tbuckley/cabot-search huggingface dataset:
Promotion of smoking cessation in developing countries: a framework for urgent public health interventions
Authors: A S M Abdullah, C G Husten
Journal: Thorax (2004)

The rapid rise in smoking in many developing countries will have devastating consequences; by 2030 the developing world is expected to have 7 million deaths annually from tobacco use. Many smokers express a desire to quit, but they often fail because they are addicted to tobacco. Although a number of cessation aids are now available in the developed world, their applicability and affordability in developing countries is less clear. Successful interventions will require many stakeholder groups to take action at the local, national, and international levels. We discuss smoking cessation as a means of reducing disease burden, examine factors that may limit the promotion of smoking cessation in developing countries, and propose a framework for public health action. This framework should comprise intervention with healthcare professionals, strengthening national commitment, development of a model for developing countries, changing the social acceptability of smoking, strengthening community participation, integration of smoking cessation with other healthcare services, specifying the role of healthcare professionals, development of guidelines, mobilisation of the business community, provision of financial incentives, establishing population specific smoking cessation services, increased collaboration between countries, and development of international initiatives.
Role of vaccinating poultry against avian flu
Authors: Bob Kahn
Journal: BMJ (2005)

Methodological concerns about animal facilitated therapy with dolphinsEditor-We have the following concerns with Antonioli and Reveley's study of animal facilitated depression with dolphins in the treatment of depression. 1 The study was small (30 patients), only 13 people from the animal care programme and 12 from the outdoor nature programme completing the study.The authors used a conservative measure to estimate the number of patients required for this study, and even then fell short by 17%.Single women predominated in both arms.It is difficult to fathom how clinical raters can be blinded to the treatment hypothesis.The authors did not mention the ethnic group of the participants.Only people who could go to Honduras were able to take part in this study.Most people with mild depression will not be able to take a three week holiday.The findings are not generalisable as most people would not be able to afford to go to such a location and swimming and snorkeling are not necessarily favourite pastimes.There may be a vacation bias.If the study group sponsored the three week trip to Honduras we suspect that a free three week trip to a seaside location in Latin America would in itself be a powerful antidepressant.There may be a disappointment bias.If the control group were aware of the potential to be in a group where they could interact with dolphins for two weeks before they reached Honduras, they could be disappointed in missing out.People with depression perceive disappointment more intensely.The study could have been done in a more natural and plausible setting with common pets such as dogs or cats for a fraction of the cost.
Detection of lung cancer using ion mobility spectrometry in Japan: A pilot study
Authors: Hiroshi Handa, Teruomi Miyazawa, Kei Morikawa, Teppei Inoue, Naoki Furuya, Hirotaka Kida, Hiroki Nishine, Seiichi Nobuyama, Takeo Inoue, Masamichi Mineshita, Takehiko Hiramoto
Journal: European Respiratory Journal (2012)

Background: National Lung Screening Trial (NSLT) reported screening with low-dose CT could reduce mortality from lung cancer. Breath analysis such as canine scent, electronic nose and ion mobility spectrometry (IMS) could detect volatile organic compounds (VOC).  Objectives: To detect specific VOC peaks in lung cancer then compare lung cancer and healthy subjects.  Methods: IMS coupled to a multi-capillary column (MCC/IMS) (BioScout: B&S Analytik, Dortmund, Germany) with a 95MBq β-radiation source was used to detect VOC peaks. For the Japanese market, regulations restrict 63Ni β-radiation sources to under 100MBq. Exhaled breath samples were collected at quite breathing in 30 patients with lung cancer and 13 healthy volunteers. Peaks were characterized using Visual Now 2.2 software (B&S Analytik, Dortmund, Germany).  Results: Patients included 17 adenocarcinoma, 3 squamous cell carcinoma, 6 small cell carcinoma and 4 unclassified carcinoma. Forty-seven VOC peaks were detected and 10 VOC peaks showed significant differences between lung cancer and healthy volunteers (p  Conclusions: IMS using 95MBq β-radiation source is a feasible screening test in the detection of lung cancer. In the future, IMS may detect histological types of lung cancer and molecular mutation.
Hepatocarcinogenesis Driven by GSNOR Deficiency Is Prevented by iNOS Inhibition
Authors: Chi-Hui Tang, Wei Wei, Martha A. Hanes, Limin Liu
Journal: Cancer Research (2013)

Hepatocellular carcinoma (HCC) is one of the most common and deadly human cancers and it remains poorly managed. Human HCC development is often associated both with elevated expression of inducible nitric oxide synthase (iNOS) and with genetic deletion of the major denitrosylase S-nitrosoglutathione reductase (GSNOR/ADH5). However, their causal involvement in human HCC is not established. In mice, GSNOR deficiency causes S-nitrosylation and depletion of the DNA repair protein O6-alkylguanine-DNA-alkyltransferase (AGT) and increases rates of both spontaneous and DEN carcinogen-induced HCC. Here, we report that administration of 1400W, a potent and highly selective inhibitor of iNOS, blocked AGT depletion and rescued the repair of mutagenic O6-ethyldeoxyguanosines following DEN challenge in livers of GSNOR-deficient (GSNOR(-/-)) mice. Notably, short-term iNOS inhibition following DEN treatment had little effect on carcinogenesis in wild-type mice, but was sufficient to reduce HCC multiplicity, maximal size, and burden in GSNOR(-/-) mice to levels comparable with wild-type controls. Furthermore, increased HCC susceptibility in GSNOR(-/-) mice was not associated with an increase in interleukin 6, tumor necrosis factor-α, oxidative stress, or hepatocellular proliferation. These results suggested that GSNOR deficiency linked to defective DNA damage repair likely acts at the tumor initiation stage to promote HCC carcinogenesis. Together, our findings provide the first proof of principle that HCC development in the context of uncontrolled nitrosative stress can be blocked by pharmacologic inhibition of iNOS, possibly providing an effective therapy for patients with HCC.
Binding, internalization, and hydrolysis of low density lipoprotein in long-term lymphoid cell lines from a normal subject and a patient with homozygous familial hypercholesterolemia.
Authors: Y K Ho, M S Brown, H J Kayden, J L Goldstein
Journal: The Journal of Experimental Medicine (1976)

Long-term established human lymphoid cells were shown to possess high affinity cell surface receptors for low density lipoprotein (LDL), the major cholesterol-carrying protein in human plasma. Binding of LDL to these receptors was followed by internalization of the lipoprotein and hydrolysis of its protein and cholesteryl ester components. Cultured lymphocytes from a patient with the homozygous form of familial hypercholesterolemia lacked cell surface LDL receptors and therefore failed to take up and degrade the lipoprotein with high affinity. Cultured human lymphocytes should prove useful for further studies of: (a) the relation between cholesterol metabolism and cellular function and (b) the mechanism by which LDL binding at the cell surface leads to internalization of the lipoprotein.
Long-Term Impact of Breast-Feeding on Body Weight and Glucose Tolerance in Children of Diabetic Mothers
Authors: Elke Rodekamp, Thomas Harder, Rainer Kohlhoff, Kerstin Franke, Joachim W. Dudenhausen, Andreas Plagemann
Journal: Diabetes Care (2005)

OBJECTIVE—Offspring of diabetic mothers (ODM) are at increased risk of developing overweight and impaired glucose tolerance (IGT). Recently, we observed that early neonatal ingestion of breast milk from diabetic mothers (DBM) may dose-dependently increase the risk of overweight in childhood. Here, we investigate whether DBM intake during the late neonatal period and early infancy also influences later adipogenic and diabetogenic risk in ODM. RESEARCH DESIGN AND METHODS—A total of 112 ODM were evaluated for influence of DBM ingestion during the late neonatal period (2nd–4th neonatal week) and early infancy on relative body weight (RBW) and glucose tolerance in early childhood. RESULTS—Exclusive breast-feeding was associated with increased childhood RBW (P = 0.011). Breast-fed ODM had an increased risk of overweight (odds ratio 1.98 [95% CI 1.12–3.50]). Breast-feeding duration was also positively related to childhood RBW (P = 0.004) and 120-min blood glucose during an oral glucose tolerance test (P = 0.022). However, adjustment for the DBM volume ingested during the early neonatal period, i.e., 1st week of life, eliminated all these relations with late neonatal breast-feeding and its duration. Interestingly, no relationship was observed between maternal blood glucose in the middle of the third trimester and the outcome. CONCLUSIONS—Neither late neonatal DBM intake nor the duration of breast-feeding has an independent influence on childhood risk of overweight or IGT in ODM. Therefore, the 1st week of life appears to be the critical window for nutritional programming in ODM by ingestion of maternal “diabetic” breast milk.
Electric foot shock stress-induced exacerbation of α-galactosylceramide-triggered apoptosis in mouse liver
Authors: Yoichi Chida, Nobuyuki Sudo, Junko Sonoda, Hiroshi Sogawa, Chiharu Kubo
Journal: Hepatology (2004)

Recently, liver natural killer T (NKT) cells, which are specifically stimulated by alpha-galactosylceramide (alpha-GalCer), were found to play a critical role in intrahepatic immunity to several infections and certain hepatic disorders. However, the role of psychophysical stress on NKT cell-dependent liver injury induced by alpha-GalCer still remains to be elucidated. In this study, we employed inescapable electric foot shock as the mode of psychophysical stress and evaluated its effect on alpha-GalCer-induced hepatitis. Pre-exposure of 12 hours of foot shock stress before alpha-GalCer administration significantly enhanced alpha-GalCer-triggered increase in serum alanine aminotransferase levels, followed by increases in both liver caspase-3 activity and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive hepatocytes, thus indicating that the liver NKT cell-dependent apoptotic response was exacerbated by stress. Foot shock stress also significantly increased both the number of liver NKT cells and Fas expression levels on hepatocytes. Pretreatment with RU-486, a glucocorticoid (GC) receptor antagonist, completely reversed such stress-induced enhancement of the alpha-GalCer-triggered serum alanine aminotransferase and hepatocyte Fas antigen responses. In contrast, such a reversal effect was not found in the mice pretreated with naloxone, a micro-opioid receptor antagonist, which thus suggests that an elevation of endogenous GCs, but not beta-endorphin, as responsible for such stress-induced aggravation in mouse hepatitis models. In conclusion, foot shock stress-induced elevation of endogenous GCs exacerbates alpha-GalCer-initiated hepatic apoptosis through the expansion of liver NKT cells and the up-regulation of hepatocyte Fas antigen.
Low–Estrogen Receptor–Positive Breast Cancer: The Impact of Tissue Sampling, Choice of Antibody, and Molecular Subtyping
Authors: Emad A. Rakha, Andrew H.S. Lee, Joseph Roberts, Nadia M. Villena Salinas, Zsolt Hodi, Ian O. Ellis, Jorge S. Reis-Filho
Journal: Journal of Clinical Oncology (2012)
MRI findings in soccer players with long-standing adductor-related groin pain and asymptomatic controls
Authors: Sonia Branci, Kristian Thorborg, Birthe Højlund Bech, Mikael Boesen, Michael Bachmann Nielsen, Per Hölmich
Journal: British Journal of Sports Medicine (2014)

Soccer players are commonly affected by long-standing adductor-related groin pain (ARGP), but the clinical significance of MRI findings in these athletes is largely unknown. Our aims were (1) to evaluate whether MRI findings are associated with long-standing ARGP in soccer players, (2) to assess MRI findings in asymptomatic soccer players and non-soccer playing controls.This cross-sectional study included 28 male soccer players with long-standing ARGP, 17 male asymptomatic soccer players and 20 male asymptomatic non-soccer playing athletes of matching age and athletic exposure. Participants underwent identical standardised and reliable clinical examination, and MRI scans (3 T) of the pelvis performed by a blinded observer. Images were consensus rated by three blinded radiologists according to a standardised MRI evaluation protocol. The associations between clinical adductor-related findings and pathological MRI findings were investigated with χ(2) statistics and OR.Central disc protrusion (p=0.027) and higher grades of pubic bone marrow oedema (BMO; p=0.027) were significantly more present in symptomatic players than asymptomatic players. However, up to 71% of asymptomatic soccer players displayed different positive MRI findings, and asymptomatic soccer players had significantly higher odds (OR ranging from 6.3 to 13.3) for BMO, adductor tendinopathy and degenerative changes than non-soccer players.ARGP in soccer players was associated with central disc protrusion and higher grades of pubic BMO. Moreover, positive MRI findings were significantly more frequent in soccer players compared with non-soccer players irrespective of symptoms, suggesting that these MRI changes may be associated with soccer play itself rather than clinical symptoms.
S140 Gdf-15 Down-regulation Of Muscle Microrna Drives Increased Sensitivity To Tgf- Signalling; A Novel Mechanism In Intensive Care Unit Acquired Weakness
Authors: S. Bloch, J. Lee, T. Syburrah, U. Rosendahl, P. Kemp, M. Griffiths, M. Polkey
Journal: Thorax (2014)

<h3>Introduction</h3> Intensive care unit acquired weakness (ICUAW) is common and associated with significant morbidity. We previously identified GDF-15, a TGF-β super-family member, as a potential driver of acute muscle wasting in a novel human model of ICUAW (Crit Care Med 2013;2013;41:982). In the current study we investigated the potential mechanisms by which GDF-15 may contribute to the development of ICUAW. Dysregulation of muscle microRNAs has been described in muscle disorders. MicroRNAs are essential for muscle homeostasis and their expression can be influenced by inflammatory cytokines. Furthermore muscle microRNAs may down-regulate TGF-β signalling. However, the function of microRNAs in ICUAW has not previously been described. We hypothesised that down-regulation of muscle microRNAs, driven by GDF-15, would lead to increased sensitivity to TGF-β signalling in muscle of patients with ICUAW. <h3>Methods</h3> We conducted an observational study of 20 patients with ICUAW and 7 elective surgical controls. Subjects underwent rectus femoris muscle biopsy and blood sampling. Muscle specimens were examined for mRNA and microRNA expression of target genes by qPCR. Plasma samples were tested for GDF-15 concentration (ELISA). Histology samples were stained for pSMAD2/3 nuclear positivity. To examine the effects of GDF-15 on target genes, differentiated C2C12 myotubes were treated with GDF-15 for 4 days. The effect of over-expression of miR-181a in C2C12 myoblasts on TGF-β signalling was also examined. <h3>Results</h3> Compared with controls, patients with ICUAW had greater GDF-15 mRNA expression in muscle (median 2-fold higher; p = 0.006) and concentration in plasma (median 7239 <i>vs.</i> 2454 pg/ml; p = 0.001). MicroRNAs involved in muscle homeostasis were significantly lower in muscle from patients with ICUAW. Both log[GDF-15 mRNA] and log[plasma GDF-15] were significantly negatively correlated with log[microRNA expression]. GDF-15 treatment of myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated expression of muscle microRNAs. miR-181a suppressed TGF-β responses in myoblasts, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this, nuclear phospho-SMAD2/3 and CYR61 mRNA expression were increased in ICUAW muscle. <h3>Discussion</h3> By suppressing expression of muscle microRNAs GDF-15 may increase sensitivity to TGF-β signalling, thus promoting muscle wasting in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets in ICUAW.
Deficits in Hippocampal and Anterior Cingulate Functioning During Verbal Declarative Memory Encoding in Midlife Major Depression
Authors: J. Douglas Bremner, Meena Vythilingam, Eric Vermetten, Viola Vaccarino, Dennis S. Charney
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Prior studies showed that subjects with major depression have deficits in hippocampal-based verbal declarative memory (e.g., recall of a paragraph) and in hippocampal and prefrontal cortical functioning and structure. The purpose of the present study was to assess hippocampal and prefrontal functioning during performance of a verbal declarative memory task in subjects with midlife major depression. METHOD: Subjects with midlife major depression (N=18) and healthy subjects (N=9) underwent positron emission tomography imaging during a control task and verbal encoding of a paragraph. RESULTS: During the verbal memory encoding task the comparison subjects, but not the subjects with depression, activated the right hippocampus and prefrontal cortex (anterior cingulate), as well as the cuneus and cerebellum. CONCLUSIONS: These results are consistent with a failure of hippocampal and anterior cingulate activation in depression, and they support the hypothesis of deficits in hippocampal and anterior cingulate functioning in depression.
Randomised controlled trial of lactulose versus rifaximin for prophylaxis of hepatic encephalopathy in patients with acute variceal bleed
Authors: Sudhir Maharshi, Barjesh Chander Sharma, Siddharth Srivastava, Amit Jindal
Journal: Gut (2014)

We read with interest the article by Peter Ferenci1 on the diagnosis of minimal hepatic encephalopathy (HE), still a challenge, and Goldbecker et al 2 on the comparison of the most favoured methods for the diagnosis of HE in liver transplantation candidates. Identification and treatment of the precipitating factors are the primary therapeutic option for HE. Variceal bleed seen in 25%–30% of patients with cirrhosis is an important precipitating factor for development of HE, and associated with increased morbidity and mortality.3 ,4 Acute variceal bleed (AVB) is an important precipitating factor for development of HE. There is a role of lactulose for prophylaxis of HE after AVB;5 however, there are no data on the role of rifaximin for prophylaxis of HE after AVB. We performed this study to compare the efficacy of lactulose versus rifaximin for prophylaxis of HE after AVB in …
Association of Epigenetic Inactivation of <b> <i>RASSF1A</i> </b> with Poor Outcome in Human Neuroblastoma
Authors: Qiwei Yang, Peter Zage, David Kagan, Yufeng Tian, Roopa Seshadri, Helen R. Salwen, Shuqing Liu, Alexandre Chlenski, Susan L. Cohn
Journal: Clinical Cancer Research (2004)

To investigate the prevalence and potential clinical significance of epigenetic aberrations in neuroblastoma (NB). The methylation status of 11 genes that are frequently epigenetically inactivated in adult cancers was assayed in 13 NB cell lines. The prevalence of RASSF1A and TSP-1 methylation was also analyzed in 56 NBs and 5 ganglioneuromas by methylation-specific PCR. Associations between the methylation status of RASSF1A and TSP-1 and patient age, tumor stage, tumor MYCN status, and patient survival were evaluated. Epigenetic changes were detected in all 13 NB cell lines, although the pattern of gene methylation varied. The putative tumor suppressor gene RASSF1A was methylated in all 13 cell lines, and TSP-1 and CASP8 were methylated in 11 of 13 cell lines. Epigenetic changes of DAPK and FAS were detected in only small numbers of cell lines, whereas none of the cell lines had methylation of p16, p21, p73, RAR-beta2, SPARC, or TIMP-3. RASSF1A was also methylated in 70% of the primary NB tumors tested, and TSP-1 methylation was detected in 55% of the tumors. RASSF1A methylation was significantly associated with age >1 year (P < 0.01), high-risk disease (P < 0.016), and poor survival (P < 0.001). In contrast, no association between TSP-1 methylation and prognostic factors or survival was observed. Our results suggest that epigenetic inactivation of RASSF1A may contribute to the clinically aggressive phenotype of high-risk NB.
Curcumin Disrupts the Mammalian Target of Rapamycin-Raptor Complex
Authors: Christopher S. Beevers, Long Chen, Lei Liu, Yan Luo, Nicholas J.G. Webster, Shile Huang
Journal: Cancer Research (2009)

Curcumin (diferuloylmethane), a polyphenol natural product of the plant Curcuma longa, is undergoing early clinical trials as a novel anticancer agent. However, the anticancer mechanism of curcumin remains to be elucidated. Recently, we have shown that curcumin inhibits phosphorylation of p70 S6 kinase 1 (S6K1) and eukaryotic initiation factor 4E (eIF4E) binding protein 1 (4E-BP1), two downstream effector molecules of the mammalian target of rapamycin complex 1 (mTORC1) in numerous cancer cell lines. This study was designed to elucidate the underlying mechanism. We observed that curcumin inhibited mTORC1 signaling not by inhibition of the upstream kinases, such as insulin-like growth factor 1 receptor (IGF-IR) and phosphoinositide-dependent kinase 1 (PDK1). Further, we found that curcumin inhibited mTORC1 signaling independently of protein phosphatase 2A (PP2A) or AMP-activated protein kinase AMPK-tuberous sclerosis complex (TSC). This is evidenced by the findings that curcumin was able to inhibit phosphorylation of S6K1 and 4E-BP1 in the cells pretreated with PP2A inhibitor (okadaic acid) or AMPK inhibitor (compound C), or in the cells expressing dominant-negative (dn) PP2A, shRNA to PP2A-A subunit, or dn-AMPKalpha. Curcumin did not alter the TSC1/2 interaction. Knockout of TSC2 did not affect curcumin inhibition of mTOR signaling. Finally, we identified that curcumin was able to dissociate raptor from mTOR, leading to inhibition of mTORC1 activity. Therefore, our data indicate that curcumin may represent a new class of mTOR inhibitor.