tbuckley/cabot-search huggingface dataset:
Interleukin-10 (IL-10) Selectively Enhances CIS3/SOCS3 mRNA Expression in Human Neutrophils: Evidence for an IL-10–Induced Pathway That Is Independent of STAT Protein Activation
Authors: Marco A. Cassatella, Sara Gasperini, Chiara Bovolenta, Federica Calzetti, Marieke Vollebregt, Patrizia Scapini, Martina Marchi, Ritsu Suzuki, Asuka Suzuki, Akihiko Yoshimura
Journal: Blood (1999)
Drug points: Aseptic meningitis after treatment with amoxicillin
Authors: W Czerwenka, C Gruenwald, D Conen
Journal: BMJ (1999)

For 1989-96, when only one source of data was used for the denominator, the trend remained constant.What explanations are there for the increase in compulsory admissions?Firstly, these changes may be due to alterations in the presentation of patients with psychiatric disorders.For example, there is some evidence that a higher proportion of psychiatric patients misuse drugs and alcohol, and this may lead to more florid presentations of psychotic illness. 2 Secondly, changes in the availability of beds during this period may have increased the threshold for admission and decreased the threshold for discharge.Between 1982 and 1992, approximately 43 000 fewer psychiatric hospital beds were available, 3 and in inner city areas bed occupancy remains above 100% much of the time. 4he public's fear of violence by mentally ill patients and pressures to keep patients in hospital until it is "safe" to discharge them put further strain on the avail-ability of beds.Delays in admission and treatment caused by bed shortages may mean that patients' illnesses are becoming more severe and that compulsory treatment is being initiated in cases in which informal admissions would previously have been possible.These results have implications for resources in terms of costs and staffing.Compulsory admissions are more time consuming since they generally require that patients be assessed by two doctors and a social worker.Disturbed patients also require more intensive nursing and supervision.Patients admitted under the act have the right to appeal, and mental health tribunals are time consuming and costly.We suggest that the move to community care may have led to a paradoxical and unexpected increase in the use of coercion in the treatment of patients with mental illnesses.
Thalassaemia in Britain: a tale of two communities
Authors: P. S Gill, B. Modell
Journal: BMJ (1998)

General practice p 788 

The thalassaemias are recessively inherited haemoglobin disorders with profound implications for individuals, families, and health services.1 In the United Kingdom they occur mainly in certain minority ethnic communities, but prevalence varies within these communities. Around 3-10% of Indians, 4.5% of Pakistanis, 8% of Bangladeshis, 17% of Cypriots, 0.5-1% of Afro-Caribbeans, and 0.1% of the indigenous British carry thalassaemia.2 Carrier couples have a one in four chance in every pregnancy of having a child with a major thalassaemia. Unlike some other genetic disorders, the thalassaemias are common and manageable, requiring, as a minimum, regular blood transfusions and iron chelation treatment to prevent iron overload. The cost of supporting a patient from birth to 30 years is estimated at about £250 000.3 Haemoglobin disorders can be prevented by carrier screening and genetic counselling, with the option of …
Abnormal Regional Left Ventricular Systolic and Diastolic Function in Patients With Coronary Artery Disease Undergoing Percutaneous Coronary Intervention
Authors: Katsuhisa Ishii, Tamaki Suyama, Makoto Imai, Motoyoshi Maenaka, Asuka Yamanaka, Yasunaka Makino, Yutaka Seino, Kenei Shimada, Junichi Yoshikawa
Journal: Journal of the American College of Cardiology (2009)
Health needs assessment: Assessing health needs in developing countries
Authors: J. Wright, J. Walley
Journal: BMJ (1998)

This is the last in a series of six articles describing approaches to and topics for health needs assessment, and how the results can be used effectively

In most developing countries, the evolution of health services has been dominated by Western models of health care. These have rarely taken into account how local people explain illness, seek advice, or use traditional healing methods. The emphasis has been on hospitals and curative care rather than on trying to address local health needs equitably and effectively. Since the Alma Ata declaration on primary health care, more attention has been given to increasing coverage of basic services and preventing common diseases. However, the bias in resource allocation towards secondary care and urban areas remains.

#### Summary points

Timely and accurate information is essential if health services in developing countries are to meet the needs of their populations

Routine health information can provide an epidemiologically based assessment of ill health and identify what health services are needed

Community appraisals can provide valuable insight into patients' needs as well as empowering communities

Emergency health needs are similar whatever the disaster. Community involvement, good surveillance, and foresight are important

The global burden of disease can be represented by disability adjusted life years; these can help to identify international health needs

Health needs are changing and new challenges from chronic diseases and HIV infection must be faced. Better coverage of preventive and essential healthcare services has led to greater emphasis on improving the quality of health care and ensuring that the most efficient use is made of scarce resources. For example, infant mortality has fallen dramatically in the past two decades through interventions such as oral rehydration for diarrhoea and immunisation programmes. With fewer children dying there has been greater emphasis on the need to tackle the causes of infant …
Abstract 2194: Age and Double Product Reserve-Adjusted Modification of the Duke Treadmill Score Nomogram
Authors: Amir H Sadrzadeh Rafie, Frederick E Dewey, Gannon W Sungar, Euan A Ashley, David Hadley, Jonathan Myers, Victor F Froelicher
Journal: Circulation (2008)

The Duke Treadmill Score (DTS) is an established clinical tool for risk stratification from exercise testing. We aimed to determine if age and other variables could improve the prognostic power of the DTS and if so, to modify the DTS nomogram. From a total of 1959 patients referred for exercise testing at the Palo Alto VA Medical Center from 1997 to 2006, we studied 1759 male veterans (mean ± SD age, 57±12 years) free of heart failure. Double product (DP) was calculated by multiplying systolic BP and HR; variables and their products were subtracted to obtain the differences between rest and maximal exercise (reserve) and recovery. Cox survival analysis was performed for 157 all-cause and 53 (34%) cardiovascular deaths (CVD) during a follow-up of 5 years. Of all the hemodynamic measurements, DP reserve was the strongest predictor of CVD (Wald Z-score, −3.84; P&lt;0.00001) after adjustment for potential confounders. When the components of DTS were entered in the Cox hazard model with DP reserve and age, only DP reserve and age were chosen (P&lt;0.00001). Using the Cox coefficients, a score of [Age - DTS - 3 x (DP reserve/1000)] yielded AUC of 0.84 compared to 0.76 for the DTS. Using this equation, a nomogram was constructed by adding age and DP reserve to the original DTS nomogram. The point at which the modified DTS line intersects the line drawn from the Age - DTS line to the corresponding value for DP reserve/1000 indicates average annual CVD. We propose an age and DP reserve adjusted DTS nomogram that improves the prognostic estimates of average annual CVD over the DTS alone. This nomogram requires external validation and extension to women.
Cigarette smoke activates ER overload response in Z-AT mice
Authors: Sam Alam, Zhenjun Li, Ravi Mahadeva
Journal: European Respiratory Journal (2013)

Severe deficiency of the major anti-elastase α1-antitrypsin (AT) due to the Z (Glu342Lys) variant (Z-AT) is the commonest genetic reason for the development of COPD. Cigarette smoke (CS) accelerates decline in lung function in PiZZ homozygotes. We investigated whether CS exposed Z-AT is associated with activation of endoplasmic reticulum (ER) overload response (EOR; PERK, ATF4) compared to CS exposed normal AT (M-AT). Female transgenic mice (n=8) for M-AT or Z-AT were exposed to 4 1R3F cigarettes daily for 5 days. BALF and perfused lungs homogenized were assessed for lung injury/inflammation and EOR. CS Z-AT mice was compared with CS M-AT unless stated. Z-AT had significantly more lung injury than M-AT; wet:dry ratio of lungs (P=0.001), BALF total protein (P<0.001). ELISA and immunoblot showed Z-AT had significantly activated NF-κB than M-AT (P<0.001). Z-AT BALF had significantly increased secretion of TNF-α (428±23pg/ml vs. 248±31, P<0.001) and IL-6 (373±20pg/ml vs. 250±23, P=0.001) than M-AT. RT-PCR of lung tissues showed Z-AT had significantly upregulated mRNA for TNF-α (P<0.001) and IL-6 (P<0.001) than M-AT. RT-PCR also showed non-CS Z-AT when compared to non-CS M-AT had significant upregulation of PERK (1.4-fold increase, P=0.026) and ATF4 (1.5-fold increase, P=0.006). CS Z-AT when compared to CS M-AT had upregulated PERK (1.26-fold increase, P=0.010) and ATF4 (1.7-fold increase, P=0.002). In Z-AT mice CS activates EOR and inflammatory mediators. This predisposes Z-AT individuals to exaggerated lung inflammation. We postulate that ER accumulation of oxidized polymer Z-AT activates EOR; PERK-dependant NF-κB resulting in exaggerated inflammatory phenotype in Z-AT.
Psychopathological effects of solitary confinement
Authors: S Grassian
Journal: American Journal of Psychiatry (1983)

Psychopathological reactions to solitary confinement were extensively described by nineteenth-century German clinicians. In the United States there have been several legal challenges to the use of solitary confinement, based on allegations that it may have serious psychiatric consequences. The recent medical literature on this subject has been scarce. The author describes psychiatric symptoms that appeared in 14 inmates exposed to periods of increased social isolation and sensory restriction in solitary confinement and asserts that these symptoms form a major, clinically distinguishable psychiatric syndrome.
MicroRNA‐125b attenuates epithelial‐mesenchymal transitions and targets stem‐like liver cancer cells through small mothers against decapentaplegic 2 and 4
Authors: Jun‐Nian Zhou, Quan Zeng, Hai‐Yang Wang, Biao Zhang, Si‐Ting Li, Xue Nan, Ning Cao, Chun‐Jiang Fu, Xin‐Long Yan, Ya‐Li Jia, Jing‐Xue Wang, Ai‐Hua Zhao, Zhi‐Wei Li, Yan‐Hua Li, Xiao‐Yan Xie, Xiao‐Mei Zhang, Yan Dong, Ying‐Chen Xu, Li‐Juan He, Wen Yue, Xue‐Tao Pei
Journal: Hepatology (2015)

Emerging evidence suggests that epithelial‐mesenchymal transitions (EMTs) play important roles in tumor metastasis and recurrence. Understanding molecular mechanisms that regulate the EMT process is crucial for improving treatment of hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) play important roles in HCC; however, the mechanisms by which miRNAs target the EMT and their therapeutic potential remains largely unknown. To better explore the roles of miRNAs in the EMT process, we established an EMT model in HCC cells by transforming growth factor beta 1 treatment and found that several tumor‐related miRNAs were significantly decreased. Among these miRNAs, miR‐125b expression was most strongly suppressed. We also found down‐regulation of miR‐125b in most HCC cells and clinical specimens, which correlated with cellular differentiation in HCC patients. We then demonstrated that miR‐125b overexpression attenuated EMT phenotype in HCC cancer cells, whereas knockdown of miR‐125b promoted the EMT phenotype in vitro and in vivo . Moreover, we found that miR‐125b attenuated EMT‐associated traits, including chemoresistance, migration, and stemness in HCC cells, and negatively correlated with EMT and cancer stem cell (CSC) marker expressions in HCC specimens. miR‐125b overexpression could inhibit CSC generation and decrease tumor incidence in the mouse xenograft model. Mechanistically, our data revealed that miR‐125b suppressed EMT and EMT‐associated traits of HCC cells by targeting small mothers against decapentaplegic ( SMAD ) 2 and 4 . Most important, the therapeutic delivery of synthetic miR‐125b mimics decreased the target molecule of CSC and inhibited metastasis in the mice model. These findings suggest a potential therapeutic treatment of miR‐125b for liver cancer. Conclusion : miR‐125b exerts inhibitory effects on EMT and EMT‐associated traits in HCC by SMAD2 and 4. Ectopic expression of miR‐125b provides a promising strategy to treat HCC. (H epatology 2015;62:801–815)
Differential osteopontin functions: The role of osteopontin isoforms
Authors: Jason D. Coombes, Wing‐Kin Syn
Journal: Hepatology (2014)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. To the Editor: Recently, Lazaro et al.1 reported that osteopontin (OPN) is a protective factor in chronic steatohepatitis (ASH) and alcoholic hepatitis (AH). Mice were treated with a complex hybrid of alcohol and a Western diet. Intragastric alcohol feeding with an ad libitum Western diet resulted in chronic ASH, while addition of a weekly alcohol binge reproduced AH. Interestingly, Spp1–/– mice (OPN‐deficient) were not protected from either chronic ASH or AH when compared with (OPN‐replete) littermates. Instead, Spp1–/– mice accumulated more neutrophils during the alcohol binge‐AH model, and developed AH even without alcohol binges. As highlighted by Lazaro et al., the apparent discrepancies could certainly be explained, in part, by differences in models (i.e., varying degrees of severity, duration, gender).1 Such divergence have also been observed in studies using carbon tetrachloride,2 3, 5,‐diethoxycarbonyl‐1,4‐dihydrocollidine,3 as well as nonhepatic models.4 In a model of airway inflammation, OPN appears to be proinflammatory during antigenic sensitization, but antiinflammatory during secondary challenge in sensitized mice.4 Neutralizing OPN in sensitized mice led to exacerbation of disease, but suppressed disease if administered prophylactically. Similarly, in the lpr–/– model of systemic lupus erythematosus, Spp1–/– mice were protected from B‐cell activation in early disease, but exhibited enhanced lymphoproliferation and kidney disease in the latter stages.5 Hence, the course of disease and timing of treatment are important. It is more likely, however, that these variable study outcomes are related to the existence (and differential effects) of OPN isoforms. Recent studies show that the intracellular OPN isoform (iOPN) is distinct from the extracellular/soluble cytokine (sOPN).6 iOPN is differentially regulated, and is likely to display biological functions quite apart from sOPN. As both iOPN and sOPN are generated from the same messenger RNA, selective silencing of either of these isoforms is not possible: Spp1–/– mice will be deficient for both of these isoforms, while the administration of OPN neutralizing antibodies or aptamers will selectively deplete only sOPN.7 Therefore, if sOPN were to "promote" and iOPN to "protect" disease, then selective depletion of sOPN (rather than genetic silencing) will be more appropriate. Indeed, our cell culture data show that the loss of iOPN (and sOPN) (with RNAi) leads to nonidentical outcomes when compared with loss of sOPN alone (OPN‐aptamer).7 Pertinently, the loss of sOPN using OPN‐aptamers led to significant repression of fibrogenesis in three models of liver injury. Thus, it would be premature to conclude that OPN is protective in chronic ASH/AH. It would be necessary to interrogate differences between sOPN and iOPN. The administration of anti‐OPN once ASH/AH has developed is also likely to be more clinically useful.7
Abstract 13066: Effects of Fructose Containing Sugars on Lipids, Blood Pressure and Uric Acid When Consumed at Up to 90th Percentile Population Consumption Levels
Authors: Joshua Lowndes, Stephanie Sinnett, Zhiping Yu, James Rippe
Journal: Circulation (2012)

Introduction: The American Heart Association (AHA) recommended that women and men not consume more than 100 or 150 kcal/day, respectively, from added sugars. Sucrose and high fructose corn syrup (H...
Reducing prescribing of highly anticholinergic antidepressants for elderly people: randomised trial of group versus individual academic
Authors: M. E C van Eijk
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To compare the effect of individual educational visits versus group visits using academic detailing to discuss prescribing of highly anticholinergic antidepressants in elderly people. <b>Design:</b> Randomised controlled trial with three arms (individual visits, group visits, and a control arm). <b>Setting:</b> Southwest Netherlands. <b>Participants:</b> 190 general practitioners and 37 pharmacists organised in 21 peer review groups were studied using a database covering all prescriptions to people covered by national health insurance in the area (about 240 000). <b>Intervention:</b> All general practitioners and pharmacists in both intervention arms were offered two educational visits. For physicians in groups randomised to the individual visit arm, 43 of 70 general practitioners participated; in the group visit intervention arm, five of seven groups (41 of 52 general practitioners) participated. <b>Main outcome measures:</b> Numbers of elderly people (60 years) with new prescriptions of highly anticholinergic antidepressants and less anticholinergic antidepressants. <b>Results:</b> An intention to treat analysis found a 26% reduction in the rate of starting highly anticholinergic antidepressants in elderly people (95% confidence interval —4% to 48%) in the individual intervention arm and 45% (8% to 67%) in the group intervention arm. The use of less anticholinergic antidepressants increased by 40% (6% to 83%) in the individual intervention arm and 29% (—7% to 79%) in the group intervention arm. <b>Conclusions:</b> Both the individual and the group visits decreased the use of highly anticholinergic antidepressants and increased the use of less anticholinergic antidepressant in elderly people. These approaches are practical means to improve prescribing by continuing medical education.
Abstract 21207: Comprehensive Assessment of Right Ventricular-Pulmonary Arterial Coupling Predicts Outcome in Pulmonary Hypertension
Authors: Marc A Simon, Vijaya Kosaraju, Christopher Deible, Joan Lacomis, Cheryl Bunner, Michael A Mathier, Hunter C Champion
Journal: Circulation (2010)

Background: Right ventricular (RV) dysfunction confers poor prognosis in pulmonary hypertension (PH). However, predicting which patients will do poorly and when remains difficult. Hemodynamic calculations of RV-pulmonary arterial (PA) coupling have been used to explain the altered physiology in PH. We hypothesized that such measures may be of prognositic value. Methods: Patients (n=27) underwent right heart catheterization with a standard 7F fluid-filled (PA) catheter and ECG-gated multislice CT (MSCT) of the chest with IV contrast timed to opacify the RV. Tests were performed within 48 hours. RV volumes were assessed by MSCT. Primary outcome was time to death, lung transplant, or hospitalization. Cox proportional hazard ratio was calculated for each variable. Results: Patient characteristics: age 52 ± 12, 9 males, mean PA pressure range 13–79 mmHg. Mean follow-up was 827 ± 137 days. There were 3 deaths and 7 lung transplants. Several variables were predictive of outcomes but with small effect (heart rate...
Effect of excluding ICU-admission on clinical outcomes in a randomized control trial studying the effect of corticosteroids in patients hospitalized with CAP
Authors: Dominic Snijders, Casper de Graaff, Tjip van der Werf, Wim Boersma
Journal: European Respiratory Journal (2012)

Introduction: recently 2 Dutch studies were performed investigating the effect of adjunctive steroids in patients with CAP. The study of Snijders (AJRCCM 2010) showed no difference in outcome, whereas de study of Meijvis (Lancet 2011) yielded a significant reduction in Length of Stay (LOS) by one day. However the Meijvis study did not include patients admitted to the ICU.  Aim: exploring the effect of ICU admission in the Snijders study on clinical outcomes.  Results: Out of 213 patients 22 (10,3%) patients were admitted to the ICU. Clinical outcomes are shown in table 1 and fig. 1. In the non-ICU group there were more late failure in the prednisolone group than in the placebo group (17 (19.1%) patients vs 6 (5.9%), p=0.007).  Conclusions: When excluding ICU-patients prednisolone did have an impact on LOS and TTCS with an increased rate of late failures.
Changes in Quality of Life and Disease-Related Symptoms in Patients with Polycythemia Vera Receiving Ruxolitinib or Best Available Therapy: RESPONSE Trial Results
Authors: Ruben Mesa, Srdan Verstovsek, Jean-Jacques Kiladjian, Martin Griesshammer, Tamas Masszi, Simon Durrant, Francesco Passamonti, Claire N. Harrison, Fabrizio Pane, Pierre Zachee, Shui He, Mark M Jones, Shreekant Parasuraman, Jingjin Li, Isabelle Côté, Dany Habr, Alessandro M. Vannucchi
Journal: Blood (2014)
Measuring improvement in dyspnoea: Absolute or relative?
Authors: Miriam Johnson, Martin Bland, Stephen Oxberry, Amy Abernethy, David Currow
Journal: European Respiratory Journal (2014)

Background: Whether minimal clinically important differences (MCID) in chronic dyspnoea intensity should be based on absolute or relative measures is debatable. We have shown a moderate effect size of 11.2mm (0-100mm visual analogue scale[VAS]) and patient anchor MCID of 9mm VAS (Johnson et al 2013) but an MCID for relative change is unknown. We addressed both issues.  Method: Pooled data analysis from 4 clinical trials of opioids for dyspnoea (213 datasets).  1) The variability of difference of dyspnoea intensity from baseline (Dd) against baseline measure (Db) for absolute and ratio values was estimated and displayed graphically.  2) Effect size cannot be calculated for relative values, so MCID estimation used a patient anchor (blinded study arm preference).  Results: 1) Dd and Db were negatively correlated. Variability of absolute measures was uniform across baseline intensities. Variability of ratio measures was very large for low baseline dyspnoea.  2) 113 preference responses were evaluable for 93 participants. Comparison of preferred and un-preferred arm ratios showed a difference of −14.4%, and −20.5% using log ratios.  Conclusions: Uniform variation in response for absolute measures and ability to calculate effect size gives preference to absolute measures in sample size calculations. Reported outcomes should be presented as absolute  and  relative measures. The MCID in chronic dyspnoea expressed as a relative reduction is 15-20% of baseline measures.