ influx via reverse mode Na+/Ca2+ exchanger (NCX) or via L-type Ca2+ channels directly activates contraction in failing human myocytes while in normal myocytes this Ca2+ is transported into the sarcoplasmic reticulum (SR) to regulate SR Ca2+ stores. Methods: Myocytes were isolated from failing human (n=6), nonfailing human (n=3) and normal feline hearts (n=9) and whole cell current and voltage clamp techniques were used to evoke and increase the duration of APs (0.5 Hz, 37 °C). Cyclopiazonic acid (CPA 10−6 M), nifedipine (NIF;10−6 M) and KB-R 7943 (KB-R; 3×10−6 M) were used to reduce SR Ca2+ uptake, Ca2+ influx via the L-type Ca2+ current and reverse mode NCX, respectively. [Na+]i was changed by dialyzing myocytes with 0, 10 and 20 mM Na+ pipette solutions. Results: Prolongation of the AP duration caused an immediate prolongation of contraction and Ca2+ transient durations in failing myocytes. The first beat after the prolonged AP was potentiated by 21±5 and 27±5% in nonfailing human and normal feline myocytes, respectively (P<0.05), but there was no significant effect in failing human myocytes (+5±4% vs. steady state). CPA blunted the potentiation of the first beat after AP prolongation in normal feline and nonfailing human myocytes, mimicking the failing phenotype. NIF reduced steady state contraction in feline myocytes but the potentiation of the first beat after AP prolongation was unaltered (21±3% vs. base, P<0.05). KB-R reduced basal contractility and abolished the potentiation of the first beat after AP prolongation (2±1% vs. steady state). Increasing [Na+]i shortened AP, Ca2+ transient and contraction durations and increased steady state and post AP prolongation contractions. Dialysis with 0 Na+ eliminated these effects. Conclusions: Ca2+ enters both normal and failing cardiac myocytes during the late portion of the AP plateau via reverse mode NCX. In (normal) myocytes with good SR function, this Ca2+ influx helps maintain and regulate SR Ca2+ load. In (failing) human myocytes with poor SR function this Ca2+ influx directly contributes to contraction. These studies suggest that the Ca2+ transient of the failing human ventricular myocytes has a higher than normal reliance on Ca2+ influx via the reverse mode of the NCX during the terminal phases of the AP.
Unwed Motherhood: A Continuing Problem
Authors: CORNELIA MORRISON FRIEDMAN
Journal: American Journal of Psychiatry (1972)

The author interviewed 200 unmarried women from diverse backgrounds who carried their pregnancies to term. Defective ego functioning was present in many of these women. Other factors that they had in common were repression of and denial of interest in their sexual lives and the absence of conscious worry about and failure to anticipate pregnancy.
Diagnostic Exome Sequencing in Persons with Severe Intellectual Disability
Authors: Joep de Ligt, Marjolein H. Willemsen, Bregje W.M. van Bon, Tjitske Kleefstra, Helger G. Yntema, Thessa Kroes, Anneke T. Vulto-van Silfhout, David A. Koolen, Petra de Vries, Christian Gilissen, Marisol del Rosario, Alexander Hoischen, Hans Scheffer, Bert B.A. de Vries, Han G. Brunner, Joris A. Veltman, Lisenka E.L.M. Vissers
Journal: New England Journal of Medicine (2012)

The causes of intellectual disability remain largely unknown because of extensive clinical and genetic heterogeneity.
Leukemia inhibitory factor inhibits HIV-1 replication and is upregulated in placentae from nontransmitting women
Authors: Bruce K. Patterson, Homira Behbahani, William J. Kabat, Yvonne Sullivan, Maurice R.G. O’Gorman, Alan Landay, Zareefa Flener, Nadia Khan, Ram Yogev, Jan Andersson
Journal: Journal of Clinical Investigation (2001)

The placenta may play a critical role in inhibiting vertical transmission of HIV-1. Here we demonstrate that leukemia inhibitory factor (LIF) is a potent endogenous HIV-1-suppressive factor produced locally in placentae. In vitro, LIF exerted a potent, gp130-LIFRbeta-dependent, HIV coreceptor-independent inhibition of HIV-1 replication with IC50 values between 0.1 pg/ml and 0.7 pg/ml, depending on the HIV-1 isolate. LIF also inhibited HIV-1 in placenta and thymus tissues grown in ex vivo organ culture. The level of LIF mRNA and the incidence of LIF protein-expressing cells were significantly greater in placentae from HIV-1-infected women who did not transmit HIV-1 to their fetuses compared with women who transmitted the infection, but they were not significantly different from placentae of uninfected mothers. These findings demonstrate a novel pathway for endogenous HIV suppression that may prove to be an effective immune therapy for HIV infection.
Toxicological Disruption of Signaling Homeostasis: Tyrosine Phosphatases as Targets
Authors: James M. Samet, Tamara L. Tal
Journal: The Annual Review of Pharmacology and Toxicology (2010)

The protein tyrosine phosphatases (PTPs) consist of a diverse group of enzymes whose activity opposes that of the tyrosine kinases. As such, the PTPs have critical roles in maintaining signaling quiescence in resting cells and in restoring homeostasis by effecting signal termination. Interest in these enzymes has increased in recent years following the discovery that the activity of PTPs is modulated through redox mechanisms during signaling. The molecular features that enable redox regulation of PTPs during physiological signaling also render them highly susceptible to oxidative and electrophilic inactivation by a broad spectrum of structurally disparate xenobiotic compounds. The loss of PTP activity results in a profound disregulation of protein phosphotyrosine metabolism, leading to widespread and persistent activation of signaling cascades in the cell.
Effect of oxidant air pollutants on the respiratory system: insights from experimental animal research
Authors: P Chitano, JJ Hosselet, CE Mapp, LM Fabbri
Journal: European Respiratory Journal (1995)

In the present paper, we have reviewed experimental animal studies on the effects of the two most important oxidant airborne pollutants, nitrogen dioxide and ozone, on the respiratory system. The toxic effects depend on concentration and length of exposure, and are generally similar for both oxidants, with ozone operative at lower concentrations. High doses of both oxidants cause death due to lung oedema. Exposure to sublethal levels causes functional alterations such as airflow limitation and airway hyperresponsiveness to bronchoconstrictor stimuli. These effects, which are generally reversible, are associated with epithelial injury, oedema and airway and parenchymal infiltration by inflammatory cells. Loss of cilia of airway epithelium and necrosis of type I alveolar epithelial cells are the most prominent consequences at the epithelial level. Inflammation is characterized by early neutrophilic infiltration, followed by an increased number of mononuclear cells, predominantly alveolar macrophages. After long-term exposure, whilst nitrogen dioxide causes predominantly emphysema, ozone produces mainly pulmonary fibrosis. Biochemical effects include lipid peroxidation, increased antioxidant metabolism, and alteration of enzyme activity. Nitrogen dioxide and ozone may also alter the immunological response and reduce the defence against infections, increasing the susceptibility of exposed animals to infections.
Effects of intermittent hypoxia on erythropoietin, soluble erythropoietin receptor and ventilation in humans
Authors: J.V. Brugniaux, V. Pialoux, G.E. Foster, C.T.C. Duggan, M. Eliasziw, P.J. Hanly, M.J. Poulin
Journal: European Respiratory Journal (2010)

Erythropoietin (EPO) and soluble EPO receptors (sEPOR) have been proposed to play a central role in the ventilatory acclimatisation to continuous hypoxia in mice. In this study, we demonstrated for the first time in humans (n = 9) that sEPOR is downregulated upon daytime exposure to 4 days of intermittent hypoxia (IH; 6 h·day −1 , cycles of 2 min of hypoxia followed by 2 min of reoxygenation; peak end-tidal oxygen tension ( P ET,O 2 ) 88 Torr, nadir P ET,O 2 45 Torr), thereby allowing EPO concentration to rise. We also determined the strength of the association between these haematological adaptations and alterations in the acute hypoxic ventilatory response (AHVR). We observed a nadir in sEPOR on day 2 (-70%), concomitant with the peak in EPO concentration (+50%). Following exposure to IH, tidal volume ( V T ) increased, respiratory frequency remained unchanged, and minute ventilation ( V ′ E ) was increased. There was a negative correlation between EPO and sEPOR (r = -0.261; p = 0.05), and between sEPOR and V T (r = -0.331; p = 0.02). EPO was positively correlated with V ′ E (r = 0.458; p = 0.001). In conclusion, the downregulation of sEPOR by IH modulates the subsequent EPO response. Furthermore, the alterations in AHVR and breathing pattern following IH appear to be mediated, at least in part, by the increase in EPO.