Regulation of dopamine receptors in the MtT/W15 transplantable pituitary tumor by estrogen

We investigated the effects of estrogens on the regulation of dopamine receptors in the MtT/W15 transplantable rat pituitary tumor. Diethylstilbestrol (DES) and 17[beta]-estradiol treatment in female rats significantly decreased the number of dopamine binding sites (Bmax) from 85 +/- 3.9 fmol/mg protein in untreated rats to 9.2 +/- 1.2 and 8.2 +/- 2.8 fmol/mg protein in DES and 17[beta]-estradiol-treated rats, respectively, while the binding affinities (Kd) did not change significantly. Testosterone treatment did not change the Bmax, while ovariectomy resulted in a significant increase in the Bmax (146.3 +/- 6.7 fmol/mg protein). The effects of DES on the Bmax were reversible, since removal of the DES for one week before sacrificing the animals led to a marked increase in the Bmax (54.9 +/- 3.1 fmol/mg protein).Pituitaries from normal female rats treated with DES for 6 and 9 weeks had a significant decrease in the Bmax.These results show that the number of dopamine binding sites in the membranes of MtT/W15 tumors is decreased by estrogen treatment and that this effect is reversible after removal of the estrogenic stimulus.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26273/1/0000358.pd

Climate Change and invasibility of the Antarctic benthos

Benthic communities living in shallow-shelf habitats in Antarctica (<100-m depth) are archaic in their structure and function. Modern predators, including fast-moving, durophagous (skeleton-crushing) bony fish, sharks, and crabs, are rare or absent; slow-moving invertebrates are the top predators; and epifaunal suspension feeders dominate many soft substratum communities. Cooling temperatures beginning in the late Eocene excluded durophagous predators, ultimately resulting in the endemic living fauna and its unique food-web structure. Although the Southern Ocean is oceanographically isolated, the barriers to biological invasion are primarily physiological rather than geographic. Cold temperatures impose limits to performance that exclude modern predators. Global warming is now removing those physiological barriers, and crabs are reinvading Antarctica. As sea temperatures continue to rise, the invasion of durophagous predators will modernize the shelf benthos and erode the indigenous character of marine life in Antarctica

Catching Element Formation In The Act

Gamma-ray astronomy explores the most energetic photons in nature to address some of the most pressing puzzles in contemporary astrophysics. It encompasses a wide range of objects and phenomena: stars, supernovae, novae, neutron stars, stellar-mass black holes, nucleosynthesis, the interstellar medium, cosmic rays and relativistic-particle acceleration, and the evolution of galaxies. MeV gamma-rays provide a unique probe of nuclear processes in astronomy, directly measuring radioactive decay, nuclear de-excitation, and positron annihilation. The substantial information carried by gamma-ray photons allows us to see deeper into these objects, the bulk of the power is often emitted at gamma-ray energies, and radioactivity provides a natural physical clock that adds unique information. New science will be driven by time-domain population studies at gamma-ray energies. This science is enabled by next-generation gamma-ray instruments with one to two orders of magnitude better sensitivity, larger sky coverage, and faster cadence than all previous gamma-ray instruments. This transformative capability permits: (a) the accurate identification of the gamma-ray emitting objects and correlations with observations taken at other wavelengths and with other messengers; (b) construction of new gamma-ray maps of the Milky Way and other nearby galaxies where extended regions are distinguished from point sources; and (c) considerable serendipitous science of scarce events -- nearby neutron star mergers, for example. Advances in technology push the performance of new gamma-ray instruments to address a wide set of astrophysical questions.Comment: 14 pages including 3 figure

Increased versus stable doses of inhaled corticosteroids for exacerbations of chronic asthma in adults and children.

BACKGROUND: People with asthma may experience exacerbations or "attacks" during which their symptoms worsen and additional treatment is required. Written action plans may advocate doubling the dose of inhaled steroids in the early stages of an asthma exacerbation to reduce the severity of the attack and to prevent the need for oral steroids or hospital admission. OBJECTIVES: To compare the clinical effectiveness and safety of increased versus stable doses of inhaled corticosteroids (ICS) as part of a patient-initiated action plan for home management of exacerbations in children and adults with persistent asthma. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, which is derived from searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) to March 2016. We handsearched respiratory journals and meeting abstracts. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared increased versus stable doses of ICS for home management of asthma exacerbations. We included studies of children or adults with persistent asthma who were receiving daily maintenance ICS. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials, assessed quality and extracted data. We contacted authors of RCTs for additional information. MAIN RESULTS: This review update added three new studies including 419 participants to the review. In total, we identified eight RCTs, most of which were at low risk of bias, involving 1669 participants with mild to moderate asthma. We included three paediatric (n = 422) and five adult (n = 1247) studies; six were parallel-group trials and two had a cross-over design. All but one study followed participants for six months to one year. Allowed maintenance doses of ICS varied in adult and paediatric studies, as did use of concomitant medications and doses of ICS initiated during exacerbations. Investigators gave participants a study inhaler containing additional ICS or placebo to be started as part of an action plan for treatment of exacerbations.The odds of treatment failure, defined as the need for oral corticosteroids, were not significantly reduced among those randomised to increased ICS compared with those taking their usual stable maintenance dose (odds ratio (OR) 0.89, 95% confidence interval (CI) 0.68 to 1.18; participants = 1520; studies = 7). When we analysed only people who actually took their study inhaler for an exacerbation, we found much variation between study results but the evidence did not show a significant benefit of increasing ICS dose (OR 0.84, 95% CI 0.54 to 1.30; participants = 766; studies = 7). The odds of having an unscheduled physician visit (OR 0.96, 95% CI 0.66 to 1.41; participants = 931; studies = 3) or acute visit (Peto OR 0.98, 95% CI 0.24 to 3.98; participants = 450; studies = 3) were not significantly reduced by an increased versus stable dose of ICS, and evidence was insufficient to permit assessment of impact on the duration of exacerbation; our ability to draw conclusions from these outcomes was limited by the number of studies reporting these events and by the number of events included in the analyses. The odds of serious events (OR 1.69, 95% CI 0.77 to 3.71; participants = 394; studies = 2) and non-serious events, such as oral irritation, headaches and changes in appetite (OR 2.15, 95% CI 0.68 to 6.73; participants = 142; studies = 2), were neither increased nor decreased significantly by increased versus stable doses of ICS during an exacerbation. Too few studies are available to allow firm conclusions on the basis of subgroup analyses conducted to investigate the impact of age, time to treatment initiation, doses used, smoking history and the fold increase of ICS on the magnitude of effect; yet, effect size appears similar in children and adults. AUTHORS' CONCLUSIONS: Current evidence does not support increasing the dose of ICS as part of a self initiated action plan to treat exacerbations in adults and children with mild to moderate asthma. Increased ICS dose is not associated with a statistically significant reduction in the odds of requiring rescue oral corticosteroids for the exacerbation, or of having adverse events, compared with a stable ICS dose. Wide confidence intervals for several outcomes mean we cannot rule out possible benefits of this approach

Markov clustering versus affinity propagation for the partitioning of protein interaction graphs

<p>Abstract</p> <p>Background</p> <p>Genome scale data on protein interactions are generally represented as large networks, or graphs, where hundreds or thousands of proteins are linked to one another. Since proteins tend to function in groups, or complexes, an important goal has been to reliably identify protein complexes from these graphs. This task is commonly executed using clustering procedures, which aim at detecting densely connected regions within the interaction graphs. There exists a wealth of clustering algorithms, some of which have been applied to this problem. One of the most successful clustering procedures in this context has been the Markov Cluster algorithm (MCL), which was recently shown to outperform a number of other procedures, some of which were specifically designed for partitioning protein interactions graphs. A novel promising clustering procedure termed Affinity Propagation (AP) was recently shown to be particularly effective, and much faster than other methods for a variety of problems, but has not yet been applied to partition protein interaction graphs.</p> <p>Results</p> <p>In this work we compare the performance of the Affinity Propagation (AP) and Markov Clustering (MCL) procedures. To this end we derive an unweighted network of protein-protein interactions from a set of 408 protein complexes from <it>S. cervisiae </it>hand curated in-house, and evaluate the performance of the two clustering algorithms in recalling the annotated complexes. In doing so the parameter space of each algorithm is sampled in order to select optimal values for these parameters, and the robustness of the algorithms is assessed by quantifying the level of complex recall as interactions are randomly added or removed to the network to simulate noise. To evaluate the performance on a weighted protein interaction graph, we also apply the two algorithms to the consolidated protein interaction network of <it>S. cerevisiae</it>, derived from genome scale purification experiments and to versions of this network in which varying proportions of the links have been randomly shuffled.</p> <p>Conclusion</p> <p>Our analysis shows that the MCL procedure is significantly more tolerant to noise and behaves more robustly than the AP algorithm. The advantage of MCL over AP is dramatic for unweighted protein interaction graphs, as AP displays severe convergence problems on the majority of the unweighted graph versions that we tested, whereas MCL continues to identify meaningful clusters, albeit fewer of them, as the level of noise in the graph increases. MCL thus remains the method of choice for identifying protein complexes from binary interaction networks.</p

A retrospective study on the use of post-operative colonoscopy following potentially curative surgery for colorectal cancer in a Canadian province

BACKGROUND: Surveillance colonoscopy is commonly recommended following potentially curative surgery for colorectal cancer. We determined factors associated with patients undergoing a least one colonoscopy within five years of surgery. METHODS: In this historical cohort study, data on 3918 patients age 30 years or older residing in Alberta, Canada, who had undergone a potentially curative surgical resection for local or regional stage colorectal cancer between 1983 and 1995 were obtained from the provincial cancer registry, ministry of health and cancer clinic charts. Kaplan-Meier estimates of the probability of undergoing a post-operative colonoscopy were calculated for patient, tumor and treatment-related variables of interest. RESULTS: A colonoscopy was performed within five years of surgery in 1979 patients. The probability of undergoing a colonoscopy for those diagnosed in the 1990s was greater than for those diagnosed earlier (0.65 vs 0.55, P < 0.0001). The majority of the difference was seen at one-year following surgery, consistent with changes in surveillance practices. Those most likely to undergo a colonoscopy were those under age 70 (0.74 vs 0.50 for those age 70 – 79, P < 0.0001), who underwent a pre-operative colonoscopy (0.69 vs 0.54, P < 0.0001), and who underwent a resection with reanastomosis (0.62 vs 0.47 for abdominoperineal resection, P < 0.0001) by a surgeon who performs colonoscopies (0.68 vs 0.54, P < 0.0001). CONCLUSIONS: The majority of patients undergo colonoscopy following colorectal cancer surgery. However, there are important variations in surveillance practices across different patient and treatment characteristics

Study Protocol: The Behaviour and Pain in Dementia Study (BePAID)

<p>Abstract</p> <p>Background</p> <p>People with dementia admitted to the acute hospital often receive poor quality care particularly with regards to management of behavioural and psychiatric symptoms of dementia (BPSD) and of pain. There have been no UK studies on the prevalence and type of pain or BPSD in people with dementia in this setting, or on how these may impact on patients, carers, staff and costs of care.</p> <p>Methods/Design</p> <p>We shall recruit older people with dementia who have unplanned acute medical admissions and measure the prevalence of BPSD using the Behave-AD (Behaviour in Alzheimer's Disease) and the CMAI (Cohen Mansfield Agitation Inventory). Pain prevalence and severity will be assessed by the PAINAD (Pain Assessment in Advanced Dementia) and the FACES pain scale. We will then analyse how these impact on a variety of outcomes and test the hypothesis that poor management of pain is associated with worsening of BPSD.</p> <p>Discussion</p> <p>By demonstrating the costs of BPSD to individuals with dementia and the health service this study will provide important evidence to drive improvements in care. We can then develop effective training for acute hospital staff and alternative treatment strategies for BPSD in this setting.</p

How accurate appraisal of behavioral costs and benefits guides adaptive pain coping

Coping with pain is a complex phenomenon encompassing a variety of behavioral responses and a large network of underlying neural circuits. Whether pain coping is adaptive or maladaptive depends on the type of pain (e.g., escapable or inescapable), personal factors (e.g., individual experiences with coping strategies in the past), and situational circumstances. Keeping these factors in mind, costs and benefits of different strategies have to be appraised and will guide behavioral decisions in the face of pain. In this review we present pain coping as an unconscious decision-making process during which accurately evaluated costs and benefits lead to adaptive pain coping behavior. We emphasize the importance of passive coping as an adaptive strategy when dealing with ongoing pain and thus go beyond the common view of passivity as a default state of helplessness. In combination with passive pain coping, we highlight the role of the reward system in reestablishing affective homeostasis and discuss existing evidence on a behavioral and neural level. We further present neural circuits involved in the decision-making process of pain coping when circumstances are ambiguous and, therefore, costs and benefits are difficult to anticipate. Finally, we address the wider implications of this topic by discussing its relevance for chronic pain patients

Exploring the relationship between experiential avoidance, coping functions and the recency and frequency of self-harm

This study investigated the relationship between experiential avoidance, coping and the recency and frequency of self-harm, in a community sample (N = 1332, aged 16–69 years). Participants completed online, self-report measures assessing self-harm, momentary affect, experiential avoidance and coping in response to a recent stressor. Participants who had self-harmed reported significantly higher levels of experiential avoidance and avoidance coping, as well as lower levels of approach, reappraisal and emotional regulation coping, than those with no self-harm history. Moreover, more recent self-harm was associated with lower endorsement of approach, reappraisal and emotion regulation coping, and also higher levels of both avoidance coping and experiential avoidance. Higher experiential avoidance and avoidance coping also predicted increased lifetime frequency of self-harm. Conversely, increased approach and reappraisal coping were associated with a decreased likelihood of high frequency self-harm. Although some of the effects were small, particularly in relation to lifetime frequency of self-harm, overall our results suggest that experiential avoidance tendency may be an important psychological factor underpinning self-harm, regardless of suicidal intent (e.g. including mixed intent, suicidal intent, ambivalence), which is not accounted for in existing models of self-harm