Nonequilibrium electron rings for synchrotron radiation production.
Electron storage rings used for the production of synchrotron radiation (SR) have an output photon brightness that is limited by the equilibrium beam emittance. By using interleaved injection and ejection of bunches from a source with repetition rate greater than 1 kHz, we show that it is practicable to overcome this limit in rings of energy ∼1 GeV. Sufficiently short kicker pulse lengths enable effective currents of many milliamperes, which can deliver a significant flux of diffraction-limited soft x-ray photons. Thus, either existing SR facilities may be adapted for nonequilibrium operation, or the technique applied to construct SR rings smaller than their storage ring equivalent.


Dynamic properties of a hexadecamolybdenum wheel: studies in solution and density functional theory calculations.
Variable temperature (1)H NMR studies of the host-guest complex [Mo(16)O(16)S(16)(OH)(16)(H(2)O)(4)(PDA)(2)](4-) (1 ; PDA(2-) = phenylenediacetate) previously carried out in D(2)O have revealed a complex behavior in solution, involving a gliding motion of both parallel phenyl rings of the PDA(2-) ligands. In the present work, we present new NMR spectra carried out in the aprotic solvent CD(3)CN, which allow the observation of the proton signals associated with the bridging hydroxo groups of the inorganic host. The new spectra provide detailed information about the concerted reorganization of the guest components, that is, PDA(2-) and water molecules. The existence of an equilibrium between two distinct isomers differing in the linking mode between the inorganic host and the two equivalent PDA(2-) ligands is evidenced. This equilibrium appears strongly dependent upon the temperature, leading to a complete inversion of the distribution between 300 and 226 K. The thermodynamic data related to the isomerization reaction have been determined (Delta(r)H = -50.5 kJ mol(-1) and Delta(r)S = -215 J mol(-1) K(-1)). Furthermore, at low temperature, one of the isomers exists in two conformations, only differing in the H-bond network involving the inner water molecules. Density functional theory calculations were carried out to push ahead the interpretations obtained from experiment, identify the isomers of 1, and specify the role and the positions of the guest water molecules. Among the various structures that have been calculated for 1, three fall in a narrow energy range and should correspond to the species characterized by variable-temperature (1)H NMR experiments in CD(3)CN. Finally, this study shows how the internal disposition of the ligands affects the ellipticity of the Mo(16) ring which varies from one isomer to the other in the 0.73-1 range and highlights solvation of the ring as one of the key parameters for the conformational design of these flexible host-guest systems.


Standardized Criteria Increases Palliative Care Consultation Utilization in Patients With End-Stage Liver Disease: A Pilot Study.
Context: Patients with end-stage liver disease have high symptom burden and high healthcare utilization, which may be improved by palliative care consultation. Objectives: We sought to determine if implementing standardized palliative care consultation criteria in hospitalized patients with end-stage liver disease would increase palliative care utilization and improve patient outcomes. Methods: We conducted a retrospective cohort study of hospitalized patients with end-stage liver disease. Patients under the age of 18, received a previous liver transplant, or admitted for liver transplantation were not included. Patients with end-stage liver disease meeting two or more of the following criteria were included: (i)Child Pugh C cirrhosis, (ii)2 or more liver related hospitalizations within 6 months, (iii) current alcohol use with alcoholic cirrhosis, and (iv) unsuitable for transplantation work up. We compared consults before and after implementation of the criteria, and we compared outcomes in patients who did and did not see palliative care. Results: With implementation, consults increased (2/25 (8%) vs 11/33 (33%), p = .020). Palliative care was associated with higher completion of health care representative documentation (66.7% vs 35.7%, P = .20) and physician orders for scope of treatment forms (16.7% vs 0%, P = 0.13). Patients seen by palliative care had a higher rate of discharges with hospice (30.8% vs 0, P = .002). Conclusions: Implementation of standardized palliative care consultation criteria for patients with end-stage liver disease increased palliative care utilization. Patients seen by palliative care had increased discharges with hospice services and a trend towards higher completion rates of advanced directives.


Alzheimer Dementia Detection Based on Time-series Instability of Heart Rate.
Towards early detection of Alzheimer dementia (AD), this paper focuses on time-series instability of heart rate of AD patient, and proposes the AD detection method based on heart rate acquired by an unconstrained mattress sensor for daily life use. Through the human subject experiments on 124 days of heart rate of one AD patient and 39 days of heart rate of 21 healthy subjects, the following implication have been revealed: (1) an accuracy of the proposed AD detection method based on the time-series features of heart rate is approximately 98%; and (2) the time-series instability of heart rate is found in the rapid oscillation of heart rate (i.e., an increase/decrease of heart rate over 2 seconds).


Cell contact, prostaglandin E(2) and transforming growth factor beta 1 play non-redundant roles in human mesenchymal stem cell induction of CD4+CD25(High) forkhead box P3+ regulatory T cells.
Adult human mesenchymal stromal or stem cells (MSC) can differentiate into a variety of cell types and are candidate cellular therapeutics in regenerative medicine. Surprisingly, these cells also display multiple potent immunomodulatory capabilities, including allosuppression, making allogeneic cell therapy a possibility. The exact mechanisms involved in regulatory T cell induction by allogeneic human MSC was examined, using purified CD4+ populations and well-characterized bone marrow-derived adult human MSC. Allogeneic MSC were shown to induce forkhead box P3 (FoxP3)+ and CD25+ mRNA and protein expression in CD4+ T cells. This phenomenon required direct contact between MSC and purified T cells, although cell contact was not required for MSC induction of FoxP3 expression in an unseparated mononuclear cell population. In addition, through use of antagonists and neutralizing antibodies, MSC-derived prostaglandins and transforming growth factor (TGF)-beta1 were shown to have a non-redundant role in the induction of CD4+CD25+FoxP3+ T cells. Purified CD4+CD25+ T cells induced by MSC co-culture expressed TGF-beta1 and were able to suppress alloantigen-driven proliferative responses in mixed lymphocyte reaction. These data clarify the mechanisms of human MSC-mediated allosuppression, supporting a sequential process of regulatory T cell induction involving direct MSC contact with CD4+ cells followed by both prostaglandin E(2) and TGF-beta1 expression. Overall, this study provides a rational basis for ongoing clinical studies involving allogeneic MSC.


The comparative pharmacokinetics of 3H-dihydrostreptomycin in solution and liposomal form in normal and Mycobacterium tuberculosis infected mice.
In intact and tuberculous mice a comparative pharmacokinetics of 3H-dihydrostreptomycin (DHS) encapsulated into the liposomes (LE) prepared from egg lecithin and soluble form of DHS (SOL) after their intravenous administration has been studied. The values of the total area under the serum concentration--time curve of DHS (AUC 0----infinity), administered in the LE form was 8.8 times higher in normal and 5.9 times higher in mice with advanced tuberculosis than in mice treated with soluble form of DHS (SOL). AUC 0----infinity values in spleen and liver were 2.2 and 4.5 times higher, respectively, in use of LE form, where as AUC 0----infinity values in lungs and kidneys were independent from the drug form of DHS in normal mice. DHS levels in lungs of tuberculous mice were 3 times higher 3 hours after administration of LE in comparison with those after SOL DHS. AUC 0----infinity values in spleen and liver of tuberculous mice were 9.2 and 7.3 times higher, respectively, in comparison with those after SOL DHS. AUC 0----infinity values in kidneys of tuberculous mice didn't differ significantly independently from the use of one or another form of the drug.


Domestic violence: a Resource Manual for Healthcare Providers for the State of Delaware. Part 3: Health Care Provider's Response.
The Medical Subcommittee of the Delaware Domestic Violence Coordinating Council (DVCC) has worked on and completed Domestic Violence: A Resource Manual for Healthcare Providers for the State of Delaware. It is both an educational tool and a handy resource for documentation and reference, with many examples of clinical guidelines, screening questions and checklists for safety screening. It is intended for all healthcare providers, not just physicians. The Delaware Medical Journal will be reprinting three very important chapters from this manual: Understanding Domestic Violence (October 2000), Legal issues (November 2000), and Health Care Provider's Response.


The Interplay between Message Framing and Message Recipients' Regulatory Focus in Promoting HPV Prevention Strategies.
Limited awareness and low uptake rate of Human papillomavirus (HPV) prevention strategies among females require the development of more effective educational interventions. Regulatory focus theory posits the matching of framing valence with the recipients' regulatory focus increases persuasiveness. Following regulatory focus theory, we examined how individual regulatory focus changed the effects of gain- and loss-framed messages on promoting consistent condom use and HPV DNA testing for HPV prevention. We also explored whether this interaction effect impacts the influences of target individuals' initial attitudes about condom use and HPV DNA testing on post attitudes and intentions. Results of Study 1 showed that, in general, the gain-framed message fit with regulatory focus (i.e., promotion focus) promoted more positive attitudes about consistent condom use than the gain-framed message nonfit with their regulatory focus (i.e., prevention focus).Nevertheless, the gain-framed message nonfit with regulatory focus (i.e., prevention focus) strengthened the negative relationship between initial attitudes and intentions, which promoted the intentions to use condom consistently among people who initially held negative attitudes toward consistent condom use. In Study 2, we did not observe a significant interaction effect of message framing and regulatory focus in the HPV DNA testing context. However, we observed that the gain-framed message nonfit with regulatory focus (i.e., prevention focus) led to the changes in the significance of the initial attitudes - post attitudes relationship from significant to non-significant. Thus, the reliance on initial negative attitudes about HPV DNA testing in decision-making decreased. Theoretical and practical implications of our research were discussed.


Microgravity mediated changes in phytoferritin accumulation in soybean root cap cells.
Phytoferritin is an iron-protein complex analogous to the ferritin found in mammalian, bacteria and fungi cells. Phytoferritin molecules are large proteins, about 10.5 nm in diameter, visualised in an electron microscope as discrete, electron dense particles with iron-containing core, where several thousand atoms of iron lie within the proteinaceous shell (apoferritin). In higher plants, a plastid stroma is the site of phytoferritin storage. Phytoferritin is seen in all types of plastids. It is considered to be a mechanism used by cells to store iron in a non-toxic form. Phytoferritin-bound iron may subsequently be used to form iron-containing components. It was shown that low levels of phytoferritin are synthesised in normal green leaves, whereas chlorotic leaves do not have a measurable amount of phytoferritin and leaves of iron-loaded seedlings contain a high level of total iron, and phytoferritin well-filled by iron. Phytoferritin accumulation was observed in photosynthetic inactivity chloroplasts during senescence and disease. In this study we analised the effects of microgravity and ethylene on production of phytoferritin in the root cap columella cells of soybean seedlings.


What is the difference between Helicobacter pylori-associated dyspepsia and functional dyspepsia?
Advances in basic and clinical research have revealed that Helicobacter pylori (H. pylori) infection plays an important role in the development of gastroduodenal dysmotility and hypersensitivity, as also in dyspepsia symptoms. In addition, recent studies have proposed an inflammation-immunological model for the pathogenesis of functional dyspepsia. Since H. pylori is the major microbe that provokes a gastroduodenal inflammatory response, it should not be overlooked when considering the pathophysiology of dyspepsia symptoms. In fact, population-based studies have demonstrated that H. pylori is detected more frequently in dyspepsia patients. However, although many clinical studies tried to reveal the association of H. pylori infection with gastric motility dysfunction or hypersensitivity, the results have been conflicting. On the other hand, many etiological features were revealed for the development of H. pylori-associated dyspepsia, such as abnormal ghrelin or leptic secretion, altered expression of muscle-specific microRNAs, and duodenal inflammatory cell infiltration. In addition, therapeutic strategy for H. pylori-associated dyspepsia would be different from H. pylori-negative functional dyspepsia. This review focuses the issue of whether H. pylori-associated dyspepsia should be considered as a different disease entity from functional dyspepsia.


Nanobodies in cytokine‑mediated immunotherapy and immunoimaging (Review).
Cytokines are the main regulators of innate and adaptive immunity, mediating communications between the cells of the immune system and regulating biological functions, including cell motility, differentiation, growth and apoptosis. Cytokines and cytokine receptors have been used in the treatment of tumors and autoimmune diseases, and to intervene in cytokine storms. Indeed, the use of monoclonal antibodies to block cytokine‑receptor interactions, as well as antibody‑cytokine fusion proteins has exhibited immense potential for the treatment of tumors and autoimmune diseases. Compared with these traditional types of antibodies, nanobodies not only maintain a high affinity and specificity, but also have the advantages of high thermal stability, a high capacity for chemical manipulation, low immunogenicity, good tissue permeability, rapid clearance and economic production. Thus, nanobodies have extensive potential for use in the diagnosis and treatment of cytokine‑related diseases. The present review summarizes the application of nanobodies in cytokine‑mediated immunotherapy and immunoimaging.


Influence of Baseline Diastolic Blood Pressure on the Effects of Systolic Blood Pressure Lowering on Cognitive Function in Type 2 Diabetes Mellitus.
Lowering of systolic blood pressure (SBP) in patients with low diastolic blood pressure (DBP), can further lower DBP. This can potentially decrease cerebral perfusion and cognition. We examined the influence of baseline DBP on the effect of lowering SBP on cognition. This is a post hoc analysis of the Memory in Diabetes (MIND) substudy (N = 1,430) of the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (NCT00000620). Standard neuropsychological tests (Digit Symbol Substitution Test [DSST], Mini-Mental State Examination [MMSE], Rey Auditory Verbal Learning Test [RAVLT], and Stroop test) were performed at baseline and months 20 and 40. We compared the effects of intensive (goal SBP <120 mm Hg) vs. standard (goal SBP <140 mm Hg) SBP control on the changes in the 4 test scores from baseline to the averages of months 20 and 40 across the range of baseline DBP using cubic spline terms. Mean age was 63 ± 6 years, 55% were women and 66% White. Participates with lower baseline DBP were older, had more cardiovascular events and a longer duration of diabetes. There was no difference in the change in DSST (-0.22; 95% CI -0.97, 0.52), MMSE (-0.14; 95% CI -0.34, 0.06), RAVLT (-0.12; 95% CI -0.29, 0.06), and Stroop interference (-0.47; 95% CI -1.76, 0.82) in the intensive vs. standard SBP intervention. There was no interaction between baseline DBP and change in scores with the SBP intervention. Intensive SBP reduction does not adversely affect cognition, even in those with low baseline DBP.


Lack of genotoxicity potential and safety assessment of 4-(2-hydroxyethyl) morpholine present as an impurity in pharmaceuticals and nutritional supplements.
4-(2-Hydroxyethyl) morpholine (HEM) is widely used as a building block of macromolecules in the manufacture of pharmaceuticals and dietary supplements and could remain as an impurity in the finished products. An evaluation of HEM was conducted to identify endpoints that could be used to determine the point-of-departure (POD) for use in assessing the potential risk from exposure to HEM. No oral repeated dose toxicological studies were located for HEM. Therefore, suitable analogue(s) were identified. Although oral repeated dose studies were available for the analogues, the studies were not of sufficient duration for use in the assignment of a POD for risk evaluation. Accordingly, the Threshold of Toxicological Concern (TTC) approach, which proposes that a de minimis value can be derived to qualitatively assess risk, was considered for HEM. To determine the appropriate TTC approach (genotoxic or non-genotoxic), the genotoxicity of HEM and its analogues were evaluated. The weight of the evidence indicated that HEM, and the appropriate analogues, are not genotoxic. Considering the chemical structure of HEM, the non-genotoxic Cramer class III TTC value of 1.5 μg/kg bw/day was determined to be appropriate for use in safety assessment of HEM as an impurity in products intended for human consumption.


Phospholipase A(2) digestion of cardiolipin bound to bovine cytochrome c oxidase alters both activity and quaternary structure.
Phospholipase A(2) from Crotalus atrox hydrolyzes all of the phospholipids that are associated with purified, detergent-solubilized cytochrome c oxidase; less than 0.05 mol cardiolipin (CL)(1) remains bound per mol enzyme. Coincident with the hydrolysis of cardiolipin is a reversible decrease of 45-50% in the electron transport activity of the dodecylmaltoside-solubilized enzyme. Full activity is recoverable (90-98%) by addition of exogenous cardiolipin, but not by either phosphatidylcholine or phosphatidylethanolamine. Unexpectedly, cleavage of cardiolipin causes the dissociation of both subunits VIa and VIb from the enzyme. These are the two subunits that form the major protein-protein contacts between the two monomeric units within the dimeric complex. Although hydrolysis of CL by phospholipase A(2) and loss of these subunits is linked, the reverse process does not occur, i.e., removal of subunits VIa and VIb does not cause dissociation of the two functionally important, tightly bound cardiolipins. Nor does addition of exogenous cardiolipin result in reassociation of the two subunits with the remainder of the complex. We conclude that cardiolipin is not only essential for full electron transport activity, but also has an important structural role in stabilizing the association of subunits VIa and VIb within the remainder of the bovine heart enzyme.


Toxic equivalent concentrations (TEQs) for baseline toxicity and specific modes of action as a tool to improve interpretation of ecotoxicity testing of environmental samples.
The toxic equivalency concept is a widely applied method to express the toxicity of complex mixtures of compounds that act via receptor-mediated mechanisms such as induction of the arylhydrocarbon or estrogen receptors. Here we propose to extend this concept to baseline toxicity, using the bioluminescence inhibition test with Vibrio fischeri, and an integrative ecotoxicity endpoint, algal growth rate inhibition. Both bioassays were validated by comparison with literature data and quantitative structure-activity relationships (QSARs) for baseline toxicity were developed for all endpoints. The novel combined algae test, with Pseudokirchneriella subcapitata, allows for the simultaneous evaluation of specific inhibition of photosynthesis and growth rate. The contributions of specific inhibition of photosynthesis and non-specific toxicity could be differentiated by comparing the time and endpoint pattern. Photosynthesis efficiency, measured with the saturation pulse method after 2 h of incubation, served as indicator of specific inhibition of photosynthesis by photosystem II inhibitors. Diuron equivalents were defined as toxicity equivalents for this effect. The endpoint of growth rate over 24 h served to derive baseline toxicity equivalent concentrations (baseline-TEQ). By performing binary mixture experiments with reference compounds and complex environmental samples from a sewage treatment plant and a river, the TEQ concept was validated. The proposed method allows for easier interpretation and communication of effect-based water quality monitoring data and provides a basis for comparative analysis with chemical analytical monitoring.


Systematic Review of the Role of Targeted Therapy in Metastatic Neuroendocrine Tumors.
Targeted therapies [interferon (IFN), vascular endothelial growth factor (VEGF) inhibitors, and somatostatin analogs (SSA)] have become an integral part of the neuroendocrine tumor (NET) treatment paradigm. We systematically reviewed the available literature to assess the overall beneficial and negative effects of targeted therapy on progression-free survival (PFS), overall survival (OS), response rate (RR), and toxicity. Randomized controlled trials (RCT) were identified from MEDLINE, Embase, other major databases, and an electronic search of major conferences. Abstract review, quality assessment, and data abstraction were performed independently by 2 investigators. Meta-analyses were conducted using the generic inverse variance method with a random-effects model, with studies pooled according to drug class and/or control arm for clinical homogeneity. Fifteen RCT [SSA, n = 2; mammalian target of rapamycin (mTOR)/VEGF inhibitors, n = 4; IFN, n = 3; targeted therapy added to everolimus, n = 2, and other, n = 4] investigating 2,790 patients were included. Overall, targeted agents improved PFS (HR 0.54; 95% CI 0.40-0.73) but not OS (HR 0.86; 95% CI 0.72-1.01). SSA improved PFS (HR 0.41; 95% CI 0.29-0.58) but not OS (HR 1.00; 95% CI 0.58-1.74). mTOR/VEGF inhibitors improved PFS (HR 0.48; 95% CI 0.32-0.72) but not OS (HR 0.82; 95% CI 0.58-1.17). Targeted therapies added to everolimus or IFN did not improve either PFS or OS. The RR overall was improved (OR 2.85; 95% CI 1.77-4.59) but toxicity was increased (meta-analysis not performed). The addition of targeted therapies improves PFS but not OS in NET. The evidence is strongest for VEGF inhibitors and SSA. There is an ongoing need for well-designed RCT to inform the optimal use of targeted therapies in NET.


Single-Dimer Formation Rate Reveals Heterogeneous Particle Surface Reactivity.
Biofunctionalized micro- and nanoparticles are important for a wide range of applications, but methodologies to measure, modulate, and model interactions between individual particles are scarce. Here, we describe a technique to measure the aggregation rate of two particles to a single dimer, by recording the trajectory that a particle follows on the surface of another particle as a function of time. The trajectory and the interparticle potential are controlled by a magnetic field. Particles were studied with and without conjugated antibodies in a wide range of pH conditions. The data shows that the aggregation process strongly depends on the particle surface charge density and hardly on the antibody surface coverage. Furthermore, microscopy videos of single particle dimers reveal the presence of reactive patches and thus heterogeneity in the particle surface reactivity. The aggregation rates measured with the single-dimer experiment are compared to data from an ensemble aggregation experiment. Quantitative agreement is obtained using a model that includes the influence of surface heterogeneity on particle aggregation. This single-dimer experiment clarifies how heterogeneities in particle reactivity play a role in colloidal stability.


Clot dynamics and mortality: The MA-R ratio.
The coagulopathy of trauma, illustrated by a short R-time, is common and well understood. The physiology behind this may be early thrombin burst with rapid clot formation. Rapid consumption of fibrinogen, however, may result in weak clot and substrate depletion, resulting in low MA. While these characteristics are interesting, utilizing thromboelastography (TEG) to identify those at risk of subsequent bleeding diathesis, especially in those who do not demonstrate early signs of physiologic derangement, is challenging. We have developed a novel ratio utilizing TEG values to describe patients at specific risk of traumatic coagulopathy. The purpose of this study was to create a single TEG value, which would reflect both the hypercoagulability and hypocoagulability of TIC. We hypothesized that this ratio, at admission, would be indicative of TIC and predictive of both blood product transfusion volumes and subsequent mortality. Patients admitted via the highest activation criteria at one of two Level I trauma centers were included if they received at least 1 unit of packed red blood cells in the first 24 hours of admission. The admission TEG was collected, and a ratio was calculated by dividing the MA by the R-time (MA-R). MA-R quartiles were developed, and multivariable logistic regression was utilized to determine odds of mortality. Three hundred thirty patients with admission TEG were included. In all patients, median age was 35 years (interquartile range, 25-54 years), Injury Severity Score (ISS) was 20 (interquartile range, 13-29), 76% were male, and 43% had penetrating trauma. The MA-R groups were based on quartiles. Multivariable analysis, controlling for mechanism of injury, ISS, and admission pH, showed that increasing ratios were associated with decreased odds of death. The lowest MA-R ratios were also significantly associated with higher ISS, higher rates of blunt injury, and higher plasma utilization without a significant difference in packed red blood cell administration. Patients with the lowest MA-R ratios demonstrated the highest mortality rates. This novel ratio may prove highly useful to predict at-risk patients early, when other physiologic indicators are absent. The mechanism driving this finding may rest in fibrinogen depletion, resulting in weak clot. Patients with low MA-R ratios may benefit from earlier resuscitation with cryoprecipitate, rather than the traditional use of plasma found in current massive transfusion protocols. Prognostic study, Level I.


Dynamics of thin-film thermal detectors in infrared imaging systems. 1: basic equations and fourier analysis.
The complete Fourier analysis in space and time is performed for a three-dimensional model of thin-film thermal-imaging systems. The model includes heat losses by thermal radiation and by heat conduction within the film as well as into the adjacent medium. Dirac delta functions are used for the description of the specific heat and the thermal conductivity. The exact solutions of the basic heat equation are applied for a comparison of different types of the Panicon, a passive thermal imaging device. The relevant temperature response is illustrated in the Fourier space. The inclusion of the adjacent medium implies an occasional maximum of the response function in k space.


Pediatric resources on the Internet.
This article introduces the podiatric physician interested in pediatrics to the resources available on the Internet. It surveys search engines, gateway sites on the World Wide Web leading to a wealth of pediatric information and services, and features such as electronic mail, news-groups, and Gopher sites. Examples illustrate how such resources can be helpful to the practicing podiatrist.


Relationship of patient characteristics and inpatient rehabilitation services to 5-year outcomes following spinal cord injury: A follow up of the SCIRehab project.
To examine associations of patient characteristics and treatment quantity delivered during inpatient spinal cord injury (SCI) rehabilitation with outcomes at 5 years post-injury and compare them to the associations found at 1 year post-injury. Observational study using Practice-Based Evidence research methodology in which clinicians documented treatment details. Regression modeling was used to predict outcomes. Five inpatient SCI rehabilitation centers in the US. Participants were 792 SCIRehab participants who were >12 years of age, gave informed consent, and completed both a 1-year and 5-year post-injury interview. Outcome data were derived from Spinal Cord Injury Model Systems (SCIMS) follow-up interviews at 5 years post-injury and, similar to the 1-year SCIMS outcomes, included measures of physical independence, societal participation, life satisfaction, and depressive symptoms, as well as place of residence, school/work attendance, rehospitalization, and presence of pressure ulcers. Consistent with 1-year findings, patient characteristics continue to be strong predictors of outcomes 5-years post-injury, although several variables add to the prediction of some of the outcomes. More time in physical therapy and therapeutic recreation were positive predictors of 1-year outcomes, which held less true at 5 years. Greater time spent with psychology and social work/case management predicted greater depressive symptomatology 5-years post-injury. Greater clinician experience was a predictor at both 1- and 5 -years, although the related positive outcomes varied across years. Various outcomes 5-years post-injury were primarily explained by pre-and post-injury characteristics, with little additional variance offered by the quantity of treatment received during inpatient rehabilitation.


Prognostic impact of young age on stage IV prostate cancer treated with primary androgen deprivation therapy.
To elucidate whether the disease characteristics and prognosis of stage IV prostate cancer treated with primary androgen deprivation therapy differ between young and elderly patients. A total of 3006 patients identified from the database of the Japan Study Group of Prostate Cancer were included in the analysis according to the following entry criteria: age of 75 years or less and stage IV disease. These patients were stratified into three groups: young (aged ≤ 55 years); middle-aged (aged ≧ 56 and ≤ 65 years); and elderly (aged ≧ 66 and ≤ 75 years). Their prognoses were analyzed both within age groups and according to whether or not there was metastasis. The proportion of lymph node metastasis was significantly higher in the young group than in the elderly group (P = 0.007), and there were no significant differences in other factors among age groups. The overall survival rate at 5 years in the young group was significantly worse than that in the middle-aged and elderly groups (26.6%, 59.7% and 55.3%, respectively) in patients with stage IV disease with metastasis, although there was no difference among age groups in patients with stage IV disease without metastasis. Multivariate analysis showed that younger age was an independent strong prognostic factor in stage IV disease with metastasis. Young men with metastatic prostate cancer have a poor prognosis. Young age is an independent prognostic factor in stage IV metastatic prostate cancer patients treated with primary androgen deprivation therapy.


Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for rapid diagnosis of neonatal sepsis.
The difficulties in diagnosis of neonatal sepsis are due to varied clinical presentation, low sensitivity of blood culture which is considered the gold standard and empirical antibiotic usage affecting the outcome of results. Though polymerase chain reaction (PCR) based detection of bacterial 16S rRNA gene has been reported earlier, this does not provide identification of the causative agent. In this study, we used restriction fragment length polymorphism (RFLP) of amplified 16S rRNA gene to identify the organisms involved in neonatal sepsis and compared the findings with blood culture. Blood samples from 97 neonates were evaluated for diagnosis of neonatal sepsis using BacT/Alert (automated blood culture) and PCR-RFLP. Bacterial DNA was detected by 16S rRNA gene PCR in 55 cases, while BacT/Alert culture was positive in 34 cases. Staphylococcus aureus was the most common organism detected with both methods. Klebsiella spp. was isolated from four samples by culture but was detected by PCR-RFLP in five cases while Acinetobacter spp. was isolated from one case but detected in eight cases by PCR-RFLP. The sensitivity of PCR was found to be 82.3 per cent with a negative predictive value of 85.7 per cent. Eighty of the 97 neonates had prior exposure to antibiotics. The results of our study demonstrate that PCR-RFLP having a rapid turnaround time may be useful for the early diagnosis of culture negative neonatal sepsis.


Exploring the association between macroeconomic indicators and dialysis mortality.
Mortality on dialysis varies greatly worldwide, with patient-level factors explaining only a small part of this variation. The aim of this study was to examine the association of national-level macroeconomic indicators with the mortality of incident dialysis populations and explore potential explanations through renal service indicators, incidence of dialysis, and characteristics of the dialysis population. Aggregated unadjusted survival probabilities were obtained from 22 renal registries worldwide for patients starting dialysis in 2003-2005. General population age and health, macroeconomic indices, and renal service organization data were collected from secondary sources and questionnaires. Linear modeling with log-log transformation of the outcome variable was applied to establish factors associated with survival on dialysis. Two-year survival on dialysis ranged from 62.3% in Iceland to 89.8% in Romania. A higher gross domestic product per capita (hazard ratio=1.02 per 1000 US dollar increase), a higher percentage of gross domestic product spent on healthcare (1.10 per percent increase), and a higher intrinsic mortality of the dialysis population (i.e., general population-derived mortality risk of the dialysis population in that country standardized for age and sex; hazard ratio=1.04 per death per 10,000 person years) were associated with a higher mortality of the dialysis population. The incidence of dialysis and renal service indicators were not associated with mortality on dialysis. Macroeconomic factors and the intrinsic mortality of the dialysis population are associated with international differences in the mortality on dialysis. Renal service organizational factors and incidence of dialysis seem less important.


Effectiveness and Acceptance of Multimodal Antibiotic Stewardship Program: Considering Progressive Implementation and Complementary Strategies.
Multiple modes of interventions are available when implementing an antibiotic stewardship program (ASP), however, their complementarity has not yet been assessed. In a 938-bed hospital, we sequentially implemented four combined modes of interventions over one year, centralized by one infectious diseases specialist (IDS): (1) on-request infectious diseases specialist consulting service (IDSCS), (2) participation in intensive care unit meetings, (3) IDS intervention triggered by microbiological laboratory meetings, and (4) IDS intervention triggered by pharmacist alert. We assessed the complementarity of the different cumulative actions through quantitative and qualitative analysis of all interventions traced in the electronic medical record. We observed a quantitative and qualitative complementarity between interventions directly correlating to a decrease in antibiotic use. Quantitatively, the number of interventions has doubled after implementation of IDS intervention triggered by pharmacist alert. Qualitatively, these kinds of interventions led mainly to de-escalation or stopping of antibiotic therapy (63%) as opposed to on-request IDSCS (32%). An overall decrease of 14.6% in antibiotic use was observed (p = 0.03). Progressive implementation of the different interventions showed a concrete complementarity of these actions. Combined actions in ASPs could lead to a significant decrease in antibiotic use, especially regarding critical antibiotic prescriptions, while being well accepted by prescribers.


Malaria burden and costs of intensified control in Bhutan, 2006-14: an observational study and situation analysis.
The number of malaria cases has fallen in Bhutan in the past two decades, and the country has a goal of complete elimination of malaria by 2016. The aims of this study are to ascertain the trends and burden of malaria, the costs of intensified control activities, the main donors of funding for the control activities, and the costs of different preventive measures in the pre-elimination phase (2006-14) in Bhutan. We undertook a descriptive analysis of malaria surveillance data from 2006 to 2014, using data from the Vector-borne Disease Control Programme (VDCP) run by the Department of Public Health of Bhutan's Ministry of Health. Malaria morbidity and mortality in local Bhutanese people and foreign nationals were analysed. The cost of different control and preventive measures were calculated, and the average numbers of long-lasting insecticidal nests per person were estimated. A total of 5491 confirmed malaria cases occurred in Bhutan between 2006 and 2014. By 2013, there was an average of one long-lasting insecticidal net for every 1·51 individuals. The cost of procuring long-lasting insecticidal nets accounted for more than 90% of the total cost of prevention measures. The Global Fund to Fight AIDS, Tuberculosis and Malaria was the main international donor, accounting for more than 80% of the total funds. The malaria burden in Bhutan decreased significantly during the study period with high coverage of long-lasting insecticidal nets. The foreseeable challenges that require national attention to maintain a malaria-free status after elimination are importation of malaria, especially from India; continued protection of the population in endemic districts through complete coverage with long-lasting insecticidal nets and indoor residual spraying; and exploration of local funding modalities post-elimination in the event of a reduction in international funding. None.


Precursor lesions of mucinous carcinoma of the breast: analysis of 130 cases.
Mucinous mammary carcinoma (MC) is a tumor type with relatively favorable prognosis. Unlike the circumstances surrounding conventional invasive duct carcinoma, data are limited regarding precursor lesions for MC. This study characterizes patterns of mucinous ductal carcinoma in situ (DCIS) as a precursor lesion for MC. All slides from 130 cases of MC encountered between 2000 and 2011 at Henry Ford Hospital, Detroit, MI were reviewed to subclassify MC, identify DCIS, and explore transition patterns from DCIS to MC. Calponin, p63, chromogranin, synaptophysin, CD56, and MIB-1 immunostaining analyses were performed in 65 cases. Among 106 cases of pure (71 type A, 35 type B) and 24 cases of mixed MC, DCIS appeared in 88 (68%) specimens, with all but 4 showing luminal mucin accumulation. Dominant patterns of mucinous DCIS were cribriform/solid (66), cribriform and papillary (7), papillary (5), micropapillary (3), and flat (3). Fifty-seven (68%) cases of mucinous DCIS demonstrated transitions from DCIS to MC. Luminal mucinous distention, focal flattening and attenuation of the epithelium, and disruption of the duct wall resulting in a mucocele-like extravasation of malignant epithelia with escaping mucin was a transition pattern seen with all architectures of DCIS and in all types of MC. This was the only pattern of transition to type A MC. The epithelial outpouching, formation of a cleft with accumulation of mucin around the epithelium, and transition into mucin pools with floating tumor cell clusters was the second transition pattern that went from cribriform/solid DCIS to type B and mixed MC. DCIS preceding aggressive phenotypes of MC (type B and mixed) more often had a cribriform/solid architecture, higher nuclear grade, and higher Ki-67-labeling index (all P<0.05). In summary, mucinous DCIS is a precursor to MC with distinctive features that link patterns of DCIS with aggressive MC phenotypes. The 2 observed transitions between mucinous DCIS and MC suggest that pathogenesis of different types of MC is different correlating with less or more aggressive behavior of the latter.


Development and characterization of pituitary GH3 cell clones stably transfected with a human proinsulin cDNA.
Successful beta-cell replacement therapy in insulin-dependent (type I) diabetes is hindered by the scarcity of human donor tissue and by the recurrence of autoimmune destruction of transplanted beta cells. Availability of non-beta cells, capable of releasing insulin and escaping autoimmune recognition, would therefore be important for diabetes cell therapy. We developed rat pituitary GH3 cells stably transfected with a furin-cleavable human proinsulin cDNA linked to the rat PRL promoter. Two clones (InsGH3/clone 1 and 7) were characterized in vitro with regard to basal and stimulated insulin release and proinsulin transgene expression. Mature insulin secretion was obtained in both clones, accounting for about 40% of total released (pro)insulin-like products. Immunocytochemistry of InsGH3 cells showed a cytoplasmic granular insulin staining that colocalized with secretogranin II (SGII) immunoreactivity. InsGH3 cells/clone 7 contained and released in vitro significantly more insulin than clone 1. Secretagogue-stimulated insulin secretion was observed in both InsGH3 clones either under static or dynamic conditions, indicating that insulin was targeted also to the regulated secretory pathway. Proinsulin mRNA levels were elevated in InsGH3 cells, being significantly higher than in betaTC3 cells. Moreover, proinsulin gene expression increased in response to various stimuli, thereby showing the regulation of the transfected gene at the transcriptional level. In conclusion, these data point to InsGH3 cells as a potential beta-cell surrogate even though additional engineering is required to instruct them to release insulin in response to physiologic stimulations.


The effect of alignment on the rate-dependent behavior of a main-chain liquid crystal elastomer.
This study investigated the effect of alignment on the rate-dependent behavior of a main-chain liquid crystal elastomer (LCE). Polydomain nematic LCE networks were synthesized from a thiol-acrylate Michael addition reaction in the isotropic state. The polydomain networks were stretched to different strain levels to induce alignment then crosslinked in a second stage photopolymerization process. The LCE networks were subjected to dynamic mechanical tests to measure the temperature-dependent storage modulus and uniaxial tension load-unload tests to measure the rate-dependence of the Young's modulus, mechanical dissipation, and characteristics of the soft stress response. Three-dimensional (3D) digital image correlation (DIC) was used to characterize the effect of domain/mesogen relaxation on the strain fields. All LCE networks exhibited a highly rate-dependent stress response with significant inelastic strains after unloading. The Young's modulus of the loading curve and hysteresis of the load-unload curves showed a power-law dependence on the strain rate. The Young's modulus increased with alignment and larger anisotropy and a smaller power-law exponent was measured for the Young's modulus and hysteresis for the highly aligned monodomains. The polydomain and pre-stretched networks loaded perpendicular to the alignment direction exhibited a soft stress response that featured a rate-dependent peak stress, strain-softening, and strain-stiffening. The 3D-DIC strain fields for the polydomain network and programmed networks stretched in the perpendicular direction were highly heterogeneous, showing regions of alternating higher and lower strains. The strain variations increased initially with loading, peaked during the strain softening part of the stress response, then decreased during the strain stiffening part of the stress response. Greater variability was measured for lower strain rates. These observations suggest that local domain/mesogen relaxation led to the development of the heterogeneous strain patterns and strain softening in stress response. These findings improved understanding of the kinetics of mesogen relaxation and its contributions to the rate-dependent stress response and mechanical dissipation.


Immunohistochemical localization of glial fibrillary acidic protein in human glial neoplasms.
The presence and distribution of glial fibrillary acidic protein in fixed, paraffin embedded tissue were studied in 85 human intracranial neoplasms, using the peroxidase-anti-peroxidase method. In some cases, indirect immunofluorescence of frozen sections was used as well. In normal tissue, only the cell processes and perikarya of fibrous astrocytes were stained. Immunostaining was also observed in the following glial neoplasms: astrocytomas (all varieties), astroblastoma, subependymal giant cell astrocytoma, subependymoma, glioblastoma multiforme and ependymoma. The astrocytic elements of mixed gliomas and of medulloblastomas undergoing glial differentiation were likewise strongly stained. In contrast, oligodendrogliomas, meningiomas, pituitary adenomas, sarcomas, lymphomas and metastatic carcinomas were negative. Either a perikaryal or a diffuse fibrillary staining pattern was observed. Combination of the two patterns occasionally occurred. The perikaryal staining was prominent in gemistocytic astrocytomas and in astroblastomas. A distinct negative correlation existed between the degree of anaplasia and the intensity of immunostaining.


Disrupted redox homeostasis and aberrant redox gene expression in porcine oocytes contribute to decreased developmental competence.
The objective of this study was to identify specific redox-related genes whose function contributes to oocyte quality and to characterize the role of redox homeostasis in oocyte development. We determined the redox genes glutaredoxin 2 (GLRX2), protein disulfide isomerase family A, members 4 and 6 (PDIA4, PDIA6), and thioredoxin reductase 1 (TXNRD1) were differentially expressed between adult (more competent) and prepubertal (less competent) porcine in vitro-matured (IVM) oocytes. The association between these genes and oocyte quality was further validated by comparing transcript abundance in IVM with that in in vivo-matured (VVM) prepubertal and adult oocytes. By maturing oocytes in variable redox environments, we demonstrated that a balanced redox environment is important for oocyte quality, and over-reduction of the environment is as detrimental as excess oxidation. Critical levels of reactive oxygen species (ROS) and glutathione (GSH) are required for oocyte competence. Elevated GSH and lower ROS in prepubertal oocytes suggest disrupted redox homeostasis exists in these cells. By further comparing GLRX2, PDIA4, PDIA6, and TXNRD1 expression levels in oocytes matured under these different redox environments, we found aberrant expression patterns in prepubertal oocytes but not in adult oocytes when the maturation medium contained high concentrations of antioxidants. These results suggest that prepubertal oocytes are less competent in regulating redox balance than adult oocytes, contributing to lower oocyte quality. In conclusion, aberrant redox gene expression patterns and disrupted redox homeostasis contribute to decreased developmental competence in prepubertal and IVM porcine oocytes. The balance between ROS and GSH plays an important role in oocyte quality.


Social calls of the little auk (Alle alle) reflect body size and possibly partnership, but not sex.
Source-filter theory posits that an individual's size and vocal tract length are reflected in the parameters of their calls. In species that mate assortatively, this could result in vocal similarity. In the context of mate selection, this would mean that animals could listen in to find a partner that sounds-and therefore is-similar to them. We investigated the social calls of the little auk (Alle alle), a highly vocal seabird mating assortatively, using vocalizations produced inside 15 nests by known individuals. Source- and filter-related acoustic parameters were used in linear mixed models testing the possible impact of body size. A principal component analysis followed by a permuted discriminant function analysis tested the effect of sex. Additionally, randomization procedures tested whether partners are more vocally similar than random birds. There was a significant effect of size on the mean fundamental frequency of a simple call, but not on parameters of a multisyllable call with apparent formants. Neither sex nor partnership influenced the calls-there was, however, a tendency to match certain parameters between partners. This indicates that vocal cues are at best weak indicators of size, and other factors likely play a role in mate selection.


Turning Towards or Turning Away: A Comparison of Mindfulness Meditation and Guided Imagery Relaxation in Patients with Acute Depression.
Disengaging from maladaptive thinking is an important imperative in the treatment of depression. Mindfulness training is aimed at helping patients acquire relevant skills for this purpose. It remains unclear, however, whether this practice is helpful when patients are acutely depressed. In order to investigate effects of mindfulness on symptoms and self-regulatory capacities in this group, the current study compared a brief training in mindfulness (n = 19) to guided imagery relaxation (n = 18). Participants were introduced to the respective techniques in a single session, and practised daily over one week. Self-reported severity of symptoms, difficulties in emotion-regulation, attentional control, the ability to decentre, and mindfulness were assessed pre and postintervention, and at a one-week follow-up. Symptoms of depression significantly decreased and self-regulatory functioning significantly increased in both groups, with changes being maintained during follow-up. When controlling for change in depressive symptoms, results showed significantly higher improvements in emotion regulation at follow-up in the mindfulness group. The ability to decentre predicted changes in symptoms from pre to postintervention, while mindfulness skills predicted changes in symptoms during the maintenance phase. The findings suggest that both practices can help to instigate reductions in symptoms and enhance self-regulatory functioning in depression. However, in order to improve emotion regulation above levels explained by reductions in symptoms more intentional mental training seems necessary. Furthermore, while the ability to disengage from negative patterns of thinking seems crucial for initial reduction of symptoms, maintenance of gains might require broader skills in mindfulness.


Animal study on electromagnetic field biological potency.
This recent basic research study used an animal model protocol to assess specific biomarkers of the effect of non-ionising, non-thermal radiation (2450 MHz microwave radiation at 5-15 mW/cm2) on bone marrow, peripheral blood, and bronchoalveolar free cell populations. Of 40 male Wistar rats taken in the study, 20 animals of the experimental group were irradiated for 2 hours a day, 5 days a week, and subsequently killed on days 1, 8, 16, and 30 of the experiment. The remaining 20 rats served as control. All animals were previously intratracheally instilled with biologically inert microspheres to see the influence of irradiation on lung retention kinetics. The cell response to chosen electromagnetic irradiation was followed quantitatively and qualitatively using the standard laboratory methods. The results of peripheral blood cell response suggested a decreasing tendency in total leukocyte count and in relative lymphocyte count in the treated group. A slight increase was also observed in granulocyte count and in the absolute count of peripheral blood erythrocytes over control animals.


A 6-month controlled naltrexone study: combined effect with cognitive behavioral therapy in outpatient treatment of alcohol dependence.
In several studies, patients with alcohol dependence treated with the opioid antagonist naltrexone have shown fewer relapses to heavy drinking than those receiving placebo. An interaction between the naltrexone effect and the type of psychological therapy has been observed. A 6-month, double-blind, placebo-controlled, parallel-group study was performed at 10 different investigation sites. After a placebo run-in period of 1 week, 118 patients were randomized into 4 treatment groups-50 mg of naltrexone daily or placebo in combination with either cognitive behavioral therapy (CBT) or supportive therapy. The CBT was performed over nine sessions according to the manual of Project MATCH (Matching Alcoholism Treatments to Client Heterogeneity). The supportive therapy was defined as "the treatment as usual." Alcohol consumption, craving, carbohydrate-deficient transferrin, medication compliance by tablet count, and adverse clinical events were assessed at all visits. Other liver enzymes and psychiatric symptoms were also determined. Ninety-one (77%) patients completed the study, and 92 (78%) were 80% compliant with the medication regimen. A lower percentage of heavy-drinking days was shown in the naltrexone group (p = 0.045) compared with the placebo group, as was a lower craving score (p = 0.029). These results are supported by the lower levels of liver enzyme activities (p < 0.010 for aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase), but not by the carbohydrate-deficient transferrin levels, in the naltrexone group. The mean time period before the first day of heavy drinking was longer for the group treated with CBT (p = 0.010), especially in combination with naltrexone (p = 0.007). Naltrexone was well tolerated, and no patients discontinued the study due to side effects. This study supports the effect of naltrexone in outpatient treatment of alcohol dependence and suggests that a beneficial interaction effect with CBT can be expected.


Nanofiber-mediated controlled release of siRNA complexes for long term gene-silencing applications.
Nanofiber scaffold-mediated delivery of small-interfering RNA (siRNA) holds great potential in regenerative medicine by providing biomimicking topographical signals and enhanced gene silencing effects to seeded cells. While the delivery of naked siRNA was demonstrated previously using poly (ε-caprolactone) (PCL) nanofibers, the resulting siRNA release kinetics and gene knockdown efficiencies were sub-optimal. In this study, we investigated the feasibility of encapsulating siRNA and transfection reagent (TKO) complexes within nanofibers comprising of a copolymer of caprolactone and ethyl ethylene phosphate (PCLEEP, diameter ∼ 400 nm). Sustained release of bioactive naked siRNA and siRNA/TKO complexes were obtained for at least 28 days. By copolymerizing EEP with caprolactone, siRNA release was significantly enhanced (total siRNA that was released by day 49 was ∼ 89.3-97.2% as compared to previously reported 3% by plain PCL nanofiber delivery). Using GAPDH as the model protein, bioactivity analyses by supernatant transfection revealed the partial retention of bioactivity of naked siRNA and siRNA/TKO complexes for at least 30 days. In particular, GAPDH siRNA/TKO supernatant alone induced significant gene silencing (∼40%), indicating the feasibility of co-encapsulating siRNA and transfection reagent within a single scaffold construct for sustained delivery. Direct culture of cells on siRNA incorporated scaffolds for scaffold-mediated gene transfection revealed significant gene knockdown even in the absence of transfection reagent (21.3% knockdown efficiency by scaffolds incorporating naked siRNA only). By encapsulating siRNA/TKO complexes, more significant gene knockdown was obtained (30.9% knockdown efficiency as compared to previously reported 18% by plain PCL scaffold-mediated transfection). Taken together, the results demonstrated the feasibility of co-encapsulating siRNA-transfection reagent complexes within a single nanofiber construct for sustained siRNA delivery and enhanced gene knockdown efficiency. The study also highlights the potential of PCLEEP as a platform for tailoring siRNA release kinetics for long-term gene silencing applications.


Prolonging the past counteracts the pull of the present: protracted speciation can explain observed slowdowns in diversification.
Phylogenetic trees show a remarkable slowdown in the increase of number of lineages towards the present, a phenomenon which cannot be explained by the standard birth-death model of diversification with constant speciation and extinction rates. The birth-death model instead predicts a constant or accelerating increase in the number of lineages, which has been called the pull of the present. The observed slowdown has been attributed to nonconstancy of the speciation and extinction rates due to some form of diversity dependence (i.e., species-level density dependence), but the mechanisms underlying this are still unclear. Here, we propose an alternative explanation based on the simple concept that speciation takes time to complete. We show that this idea of "protracted" speciation can be incorporated in the standard birth-death model of diversification. The protracted birth-death model predicts a realistic slowdown in the rate of increase of number of lineages in the phylogeny and provides a compelling fit to four bird phylogenies with realistic parameter values. Thus, the effect of recognizing the generally accepted fact that speciation is not an instantaneous event is significant; even if it cannot account for all the observed patterns, it certainly contributes substantially and should therefore be incorporated into future studies.


Minor increase in risk of road traffic accidents after prescriptions of antidepressants: a study of population registry data in Norway.
Experimental studies have shown that both depression and the use of antidepressants may impair the ability to drive a motor vehicle. Population-based studies have been inconclusive. Differences in results have been shown for cyclic, sedating antidepressants and newer, nonsedating antidepressants. The objective of the present study was to examine whether the use of antidepressants by drivers increased the risk of being involved in traffic accidents. From April 2004 to September 2006, information on prescriptions, road accidents, and emigrations/deaths was obtained from 3 Norwegian population-based registries. Data on people between the ages 18-69 (N = 3.1 million) were linked. Exposure consisted of receiving prescriptions for any antidepressants. Standardized incidence ratios (SIRs) were calculated by comparing the incidence of accidents during time exposed with the incidence over the time not exposed. Sedating antidepressants (tricyclic antidepressants, mianserin, and mirtazapine) were studied together as one group, and newer, nonsedating antidepressants (selective serotonin reuptake inhibitors, moclobemide, venlafaxine, and reboxetine) as another. During the study period, 20,494 road accidents with personal injuries occurred, including 204 and 884 in which the driver was exposed to sedating antidepressants or newer, nonsedating antidepressants, respectively. The traffic accident risk increased slightly for drivers who had received prescriptions for sedating antidepressants (SIR = 1.4, 95% CI = 1.2 to 1.6) or nonsedating antidepressants (SIR = 1.6, 95% CI = 1.5 to 1.7). The SIR estimates were similar for male and female drivers and slightly higher for young drivers (18-34 years of age) using older sedative antidepressants. SIR estimates did not change substantially for different time periods after dispensing of the prescription, for concomitant use of other impairing drugs, or for new users. There was a slightly increased risk of being involved in a traffic accident after having received a prescription for any antidepressants. In the present study, it was not possible to determine whether this increase was due to the antidepressant, the effect of the depression, or characteristics of the patients being prescribed these drugs.


Contemporary imaging of patients with a renal mass: does size on computed tomography equal pathological size?
To evaluate the difference between radiographic size on computed tomography (CT) and the pathological size of renal tumours, in contemporary patients. We retrospectively reviewed the records of 521 patients undergoing surgical resection of a renal mass between 2000 and 2007, who had tumour sizes recorded from both preoperative CT and pathological evaluation of the tumour specimen. Data on histological tumour type were also extracted. The paired Student's t-test was used to compare the mean radiographic size as measured on CT with the mean pathological size, with P < 0.05 considered to indicate statistical significance. For all patients, the mean radiographic size and mean pathological size was 4.79 and 4.69 cm, respectively (P = 0.02). Therefore, on average, radiographic size overestimated pathological size by 1 mm. In patients with a tumour of 4-7 cm, radiographic size overestimated pathological size by 0.21 cm (P = 0.007). However, there was no significant difference in patients with a tumour of <4 cm or >7 cm. Using contemporary patients, there was a statistically significant overestimation of renal tumour sizes by CT compared with the pathological assessment. However, the overall difference between radiographic and pathological tumour size was 1 mm, suggesting that CT provides an accurate method with which to estimate renal tumour size.


Structural features of the cell surface receptor for transferrin that is recognized by the monoclonal antibody OKT9.
The monoclonal antibody OKT9 reacts specifically with the receptors for transferrin on human cells (Sutherland, D. R., Delia, D., Schneider, C., Newman, R. A., Kemshead, J., and Greaves, M. F. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 4515-4519; in Leukemia Markers (Knapp, W., ed) pp. 157-160, Academic Press, New York) and has been used to isolate and characterize this receptor. The receptor is a dimeric glycoprotein (Mr = 180,000) composed of two subunits (Mr = 90,000) and has a pI of approximately 5.2. The transferrin receptor appears to be a transmembrane molecule and is phosphorylated, the phosphate group being predominantly on serine residues. The cell surface form of the molecular possesses both complex and high mannose oligosaccharide chains, which do not appear to have a direct role in antibody (OKT9) binding. The molecule can be cleaved into a Mr = 70,000 fragment from the cell surface, suggesting that the major part of the receptor is exposed to the extracellular environment. The released Mr = 70,000 fragments are not disulfide-linked and possess the antibody (OKT9)- and transferrin-binding sites. Cross-linking studies using radiolabeled transferrin suggest that two molecules of transferrin are bound to each Mr = 180,000 receptor dimer.


Involvement of the central nervous system in the general response to pulmonary blast injury.
The local, general, and cerebral responses of rabbits exposed to pulmonary blasts were examined to define the role of vagal afferentation in cardiorespiratory as well as metabolic control after a blast injury. Two series of experiments were conducted on rabbits to analyze the general, local, and cerebral responses to pulmonary injury caused by blast overpressure, and to evaluate the effects of bilateral vagotomy on the general, local, and cerebral responses to local (pulmonary) blast injury. The blast wave was generated in laboratory conditions using an air-driven shock tube that was able to cause moderate pulmonary blast injury, i.e., four pulmonary contusions characterized as confluent ecchymoses involving 30 to 60% of the lungs. One group of animals was subjected to pulmonary deafferentation, performed by bilateral transections of the vagus, glossopharyngeal, and hypoglossal nerves. Numerous hemodynamic as well as biochemical parameters were observed in systemic circulation and in lung and brain (medulla oblongata) tissues. After observation during the early posttraumatic period, rabbits were sacrificed by decapitation 30 minutes after the blast injury. On the basis of obtained results, it was concluded that vagal afferents have an important role in the modification of general and local responses to a pulmonary blast injury. Furthermore, it was suggested that functional changes in medulla oblongata may be the consequences of afferent neural impulses from the injured region (lungs) rather than consequences of ischemia, energy transfer to the brain, or both.


Effects of social support, hope and resilience on depressive symptoms within 18 months after diagnosis of prostate cancer.
The prevalence of depression symptoms and related modifiable factors in prostate cancer (PCa) are not well evaluated. We aimed to assess the effects of perceived social support, hope and resilience on depressive symptoms within 18 months after diagnosis of PCa, and to evaluate the role of hope and resilience as mediators of that relationship. A cross-sectional study was analyzed in consecutive inpatients with PCa during the months of January 2018 and August 2019. A total of 667 patients eligible for this study completed questionnaires on demographic and clinic variables, Center for Epidemiologic Studies Depression Scale, Multidimensional Scale of Perceived Social Support, Adult Hope Scale, and Resilience Scale (14 items). All registered patients were all volunteers and anonymous. Depressive symptoms, perceived social support, hope and resilience were measured anonymously. Out of 667 patients, a total of 564 effective respondents (< 30% missing data) became our subjects. Hierarchical linear regression was used to identify the factors associated with depressive symptoms. Asymptotic and resampling strategies were used to conduct the mediating effects of hope and resilience. The prevalence of depressive symptoms was 65.9% in PCa patients. Hierarchical regression analyses indicated that perceived social support, hope, and resilience together accounted for 27.5% variance of depressive symptoms. Support from family, hope, and resilience significantly associated with depressive symptoms, respectively. Hope (a*b = - 0.0783, BCa95% CI: - 0.134 to - 0.0319, p < 0.05), and resilience (a*b = - 0.1315, BCa95% CI: - 0.1894 to - 0.0783, p < 0.05) significantly mediated the association between perceived social support and depressive symptoms. The high prevalence of depressive symptoms among PCa patients should receive more attention. Perceived social support, hope and resilience could be positive resources for combating depressive symptoms, and hope and resilience mediated the association between perceived social support and depressive symptoms. Enhancing social support, particularly the support form family, and improving patients' outlook and resilience may be potential targets for future psychosocial interventions aimed at reducing depressive symptoms.


Low molecular weight heparin ablates lung cancer cisplatin-resistance by inducing proteasome-mediated ABCG2 protein degradation.
Cancer side population (SP) cells, which are often referred to as cancer stem cells, are thought to be responsible for lung cancer chemotherapy resistance, and currently no drug can specifically target these cells. We hypothesize low-molecular-weight heparin (LMWH) may affect the biological properties of SP cells and could be used to clinically target these cells. To test this, SP cells were isolated from cisplatin (DDP)-resistant lung adenocarcinoma A549/DDP cells by flow cytometric sorting. Compared to non-SP cells, SP cells formed increased numbers of colonies in vitro, and had a 1000-fold increase in tumorigenicity in vivo. Proliferation and apoptosis assays demonstrated LMWH had no significant effect on lung SP cell proliferation or apoptosis. However, LMWH reduced lung SP cell colony formation ability and protein expression of the multidrug transporter, ABCG2, by FACS and western blot analyses without affecting its mRNA levels by RT-PCR. Consistently, immunohistochemistry stainings of ABCG2 in LMWH-treated tumor tissues were significantly reduced compared with those in controls. Further, we found proteasomal inhibitor MG132, but not lysosomal inhibitors leupeptin and pepstatin A, could restore ABCG2 protein levels in LMWH-treated SP cells. These suggest LMWH ablates lung SP cell chemoresistance by proteasome-mediated reduction of ABCG2 protein levels without affecting its mRNA levels. We also determined LMWH combined with cisplatin could overcome cisplatin-resistance and induced lung SP cells apoptosis both in vitro and in vivo. This study provides an experimental basis for using a combination of LMWH, which targets lung SP cells, with chemotherapy to improve lung cancer survival.


Effects of some cytoskeleton inhibitors on ooplasmic segregation in the Nereis virens egg.
The ooplasmic segregation in the Nereis virens egg starts after completion of cortical reaction. During ooplasmic segregation the radial symmetrical pattern of the oocyte transforms into polarized stratified structure with different kinds of cytoplasm regularly distributed along the animal-vegetal axis. The beginning of oocyte polarization is associated with the generation of the mitotic spindle and is sensitive to microtubule inhibitors. By analyzing the effect of colchicine, taxol, nocodazole and cytochalasin B, we show that the mechanisms of ooplasmic segregation have an integrated complex nature and include interactions of microtubules and microfilaments. The inhibition of any of these elements delays or disturbs the ooplasmic segregation and simultaneous disruption of microtubules and microfilaments functions leads to total cessation of the process.


Comparison of hospitalists and nonhospitalists regarding core measures of pneumonia care.
To examine whether compliance with national indicators of care differed amongst hospitalists and nonhospitalists. Retrospective, observational cohort study. Patients admitted from September 2004 through January 2005 to a community teaching hospital with a principal diagnosis of community-acquired pneumonia were included. Patient exclusions were any immunosuppressive illness or therapy within the past 3 months, comfort care only, or care provided by house staff. Patient variables of age, length of stay (LOS), time to initial antibiotic therapy, blood cultures drawn, use of deep venous thrombosis (DVT) prophylaxis, administration of pneumococcal vaccine or documentation of ineligibility for it, and name of attending physician were collected. Dichotomous variables were compared using chi(2)-analysis, and continuous variables were compared using the Student t test. A total of 158 patients were treated by 58 physicians; 68 patients by 12 hospitalists and 90 patients by 46 nonhospitalists. Patients did not differ in age, LOS, likelihood of receiving timely antibiotics, or having blood cultures drawn before antibiotics. Hospitalist patients were more likely to have been given inpatient DVT prophylaxis (96.9% vs 61.9%; P < .001) and to have had a pneumococcal vaccine administered or a documented reason why it was not given (88.2% vs 65.6%; P = .001). This is the first study to suggest that pneumonia patients cared for by hospitalists were more likely to receive 2 important quality care processes.


Pneumopericarditis: A Case of Acute Chest Pain with ST Segment Elevation.
Pneumopericarditis describes a clinical scenario where fluid and air are found within the pericardial space. Although infrequent, pneumopericarditis should be considered in patients presenting with acute chest pain as a differential diagnosis. This is relevant in patients with history of upper gastrointestinal (GI) surgery, as this may lead to a fistula communicating the GI tract and the pericardium. We report a 42-year-old man with history of numerous surgical interventions related to a Nissen fundoplication that presented with acute chest pain and inferior lead ST segment elevations. Emergent coronary angiography was negative for coronary vascular disease but fluoroscopy revealed air in the pericardial space. Subsequent radiographic studies helped confirm air in the pericardial space with a fistulous communication to the stomach. Ultimate treatment for this defect was surgical closure.


Annular Flow in the Upper Esophageal Sphincter Demonstrated with Dynamic 320-row Area Detector Computed Tomography.
Understanding bolus flow patterns in swallowing (rheology, the study of flow) is fundamental to assessment and treatment of dysphagia. These patterns are complex and poorly understood. A liquid swallow is typically biphasic, including air, so the actual bolus has both liquid and gas phases. We report a novel observation of annular two-phase flow (a ring of liquid around a core of air) as thin liquids passed through the upper esophageal sphincter (UES). Dynamic CT was performed on 27 healthy asymptomatic volunteers swallowing liquid barium in a semi-reclining position. Each subject swallowed 3, 10, and 20 ml of either thin (14 subjects) or thick liquid (13 subjects). Sagittal and axial images were analyzed. Flow patterns in the UES were assessed on cross-sectional images. Annular flow was seen in the majority of subjects with thin liquid but few with thick liquid swallows. The percentage of Annular flow during UES opening was 3 ml 58%, 10 ml 58%, 20 ml 56% in thin and 3 ml 0%, 10 ml 4%, 20 ml 1% in thick. Annular flow was usually observed from the second or third frames after onset of UES opening. The other pattern, Plug flow was seldom seen with thin but was typical with thick liquid swallows. Annular flow was the most common pattern for thin liquids (but not thick liquids) passing through the UES. Annular flow has been defined as a liquid continuum adjacent to the channel wall with a gas continuum (core) in the center of the channel. The two regions are demarcated by a gas-liquid interface. Annular flow is typical for two-phase gas-liquid flow in a vertical or inclined channel. It results from the interaction of viscosity with cohesive and adhesive forces in the two phases. We infer that the difference in flow pattern between thin liquid-air and thick liquid-air boluses resulted from the differing magnitudes of viscous forces.


Principles of minimize bleeding and the transfusion of blood and its components in operated patients - surgical aspects.
One of the target of perioperative tratment in surgery is decreasing intraoperative bleeding, which increases the number of perioperative procedures, mortality and treatment costs, and also causes the risk of transfusion of blood and its components. Trying to minimize the blood loss(mainly during the operation) as well as the need to transfuse blood and its components (broadly understood perioperative period) should be standard treatment for a patient undergoing a procedure. In the case of this method, the following steps should be taken: 1) in the preoperative period: identyfication of risk groups as quickly as possible, detecting and treating anemia, applying prehabilitation, modyfying anticoagulant treatment, considering donating one's own blood in some patients and in selected cases erythropoietin preparations; 2) in the perioperative period: aim for normothermia, normovolemia and normoglycemia, use of surgical methods that reduce bleeding, such as minimally invasive surgery, high-energy coagulation, local hemostatics, prevention of surgical site infection, proper transfusion of blood and its components if it occurs; 3) in the postoperative period: monitor the condition of patients, primarily for the detection of bleeding, rapid reoperation if required, suplementation (oral administration preferred) nutrition with microelements (iron) and vitamins, updating its general condition. All these activities, comprehensively and in surgical cooperation with the anesthesiologist, should reduce the blood loss and transfusion of blood and its components.


A multi-view convolutional neural network method combining attention mechanism for diagnosing autism spectrum disorder.
Autism Spectrum Disorder (ASD) is a neurodevelopmental condition whose current psychiatric diagnostic process is subjective and behavior-based. In contrast, functional magnetic resonance imaging (fMRI) can objectively measure brain activity and is useful for identifying brain disorders. However, the ASD diagnostic models employed to date have not reached satisfactory levels of accuracy. This study proposes the use of MAACNN, a method that utilizes multi-view convolutional neural networks (CNNs) in conjunction with attention mechanisms for identifying ASD in multi-scale fMRI. The proposed algorithm effectively combines unsupervised and supervised learning. In the initial stage, we employ stacked denoising autoencoders, an unsupervised learning method for feature extraction, which provides different nodes to adapt to multi-scale data. In the subsequent stage, we perform supervised learning by employing multi-view CNNs for classification and obtain the final results. Finally, multi-scale data fusion is achieved by using the attention fusion mechanism. The ABIDE dataset is used to evaluate the model we proposed., and the experimental results show that MAACNN achieves superior performance with 75.12% accuracy and 0.79 AUC on ABIDE-I, and 72.88% accuracy and 0.76 AUC on ABIDE-II. The proposed method significantly contributes to the clinical diagnosis of ASD.


The Omics Dashboard for interactive exploration of gene-expression data.
The Omics Dashboard is a software tool for interactive exploration and analysis of gene-expression datasets. The Omics Dashboard is organized as a hierarchy of cellular systems. At the highest level of the hierarchy the Dashboard contains graphical panels depicting systems such as biosynthesis, energy metabolism, regulation and central dogma. Each of those panels contains a series of X-Y plots depicting expression levels of subsystems of that panel, e.g. subsystems within the central dogma panel include transcription, translation and protein maturation and folding. The Dashboard presents a visual read-out of the expression status of cellular systems to facilitate a rapid top-down user survey of how all cellular systems are responding to a given stimulus, and to enable the user to quickly view the responses of genes within specific systems of interest. Although the Dashboard is complementary to traditional statistical methods for analysis of gene-expression data, we show how it can detect changes in gene expression that statistical techniques may overlook. We present the capabilities of the Dashboard using two case studies: the analysis of lipid production for the marine alga Thalassiosira pseudonana, and an investigation of a shift from anaerobic to aerobic growth for the bacterium Escherichia coli.


Clear cell cancer of the uterine corpus: the association of clinicopathologic parameters and treatment on disease progression.
This paper presents a single-institution experience regarding the clinicopathologic features and treatment strategies used in uterine clear cell cancer (UCC), a rare, aggressive histologic subtype of uterine cancer with poor prognosis and discusses parameters associated with progression-free survival (PFS) and overall survival (OS). A retrospective chart review was performed on all patients (n = 80) diagnosed with UCC and treated between 1994 and 2009 at a single academic institution. Data on demographics, FIGO stage, treatment regimens, and recurrences were collected. Patients with early-stage UCC had an excellent survival regardless of adjuvant therapy. Advanced-stage patients had a worse survival. Vaginal apex brachytherapy was associated with an increased OS (P = 0.02) but not PFS (P = 0.10). The use of platinum-based chemotherapy in combination with vaginal apex brachytherapy did not significantly improve survival. Innovative therapies still need to be identified for this uncommon uterine cancer.


Leadership Training in Otolaryngology Residency.
Although residency training offers numerous leadership opportunities, most residents are not exposed to scripted leadership instruction. To explore one program's attitudes about leadership training, a group of otolaryngology faculty (n = 14) and residents (n = 17) was polled about their attitudes. In terms of self-perception, more faculty (10 of 14, 71.4%) than residents (9 of 17, 52.9%; P = .461) considered themselves good leaders. The majority of faculty and residents (27 of 31) thought that adults could be taught leadership ability. Given attitudes about leadership ability and the potential for improvement through instruction, consideration should be given to including such training in otolaryngology residency.


[Nursing students' perception of the learning process in a hospital setting].
The aim of this study was to identijf how nursing students perceive and experience the learning process during curricular practice in a hospital setting. A qualitative, retrospective, documentary study was developed in an undergraduate nursing course. Data were comprised of 162 posts made by 34 students in the online discussion forum of the Learning Management System Moodle, during the first half of 2011. The following themes emergedfrom t he thematic content analysis: "nursing students' understanding about the professional practice," and "the teaching and learning process in the perspective of nursing students." The study demonstrated that the forum was a place for reporting experiences such as the description of the physical area, performing procedures, perception of nursing care activities, conJlicts with peers, coping with death and learning evaluation. The online discussion forum needs to be used by professors as a space of interaction so as to contribute to professional training.


Acute myeloid leukemia fusion proteins deregulate genes involved in stem cell maintenance and DNA repair.
Acute myelogenous leukemias (AMLs) are genetically heterogeneous and characterized by chromosomal rearrangements that produce fusion proteins with aberrant transcriptional regulatory activities. Expression of AML fusion proteins in transgenic mice increases the risk of myeloid leukemias, suggesting that they induce a preleukemic state. The underlying molecular and biological mechanisms are, however, unknown. To address this issue, we performed a systematic analysis of fusion protein transcriptional targets. We expressed AML1/ETO, PML/RAR, and PLZF/RAR in U937 hemopoietic precursor cells and measured global gene expression using oligonucleotide chips. We identified 1,555 genes regulated concordantly by at least two fusion proteins that were further validated in patient samples and finally classified according to available functional information. Strikingly, we found that AML fusion proteins induce genes involved in the maintenance of the stem cell phenotype and repress DNA repair genes, mainly of the base excision repair pathway. Functional studies confirmed that ectopic expression of fusion proteins constitutively activates pathways leading to increased stem cell renewal (e.g., the Jagged1/Notch pathway) and provokes accumulation of DNA damage. We propose that expansion of the stem cell compartment and induction of a mutator phenotype are relevant features underlying the leukemic potential of AML-associated fusion proteins.


An examination of strength and concentric work ratios during variable range of motion training.
Variable range of motion (ROM) training consists of partial ROM resistance training with the countermovement being performed at a different phase of the movement for each set. In this study, we assessed the effect of this method of training on peak force, load lifted, and concentric work performed. Six male subjects with resistance training backgrounds (age 20.2 +/- 1.3 years, height 179.4 +/- 4.6 cm, weight 89.6 +/- 9.9 kg, 6-repetition maximum [6RM] bench press 92.5 +/- 14.3 kg) participated in this study. Testing consisted of 6RM bench press strength tests during full (FULL), three quarter ((3/4)), one half ((1/2)), and one quarter ((1/4)) ROM from full elbow extension bench press performed on a Smith machine. The 6RM load, peak force (PF), and concentric work (W) performed during each ROM was examined using a one-way analysis of variance performed at an alpha level of p < 0.05. The 6RM load increased significantly as the ROM was decreased for all tests (FULL = 92.5 +/- 14.3 kg, (3/4) = 102.1 +/- 14.3 kg, (1/2) = 123.3 +/- 23.6 kg, (1/4) = 160.9 +/- 26.2 kg). PF during each test was significantly higher during the (1/4) (1924.8 +/- 557.9 N) and (1/2) (1859.4 +/- 317.1 N) ROM from full elbow extension bench press when compared with the (3/4) (1242.2 +/- 254.6 N) and FULL (1200.5 +/- 252.5 N) ROM exercise. Although higher force levels were evident, the restriction in barbell displacement resulted in a subsequent reduction in W as the lifting ROM was reduced. These results suggest that variable ROM resistance training results in increased force production as the ROM diminishes.


Added Value of Selective Intra-arterial Cone-Beam CT Angiography in the Management of Visceral Artery Aneurysms.
The aim of this study is to evaluate the value of selective intra-arterial cone-beam computed tomography angiography (CBCTA) relative to conventional computed tomography angiography (CTA) in understanding visceral artery aneurysm (VAA) morphology, and its impact on treatment planning. Between January 2017 and August 2021, all patients who had a diagnosis of VAA and underwent intraoperative CBCTA imaging were retrospectively reviewed. Impact on treatment decisions, optimal C-arm angulations derived from CBCTA, and additional radiation exposure were reported. Two blinded independent reviewers qualitatively reviewed CBCTA and conventional CTA images. A 5-point Likert scale (1=poor image quality, 5=excellent image quality) was used to assess the overall image quality of each modality. Number of vessels arising from the aneurysm sac was counted. A total of 16 patients had a diagnosis of VAA during the study period, of whom 10 patients had intraoperative CBCTA and conventional CTA available for review. Out of 10 patients, 7 underwent successful endovascular treatment, 2 were deemed not amenable for endovascular embolization based on intraoperative CBCTA findings, and 1 had resolved pseudoaneurysm. Total fluoroscopy time and radiation dose (dose area product [DAP] and skin dose) for all procedures were 27.7 ± 19.9 minutes, 28 362 (±18 651) µGy*m2, and 1879 (±1734) mGy, respectively. Radiation exposure from CBCTA (DAP and skin dose) was 5703 (±3967) µGy*m2 and 223.6 (±141.3) mGy, respectively. In patients who underwent endovascular treatment, the proportional DAP from CBCTA was 18.3% (±15.3%) of the total procedural radiation dose. Qualitative rating of overall image quality of CBCTA images was superior to CTA images (mean score: 4.55 vs 3, p<0.001). More branch vessels arising from the VAA were identified by all reviewers in CBCTA as compared with conventional CTA (median, min-max: 3, 0-4 vs 2,1-3 vessels). Intraoperative CBCTA after selective intra-arterial contrast injection, with better spatial resolution, provided better delineation of visceral aneurysm morphology as compared with conventional, intravenous CTA and enabled optimal treatment planning at a reasonable additional radiation exposure. Visceral artery aneurysms (VAA) are often diagnosed incidentally by conventional computed tomographic angiography (CTA). Endovascular treatment typically requires selective angiographies at multiple projections to better understand aneurysm morphology, location, and efferent branch vessels. Intra-arterial cone-beam CT angiography (CBCTA) for VAA has the advantage of selective contrast opacification, better spatial resolution, and three-dimensional/multi-planar visualization of aneurysm morphology. In addition, CBCTA enables identification of optimal C-arm working projection for subsequent endovascular treatment. The aim of this study is to evaluate the value of intraoperative CBCTA relative to conventional CTA in understanding visceral artery aneurysm morphology and its impact on treatment planning.


Liquid-chromatographic determination of urinary pentachlorophenol.
We developed and evaluated a simple liquid-chromatographic method for urinary pentachlorophenol (PCIP) determination with ultraviolet detection. PCIP and the internal standard (2,3,5,6-tetrachlorophenol, TCP) were extracted with a solid-phase extraction column, and 50 microL of the collected eluate was injected into the chromatograph. The intra-assay and interassay CVs were 6.6% (n = 20) and 7.9% (n = 10), respectively. The analytical recoveries varied from 89% to 96%, with absolute recoveries ranging from 82% to 88%. Thirty urine specimens collected from 30 unexposed individuals were analyzed by the current method, and results were all less than the minimum detection limit, 0.25 mg/L. Results for five specimens from workers who had been exposed to PCIP ranged from 7.0 to 12.4 mg/L. The standard curve was linear to 300 mg/L. This procedure is adaptable to automated analysis, and therefore suitable for monitoring industrial exposure of workers.


Next day discharge rate has little use as a quality measure for individual physician performance.
Emergency Department (ED) physicians' next day discharge rate (NDDR), the percentage of patients who were admitted from the ED and subsequently discharged within the next calendar day was hypothesized as a potential measure for unnecessary admissions. The objective was to determine if NDDR has validity as a measure for quality of individual ED physician performance. Hospital admission data was obtained for thirty-six ED physicians for calendar year 2015. Funnel plots were used to identify NDDR outliers beyond 95% control limits. A mixed model logistic regression was built to investigate factors contributing to NDDR. To determine yearly variation, data from calendar years 2014 and 2016 were analyzed, again by funnel plots and logistic regression. Intraclass correlation coefficient was used to estimate the percent of total variation in NDDR attributable to individual ED physicians. NDDR varied significantly among ED physicians. Individual ED physician outliers in NDDR varied year to year. Individual ED physician contribution to NDDR variation was minimal, accounting for 1%. Years of experience in Emergency Medicine practice was not correlated with NDDR. NDDR does not appear to be a reliable independent quality measure for individual ED physician performance. The percent of variance attributable to the ED physician was 1%.


Constitutive endocytic cycle of the CB1 cannabinoid receptor.
The CB1 cannabinoid receptor (CB1R) displays a significant level of ligand-independent (i.e. constitutive) activity, either when heterologously expressed in nonneuronal cells or in neurons where CB1Rs are endogenous. The present study investigates the consequences of constitutive activity on the intracellular trafficking of CB1R. When transfected in HEK-293 cells, CB1R is present at the plasma membrane, but a substantial proportion ( approximately 85%) of receptors is localized in intracellular vesicles. Detailed analysis of CB1-EGFP expressed in HEK-293 cells shows that the intracellular CB1R population is mostly of endocytic origin and that treatment with inverse agonist AM281 traps CB1R at the plasma membrane through a monensin-sensitive recycling pathway. Co-transfection with dominant positive or dominant negative mutants of the small GTPases Rab5 and Rab4, but not Rab11, profoundly modifies the steady-state and ligand-induced intracellular distribution of CB1R, indicating that constitutive endocytosis is Rab5-dependent, whereas constitutive recycling is mediated by Rab4. In conclusion, our results indicate that, due to its natural constitutive activity, CB1R permanently and constitutively cycles between plasma membrane and endosomes, leading to a predominantly intracellular localization at steady state.


Exploitation of stimulated Raman scattering in short-pulse fiber amplifiers.
Stimulated Raman scattering (SRS) generally limits the performance of short-pulse fiber amplifiers. We present the results of experiments that show that, under some conditions, SRS can extend the performance of amplifiers limited by nonlinear phase accumulation. The Stokes spectrum can be free of distortions arising from self-phase modulation and can circumvent the gain-narrowing limit of the amplifier. The generation of 1 microJ and 90 fs pulses from a single-mode fiber amplifier illustrates the potential of the process.


Belief and recollection of autobiographical memories.
In three experiments, undergraduates rated autobiographical memories on scales derived from existing theories of memory. In multiple regression analyses, ratings of the degree to which subjects recollected (i.e., relived) their memories were predicted by visual imagery, auditory imagery, and emotions, whereas ratings of belief in the accuracy of their memories were predicted by knowledge of the setting. Recollection was predicted equally well in between- and within-subjects analyses, but belief consistently had smaller correlations and multiple regression predictions between subjects; individual differences in the cognitive scales that we measured could not account well for individual differences in belief. In contrast, measures of mood (Beck Depression Index) and dissociation (Dissociative Experience Scale) added predictive value for belief, but not for recollection. We also found that highly relived memories almost always had strong visual images and that remember/know judgments made on autobiographical memories were more closely related to belief than to recollection.


Work stressors and alcohol consumption among white-collar workers: a signal detection approach.
Previous findings regarding the relationship between work stress and alcohol consumption are inconsistent and inconclusive. One of the primary reasons for the inconsistency of the findings is that simple models, such as multiple regression analysis or analysis of variance (ANOVA), have been conventionally adopted in studies examining the relationship between work stressors and alcohol consumption. Since higher order interactions of multiple work stressors, which lead to heavy alcohol consumption, might not be fully uncovered within the framework of a multiple regression analysis or ANOVA, another approach to exploring the interactions of work stressors is presented in this study. A signal detection analysis method was used to evaluate higher order interactions of work stress variables and to obtain basic information on 465 Japanese male white-collar workers. Of 11 work stressor or work position variables, four significant predictors of heavy alcohol consumption were identified. Two procedures were successfully performed in this study: (1) evaluating several higher order interactions of work stressors associated with heavy alcohol consumption, and (2) obtaining basic information to permit dividing the subjects into subgroups for further analysis using models and independent variables unique to each subgroup.


Factors Affecting the Binding of Diltiazem to Rainbow Trout Plasma: Implications for the Risk Assessment of Pharmaceuticals in Aquatic Systems.
The accumulation of organic toxicants in fish plasma, and how they partition between the bound and unbound fraction once absorbed, are important metrics in models that seek to predict the risk of such contaminants in aquatic settings. Rapid equilibrium dialysis of diltiazem, an ionizable weak base and important human pharmaceutical contaminant of freshwaters, was conducted with rainbow trout (Oncorhynchus mykiss) plasma. The effect of fed state, fish sex, fish strain/size, and dialysis buffer pH on the binding of radiolabeled diltiazem (9 ng ml-1 ) was assessed. In fed fish, 24.6%-29.5% of diltiazem was free, unbound to plasma proteins. Although starvation of fish resulted in a decrease in plasma protein, the bound fraction of diltiazem remained relatively constant. Consequently, the protein-bound concentration of diltiazem increased with length of starvation. In general, rainbow trout strain was a significant factor affecting plasma binding, although the two strains tested also differed markedly in size. Dialysis buffer pH significantly influenced plasma binding, with a higher unbound diltiazem fraction at pH 6.8 than pH 8.0. These data indicate that empirical measures of plasma binding in fish are important for accurate risk assessment and that the physiological status of a fish is likely to impact its sensitivity to toxicants such as diltiazem. Environ Toxicol Chem 2022;41:3125-3133. © 2022 SETAC.