tbuckley/cabot-search huggingface dataset:
Abstract 3804: CPA-7, an inhibitor of STAT3, is a potent tumoricidal agent in peripheral tumor models and is impermeable to the CNS
Authors: Hikmat Assi, Chris Paran, Jon Savakus, James Hoeschle, Leda Raptis, Pedro R. Lowenstein, Maria G. Castro
Journal: Cancer Research (2014)

Abstract Analogues of the prototypical cancer drug cisplatin number by the hundreds with variable effects on DNA and signal transduction. Of these compounds, CPA-7 has been shown to elicit potent tumoricidal activity by preferentially targeting STAT3 in transformed cells. In this study, we characterized the response of rodent and human glioma cells to STAT3 inhibition by CPA-7. In addition, we determined if CPA-7 administration is sufficient for the induction of tumor regression in intracranial and peripheral mouse tumor models. Cultured glioma cells treated with CPA-7 ceased to proliferate and underwent apoptosis. Induction of apoptosis was associated with reduction of phosphorylated STAT3 and downstream transcriptional products such as cyclin D, survivin, and Bcl-xl. Although CPA-7 inhibits STAT3 preferentially, we observed an inhibition of STAT1 at doses higher than 30uM. Furthermore, mice bearing GL26 flank tumors underwent complete tumor regression in response to CPA-7 administration. This potent therapeutic effect of CPA-7 could not be duplicated in mice bearing intracranial GL26 brain tumors as that group became moribund at the same time as vehicle treated mice. Western blot and immunohistochemistry analysis of tumors isolated from CPA-7 treated mice demonstrated a reduction of phosphorylated STAT3 in peripheral but not intracranial tumors. This data suggests that CPA-7 is impermeable to the brain as a consequence of its molecular structure. Permeability measurements of CPA-7 using the PAMPA assay support this notion. These observations were corroborated in the B16-f0 and B16-f10 mouse melanoma models. Inhibition of STAT3 has been shown to be an effective strategy at inducing tumor regression in multiple cancer types. Although the discovery of effective and specific inhibitors has been limited, we believe that CPA-7 is a compound with potential therapeutic activity for peripheral solid tumors and warrants further evaluation and pharmacological characterization. Supported by NIH/NINDS Citation Format: Hikmat Assi, Chris Paran, Jon Savakus, James Hoeschle, Leda Raptis, Pedro R. Lowenstein, Maria G. Castro. CPA-7, an inhibitor of STAT3, is a potent tumoricidal agent in peripheral tumor models and is impermeable to the CNS. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3804. doi:10.1158/1538-7445.AM2014-3804
The Aftermath of Road Accidents, by Mitchell
Authors: I. Higginson
Journal: BMJ (1997)

Mitchell Routledge, £45, pp 256 ISBN 0 415 13052 2

Since I narrowly escaped injury in a serious car crash four years ago, my back seat driving has been on a par with my mother's. Such anxieties are not the only lasting effect, and the intensity of the flashbacks still surprises me. Psychological sequelae were an aspect of road accidents I had never really considered until I personally experienced them.

The psychological and social consequences of road crashes have been poorly studied, especially in populations not attending hospital. The Aftermath of Road …
Different side effect profiles of risperidone and clozapine in 20 outpatients with schizophrenia or schizoaffective disorder: a pilot study
Authors: D G Daniel, T E Goldberg, D R Weinberger, J E Kleinman, D Pickar, L J Lubick, T S Williams
Journal: American Journal of Psychiatry (1996)

The purpose of this study was to compare the side effect +profiles of clozapine and risperidone.The subjects were 20 outpatients with schizophrenia or schizoaffective disorder who were clinically stable on a regimen of clozapine at the time of screening. They underwent a randomized-order crossover comparison of 6 weeks of risperidone treatment and 6 weeks of clozapine treatment. Clinical and neurocognitive variables were assessed by raters blind to medication status, and severity of side effects was determined from patients' self-reports.Side effect measures, but not clinical ratings, were significantly different after 6 weeks of treatment with the two drugs. Patients required more benztropine for motor effects and complained of more insomnia with risperidone and more sedation with clozapine. Body weight was higher at the end of clozapine treatment than at the end of risperidone treatment.In this exploratory study, the side effect profiles of clozapine and risperidone were consistent with the different pharmacodynamic profiles of the two drugs.
Audit of the impact of introducing exhaled nitric oxide (FENO) monitoring to an adult asthma clinic in a district general hospital
Authors: Alfred Wong, Donna Orr, Louise MacKay, Gareth Davies, Lynda Howieson, Andrew Smith
Journal: European Respiratory Journal (2011)

Background: FENO can assist in diagnosis of asthma and enhanced optimization of inhaled corticosteroid (ICS) therapy.

Methods: Data for the first 67 patients to undergo FENO testing with NiOX MINO in a secondary care adult asthma clinic were collected. ICS doses are expressed as mean±SD daily beclomethasone or equivalent.

Results: FENO was performed in 17 patients undergoing diagnostic workup for asthma. The need for histamine challenge testing was prevented in 10 patients with normal spirometry and FENO; six patients were subsequently discharged who would otherwise have required followed up. Of the 50 patients with asthma receiving ICS, FENO was high (>45ppb) in 15, intermediate (25-45ppb) in 8 and normal (<25ppb) in 27. FENO altered decision-making in 22 (44%) patients by permitting a reduction (n=3) or maintenance (n=12) in ICS in patients who would otherwise have had their dose increased, and a reduction in 7 patients who would have had their ICS dose maintained. There was more appropriate matching of ICS dose changes to FENO, with a reduction in ICS dose in patients with normal FENO (1603±874μg to 1381±926μg; p=0.017), no change in the intermediate FENO group (1738±639μg to 1800±513μg; p=0.35), and an increased dose in the high FENO group (2140±767μg to 2733±683μg; p=0.007).

Conclusions: In almost half of patients tested, FENO prevented the need for a) bronchial challenge testing in patients undergoing diagnostic workup for asthma and b) permitted reduction in overall steroid burden in patients receiving ICS compared to a conventional approach. Patients will be followed to see what impact FENO has on overall asthma control and steroid dose burden.
Abstract 56: Prognosis of Patients with Acute Myocardial Infarction by Hospital Discharge Diagnosis
Authors: Emily B Levitan, Olusola T Olubowale, Christopher Gamboa, Todd M Brown, Paul Muntner, J D Rhodes, Monika M Safford
Journal: Circulation (2014)

Background: Research on acute myocardial infarction (AMI) in medical claims largely focuses on hospitalizations where AMI is the primary discharge diagnosis (dx). Limited data are available on AMIs occurring as a secondary dx during hospitalization. Hypothesis: We hypothesized that mortality following AMI is higher when the primary dx is not AMI. Methods: We examined REasons for Geographic And Racial Differences in Stroke (REGARDS) study participants with definite or probable AMIs adjudicated using published guidelines. Participants were categorized by hospital discharge dx from the discharge summary: primary dx, secondary dx, or no dx of AMI. All-cause and cardiovascular mortality after AMI, detected though active follow-up and the National Death Index, were compared using Kaplan-Meier curves with log-rank tests and Cox proportional hazard models adjusted for sociodemographics, medical history, and characteristics of the AMI (clinical evidence of ischemia, peak troponin, and heart failure during hospitalization). Results: Of 877 participants with AMI, 37% had AMI as primary dx, 12% had AMI as a secondary dx, and 51% had no dx of AMI. All-cause mortality (n = 284) was higher among participants with AMI as a secondary dx or without a dx of AMI than among participants with AMI as primary dx, but cardiovascular mortality (n = 150) was similar across groups ( Figure ). Compared to participants with AMI as primary dx, adjusted hazard ratios for all-cause mortality were 1.03 (95% CI 0.68-1.57) and 1.17 (95% CI 0.84-1.62) and for cardiovascular mortality were 0.79 (95% CI 0.46-1.37) and 0.91 (95% CI 0.60-1.38) for participants with AMI as a secondary dx and without a dx of AMI, respectively. Conclusions: Studies of AMI based on primary discharge dx likely under count the number of AMIs and exclude a population with similar prognosis in terms of all-cause and CVD mortality, once clinical differences considered. Further study into the characteristics, in-hospital and post-discharge management of these patients may be warranted.
Potential for using a hermetically-sealed, positive-pressured isocage system for studies involving germ-free mice outside a flexible-film isolator
Authors: Jisun Paik, Olesya Pershutkina, Stacey Meeker, Jaehun J Yi, Susan Dowling, Charlie Hsu, Adeline M Hajjar, Lillian Maggio-Price, David A C Beck
Journal: Gut Microbes (2015)

Germ-free mice are used to examine questions about the role of the gut microbiota in development of diseases. Generally these animals are maintained in semi-rigid or flexible-film isolators to ensure their continued sterility or, if colonized with specific microbiota, to ensure that no new species are introduced. Here, we describe the use of a caging system in which individual cages are hermetically sealed and have their own filtered positive airflow. This isopositive caging system requires less space and reduces animal housing costs. By using strict sterile techniques, we kept mice germ-free in this caging system for 12 weeks. We also used this caging system and approach to conduct studies evaluating a) the stability of the microbiome in germ-free mice receiving a fecal transplant and b) the stability of dietary-induced microbiota changes in fecal-transplanted mice. As has been shown in fecal transfer studies in isolators, we found that the transferred microbiota stabilizes as early as 2 weeks post transfer although recipient microbiota did not completely recapitulate those of the donors. Interestingly, we also noted some sex effects in these studies indicating that the sex of recipients or donors may play a role in colonization of microbiota. However, a larger study will be needed to determine what role, if any, sex plays in colonization of microbiota. Based on our studies, an isopositive caging system may be utilized to test multiple donor samples for their effects on phenotypes of mice in both normal and disease states even with limited available space for housing.
Hydrogels: Properties, Preparation, Characterization and Biomedical, Applications in Tissue Engineering, Drug, Delivery and Wound Care
Authors: Mohammad Sirousazar, Mehrdad Forough, Khalil Farhadi, Yasaman Shaabani, Rahim Molaei
Journal: Advanced Healthcare Materials (2014)

This chapter contains sections titled: Introduction Types of Hydrogels Properties of Hydrogels Preparation Methods of Hydrogels Characterization of Hydrogels Biomedical Applications of Hydrogels Hydrogels for Wound Management Recent Developments on Hydrogels Conclusions
Abstract 13079: Synergistic Effect of Human Cardiac Stem Cells and Bone Marrow Mesenchymal Stem Cells to Reduce Infarct Size and Restore Cardiac Function
Authors: Adam R Williams, Konstantinos E Hatzistergos, Decio Carvalho, Viky Suncion, Fred McCall, Jacques P Mather, Azorides R Morales, Mark A Sussman, Jose Da Silva, Alan W Heldman, Joshua M Hare
Journal: Circulation (2011)

Adam R Williams, 2011 Finalist and Presenting Author
The RDoC framework: facilitating transition from ICD/DSM to dimensional approaches that integrate neuroscience and psychopathology
Authors: Bruce N. Cuthbert
Journal: World Psychiatry (2014)

In 2008, the National Institute of Mental Health (NIMH) included in its new Strategic Plan the following aim: "Develop, for research purposes, new ways of classifying mental disorders based on dimensions of observable behavior and neurobiological measures". The implementation of this aim was named the Research Domain Criteria project, or RDoC. RDoC is a programmatic initiative that will fund grants, contracts, early-phase trials, and similar activities for the purpose of generating studies to build a research literature that can inform future versions of psychiatric nosologies based upon neuroscience and behavioral science rather than descriptive phenomenology. RDoC departs markedly from the DSM and ICD processes, in which extensive workgroup meetings generate final and finely-honed sets of diagnoses that are modified in field tests only if problems with clinical utility arise. Rather, in keeping with its provenance as an experimental system, the RDoC provides a framework for conducting research in terms of fundamental circuit-based behavioral dimensions that cut across traditional diagnostic categories. While an important aim of the project is to validate particular dimensions as useful for eventual clinical work, an equally important goal is to provide information and experience about how to conceive and implement such an alternative approach to future diagnostic practices that can harness genetics and neuroscience in the service of more effective treatment and prevention. This paper summarizes the rationale for the RDoC project, its essential features, and potential methods of transitioning from DSM/ICD categories to dimensionally-oriented designs in research studies.
Stethoscopes: Are we doing enough to reduce healthcare-associated infections?
Authors: Sarah Boot, Alison Gill, Kate Williams
Journal: European Respiratory Journal (2013)

Background: The national drive to reduce the number of healthcare-associated infections (HCAI) and the importance of hand decontamination with hand-washing and alcohol gel, are well established. Studies have shown that bacterial contamination of stethoscopes is common and that regular cleaning can reduce the potential for cross-infection. Yet little emphasis is placed on cleaning a piece of equipment that has direct contact with all patients examined.

Method: All ‘source isolation’ rooms on 7 wards (Respiratory, CF, Respiratory HDU, Elderly & General Medicine) were investigated for the presence of a single patient use stethoscope in accordance with local recommendations. Four respiratory ward rounds (n=52 patients) were observed and doctors were surveyed as to when they last cleaned their stethoscopes.

Results: Only the CF unit and respiratory HDU achieved 100% compliance, with a stethoscope next to every bedside. Respiratory medicine performed poorly and less well than both general medicine and elderly medicine (53% vs 67%).

No doctor (n=25) reported cleaning their stethoscope after every use or even every day as recommended.

Observing the ward rounds a doctor was observed cleaning their stethoscope with soap and water, as opposed to with alcohol as recommended. In three cases the patient’s stethoscope was not used in preference to the doctor’s own. Alcohol wipes were not utilised by any doctor.

Conclusion: This audit demonstrates that standards are not being met and this may result in transmission of HCAIs. The impact of the ‘bare below elbows’ and ‘wash you hands’ policies on levels of MRSA has been significant so improving staff knowledge of this potential contaminant is vital.
Abstract 11530: Age-Specific Differences Between Conventional and Ambulatory Daytime Blood Pressure Values
Authors: David Conen, Stefanie Aeschbacher, Lutgarde Thijs, Yan Li, José Boggia, Kei Asayama, Tine W Hansen, Masahiro Kikuya, Kristina Björklund-Bodegård, Takayoshi Ohkubo, Jørgen Jeppesen, Yu-Mei Gu, Christian Torp-Pedersen, Eamon Dolan, Tatiana Kuznetsova, Katarzyna Stolarz-Skrzypek, Valérie Tikhonoff, Tobias Schoen, Sofia Malyutina, Edoardo Casiglia, Yuri Nikitin, Lars Lind, Edgardo Sandoya, Kalina Kawecka-Jaszcz, Luis Mena, Gladys E Maestre, Jan Filipovsky, Yutaka Imai, Eoin O’Brien, Ji-Guang Wang, Lorenz Risch, Jan A Staessen
Journal: Circulation (2014)

Introduction: Mean daytime ambulatory blood pressure (ABP) values are considered to be lower than conventional BP (CBP) values, but data on this relation among younger individuals &lt;50 years are scarce. To address this issue, we performed a collaborative analysis in a large group of participants representing a wide age range. Methods: CBP and 24-hour ABP were measured in 9550 individuals not taking BP lowering treatment from 13 population based cohorts. We compared the individual differences between daytime ABP and CBP according to 10-year age categories. Age-specific prevalences of white-coat hypertension and masked hypertension were calculated based on guideline-recommended thresholds. Results: Among individuals aged 18-30, 30-40 and 40-50 years, mean daytime systolic and diastolic ABP were significantly higher than the corresponding CBP (6.0, 5.2 and 4.7 mmHg for systolic BP; 2.5, 2.7 and 1.7 mmHg for diastolic BP, all p&lt;0.0001) (Figure). Systolic and diastolic BP indices were similar in participants aged 50-60 years (p=0.20 and 0.11, respectively). In individuals aged 60-70 and ≥70 years, CBP was significantly higher than daytime ABP (5.0 and 13.0 mmHg for systolic BP; 2.0 and 4.2 mmHg for diastolic BP, all p&lt;0.0001) (Figure). Accordingly, the prevalence of white coat hypertension exponentially increased from 2.2% to 19.5% from those aged 18-30 years to those aged ≥70 years, with some variation between men and women (prevalence 8.0% versus 6.1%, p=0.0003). Masked hypertension was more prevalent among men (21.1% versus 11.4%, p&lt;0.0001). The age-specific prevalence of masked hypertension was 18.2%, 27.3%, 27.8%, 20.1% 13.6% and 10.2% in men, and 9.0%, 9.9%, 12.2%, 11.9%, 14.7% and 12.1% in women. Conclusions: In this large collaborative analysis we found that the relation between daytime ABP and CBP strongly varies by age. These findings may have important implications for the diagnosis of hypertension and its subtypes in clinical practice.
Abstract 3988: The omega-3 fatty acids DHA and EPA inhibit medulloblastoma growth
Authors: Linda M. Ljungblad, Malin Wickström, John-Inge Johnsen, Per Kogner, Helena Gleissman
Journal: Cancer Research (2014)

Abstract Background/Aim: Docosahexaenoic acid (DHA) and eicosapentaenic acid (EPA) are two essential omega-3 polyunsaturated fatty acid that have been shown to exert antitumoral effects in several cancer types, both in vitro and in vivo. DHA has also been shown to protect neural cells from apoptosis and is of importance in the maintenance of normal brain development and function. Medulloblastoma (MB) is the most common malignant brain tumor in children with a poor 5-year survival of only 50-60%. It is a highly invasive embryonal neuroepithelial tumor that arises in the cerebellum and has a tendency to disseminate throughout the CNS early in its course. Multimodal treatment is always necessary in the form of surgery, radiotherapy and chemotherapy. However, treatment for this disease often results in significant endocrinological and intellectual sequelae. The neuroprotective and antitumoral properties of omega-3 fatty acids could therefore be of great benefit in this patient group. Here we aim to investigate the effect of DHA and EPA in medulloblastoma. Methods: Cytotoxic activity of DHA and EPA was studied in cell viability assay in a panel of medulloblastoma cell lines. The molecular mechanisms were characterized using cell- and molecular biology techniques. Results: By adding different concentrations of DHA and EPA we could demonstrate IC50s ranging between 1.9 and 46 µM for DHA and 3.8 and 68 µM for EPA in the six examined medulloblastoma cell lines. All cell lines showed greater sensitivity for DHA than EPA. Preliminary data showed that treatment with DHA inhibited the prostaglandin E2 production in medulloblastoma cells, indicating a possible mechanism of action. Conclusions: Medulloblastoma cells are highly sensitive to omega-3 induced toxicity. Previous studies have showed that DHA can protect neurons from apoptosis. Therefore, omega-3 fatty acids are good candidates for improving medulloblastoma therapy by acting as both “sword and shield” by killing off cancer cells while protecting healthy neurons from therapy induced toxicity, thus possibly both inhibiting tumor growth and reducing the sequelae associated with other modes of brain tumor treatment. Citation Format: Linda M. Ljungblad, Malin Wickström, John-Inge Johnsen, Per Kogner, Helena Gleissman. The omega-3 fatty acids DHA and EPA inhibit medulloblastoma growth. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3988. doi:10.1158/1538-7445.AM2014-3988
GPs demand that the government cut their workload
Authors: Zosia Kmietowicz
Journal: BMJ (2001)

GPs applauded their leader this week for highlighting the crisis in the profession and pledging to fight for better working conditions in the coming months.

Dr John Chisholm, chairman of the BMA's General Practitioners Committee (GPC), received a standing ovation and rapturous applause after he delivered his keynote speech to the annual conference of representatives of local medical committees in London. In particular, the GPC leadership was praised for carrying out its recent ballot of the United Kingdom's 36 000 GPs, more than half of whom said they would consider resigning from their current NHS contracts if things had not improved by next April.

“The results [of the ballot] give politicians an incontrovertible message,” said Dr Chisholm. He continued: “It is essential that the new Westminster government takes urgent steps to begin to reduce GP workload and to improve GP recruitment-that it moves beyond its previous failure to understand and act upon the serious problems we face-for the results of the ballot give the GPC's negotiators a clear negotiating mandate: a mandate to secure improvement for our patients and our colleagues. The government cannot and will not be allowed to ignore the overwhelming ‘yes’ ballot.”

However, …
Abstract ES8-3: Epigenetic heterogeneity in cancer
Authors: Kornelia Polyak
Journal: Cancer Research (2015)

Abstract Heterogeneity of cancer cells within tumors is a major challenge in clinical oncology as it underlies tumor progression and therapeutic resistance. Cancer cells can have varying genotypes, epigenetic states such as DNA methylation and chromatin patterns, and phenotypes. The high frequency of somatic mutations in genes encoding for epigenetic regulators and transcription factors in breast cancer highlight the importance of perturbed epigenetic programs in breast tumorigenesis. Some forms of epigenetic heterogeneity within tumors is due to variability for cellular differentiation states such as luminal and basal features, whereas other forms reflect transient cellular states sometimes triggered by microenvironmental signals. Cellular epigenetic heterogeneity within tumors thought to play key roles in metastatic progression and therapeutic resistance. Thus, its better understanding and our ability to modulate it are critical for the design of more effective cancer treatment strategies. In contrast to genetic alterations, epigenetic states are reversible and due to intense research in this area, the number of compounds for their modulation is rapidly increasing. Because epigenetic modulators likely to work best in combination with other agents, the design of clinical trials testing their efficacy requires novel approaches. Citation Format: Kornelia Polyak. Epigenetic heterogeneity in cancer [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr ES8-3.