Drying and temperature induced conformational changes of nucleic acids and stallion sperm chromatin in trehalose preservation formulations.
Even though dried sperm is not viable, it can be used for fertilization as long as its chromatin remains intact. In this study, we investigated drying- and temperature-induced conformational changes of nucleic acids and stallion sperm chromatin. Sperm was diluted in preservation formulations with and without sugar/albumin and subjected to convective drying at elevated temperatures on glass substrates. Accumulation of reactive oxygen species was studied during storage at different temperatures, and the sperm chromatin structure assay was used to assess DNA damage. Fourier transform infrared spectroscopy was used to identify dehydration and storage induced conformational changes in isolated DNA and sperm chromatin. Furthermore, hydrogen bonding in the preservation solutions associated with storage stability were investigated. Reactive oxygen species and DNA damage in dried sperm samples were found to accumulate with increasing storage temperature and storage duration. Non-reducing disaccharides (i.e., trehalose, sucrose) and albumin counteracted oxidative stress and preserved sperm chromatin during dried storage, whereas glucose increased DNA damage during storage. When sperm was dried in the presence of trehalose and albumin, no spectral changes were detected during storage at refrigeration temperatures, whereas under accelerated aging conditions, i.e., storage at 37 °C, spectral changes were detected indicating alterations in sperm chromatin structure.


Integrating Structure and Function in Conceptualizing and Assessing Pathological Traits.
The Diagnostic and Statistical Manual of Mental Disorders' (5th Edition) Alternative Model of Personality Disorders includes a dimensional trait model to describe individual differences in the manifestation of personality pathology. Empirically derived quantitative trait models of psychopathology address many of the structural problems of classical diagnostic schemes (e.g., nonbinary distributions, excessive comorbidity, and diagnostic heterogeneity). However, they are largely based on the structure of individual differences in the manifestation of psychopathology. In contrast, clinical theories of personality disorder, which are the foundation of intervention efforts, are based on the function of maladaptive behavior. This distinction is akin to the difference between morphology and physiology in the broader biological sciences. A structure-function divide in the focus of empirical and clinical work contributes to a lack of integration and difficulties with translation. Here we discuss this tension and argue for the need to bridge this divide and adopt research efforts that integrate structure and function of personality traits. Specifically, we suggest that between-person structure identifies the principal domains of functioning, but to understand dysfunction personality must be conceptualized and studied as an ensemble of contextualized dynamic processes.


Feasibility study of using brine for carbon dioxide capture and storage from fixed sources.
A laboratory-scale reactor was developed to evaluate the capture of carbon dioxide (CO2) from a gas into a liquid as an approach to control greenhouse gases emitted from fixed sources. CO2 at 5-50% concentrations was passed through a gas-exchange membrane and transferred into liquid media--tap water or simulated brine. When using water, capture efficiencies exceeded 50% and could be enhanced by adding base (e.g., sodium hydroxide) or the combination of base and carbonic anhydrase, a catalyst that speeds the conversion of CO2 to carbonic acid. The transferred CO2 formed ions, such as bicarbonate or carbonate, depending on the amount of base present. Adding precipitating cations, like Ca++, produced insoluble carbonate salts. Simulated brine proved nearly as efficient as water in absorbing CO2, with less than a 6% reduction in CO2 transferred. The CO2 either dissolved into the brine or formed a mixture of gas and ions. If the chemistry was favorable, carbonate precipitate spontaneously formed. Energy expenditure of pumping brine up and down from subterranean depths was modeled. We conclude that using brine in a gas-exchange membrane system for capturing CO2 from a gas stream to liquid is technically feasible and can be accomplished at a reasonable expenditure of energy.


Dark brown amniotic fluid-identification of contributing pigments.
A total of 208 second trimester amniotic fluid samples were examined visually and spectrophotometrically for pigmentation. Of these, 15 samples had dark brown colouration. Fourteen of the 15 samples had chemically detectable haemoglobin derived pigments and one had meconium only. All 15 of the pigmented amniotic fluid samples had haemoglobin A and eight also had haemoglobin F. None of the remaining 193 amniotic fluid samples contained abnormal pigmentation. Four of the pregnancies from which the dark brown amniotic fluid was obtained failed to continue to term; in three of these myoglobin was detected.


Immunohistochemical characterization of brain-invasive meningiomas.
Brain-invasive meningiomas have an adverse prognosis, so it is important to detect and correctly evaluate brain invasion by light microscopy. Furthermore, the underlying biological mechanisms responsible for brain-invasive growth are incompletely understood. The primary aim of this study was to identify immunohistochemical markers that could improve identification and evaluation of brain invasion in meningiomas. A second aim was to investigate the process of brain invasion using immunohistochemical markers of proliferation, extracellular matrix modulation, and cell adhesion. From a series of 196 human meningiomas, 67 cases were selected for analysis because of the presence of brain tissue in tumor specimens. Fourteen of these 67 meningiomas were brain-invasive. Invasiveness was determined primarily by evaluation of hematoxylin-erytrosin-saffron- (HES-) stained specimens, although glial fibrillary acidic protein (GFAP), anti-collagen IV, and cluster of differentiation 44 (CD44) markers provided additional information. It was important to examine microscopic sections from various levels of the paraffin-embedded tissue block to adequately assess invasiveness. Sections stained using antibodies against Ki-67/MIB-1, phospohistone-H3 (PHH3), matrix metalloproteinase-9 (MMP-9), cathepsin D, plasminogen activator inhibitor-1 (PAI-1), and E-cadherin antigens were used to characterize brain-invasive meningiomas and to investigate the process of brain invasion. Only increased expression of the extracellular matrix modulator MMP-9 correlated with brain-invasive growth (p=0.025). Examination of HES-stained sections identified brain invasion. Use of relevant immunohistochemical markers did not contribute substantially to this evaluation. Evaluation of stepwise sections should be considered when brain-invasive growth is suspected. MMP-9 may be an important mediator of brain-invasive growth.


Overuse injuries in ultraendurance triathletes.
Overuse injuries represent the largest percentage of sports-related injuries requiring medical treatment. These injuries represent a substantial health issue for the millions of adults who have made physical activity an integral part of their lifestyle, but may be even more important to those pursuing ultraendurance exercise. The purposes of this study were to report the type and incidence of overuse injuries in ultraendurance triathletes and to relate training practices to injury occurrence. Data was gathered from the responses of 95 competitors (75 men, 20 women) in the 1986 Hawaii Ironman Triathlon who completed a training and medical history questionnaire. In this sample, virtually all (91%) sustained at least one soft tissue, overuse injury during the previous year's training. The area of the body most frequently involved was the back, but the most common pattern was to have multiple areas involved. Because of the consistent combinations of injuries, mechanical abnormalities, such as diminished shock absorption, may have contributed to injury. Training habits were extremely variable and not directly related to either the incidence or type of injury.


An automated method for the determination of sulfate.
An automated method of sulfate analysis is described, which can detect sulfate concentrations as low as 2.5 mug per ml water. The assay is based on the reaction of sodium rhodizonate and barium forming a colored complex. Sulfate quantitavely interferes with this reaction. The assay is reproducible in the range of 2.5 to 30 mug sulfate per ml water. This method conveniently and accurately measures water soluble sulfate filtered from the air, and is especially useful in assaying samples containing microgram quantities of sulfate from experimental inhalation apparatus.


Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.
The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.


Oncostatin M suppresses metastasis of lung adenocarcinoma by inhibiting SLUG expression through coordination of STATs and PIASs signalings.
Oncostatin M (OSM) is linked with multiple biological responses including growth and differentiation. Previous reports showed inhibitory effects of OSM in tumor progression while others showed promoting effects. The dual role of OSM in the development of various cancers is still unclear. We previously described OSM-mediated SLUG suppression, leading to repressed metastasis of lung adenocarcinoma (LAC) cells. However, the underlying mechanism remains elusive. Here, we showed that OSM suppresses SLUG express in LAC cells through a STAT1-dependent transcriptional inhibition. Knockdown of STAT1 reversed the OSM-suppressed SLUG expression and rescued the OSM-mediated inhibition of cell proliferation, migration, and invasion in vitro, as well as pulmonary metastasis in vivo. STAT1 suppressed SLUG transcription through binding to its promoter region in response to OSM. Furthermore, PIAS4, a co-repressor of STAT, and HDAC1 were able to bind to STAT1 on SLUG promoter region, resulting in reduced H3K9 acetylation and suppressed SLUG expression upon OSM treatment. In contrast, PIAS3 bound to activated STAT3, another effector of OSM, in response to OSM and blocked the binding of STAT3 to SLUG promoter region, preventing STAT3-dependent activation of SLUG transcription. Our findings suggested that OSM suppresses SLUG expression and tumor metastasis of LAC through inducing the inhibitory effect of the STAT1-dependent pathway and suppressing the activating effect of STAT3-dependent signaling. These results can serve as a scientific basis for the potential therapeutic intervention of OSM in cancer cells.


Lesion load of the corticospinal tract predicts motor impairment in chronic stroke.
Previous studies have shown motor impairment after a stroke relates to lesion size and location, but unexplained variability in recovery still exists. In this study, we used lesion-mapping techniques in combination with diffusion tensor imaging to quantitatively test the hypothesis that motor recovery in patients with chronic stroke is inversely related to the proportion of the corticospinal tract (CST) affected by the lesion. We studied 50 patients with chronic stroke, all of whom presented with moderate to severe motor impairments in the acute stage, using high-resolution anatomic MRI. We evaluated the degree of motor impairment with the Upper Extremity module of the Fugl-Meyer Assessment. To analyze the relationship between CST damage and impairment scores, we calculated a CST-lesion load for each patient by overlaying the patient's lesion map with a probabilistic tract derived from diffusion tensor images of age-matched healthy subjects. CST-lesion load was a significant predictor of motor deficit. Infarct size, despite correlating with motor scores, did not significantly predict impairment. Our results show the degree of functional motor deficit after a stroke is highly dependent on the overlap of the lesion with the CST and not lesion size per se. In the future, automated calculation of CST-lesion load may allow more precise prediction of motor impairment after stroke.


Comparison of Dietary Quality and Surgical Satisfaction Between Patients With Suboptimal and Optimal Weight Loss After Sleeve Gastrectomy Using Food Tolerance Score and Bariatric Analysis and Reporting Outcome System Questionnaires.
This study aimed to assess the association of dietary quality and surgical satisfaction with the amount of total weight loss (TWL) 1 year after laparoscopic sleeve gastrectomy (LSG) using the food tolerance score (FTS) and Bariatric Analysis and Reporting Outcome System (BAROS) questionnaires. This single-center retrospective study included patients who underwent LSG due to morbid obesity. Only those who have 1-year follow-up data were included and divided into 2 groups: suboptimal TWL (STWL) ≤20% and optimal TWL (OTWL) >20%. Clinical data and questionnaires recorded 1 year after surgery were collected. FTS was used to evaluate the degree of food tolerance, and BAROS assessed surgical outcomes, including weight loss, comorbidity changes, and quality of life (QoL). The total FTS and BAROS scores of the 2 groups were compared. Of 580 patients, 159 were included. Patients in STWL (n=17) were significantly older than those in OTWL (n=142) (42.24±9.28 vs. 35.92±8.71 years old, P=0.006). The total FTS (1-30 points) for STWL and OTWL were 24.88±3.43 and 25.04±3.14, respectively (P=0.845). Although the total BAROS scores (maximum: 9 points) were significantly lower in STWL than in OTWL (5.96±1.48 vs. 7.20±1.40, P<0.001). The only variable that made this difference was weight loss. There were no significant differences in other variables, such as medical conditions, QoL, and complications. In terms of FTS and BAROS score, there is no difference in postoperative satisfaction and QoL between STWL and OTWL after LSG, except for the degree of weight loss.


Meaning of leprosy for people who have experienced treatment during the sulfonic and multidrug therapy periods.
to analyze the meanings of leprosy for people treated during the sulfonic and multidrug therapy periods. qualitative nature study based on the Vigotski's historical-cultural approach, which guided the production and analysis of data. It included eight respondents who have had leprosy and were submitted to sulfonic and multidrug therapy treatments. The participants are also members of the Movement for Reintegration of People Affected by Leprosy. the meanings were organized into three meaning cores: spots on the body: something is out of order; leprosy or hanseniasis? and leprosy from the inclusion in the Movement for Reintegration of People Affected by Leprosy. the meanings of leprosy for people submitted to both regimens point to a complex construction thereof, indicating differences and similarities in both treatments. Health professionals may contribute to the change of the meanings, since these are socially constructed and the changes are continuous.


Targeting tumour-intrinsic N7-methylguanosine tRNA modification inhibits MDSC recruitment and improves anti-PD-1 efficacy.
Intrahepatic cholangiocarcinoma (ICC) exhibits very low response rate to immune checkpoint inhibitors (ICIs) and the underlying mechanism is largely unknown. We investigate the tumour immune microenvironment (TIME) of ICCs and the underlying regulatory mechanisms with the aim of developing new target to inhibit tumour growth and improve anti-programmed cell death protein-1 (PD-1) efficacy. Tumour tissues from patients with ICC together with hydrodynamic ICC mouse models were employed to identify the key cell population in TIME of ICCs. Functional analysis and mechanism studies were performed using cell culture, conditional knockout mouse model and hydrodynamic transfection ICC model. The efficacy of single or combined therapy with anti-PD-1 antibody, gene knockout and chemical inhibitor were evaluated in vivo. Polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) are enriched in advanced ICCs and significantly correlated with N7-methylguanosine tRNA methyltransferase METTL1. Using diverse in vivo cancer models, we demonstrate the crucial immunomodulator function of METTL1 in regulation of PMN-MDSC accumulation in TIME and ICC progression. Mechanistically, CXCL8 in human and Cxcl5 in mouse are key translational targets of METTL1 that facilitate its function in promoting PMN-MDSC accumulation in TIME and ICC progression in vivo. Co-blockade of METTL1 and its downstream chemokine pathway enhances the anti-PD-1 efficacy in ICC preclinical mouse models. Our data uncover novel mechanisms underlying chemokine regulation and TIME shaping at the layer of messenger RNA translation level and provide new insights for development of efficient cancer immunotherapeutic strategies.


Sir Robert Boyle and his unique case report on depressed cranial fracture.
Sir Robert Boyle is one of the foremost English scientists in history. He received his inspiration from the scientific approaches initiated by Galileo and his disciple, Torricelli. Through rigorous experimentation, Boyle established the fundamental gas laws as we know them today. Although not a physician himself, he contributed enormously to the practice of medical sciences. His voluminous observations and writings represent a landmark in the history of human thought. This article summarizes the scientific contributions of Robert Boyle, with particular emphasis on his contributions to medicine. Boyle wrote a unique case report describing in detail a patient with depressed cranial fracture who underwent successful surgery. Although on only a single case report, it provides us with a unique and rare opportunity to look at the practice of neurosurgery in the mid-17th century. Also presented in this article is Boyle's accurate description of a horse with holoprosencephaly, which was perhaps the first in history. The oft-quoted axiom in clinical medicine "First, do no harm (primum non nocere)" attributed to Sydenham, may be partially credited to Robert Boyle as well.


Outer membrane proteins of Pseudomonas.
In this review, we describe the outer membrane proteins of Pseudomonas aeruginosa and related strains from the Pseudomonas fluorescens rRNA homology group of the Pseudomonadaceae, with emphasis on the physiological function and biochemical characteristics of these proteins. The use of opr (for outer membrane protein) is proposed as the genetic designation for the P. aeruginosa outer membrane proteins and letters are assigned, in conjunction with this designation, to known outer membrane proteins. Proteins whose primary functions involve pore formation, transport of specific substrates, cell structure determination and membrane stabilization are discussed. The conservation of selected proteins in the above Pseudomonas species is also examined.


Preclinical Efficacy and Molecular Mechanism of Targeting CDK7-Dependent Transcriptional Addiction in Ovarian Cancer.
Ovarian cancer remains a significant cause of gynecologic cancer mortality, and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential antitumor activities and molecular mechanisms of other epigenetic or transcriptional therapies have not been systematically determined. Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors. Mechanistically, CDK7 represented a previously unappreciated actionable vulnerability in ovarian cancer, and CDK7 inhibition led to a pronounced dysregulation of gene transcription, with a preferential repression of E2F-regulated genes and transcripts associated with super-enhancers. Our findings revealed the molecular underpinnings of THZ1 potency and established pharmaceutically targeting transcriptional addiction as a promising therapeutic strategy in aggressive ovarian cancer. Mol Cancer Ther; 16(9); 1739-50. ©2017 AACR.


Polarimetry diagnostic on OMEGA EP using a 10-ps, 263-nm probe beam.
A polarimetry diagnostic was built and characterized for magnetic-field measurements in laser-plasma experiments on the OMEGA EP laser. This diagnostic was built into the existing 4ω (263-nm) probe system that employs a 10-ps laser pulse collected with an f/4 imaging system. The diagnostic measures the rotation of the probe beam's polarization. The polarimeter uses a Wollaston prism to split the probe beam into orthogonal polarization components. Spatially localized intensity variations between images indicate polarization rotation. Magnetic fields can be calculated by combining the polarimetry data with the measured plasma density profile obtained from angular filter refractometry.


Quantification of sesquiterpene lactones in Parthenium hyterophorous by normal-phase HPLC.
This paper describes the development of a normal-phase liquid chromatography ultraviolet-diode array detection method for the simultaneous quantification of parthenin and coronopilin in the leaves and flowers of Parthenium hysterophorous. The compounds were analyzed on a Merck Si60 silica column (5 µm, 250 × 4 mm) using an isocratic 15:85 mixture of isopropyl alcohol and hexane. The calibration curves resulting from the reference compounds in the concentration range of 200-2,000 ng exhibited acceptable linearity (r > 0.999). The method was developed to study the levels of parthenin and coronopilin in the leaves and flowers of P. hysterophorous collected during different seasons, and the method was validated by analyzing the spiked samples.


Effect of treatment and withdrawal from chronic lithium in rats on stimulant-induced responses.
Chronic lithium (Li) administration to rats was found to inhibit the hyperactivity induced by 0.5 mg/kg d-amphetamine but not that induced by 1.0 mg/kg d-amphetamine. Contradictory results on the ability of Li to inhibit amphetamine-induced hyperactivity may be due to the different dosages of amphetamine employed. 2 days after withdrawal from 3 weeks of chronic Li administration, rats showed no rebound supersensitivity of the hyperactivity response to 0.5 mg/kg d-amphetamine. Surprisingly, Li-withdrawn rats showed a marked subsensitivity of the stereotypy response to apomorphine. Such subsensitivity to apomorphine in Li withdrawal may relate to recent reports of homovanillic acid increases in rat brain in Li withdrawal, and to clinical reports of Li withdrawal inducing psychosis.


Xenotransplantation of porcine islet cells as a potential option for the treatment of type 1 diabetes in the future.
Solid organ and cell transplantation, including pancreatic islets constitute the treatment of choice for chronic terminal diseases. However, the clinical use of allogeneic transplantation is limited by the growing shortage of human organs. This has prompted us to initiate a unique multi-center and multi-team effort to promote translational research in xenotransplantation to bring xenotransplantation to the clinical setting. Supported by the German Research Foundation, an interdisciplinary group of surgeons, internal medicine doctors, diabetologists, material sciences experts, immunologists, cell biologists, virologists, veterinarians, and geneticists have established a collaborative research center (CRC) focusing on the biology of xenogeneic cell, tissue, and organ transplantation. A major strength of this consortium is the inclusion of members of the regulatory bodies, including the Paul-Ehrlich Institute (PEI), infection specialists from the Robert Koch Institute and PEI, veterinarians from the German Primate Center, and representatives of influential ethical and religious institutions. A major goal of this consortium is to promote islet xenotransplantation, based on the extensive expertise and experience of the existing clinical islet transplantation program. Besides comprehensive approaches to understand and prevent inflammation-mediated islet xenotransplant dysfunction [immediate blood-mediated inflammatory reaction (IBMIR)], we also take advantage of the availability of and experience with islet macroencapsulation, with the goal to improve graft survival and function. This consortium harbors a unique group of scientists with complementary expertise under a cohesive program aiming at developing new therapeutic approaches for islet replacement and solid organ xenotransplantation.


Aging, nutrition, and the continuum of health care.
The interrelations of aging, nutrition, and the continuum of health care have been discussed in terms of four issues, all of which focus on how to convince modern societies that meaningful attention to the triad is not only desirable but, in the light of the alternative, practically mandatory. The action steps required consist by and large of convincing societal leadership who in turn can convince their followers that meaningful attention to the aging-nutrition-health triad can produce better lives for all. The attention must be directed at all human life from conception to death. Properly applied throughout life, the attention can dramatically decrease the misery and waste currently imposed by life-style diseases and disabilities. To highlight the tangible and appeal to the pecuniary qualities of mankind, attention has been focused particuarly on the cost-effectiveness of such attention. The fractionation of the triad's components into individual units each furthered by its own proponents is not only wasteful of scarce resources but dangerous to individuals and their societies. Professionally trained scientists concerned with nutrition are keys to the catalysis of societal comprehension of the triad's interrelations. They have the education, training, experience and contacts at all levels to lead the leaders who in turn will convince societies worldwide that integration of aging, nutrition, and the continuum of health care at all phases of the life cycle is desirable, mandatory, effective, and economically sound.


The Predictive Value of Proportional Evaluation Based on the Metabolic Activity of Cervical Lymph Nodes on PET/CT Imaging in Patients with Larynx Cancer.
We aimed to evaluate the proportional values of maximum standardized uptake value (SUVmax) for cervical lymph nodes on 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) for prediction of the presence of metastasis in patients with larynx squamous cell cancer (LSCC). This retrospective study involved 43 patients with LSCC. All patients underwent resection of the primary tumor and neck dissection within 4 weeks after undergoing 18F-FDG PET/CT examinations. Receiver operating characteristic (ROC) analysis was performed to evaluate the lymph node SUVmax/primary tumor SUVmax (SUVmaxLN/SUVmaxPT), lymph node SUVmax/aortic SUVmax (SUVmaxLN/SUVmaxA), and lymph node SUVmax/ liver SUVmax (SUVmaxLN/SUVmaxL) ratios for diagnosis of lymph node metastasis. SUVmaxLN/SUVmaxA, SUVmaxLN/SUVmaxL, and SUVmaxLN/SUVmaxPT rates were significantly higher in metastatic lymph nodes compared to non-metastatic nodes. ROC analysis for metastasis showed that the cut-off thresholds were 3.87 for SUVmaxLN; 1.78 for SUVmaxLN /SUVmaxA; 1.08 for SUVmaxLN/SUVmaxL; and 0.36 for SUVmaxLN/SUVmaxPT. The diagnostic sensitivity, specificity and AUC were 83.7%, 77%, 0.856 for SUVmaxLN; 79.7%, 84%, 1.78 for SUVmaxLN/SUVmaxA; 84.1%, 76%, 0.833 for SUVmaxLN/SUVmaxL; and 53.6%, 76%, 0.666 for SUVmaxLN/SUVmaxPT, respectively. SUVmaxLN/SUVmaxA, SUVmaxLN/SUVmaxL, and SUVmaxLN/SUVmaxPT ratios can be safely used for diagnosis of cervical lymph node metastasis in patients with LSCC.


Word recognition in noise at higher-than-normal levels: decreases in scores and increases in masking.
Under certain conditions, speech recognition in noise decreases above conversational levels when signal-to-noise ratio is held constant. The current study was undertaken to determine if nonlinear growth of masking and the subsequent reduction in "effective" signal-to-noise ratio accounts for this decline. Nine young adults with normal hearing listened to monosyllabic words at three levels in each of three levels of a masker shaped to match the speech spectrum. An additional low-level noise equated audibility by producing equivalent masked thresholds for all subjects. If word recognition was determined entirely by signal-to-noise ratio and was independent of overall speech and masker levels, scores at a given signal-to-noise ratio should remain constant with increasing level. Masked pure-tone thresholds measured in the speech-shaped maskers increased linearly with increasing masker level at lower frequencies but nonlinearly at higher frequencies, consistent with nonlinear growth of upward spread of masking that followed the peaks in the spectrum of the speech-shaped masker. Word recognition declined significantly with increasing level when signal-to-noise ratio was held constant which was attributed to nonlinear growth of masking and reduced "effective" signal-to-noise ratio at high speech-shaped masker levels, as indicated by audibility estimates based on the Articulation Index.


Differential proteomic analysis of replanted Rehmannia glutinosa roots by iTRAQ reveals molecular mechanisms for formation of replant disease.
The normal growth of Rehmannia glutinosa, a widely used medicinal plant in China, is severely disturbed by replant disease. The formation of replant disease commonly involves interactions among plants, allelochemicals and microbes; however, these relationships remain largely unclear. As a result, no effective measures are currently available to treat replant disease. In this study, an integrated R. glutinosa transcriptome was constructed, from which an R. glutinosa protein library was obtained. iTRAQ technology was then used to investigate changes in the proteins in replanted R. glutinosa roots, and the proteins that were expressed in response to replant disease were identified. An integrated R. glutinosa transcriptome from different developmental stages of replanted and normal-growth R. glutinosa produced 65,659 transcripts, which were accurately translated into 47,818 proteins. Using this resource, a set of 189 proteins was found to be significantly differentially expressed between normal-growth and replanted R. glutinosa. Of the proteins that were significantly upregulated in replanted R. glutinosa, most were related to metabolism, immune responses, ROS generation, programmed cell death, ER stress, and lignin synthesis. By integrating these key events and the results of previous studies on replant disease formation, a new picture of the damaging mechanisms that cause replant disease stress emerged. Replant disease altered the metabolic balance of R. glutinosa, activated immune defence systems, increased levels of ROS and antioxidant enzymes, and initiated the processes of cell death and senescence in replanted R. glutinosa. Additionally, lignin deposition in R. glutinosa roots that was caused by replanting significantly inhibited tuberous root formation. These key processes provide important insights into the underlying mechanisms leading to the formation of replant disease and also for the subsequent development of new control measures to improve production and quality of replanted plants.


Primary care physicians' work conditions and their confidence in managing multimorbidity: a quantitative analysis using Job Demands-Resources Model.
Multimorbidity is a global issue that presents complex challenges for physicians, patients, and health systems. However, there is a lack of research on the factors that influence physicians' confidence in managing multimorbidity within primary care settings, particularly regarding physicians' work conditions. Drawing on the Job Demands-Resources Model, this study aims to investigate the level of confidence among Chinese primary care physicians in managing multimorbidity and examine the predictors related to their confidence. Data were collected from 224 physicians working in 38 Community Healthcare Centres (CHCs) in Shanghai, Shenzhen, Tianjin, and Jinan, China. Work-family conflict (WFC) perceived organizational support (POS), self-directed learning (SDL), and burnout were measured. Physicians' confidence was assessed using a single item. Mediation effect analysis was conducted using the Baron and Kenny method. The results showed that the mean confidence score for physicians managing multimorbidity was 3.63 out of 5, only 20.10% rating their confidence level as 5. WFC negatively related physicians' confidence and POS positively related physicians' confidence in multimorbid diagnosis and treatment. Burnout fully mediated the relationship between WFC and physicians' confidence, and SDL partially mediated the relationship between POS and physicians' confidence. The confidence level of Chinese primary care physicians in managing multimorbidity needs improvement. To enhance physicians' confidence in managing multimorbid patients, CHCs in China should address WFC and burnout and promote POS and SDL.


Long-term suppression of Salmonella aortitis with an oral antibiotic.
An aneurysm of the aortic arch infected with Salmonella choleraesuis is presumed to be inevitably fatal unless the patient receives corrective surgery and antibiotic therapy. I report such a case in a patient who refused surgery and who has been maintained free of infectious symptoms for over 26 months using trimethoprim-sulfamethoxazole administered orally.


On the existence of designer magnetic superatoms.
The quantum states in small, compact metal clusters are bunched into electronic shells with electronic orbitals resembling those in atoms, enabling classification of stable clusters as superatoms. The filling of superatomic orbitals, however, does not generally follow Hund's rule, and it has been proposed that magnetic superatoms can be stabilized by doping simple metal clusters with magnetic atoms. Here, we present evidence of the existence of a magnetic superatom and the determination of its spin moment. Our approach combines first principles studies with negative ion photoelectron experiments and enables a unique identification of the ground state and spin multiplicity. The studies indicate VNa8 to be a magnetic superatom with a filled d-subshell and a magnetic moment of 5.0 μB. Its low electron affinity is consistent with filled subshell and enhanced stability. The synthesis of this species opens the pathway to investigate the spin-dependent electronics of the new magnetic motifs.


Congenital Gaucher disease with nonimmune hydrops/erythroblastosis, infantile arterial calcification, and neonatal hepatitis/fibrosis. Clinicopathologic report with enzymatic and genetic analysis.
The findings in a stillborn female fetus of 31 weeks' gestation with congenital Gaucher disease, nonimmune hydrops/erythroblastosis, infantile arterial calcification, and neonatal hepatitis/fibrosis are presented, the first report of this complete constellation. Prior reports describe two similar patients. One lacked the hepatocellular features of giant cell hepatitis although manifesting hepatic fibrosis; the second lacked hepatic pathology. The diagnosis of Gaucher disease herein was established by microscopic examination of the proband, enzymatic analysis of trophoblast, and enzymatic and genetic study of the parents. The father was heterozygous for a recombinant glucocerebrosidase gene; the mother demonstrated a unique frame shift mutation. Thus the fetus is a compound heterozygote for a null and a severe mutation. Studies of parental DNA were negative for the D409H mutation of type IIIc Gaucher disease. Genetic studies were not performed of the ENPP1 gene, mutations of which are associated with idiopathic infantile arterial calcification.


Living settings and cognitive impairment are stronger predictors of nursing home admission after hip fracture surgery than physical comorbidities A nationwide Danish cohort study.
Sustaining a hip fracture is a life changing event for many elderlies. While doctors and researchers tend to be preoccupied with mortality and complication rates, patients are more concerned by other aspects e.g. loss of independence and ability to remain in their own home. This study aimed to i) determine age-stratified one-year event rates of admission to nursing home after discharge, and ii) identify risk factors associated with nursing home admission. Community dwelling patients aged 60-100 years undergoing their first hip fracture surgery in 2005 - 2015 were identified in nationwide administrative registries. Outcome was admission to nursing home within one year of discharge. To assess risk factors, we performed age-stratified cumulative incidence curves and multivariate cause specific cox regression models adjusted for age, sex, social factors, and comorbidities. A total of 53,157 patients were included. One-year risk increased with advancing age from 3.2% of patients aged 60 to 69, up to 22.4% in the eldest group aged 90-100 years. Living alone and dementia were strong risk factors HR 9.22 [95% CI 5.60-15.18, p = <0.0001] and HR 6.73 [95% CI 4.80- 9.44, p = 0.0001] respectively for patients aged 60 to 69 years, the effect decreased with higher age down to HR 2.75 [95% CI 2.12- 3.57, p = <0.0001] and HR 2.15 [95% CI 1.88- 2.46, p = <0.0001] for patients ≥ 90 years. Other important risk factors were pre-injury home care, Parkinson's disease and depression. Surprisingly, physical comorbidities i.e. kidney disease, chronic obstructive pulmonary disease, diabetes and cancer did not increase the risk of nursing home admission. Future initiatives aimed to reduce loss of independence and nursing home admission, among patients with first time hip fracture, should devote attention to living settings and cognitive impairment rather than physical comorbidity.


Mammographic positioning: evaluation from the view box.
To evaluate the quality of breast positioning for mediolateral oblique (MLO) and craniocaudal (CC) views, a prospective study of 1,000 consecutive bilateral screening mammographic examinations was performed. Six criteria were tested, including depth of tissue seen, inferior extent of the pectoral muscle relative to the posterior nipple line, presence of fibroglandular tissue at the posterior edge of the film, and whether the nipple was in profile. Pectoral muscle was depicted to within 1 cm of the nipple line or below it on 1,612 of the 2,000 MLO mammograms (81%); all fibroglandular tissue was depicted on 1,532 MLO mammograms (77%). The depth of tissue depicted on the CC mammogram was within 1 cm greater or less than the depth on the MLO mammogram on 1,586 CC mammograms (79%); the pectoral muscle was seen on 646 CC mammograms (32%). The nipple was in profile in 1,769 MLO mammograms (88%) and 1,783 CC mammograms (89%) but not in profile in either view in 83 cases (4%). Overall improvement was seen in 400 of 587 examinations (68%) when new mammograms were compared with previous mammograms. These criteria can be used to evaluate positioning performance and for quality control.


Molecular subtyping methods for detection of Salmonella enterica serovar Oranienburg outbreaks.
This study involved 82 Salmonella enterica serovar Oranienburg isolates from patients with gastroenteritis and/or focal infections, healthy carriers, and cuttlefish chips which were epidemiologically linked to a major outbreak that had affected 1,505 people in Japan between 1998 and 1999. We concurrently investigated four different molecular subtyping methods using human salmonellosis-associated Salmonella serovars and their applicability in detection of serovar Oranienburg in an outbreak. Pulsed-field gel electrophoresis (PFGE), enterobacterial repetitive intergenic sequence PCR (ERIC2-PCR), or 16S/23S rRNA ribotyping provided a high degree of interserovar discrimination for most of the serovars, with PFGE being the most discriminatory. For intraserovar typing of serovar Oranienburg, ERIC2-PCR was found to be the most sensitive. Native plasmid profiling, however, revealed nine different subgroups among epidemiologically and genetically related outbreak strains. Using these methods, a link was confirmed between food (cuttlefish chips) and patients in the serovar Oranienburg outbreak. This study underscores the limitations of chromosome-based and plasmid-based typing methods.


Secondary prevention of non-fatal deliberate self-harm. The green card study.
In an attempt to address the low compliance with offers of treatment shown by patients after episodes of non-fatal deliberate self-harm (DSH), patients who had harmed themselves for the first time were offered rapid, easy access to on-call trainee psychiatrists in the event of further difficulties, and they were encouraged to seek help at an early stage should such problems arise. The follow-up data obtained after one year showed a significant reduction of actual or seriously threatened DSH in the experimental group, who also made considerably less demands on medical and psychiatric services, when compared with controls.


Thirteen years of migration of Kirschner wires: A mediastinal foreign body.
Kirschner wires used for orthopedic fixation can rarely migrate over time. A 26-year-old male patient in whom two Kirschner wires were inserted 13 years ago for the stabilization of the right sternoclavicular joint dislocation and migrated into the anterior mediastinum and left hilum was admitted to our clinic. Incidentally detected Kirschner wires on chest radiography were removed by superior mini-sternotomy. In conclusion, since migration of Kirschner wires may cause serious complications, these patients should be followed closely and the wires should be removed once migration is detected.


delta-opioid receptor mobilization of intracellular calcium in SH-SY5Y cells: lack of evidence for delta-receptor subtypes.
delta-opioid receptor agonists mobilize intracellular Ca2+([Ca2+]i) in SH-SY5Y cells when applied in the presence of muscarinic agonists. The putative delta 1 receptor agonist [D-Pen2,D-Pen5]-enkephalin (DPDPE) elevated [Ca2+]i with an EC50 of 11 nM and the putative delta 2 agonist deltorphin II elevated [Ca2+]i, with an EC50 of 14 nM. The maximal elevations of [Ca2+]i caused by both agonists were not different, nor were maximally effective concentrations of DPDPE (1 microM) and deltorphin II (1 microM) applied together more effective than either agonist applied alone. The elevations of [Ca2+]i caused by DPDPE (1 microM) and deltorphin II (1 microM), in the presence of carbachol, desensitized rapidly with continued opioid exposure and the cross-desensitization between PDPDE and deltorphin II was complete. The putative delta 1 selective antagonist 7-benzylidenenaltrexone (BNTX) and the putative delta 2 selective antagonist naltriben both reduced the elevations of [Ca2+]i caused by DPDPE (30 nM) and deltorphin II (10 nM), by greater than 50% at concentrations of less than 10 nM. In SH-SY5Y cells delta-receptor mediated elevation of [Ca2+]i is mediated by a population of receptors, which does not discriminate between agonists and antagonists purportedly selective for delta 1 or delta 2 receptors.


CUEDC2 suppresses glioma tumorigenicity by inhibiting the activation of STAT3 and NF-κB signaling pathway.
CUEDC2, a CUE domain containing 2 protein, plays critical roles in many biological processes, such as cell cycle, inflammation and tumorigenesis. However, whether CUEDC2 was involved in tumorigenesis of glioma and the possible mechanism remains to be elucidated. In the present study, our results implied that the expression of CUEDC2 was lower in the glioma tissue and glioma cell lines than that of normal tissue and asctrocyte cells. Downregulation of endogenous CUEDC2 in glioma U251 cell lines by RNAi promoted the tumor cells proliferation, migration, invasion and glioma neurosphere formation, while, overexpression of CUEDC2 showed the opposite effect. Further studies showed that overexpression of CUEDC2 suppressed the activation and nuclear translocation of phosphorylated-STAT3 (p-STAT3) but the level of p-STAT3 increased after interfering with the expression of CUEDC2. Moreover, CUEDC2 expression has an inhibitory effect on the activation of NF-κB. Thus, our studies suggested that the decreased expression of CUEDC2 in glioma led to the activation of transcription factor STAT3 and NF-κB signaling pathway which may be related to the tumorigenicity in glioma.


Comparison of dietary energy intakes and sources by race, sex, and age for adults in Mississippi.
Energy intake and sources and alcohol and caffeine consumption of 384 Mississippians older than 34 were studied by 24-hour recall. The data were compared by race, sex, and age. Whites consumed more energy and had more adequate energy intake than blacks. Energy intake was more adequate in women than in men. The mean protein intake for all groups, except black men, was in excess of the Recommended Dietary Allowance (RDA). Protein represented 12% of the calories consumed daily by whites and 14% by blacks. Both figures are slightly more than the RDA for this age group. Whites consumed 66 gm fat and blacks 56 gm, representing 33% of total energy for whites and 38% for blacks. The mean cholesterol consumption was 339 mg for blacks and 310 mg for whites. Men consumed slightly more cholesterol than women. Whites consumed 334 gm total carbohydrates and blacks 202 gm. Starch and sugar provided 59% of total energy for whites and 52% for blacks. Whites drank 4 times more alcohol than blacks, with alcohol representing 3% of energy for whites and 1% for blacks. Whites consumed 2.5 times more caffeine than blacks. Young individuals consumed more caffeine than older ones. This study clearly shows a significant racial difference in energy content and sources in the diet of adults in Mississippi.


Initial clinical experience with the Toronto Stentless Porcine Valve.
We report our initial experience from April 1992 to November 1993 with a stentless porcine valve (Toronto SPV Valve, St. Jude Medical) for aortic valve replacement (AVR) in 21 consecutive patients and compare this group to a matched cohort that underwent AVR with a Hancock II (Medtronic) bioprosthesis. There were no hospital deaths in either group. Postoperative hospitalization was 5.5 +/- 0.8 versus 7.0 +/- 2.3 days (p = 0.004). Aortic cross-clamp time was 114.5 +/- 15.7 min in the SPV group and 96.0 +/- 25.0 min in the Hancock II group (p = 0.003). Complications in the SPV group were: one patient suffered perioperative infarction, one patient required late reoperation for left main stenosis, and one patient died suddenly following femoral thrombectomy at another center. Complications in the Hancock II group included: one patient with postoperative low output syndrome, and two late deaths (one from an aortic dissection and the other from chronic liver disease secondary to alcohol abuse). Comparison data indicate that the average size valve implanted in the SPV group was higher than in the Hancock II group (26.3 +/- 1.9 vs 24.0 +/- 1.9, p = 0.001). In the SPV group, 16 patients had 0 or trivial regurgitation and 1+ regurgitation was seen in 5 patients; regurgitation did not change over a 12-month follow-up. We observed a decrease in gradients over time (p < 0.01). Our results are compatible with a hypothesis that the ventricle undergoes remodeling over time, once the obstruction is relieved. We think the stentless design is an important feature that allows this to occur.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing the impact of VOC-contaminated groundwater on surface water at the city scale.
This study is believed to be one of the first to assess the impact of urban VOC-(volatile organic compound) contaminated groundwater on river-water quality at the city scale. A network of riverbed piezometers was used to study the 7.4-km urbanised reach of the River Tame that flows across the groundwater-effluent unconfined Triassic sandstone aquifer underlying the city of Birmingham (UK). Aquifer groundwater contained significant chlorinated VOC contamination due to the city's industrial heritage. Chlorinated VOC-contaminated baseflow was widespread along the reach with trichloroethene (TCE) dominant. VOC concentrations in riverbed piezometers were in the range 0.1-100 microg/l with typical regulatory limits occasionally exceeded by an order of magnitude. Although anaerobic biodegradation products such as cis-dichloroethene were widespread, they were unlikely to have formed in the generally aerobic riverbed. The lack of anaerobic conditions was ascribed to insufficient accumulation of low-permeability, organic-carbon rich riverbed sediments in this medium-high energy river. Assumptions a priori that natural attenuation of chlorinated VOCs will occur via reductive dechlorination in urban riverbeds are likely in error, particularly where deposits of medium-high permeability exist transmitting much of the baseflow. Surface-water quality impacts were nevertheless still low with in-river TCE increasing by just 2 microg/l over the 7.4-km reach. Agreement of baseflow contaminant flux estimates based on five flow-concentration product methods was achieved to within an order of magnitude with 22-200 kg/yr of TCE estimated to discharge to the 7.4-km reach (equivalent to 0.8-7.5 mg/d/m2 of riverbed). Such uncertainty was not regarded as unreasonable when the large measurement scale and geological and chemical heterogeneities are considered. Improved flux estimation methods and greater monitoring densities are nevertheless warranted. Considering Birmingham's long industrial history and known incidence of VOC-contaminated groundwater, the city-scale impact of VOC-contaminated groundwater upon surface-water quality was judged to be relatively modest.


Extraocular Motor System Exhibits a Higher Expression of Neurotrophins When Compared with Other Brainstem Motor Systems.
Extraocular motoneurons resist degeneration in diseases such as amyotrophic lateral sclerosis. The main objective of the present work was to characterize the presence of neurotrophins in extraocular motoneurons and muscles of the adult rat. We also compared these results with those obtained from other cranial motor systems, such as facial and hypoglossal, which indeed suffer neurodegeneration. Immunocytochemical analysis was used to describe the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 in oculomotor, trochlear, abducens, facial, and hypoglossal nuclei of adult rats, and Western blots were used to describe the presence of neurotrophins in extraocular, facial (buccinator), and tongue muscles, which are innervated by the above-mentioned motoneurons. In brainstem samples, brain-derived neurotrophic factor was present both in extraocular and facial motoneuron somata, and to a lesser degree, in hypoglossal motoneurons. Neurotrophin-3 was present in extraocular motor nuclei, while facial and hypoglossal motoneurons were almost devoid of this protein. Finally, nerve growth factor was not present in the soma of any group of motoneurons, although it was present in dendrites of motoneurons located in the neuropil. Neuropil optical density levels were higher in extraocular motoneuron nuclei when compared with facial and hypoglossal nuclei. Neurotrophins could be originated in target muscles, since Western blot analyses revealed the presence of the three molecules in all sampled muscles, to a larger extent in extraocular muscles when compared with facial and tongue muscles. We suggest that the different neurotrophin availability could be related to the particular resistance of extraocular motoneurons to neurodegeneration.


The early career progress of baccalaureate healthcare management students.
Programs in healthcare management are increasingly asked to demonstrate program outcomes by identifying graduates working in the profession of healthcare management. In particular, standards under AUPHA's certification process for undergraduate programs require that programs identify programmatic and educational outcomes. However, little is known about the career track of undergraduate healthcare management graduates. This paper describes management roles and settings for the graduates of a baccalaureate program in healthcare management, and presents salary and career progression information obtained from a recent alumni survey. Findings and implications are important to highlight the success of program graduates, and support the value of undergraduate programs in healthcare management.


Diminishing weed control exacerbates maize yield loss to adverse weather.
Both weed interference and adverse weather can cause significant maize yield losses. However, most climate change projections on maize yields ignore the fact that weeds are widespread in maize production. Herein, we examine the effects of weed control and weather variability on maize yield loss due to weeds by using machine learning techniques on an expansive database of herbicide efficacy trials spanning 205 weather environments and 27 years. Late-season control of all weed species was the most important driver of maize yield loss due to weeds according to multiple analyses. Average yield losses of 50% were observed with little to no weed control. Furthermore, when the highest levels of weed control were not achieved, drier, hotter conditions just before and during silking exacerbated maize yield losses due to weeds. Current climate predictions suggest much of the US maize-growing regions will experience warmer, drier summers. This, coupled with the growing prevalence of herbicide resistance, increases the risk of maize yield loss due to weeds in the future without transformational change in weed management systems.


New developments in social interdependence theory.
Social interdependence theory is a classic example of the interaction of theory, research, and practice. The premise of the theory is the way that goals are structured determines how individuals interact, which in turn creates outcomes. Since its formulation nearly 60 years ago, social interdependence theory has been modified, extended, and refined on the basis of the increasing knowledge about, and application of, the theory. Researchers have conducted over 750 research studies on the relative merits of cooperative, competitive, and individualistic efforts and the conditions under which each is appropriate. Social interdependence theory has been widely applied, especially in education and business. These applications have resulted in revisions of the theory and the generation of considerable new research. The authors critically analyze the new developments resulting from extensive research on, and wide-scale applications of, social interdependence theory.


Understanding advance care planning within the South Asian community.
Advance care planning (ACP) is a process of reflection on and communication of a person's future health-care preferences. Evidence suggests visible minorities engage less in ACP. The South Asian ethnic group is the largest visible minority group in Canada, and information is needed to understand how ACP is perceived and how best to approach ACP within this diverse community. To explore perspectives of South Asian community members towards ACP. Peer-to-peer inquiry. South Asian community members who graduated from the Patient and Community Engagement Research programme (PaCER) at the University of Calgary utilized the PaCER method (SET, COLLECT and REFLECT) to conduct a focus group, family interviews and a community forum. Fifty-seven community-dwelling men and women (22-86 years) who self-identified with the South Asian community in Calgary, Alberta, Canada. The concept of ACP was mostly foreign to this community and was often associated with other end-of-life issues such as organ donation and estate planning. Cultural aspects (e.g. trust in shared family decision making and taboos related to discussing death), religious beliefs (e.g. fatalism) and immigration challenges (e.g. essential priorities) emerged as barriers to participation in ACP. However, participants were eager to learn about ACP and recommended several engagement strategies (e.g. disseminate information through religious institutions and community centres, include families in ACP discussions, encourage family physicians to initiate discussions and translate materials). Use of a patient engagement research model proved highly successful in understanding South Asian community members' participation in ACP.


Bead mediated separation of microparticles in droplets.
Exchange of components such as particles and cells in droplets is important and highly desired in droplet microfluidic assays, and many current technologies use electrical or magnetic fields to accomplish this process. Bead-based microfluidic techniques offer an alternative approach that uses the bead's solid surface to immobilize targets like particles or biological material. In this paper, we demonstrate a bead-based technique for exchanging droplet content by separating fluorescent microparticles in a microfluidic device. The device uses posts to filter surface-functionalized beads from a droplet and re-capture the filtered beads in a new droplet. With post spacing of 7 μm, beads above 10 μm had 100% capture efficiency. We demonstrate the efficacy of this system using targeted particles that bind onto the functionalized beads and are, therefore, transferred from one solution to another in the device. Binding capacity tests performed in the bulk phase showed an average binding capacity of 5 particles to each bead. The microfluidic device successfully separated the targeted particles from the non-targeted particles with up to 98% purity and 100% yield.


The central nervous system in childhood leukemia. III. Mineralizing microangiopathy and dystrophic calcification.
We determined the prevalence, histopathologic features, and clinical correlations of a distinctive vascular lesion within the central nervous system (CNS) of children who died with acute lymphoblastic leukemia (ALL). Of 163 brains examined at autopsy, 28 (17%) had a noninflammatory mineralizing microangiopathy, usually accompanied by varying amounts of necrosis and calcification in adjacent neural tissue. The lesion always involved the lenticular nucleus with or without additional involvement of cerebral cortex. It was not the cause of death in any patient. An analysis of clinical features common to patients with microangiopathy indicated that cranial irradiation, in doses as low as 1500 rad, had induced the degenerative process. Survival beyond 10 months from the time of irradiation and multiple postirradiation CNS leukemic relapses, both had significant influences on the development of the lesion. Chemotherapy, particularly systemic or intrathecal methotrexate, might have contributed to the disease process, but apparently was not the instigating factor. Patients at greatest risk for developing microangiopathy are those under 10 years of age at the time of cranial irradiation, who then live more than 10 months and develop multiple CNS leukemic relapses.


A cohort study of correlation between body mass index and age at menarche in healthy Bengali girls.
There are contradictory reports of lowering of age at menarche due to increasing body mass index (BMI) in the population. It is not known if a greater BMI at menarche is associated with a lower menarcheal age in healthy Bengali girls of normal nutrition. In this study the age at menarche was determined in 273 Bengali girls of middle income families. It was assessed whether BMI standard deviation scores (SDS) at menarche, BMI SDS at one year preceding menarche and BMI increments during that year were in correlation with age at menarche. The age of the girls with adequate nutrition was 8-16 years. They were examined for BMI, pubertal breast staging and age at menarche over a 4-year follow-up period. BMI SDS were calculated from National Center for Health Statistics (NCHS) normative data. The median age at menarche of 12.0 (range 10.0 - 16.0) years did not correlate with BMI SDS at menarche or BMI SDS at one year preceding menarche in this cohort. In univariate analysis, BMI increments for a given breast stage did not significantly lower the age at menarche. The change of BMI in the year preceding menarche did not correlate with age at menarche. The age at menarche in healthy Bengali girls of middle income families was similar to that of other Indian observations. There was no influence of BMI increments or that of BMI SDS prior to or at menarche on age at menarche.


Outcome of patients with cedar asthma with continuous exposure.
After an average follow-up of 6.5 yr (range 1 to 13), 48 of 48 patients with cedar asthma, who were still working in the same industry, were re-examined. In all of them, the diagnosis of cedar asthma had been confirmed with a specific challenge inhalation test with plicatic acid. We graded the severity of asthma symptoms and the requirement for antiasthma medications at the time of diagnosis and at the time of follow-up visit. Spirometry and measurement of airway responsiveness to methacholine (PC20 methacholine) were also done on both visits. The increase or decrease in asthma symptoms, medications requirement, FEV1 and PC20 methacholine between the follow-up and the diagnostic visit were used to determine the outcome of the patients. Using these parameters, 10.4% of patients improved, 62.5% remained stable, 37.5% deteriorated, and none recovered. Among the characteristics of the patients observed at the time of diagnosis, the age of the patient, the atopic status, smoking habit, and the presence of specific IgE to plicatic acid were not useful in predicting the eventual outcome. Reduction of exposure by transfer to a less dusty job and the use of an airstream helmet did not prevent deterioration of asthma. Only the use of the twin-cartridge respirator was associated with a favorable outcome. We conclude that among cedar asthmatics who remained exposed to cedar dust for an average of 6.5 yr, over one-third showed marked deterioration of their asthma symptoms. There is also no way to predict who will deteriorate. A decrease in the amount of exposure to cedar dust does not prevent deterioration of asthma. This suggests that the ideal management of cedar asthma is removal from exposure.


Acute erythroleukemia--M6B.
Acute Erythroleukemia is a rare disorder of hematopoietic system, accounts for 1-3% of all acute leukemia and 15% of myeloid leukemia. Recently, the World Health Organisation & Society of Haematopathology proposed a change in the categorization, with M6a and M6b subgroups of the original FAB classification. Hereby we report a case of acute erythroleukemia--M6b subtype, presented with pain abdomen and vomiting. The patient died within two days. The case is being reported for its rarity and uncommon presentation.


TNFalpha blockade in human diseases: an overview of efficacy and safety.
Tumor necrosis factor-alpha (TNFalpha) antagonists including antibodies and soluble receptors have shown remarkable efficacy in various immune-mediated inflammatory diseases (IMID). As experience with these agents has matured, there is an emerging need to integrate and critically assess the utility of these agents across disease states and clinical sub-specialties. Their remarkable efficacy in reducing chronic damage in Crohn's disease and rheumatoid arthritis has led many investigators to propose a new, 'top down' paradigm for treating patients initially with aggressive regimens to quickly control disease. Intriguingly, in diseases such as rheumatoid arthritis and asthma, anti-TNFalpha agents appear to more profoundly benefit patients with more chronic stages of disease but have a relatively weaker or little effect in early disease. While the spectrum of therapeutic efficacy of TNFalpha antagonists widens to include diseases such as recalcitrant uveitis and vasculitis, these agents have failed or even exacerbated diseases such as heart failure and multiple sclerosis. Increasing use of these agents has also led to recognition of new toxicities as well as to understanding of their excellent long-term tolerability. Disconcertingly, new cases of active tuberculosis still occur in patients treated with all TNFalpha antagonists due to lack of compliance with recommendations to prevent reactivation of latent tuberculosis infection. These safety issues as well as guidelines to prevent treatment-associated complications are reviewed in detail in this article. New data on mechanisms of action and development of newer TNFalpha antagonists are discussed in a subsequent article in the Journal. It is hoped that these two review articles will stimulate a fresh assessment of the priorities for research and clinical innovation to improve and extend therapeutic use and safety of TNFalpha antagonism.


Hydrolysis of butteroil by immobilized lipase using a hollow-fiber reactor: part I. lipase adsorption studies.
Adsorption of proteins from a crude preparation containing a lipase from Aspergillus niger on microporous polypropylene hollow fibers was studied at six different temperatures. Langmuir isotherms accurately describe the overall adsorption equilibria. Lipase is selectively adsorbed relative to the other proteins in the crude preparation. Hence, immobilization also provides further purification of the lipase. The predictions of the Langmuir model for the change in the specific activity of lipase upon adsorption are consistent with experimental results. The loading capacity of the hollow fibers decreases and the adsorption constant increases as temperature is increased. This effect is more significant in the case of lipolytic activity than it is for the total amount of adsorbed protein. Small, positive enthalpy changes are associated with the adsorption of lipase on these hydrophobic membranes.


Change in neurodevelopmental outcomes for extremely premature infants over time: a systematic review and meta-analysis.
Survival rates of extremely premature infants are rising, but changes in neurodevelopmental impairment (NDI) rates are unclear. Our objective was to perform a systematic review of intrainstitutional variability of NDI over time. Systematic review and meta-analysis. Ovid MEDLINE, Embase, PubMed, Cochrane Library and Google Scholar. Study eligibility: (1) at least two discrete cohorts of infants born <27 weeks' gestation or <1000 g birth weight, (2) one cohort born after 1990 and at least one subsequent cohort of similar gestational age, (3) all cohorts cared for within the same Neonatal Intensive Care Unit(s) (NICU) and (4) neurodevelopmental outcomes at 18-36 months corrected age. Change in NDI rates. Quality, validity and bias were assessed using Grading of Recommendations, Assessment, Development, and Evaluation and Quality in Prognosis Studies guidelines. Of 203 publications, 15 were eligible, including 13 229 infants. At the first time point, average NDI rate across study groups weighted by sample size was 41.0% (95% CI 34.0% to 48.0%). The average change in NDI between time points was -3.3% (95% CI -8·8% to 2.2%). For each added week of gestation at birth, the rate of NDI declined by 9.7% (95% CI 6.2% to 13.3%). Most studies exhibited moderate-severe bias in at least one domain, especially attrition rates. When comparing discrete same-centre cohorts over time, there was no significant change in NDI rates in infants born <27 weeks' gestation or <1000 g. Higher survival rates unaccompanied by improvement in neurodevelopment highlight urgency for renewed focus on the causes of NDI and evidence-based strategies to reduce brain injury.


AN EXPERIMENTAL STUDY OF PATERNITY AND TAIL ORNAMENTATION IN THE BARN SWALLOW (HIRUNDO RUSTICA).
Previous studies of the socially monogamous barn swallow (Hirundo rustica) have shown that males that most frequently engage in extrapair copulations and whose partners are least involved in copulations with extrapair males are those with long tail ornaments. In this study, through the use of three highly polymorphic microsatellite markers, we analyze the relationships between length of tail ornaments of male barn swallows and proportion of nestlings fathered in own broods, number of offspring fathered in broods of other pairs, and total number of offspring fathered, using both a correlational and an experimental approach. Consistent with our predictions, we show that males with either naturally long or experimentally elongated tails have higher paternity (proportion of biological offspring in own broods), and they produce more biological offspring during the whole breeding season than males with naturally short or experimentally shortened tails. Males with naturally long tails also had more offspring in extrapair broods than short-tailed males, but the effect of tail manipulation on the number of offspring fathered in extrapair broods, although being in the predicted direction, was not statistically significant. Cuckolded males that did not fertilize extrapair females had smaller postmanipulation tail length than cuckolders. We conclude that there is a causal, positive relationship between male tail length and paternity. Since female barn swallows have extensive control over copulation partners and heritability of tail length is high, this study shows that female choice is a component of selection for larger male ornaments. Benefits from extrapair fertilizations to females may arise because they acquire "good" genes for sexual attractiveness or high viability for their offspring.


Role of miRNAs in development and disease: Lessons learnt from small organisms.
MicroRNAs (miRNAs) constitute a class of small (18-22 nucleotides) non-coding RNAs that regulate gene expression at the post-transcriptional level. Caenorhabditis elegans, Drosophila melanogaster, and many other small organisms have been instrumental in deciphering the biological functions of miRNAs. While some miRNAs from small organisms are highly conserved across the taxa, others are organism specific. The miRNAs are known to play a crucial role during development and in various cellular functions such as cell survival, cell proliferation, and differentiation. The miRNAs associated with fragile X syndrome, Parkinson's disease, Alzheimer's disease, diabetes, cancer, malaria, infectious diseases and several other human diseases have been identified from small organisms. These organisms have been used as platforms in deciphering the functions of miRNAs in the pathogenesis of human diseases and to study miRNA biogenesis. Small organisms have also been used in the development of miRNA-based diagnostic, prognostic and therapeutic strategies. The molecular techniques such as genome sequencing, northern blot analysis, and quantitative RT-PCR, have been used in deciphering the functions of miRNAs in small organisms. How miRNAs from small organisms especially those from Drosophila and C. elegans regulate development and disease pathogenesis is the focus of this review. The outstanding questions raised by our current understanding are discussed.


Different approaches to acute organophosphorus poison treatment.
Organophosphorus compounds (OPCs) have a wide variety of applications and are a serious threat for self-poisoning, unintentional misuse, terrorist attack, occupational hazard and warfare attack. The present standard treatment has been reported to be unsatisfactory. Many novel approaches are being used and tested for acute organophosphorus (OP) poison treatment. The bioscavenger concept captured high attention among the scientific community during the last few decades. Other approaches like alkalinisation of blood plasma/serum and use of weak inhibitors against strong inhibitors, though it showed promising results, did not get such wide attention. The introduction of a novel broad-spectrum oxime has also been in focus. In this mini-review, an update of the overview of four different approaches has been discussed. The standard therapy that is atropine+oxime+benzodiazepine along with supportive measures will continue to be the best option with only the replacement of a single oxime to improve its broad-spectrum efficacy.


Choanal atresia.
The epidemiology of choanal atresia is not always clear. it is a rare phenomenon having an incidence of between 1 in 6,000 to 1 in 8,000 live births. It exhibits a slightly female-to male preponderance, 51% to 53% versus 49% to 47%, in some studies. The unilateral form of choanal atresia is more common than bilateral, 60% to 64% versus 40% to 36%. The right nasal passage is affected more often than the left in unilateral lesions, and in 90% and more of lesions the atretic portion is bony rather than membranous.


Visualization of nutritive perfusion following tourniquet ischemia in arterial pattern skin flaps: effect of vasoactive medication.
We present an experimental model that makes it possible to investigate the effects of global ischemia and reperfusion on microvascular perfusion and viability of ill-proportioned (poorly designed) arterial pattern skin flaps in hairless mice. Skin flaps were created on the ears of hairless mice by dissecting two of three nutritional vessel bundles at the ear base. Under these nonischemic conditions, 19 percent of the total flap area went on to necrose (as a result of poor flap design). Global ischemia was induced to the flap tissue for 6 hours with a tourniquet clamp directly after flap incision. The extension of perfused tissue area and flap viability were assessed at the microcirculatory level by intravital video microscopy at 1, 3, 6, and 18 hours and 7 days after reperfusion in animals treated with either normal saline (control) or the vasoactive drug buflomedil hydrochloride (3 mg/kg of body weight per day, i.v., starting 4 hours prior to flap creation and continued at daily intervals until the end of the experiments). In untreated animals (n = 18), 1 hour after clamp release we observed reperfusion of 39.55 percent (38.5/44.9) of total flap area. Reperfusion remained unchanged within the following 5 hours. Within the next 12 hours, reperfused flap area was dramatically reduced to 21.9 percent (15.1/58.4). Seven days thereafter, only 18.8 percent (10.9/42.2) of total flap area remained viable. In contrast, we found in buflomedil-treated animals (n = 18) that 57.3 percent (53.5/62.9) of the total flap tissue was reperfused within the first hour after clamp release (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)


A three-month, multicenter, double-masked study of the safety and efficacy of travoprost 0.004%/timolol 0.5% ophthalmic solution compared to travoprost 0.004% ophthalmic solution and timolol 0.5% dosed concomitantly in subjects with open angle glaucoma or ocular hypertension.
The primary objective of this study was to compare the intraocular pressure (IOP)-lowering efficacy of travoprost 0.004%/timolol 0.5% fixed combination to the concomitant administration of travoprost 0.004% (TRAVATAN) and timolol 0.5% in subjects with open angle glaucoma or ocular hypertension. This was a randomized, multicenter, double-masked, active-controlled, parallel group study. Three hundred sixteen patients with open angle glaucoma or ocular hypertension were randomly assigned to travoprost 0.004%/timolol 0.5% ophthalmic solution fixed combination once daily in the morning or concomitant administration of timolol 0.5% once daily in the morning and travoprost 0.004% ophthalmic solution once daily in the evening. The efficacy and safety of the fixed combination were compared with concomitant therapy over three months. The primary efficacy outcome measure was mean intraocular pressure. Both travoprost 0.004%/timolol 0.5% fixed combination and the concomitant administration of travoprost 0.004% and timolol 0.5% produced statistically significant reductions from baseline in IOP, with mean IOP ranging from 15.2 to 16.5 mm Hg in the patients using travoprost 0.004%/timolol 0.5% fixed combination compared with 14.7 to 16.1 mm Hg in the concomitant group. The upper 95.1% confidence limit for the differences in mean IOP (fixed combination minus concomitant) was < or =1.5 mm Hg at 7 of 9 visits, including all three 8 AM time points, 24-hours post-dose. Mean IOP reductions from baseline ranged from 7.4 to 9.4 mm Hg in the fixed combination group compared with 8.4 to 9.4 mm Hg with concomitant therapy. Safety analysis demonstrated equivalent safety between the two treatment groups. A fixed combination of travoprost 0.004% and timolol 0.5% produced clinically relevant IOP reductions in patients with open angle glaucoma or ocular hypertension that were comparable to concomitant therapy with its components. Safety and tolerability of the fixed combination were also equivalent to concomitant therapy. Travoprost 0.004%/timolol 0.5% fixed combination offers IOP reduction equivalent to concomitant therapy, with potential benefits that include convenience (fewer bottles and drops per day), improved compliance, cost savings (based on fewer co-payments), and elimination of potential washout effects.


Microsatellite alterations in uterine leiomyomas.
Recent studies have shown that microsatellites instability (MI) has a leading role in the development of different types of cancer: a high rate of di-tri or tetranucleotide repeats have been found in familial polyposis and in sporadic colorectal, gastric, breast and endometrial carcinomas. In the present study, we selected the DNA of 23 histological samples from patients with uterine leimyomas, aged between 24 and 65 years. The negative portion was divided from the pathological portion in the same sample of each patient. Each sample was analyzed for 7 microsatellites (D25123, Mfd39, 635. 636. Mfd67, D11S905, SCZD1 and DM) through double amplification with the PCR using external and internal primer couples. Seven of 23 samples analyzed on the denaturant gel of acrylamide (30.4%) were positive for microsatellite alterations. The recurrence of these alterations, which appear in our study, suggest their involvement in benign transformation of smooth muscle cells.


[Karyometry of the tumor epitheliocytes in the dysplastic sections of serous tumors and in serous cancers of the ovaries].
With the help of Integral-2MT cytoanalyzer, the average area of nuclei and the percentage of epitheliocytes with small, medium and large nuclei at the site of dysplasia of serous cysts and serous ovarian carcinomas have been evaluated. An increase in the degree of dysplasia of tumorous epithelium is associated with an increase in the average area of nuclei and the number of cells with medium nuclei. A decrease in the degree of differentiation of serous ovarian carcinomas is accompanied by increasing percentage of cells with large nuclei. Preoperative chemotherapy does not affect this regularity.


Phase stability in the systems AeAl(2-x)Mgx (Ae = Ca, Sr, Ba): electron concentration and size controlled variations on the laves phase structural theme.
The systems AeAl(2-x)Mgx (Ae = Ca, Sr, Ba) display electron concentration induced Laves phase structural changes. However, the complete sequence MgCu2 --> MgNi2 --> MgZn2 with increasing x (decreasing electron count) is only observed for Ae = Ca. Compounds SrAl(2-x)Mgx (0 < x < or = 2) and BaAl(2-x)Mgx (x = 0.85 and 2.0) were synthesized and structurally characterized by X-ray diffraction experiments. For the Sr system the structural sequence CeCu2 --> MgNi2 --> MgZn2 occurs with increasing Mg content x. Thus, larger Sr does not allow the realization of the MgCu2 structure at low x. For Ae = Ba a binary compound BaAl2 does not exist, but more Ba-rich Ba7Al13 forms. The reinvestigation of the crystal structure of Ba7Al13 by selected area and convergent beam electron diffraction in a transmission electron microscope revealed a superstructure, which subsequently could be refined from single X-ray diffraction data. The formula unit of the superstructure is Ba21Al40 (space group P31m, Z = 1, a = 10.568(1) angstroms, c = 17.205(6) angstroms). In Ba21Al40 a size match problem between Ba and Al present in Ba7Al13 is resolved. The structure of Ba7Al13 (Ba21Al40) can be considered as a Ba excess variant of the hexagonal MgNi2 Laves phase type structure. An incommensurately modulated variant of the MgNi2 structure is obtained for phases BaAl(2-x)Mgx with x = 0.8-1. At even higher Mg concentrations a structural change to the proper MgZn2 type structure takes place.


Identification and quantification of free, conjugate and total phenolic compounds in leaves of 20 sweetpotato cultivars by HPLC-DAD and HPLC-ESI-MS/MS.
The study systematically investigated free, conjugate and total phenolics (phenolic acids and flavonoids) in leaves of 19 Chinese and one American sweetpotato cultivars grown in China. Three extraction/hydrolytic methods (direct extraction and acidic and basic hydrolysis) for sample preparation were employed to obtain different forms of phenolics. Twenty-nine phenolics were separated and identified using HPLC-DAD and HPLC-ESI-MS/MS. Three quercetin glycosides were characterised for the first time from this plant. Contents of the principal phenolics identified were determined by the HPLC-DAD procedure, which was validated in terms of linearity, precision, accuracy and limit of detection and quantification. Moreover, to the best of our knowledge, it is the first to reveal and demonstrate artifacts of esterification during acidic methanolic and ethanolic hydrolysis, and chromatographic behaviours, UV spectra and MS data of 20 hydroxycinnamic acid methyl and ethyl esters were obtained using acidic methanolic and ethanolic hydrolysis.


[Medical research in paediatrics: ethical issues].
Since 1947 (the Nuremberg Code), the ethics of experimentation on human beings is based on the principle of the informed consent of the subjects participating in the research. In this context, research in paediatrics raised particular and difficult problems. International regulations have evolved in a way that has permitted paediatric research, within strict limits. However, recent studies have shown that the level of clinical paediatric research remains weak. There are economic reasons for this. But it also reveals the persistence of an ethical conflict: some people fear that a relativisation of the principle of consent (proxy consent) will lead to weakened protection for the most vulnerable subjects, including children. The ethics of responsibility requires a balance between the protection of the child as an individual (who should never become a medical guinea-pig) and the protection of children as a group (who should never be deprived of the benefits of the medical research).


Stability of evaporating water when heated through the vapor and the liquid phases.
The stability of a water layer of uniform thickness held in a two-dimensional container of finite or semi-infinite extent is examined using linear stability theory. The liquid-vapor interface can be heated both through the liquid and through the vapor, as previously experimentally reported. The need to introduce a heat transfer coefficient is eliminated by introducing statistical rate theory (SRT) to predict the evaporation flux. There are no fitting or undefined parameters in the expression for the evaporation flux. The energy transport is parametrized in terms of the evaporation number, Eev, that for a given experimental circumstance can be predicted. The critical Marangoni number for the finite, Macf, and for the semi-infinite system, Mac(infinity), can be quantitatively predicted. Experiments in which water evaporated from a stainless-steel funnel and from a polymethyl methacrylate (PMMA) funnel into its vapor have been previously reported. Marangoni convection was observed in the experiments that used the stainless-steel funnel but not with the PMMA funnel even though the Marangoni number for the PMMA funnel was more than 27,000. The SRT-based stability theory indicates that the critical value of the Marangoni number for the experiments with the PMMA funnel was greater than the experimental value of the Marangoni number in each case; thus, no Marangoni convection was predicted to result from an instability. The observed convection with the stainless-steel funnel resulted from a temperature gradient imposed along the interface.


Morphological Changes in the Myocardium of Patients with Post-Acute Coronavirus Syndrome: A Study of Endomyocardial Biopsies.
The clinical manifestation study of post-acute sequelae of SARS-CoV-2 infection (PASC) has shown a lack of knowledge regarding its morphology and pathogenesis. The aim of this research was to investigate morphological manifestations of PASC in the myocardium. The study included 38 patients requiring endomyocardial biopsy (EMB) during the post-acute phase of coronavirus infection and a control group including patients requiring EMB prior to the SARS-CoV-2 pandemic. The patients' clinical and laboratory data were analyzed. Histological examination and immunohistochemistry (IHC) of the myocardial tissue was conducted with antibodies to CD3, CD68, HLA-DR, MHC1, C1q, VP1 enteroviruses, spike protein SARS-CoV-2, Ang1, von Willebrand factor (VWF), and VEGF. The morphometric analysis included counting the mean number of inflammatory infiltrate cells per mm2 and evaluating the expression of SARS-CoV-2 spike protein, HLA-DR, MHC1, C1q, Ang1, VWF, and VEGF using a scoring system. If the expression of SARS-CoV-2 spike protein was >3 points, an additional IHC test with antibodies to ACE2, CD16 as well as RT-PCR testing of the myocardial tissue were performed. For two patients, immunofluorescence tests of the myocardial tissue were performed using antibody cocktails to SARS-CoV-2 spike protein/CD16, SARS-CoV-2 spike protein/CD68, CD80/CD163. The statistical data analysis was carried out using the Python programming language and libraries such as NumPy, SciPy, Pandas, and Matplotlib. The study demonstrated a significant increase in the number of CD68+ macrophages in the myocardium of PASC patients compared to patients who did not have a history of COVID-19 (p = 0.014 and p = 0.007 for patients with and without myocarditis, respectively), predominantly due to M2 macrophages. An increase in the number of CD68+ macrophages was more frequently observed in patients with shorter intervals between the most recent positive SARS-CoV-2 PCR test and the time of performing the EMB (r = -0.33 and r = -0.61 for patients with and without myocarditis, respectively). The expression scores of Ang1, VEGF, VWF, and C1q in PASC patients did not significantly differ from those in EMB samples taken before 2019. The myocardium of PASC patients demonstrated a significant increase in the number of CD68+ macrophages and a decrease in the expression of markers associated with angiopathy. No evidence of coronavirus-associated myocarditis was observed in any PASC patient.


MiR-155 enhances phagocytosis of alveolar macrophages through the mTORC2/RhoA pathway.
Alveolar macrophage phagocytosis is significantly reduced in Chronic obstructive pulmonary disease, and cigarette smoke extract is one of the chief reasons for this decrease. Nevertheless, the specific underlying mechanism remains elusive. In this study, the role and possible mechanism of miR-155-5p/mTORC2/RhoA in the phagocytosis of mouse alveolar macrophages (MH-S) were explored. Our results revealed that cigarette smoke extract intervention reduced MH-S cell phagocytosis and miR-155-5p expression. Meanwhile, the dual-luciferase reporter assay validated that Rictor is a target of miR-155-5p. On the one hand, transfecting miR-155-5p mimic, mimic NC, miR-155-5p inhibitor, or inhibitor NC in MH-S cells overexpressing miR-155-5p increased the Alveolar macrophage phagocytotic rate, up-regulated the expression level of RhoA and p-RhoA, and down-regulated that of mTOR and Rictor mRNA and protein. On the other hand, inhibiting the expression of miR-155-5p lowered the phagocytotic rate, up-regulated the expression of mTOR, Rictor mRNA, and protein, and down-regulated the expression of RhoA and p-RhoA, which taken together, authenticated that miR-155-5p participates in macrophage phagocytosis via the mTORC2/RhoA pathway. Finally, confocal microscopy demonstrated that cells overexpressing miR-155-5p underwent cytoskeletal rearrangement during phagocytosis, and the phagocytic function of cells was enhanced, signaling that miR-155-5p participated in macrophage skeletal rearrangement and enhanced alveolar macrophage phagocytosis by targeting the expression of Rictor in the mTORC2/RhoA pathway.


Who goes to the bargaining table? The influence of gender and framing on the initiation of negotiation.
Unlike typical negotiation experiments, these studies investigated when men and women initiate negotiations in the absence of overt prescriptions to negotiate. Using a new experimental paradigm, the authors showed that the framing of situations is a critical driver of gender differences in initiating negotiations. Drawing on literature on language, power, and politeness, the authors argued that framing situations as opportunities for negotiation is particularly intimidating to women, as this language is inconsistent with norms for politeness among low-power individuals, such as women. By contrast, framing situations as opportunities for asking is much less intimidating to women, as this language is more polite and role-consistent. Consequently, gender differences in initiating negotiations persisted when situations were framed as opportunities for negotiation yet were eliminated when situations were framed as opportunities to ask. Moreover, primed power attenuated gender differences in aversive reactions to the negotiation frame. In all, the studies presented begin to elucidate the reasons for gender differences in initiating negotiations and further illustrate that such effects depend on the situation.


Ibuprofen ion-exchange fiber complex: improved dissolution and gastric tolerance based on ion exchange.
The purpose of the present study is to develop a novel method to improve the dissolution of water-insoluble drug ibuprofen and the gastric tolerance of this non-steroidal anti-inflammatory drug which has potentially serious gastrointestinal side effects. This method is based on ion exchange of ion-exchange fibers. Water-insoluble drug ibuprofen was dispersed in deionized water, and then the ion-exchange fibers in OH(-) type was immersed in it. Ibuprofen and the active groups of the ion-exchange fibers combined into ion pairs based on the acid-base reaction. This drug carrier did not release drugs in deionized water, but in water solution containing other ions it would release the drugs into the solution by ion exchange. Confirmed by the X-ray diffraction and the scanning electron microscopy, the ibuprofen combined onto the ion-exchange fibers was in a highly molecular level dispersed state. The improved dissolution of ibuprofen ion-exchange fiber complexes is likely to originate from this ibuprofen's highly dispersed state. Due to this, ibuprofen's highly dispersed state, ibuprofen ion-exchange fiber complexes significantly decreases the gastrointestinal side effects of ibuprofen by avoiding the solid ibuprofen's educing. The present study showed that ibuprofen ion-exchange fiber complexes have the two-fold advantages. One is to improve the dissolution of ibuprofen. The other is to decrease the ibuprofen's gastrointestinal toxicity.


Molecular Mediators of Estrogen Reduction-induced Otolith Shedding.
Previous study suggested that estradiol (E2) plays an important role in otolith shedding by regulating the expression of otoconin 90 (OC90). The purpose of this article is to provide further data on the effect and mechanism of E2 on the morphology of otolith. The rats receiving bilateral ovariectomy (OVX) were used as animal models. Co-immunoprecipitation was used to observe the relationship between estrogen receptor (ER) and estrogen-related receptor α (ERRα). The morphology of otolith was observed under the scanning electron microscopy. Western blotting and qPCR were used for quantitative analysis of the roles of ER and ERRα in regulating OC90 expression. The looser otoliths were observed in rats receiving bilateral OVX, which could be reversed by supplementation with E2. The level of ERRα was decreased in bilateral OVX rats. ER and ERRα interacted with each other on the regulation of the expression of OC90. Our results suggest ER and ERRα are both important downstream receptors involved in regulating OC90 expression in utricles of rats, and ERRα probably functions by interacting with ER. This provides evidence for the mechanism of otolith shedding. And it may be significant for future studies of targeted prevention and therapies for benign paroxysmal positional vertigo.


Metabolic effects of carbenoxolone in rat liver.
The action of carbenoxolone on hepatic energy metabolism was investigated in the perfused rat liver and isolated mitochondria. In perfused livers, carbenoxolone (200-300 microM) increased oxygen consumption, glucose production and glycolysis from endogenous glycogen. Gluconeogenesis from lactate or fructose, an energy-dependent process, was inhibited. This effect was already evident at a concentration of 25 microM. The cellular ATP levels and the adenine nucleotide content were decreased by carbenoxolone, whereas the AMP levels were increased. In isolated mitochondria, carbenoxolone stimulated state IV respiration and decreased the respiratory coefficient with the substrates beta-hydroxybutyrate and succinate. The ATPase of intact mitochondria was stimulated, the ATPase of uncoupled mitochondria was inhibited, and the ATPase of disrupted mitochondria was not altered by carbenoxolone. These results indicate that carbenoxolone acts as an uncoupler of oxidative phosphorylation and, possibly, as an inhibitor of the ATP/ADP exchange system. The inhibitory action of carbenoxolone on mitochondrial energy metabolism could be contributing to induce the mitochondrial permeability transition (MPT), a key phenomenon in apoptosis. The results of the present study can explain, partly at least, the in vivo hepatotoxic actions of carbenoxolone that were found in a previous clinical evaluation.


Effect of albumin binding on extraction of sulfobromophthalein by perfused elasmobranch liver: evidence for dissociation-limited uptake.
We investigated the role of serum albumin in the hepatic uptake of organic anions by determining the effect of added bovine albumin on sulfobromophthalein (BSP) uptake in skates, an animal which naturally lacks this protein. A single-pass perfused liver model was used to determine steady-state net uptake rates as the BSP or BSP and albumin concentrations were systematically varied. Results indicated that two different steps in the uptake process are capable of limiting the uptake rate depending on the albumin and BSP concentrations selected. At higher rates of uptake corresponding to higher BSP concentrations (up to 112 microM), saturation kinetics were observed as the BSP concentration was varied, with apparent Km and Vmax values which were independent of the albumin concentration (0.05 to 0.75%). These data suggest that under these conditions uptake is limited by a saturable step intrinsic to the liver. In contrast, for lower BSP concentrations and albumin concentrations below about 0.5%, a different kinetic pattern was seen which suggested that the rate-limiting step in uptake was transfer of BSP from albumin to the liver. The latter data were found to be consistent with a model in which the limiting step in the transfer process is spontaneous dissociation of the BSP from binding sites on albumin within the sinusoid. These results suggest that skate liver clears BSP from albumin solutions by a two-step mechanism in which dissociation from albumin is followed by a saturable process consistent with carrier-mediated transport. The albumin concentration and uptake velocity are important factors in determining which of these steps limits the uptake rate. Clearance is efficient and irreversible even though elasmobranch liver lacks high-affinity cytosolic binding proteins for BSP, and elasmobranch plasma does not normally contain albumin.


Analysis of cytosolic heteroglycans from leaves of transgenic potato (Solanum tuberosum L.) plants that under- or overexpress the Pho 2 phosphorylase isozyme.
During starch degradation, chloroplasts export neutral sugars into the cytosol where they appear to enter a complex glycan metabolism. Interactions between glycans and glucosyl transferases residing in the cytosol were studied by analyzing transgenic potato (Solanum tuberosum L.) plants that possess either decreased or elevated levels of the cytosolic (Pho 2) phosphorylase isoform. Water-soluble heteroglycans (SHGs) were isolated from these plants and were characterized. SHG contains, as major constituents, arabinose, rhamnose, galactose and glucose. Non-aqueous fractionation combined with other separation techniques revealed a distinct pool of the SHG that is located in the cytosol. Under in vitro conditions, the cytosolic heteroglycans act as glucosyl acceptor selectively for Pho 2. Acceptor sites were characterized by a specific hydrolytic degradation following the Pho 2-catalyzed glucosyl transfer. The size distribution of the cytosolic SHG increased during the dark period, indicating a distinct metabolic activity related to net starch degradation. Antisense inhibition of Pho 2 resulted in increased glucosyl and rhamnosyl contents of the glycans. Overexpression of Pho 2 decreased the content of both residues. Compared with the wild type, in both types of transgenic plants the size of the cytosolic glycans was increased.