Recombinant gamma interferon induces hypertriglyceridemia and inhibits post-heparin lipase activity in cancer patients.

Animals suffering from malignancy or chronic infection develop characteristic metabolic abnormalities, including a well-defined hypertriglyceridemic state. These abnormalities have been attributed to release of one or more mediators from activated macrophages. We report that cancer patients receiving RIFN-gamma, a potent macrophage activator, at doses of greater than or equal to 0.25 mg/m2/d i.m. show marked increases in triglyceride but not in cholesterol levels (pretreatment triglyceride level of 180 +/- 190 mg/dl [mean +/- SD] vs. a day-14 level of 370 +/- 242 mg/dl, n = 23, p less than 0.001 by the paired t test). This hypertriglyceridemia was characterized by an increase in very low-density lipoproteins and a decrease in plasma post-heparin lipase activity, consistent with defective triglyceride clearance (mean pretreatment lipase level of 2.1 mumol/ml/h vs. a day-14 level of 1.2 mumol/ml/h, n = 6, p = 0.02 by the paired t test). rIFN-gamma did not directly inhibit lipoprotein lipase enzymatic activity in vitro. Other possible mechanisms of action, such as suppression of lipase by an rIFN-gamma-induced mediator released from activated macrophages, or a direct effect of interferon on lipase biosynthesis, require further investigation. Our observations provide evidence that factors produced by the immune system can regulate lipid metabolism in man

Experiences of Inpatient Bone Marrow Transplantation Nurses and Providers Using Electronic Symptom Reporting

Purpose To investigate the use of electronic patient-reported outcomes (PROs) to assess symptoms and how they can provide opportunities to clinicians to address symptoms in a timely manner to improve clinical care. As part of a larger study to evaluate whether providing standardized symptom reports to the medical team would decrease the time to treatment of reported symptoms in hematopoietic stem-cell transplant recipients, we assessed nurses’ and providers’ perceptions of electronic symptom reporting. Methods Semistructured interviews of RNs, MDs, NPs and PAs were conducted at an academic cancer center in the southeastern United States. Nurses’ and providers’ perceptions of electronic symptom reporting were explored. Interviews were audio-recorded, transcribed, and coded by two investigators to identify major themes. Results Fourteen RNs and seven providers (MDs, PAs, and NPs) participated in the interviews. Three main themes emerged from the interviews: electronic symptom reporting may improve assessment and care, integrating symptom reporting into nurse workflow presents difficulties, and there are barriers for completion of surveys. Conclusion The majority of nurses and providers believed that the inclusion of electronic symptom reporting in bone marrow transplantation inpatient units has the potential to improve care but that barriers to implementation remain

Undergraduate medical student perceptions and use of Evidence Based Medicine: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Many medical schools teach the principles of Evidence Based Medicine (EBM) as a subject within their medical curriculum. Few studies have explored the barriers and enablers that students experience when studying medicine and attempting to integrate EBM in their clinical experience. The aim of this study was to identify undergraduate medical student perceptions of EBM, including their current use of its principles as students and perceived future use as clinicians.</p> <p>Methods</p> <p>Third year medical students were recruited via email to participate in focus group discussions. Four focus groups were conducted separately across four hospital sites. All focus groups were conducted by the same facilitator. All discussions were transcribed verbatim, and analysed independently by the two authors according to the principles of thematic analysis.</p> <p>Results</p> <p>Focus group discussions were conducted with 23 third-year medical students, representing three metropolitan and one rural hospital sites. Five key themes emerged from the analysis of the transcripts: (1) Rationale and observed use of EBM in practice, (2) Current use of EBM as students, (3) Perceived use of EBM as future clinicians, (4) Barriers to practicing EBM, and (5) Enablers to facilitate the integration of EBM into clinical practice. Key facilitators for promoting EBM to students include competency in EBM, mentorship and application to clinical disciplines. Barriers to EBM implementation include lack of visible application by senior clinicians and constraints by poor resourcing.</p> <p>Conclusions</p> <p>The principles and application of EBM is perceived by medical students to be important in both their current clinical training and perceived future work as clinicians. Future research is needed to identify how medical students incorporate EBM concepts into their clinical practice as they gain greater clinical exposure and competence.</p

Chiral Polymerization in Open Systems From Chiral-Selective Reaction Rates

We investigate the possibility that prebiotic homochirality can be achieved exclusively through chiral-selective reaction rate parameters without any other explicit mechanism for chiral bias. Specifically, we examine an open network of polymerization reactions, where the reaction rates can have chiral-selective values. The reactions are neither autocatalytic nor do they contain explicit enantiomeric cross-inhibition terms. We are thus investigating how rare a set of chiral-selective reaction rates needs to be in order to generate a reasonable amount of chiral bias. We quantify our results adopting a statistical approach: varying both the mean value and the rms dispersion of the relevant reaction rates, we show that moderate to high levels of chiral excess can be achieved with fairly small chiral bias, below 10%. Considering the various unknowns related to prebiotic chemical networks in early Earth and the dependence of reaction rates to environmental properties such as temperature and pressure variations, we argue that homochirality could have been achieved from moderate amounts of chiral selectivity in the reaction rates.Comment: 15 pages, 6 figures, accepted for publication in Origins of Life and Evolution of Biosphere

Varicella-Zoster viruses associated with post-herpetic neuralgia induce sodium current density increases in the ND7-23 Nav-1.8 neuroblastoma cell line

Post-herpetic neuralgia (PHN) is the most significant complication of herpes zoster caused by reactivation of latent Varicella-Zoster virus (VZV). We undertook a heterologous infection in vitro study to determine whether PHN-associated VZV isolates induce changes in sodium ion channel currents known to be associated with neuropathic pain. Twenty VZV isolates were studied blind from 11 PHN and 9 non-PHN subjects. Viruses were propagated in the MeWo cell line from which cell-free virus was harvested and applied to the ND7/23-Nav1.8 rat DRG x mouse neuroblastoma hybrid cell line which showed constitutive expression of the exogenous Nav 1.8, and endogenous expression of Nav 1.6 and Nav 1.7 genes all encoding sodium ion channels the dysregulation of which is associated with a range of neuropathic pain syndromes. After 72 hrs all three classes of VZV gene transcripts were detected in the absence of infectious virus. Single cell sodium ion channel recording was performed after 72 hr by voltage-clamping. PHN-associated VZV significantly increased sodium current amplitude in the cell line when compared with non-PHN VZV, wild-type (Dumas) or vaccine VZV strains ((POka, Merck and GSK). These sodium current increases were unaffected by acyclovir pre-treatment but were abolished by exposure to Tetrodotoxin (TTX) which blocks the TTX-sensitive fast Nav 1.6 and Nav 1.7 channels but not the TTX-resistant slow Nav 1.8 channel. PHN-associated VZV sodium current increases were therefore mediated in part by the Nav 1.6 and Nav 1.7 sodium ion channels. An additional observation was a modest increase in message levels of both Nav1.6 and Nav1.7 mRNA but not Nav 1.8 in PHN virally infected cells

The comparative osmoregulatory ability of two water beetle genera whose species span the fresh-hypersaline gradient in inland waters (Coleoptera: Dytiscidae, Hydrophilidae).

A better knowledge of the physiological basis of salinity tolerance is essential to understanding the ecology and evolutionary history of organisms that have colonized inland saline waters. Coleoptera are amongst the most diverse macroinvertebrates in inland waters, including saline habitats; however, the osmoregulatory strategies they employ to deal with osmotic stress remain unexplored. Survival and haemolymph osmotic concentration at different salinities were examined in adults of eight aquatic beetle species which inhabit different parts of the fresh-hypersaline gradient. Studied species belong to two unrelated genera which have invaded saline waters independently from freshwater ancestors; Nebrioporus (Dytiscidae) and Enochrus (Hydrophilidae). Their osmoregulatory strategy (osmoconformity or osmoregulation) was identified and osmotic capacity (the osmotic gradient between the animal's haemolymph and the external medium) was compared between species pairs co-habiting similar salinities in nature. We show that osmoregulatory capacity, rather than osmoconformity, has evolved independently in these different lineages. All species hyperegulated their haemolymph osmotic concentration in diluted waters; those living in fresh or low-salinity waters were unable to hyporegulate and survive in hyperosmotic media (> 340 mosmol kg(-1)). In contrast, the species which inhabit the hypo-hypersaline habitats were effective hyporegulators, maintaining their haemolymph osmolality within narrow limits (ca. 300 mosmol kg(-1)) across a wide range of external concentrations. The hypersaline species N. ceresyi and E. jesusarribasi tolerated conductivities up to 140 and 180 mS cm(-1), respectively, and maintained osmotic gradients over 3500 mosmol kg(-1), comparable to those of the most effective insect osmoregulators known to date. Syntopic species of both genera showed similar osmotic capacities and in general, osmotic responses correlated well with upper salinity levels occupied by individual species in nature. Therefore, osmoregulatory capacity may mediate habitat segregation amongst congeners across the salinity gradient

Seizure control in patients with epilepsy: the physician vs. medication factors

<p>Abstract</p> <p>Background</p> <p>Little is known about the relationship between types of healthcare providers and outcomes in patients with epilepsy. This study compares the relative effects of provider type (epileptologist vs. other neurologist) and pharmacologic treatment (newer vs. older antiepileptic drugs) on seizure control in patients with epilepsy.</p> <p>Methods</p> <p>We conducted a retrospective study of patients with medication-resistant epilepsy. Consecutive charts of 200 patients were abstracted using a standard case report form. For each patient, data included seizure frequency and medication use prior to, and while being treated by an epileptologist. Changes in seizure frequency were modeled using a generalized linear model.</p> <p>Results</p> <p>After transferring care from a general neurologist to specialized epilepsy center, patients experienced fewer seizures (p < 0.001) and were more frequently seizure-free (p < 0.001). The improved seizure control was not related to treatment with newer vs. older antiepileptic drugs (p = 0.305).</p> <p>Conclusion</p> <p>Our findings suggest an association between subspecialty epilepsy care and improved seizure control in patients with medication-resistant epilepsy. Further research should prospectively determine whether patients with medication-resistant epilepsy would benefit from being routinely referred to an epilepsy specialist.</p

The Working After Cancer Study (WACS): a population-based study of middle-aged workers diagnosed with colorectal cancer and their return to work experiences

<p>Abstract</p> <p>Background</p> <p>The number of middle-aged working individuals being diagnosed with cancer is increasing and so too will disruptions to their employment. The aim of the Working After Cancer Study is to examine the changes to work participation in the 12 months following a diagnosis of primary colorectal cancer. The study will identify barriers to work resumption, describe limitations on workforce participation, and evaluate the influence of these factors on health-related quality of life.</p> <p>Methods/Design</p> <p>An observational population-based study has been designed involving 260 adults newly-diagnosed with colorectal cancer between January 2010 and September 2011 and who were in paid employment at the time they were diagnosed. These cancer cases will be compared to a nationally representative comparison group of 520 adults with no history of cancer from the general population. Eligible cases will have a histologically confirmed diagnosis of colorectal cancer and will be identified through the Queensland Cancer Registry. Data on the comparison group will be drawn from the Household, Income and Labour Dynamics in Australia (HILDA) Survey. Data collection for the cancer group will occur at 6 and 12 months after diagnosis, with work questions also asked about the time of diagnosis, while retrospective data on the comparison group will be come from HILDA Waves 2009 and 2010. Using validated instruments administered via telephone and postal surveys, data will be collected on socio-demographic factors, work status and circumstances, and health-related quality of life (HRQoL) for both groups while the cases will have additional data collected on cancer treatment and symptoms, work productivity and cancer-related HRQoL. Primary outcomes include change in work participation at 12 months, time to work re-entry, work limitations and change in HRQoL status.</p> <p>Discussion</p> <p>This study will address the reasons for work cessation after cancer, the mechanisms people use to remain working and existing workplace support structures and the implications for individuals, families and workplaces. It may also provide key information for governments on productivity losses.</p> <p>Study Registration</p> <p>Australian and New Zealand Clinical Trial Registry No. <a href="http://www.anzctr.org.au/ACTRN12611000530921.aspx">ACTRN12611000530921</a></p

Asteroseismology and Interferometry

Asteroseismology provides us with a unique opportunity to improve our understanding of stellar structure and evolution. Recent developments, including the first systematic studies of solar-like pulsators, have boosted the impact of this field of research within Astrophysics and have led to a significant increase in the size of the research community. In the present paper we start by reviewing the basic observational and theoretical properties of classical and solar-like pulsators and present results from some of the most recent and outstanding studies of these stars. We centre our review on those classes of pulsators for which interferometric studies are expected to provide a significant input. We discuss current limitations to asteroseismic studies, including difficulties in mode identification and in the accurate determination of global parameters of pulsating stars, and, after a brief review of those aspects of interferometry that are most relevant in this context, anticipate how interferometric observations may contribute to overcome these limitations. Moreover, we present results of recent pilot studies of pulsating stars involving both asteroseismic and interferometric constraints and look into the future, summarizing ongoing efforts concerning the development of future instruments and satellite missions which are expected to have an impact in this field of research.Comment: Version as published in The Astronomy and Astrophysics Review, Volume 14, Issue 3-4, pp. 217-36