Study of the Efficacy of Pipelle Biopsy Technique to Diagnose Endometrial Diseases in Abnormal Uterine Bleeding.
Pipelle biopsy is ideal for obtaining endometrial sample in outpatient department. It samples only 4% of the endometrial surface and has sensitivity up to 97%. A positive biopsy can avoid inconvenience to a patient, but a nonspecific finding should be interpreted with caution. Thus, the objectives of this study were to analyze the efficacy of pipelle biopsy by adequacy of the sample obtained and also to establish the reliability by comparing the histopathology report obtained by pipelle biopsy with that of the hysterectomy specimen. A prospective study conducted at a tertiary care hospital on 104 women with abnormal uterine bleeding (AUB). They were scheduled for pipelle endometrial sampling before hysterectomy. The sensitivity, specificity, negative and positive predictive values, and accuracy of pipelle biopsy in diagnosing various endometrial pathologies were analyzed. The validity of pipelle biopsy was studied for endometrial hyperplasia and carcinoma and their statistical significance was tested. The overall concordance rate was 63.8%. The sensitivity, specificity, positive and negative predictive values, and accuracy of pipelle biopsy for endometrial hyperplasia was 64.2%, 88.8%, 94.1%, 85.5%, and 47.3% and for endometrial carcinoma was 75%, 100%, 100%, 97.9%, and 98%, respectively. The P value for endometrial hyperplasia and carcinoma was 0.001 (statistically significant). Pipelle biopsy is valuable in diagnosing endometrial pathology of AUB cases. It has very high sensitivity and specificity for endometrial malignancies. A hysteroscopic dilatation and curettage is required for definitive diagnosis in cases of polyps and focal endometrial lesions.


Nosocomial Infections Are Frequent and Negatively Impact Outcomes in Hospitalized Patients With Cirrhosis.
Nosocomial infections (NIs) can be a major cause of morbidity and mortality in cirrhosis. This study aims to define the determinants of NI development and its impact on 30-day outcomes among hospitalized patients with cirrhosis. North American Consortium for the Study of End-Stage Liver Disease enrolled patients with cirrhosis who were admitted nonelectively. Admission variables and 30-day outcomes were compared between patients with and without NI. These were also compared based on whether there was an isolated admission infection, NI, or both. Models were created for NI development using admission variables and for 30-day mortality. The study included 2,864 patients; of which, 15% (n = 436) developed NI. When comparing NI vs no NI, 1,866 patients were found to be infection free, whereas 562 had admission infections only, 228 had only NI, and 208 had both infections. At admission, patients with NI were more likely to be infected and have advanced cirrhosis. NIs were associated with higher rates of acute-on-chronic liver failure, death, and transplant regardless of admission infections. Patients with NI had higher respiratory infection, urinary tract infection, Clostridium difficile infection, fungal infections, and infection with vancomycin-resistant enterococci compared with patients without NI. Risk factors for NIs were admission infections, model for end-stage liver disease (MELD) > 20, systemic inflammatory response syndrome criteria, proton pump inhibitor, rifaximin, and lactulose use, but the regression model (sensitivity, 0.67; specificity, 0.63) was not robust. Age, alcohol etiology, admission MELD score, lactulose use, acute-on-chronic liver failure, acute kidney injury, intensive care unit, and NI increased the risk of death, whereas rifaximin decreased the risk of death. NIs are prevalent in hospitalized patients with cirrhosis and are associated with poor outcomes. Although higher MELD scores and systemic inflammatory response syndrome are associated with NI, all hospitalized patients with cirrhosis require vigilance and preventive strategies.


Nontarget-to-nontarget interval determines the nontarget P300 in an auditory equiprobable Go/NoGo task.
Increases in the target-to-target interval (TTI) systematically enhance the amplitude of the target P300 ERP component. Research examining changes in nontarget P300 related to nontarget-to-nontarget interval (NNI) or sequential probability manipulations has produced inconsistent results, with some studies reporting no enhancement in nontarget P300 and others finding response profiles analogous to TTI effects. Our aim was to clarify these differences. All participants completed a specially designed auditory equiprobable Go/NoGo task with manipulations of TTI and NNI while their EEG activity was recorded. P300 amplitudes were extracted using temporal PCA with Varimax rotation. P3b to targets and nontargets increased systematically as respective TTIs/NNIs increased, but this change did not differ between stimulus types. The Slow Wave did not show any effect of interval, but was more positive to targets than nontargets when interval was collapsed. P3b findings show that matching-stimulus interval effects are not restricted to targets, but discrepancies relative to previous research suggest that NNI effects in P3b may depend on additional processing of nontarget stimuli.


The Role of Human Adult Peripheral and Umbilical Cord Blood Platelet-Rich Plasma on Proliferation and Migration of Human Skin Fibroblasts.
Wound healing is a complex and dynamic process following damage in tissue structures. Due to extensive skin damage caused by burn injuries, this study determined the role of human adult peripheral and umbilical cord blood platelet-rich plasma on proliferation and migration in human skin fibroblasts. Platelet-rich plasma (5, 10, 15, 20 and 50% PRP) from human umbilical cord blood and adult peripheral blood were provided and added to fibroblasts cultured from a human skin sample. Migration and proliferation of fibroblasts were assessed in comparison to 10% FBS and by the fibroblast responses to a concentration gradient. All components of the umbilical cord blood PRP significantly stimulated the growth of fibroblasts when compared to the negative control. Fibroblast growth was enhanced in a dose dependent manner. All fibroblast cultures retained normal morphology. No significant difference was noted between umbilical cord blood and adult peripheral blood PRP preparations regarding cell proliferation and migration, but the difference to 10% FBS was significant. 1% and 50% PRP reduced cellular proliferation. The 20% umbilical cord blood PRP and 10% adult peripheral blood PRP had a significant stimulatory effect on the migration of the skin fibroblast cells in comparison with 10% FBS. As PRP could promote the migration and proliferation of dermal fibroblasts, it can be safely added in cultures when treatment of chronic wounds without triggering the immune response is needed.


A monoclonal natural autoantibody that promotes remyelination suppresses central nervous system inflammation and increases virus expression after Theiler's virus-induced demyelination.
We have used an established experimental model of multiple sclerosis to investigate the potential beneficial relationship between natural autoimmunity and remyelination after central nervous system (CNS) demyelination. Intracerebral infection of SJL/J mice with Theiler's murine encephalomyelitis virus (TMEV) produces chronic, progressive, inflammatory CNS demyelination. Chronically infected SJL/J mice show minimal spontaneous remyelination, which is in part due to a T cell-mediated immune response inhibiting myelin repair. We previously identified a monoclonal natural autoantibody, designated SCH94.03, that promotes remyelination when passively transferred to chronically infected SJL/J mice. The mechanism whereby SCH94.03 promotes remyelination is unknown, although previous reports suggest that natural autoantibodies can modulate immune system function. In this report we demonstrate that treatment with SCH94.03 reduced by 2- to 3-fold the number of CD4(+) and CD8(+) cells infiltrating the CNS of SJL/J mice chronically infected with TMEV, in the absence of global lymphocyte depletion. Associated with the decreased inflammation was a 2- to 3-fold increase in virus antigen expression without a significant increase in viral RNA or virus titers. Treatment with SCH94.03 also suppressed the humoral immune response to a T cell-dependent antigen in chronically infected mice. Immunohistochemical staining showed that SCH94.03 labeled MHC class II-positive dendritic cells in peripheral lymphoid organs. These results are consistent with the proposed immunomodulatory function of natural autoantibodies and suggest that one mechanism whereby SCH94.03 promotes CNS remyelination in chronically infected SJL/J mice is through inhibition of a pathogenic immune response.


The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.
To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.


Ras signaling mechanisms underlying impaired GluR1-dependent plasticity associated with fragile X syndrome.
Fragile X syndrome, caused by the loss of FMR1 gene function and loss of fragile X mental retardation protein (FMRP), is the most commonly inherited form of mental retardation. The syndrome is characterized by associative learning deficits, reduced risk of cancer, dendritic spine dysmorphogenesis, and facial dysmorphism. However, the molecular mechanism that links loss of function of FMR1 to the learning disability remains unclear. Here, we report an examination of small GTPase Ras signaling and synaptic AMPA receptor (AMPA-R) trafficking in cultured slices and intact brains of wild-type and FMR1 knock-out mice. In FMR1 knock-out mice, synaptic delivery of GluR1-, but not GluR2L- and GluR4-containing AMPA-Rs is impaired, resulting in a selective loss of GluR1-dependent long-term synaptic potentiation (LTP). Although Ras activity is upregulated, its downstream MEK (extracellular signal-regulated kinase kinase)-ERK (extracellular signal-regulated kinase) signaling appears normal, and phosphoinositide 3-kinase (PI3K)-protein kinase B (PKB; or Akt) signaling is compromised in FMR1 knock-out mice. Enhancing Ras-PI3K-PKB signaling restores synaptic delivery of GluR1-containing AMPA-Rs and normal LTP in FMR1 knock-out mice. These results suggest aberrant Ras signaling as a novel mechanism for fragile X syndrome and indicate manipulating Ras-PI3K-PKB signaling to be a potentially effective approach for treating patients with fragile X syndrome.


Large-Scale Clonal Analysis Resolves Aging of the Mouse Hematopoietic Stem Cell Compartment.
Aging is linked to functional deterioration and hematological diseases. The hematopoietic system is maintained by hematopoietic stem cells (HSCs), and dysfunction within the HSC compartment is thought to be a key mechanism underlying age-related hematopoietic perturbations. Using single-cell transplantation assays with five blood-lineage analysis, we previously identified myeloid-restricted repopulating progenitors (MyRPs) within the phenotypic HSC compartment in young mice. Here, we determined the age-related functional changes to the HSC compartment using over 400 single-cell transplantation assays. Notably, MyRP frequency increased dramatically with age, while multipotent HSCs expanded modestly within the bone marrow. We also identified a subset of functional cells that were myeloid restricted in primary recipients but displayed multipotent (five blood-lineage) output in secondary recipients. We have termed this cell type latent-HSCs, which appear exclusive to the aged HSC compartment. These results question the traditional dogma of HSC aging and our current approaches to assay and define HSCs.


Evaluating behavioral health services in Minnesota's Medicaid population using the Experience of Care and Health Outcomes (ECHO) Survey.
Performance data on Medicaid managed behavioral health care are for the most part unavailable. The purpose of the current study is to provide a benchmark of Medicaid enrollees' evaluations of access to, and quality of, behavioral health services and to examine the factors that influence these ratings. Eight hundred eighty-five Minnesota Medicaid managed care enrollees who received behavioral health services in 2000 completed the Experience of Care and Health Outcomes Survey, a multidimensional satisfaction survey that included measures of access to services, communication with clinicians, functional improvement, and the effect of treatment. Between 29 and 59 percent of the respondents gave the highest possible ratings to the behavioral health services they received. Access to services and functional improvements were rated less favorably than communication with clinicians and the effects of treatment. Ratings within certain domains varied by age, race, education, and region.


Optoacoustic trace-gas monitoring with near-infrared diode lasers.
An inexpensive resonant optoacoustic monitoring system using near-infrared laser diodes was developed. It was demonstrated that wavelength modulation at the resonance frequency of the cell provides a superior signal-to-noise ratio compared with amplitude modulation and eliminates background drifts and fluctuations. The system was tested out on ammonia. Its sensitivity is 8 parts in 10(9) (S/N = 1) at atmospheric pressure, which corresponds to a minimum detectable absorption coefficient of approximately 3.5 × 10(-11) cm(-1) W(-1). The pressure dependence of the optoacoustic resonance was also investigated. The monitor can be used as a continuous flow-through system up to a flow rate of approximately 3.5 L/min.


The acute effects of classic psychedelics on memory in humans.
Memory plays a central role in the psychedelic experience. The spontaneous recall and immersive reliving of autobiographical memories has frequently been noted by researchers and clinicians as a salient phenomenon in the profile of subjective effects of classic psychedelic drugs such as psilocybin, LSD, and ayahuasca. The ability for psychedelics to provoke vivid memories has been considered important to their clinical efficacy. This review aims to examine and aggregate the findings from experimental, observational, and qualitative studies on the acute modulation of memory by classic psychedelics in humans. A literature search was conducted using PubMed and PsycInfo as well as manual review of references from eligible studies. Publications reporting quantitative and/or qualitative findings were included; animal studies and case reports were excluded. Classic psychedelics produce dose-dependently increasing impairments in memory task performance, such that low doses produce no impairment and higher doses produce increasing levels of impairment. This pattern has been observed in tasks assessing spatial and verbal working memory, semantic memory, and non-autobiographical episodic memory. Such impairments may be less pronounced among experienced psychedelic users. Classic psychedelics also increase the vividness of autobiographical memories and frequently stimulate the recall and/or re-experiencing of autobiographical memories, often memories that are affectively intense (positively or negatively valenced) and that had been avoided and/or forgotten prior to the experience. Classic psychedelics dose-dependently impair memory task performance but may enhance autobiographical memory. These findings are relevant to the understanding of psychological mechanisms of action of psychedelic-assisted psychotherapy.


Autosomal dominant polycystic kidney disease and transplantation.
Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder affecting 1 in 1,000 people and responsible for 10% of cases of the end stage renal disease (ESRD). Apart from renal manifestations, changes in other organs may be present. In the absence of contraindications, patients with ADPKD and ESRD should be referred to renal transplantation. The ADPKD patient may also need liver transplantation, or combined liver and kidney transplantation. Also, the patient with ADPKD may become a potential organ donor. The aim of our paper is to review the problems that the physicians deal with in ADPKD patients in pre- and post-transplant period.


The legacy lead deposition in soils and its impact on cognitive function in preschool-aged children in the United States.
Surface soil contamination has been long recognized as an important pathway of human lead exposure, and is now a worldwide health concern. This study estimates the causal effects of exposure to lead in topsoil on cognitive ability among 5-year-old children. We draw on individual level data from the 2000 U.S. Census, and USGS data on lead in topsoil covering a broad set of counties across the United States. Using an instrumental variable approach relying on the 1944 Interstate Highway System Plan, we find that higher lead in topsoil increases considerably the probability of 5-year-old boys experiencing cognitive difficulties such as learning, remembering, concentrating, or making decisions. Living in counties with topsoil lead concentration above the national median roughly doubles the probability of 5-year-old boys having cognitive difficulties. Nevertheless, it does not seem to affect 5-year-old girls, consistent with previous studies. Importantly, the adverse effects of lead exposure on boys are found even in counties with levels of topsoil lead concentration considered low by the guidelines from the U.S. EPA and state agencies. These findings are concerning because they suggest that legacy lead may continue to impair cognition today, both in the United States and in other countries that have considerable lead deposition in topsoil.


Enterovirus D68 in Hospitalized Children: Sequence Variation, Viral Loads and Clinical Outcomes.
An outbreak of enterovirus D68 (EV-D68) caused severe respiratory illness in 2014. The disease spectrum of EV-D68 infections in children with underlying medical conditions other than asthma, the role of EV-D68 loads on clinical illness, and the variation of EV-D68 strains within the same institution over time have not been described. We sought to define the association between EV-D68 loads and sequence variation, and the clinical characteristic in hospitalized children at our institution from 2011 to 2014. May through November 2014, and August to September 2011 to 2013, a convenience sample of nasopharyngeal specimens from children with rhinovirus (RV)/EV respiratory infections were tested for EV-D68 by RT-PCR. Clinical data were compared between children with RV/EV-non-EV-D68 and EV-D68 infections, and among children with EV-D68 infections categorized as healthy, asthmatics, and chronic medical conditions. EV-D68 loads were analyzed in relation to disease severity parameters and sequence variability characterized over time. In 2014, 44% (192/438) of samples tested positive for EV-D68 vs. 10% (13/130) in 2011-13 (p<0.0001). PICU admissions (p<0.0001) and non-invasive ventilation (p<0.0001) were more common in children with EV-D68 vs. RV/EV-non-EV-D68 infections. Asthmatic EV-D68+ children, required supplemental oxygen administration (p = 0.03) and PICU admissions (p <0.001) more frequently than healthy children or those with chronic medical conditions; however oxygen duration (p<0.0001), and both PICU and total hospital stay (p<0.01) were greater in children with underlying medical conditions, irrespective of viral burden. By phylogenetic analysis, the 2014 EV-D68 strains clustered into a new sublineage within clade B. This is one of the largest pediatric cohorts described from the EV-D68 outbreak. Irrespective of viral loads, EV-D68 was associated with high morbidity in children with asthma and co-morbidities. While EV-D68 circulated before 2014, the outbreak isolates clustered differently than those from prior years.


The experience of the family caregivers' role: a qualitative study.
In Ireland, there is a dearth of research exploring the perceived health and social care needs and experiences of family caregivers of older people. In response, this research study was conducted to explore the profile, role and needs of family caregivers as a means of understanding their experience of caring. The study also set out to identify coping strategies employed by caregivers and explore positive aspects of the caring relationship in relation to quality of life, information needs, day care and respite care, transport and emotional support. A multimethod approach used interviews, focus groups and postal questionnaires. In the main study a pretested questionnaire, comprising closed and open questions was used with a stratified, systematically randomized sample of caregivers in urban and rural home care settings, of which 52% of respondents to the questionnaire volunteered to partake in in-depth interviews. This article per deals predominantly with the findings arising from 10 in-depth qualitative interviews. The data yielded a rich and meaningful picture of the caregiving experience, profiling the complex nature of this diverse and multifaceted role. Findings showed that three main categories emanated from the data: the caring role-context and attitudes, the impact of caring and the need to support the carers' role. The need to develop continually an understanding of the effectiveness of specific health and social care interventions was also of paramount importance. The anticipated continuing demand for family care means that caregivers' needs and perspectives need to be integrated into future service planning and decision-making processes, in partnership with statutory and voluntary bodies. While this was the first study of its type in Ireland, the issues raised reflect the findings of other published studies and have important lessons for family carers and health care practitioners generally.


Closing the cohesin ring: structure and function of its Smc3-kleisin interface.
Through their association with a kleisin subunit (Scc1), cohesin's Smc1 and Smc3 subunits are thought to form tripartite rings that mediate sister chromatid cohesion. Unlike the structure of Smc1/Smc3 and Smc1/Scc1 interfaces, that of Smc3/Scc1 is not known. Disconnection of this interface is thought to release cohesin from chromosomes in a process regulated by acetylation. We show here that the N-terminal domain of yeast Scc1 contains two α helices, forming a four-helix bundle with the coiled coil emerging from Smc3's adenosine triphosphatase head. Mutations affecting this interaction compromise cohesin's association with chromosomes. The interface is far from Smc3 residues, whose acetylation prevents cohesin's dissociation from chromosomes. Cohesin complexes holding chromatids together in vivo do indeed have the configuration of hetero-trimeric rings, and sister DNAs are entrapped within these.


Facilitation of intracellular H(+) ion mobility by CO(2)/HCO(3)(-) in rabbit ventricular myocytes is regulated by carbonic anhydrase.
Intracellular H(+) mobility was estimated in the rabbit isolated ventricular myocyte by diffusing HCl into the cell from a patch pipette, while imaging pH(i) confocally using intracellular ratiometric SNARF fluorescence. The delay for acid diffusion between two downstream regions approximately 40 microm apart was reduced from approximately 25 s to approximately 6 s by replacing Hepes buffer in the extracellular superfusate with a 5 % CO(2)/HCO(3)(-) buffer system (at constant pH(o) of 7.40). Thus CO(2)/HCO(3)(-) (carbonic) buffer facilitates apparent H(+)(i) mobility. The delay with carbonic buffer was increased again by adding acetazolamide (ATZ), a membrane permeant carbonic anhydrase (CA) inhibitor. Thus facilitation of apparent H(+)(i) mobility by CO(2)/HCO(3)(-) relies on the activity of intracellular CA. By using a mathematical model of diffusion, the apparent intracellular H(+) equivalent diffusion coefficient (D(H)(app)) in CO(2)/HCO(3)(-)-buffered conditions was estimated to be 21.9 x 10(-7) cm(2) s(-1), 5.8 times faster than in the absence of carbonic buffer. Facilitation of H(+)(i) mobility is discussed in terms of an intracellular carbonic buffer shuttle, catalysed by intracellular CA. Turnover of this shuttle is postulated to be faster than that of the intrinsic buffer shuttle. By regulating the carbonic shuttle, CA regulates effective H(+)(i) mobility which, in turn, regulates the spatiotemporal uniformity of pH(i). This is postulated to be a major function of CA in heart.


Delayed induction and long-term effects of mild hypothermia in a focal model of transient cerebral ischemia: neurological outcome and infarct size.
The goals of this study were to determine the effects of delaying induction of mild hypothermia (33 degrees C) after transient focal cerebral ischemia and to ascertain whether the neuroprotective effects of mild hypothermia induced during the ischemic period are sustained over time. In the first study, rats underwent 2 hours of middle cerebral artery (MCA) occlusion. Animals in one group were maintained under normothermic conditions (N group, 23 rats) throughout the period of ischemia and reperfusion. Rats in four additional groups were exposed to 2 hours of hypothermia, which commenced at ischemia onset (H0 group, 11 rats) or with delays of 90 (H90 group, 10 rats), 120 (H120 group, 10 rats), or 180 (H180 group, five rats) minutes, and allowed to survive for 3 days. In the second study, animals underwent 1.5 hours of MCA occlusion and were maintained under normothermic (48 rats) or hypothermic (44 rats) conditions during the ischemia period, after which they survived for 3 days, 1 week, or 2 months. All animals were evaluated for neurological findings at 24 hours and 48 hours postischemia and before they were killed. Regions of infarct were determined by examining hematoxylin and eosinstained brain slices obtained at six coronal levels. Mild hypothermia conferred significant degrees of neuroprotection in terms of survival, behavioral deficits, and histopathological changes, even when its induction was delayed by 120 minutes after onset of MCA occlusion (p < 0.05) compared with normothermic conditions. Furthermore, the neuroprotective effect of mild hypothermia (2-hour duration) that was induced during the ischemia period was sustained over 2 months. These studies lend further support to the use of mild hypothermia in the treatment of stroke.


A single coxsackievirus B2 capsid residue controls cytolysis and apoptosis in rhabdomyosarcoma cells.
Coxsackievirus B2 (CVB2), one of six human pathogens of the group B coxsackieviruses within the enterovirus genus of Picornaviridae, causes a wide spectrum of human diseases ranging from mild upper respiratory illnesses to myocarditis and meningitis. The CVB2 prototype strain Ohio-1 (CVB2O) was originally isolated from a patient with summer grippe in the 1950s. Later on, CVB2O was adapted to cytolytic replication in rhabdomyosarcoma (RD) cells. Here, we present analyses of the correlation between the adaptive mutations of this RD variant and the cytolytic infection in RD cells. Using reverse genetics, we identified a single amino acid change within the exposed region of the VP1 protein (glutamine to lysine at position 164) as the determinant for the acquired cytolytic trait. Moreover, this cytolytic virus induced apoptosis, including caspase activation and DNA degradation, in RD cells. These findings contribute to our understanding of the host cell adaptation process of CVB2O and provide a valuable tool for further studies of virus-host interactions.


Comparative Genomics and Proteomic Analysis of Assimilatory Sulfate Reduction Pathways in Anaerobic Methanotrophic Archaea.
Sulfate is the predominant electron acceptor for anaerobic oxidation of methane (AOM) in marine sediments. This process is carried out by a syntrophic consortium of anaerobic methanotrophic archaea (ANME) and sulfate reducing bacteria (SRB) through an energy conservation mechanism that is still poorly understood. It was previously hypothesized that ANME alone could couple methane oxidation to dissimilatory sulfate reduction, but a genetic and biochemical basis for this proposal has not been identified. Using comparative genomic and phylogenetic analyses, we found the genetic capacity in ANME and related methanogenic archaea for sulfate reduction, including sulfate adenylyltransferase, APS kinase, APS/PAPS reductase and two different sulfite reductases. Based on characterized homologs and the lack of associated energy conserving complexes, the sulfate reduction pathways in ANME are likely used for assimilation but not dissimilation of sulfate. Environmental metaproteomic analysis confirmed the expression of 6 proteins in the sulfate assimilation pathway of ANME. The highest expressed proteins related to sulfate assimilation were two sulfite reductases, namely assimilatory-type low-molecular-weight sulfite reductase (alSir) and a divergent group of coenzyme F420-dependent sulfite reductase (Group II Fsr). In methane seep sediment microcosm experiments, however, sulfite and zero-valent sulfur amendments were inhibitory to ANME-2a/2c while growth in their syntrophic SRB partner was not observed. Combined with our genomic and metaproteomic results, the passage of sulfur species by ANME as metabolic intermediates for their SRB partners is unlikely. Instead, our findings point to a possible niche for ANME to assimilate inorganic sulfur compounds more oxidized than sulfide in anoxic marine environments.


Microcalorimetric study of ammonia chemisorption on H3PW12O40 supported onto mesoporous synthetic carbons and SBA-15.
Keggin tungstophosphoric acid supported onto mesoporous and meso-microporous materials was studied by ammonia microcalorimetry. Experiments were performed at high and low temperatures to separate the contributions of chemisorption and physisorption, low-temperature data being potentially important for the ambient temperature purification processes. Analysis of thermokinetic data obtained from heat output curves at an elevated temperature allows one to distinguish the transition between reaction of ammonia with the acid sites and the onset of physical sorption. Thermokinetic data are also sensitive to the pore structure of the support materials, with faster sorption registered in the case of materials with the open mesoporous structure. The SBA-15 supported acid shows the maximum ammonia uptake and the strongest acid sites among the three materials studied. The dynamics of sorption, characterized by the thermokinetic parameter, appears to be better in the two materials possessing open pore structure, mesoporous carbon Novacarb and especially the mesoporous silica SBA-15.


Facial nerve grading instruments: systematic review of the literature and suggestion for uniformity.
A variety of facial nerve grading scales have been developed over the years with the intended goals of objectively documenting facial nerve function,tracking recovery, and facilitating communication between practitioners. Numerous scales have been proposed; however, all are subject to limitation because of varying degrees of subjectivity, reliability, or longitudinal applicability. At present, such scales remain the only widely accessible modalities for facial functional assessment. The authors' objective was to ascertain which scales(s) best accomplish the goals of objective assessment. A systematic review of the English language literature was performed to identify facial nerve grading instruments. Each system was evaluated against the following criteria: convenience of clinical use, regional scoring, static and dynamic measures, features secondary to facial palsy (e.g., synkinesis), reproducibility with low interobserver and intraobserver variability, and sensitivity to changes over time and/or following interventions. From 666 articles, 19 facial nerve grading scales were identified. Only the Sunnybrook Facial Grading Scale satisfied all criteria. The Facial Nerve Grading Scale 2.0 (or revised House-Brackmann Scale) fulfilled all criteria except intraobserver reliability, which has not been assessed. Facial nerve grading scales intend to provide objectivity and uniformity of reporting to otherwise subjective analysis. The Facial Nerve Grading Scale 2.0 requires further evaluation for intraobserver reliability. The Sunnybrook Facial Grading Scale has been robustly evaluated with respect to the criteria prescribed in this article. Although sophisticated technology-based methodologies are being developed for potential clinical application,the authors recommend widespread adoption of the Sunnybrook Facial Grading Scale as the current standard in reporting outcomes of facial nerve disorders.


14-3-3 CSF levels in sporadic Creutzfeldt-Jakob disease differ across molecular subtypes.
The 14-3-3 protein is a physiological cellular protein expressed in various tissues, and its release to CSF reflects extensive neuronal damage as in Creutzfeldt-Jakob disease (CJD), but also in other neurological diseases. 14-3-3 protein in CSF in the proper clinical context is a reliable diagnostic tool for sporadic CJD. However, the sensitivity varies across molecular CJD subtypes. We determined the level of the 14-3-3 protein in CSF from 70 sporadic CJD patients with distinct molecular subtypes using an improved enzyme-linked immunosorbent assay (ELISA) protocol technique. The 14-3-3 levels varied markedly across various molecular subtypes. The most elevated levels of 14-3-3 protein were observed in the frequently occurring and classical subtypes, whereas the levels were significantly lower in the subtypes with long disease duration and atypical clinical presentation. PRNP codon 129 genotype, PrP(sc) isotype, disease stage and clinical subtype influenced the 14-3-3 level and the test sensitivity. The 14-3-3 protein levels differ across molecular subtypes and might be used for their early pre-mortem identification when the codon 129 genotype is known, especially for the less common molecular subtypes such as MV2 and MM2.


Total body calcium in rheumatoid arthritis: effects of disease activity and corticosteroid treatment.
Rheumatoid arthritis may be associated with generalised as well as periarticular osteoporosis. To assess the extent of bone loss and the influence of corticosteroid treatment total body calcium was measured by in-vivo neutron activation analysis in 63 patients with rheumatoid arthritis treated with non-steroidal anti-inflammatory drugs alone and 31 treated with additional low-dose corticosteroids. The results were compared with those in 40 normal controls matched for age, sex, and menopausal state. There were significant reductions in mean total body calcium in the group treated with non-steroidal anti-inflammatory drugs (5.3% in men; 6.8% in women) and greater reductions in the corticosteroid-treated patients (11.5% in men, 15.5% in women). The reduction was correlated with disease duration and activity in the patients treated with non-steroid anti-inflammatory drugs alone. Measured total body calcium was significantly less than the values predicted when this relation was used in the corticosteroid-treated patients. The data suggest that increased bone loss in patients with rheumatoid arthritis treated with corticosteroids is attributable to drug treatment rather than disease activity. Many patients with rheumatoid arthritis treated with low-dosage corticosteroids and some postmenopausal women with the disease are likely to be at risk from the complications of osteoporosis.


Epistemic struggles: The role of advocacy in promoting epistemic justice and rights in mental health.
Advocacy for people using health and social care services is widely promoted but its theoretical foundation is under-developed and its impact poorly conceptualised. This paper explores the liberatory potential of independent advocacy, using Fricker's concept of 'epistemic injustice' as a framework. People experiencing mental distress are particularly vulnerable to epistemic injustices as a consequence of deeply embedded social stigma resulting in a priori assumptions of irrationality and unreliability such that their knowledge is often discounted or downgraded. The mental health service user/survivor movement is at the forefront of validating personal experience and narrative to secure a different ontological and epistemological basis for mental distress. A foundational strand of this is advocacy to enable people to give voice to their experience. The case of independent mental health advocacy (IMHA) services under mental health legislation in England, provides an opportunity to critically examine whether advocacy can promote epistemic justice as a result of the legally sanctioned encounter between clinical assessment and subjective experience, pivoting on judgements about risk. This paper draws on empirical data from a national evaluation of IMHA services, which included 90 individual interviews with people subject to detention and three focus groups with mental health service users. Fricker's concept of epistemic injustice is used as a lens to investigate how this type of advocacy might mitigate forms of epistemic injustice, and thereby promote greater social justice in mental health. The concept of epistemic injustice provides a valuable theoretical basis for understanding the worth of advocacy in addressing testimonial injustice as well as its relative weakness in overcoming hermeneutical injustice. The challenge of independent advocacy to the dominant discourse within mental health is considered and questions raised about the place of advocacy in modern democratic mental health systems.


Allergic airway inflammation by nasal inoculation of particulate matter (PM2.5) in NC/Nga mice.
To evaluate the effect of airborne particulate matter 2.5 (PM2.5) in winter on airway inflammation, water-soluble supernatant (Sup) and water-insoluble precipitate (Pre) in PM2.5 were inoculated in NC/Nga mice with high sensitivity to mite allergens. Sup with aluminum oxide was injected intraperitoneally for sensitization. Five days later, Sup, Pre or both Sup and Pre were inoculated via the nasal route five times for more sensitization and a challenge inoculation on the 11th day in NC/Nga mice. On the 12th day, mice were examined for airway hyperresponsiveness (AHR), BALF cell count and IL-1β concentration, mRNA expression of Th1 and Th2 cytokines, chemokines such as eotaxin 1 and eotaxin 2, inflammasomal complex molecules such as IL-1β, caspase 1 and the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) in lung tissue as well as histopathology. The synergistic effect of Sup and Pre was observed in terms of increases in AHR, BALF cells, the mRNA expression of IL-13, eotaxin1 and IL-1β, and the IL-1β concentration in BALF. Intracellular deposits of insoluble particulates were observed in macrophages around inflammatory granulation of the mouse group treated with Sup and Pre. These results suggest that PM2.5 can induce airway hyperresponsiveness in mice with genetically high sensitivity to mite allergens by an inflammasome-associated mechanism and synergistic action of insoluble particulates and soluble components.


Wire-Shaped Supercapacitors with Organic Electrolytes Fabricated via Layer-by-Layer Assembly.
A wire-shaped supercapacitor (WSS) has structural advantages of high flexibility and ease of incorporation into conventional textile substrates. In this work, we report a thin reproducible WSS fabricated via layer-by-layer (LbL) assembly of multiwalled carbon nanotubes (MWCNTs), combined with an organic electrolyte of propylene carbonate (PC)-acetonitrile (ACN)-lithium perchlorate (LiClO4)-poly(methyl methacrylate) (PMMA) that extends the voltage window to 1.6 V. The MWCNTs were uniformly deposited on a curved surface of a thin Au wire using an LbL assembly technique, resulting in linearly increased areal capacitance of the fabricated WSS. Vanadium oxide was coated on the LbL-assembled MWCNT electrode to induce pseudocapacitance, hence enhancing the overall capacitance of the fabricated WSS. Both the cyclic stability of the WSS and the viscosity of the electrolyte could be optimized by controlling the mixing ratio of PC to ACN. As a result, the fabricated WSS exhibits an areal capacitance of 5.23 mF cm-2 at 0.2 mA cm-2, an energy density of 1.86 μ W h cm-2, and a power density of 8.5 mW cm-2, in addition to a high cyclic stability with a 94% capacitance retention after 10 000 galvanostatic charge-discharge cycles. This work demonstrates a great potential of the fabricated scalable WSS in the application to high-performance textile electronics as an integrated energy storage device.


HLA-DR typing using DNA amplification by the polymerase chain reaction and sequential hybridization to sequence-specific oligonucleotide probes.
A series of sequence-specific oligonucleotides (SSOs) have been used to type alleles at the HLA-DRB1 locus. Genomic DNA was amplified to high copy number by the polymerase chain reaction (PCR) and hybridizations of the dot-blotted, amplified DNA to a series of 14 SSOs enabled the identification of the major specificities DR1-DRw14. Certain alleles (DR3 and DR4) could be rapidly and accurately identified by running the products of allele-specific amplification of genomic DNA on agarose gels. This approach facilitated the typing of serological specificities such as subtypes of DR3 (DRw17 and DRw18) as well as alleles previously detected by the mixed lymphocyte reaction including subtypes of DR4 (Dw4, Dw10, Dw13, Dw14, and Dw15). The HLA-DR types obtained by SSO probing conformed to rules of Mendelian inheritance when they were applied to a series of 75 families. A full DR type could be obtained from many individuals simultaneously without needing to separate or store viable lymphocytes. Thus, this technique may have considerable implications for the analysis of disease associations with HLA class II alleles, particularly in circumstances where facilities for the initial preparation and storage of the samples may be limited.


Association of serum levels of lipoprotein A-I and lipoprotein A-I/A-II with high on-treatment platelet reactivity in patients with ST-segment elevation myocardial infarction.
High-density lipoproteins (HDLs) are a very heterogeneous group of particles. Little is known about the impact of their subfractions including lipoprotein A-I (LpA-I) and lipoprotein A-I/A-II (LpA-I/A-II) on platelet function and high on-treatment platelet reactivity (HPR), particularly in the acute phase of ST-segment elevation myocardial infarction (STEMI). The aim of the study was to evaluate the relationship between serum levels of LpA-I and LpA-I/A-II and HPR in STEMI patients. Fifty-two consecutive STEMI patients (26.9% women, mean age 60.6±9.1 years) were enrolled into this study. Clinical and demographic data were collected and HDL subfractions were measured by rocket immunoelectrophoresis. Platelet reactivity was assessed using light transmission aggregometry and quantitative flow cytometry. We found a positive correlation between platelet aggregation after both ADP-5 and ADP-20 stimulation and serum level of LpA-I. Compared with subjects with satisfactory platelet response to clopidogrel, patients with HPR had 32.44% higher serum level of LpA-I (p=0.021). On the other hand, patients with HPR assessed by ADP-5 stimulation had 22.13% lower serum level of LpA-I/A-II (p=0.040). Regression analysis showed that LpA-I [odds ratio (OR) 1.03; 95% confidence interval (CI) 1-1.07; p=0.049] and current smoking (OR 0.18; 95% CI 0.04-0.81; p=0.025) were independent predictors of HPR. With receiver operating characteristic (ROC) curve analysis, we designated the cut-off point at serum level of 57.52 mg/dL for LpA-I for predicting HPR (AUC=0.71, p=0.010). This study showed that higher serum level of LpA-I measured in the acute phase of STEMI is an independent risk factor for HPR. Our study is the first to demonstrate an important and distinct activity of LpA-I and LpA-I/A-II that can prove pleiotropic and different functions of HDL subfractions in acute STEMI.


Effects of different shear rates on the attachment and detachment of platelet thrombi.
Thrombosis and hemostasis take place in flowing blood, which generates shear forces. The effect of different shear rates, particularly pathological forces, on platelet thrombus formation remains to be fully elucidated. The present study observed the morphological characteristics and hierarchical structure of thrombi on the collagen surface at a wide range of wall shear rates (WSRs) and examined the underlying mechanisms. Calcein AM‑labeled whole blood was perfused over a collagen‑coated surface at different shear rates set by a Bioflux 200 microfluidic device and the thrombi formed were assessed for area coverage, the height and the hierarchical structure defined by the extent of platelet activation and packing density. The factors that affect thrombus formation were also investigated. Platelet thrombus formation varied under different WSRs, for example, dispersed platelet adhesion mixed with erythrocytes was observed at 125‑250 s(‑1), extensive and thin platelet thrombi were observed at 500‑1,500 s(‑1), and sporadic, thick thrombi were observed at pathological WSRs of 2,500‑5,000 s(‑1), which showed a tendency to be shed. With increasing WSRs, the height of the thrombi showed an increasing linear trend, whereas the total fluorescence intensity and area of the thrombi exhibited a parabolic curve‑like change, with a turning point at a WSR of 2,500 s(‑1). The number of thrombi, the average fluorescence intensity and the area per thrombus showed similar trends, with an initial upwards incline followed by a decline. The thrombi formed at higher WSRs had a thicker shell, which led to a more densely packed core. Platelet thrombus formation under shear‑flow was regulated by the adhesive strength, which was mediated by receptor‑ligand interaction, the platelet deposition induced by shear rates and the detachment by the dynamic force of flow. This resulted in a balance between thrombus attachment, including adhesion and aggregation, and detachment. Collectively, compared with physiological low WSRs, pathological high WSRs caused thicker and more easily shed thrombi with more condensed cores, which was regulated by an attachment‑detachment balance. These results provide novel insights into the properties of thrombus formation on collagen at different WSRs, and offers possible explanations for certain clinical physiopathological phenomena, including physical hemostasis and pathological thrombosis.


Novel electrochemical synthesis of copper oxide nanoparticles decorated graphene-β-cyclodextrin composite for trace-level detection of antibiotic drug metronidazole.
Over the past decades, the synthesis of inorganic and organic nanocomposites has received much attention in the range of fields including electroanalysis of organic chemicals. In this regard, we have prepared copper oxide nanoparticle (CuO NPs) decorated graphene/β-cyclodextrin (GR-β-CD) composites using a simple electrochemical methodology, where the CuO NPs are electrodeposited on GR-β-CD composite modified electrodes. A stable GR-β-CD composite was prepared by sonication of GR in β-CD aqueous solution. As-prepared GR-β-CD/CuO NPs composites were characterized by the high-resolution scanning electron microscopy, X-ray diffraction, and Raman spectroscopy. Cyclic voltammetry results reveal that the GR-β-CD/CuO NPs composite modified electrode exhibits an excellent catalytic activity and lower reduction potential towards the electrochemical detection of metronidazole (MTZ) over other modified electrodes including GR, GR-β-CD, and CuO NPs. Under optimized conditions, amperometry was used for the determination of MTZ using GR-β-CD/CuO NPs composite modified electrodes. The response of MTZ using the composite electrodes was linear over the range from 0.002 to 210.0 µM. This sensor showed the lowest limit of detection of 0.6 nM and was much lower than the previously reported MTZ sensors. In addition, the sensor is highly sensitive, selective and durable in the presence of a range of potentially interfering electroactive compounds.


Single-Contrast CT for Detecting Bowel Injuries in Penetrating Abdominopelvic Trauma.
Many centers advocate use of triple-contrast (IV, oral, and rectal) CT for assessing hemodynamically stable patients with penetrating abdominopelvic trauma. Enteric contrast material has several disadvantages, leading our practice to pursue use of single-contrast (IV) CT. We conducted a retrospective review of electronic medical records at our institution to assess the accuracy of single-contrast CT for diagnosing bowel injuries in cases of penetrating abdominopelvic trauma. We retrospectively reviewed patients who presented to our emergency department between January 1, 2004, and March 1, 2014, with penetrating abdominopelvic trauma, underwent an abdominopelvic CT, and had surgery performed thereafter. We reviewed pertinent emergency department records for details regarding the site of injury, the number of injuries per patient, and the type of weapon used. We correlated CT reports with operative notes for presence and sites of bowel injury. A total of 274 patients (median age, 27 years old) met our inclusion criteria; 77% had sustained gunshot wounds (GSWs). CT showed bowel injury in 173 cases; surgery revealed bowel injury in 162 cases. CT had 142 true-positive, 31 false-positive, 81 true-negative, and 20 false-negative cases, resulting in sensitivity of 88%, specificity of 72%, positive predictive value of 82%, and negative predictive value of 80% for detecting bowel injuries. CT had the highest sensitivity and specificity in patients with multiple GSWs (94% and 79%, respectively) and those with injuries to the stomach and rectum. Single-contrast CT can show bowel injuries in patients with penetrating abdominopelvic trauma with accuracy comparable with that reported for triple-contrast CT.


Improving the oral health status of all Americans: roles and responsibilities of academic dental institutions: the report of the ADEA President's Commission.
Academic dental institutions are the fundamental underpinning of the nation's oral health. Education, research, and patient care are the cornerstones of academic dentistry that form the foundation upon which the dental profession rises to provide care to the public. The oral health status of Americans has improved dramatically over the past twenty-five to thirty years. In his 2000 report on oral health, the Surgeon General acknowledges the success of the dental profession in improving the oral health status of Americans over the past twenty-five years, but he also juxtaposes this success to profound and consequential disparities in the oral health of Americans. In 2002, the American Dental Education Association brought together an ADEA President's Commission of national experts to explore the roles and responsibilities of academic dental institutions in improving the oral health status of all Americans. They have issued this report and made a variety of policy recommendations, including a Statement of Position, to the 2003 ADEA House of Delegates. The commission's work will help guide ADEA in such areas as: identifying barriers to oral health care, providing guiding principles for academic dental institutions, anticipating workforce needs, and improving access through a diverse workforce and the types of oral health providers, including full utilization of allied dental professionals and collaborations with colleagues from medicine.


Ethical decision-making in intensive care: are nurses suitable patient advocates?
According to the United Kingdom Central Council for Nursing, Midwifery and Health Visiting (UKCC) code of conduct (1992), nurses in Britain are expected to act as patient advocates. An advocate is someone who 'pleads for another' (Concise Oxford Dictionary 1982). However, it has been shown that advocacy is a complex issue and it is debatable as to whether or not it is a legitimate attribute of the role of the nurse (Gates 1995). Mallik (1997) also finds that advocacy can be a risky career option. Professional codes of conduct spell out duties, but do not give moral guidance. Phrases such as 'promote and safeguard the well-being of the patient' (UKCC 1992) are used, but although undoubtedly well-intentioned, this is platitudinous and these codes commonly shed little light on how to define an action that is to the patient's benefit or detriment. It is tempting to suggest that they are used as a drunken man uses a street lamp; more for support than illumination. Castledine (1981) identified a number of factors that would make a nurse an inappropriate advocate and these will be discussed within the context of intensive care units (ICUs).


Increased physician-reported sleep apnea: the National Ambulatory Medical Care Survey.
Despite increased recognition of sleep apnea as a major health problem, little is known about physician practice patterns regarding this condition. We used the National Ambulatory Medical Care Survey (NAMCS) data between the years of 1990 to 1998, a weighted estimate of the frequency of physicians' diagnoses nationwide in their outpatient practices, to address the following questions: (1) has there been an increase in physician reporting of sleep apnea, (2) which physicians reported diagnoses of sleep apnea, and (3) what are the demographic characteristics of patients with diagnoses of sleep apnea? During this 9-year period, there was a 12-fold increase in the diagnosis of sleep apnea in outpatients, from 108,121 to 1,305,624 diagnoses (p < 0.001). Among other primary sleep disorders, only insomnia had an increase in reporting (fourfold, p < 0.001). Report of sleep apnea was greatest among primary care providers (37%), pulmonologists (24%), and otolaryngologists (18%). Sleep apnea was reported more often in men than in women (3:1, respectively), and 80% of diagnoses occurred in the following age groups: 30 to 39 years (12%), 40 to 49 years (33%), 50 to 59 years (27%), and 60 to 69 years (12%). Conditions associated with sleep apnea included hypertension (10%), obesity (6%), and COPD (7%). Increased reporting of sleep apnea by NAMCS physicians was associated with increases in the number of accredited sleep laboratories and the number of sleep publications in the medical literature during the period of review (p < 0.001). Sleep apnea is recognized increasingly by physicians. Further investigation is necessary to define those factors that influence physician recognition and reporting of sleep apnea, and approaches associated with optimum patient outcomes.


Targeting the gut layers in Crohn's disease: mucosal or transmural healing?
Although the landmark of Crohn's Disease (CD) is the transmural inflammation, mucosal healing (MH), which is assessed by colonoscopy, is currently the gold standard of CD management. Transmural healing (TH) is a new concept evaluated by cross-sectional imaging (CSI) techniques, such as bowel ultrasound (US), computed tomography enterography (CTE), and magnetic resonance enterography (MRE). Little is known about the clinical significance of persisting mural disease and the predictive value of complete TH. The authors reviewed the available literature on TH and its meaning as predictor of long-term outcomes in CD, to explore if TH may be a better target compared to MH in CD patients, in terms of disease outcome, such as medication changes, hospitalization, or surgery. Some evidence suggests that achieving TH has a predictive value in CD management and correlates with better disease outcome than MH, although existing studies are few and with limitations. A definitive definition of TH is not yet established and the frequency or the preferred modality of TH evaluation remains unclear. Implementing TH in treat-to-target approach may enable stricter disease monitoring with noninvasive methods and finally change the disease course, preventing irreversible bowel damage.


Exploring communities' and health workers' perceptions of indicators and drivers of malaria decline in Malindi, Kenya.
Since 2000, a decrease in malaria burden has been observed in most endemic countries. Declining infection rates and disease burden and reduction in asymptomatic carriers are the outcome of improved quality of care and related health system factors. These include improved case management through better diagnosis, implementation of highly effective antimalarial drugs and increased use of bednets. We studied communities' and health workers' perceptions of indicators and drivers in the context of decreasing malaria transmission in Malindi, Kenya. A variety of qualitative methods that included participatory rural appraisal (PRA) tools such as community river of life and trend lines, focus group discussions (FGDs) and key informant interviews were used. Studies took place between November 2013 and April 2014. Providing residents with bednets contributed to malaria reduction, and increasing community awareness on the causes and symptoms of malaria and improved malaria treatment were also perceived to contribute to the decline of malaria. The study identified three perceived drivers to the reported decline in malaria: a) community health workers' enhanced awareness creation towards household owners regarding malaria-related activities through visitations and awareness sessions, b) Women involvement in Savings Internal Lending Community was perceived to have increased their financial base, thereby improving their decision-making power towards the care of their sick child(ren), c) Non Governmental Organizations (NGOs) and partners played a promoter part in health and general economic development initiatives. To achieve the goal of malaria elimination, collaboration between governmental and NGOs will be crucial when improving the financial base of women and enhancing participation of community health workers.


Health information exchange among US hospitals.
To determine the proportion of US hospitals engaged in health information exchange (HIE) with unaffiliated providers and to identify key hospital-level and market-level factors associated with participating in exchange. Using the 2009 American Hospital Association Information Technology survey, supplemented by Dartmouth Atlas, Area Resource File, and other national data, we examined which hospitals participated in regional efforts to electronically exchange clinical data. We used logistic regression models to determine hospital-level characteristics and market-level characteristics associated with hospitals' likelihood of participating in HIE. We found that 10.7% of US hospitals engaged in HIE with unaffiliated providers. In communities where exchange occurred, for-profit hospitals and those with a small market share were far less likely to engage in HIE than nonprofit hospitals or those with a larger market share. Hospitals in more concentrated markets were more likely to exchange and hospitals in markets with higher Medicare spending were less likely to exchange. At the start of implementation of the Health Information Technology for Economic and Clinical Health (HITECH) Act, only a small minority of US hospitals electronically exchange clinical data with unaffiliated providers. Health information exchange is a key part of reforming the healthcare system, and factors related to competitiveness may be holding some providers back.


The maxi-K channel opener BMS-204352 attenuates regional cerebral edema and neurologic motor impairment after experimental brain injury.
Large-conductance, calcium-activated potassium (maxi-K) channels regulate neurotransmitter release and neuronal excitability, and openers of these channels have been shown to be neuroprotective in models of cerebral ischemia. The authors evaluated the effects of postinjury systemic administration of the maxi-K channel opener, BMS-204352, on behavioral and histologic outcome after lateral fluid percussion (FP) traumatic brain injury (TBI) in the rat. Anesthetized Sprague-Dawley rats (n = 142) were subjected to moderate FP brain injury (n = 88) or surgery without injury (n = 54) and were randomized to receive a bolus of 0.1 mg/kg BMS-204352 (n = 26, injured; n = 18, sham), 0.03 mg/kg BMS-204352 (n = 25, injured; n = 18, sham), or 2% dimethyl sulfoxide (DMSO) in polyethylene glycol (vehicle, n = 27, injured; n = 18, sham) at 10 minutes postinjury. One group of rats was tested for memory retention (Morris water maze) at 42 hours postinjury, then killed for evaluation of regional cerebral edema. A second group of injured/sham rats was assessed for neurologic motor function from 48 hours to 2 weeks postinjury and cortical lesion area. Administration of 0.1 mg/kg BMS-204352 improved neurologic motor function at 1 and 2 weeks postinjury (P < 0.05) and reduced the extent of cerebral edema in the ipsilateral hippocampus, thalamus, and adjacent cortex (P < 0.05). Administration of 0.03 mg/kg BMS-204352 significantly reduced cerebral edema in the ipsilateral thalamus (P < 0.05). No effects on cognitive function or cortical tissue loss were observed with either dose. These results suggest that the novel maxi-K channel opener BMS-204352 may be selectively beneficial in the treatment of experimental TBI.


Cerebral blood flow in rats during physiological and humoral stimuli.
The technique for estimating cerebral blood flow (CBF) in anesthetized rats by injecting 133Xe into the internal carotid artery represents a potentially useful and inexpensive model for screening cerebral vascular responses to pathophysiological and pharmacological stimuli. We have examined associated neuropathology, the validity and the reproducibility of the method, and made comparisons of initial slope estimates of CBF with those obtained by stochastic analysis. Initial slope estimates (CBF = 1.62 +/- 0.04 ml min-1g-1, X +/- SE, N = 38) were linearly related to stochastic measurements (CBF = 1.42 +/- 0.09 ml min-1g-1, N = 6), and overestimated mean CBF by about 15%. A reactivity to CO2 of 0.05 ml min-1g-1 per mm Hg, and an auto-regulation range of 70 to 180 mm Hg were found. CBF responses to the intra-arterial infusion of aminergic drugs were determined before and after opening of the blood-brain barrier with hypertonic urea. Serotonin reduced CBF after, but not before, the administration of urea. Acetylcholine increased CBF when the barrier was intact, the effect being augmented when the barrier was disrupted; these responses were reduced by atropine. Histamine increased CBF only after barrier opening, and this response was attenuated by the H2-receptor antagonist, metiamide. These studies indicate that initial slope estimates of CBF derived in rats from intracarotid 133Xe injection, which represents an inexpensive and simplified approach for screening cerebral circulatory adjustments, may facilitate the characterization of stimuli affecting CBF.


Transcatheter pulmonary valve replacement in pediatric patients.
Right ventricular outflow tract (RVOT) dysfunction is common among individuals with congenital heart disease (CHD). Surgical intervention often carries prohibitive risks due to the need for sequential pulmonary valve (PV) replacements throughout their life in the majority of cases. Transcatheter pulmonary valve replacement (tPVR) is one of the most exciting recent developments in the treatment of CHD and has evolved to become an attractive alternative to surgery in patients with RVOT dysfunction. In this review, we examine the pathophysiology of RVOT dysfunction, indications for tPVR, and the procedural aspect. Advancements in clinical application and valve technology will also be covered. tPVR is widely accepted as an alternative to surgery to address RVOT dysfunction, but still significant numbers of patients with complex RVOT morphology deemed not suitable for tPVR. As the technology continues to evolve, new percutaneous valves will allow such complex RVOT patient to benefit from tPVR.


An atlas of the Epstein-Barr virus transcriptome and epigenome reveals host-virus regulatory interactions.
Epstein-Barr virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration.


Reliability of sports related functional tests with emphasis on speed and agility in young athletes.
The aim of the present investigation was to test the reliability of two sports related functional tests, a speed test (slalom-test) and an agility test (hurdle-test). Eleven athletes aged 11 years (8 boys, 3 girls) participated voluntarily in the study. All subjects completed four different test sessions for both the slalom-test and the hurdle-test using six standard track hurdles placed at 2-m intervals along a 12-m length of track. There were no significant differences between testing sessions for either the slalom-test (P=0.99) or the hurdle-test (P=0.96), showing no systematic variation between test times. The intraclass correlation coefficients were 0.96 and 0.90 respectively, indicating a good reliability. We conclude that the slalom-test and the hurdle-test are reliable sports related functional tests for measuring speed and agility in groups of young athletic individuals.


Possible Use of Blood Tryptophan Metabolites as Biomarkers for Coronary Heart Disease in Sudden Unexpected Death.
Coronary heart disease (CHD) is the major cause of death in sudden unexpected death (SUD) cases. Tryptophan (TRP) and its metabolites are correlated with the CHD patient but less studies in the SUD. The aim of this study was to evaluate the relationship of TRP and its metabolites with the CHD in the SUD cases. Blood samples and heart tissues were collected from CHD subjects (n = 31) and the control group (n = 72). Levels of kynurenine (KYN), kynurenic acid (KYA), xanthurenic acid (XAN), 3-hydroxyanthranillic acid (HAA), quinolinic acid (QA), picolinic acid (PA) and 5-hydroxyindoleacetic acid (HIAA) were determined by HPLC-DAD. A severity of heart occlusion was categorized into four groups, and the relationship was measured with the TRP metabolites. The HIAA and The KYN levels significantly differed (p < 0.01) between the CHD group and the control group. Lower levels of QA/XAN, PA/KA, HAA/XAN, KYN/XAN and KYN/TRP were found in the CHD group. However, PA/HAA, PA/HIAA, PA/KYN and XAN/KA values in the CHD group were higher than the control group (p < 0.05). This study revealed that the values of PA/KA and PA/HAA provided better choices for a CHD biomarker in postmortem bodies.


Cell patterning via linker-free protein functionalization of an organic conducting polymer (polypyrrole) electrode.
The interaction of proteins and cells with polymers is critical to their use in scientific and medical applications. In this study, plasma immersion ion implantation (PIII) was used to modify the surface of the conducting polymer, polypyrrole, which possesses electrical properties. PIII treatment enabled persistent, covalent binding of the cell adhesive protein, tropoelastin, without employing chemical linking molecules. In contrast tropoelastin was readily eluted from the untreated surface. Through this differential persistence of binding, surface bound tropoelastin supported cell adhesion and spreading on the PIII treated but not the untreated polypyrrole surface. The application of a steel shadow mask during PIII treatment allowed for spatial definition of tropoelastin exclusively to PIII treated regions. The general applicability of this approach to other extracellular matrix proteins was illustrated using collagen I, which displayed similar results to tropoelastin but required extended washing conditions. This approach allowed fine patterning of cell adhesion and spreading to tropoelastin and collagen, specifically on PIII treated polypyrrole regions. We therefore present a methodology to alter the functionality of polypyrrole surfaces, generating surfaces that can spatially control cellular interactions through protein functionalization with the potential for electrical stimulation.


Blockade of deoxyribonucleic acid synthesis by deuterium oxide.
Interference with deoxyribonucleic acid replication need not be a primary mechanism in the blockade of cell division by deuterium oxide, but current hypotheses on the molecular basis of the blockade do suggest that such interference might take place under appropriate conditions. Autoradiographic experiments support the suggestion, for whereas normal sea urchin eggs incorporate H(3)-thymidine into deoxyribonucleic acid from almost the beginning of development, cells immersed in deuterium-enriched media do not. Blockade of mitosis and inhibition of thymidine incorporation are simultaneously relieved when the eggs are returned to normal water.


Performance of Automated Telemetry in Diagnosing QT Prolongation in Critically Ill Patients.
QT prolongation increases the risk of ventricular arrhythmia and is common among critically ill patients. The gold standard for QT measurement is electrocardiography. Automated measurement of corrected QT (QTc) by cardiac telemetry has been developed, but this method has not been compared with electrocardiography in critically ill patients. To compare the diagnostic performance of QTc values obtained with cardiac telemetry versus electrocardiography. This prospective observational study included patients admitted to intensive care who had an electrocardiogram ordered simultaneously with cardiac telemetry. Demographic data and QTc determined by electrocardiography and telemetry were recorded. Bland-Altman analysis was done, and correlation coefficient and receiver operating characteristic (ROC) coefficient were calculated. Fifty-one data points were obtained from 43 patients (65% men). Bland-Altman analysis revealed poor agreement between telemetry and electrocardiography and evidence of fixed and proportional bias. Area under the ROC curve for QTc determined by telemetry was 0.9 (P < .001) for a definition of prolonged QT as QTc ≥ 450 milliseconds in electrocardiography (sensitivity, 88.89%; specificity, 83.33%; cutoff of 464 milliseconds used). Correlation between the 2 methods was only moderate (r = 0.6, P < .001). QTc determination by telemetry has poor agreement and moderate correlation with electrocardiography. However, telemetry has an acceptable area under the curve in ROC analysis with tolerable sensitivity and specificity depending on the cutoff used to define prolonged QT. Cardiac telemetry should be used with caution in critically ill patients.


Anemia identified one month after renal transplantation is predictive of anemia identified after twelve months.
The aim of this study was to evaluate whether anemia identified earlier than 3 months postengraftment in modern era could be predictive of anemia at 12 months. Cross-sectional and cohort studies based on retrospective analysis of existing clinical records were performed. Data on recipient's age at transplantation, follow-up serum creatinine (SCR) and hemoglobin (Hb) on day 7 (D7), at month 1 (M1) and at month 3 (M3) postengraftment were collected. Outcome was anemia identified at 12 months (M12) postengraftment. There were 75 patients on D7, 74 at M1 and 61 at M3. Multiple linear regression model that included recipient's age at transplantation, Hb and creatinine on D7 and tested the risk for anemia at M12 retained only the age in the model, with the coefficient of 0,84 (P=0,001). The same model at M1 retained Hb and age, with the coefficients of 0,26 (P=0,03) and 0,81 (P=0,0002), respectively and at M3 it retained Hb and age, with the coefficients of 0,41 (P=0,004) and 0,70 (P=0,003), respectively. Anemia identified at M1 after renal transplantation is predictive of anemia at M12.


Electricity generation from wastewaters with starch as carbon source using a mediatorless microbial fuel cell.
Microbial fuel cells represent a new method for producing electricity from the oxidation of organic matter. A mediatorless microbial fuel cell was developed using Escherichia coli as the active bacterial component with synthetic wastewater of potato extract as the energy source. The two-chamber fuel cell, with a relation of volume between anode and cathode chamber of 8:1, was operated in batch mode. The response was similar to that obtained when glucose was used as the carbon source. The performance characteristics of the fuel cell were evaluated with two different anode and cathode shapes, platinised titanium strip or mesh; the highest maximum power density (502mWm(-2)) was achieved in the microbial fuel cell with mesh electrodes. In addition to electricity generation, the MFC exhibited efficient treatment of wastewater so that significant reduction of initial oxygen demand of wastewater by 61% was observed. These results demonstrate that potato starch can be used for power generation in a mediatorless microbial fuel cell with high removal efficiency of chemical oxygen demand.


Acremonium implicatum, a Seed-Transmitted Endophytic Fungus in Brachiaria Grasses.
The pan-tropical grass genus Brachiaria comprises about 100 species, several of which are forages of economic importance, particularly in tropical America. Acremonium implicatum is a fungus that forms an endophytic association with at least some of these economically important grasses. To ascertain whether A. implicatum can be seed transmitted in Brachiaria species, we vegetatively propagated, under greenhouse conditions, 20 tillers from an endophyte-infected mother plant obtained from each of 14 Brachiaria hybrids and species. Ten tillers of each genotype were treated with the fungicide tebuconazole to eliminate the endophyte, and the other 10 were left untreated. Seeds were then harvested individually from all 20 of these genetically identical plants, germinated, and the seedlings grown. A previously developed polymerase chain reaction-based method used a pair of endophyte-specific primers to amplify a diagnostic 500-bp DNA fragment. The seedlings generated from seeds harvested from endophyte-infected plants also tested positive, whereas those from seeds of endophyte-free plants showed no amplification products. This is the first report of A. implicatum being transmitted through seeds of Brachiaria grasses.


Auxin gradients are associated with polarity changes in trees.
Models of plant growth and development propose that changes in cell polarity are mediated by gradients of the plant hormone auxin. With use of gas chromatography-mass spectrometry, we measured the redistribution of endogenous auxin in stems of quaking aspen trees (Populus tremuloides) after wounding. Persistent (lasting at least 24 hours) auxin gradients were observed in the region of the cambium where cell polarity was changing. A computer model of the auxin redistribution shows agreement with measured concentrations.


Identification of decision criteria for revision surgery among patients with proximal junctional failure after surgical treatment of spinal deformity.
Multicenter, retrospective, consecutive case series. This study aims to identify demographic and radiographical characteristics that influence the decision to perform revision surgery among patients with proximal junctional failure (PJF). Revision rates after PJF remain relatively high, yet the decision criteria for performing revision surgical procedures are not uniform and vary by surgeon. A better understanding of the factors that impact the decision to perform revision surgery is important in order to improve efficiency of surgical treatment of adult spinal deformity. A cohort of 57 patients with PJF was identified retrospectively from 1218 consecutive patients with adult spinal deformity. PJF was identified on the basis of 10° postoperative increase in kyphosis between upper instrumented vertebra (UIV) and UIV +2, along with 1 or more of the following: fracture of the vertebral body of UIV or UIV +1, posterior osseoligamentous disruption, or pullout of instrumentation at the UIV. Univariate statistical analysis was performed using t tests and Fisher exact tests. Multivariate analysis was performed using logistic regression. Twenty-seven (47.4%) patients underwent revision surgery within 6 months of the index operation. Regression results revealed that patients with combined posterior/anterior approaches at index were significantly more likely to undergo revision (P = 0.001) as were patients with more extreme proximal junctional kyphosis angulation (P = 0.034). Patients sustaining trauma were also significantly more likely to undergo revision (P = 0.019). Variables approaching but not reaching significance as predictors of revision included female sex (P = 0.066) and higher sagittal vertical axis (SVA) (P = 0.090). The decision to perform revision surgery is complicated and varies by surgeon. Factors that seem to influence this decision include traumatic etiology of PJF, severity of proximal junctional kyphosis angulation, higher SVA, and female sex. Factors that were expected to influence revision but had no statistical effect included soft tissue versus bony mode of failure, age, levels fused, and upper thoracic versus thoracolumbar proximal junction.


Multimodal Monitoring of Cardiovascular Responses to Postural Changes.
In the poorly understood relationship between orthostatic hypotension and falls, next to blood pressure (BP), baroreflex sensitivity (BRS) and cerebral autoregulation (CAR) may be key measures. The posture- and movement dependency of orthostatic hypotension requires continuous and unobtrusive monitoring. This may be possible using simultaneous photoplethysmography (PPG), electrocardiography (ECG), and near-infrared spectroscopy (NIRS) signal recordings, from which pulse wave velocity (PWV; potentially useful for BP estimation), BRS and CAR can be derived. The PPG, NIRS and PWV signal correlation with BP and BRS/CAR reliability and validity need to be addressed. In 34 healthy adults (mean age 25 years, inter quartile range 22-45; 10 female), wrist and finger PPG, ECG, bifrontal NIRS (oxygenated and deoxygenated hemoglobin) and continuous BP were recorded during sit to stand and supine to stand movements. Sixteen participants performed slow and rapid supine to stand movements; eighteen other participants performed a 1-min squat movement. Pulse wave velocity (PWV) was defined as the inverse of the ECG R-peak to PPG pulse delay; PPG, NIRS and PWV signal correlation with BP as their Pearson correlations with mean arterial pressure (MAP) within 30 s after the postural changes; BRS as inter beat interval drop divided by systolic BP (SBP) drop during the postural changes; CAR as oxygenated hemoglobin drop divided by MAP drop. BRS and CAR were separately computed using measured and estimated (linear regression) BP. BRS/CAR reliability was defined by the intra class correlation between repeats of the same postural change; validity as the Pearson correlation between BRS/CAR values based on measured and estimated BP. The highest correlation with MAP was found for finger PPG and oxygenated hemoglobin, ranging from 0.75-0.79 (sit to stand), 0.66-0.88 (supine to stand), and 0.82-0.94 (1-min squat). BRS and CAR reliability was highest during the different supine to stand movements, ranging from 0.17 - 0.49 (BRS) and 0.42-0.75 (CAR); validity was highest during rapid supine to stand movements, 0.54 and 0.79 respectively. PPG-ECG-NIRS recordings showed high correlation with BP and enabled computation of reliable and valid BRS and CAR estimates, suggesting their potential for continuous unobtrusive monitoring of orthostatic hypotension key measures.


Mobility of ribosomes bound to microsomal membranes. A freeze-etch and thin-section electron microscope study of the structure and fluidity of the rough endoplasmic reticulum.
The lateral mobility of ribosomes bound to rough endoplasmic reticulum (RER) membranes was demonstrated under experimental conditions. High-salt-washed rough microsomes were treated with pancreatic ribonuclease (RNase) to cleave the mRNA of bound polyribosomes and allow the movement of individual bound ribosomesmfreeze-etch and thin-section electron microscopy demonstrated that, when rough microsomes were treated with RNase at 4 degrees C and then maintained at this temperature until fixation, the bound ribosomes retained their homogeneous distribution on the microsomal surface. However, when RNase-treated rough microsomes were brought to 24 degrees C, a temperature above the thermotropic phase transition of the microsomal phospholipids, bound ribosomes were no longer distributed homogeneously but, instead, formed large, tightly packed aggregates on the microsomal surface. Bound polyribosomes could also be aggregated by treating rough microsomes with antibodies raised against large ribosomal subunit proteins. In these experiments, extensive cross-linking of ribosomes from adjacent microsomes also occurred, and large ribosome-free membrane areas were produced. Sedimentation analysis in sucrose density gradients demonstrated that the RNase treatment did not release bound ribosomes from the membranes; however, the aggregated ribosomes remain capable of peptide bond synthesis and were released by puromycin. It is proposed that the formation of ribosomal aggregates on the microsomal surface results from the lateral displacement of ribosomes along with their attached binding sites, nascent polypeptide chains, and other associated membrane proteins; The inhibition of ribosome mobility after maintaining rough microsomes at 4 degrees C after RNase, or antibody, treatment suggests that the ribosome binding sites are integral membrane proteins and that their mobility is controlled by the fluidity of the RER membrane. Examination of the hydrophobic interior of microsomal membranes by the freeze-fracture technique revealed the presence of homogeneously distributed 105-A intramembrane particles in control rough microsomes. However, aggregation of ribosomes by RNase, or their removal by treatment with puromycin, led to a redistribution of the particles into large aggregates on the cytoplasmic fracture face, leaving large particle-free regions.


Korean translation of the CONSORT 2010 Statement: updated guidelines for reporting parallel group randomized trials.
The Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement, updated in March 2010, includes a 25-item checklist and flow diagram. Adherence to this statement is a minimum requirement for the complete, clear, and transparent reporting of randomized trials. We translated the CONSORT 2010 Statement into Korean to promote the widespread adherence to CONSORT in South Korea and to facilitate the adoption of complete, clear, and transparent reporting. The Korean version of the CONSORT is available at http://www.e-epih.org/.


Impaired Cardiac Reserve on Dobutamine Stress Echocardiography Predicts the Development of Hepatorenal Syndrome.
Cardiac dysfunction has been implicated in the genesis of hepatorenal syndrome (HRS). It is unclear whether a low cardiac output (CO) or attenuated contractile response to hemodynamic stress can predict its occurrence. We studied cardiovascular hemodynamics in cirrhosis and assessed whether a diminished cardiac reserve with stress testing predicted the development of HRS on follow-up. Consecutive patients undergoing liver transplant workup with dobutamine stress echocardiography (DSE) were included. CO was measured at baseline and during low-dose dobutamine infusion at 10 μg/kg/min. HRS was diagnosed using guideline-based criteria. A total of 560 patients underwent DSE, of whom 488 were included after preliminary assessment. There were 64 (13.1%) patients with established HRS. The HRS cohort had a higher baseline CO (8.0 ± 2 vs 6.9 ± 2 L/min; P < 0.001) and demonstrated a blunted response to low-dose dobutamine (ΔCO 29 ± 22% vs 44 ± 32%, P < 0.001) driven primarily by inotropic incompetence. Optimal cutpoint for ΔCO in patients with HRS was determined to be <25% and was used to define a low cardiac reserve. Among the 424 patients without HRS initially, 94 (22.1%) developed HRS over a mean follow-up of 1.5 years. Higher proportion with a low cardiac reserve developed HRS (52 [55.0%] vs 56 [16.9%]; hazard ratio 4.5; 95% confidence interval 3.0-6.7; P < 0.001). In a Cox multivariable model, low cardiac reserve remained the strongest predictor for the development of HRS (hazard ratio 3.9; 95% confidence interval 2.2-7.0; P < 0.001). Patients with HRS demonstrated a higher resting CO and an attenuated cardiac reserve on stress testing. On longitudinal follow-up, low cardiac reserve was an independent predictor for the development of HRS. Assessment of cardiac reserve with DSE may provide a novel noninvasive risk marker for developing HRS in patients with advanced liver disease.HRS is a life-threatening complication of liver disease. We studied whether an inability to increase cardiac contraction in response to stress can assist in the prediction of HRS. We demonstrate that patients with liver disease who exhibit cardiac dysfunction during stress testing had a 4-fold increased risk of developing HRS. This may improve our ability for early diagnosis and treatment of patients at a higher risk of developing HRS.


Comparative Transcriptome Profiles of Human Blood in Response to the Toll-like Receptor 4 Ligands Lipopolysaccharide and Monophosphoryl Lipid A.
Monophosphoryl lipid A (MPLA), a less toxic derivative of lipopolysaccharide (LPS), is employed as a vaccine adjuvant and is under investigation as a non-specific immunomodulator. However, the differential response of human leukocytes to MPLA and LPS has not been well characterized. The goal of this study was to compare the differential transcriptomic response of human blood to LPS and MPLA. Venous blood from human volunteers was stimulated with LPS, MPLA or vehicle. Gene expression was determined using microarray analysis. Among 21,103 probes profiled, 136 and 130 genes were differentially regulated by LPS or MPLA, respectively. Seventy four genes were up-regulated and 9 were down-regulated by both ligands. The remaining genes were differentially induced by either agent. Ingenuity Pathway Analysis predicted that LPS and MPLA share similar upstream regulators and have comparable effects on canonical pathways and cellular functions. However, some pro-inflammatory cytokine and inflammasome-associated transcripts were more strongly induced by LPS. In contrast, only the macrophage-regulating chemokine CCL7 was preferentially up-regulated by MPLA. In conclusion, LPS and MPLA induce similar transcriptional profiles. However, LPS more potently induces pro-inflammatory cytokine and inflammasome-linked transcripts. Thus, MPLA is a less potent activator of the pro-inflammatory response but retains effective immunomodulatory activity.


Studies on the fate of the glutathione and cysteine conjugates of acetaminophen in mice.
Studies were conducted in mice to examine the origin and fate of the amino acid-containing conjugates of acetaminophen (APAP). Collection of bile containing [14C]APAP metabolites (mainly the glutathione conjugate) in common duct-cannulated mice given a 250 mg/kg oral dose of the drug reduced by greater than 70% the urinary excretion of the cysteine and mercapturic acid conjugates of APAP. This confirmed previous reports which indicated that these urinary metabolites originated from the glutathione conjugate excreted in bile. The urinary excretion of cysteine and mercapturic acid conjugates was not altered, however, by ligation of the common bile duct in mice given APAP. Thus, biliary excretion of the glutathione conjugate is not obligatory for the appearance of cysteine and mercapturic acid conjugates in urine. Intravenous administration of purified glutathione conjugate to mice having a bile-duct cannula indicated that this conjugate did not appear in bile but appeared in urine primarily in the form of the cysteine conjugate. An identical pattern of excretion was observed after an iv dose of the purified cysteine conjugate of APAP to bile duct-cannulated mice. These results indicated that, if the glutathione conjugate leaves the liver via the blood, it is rapidly converted to the cysteine conjugate which is eliminated in urine. This conversion takes place at multiple sites in the body and evidence is presented to implicate both intestine and kidney in the process. The appearance of a small amount of glutathione conjugate in urine (16%) after an iv dose of the cysteine conjugate indicates that formation of the glutathione of APAP can occur by a route that does not involve direct conjugation of reactive metabolites of the drug with glutathione.


Plastic phase-locking and magnetic mismatch response to auditory deviants in temporal lobe epilepsy.
The magnetic equivalent (MMNm) of mismatch negativity may reflect auditory discrimination and sensory memory. To study whether temporal lobe epilepsy (TLE) affects automatic central auditory-change processing, we recorded magnetoencephalographic (MEG) responses to standard and duration-deviant sounds in 12 TLE patients and 12 age-matched controls, and repeated MEG measurement in 8 patients 6-30 months following epilepsy surgery and in 6 controls 3-8 months after their first measurement. We compared the MMNm between patients and controls, and also evaluated intertrial phase coherences as indexed by phase-locking factors (PLF) using wavelet-based analyses. We observed longer MMNm latencies for patients than for controls. Dipole modeling and minimum-current estimates together showed bi-frontotemporal sources for MMNm. The phase locking across trials was dominant at the 4- to 14-Hz band, and the main difference in PLF between deviant- and standard-evoked responses occurred in the time frame of 150-250 ms after stimulus onset. Notably, in the 5 patients who became seizure free after removal of right temporal epileptic focus, the phase-locking phenomena resulting from deviant stimuli were enhanced, and even more distributed in the frontotemporal regions. We conclude that mesial TLE might affect auditory-change detection, and a successful surgery causes a possible plastic change in phase locking of deviant-evoked signals.


The organochlorine pesticide residues and antioxidant enzyme activities in human breast tumors: is there any association?
The levels of some organochlorine pesticides (OCP)s (hexachlorobenzene, HCB, alpha-hexachlorocyclohexane, alpha-HCH, beta-HCH, gamma-HCH, heptachlorepoxide, HE, bis (4-chlorophenyl)-1,1-dichloroethene, p.p'DDE, bis (4-chlorophenyl)-1,1,1-trichloroethane, p.p' DDT and total DDT (E-DDT) and antioxidant enzyme activities namely Cu, Zn superoxide dismutase (SOD), catalase (CAT), selenium-dependent glutathione peroxidase (Se-GSH-Px), total glutathione peroxidase (T-GSH-Px), selenium independent glutathione peroxidase (GSH-Px II), glutathione reductase (GRd), level of reduced glutathione (GSH) and lipid peroxidation (LP), glutathione S-transferase (GST) activity toward several substrates including 1-chloro-2,4-dinitrobenzene (CDNB), 1,2-dichloro-4-nitrobenzene (DCNB), ethacrynic acid (EAA), 1,2-epoxy-3-(p-nitrophenoxy)-propane (ENPP) were measured in tumor and surrounding tumor free tissues of 24 female breast cancer patients and was evaluated whether there exist any association between the levels of OCPs and antioxidants. The mean levels of GSH, alpha-BHC, gamma-BHC and HE, and activities of SOD, Se-GSH-Px, T-GSH-Px, GSH-Px II,GRd, GST CDNB, and GST DCNB were significantly higher in tumors than in controls. In tumors, significant correlations were noted between: SOD and y-BHC; Se-GSH-Px and gamma-BHC; T-GSH-Px and gamma-BHC; GSH-Px II and alpha-BHC, gamma-BHC; GSH and alpha-BHC, gamma-BHC, HE; GRd and alpha-BHC; CDNB GST and alpha-BHC, gamma-BHC. These results show that free-radical mediated oxidative stress is, at least partly, associated with some of these OCP residues in human breast tumors.


Adverse Experiences in Early Childhood and Kindergarten Outcomes.
To examine associations between adverse childhood experiences (ACEs) in early childhood and teacher-reported academic and behavioral problems in kindergarten. We conducted a secondary analysis of data from the Fragile Families and Child Wellbeing Study, a national urban birth cohort. Subjects with primary caregiver-reported information on ACE exposures ascertained at 5 years and teacher-reported outcomes at the end of the child's kindergarten year were included. Outcomes included teacher ratings of academic skills, emergent literacy skills, and behavior. We included 8 ACE exposures on the basis of the original Centers for Disease Control and Prevention Kaiser study and created an ACE score by summing individual adversities. We examined the associations between teacher-reported academic and behavioral outcomes and ACE scores by using logistic regression. In the study sample, 1007 children were included. Fifty-five percent had experienced 1 ACE and 12% had experienced ≥ 3. Adjusting for potential confounders, experiencing ≥ 3 ACEs was associated with below-average language and literacy skills (adjusted odds ratio [AORs]: 1.8; 95% confidence interval [CI]: 1.1-2.9) and math skills (AOR: 1.8, 95% CI: 1.1-2.9), poor emergent literacy skills, attention problems (AOR: 3.5, 95% CI: 1.8-6.5), social problems (AOR: 2.7, 95% CI: 1.4-5.0), and aggression (AOR: 2.3, 95% CI: 1.2-4.6). In this study of urban children, experiencing ACEs in early childhood was associated with below-average, teacher-reported academic and literacy skills and behavior problems in kindergarten. These findings underscore the importance of integrated approaches that promote optimal development among vulnerable children.


Virulence from vesicles: Novel mechanisms of host cell injury by Escherichia coli O104:H4 outbreak strain.
The highly virulent Escherichia coli O104:H4 that caused the large 2011 outbreak of diarrhoea and haemolytic uraemic syndrome secretes blended virulence factors of enterohaemorrhagic and enteroaggregative E. coli, but their secretion pathways are unknown. We demonstrate that the outbreak strain releases a cocktail of virulence factors via outer membrane vesicles (OMVs) shed during growth. The OMVs contain Shiga toxin (Stx) 2a, the major virulence factor of the strain, Shigella enterotoxin 1, H4 flagellin, and O104 lipopolysaccharide. The OMVs bind to and are internalised by human intestinal epithelial cells via dynamin-dependent and Stx2a-independent endocytosis, deliver the OMV-associated virulence factors intracellularly and induce caspase-9-mediated apoptosis and interleukin-8 secretion. Stx2a is the key OMV component responsible for the cytotoxicity, whereas flagellin and lipopolysaccharide are the major interleukin-8 inducers. The OMVs represent novel ways for the E. coli O104:H4 outbreak strain to deliver pathogenic cargoes and injure host cells.


Obesity accelerates the progression of coronary atherosclerosis in young men.
Obesity is a risk factor for adult coronary heart disease and is increasing in prevalence among youths as well as adults. Results regarding the association of obesity with atherosclerosis are conflicting, particularly when analyses account for other risk factors. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study collected arteries, blood, and other tissue from approximately 3000 persons aged 15 to 34 years dying of external causes and autopsied in forensic laboratories. We measured gross atherosclerotic lesions in the right coronary artery (RCA), American Heart Association (AHA) lesion grade in the left anterior descending coronary artery (LAD), serum lipid concentrations, serum thiocyanate (for smoking), intimal thickness of renal arteries (for hypertension), glycohemoglobin (for hyperglycemia), and adiposity by body mass index (BMI) and thickness of the panniculus adiposus. BMI in young men was associated with both fatty streaks and raised lesions in the RCA and with AHA grade and stenosis in the LAD. The effect of obesity (BMI>30 kg/m(2)) on RCA raised lesions was greater in young men with a thick panniculus adiposus. Obesity was associated with non-HDL and HDL (inversely) cholesterol concentrations, smoking (inversely), hypertension, and glycohemoglobin concentration, and these variables accounted for approximately 15% of the effect of obesity on coronary atherosclerosis in young men. BMI was not associated with coronary atherosclerosis in young women although there was trend among those with a thick panniculus adiposus. Obesity is associated with accelerated coronary atherosclerosis in adolescent and young adult men. These observations support the current emphasis on controlling obesity to prevent adult coronary heart disease.