Intra-arterial 5-bromo-2-deoxyuridine (BUR) radiosensitization with external beam radiation in rhesus monkeys: A toxicity study

A primate toxicity study was performed to test the hypothesis that BUdR does not increase the likelihood of unilateral or bilateral central nervous system damage secondary to radiation therapy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45393/1/11060_2004_Article_BF00177431.pd

Comparison of Airway Intubation Devices When Using a Biohazard Suit: A Feasibility Study

OBJECTIVES: We set out to compare emergency medicine residents\u27 intubating times and success rates for direct laryngoscopy (DL), GlideScope-assisted intubation (GS), and the Supraglottic Airway Laryngopharyngeal Tube (SALT) airway with and without biohazard gear. METHODS: Each resident passed through 2 sets of 3 testing stations (DL, GS, SALT) in succession, intubating Laerdal mannequin heads with the 3 modalities after randomization to start with or without biohazard gear. RESULTS: Thirty-seven residents participated, and 27 were male (73%); 14 (37.8%) had prior experience intubating in biohazard suits. There was a statistically significant difference in those who had prior intubation experience between DL (37, 100%), GS (32, 86.5%), and SALT (12, 32.4%) (P \u3c .001) and in median time to intubation (48 seconds, no suit; 57 seconds, with suits) (P = .03). There was no statistically significant difference between the overall times to intubate for the 3 devices. First-pass success was highest for DL (91.2%, no suit; 83.7%, suit) followed by GS (89%, no suit; 78.3%, suit) and SALT (51%, no suit; 67.6%, suit). CONCLUSION: A minority of participants had prior experience intubating in biohazard suits. Use of biohazard suits extends time to successful intubation. There was no difference in time to intubation for the 3 devices, but first-pass success was highest for DL (with or without biohazard gear)

Building pathway clusters from Random Forests classification using class votes

<p>Abstract</p> <p>Background</p> <p>Recent years have seen the development of various pathway-based methods for the analysis of microarray gene expression data. These approaches have the potential to bring biological insights into microarray studies. A variety of methods have been proposed to construct networks using gene expression data. Because individual pathways do not act in isolation, it is important to understand how different pathways coordinate to perform cellular functions. However, there are no published methods describing how to build pathway clusters that are closely related to traits of interest.</p> <p>Results</p> <p>We propose to build pathway clusters from pathway-based classification methods. The proposed methods allow researchers to identify clusters of pathways sharing similar functions. These pathways may or may not share genes. As an illustration, our approach is applied to three human breast cancer microarray data sets. We found that our methods yielded consistent and interpretable results for these three data sets. We further investigated one of the pathway clusters found using PubMatrix. We found that informative genes in the pathway clusters do have more publications with keywords, like estrogen receptor, compared with informative genes in other top pathways. In addition, using the shortest path analysis in GeneGo's MetaCore and Human Protein Reference Database, we were able to identify the links which connect the pathways without shared genes within the pathway cluster.</p> <p>Conclusion</p> <p>Our proposed pathway clustering methods allow bioinformaticians and biologists to investigate how informative genes within pathways are related to each other and understand possible crosstalk between pathways in a cluster. Therefore, building pathway clusters may lead to a better understanding of molecular mechanisms affecting a trait of interest, and help generate further biological hypotheses from gene expression data.</p

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

Help-Seeking Barriers Among Sexual and Gender Minority Individuals Who Experience Intimate Partner Violence Victimization

Sexual and gender minority (SGM) individuals experience intimate partner violence (IPV) victimization at disproportionate rates compared to cisgender and heterosexual individuals. Given the widespread consequences of experiencing IPV victimization, intervention and prevention strategies should identify readily accessible and culturally competent services for this population. SGM individuals who experience IPV victimization face unique individual-, interpersonal-, and systemic-level barriers to accessing informal and formal support services needed to recover from IPV. This chapter reviews IPV victimization prevalence rates among SGM individuals in the context of minority stress and highlights unique forms of IPV victimization affecting this population, namely identity abuse. The literature on help-seeking processes among IPV survivors in general and help-seeking patterns and barriers specifically among SGM individuals who experience IPV victimization in the context of minority stress (e.g., discrimination, internalized stigma, rejection sensitivity, identity concealment) are discussed. How minority stressors at individual, interpersonal, and structural levels act as barriers to help-seeking among SGM individuals experiencing IPV victimization is presented. The chapter concludes with a review of emerging evidence for interventions aimed at reducing help-seeking barriers among SGM individuals who face IPV victimization and a discussion of future directions for research on help-seeking barriers in this population

Prion-like domain mutations in hnRNPs cause multisystem proteinopathy and ALS

Summary Algorithms designed to identify canonical yeast prions predict that ~250 human proteins, including several RNA-binding proteins associated with neurodegenerative disease, harbor a distinctive prion-like domain (PrLD) enriched in uncharged polar amino acids and glycine. PrLDs in RNA-binding proteins are essential for the assembly of ribonucleoprotein granules. However, the interplay between human PrLD function and disease is not understood. Here, we define pathogenic mutations in PrLDs of hnRNPA2/B1 and hnRNPA1 in families with inherited degeneration affecting muscle, brain, motor neuron and bone, and a case of familial ALS. Wild-type hnRNPA2 and hnRNPA1 display an intrinsic tendency to assemble into self-seeding fibrils, which is exacerbated by the disease mutations. Indeed, the pathogenic mutations strengthen a ‘steric zipper’ motif in the PrLD, which accelerates formation of self-seeding fibrils that cross-seed polymerization of wild-type hnRNP. Importantly, the disease mutations promote excess incorporation of hnRNPA2 and hnRNPA1 into stress granules and drive the formation of cytoplasmic inclusions in animal models that recapitulate the human pathology. Thus, dysregulated polymerization caused by a potent mutant ‘steric zipper’ motif in a PrLD can initiate degenerative disease. Related proteins with PrLDs must be considered candidates for initiating and perhaps propagating proteinopathies of muscle, brain, motor neuron and bone

In thrombin stimulated human platelets Citalopram, Promethazine, Risperidone, and Ziprasidone, but not Diazepam, may exert their pharmacological effects also through intercalation in membrane phospholipids in a receptor-independent manner

Intercalation of drugs in the platelet membrane affects phospholipid-requiring enzymatic processes according to the drugs’ intercalation capability. We investigated effects of Promethazine, Citalopram, Ziprasidone, Risperidone, and Diazepam on phospholipase A2 (PLA2) and polyphosphoinositide (PPI) metabolism in thrombin-stimulated human platelets. We also examined effects of the drugs on monolayers of glycerophospholipids using the Langmuir technique. Diazepam did not influence PLA2 activity, had no effects on PPI cycle, and caused no change in mean molecular area of phospholipid monolayers. The remaining psychotropic drugs affected these parameters in different ways and levels of potency suggesting that they act by being intercalated between the molecules of adjacent membrane phospholipids, thus causing changes in substrate availability for phospholipid-hydrolyzing enzymes (PLA2 and Phospholipase C). We show that several psychotropic drugs can also have other cellular effects than receptor antagonism. These effects may be implicated in the psychotropic effects of the drugs and/or their side effects

Biology of moderately halophilic aerobic bacteria

The moderately halophilic heterotrophic aerobic bacteria form a diverse group of microorganisms. The property of halophilism is widespread within the bacterial domain. Bacterial halophiles are abundant in environments such as salt lakes, saline soils, and salted food products. Most species keep their intracellular ionic concentrations at low levels while synthesizing or accumulating organic solutes to provide osmotic equilibrium of the cytoplasm with the surrounding medium. Complex mechanisms of adjustment of the intracellular environments and the properties of the cytoplasmic membrane enable rapid adaptation to changes in the salt concentration of the environment. Approaches to the study of genetic processes have recently been developed for several moderate halophiles, opening the way toward an understanding of haloadaptation at the molecular level. The new information obtained is also expected to contribute to the development of novel biotechnological uses for these organisms

The effects of cognitive therapy versus 'treatment as usual' in patients with major depressive disorder

BACKGROUND: Major depressive disorder afflicts an estimated 17% of individuals during their lifetimes at tremendous suffering and costs. Cognitive therapy may be an effective treatment option for major depressive disorder, but the effects have only had limited assessment in systematic reviews. METHODS/PRINCIPAL FINDINGS: Cochrane systematic review methodology, with meta-analyses and trial sequential analyses of randomized trials, are comparing the effects of cognitive therapy versus 'treatment as usual' for major depressive disorder. To be included the participants had to be older than 17 years with a primary diagnosis of major depressive disorder. Altogether, we included eight trials randomizing a total of 719 participants. All eight trials had high risk of bias. Four trials reported data on the 17-item Hamilton Rating Scale for Depression and four trials reported data on the Beck Depression Inventory. Meta-analysis on the data from the Hamilton Rating Scale for Depression showed that cognitive therapy compared with 'treatment as usual' significantly reduced depressive symptoms (mean difference -2.15 (95% confidence interval -3.70 to -0.60; P<0.007, no heterogeneity)). However, meta-analysis with both fixed-effect and random-effects model on the data from the Beck Depression Inventory (mean difference with both models -1.57 (95% CL -4.30 to 1.16; P = 0.26, I(2) = 0) could not confirm the Hamilton Rating Scale for Depression results. Furthermore, trial sequential analysis on both the data from Hamilton Rating Scale for Depression and Becks Depression Inventory showed that insufficient data have been obtained. DISCUSSION: Cognitive therapy might not be an effective treatment for major depressive disorder compared with 'treatment as usual'. The possible treatment effect measured on the Hamilton Rating Scale for Depression is relatively small. More randomized trials with low risk of bias, increased sample sizes, and broader more clinically relevant outcomes are needed