Search

The MiniBooNE-DM Collaboration searched for vector-boson mediated production of dark matter using the Fermilab 8-GeV Booster proton beam in a dedicated run with 1.86×10^{20} protons delivered to a steel beam dump. The MiniBooNE detector, 490 m downstream, is sensitive to dark matter via elastic scattering with nucleons in the detector mineral oil. Analysis methods developed for previous MiniBooNE scattering results were employed, and several constraining data sets were simultaneously analyzed to minimize systematic errors from neutrino flux and interaction rates. No excess of events over background was observed, leading to a 90% confidence limit on the dark matter cross section parameter, Y=ε^{2}α_{D}(m_{χ}/m_{V})^{4}≲10^{-8}, for α_{D}=0.5 and for dark matter masses of 0.01

Mascarenhas et al. report that TRPV4 expression is upregulated in mast cells in response to the proteolytic cathelicidin fragment LL37 in a murine rosacea model and that TRPV4 loss of function attenuates mast cell degranulation. These findings render TRPV4 a translational-medical target in rosacea. However, signaling mechanisms causing increased expression of TRPV4 await elucidation. Moreover, we ask whether TRPV4-mediated Ca ++ -influx evokes mast cell degranulation., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Searches for a light sterile neutrino have been performed independently by the MINOS and the Daya Bay experiments using the muon (anti)neutrino and electron antineutrino disappearance channels, respectively. In this Letter, results from both experiments are combined with those from the Bugey-3 reactor neutrino experiment to constrain oscillations into light sterile neutrinos. The three experiments are sensitive to complementary regions of parameter space, enabling the combined analysis to probe regions allowed by the Liquid Scintillator Neutrino Detector (LSND) and MiniBooNE experiments in a minimally extended four-neutrino flavor framework. Stringent limits on sin^{2}2θ&#95;{μe} are set over 6 orders of magnitude in the sterile mass-squared splitting Δm&#95;{41}^{2}. The sterile-neutrino mixing phase space allowed by the LSND and MiniBooNE experiments is excluded for Δm&#95;{41}^{2}<0.8  eV^{2} at 95%  CL&#95;{s}.

We report results of a search for oscillations involving a light sterile neutrino over distances of 1.04 and 735 km in a ν&#95;{μ}-dominated beam with a peak energy of 3 GeV. The data, from an exposure of 10.56×10^{20} protons on target, are analyzed using a phenomenological model with one sterile neutrino. We constrain the mixing parameters θ&#95;{24} and Δm&#95;{41}^{2} and set limits on parameters of the four-dimensional Pontecorvo-Maki-Nakagawa-Sakata matrix, |U&#95;{μ4}|^{2} and |U&#95;{τ4}|^{2}, under the assumption that mixing between ν&#95;{e} and ν&#95;{s} is negligible (|U&#95;{e4}|^{2}=0). No evidence for ν&#95;{μ}→ν&#95;{s} transitions is found and we set a world-leading limit on θ&#95;{24} for values of Δm&#95;{41}^{2}≲1  eV^{2}.

The discovery of nitric oxide (NO) as an endogenously generated signaling species in mammalian cells has spawned a vast interest in the study of the chemical biology of nitrogen oxides. Of these, nitroxyl (azanone, HNO) has gained much attention for its potential role as a therapeutic for cardiovascular disease. Known targets of HNO include hemes/heme proteins and thiols/thiol-containing proteins. Recently, due to their roles in redox signaling and cellular defense, selenols and selenoproteins have also been speculated to be additional potential targets of HNO. Indeed, as determined in the current work, selenols are targeted by HNO. Such reactions appear to result only in formation of diselenide products, which can be easily reverted back to the free selenol. This characteristic is distinct from the reaction of HNO with thiols/thiolproteins. These findings suggest that, unlike thiolproteins, selenoproteins are resistant to irreversible oxidative modification, support that Nature may have chosen to use selenium instead of sulfur in certain biological systems for its enhanced resistance to electrophilic and oxidative modification., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Protein microarray technology provides a versatile platform for characterization of hundreds to thousands of proteins in a parallel and high-throughput manner. Over the last decade, applications of functional protein microarrays in particular have flourished in studying protein function at a systems level and have led to the construction of networks and pathways describing these functions. Relevant areas of research include the detection of various binding properties of proteins, the study of enzyme-substrate relationships, the analysis of host-microbe interactions, and profiling antibody specificity. In addition, discovery of novel biomarkers in autoimmune diseases and cancers is emerging as a major clinical application of functional protein microarrays. In this review, we will summarize the recent advances of functional protein microarrays in both basic and clinical applications., (Copyright © 2015. Published by Elsevier Ltd.)

Hospital readmission is an important indicator of health care quality and currently used in determining hospital reimbursement rates by Centers for Medicare & Medicaid Services. Given the important policy implications, a better understanding of factors that influence readmission rates is needed. Racial disparities in readmission have been extensively studied, but income and marital status (a postdischarge care support indicator) disparities have received limited attention. By employing three Poisson regression models controlling for different confounders on 8,718 patients in a veterans-integrated health care network, this study assessed racial, income, and martial disparities in relation to total number of readmissions. In contrast to other studies, no racial and income disparities were found, but unmarried patients experienced significantly more readmissions: 16%, after controlling for the confounders. These findings render unique insight into health care policies aimed to improve race and income disparities, while challenging policy makers to reduce readmissions for those who lack family support., (© The Author(s) 2013.)

Purpose: Globally, the prevalence of mental illness is on the rise, although few people with psychiatric disorders actually seek mental health care. One under-researched factor that may impact help-seeking behavior from health care professionals is self-efficacy. This research presents the development and validation of the Self-Efficacy to Seek Mental Health Care (SE-SMHC) scale, a nine item-self report measure. It was hypothesized that self-efficacy for seeking mental health care would be positively associated with higher rates of self-reported help-seeking behavior and higher rates of advising others in distress to access mental health treatment., Methods: A randomized population sample of 977 South Africans completed the SE-SMHC as part of a larger study on barriers to health care for mental illness. SE-SMHC data were subjected to principal component analysis, and data from the larger study were utilized to test the hypotheses., Results: Two latent factors emerged from the oblique rotation and accounted for 70% of the variance: SE-KNOW (confidence in one's ability to know how to successfully interface with mental health care systems) and SE-COPE (confidence in one's ability to cope with the consequences of seeking care). Cronbach alphas for both subscales were 0.87 and for the total scale score was 0.93. Both hypotheses were confirmed suggesting evidence of the scale's validity., Conclusions: This data suggests that the SE-SMHC demonstrates good psychometric characteristics and may be a useful research tool and screening instrument for targeted interventions.

As marine divers, pinnipeds have a high capacity for exercise at depth while holding their breath. With finite access to oxygen, these species need to be capable of extended aerobic exercise and conservation of energy. Pinnipeds must deal with common physiological hurdles, such as hypoxia, exhaustion and acidosis, that are common to all exercising mammals. The physiological mechanisms in marine mammals used for managing oxygen and carbon dioxide have sparked much research, but access to animals and tissues is difficult and requires permits. Deceased animals that are either bycaught or stranded provide one potential source for tissues, but the validity of biochemical data from post-mortem samples has not been rigorously assessed. Tissues collected from stranded diving mammals may be a crucial source to add to our limited knowledge on the physiology of some of these animals and important to the conservation and management of these species. We aim to determine the reliability of biochemical assays derived from post-mortem tissue and to promote the immediate sampling of stranded animals for the purpose of physiological research. In this study, we mapped the temporal degradation of muscle enzymes from biopsied Northern elephant seals (Mirounga angustirostris) and highlight recommendations for storage protocols for the best preservation of tissue. We also compared the enzymatic activity of different muscle groups (pectoral and latissimus dorsi) in relation to locomotion and measured the effects of four freeze-thaw cycles on muscle tissue enzyme function. Results indicate that enzymatic activity fluctuates greatly, especially with varying storage temperature, storage time, species and muscle group being assayed. In contrast, proteins, such as myoglobin, remain relatively continuous in their increase at 4°C for 48 h. Stranded animals can be a valuable source of biochemical data, but enzyme assays should be used only with great caution in post-mortem tissues.

Background: Atrophy and fatty-infiltration of lower-extremity muscle after spinal cord injury (SCI) predisposes individuals to metabolic disease and related mortality., Objectives: To determine the magnitude of atrophy and fatty-infiltration of lower-extremity muscles and related factors in a group of individuals with chronic SCI and diverse impairment., Methods: Muscle cross-sectional area and density were calculated from peripheral quantitative computed tomography scans of the 66% site of the calf of 70 participants with chronic SCI [50 male, mean age 49 (standard deviation 12) years, C2-T12, AIS A-D] and matched controls. Regression models for muscle area and density were formed using 16 potential correlates selected a priori., Results: Participants with motor-complete SCI had ≈ 32% lower muscle area, and ≈ 43% lower muscle density values relative to controls. Participants with motor-incomplete SCI had muscle area and density values that were both ≈ 14% lower than controls. Body mass (+), tetraplegia (+), motor function (+), spasticity (+), vigorous physical activity (+), wheelchair use (-), age (-), and waist circumference (-) were associated with muscle size and/or density in best-fit regression models., Conclusions: There are modifiable factors related to muscle size, body composition, and activity level that may offer therapeutic targets for preserving metabolic health after chronic SCI., Competing Interests: The authors have no conflict of interest.

Objective: To provide preliminary evidence of the types and amount of involvement by healthcare industry representatives (HCIRs) in surgery, as well as the ethical concerns of those representatives., Methods: A link to an anonymous, web-based survey was posted on several medical device boards of the website http://www. cafepharma.com. Additionally, members of two different medical device groups on LinkedIn were asked to participate. Respondents were self-identified HCIRs in the fields of orthopedics, cardiology, endoscopic devices, lasers, general surgery, ophthalmic surgery, oral surgery, anesthesia products, and urologic surgery., Results: A total of 43 HCIRs replied to the survey over a period of one year: 35 men and eight women. Respondents reported attending an average of 184 surgeries in the prior year and had an average of 17 years as an HCIR and six years with their current employer. Of the respondents, 21 percent (nine of 43) had direct physical contact with a surgical team or patient during a surgery, and 88 percent (38 of 43) provided verbal instruction to a surgical team during a surgery. Additionally, 37 percent (16 of 43) had participated in a surgery in which they felt that their involvement was excessive, and 40 percent (17 of 43) had attended a surgery in which they questioned the competence of the surgeon., Conclusions: HCIRs play a significant role in surgery. Involvement that exceeds their defined role, however, can raise serious ethical and legal questions for surgeons and surgical teams. Surgical teams may at times be substituting the knowledge of the HCIR for their own competence with a medical device or instrument. In some cases, contact with the surgical team or patient may violate the guidelines not only of hospitals and medical device companies, but the law as well. Further study is required to determine if the patients involved have any knowledge or understanding of the role that an HCIR played in their surgery., (Copyright 2014 The Journal of Clinical Ethics. All rights reserved.)

Recent discoveries of important pharmacological properties have drawn attention to the reactivity of HNO (azanone, nitroxyl) with biologically relevant substrates. Apart from its role in thiol oxidation, HNO has been reported to have nitrosative properties, for example, with tryptophan resulting in N-nitrosotryptophan formation. We have investigated the reactivity of HNO with tryptophan and small peptides containing either tryptophan or both a tryptophan and a cysteine residue. Our results point to the more reactive nature of cysteine towards HNO compared with tryptophan., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Given the prevalence of mental illness worldwide, it is important to better understand the dynamics of mental health help-seeking behavior to improve access to care. The aim of this study was to investigate if general self-efficacy (GSE) was associated with self-reported mental illness and help-seeking behavior and barriers to care in a randomized population. This study utilized a mailed questionnaire completed by 3,981 persons aged 19-64 years who resided in Western Sweden. GSE was measured and logistic regression models calculated, controlling for various sociodemographic variables. Results showed that 25% of men and 43% of women reported a lifetime prevalence of mental illness that they felt could have benefitted from treatment. Of those, 37% of the men and 27% of the women reported barriers to care. Men and women with low GSE were more likely to suffer from mental illness compared with persons high in GSE, but GSE did not enhance help-seeking behavior or perceived barriers to care. The most prevalent barriers to care for both sexes were beliefs that the illness will pass by itself, doubt whether treatment works, lack of knowledge of where to go and feelings of shame. Overall, GSE scores did not differ among those who experienced various barriers to care with the exception of two barriers only among women.

To obtain mechanistic insights into the inherent reactivity patterns for copper(I)-O2 adducts, a new cupric-superoxo complex [(DMM-tmpa)Cu(II)(O2(•-))](+) (2) [DMM-tmpa = tris((4-methoxy-3,5-dimethylpyridin-2-yl)methyl)amine] has been synthesized and studied in phenol oxidation-oxygenation reactions. Compound 2 is characterized by UV-vis, resonance Raman, and EPR spectroscopies. Its reactions with a series of para-substituted 2,6-di-tert-butylphenols (p-X-DTBPs) afford 2,6-di-tert-butyl-1,4-benzoquinone (DTBQ) in up to 50% yields. Significant deuterium kinetic isotope effects and a positive correlation of second-order rate constants (k2) compared to rate constants for p-X-DTBPs plus cumylperoxyl radical reactions indicate a mechanism that involves rate-limiting hydrogen atom transfer (HAT). A weak correlation of (k(B)T/e) ln k2 versus E(ox) of p-X-DTBP indicates that the HAT reactions proceed via a partial transfer of charge rather than a complete transfer of charge in the electron transfer/proton transfer pathway. Product analyses, (18)O-labeling experiments, and separate reactivity employing the 2,4,6-tri-tert-butylphenoxyl radical provide further mechanistic insights. After initial HAT, a second molar equiv of 2 couples to the phenoxyl radical initially formed, giving a Cu(II)-OO-(ArO') intermediate, which proceeds in the case of p-OR-DTBP substrates via a two-electron oxidation reaction involving hydrolysis steps which liberate H2O2 and the corresponding alcohol. By contrast, four-electron oxygenation (O-O cleavage) mainly occurs for p-R-DTBP which gives (18)O-labeled DTBQ and elimination of the R group.

Northern elephant seals (Mirounga angustirostris) (NES) are known to be deep, long-duration divers and to sustain long-repeated patterns of breath-hold, or apnea. Some phocid dives remain within the bounds of aerobic metabolism, accompanied by physiological responses inducing lung compression, bradycardia, and peripheral vasoconstriction. Current data suggest an absence of type IIb fibers in pinniped locomotory musculature. To date, no fiber type data exist for NES, a consummate deep diver. In this study, NES were biopsied in the wild. Ontogenetic changes in skeletal muscle were revealed through succinate dehydrogenase (SDH) based fiber typing. Results indicated a predominance of uniformly shaped, large type I fibers and elevated myoglobin (Mb) concentrations in the longissimus dorsi (LD) muscle of adults. No type II muscle fibers were detected in any adult sampled. This was in contrast to the juvenile animals that demonstrated type II myosin in Western Blot analysis, indicative of an ontogenetic change in skeletal muscle with maturation. These data support previous hypotheses that the absence of type II fibers indicates reliance on aerobic metabolism during dives, as well as a depressed metabolic rate and low energy locomotion. We also suggest that the lack of type IIb fibers (adults) may provide a protection against ischemia reperfusion (IR) injury in vasoconstricted peripheral skeletal muscle.

Current interest in copper/dioxygen reactivity includes the influence of thioether sulfur ligation, as it concerns the formation, structures, and properties of derived copper-dioxygen complexes. Here, we report on the chemistry of {L-Cu(I)}2-(O2) species L = (DMM)ESE, (DMM)ESP, and (DMM)ESDP, which are N3S(thioether)-based ligands varied in the nature of a substituent on the S atom, along with a related N3O(ether) (EOE) ligand. Cu(I) and Cu(II) complexes have been synthesized and crystallographically characterized. Copper(I) complexes are dimeric in the solid state, [{L-Cu(I)}2](B(C6F5)4)2, however are shown by diffusion-ordered NMR spectroscopy to be mononuclear in solution. Copper(II) complexes with a general formulation [L-Cu(II)(X)](n+) {X = ClO4(-), n = 1, or X = H2O, n = 2} exhibit distorted square pyramidal coordination geometries and progressively weaker axial thioether ligation across the series. Oxygenation (-130 °C) of {((DMM)ESE)Cu(I)}(+) results in the formation of a trans-μ-1,2-peroxodicopper(II) species [{((DMM)ESE)Cu(II)}2(μ-1,2-O2(2-))](2+) (1(P)). Weakening the Cu-S bond via a change to the thioether donor found in (DMM)ESP leads to the initial formation of [{((DMM)ESP)Cu(II)}2(μ-1,2-O2(2-))](2+) (2(P)) that subsequently isomerizes to a bis-μ-oxodicopper(III) complex, [{((DMM)ESP)Cu(III)}2(μ-O(2-))2](2+) (2(O)), with 2(P) and 2(O) in equilibrium (K(eq) = [2(O)]/[2(P)] = 2.6 at -130 °C). Formulations for these Cu/O2 adducts were confirmed by resonance Raman (rR) spectroscopy. This solution mixture is sensitive to the addition of methylsulfonate, which shifts the equilibrium toward the bis-μ-oxo isomer. Further weakening of the Cu-S bond in (DMM)ESDP or substitution with an ether donor in (DMM)EOE leads to only a bis-μ-oxo species (3(O) and 4(O), respectively). Reactivity studies indicate that the bis-μ-oxodicopper(III) species (2(O), 3(O)) and not the trans-peroxo isomers (1(P) and 2(P)) are responsible for the observed ligand sulfoxidation. Our findings concerning the existence of the 2(P)/2(O) equilibrium contrast with previously established ligand-Cu(I)/O2 reactivity and possible implications are discussed.

We report on a new analysis of neutrino oscillations in MINOS using the complete set of accelerator and atmospheric data. The analysis combines the ν(μ) disappearance and ν(e) appearance data using the three-flavor formalism. We measure |Δm(32)(2)| = [2.28-2.46] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.35-0.65 (90% C.L.) in the normal hierarchy, and |Δm(32)(2)| = [2.32-2.53] × 10(-3) eV(2) (68% C.L.) and sin(2)θ(23) = 0.34-0.67 (90% C.L.) in the inverted hierarchy. The data also constrain δ(CP), the θ(23} octant degeneracy and the mass hierarchy; we disfavor 36% (11%) of this three-parameter space at 68% (90%) C.L.

Purpose: The purpose of this study is to validate the Swedish translation of the WHO (Ten) and WHO (Five) Well-Being Questionnaires among three samples of Swedes., Methods: Baseline data collected in 2008 from the Health Assets Project are the data source consisting of three cohorts of Swedes aged 19-64 years: (1) a randomized general population cohort (n = 4,027); (2) employees sick-listed reported by the employer (n = 3,310); and (3) self-certified sick-listed individuals (n = 498). The psychometric properties of the scales are assessed using factor analysis, Cronbach's alpha, and examination of the relationship between scale scores and participants' self-reported adverse health conditions., Results: Factor analysis revealed a unidimensional factor structure for both scales, and Cronbach's alphas are very good to excellent. The scales correlate in the expected direction with almost all of the adverse health conditions considered., Conclusions: The Swedish translation of the WHO (Ten) and WHO (Five) Well-Being Questionnaires is psychometrically sound, but the first item of both scales has weaker psychometric qualities in comparison with other scale items.

Background: The relation of drug use to HCV treatment outcome in an insured household population has not been previously reported., Methods: Lifetime frequencies of marijuana use and non-medical use of stimulants, sedatives, and opioids; hallucinogens; and inhalants were retrospectively assessed in 259 privately insured members of an integrated health care plan treated for chronic hepatitis C virus infection (HCV+) with pegylated interferon alpha and ribavirin and examined with respect to rates of sustained virological response (SVR)., Results: The majority of patients reported chronic use of multiple illegal drugs; 61.6% reported injection drug use (IDU); 79.5% abstained from drug use during the six months prior to HCV treatment. Total frequency of individual drugs, multiple drugs, and length of abstention from drugs prior to HCV treatment were not related to impaired SVR rates. Sustained viral responses were obtained in 80.2% of patients with HCV genotype 2/3 and 45.1% of patients with genotype 1/4/6. Marijuana use during HCV treatment, reported by 8.5% of patients, was associated with higher treatment adherence (95.5% compared with 78.9%, p=0.045), but lower SVR rates (40.9% compared with 62.5%, p=0.041). In addition, drug use during HCV treatment was associated with significantly higher relapse rates, 18.8% compared with 7.7% (p=0.053)., Conclusion: A history of chronic illegal drug use should not be considered a deterrent to HCV treatment in members of an integrated health care plan who are motivated to seek treatment and closely monitored, but drug use during HCV treatment, including marijuana use, should be discouraged., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The protonation–reduction of a dioxygen adduct with [LCu(I)][B(C6F5)4], cupric superoxo complex [LCu(II)(O2(•–))]+ (1) (L = TMG3tren (1,1,1-tris[2-[N(2)-(1,1,3,3-tetramethylguanidino)]ethyl]amine)) has been investigated. Trifluoroacetic acid (HOAcF) reversibly associates with the superoxo ligand in ([LCu(II)(O2(•–))]+) in a 1:1 adduct [LCu(II)(O2(•–))(HOAcF)](+) (2), as characterized by UV–visible, resonance Raman (rR), nuclear magnetic resonance (NMR), and X-ray absorption (XAS) spectroscopies, along with density functional theory (DFT) calculations. Chemical studies reveal that for the binding of HOAcF with 1 to give 2, Keq = 1.2 × 10(5) M(–1) (−130 °C) and ΔH° = −6.9(7) kcal/mol, ΔS° = −26(4) cal mol(–1) K(–1)). Vibrational (rR) data reveal a significant increase (29 cm(–1)) in vO–O (= 1149 cm(–1)) compared to that known for [LCu(II)(O2(•–))](+) (1). Along with results obtained from XAS and DFT calculations, hydrogen bonding of HOAcF to a superoxo O-atom in 2 is established. Results from NMR spectroscopy of 2 at −120 °C in 2-methyltetrahydrofuran are also consistent with 1/HOAcF = 1:1 formulation of 2 and with this complex possessing a triplet (S = 1) ground state electronic configuration, as previously determined for 1. The pre-equilibrium acid association to 1 is followed by outer-sphere electron-transfer reduction of 2 by decamethylferrocene (Me10Fc) or octamethylferrocene (Me8Fc), leading to the products H2O2, the corresponding ferrocenium salt, and [LCu(II)(OAcF)](+). Second-order rate constants for electron transfer (ket) were determined to be 1365 M(–1) s(–1) (Me10Fc) and 225 M(–1) s(–1) (Me8Fc) at −80 °C. The (bio)chemical relevance of the proton-triggered reduction of the metal-bound dioxygen-derived fragment is discussed.

Objectives: To provide a clinical update on practical strategies to enhance the quality of communication in the palliative and end-of-life medical care settings., Data Sources: Published articles, textbooks, reports, and clinical experience., Conclusion: The components of effective and compassionate care throughout the advanced illness trajectory require thoughtful and strategic communication with patients, families, and members of the health care team. Unfortunately, few health care professionals are formally trained in communication skills., Implications for Nursing Practice: Nurses who possess self-awareness and are skilled in effective communication practices are integral to the provision of high-quality palliative care for patients and families coping with advanced malignancies., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nitroxyl (HNO), a potential heart failure therapeutic, is known to post-translationally modify cysteine residues. Among reactive nitrogen oxide species, the modification of cysteine residues to sulfinamides [RS(O)NH2] is unique to HNO. We have applied (15)N-edited (1)H NMR techniques to detect the HNO-induced thiol to sulfinamide modification in several small organic molecules, peptides, and the cysteine protease, papain. Relevant reactions of sulfinamides involve reduction to free thiols in the presence of excess thiol and hydrolysis to form sulfinic acids [RS(O)OH]. We have investigated sulfinamide hydrolysis at physiological pH and temperature. Studies with papain and a related model peptide containing the active site thiol suggest that sulfinamide hydrolysis can be enhanced in a protein environment. These findings are also supported by modeling studies. In addition, analysis of peptide sulfinamides at various pH values suggests that hydrolysis becomes more facile under acidic conditions.

Inhaled glucocorticoids are the first-line treatment for patients with persistent asthma.  However, approximately thirty percent of patients exhibit glucocorticoid insensitivity, which may involve excess metabolic clearance of the glucocorticoids by CYP3A enzymes in the lung.  CYP3A4, 3A5, and 3A7 enzymes metabolize glucocorticoids, which in turn induce CYP3A genes.  However, the mechanism of CYP3A5 mRNA regulation by glucocorticoids in lung cells has not been determined.  In hepatocytes, glucocorticoids bind to the glucocorticoid receptor (GR), which induces the expression of the constitutive androstane receptor or pregnane X receptor; both of which bind to the retinoid X receptor alpha, leading to the induction of CYP3A4, 3A5, and 3A7.  There is also evidence to suggest a direct induction of CYP3A5 by GR activation in liver cells. In this study, these pathways were evaluated as the mechanism for CYP3A5 mRNA induction by glucocorticoids in freshly isolated primary tracheal epithelial, adenocarcinomic human alveolar basal epithelial (A549), immortalized bronchial epithelial (BEAS-2B), primary normal human bronchial/tracheal epithelial (NHBE), primary small airway epithelial (SAEC), and primary lobar epithelial lung cells. In A549 cells, beclomethasone 17-monopropionate ([M1]) induced CYP3A5 mRNA through the glucocorticoid receptor. CYP3A5 mRNA induction by five different glucocorticoids was attenuated by inhibiting the glucocorticoid receptor using ketoconazole, and for beclomethasone dipropionate, using siRNA-mediated knock-down of the glucocorticoid receptor. The constitutive androstane receptor was not expressed in lung cells. SAEC cells, a primary lung cell line, expressed CYP3A5, but CYP3A5 mRNA was not induced by glucocorticoid treatment despite evaluating a multitude of cell culture conditions. None of the other lung cells expressed CYP3A4, 3A5 or 3A7 mRNA. These studies demonstrate that CYP3A5 mRNA is induced by glucocorticoids in A549 cells via the glucocorticoid receptor, but that additional undefined regulatory processes exist in primary lung cells.

The aim of this study was to explore and identify influences on frail older adults' experience of health. A sample of older adults, 11 men and 11 women aged 67-92, with diverse ratings of self-perceived health ranging from poor to excellent were selected through a purposeful strategic sampling of frail older adults taken from a broader sample from a quantitative study on health. In total, 22 individual qualitative interviews were analyzed using qualitative content analysis in which themes were developed from raw data through a systematic reading, categorization of selected text, theme development and interpretation. To feel assured and capable was the main theme, which consisted of five subthemes: managing the unpredictable body, reinforcing a positive outlook, remaining in familiar surroundings, managing everyday life, and having a sense of belonging and connection to the whole. The importance of supporting frail older adults in subjective resilience in their context is emphasized., (Copyright © 2013 Mosby, Inc. All rights reserved.)

We report measurements of oscillation parameters from ν(μ) and ν(μ) disappearance using beam and atmospheric data from MINOS. The data comprise exposures of 10.71×10(20) protons on target in the ν(μ)-dominated beam, 3.36×10(20) protons on target in the ν(μ)-enhanced beam, and 37.88 kton yr of atmospheric neutrinos. Assuming identical ν and ν oscillation parameters, we measure |Δm2| = (2.41(-0.10)(+0.09))×10(-3)  eV2 and sin2(2θ) = 0.950(-0.036)(+0.035). Allowing independent ν and ν oscillations, we measure antineutrino parameters of |Δm2| = (2.50(-0.25)(+0.23))×10(-3)  eV2 and sin2(2θ) = 0.97(-0.08)(+0.03), with minimal change to the neutrino parameters.

Hospital readmission rate has been broadly accepted as a quality measure and cost driver. However, success in reducing readmissions has been elusive. In the US, almost 20 % of Medicare inpatients are rehospitalized within 30 days, which amounts to a cost of $17 billion. Given the skyrocketing healthcare cost, policymakers, researchers and payers are focusing more than ever on readmission reduction. Both hospital comparison of readmissions as a quality measure and identification of high-risk patients for post-discharge interventions require accurate predictive modeling. However, most predictive models for readmissions perform poorly. In this study, we endeavored to explore the full potentials of predictive models for readmissions and to assess the predictive power of different independent variables. Our model reached the highest predicting ability (c-statistic =0.80) among all published studies that used administrative data. Our analyses reveal that demographics, socioeconomic variables, prior utilization and Diagnosis-related Group (DRG) all have limited predictive power; more sophisticated patient stratification algorithm or risk adjuster is desired for more accurate readmission predictions.

Background: Medication overuse headache (MOH) is a chronic headache disorder, caused by overuse of acute medication. To date, it remains unclear why some people overuse these medications. The aim of this qualitative study was to explore how individuals with MOH use medications and other strategies to manage headaches in their daily lives, and their thoughts about their own use of acute medication. Our intention was to develop a theoretical model about the development of MOH, from the perspective of those with MOH., Methods: Data collection and analysis were conducted according to grounded theory methodology. The participants were recruited via newspaper advertisements. Fourteen persons with MOH were interviewed in individual qualitative interviews., Results: The basic process leading to medication overuse was holding on to the indispensable medication. The acute medication was indispensable to the participants because they perceived it as the only thing that could prevent headaches from ruining their lives. The participants perceived headaches as something that threatened to ruin their lives. As a result, they went to great lengths trying to find ways to manage it. They tried numerous strategies. However, the only strategy actually perceived as effective was the use of acute medication and they eventually became resigned to the idea that it was the only effective aid. The acute medication thus became indispensable. Their general intention was to use as little medication as possible but they found themselves compelled to medicate frequently to cope with their headaches. They did not like to think about their medication use and sometimes avoided keeping track of the amount used., Conclusions: This qualitative study adds understanding to the process via which MOH develops from the perspective of those having MOH. Such knowledge may help bridge the gap between the perspectives of patients and health-care professionals.

Inhaled glucocorticoids, such as beclomethasone dipropionate (BDP), are the mainstay treatment of asthma. However, ≈ 30% of patients exhibit little to no benefit from treatment. It has been postulated that glucocorticoid resistance, or insensitivity, is attributable to individual differences in glucocorticoid receptor-mediated processes. It is possible that variations in cytochrome P450 3A enzyme-mediated metabolism of BDP may contribute to this phenomenon. This hypothesis was explored by evaluating the contributions of CYP3A4, 3A5, 3A7, and esterase enzymes in the metabolism of BDP in vitro and relating metabolism to changes in CYP3A enzyme mRNA expression via the glucocorticoid receptor in lung and liver cells. CYP3A4 and CYP3A5 metabolized BDP via hydroxylation ([M4] and [M6]) and dehydrogenation ([M5]) at similar rates; CYP3A7 did not metabolize BDP. A new metabolite [M6], formed by the combined action of esterases and CYP3A4 hydroxylation, was also characterized. To validate the results observed using microsomes and recombinant enzymes, studies were also conducted using A549 lung and DPX2 liver cells. Both liver and lung cells produced esterase-dependent metabolites [M1-M3], with [M1] correlating with CYP3A5 mRNA induction in A549 cells. Liver cells produced both hydroxylated and dehydrogenated metabolites [M4, M5, and M6], but lung cells produced only the dehydrogenated metabolite [M5]. These studies show that CYP3A4 and CYP3A5 metabolize BDP to inactive metabolites and suggest that differences in the expression or function of these enzymes in the lung and/or liver could influence BDP disposition in humans.

The MiniBooNE experiment at Fermilab reports results from an analysis of ν[over ¯](e) appearance data from 11.27×10(20) protons on target in the antineutrino mode, an increase of approximately a factor of 2 over the previously reported results. An event excess of 78.4±28.5 events (2.8σ) is observed in the energy range 200

Malaria continues to be a difficult disease to eradicate largely because of the widespread populations it affects and the resistance that malaria parasites have developed against once very potent therapies. The natural product artemisinin has been a boon for antimalarial chemotherapy, as artemisinin combination therapy (ACT) has become the first line of chemotherapy. Because the threat of resistance is always on the horizon, it is imperative to continually identify new treatments, comprising both advanced analogues of all antimalarial drugs, especially artemisinin, and the exploration of novel combinations, ideally with distinct mechanisms of action. Here we report for the first time the synthesis of a series of two-carbon-linked artemisinin-derived dimers, their unique structural features, and demonstration of their antimalarial efficacy via single oral dose administration in two 60-day survival studies of Plasmodium berghei infected mice. Several of the new endoperoxide chemical entities consistently demonstrated excellent antimalarial efficacy, and combinations with two non-peroxide antimalarial drugs have been studied.

Asthma is one of the most prevalent diseases in the world, for which the mainstay treatment has been inhaled glucocorticoids (GCs). Despite the widespread use of these drugs, approximately 30% of asthma sufferers exhibit some degree of steroid insensitivity or are refractory to inhaled GCs. One hypothesis to explain this phenomenon is interpatient variability in the clearance of these compounds. The objective of this research is to determine how metabolism of GCs by the CYP3A family of enzymes could affect their effectiveness in asthmatic patients. In this work, the metabolism of four frequently prescribed inhaled GCs, triamcinolone acetonide, flunisolide, budesonide, and fluticasone propionate, by the CYP3A family of enzymes was studied to identify differences in their rates of clearance and to identify their metabolites. Both interenzyme and interdrug variability in rates of metabolism and metabolic fate were observed. CYP3A4 was the most efficient metabolic catalyst for all the compounds, and CYP3A7 had the slowest rates. CYP3A5, which is particularly relevant to GC metabolism in the lungs, was also shown to efficiently metabolize triamcinolone acetonide, budesonide, and fluticasone propionate. In contrast, flunisolide was only metabolized via CYP3A4, with no significant turnover by CYP3A5 or CYP3A7. Common metabolites included 6β-hydroxylation and Δ(6)-dehydrogenation for triamcinolone acetonide, budesonide, and flunisolide. The structure of Δ(6)-flunisolide was unambiguously established by NMR analysis. Metabolism also occurred on the D-ring substituents, including the 21-carboxy metabolites for triamcinolone acetonide and flunisolide. The novel metabolite 21-nortriamcinolone acetonide was also identified by liquid chromatography-mass spectrometry and NMR analysis.

In this study we explored frail elders' experiences with and perceptions of the phenomenon of health so as to develop a deeper understanding of living with diseases and disorders in old age. Frail elders participated in qualitative interviews that explored the meaning of the phenomenon of health for them. Eleven men and 11 women, who had diverse ratings of self-perceived health ranging from poor to excellent, were selected by means of a purposeful strategic sampling of frail elders taken from a broader sample that participated in a larger quantitative study on health. In total, 22 individual interviews were analyzed using Giorgi's descriptive phenomenology. We found that frail elders described health as being in harmony and balance in everyday life, and this occurred when participants were able to adjust to the demands of their daily lives in the context of their resources and capabilities.

Many patients in the intensive care unit (ICU) have predictable medical and discharge outcomes, but some trajectories are marked with medical uncertainty. Stressed family-surrogates receive multiple medical updates from a variety of personnel. These circumstances can lead to confusion, which may result in conflicts and dissatisfaction with care. This study examined the effects of adding a family support coordinator to the surgical, neurological, and medical ICUs on family, physician, and nurse satisfaction with communication and care. A quasi-experimental design was conducted in 2 sequential phases (baseline and intervention). The data sources were 2 surveys: (1) Family Satisfaction Survey and (2) Nurse and Physician Perception and Satisfaction Survey. Family Satisfaction Survey data, a combined data set, were collected in the 3 ICUs. Nurse and Physician Perception and Satisfaction Survey data were collected from the attending physicians and critical care nurses in the medical and neurological ICUs. Results show that family ratings of satisfaction with ICU team communication and care generally increased as a result of the intervention. Overall, physician and nurse perceptions of communication and care did not change as a result of the intervention.

Unlabelled: Treatment of chronic hepatitis C infection (HCV(+) ) has historically been shown to be less effective in patients with a heavy drinking history. The effect of moderate and heavy alcohol use on treatment with pegylated interferon-alpha and ribavirin (P/R) in an insured household population has not been previously reported. We investigated the effect of alcohol on treatment outcome in a cohort of 421 treatment-naïve HCV(+) patients, members of an integrated health care plan treated with P/R between January 2002 and June 2008. A detailed drinking history was obtained for 259 (61.5%) eligible patients. Regular drinking was reported by 93.1% of patients before HCV diagnosis, by 30.9% between HCV diagnosis and treatment, by 1.9% during treatment, and 11.6% after the end of treatment. Heavy drinking patterns were reported by 67.9%, 63.5% of patients drank more than 100 kg of ethanol before initiating HCV treatment, and 29.3% reported abstaining less than the required 6 months before treatment. Despite these reports of heavy drinking, sustained virological responses (SVRs) were obtained in 80.2% of patients with HCV genotypes 2 or 3 and 45.1% of patients with genotypes 1, 4, or 6. Pretreatment drinking patterns and total alcohol intake were both unrelated to SVR rates. Abstaining less than 6 months before treatment was related to lower SVR rates in moderate, but not heavy, drinkers. HCV treatment relapse was unrelated to drinking after treatment ended., Conclusion: The amount of alcohol consumed before HCV treatment did not have a negative effect on treatment outcomes in our population. A history of heavy drinking should not be considered a deterrent to HCV treatment in members of an integrated health care plan who are closely monitored., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Cytochrome P450 2F1 (P450 2F1) is expressed exclusively in the human respiratory tract and is implicated in 3-methylindole (3MI)-induced pneumotoxicity via dehydrogenation of 3MI to a reactive electrophilic intermediate, 3-methyleneindolenine (3-MEI). Studies of P450 2F1 to date have been limited by the failure to express this enzyme in Escherichia coli. By contrast, P450 2F3, a caprine homologue that shares 84% sequence identity with P450 2F1 (86 amino acid differences), has been expressed in E. coli at yields greater than 250 nmol/L culture. We hypothesized that a limited number of sequence differences between P450s 2F1 and 2F3 could limit P450 2F1 expression in E. coli and that problematic P450 2F1 sequence elements could be identified by directed evolution. A library of P450 2F1/2F3 mutants was created by DNA family shuffling and screened for expression in E. coli. Three generations of DNA shuffling revealed a mutant (named JH&#95;2F&#95;F3&#95;1&#95;007) with 96.5% nucleotide sequence identity to P450 2F1 and which expressed 119 ± 40 pmol (n = 3, mean ± SD) hemoprotein in 1 mL microaerobic cultures. Across all three generations, two regions were observed where P450 2F3-derived sequence was consistently substituted for P450 2F1 sequence in expressing mutants, encoding nine amino acid differences between P450s 2F1 and 2F3: nucleotides 191-278 (amino acids 65-92) and 794-924 (amino acids 265-305). Chimeras constructed to specifically test the importance of these two regions confirmed that P450 2F3 sequence is essential in both regions for expression in E. coli but that other non-P450 2F1 sequence elements outside of these regions also improved the expression of mutant JH&#95;2F&#95;F3&#95;1&#95;007. Mutant JH&#95;2F&#95;F3&#95;1&#95;007 catalyzed the dehydrogenation of 3MI to 3-MEI as indicated by the observation of glutathione adducts after incubation in the presence of glutathione. The JH&#95;2F&#95;F3&#95;1&#95;007 protein differs from P450 2F1 at only 20 amino acids and should facilitate further studies of the structure-activity relationships of P450s of the 2F subfamily.

Purpose: To study the internal consistency, factorial structure, and convergent validity of the Swedish translation of the General Self-Efficacy scale (S-GSE)., Methods: The S-GSE and two items on mental and physical work capacity were completed by a randomized population cohort (n = 4,027) and two cohorts (n = 3,310 and n = 498) of incident cases of sick-leave (>14 days)., Results: S-GSE means were higher among men than women in two of the cohorts and higher in the randomized population cohort than in the two sick-leave cohorts. Internal consistency was high with α = .90. Unidimensionality was indicated and factor loadings ranged between .64 and .80. Moderate correlations (.35-.38) between the S-GSE and mental work capacity were found in all cohorts. Yet, the correlation between S-GSE and physical work capacity was weaker in the sick-leave cohorts. The psychometric properties showed similar patterns across gender., Conclusions: Across three cohorts, additionally stratified by gender, the S-GSE comprised one single latent factor and showed high internal consistency. However, since S-GSE was more strongly related to self-assessments of mental work capacity than physical work capacity regardless of sick-leave status, the S-GSE may not be a strong predictor of beliefs about physical work capacity across all populations.

The successor representation was introduced into reinforcement learning by Dayan ( 1993 ) as a means of facilitating generalization between states with similar successors. Although reinforcement learning in general has been used extensively as a model of psychological and neural processes, the psychological validity of the successor representation has yet to be explored. An interesting possibility is that the successor representation can be used not only for reinforcement learning but for episodic learning as well. Our main contribution is to show that a variant of the temporal context model (TCM; Howard & Kahana, 2002 ), an influential model of episodic memory, can be understood as directly estimating the successor representation using the temporal difference learning algorithm (Sutton & Barto, 1998 ). This insight leads to a generalization of TCM and new experimental predictions. In addition to casting a new normative light on TCM, this equivalence suggests a previously unexplored point of contact between different learning systems.

We report an improved measurement of ν(μ) disappearance over a distance of 735 km using the MINOS detectors and the Fermilab Main Injector neutrino beam in a ν(μ)-enhanced configuration. From a total exposure of 2.95×10(20) protons on target, of which 42% have not been previously analyzed, we make the most precise measurement of Δm2=[2.62(-0.28)(+0.31)(stat)±0.09(syst)]×10(-3)  eV2 and constrain the ν(μ) mixing angle sin2(2θ)>0.75 (90% C.L.). These values are in agreement with Δm2 and sin2(2θ) measured for ν(μ), removing the tension reported in [P. Adamson et al. (MINOS), Phys. Rev. Lett. 107, 021801 (2011).].

The aim of this study was to determine whether mouse CYP2A5 and CYP2F2 play critical roles in the bioactivation of 3-methylindole (3MI), a tissue-selective toxicant, in the target tissues, the nasal olfactory mucosa (OM) and lung. Five metabolites of 3MI were identified in NADPH- and GSH-fortified microsomal reactions, including 3-glutathionyl-S-methylindole (GS-A1), 3-methyl-2-glutathionyl-S-indole (GS-A2), 3-hydroxy-3-methyleneindolenine (HMI), indole-3-carbinol (I-3-C), and 3-methyloxindole (MOI). The metabolite profiles and enzyme kinetics of the reactions were compared between OM and lung, and among wild-type, Cyp2a5-null, and Cyp2f2-null mice. In lung reactions, GS-A1, GS-A2, and HMI were detected as major products, and I-3-C and MOI, as minor metabolites. In OM reactions, all five metabolites were detected in ample amounts. The loss of CYP2F2 affected formation of all 3MI metabolites in the lung and formation of HMI, GS-A1, and GS-A2 in the OM. In contrast, loss of CYP2A5 did not affect formation of 3MI metabolites in the lung but caused substantial decreases in I-3-C and MOI formation in the OM. Thus, whereas CYP2F2 plays a critical role in the 3MI metabolism in the lung, both CYP2A5 and CYP2F2 play important roles in 3MI metabolism in the OM. Furthermore, the fate of the reactive metabolites produced by the two enzymes through common dehydrogenation and epoxidation pathways seemed to differ with CYP2A5 supporting direct conversion to stable metabolites and CYP2F2 supporting further formation of reactive iminium ions. These results provide the basis for understanding the respective roles of CYP2A5 and CYP2F2 in 3MI's toxicity in the respiratory tract.

Due to its inherent reactivity, nitroxyl (HNO), must be generated in situ through the use of donor compounds, but very few physiologically useful HNO donors exist. Novel N-substituted hydroxylamines with carbon-based leaving groups have been synthesized, and their structures confirmed by X-ray crystallography. These compounds generate HNO under nonenzymatic, physiological conditions, with the rate and amount of HNO released being dependent mainly on the nature of the leaving group. A barbituric acid and a pyrazolone derivative have been developed as efficient HNO donors with half-lives at pH 7.4, 37 °C of 0.7 and 9.5 min, respectively., (© 2012 American Chemical Society)

The threat of gang violence spilling over into hospital emergency rooms has become a reality in communities of all sizes, the author reports. The keys to a successful campaign against gang violence in a hospital setting, he says, are training and education of security and clinical staffs, cooperation with law enforcement, and proper reporting procedures and protocols.

We report the results of a search for ν(e) appearance in a ν(μ) beam in the MINOS long-baseline neutrino experiment. With an improved analysis and an increased exposure of 8.2 × 10(20) protons on the NuMI target at Fermilab, we find that 2 sin(2) (θ(23))sin(2)(2θ(13))<0.12(0.20) at 90% confidence level for δ = 0 and the normal (inverted) neutrino mass hierarchy, with a best-fit of 2sin(2) (θ(23))sin(2)(2θ(13)) = 0.041(-0.031)(+0.047) (0.079(-0.053) (+0.071)). The θ(13) = 0 hypothesis is disfavored by the MINOS data at the 89% confidence level.

This Letter reports the first direct observation of muon antineutrino disappearance. The MINOS experiment has taken data with an accelerator beam optimized for ν(μ) production, accumulating an exposure of 1.71 × 10²⁰ protons on target. In the Far Detector, 97 charged current ν(μ) events are observed. The no-oscillation hypothesis predicts 156 events and is excluded at 6.3σ. The best fit to oscillation yields |Δm²| = [3.36(-0.40)(+0.46)(stat) ± 0.06(syst)] × 10⁻³ eV², sin²(2θ) = 0.86(-0.12)(+0.11)(stat) ± 0.01(syst). The MINOS ν(μ) and ν(μ) measurements are consistent at the 2.0% confidence level, assuming identical underlying oscillation parameters.

Results are reported from a search for active to sterile neutrino oscillations in the MINOS long-baseline experiment, based on the observation of neutral-current neutrino interactions, from an exposure to the NuMI neutrino beam of 7.07×10(20) protons on target. A total of 802 neutral-current event candidates is observed in the Far Detector, compared to an expected number of 754 ± 28(stat) ± 37(syst) for oscillations among three active flavors. The fraction f(s) of disappearing ν(μ) that may transition to ν(s) is found to be less than 22% at the 90% C.L.

Measurements of neutrino oscillations using the disappearance of muon neutrinos from the Fermilab NuMI neutrino beam as observed by the two MINOS detectors are reported. New analysis methods have been applied to an enlarged data sample from an exposure of 7.25×10(20) protons on target. A fit to neutrino oscillations yields values of |Δm(2)|=(2.32(-0.08)(+0.12))×10(-3) eV(2) for the atmospheric mass splitting and sin(2)(2θ)>0.90 (90% C.L.) for the mixing angle. Pure neutrino decay and quantum decoherence hypotheses are excluded at 7 and 9 standard deviations, respectively.

Introduction: Deficits in processing spatial information have been observed in clinical populations who have abnormalities within the dopamine (DA) system. As psychostimulants such as methamphetamine (MA) are particularly neurotoxic to the dopaminergic system it was of interest to examine the performance of MA-dependent individuals on a task of spatial attention., Method: 51 MA-dependent subjects and 22 age-matched non-substance abusing control subjects were tested on a Spatial Stroop attention test. MR Spectroscopy (MRS) imaging data were analyzed from 32 MA abusers and 13 controls., Results: No group differences in response time or accuracy emerged on the behavioral task with both groups exhibiting equivalent slowing when the word meaning and the spatial location of the word were in conflict. MRS imaging data from the MA abusers revealed a strong inverse correlation between NAA/Cr ratios in the Primary Visual Cortex (PVC) and spatial interference (p=0.0001). Moderate inverse correlations were also seen in the Anterior Cingulate Cortex (ACC) (p=0.02). No significant correlations were observed in the controls, perhaps due to the small sample of imaging data available (n=13)., Discussion: The strong correlation between spatial conflict suppression and NAA/Cr levels within the PVC in the MA-dependent individuals suggests that preserved neuronal integrity within the PVC of stimulant abusers may modulate cognitive mechanisms that process implicit spatial information., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The goal of the present study was to extend our previous findings on long-term methamphetamine (MA) use and drug abstinence on brain metabolite levels in an expanded group of MA-dependent individuals., Methods: Seventeen MA abusers with sustained drug abstinence (1-5 years), 30 MA abusers with short-term drug abstinence (1-6 months) and 24 non-substance using controls were studied using MR spectroscopy (MRS). MRS measures of NAA/Cr, Cho/Cr and Cho/NAA were obtained in the anterior cingulate cortex (ACC) and in the primary visual cortex (PVC)., Results: ACC-Cho/NAA values were abnormally high in the short-term abstinent group compared to controls [F(1,52) = 18.76, p < 0.0001]. No differences were observed between controls and the long-term abstinent group [F(1,39) = 0.97, p = 0.97]. New evidence of lower ACC-NAA/Cr levels were observed in the short-term abstinent MA abusers compared to controls [F(1,52) = 23.05, p < 0.0001] and long-term abstinent MA abusers [F(1,45) = 7.06, p = 0.01]. No differences were observed between long-term abstinent MA abusers and controls [F(1,39) = 0.48, p = 0.49]., Conclusions: The new findings of relative NAA/Cr normalization across periods of abstinence suggest that adaptive changes following cessation of MA abuse may be broader than initially thought. These changes may contribute to some degree of normalization of neuronal function in the ACC., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

This article describes the development of a 5-item scale that assesses family caregivers' self-efficacy in communicating with physicians about ill family members (Perceived Efficacy in Caregiver-Physician Interactions-PECPI) in the context of an evaluation study of an online training in health care communication skills for caregivers. A national sample of 197 self-identified family caregivers participated in an online webinar and completed a brief evaluation instrument before and immediately after the training. Results indicated that the webinar was effective in increasing perceived self-efficacy and self-reported knowledge about and level of preparation for medical visits. Principal component analysis indicates that the PECPI is unidimensional with a Cronbach's alpha of .91.

Background: Proteomic studies of formalin-fixed paraffin-embedded (FFPE) tissues are frustrated by the inability to extract proteins from archival tissue in a form suitable for analysis by 2-D gel electrophoresis or mass spectrometry. This inability arises from the difficulty of reversing formaldehyde-induced protein adducts and cross-links within FFPE tissues. We previously reported the use of elevated hydrostatic pressure as a method for efficient protein recovery from a hen egg-white lysozyme tissue surrogate, a model system developed to study formalin fixation and histochemical processing., Principal Findings: In this study, we demonstrate the utility of elevated hydrostatic pressure as a method for efficient protein recovery from FFPE mouse liver tissue and a complex multi-protein FFPE tissue surrogate comprised of hen egg-white lysozyme, bovine carbonic anhydrase, bovine ribonuclease A, bovine serum albumin, and equine myoglobin (55∶15∶15∶10∶5 wt%). Mass spectrometry of the FFPE tissue surrogates retrieved under elevated pressure showed that both the low and high-abundance proteins were identified with sequence coverage comparable to that of the surrogate mixture prior to formaldehyde treatment. In contrast, non-pressure-extracted tissue surrogate samples yielded few positive and many false peptide identifications. Studies with soluble formalin-treated bovine ribonuclease A demonstrated that pressure modestly inhibited the rate of reversal (hydrolysis) of formaldehyde-induced protein cross-links. Dynamic light scattering studies suggest that elevated hydrostatic pressure and heat facilitate the recovery of proteins free of formaldehyde adducts and cross-links by promoting protein unfolding and hydration with a concomitant reduction in the average size of the protein aggregates., Conclusions: These studies demonstrate that elevated hydrostatic pressure treatment is a promising approach for improving the recovery of proteins from FFPE tissues in a form suitable for proteomic analysis.

The MiniBooNE experiment at Fermilab reports results from a search for ¯ν&#95;{μ}→¯ν&#95;{e} oscillations, using a data sample corresponding to 5.66×10²⁰ protons on target. An excess of 20.9±14.0 events is observed in the energy range 475