[Applying recommendations of the Braden's scale and preventing pressure ulcers--evidences for nursing care].
The occurence risk of pressure ulcer (PU) by the patient is questioned as well as the validity of nursing care applying the Braden's scale to verify the evidences of this care in the incidence of the PU. The method of biophysiologic measures in ICU patients was used. It was found 11 patients with PU, in a 26.83% incidence. The majority (57.1%) of ulcer was in stage I. Patients with PU have lower scores than the ones without PU, showing sensitivity to predict the PU risk. It was concluded that: the evidence of nursing care was demonstrated by the density of 47.12% for the patients without PU, the incidence of PU was lower than rates of other UCUs; preventive nursing care reduces the PU.


Multicomponent Assembly of Complex Oxindoles by Enantioselective Cooperative Catalysis.
Chiral oxindoles are important chemical scaffolds found in many natural products, and their enantioselective synthesis thus attracts considerable attention. Highly diastereo- and enantioselective synthetic methods for constructing C3 quaternary oxindoles have been well-developed. However, the efficient synthesis of chiral 3-substituted tertiary oxindoles has been rarely reported due to the ease of racemization of the tertiary stereocenter via enolization. Therefore, we herein report on the multicomponent assembly (from N-aryl diazoamides, aldehydes, and enamines/indoles) of complex oxindoles by enantioselective cooperative catalysis. These reactions proceed under mild conditions and show broad substrate scope, affording the desired coupling products (>90 examples) with good to excellent stereocontrol. Additionally, this research also demonstrates the synthetic potential of this annulation by constructing the 6,6,5-tricyclic lactone core structure of Speradine A.


Heme oxygenase activity in placenta: direct dependence on oxygen availability.
Carbon monoxide (CO), which is formed endogenously from heme catalyzed by heme oxygenase (HO), is proposed to play a role in vascular control. The mRNA and protein expression of the inducible isoform of HO (HO-1) increases in response to hypoxia, and it has been assumed that HO activity also increases. This assumption requires evaluation because the catalytic activity of HO requires three molecules of O(2) for each molecule of CO formed from heme, and HO activity may be limited by O(2) availability. To test the hypothesis that low physiological O(2) concentrations limit HO activity, heme-derived CO formation by microsomal fractions of homogenates of chorionic villi of human placentas was determined after exposure to 0, 1, 5, or 21% O(2). Results revealed that HO activity was directly dependent on O(2) concentration. Thus, although hypoxia may increase HO protein and mRNA expression, there is a progressive decrease in HO activity with decreasing O(2) concentration and the dependence of HO activity on O(2) concentration is similar in chorionic villi from noninfarcted areas of preeclamptic and normotensive placenta.


Thermal activation of CaO-based sorbent and self-reactivation during CO2 capture looping cycles.
In this study, the thermal activation of different types of CaO-based sorbents was examined. Pretreatments were performed at different temperatures (800--1300 degrees C) and different durations (6--48 h) using four Canadian limestones. Sieved fractions of the limestones, powders obtained by grinding, and hydroxides produced following multiple carbonation/calcination cycles achieved in a tube furnace were examined. Pretreated samples were evaluated using two types of thermogravimetric reactors/ analyzers. The most important result was that thermal pretreatment could improve sorbent performance. In comparison to the original, pretreated sorbents showed better conversions over a longer series of CO2 cycles. Moreover, in some cases, sorbent activity actually increased with cycle number, and this effectwas especially pronounced for powdered samples preheated at 1000 degrees C. In these experiments, the increase of conversion with cycle number (designated as self-reactivation) after 30 cycles produced samples that were approximately 50% carbonated for the four sorbents examined here, and there appeared to be the potential for additional increase. These results were explained with the newly proposed pore--skeleton model. This model suggests, in addition to changes in the porous structure of the sorbent, that changes in the pore--skeleton produced during pretreatment strongly influence subsequent carbonation/ calcination cycles.


Identification of major dietary patterns in Korean adults and their association with cancer risk in the Cancer Screening Examination Cohort.
Cancer is the primary cause of disease-related death in Korea. The purposes of this study were to confirm the major dietary patterns and to evaluate whether there were associations between these identified dietary patterns and the risk of cancer based on data from the Cancer Screening Examination Cohort (CSEC) 2004-2008 of the National Cancer Center (NCC) of Korea. This study included 8 024 subjects who completed a written survey on demographics and lifestyles, as well as a 3-day dietary record. Dietary patterns were identified by factor analysis using the principal component analysis method. The associations between the identified dietary patterns and cancer risk were examined using Cox proportional hazards regression models. During a median follow-up period of 9.0 years, 425 cancer cases were newly diagnosed. We identified 4 major dietary patterns ('rice and kimchi', 'vegetables and fish', 'fruits and dairy', and 'meats and sweets'). There was a negative relation between 'rice and kimchi' pattern and the risk of non-gastrointestinal cancers only (highest vs. lowest tertile; multivariate-adjusted hazard ratio=0.60, 95% confidence interval=0.41, 0.88). The 'fruits and dairy' pattern tended to decrease the risk of cancer, and the preventive effect was noted only for gastrointestinal cancer risk. However, there was no association after adjusting for covariates. The traditional dietary pattern with high consumption of rice, kimchi, soybean paste and vegetables may decrease the cancer risk among Koreans, and strategies based on the dietary pattern may effectively reduce the cancer risk.


Removal of Cu, Zn, Pb, and Cr from Yangtze Estuary Using the Phragmites australis Artificial Floating Wetlands.
Contamination of heavy metals would threaten the water and soil resources; phytoremediation can be potentially used to remediate metal contaminated sites. We constructed the Phragmites australis artificial floating wetlands outside the Qingcaosha Reservoir in the Yangtze Estuary. Water characteristic variables were measured in situ by using YSI Professional Pro Meter. Four heavy metals (copper, zinc, lead, and chromium) in both water and plant tissues were determined. Four heavy metals in estuary water were as follows: 0.03 mg/Kg, 0.016 mg/Kg, 0.0015 mg/Kg, and 0.004 mg/Kg. These heavy metals were largely retained in the belowground tissues of P. australis. The bioaccumulation (BAF) and translation factor (TF) value of four heavy metals were affected by the salinity, temperature, and dissolved oxygen. The highest BAF of each metal calculated was as follows: Cr (0.091 in winter) > Cu (0.054 in autumn) > Pb (0.016 in summer) > Zn (0.011 in summer). Highest root-rhizome TF values were recorded for four metals: 6.450 for Cu in autumn, 2.895 for Zn in summer, 7.031 for Pb in autumn, and 2.012 for Cr in autumn. This indicates that the P. australis AFW has potential to be used to protect the water of Qingcaosha Reservoir from heavy metal contamination.


Reduced production of IL-12 and IL-12-dependent IFN-gamma release in patients with allergic asthma.
In atopic patients, allergen-specific T cells have acquired the Th2 phenotype, which is considered to be responsible for the class switch to IgE Ab formation. Because IL-12 is a key cytokine for the induction of Th1 responses, a reduced capacity to produce this cytokine could lead to aberrant Th2 development. Therefore, we examined the production of IL-12 in whole blood cultures from patients with allergic asthma (n = 15) in comparison with nonatopic control subjects (n = 15) to different stimuli. After stimulation with Staphylococcus aureus Cowan I strain (SAC) we observed a 2.6-fold reduction of IL-12 p70 production in the patient group (p < 0.005). This was not due to a general failure of monocytes from these patients to produce cytokines, because the production of IL-6 was normal. SAC also induced the production of IFN-gamma, which was blocked by neutralization of IL-12. In line with the reduced levels of IL-12 secretion, the patient group showed a 3-fold reduction of IL-12-dependent IFN-gamma production (p < 0.005). The amounts of IL-12 and IFN-gamma were positively correlated in both the patient (R = 0.51 at 0.05% SAC and R = 0.64 at 0.01% SAC) and the control groups (R = 0.64 at 0.05% SAC and R = 0.70 at 0.01% SAC). The IFN-gamma:IL-12 ratio was not different between patients and control subjects, indicating a normal response to IL-12. Diminished production of IL-12 and IFN-gamma could not be explained by an increased production of IL-10, because in SAC-stimulated cultures IL-10 was hardly induced in both groups. Furthermore, after stimulation with Escherichia coli, the production of IL-10 was similar in patients and control subjects.


Expression of heat shock proteins HSPA1A, HSPA1B and TP53 in vulval lichen planus and vulval lichen sclerosus.
Heat shock proteins (HSPs) are proteins involved in protein folding and maturation. HSP expression is induced by heat shock or other stressors including cellular damage and hypoxia. The major groups, which are classified based on their molecular weight, include HSP27, HSP40, HSP60, HSP70, HSP90, and large HSP (HSP110 and glucose-regulated protein 170). The comparison of heat shock proteins and TP53 expression is yet not well studied in both vulval lichen sclerosus and lichen planus. Our aim was to assess the HSP and TP53 gene expression in women suffering from LS or LP and compare it within these groups and also healthy controls. The inclusion criteria were willingness to donate vulval biopsies, not currently or in the prior two weeks received any local nor systemic treatment for vulval disorder, age > 18 years old. The exclusion criteria were lack of consent, current vaginal infection confirmed with microbiological studies, current local or systemic treatment for vulval disease. 45 consecutive women were recruited into the study. All appropriate vulval samples were process by genetic analysis. The mean expression (± SD) of HPSA1A for controls was 5.52 ± 3.18, for LS was 7.44 ± 2.16 and for LP was 7.89 ± 2.48. The mean expression (± SD) of HPSA1B for controls was 6.54 ± 3.41, for LS was 9.94 ± 6.88 and for LP was 9.43 ± 2.31. The mean expression (± SD) of TP53 for controls was 9.11 ± 1.14, for LS was 9.94 ± 1.27 and for LP was 10.41 ± 2.00. HSPA1A expression was 3,8 higher in women with lichen sclerosus than in control group. Heat shock protein-70 is more often expressed in LS than in healthy controls. HSP-70 not only supports tumor growth and metastasis, but on the other hand mat help to develop immune-driven treatment strategies.


Common CT Findings of Novel Coronavirus Disease 2019 (COVID-19): A Case Series.
Given the highly infectious nature of the coronavirus disease 2019 (COVID-19) virus and the lack of proven specific therapeutic drugs and licensed vaccines effective against it, early diagnosis of the disease is of paramount importance. The common chest CT imaging of confirmed COVID-19 cases is discussed here, which shows ground-glass opacity, crazy paving, and consolidation.


Primary lateral sclerosis: a distinct entity or part of the ALS spectrum?
Primary lateral sclerosis (PLS) has been traditionally viewed as a distinct upper motor neuron condition (UMN) but is increasingly regarded as a sub-phenotype within the amyotrophic lateral sclerosis (ALS) spectrum. Despite established diagnostic criteria, formal diagnosis can be challenging and the protracted diagnostic journey and uncertainty about longer-term prognosis cause considerable distress to patients and caregivers. PLS patients are invariably excluded from ALS clinical trials, while PLS pharmacological trials are lacking. There remains an unmet need for diagnostic biomarkers for upper motor neuron predominant conditions and prognostic indicators regarding prognosis, survival, and risk of conversion to ALS. Validated biomarkers will not only have implications for individualized patient care but also serve as outcome measures in pharmaceutical trials. Given the paucity of post-mortem studies in PLS, novel pathological insights are generally inferred from state-of-the-art imaging studies. Computational neuroimaging has already contributed significantly to the characterization of PLS-associated pathology in vivo and has underscored the role of neuro-inflammation, the presence of extra-motor changes, and confirmed pathological patterns similar to ALS. This systematic review assesses the current state of PLS research across clinical, neuroimaging and neuropathological domains from a combined clinical and academic perspective. We discuss patterns of pathological overlap with other ALS phenotypes, examine if the biological processes of PLS warrant therapeutic strategies distinct from ALS, and evaluate the evidence that classes PLS as a distinct clinico-pathological entity.


Amelioration of systemic fibrosis in mice by angiotensin II receptor blockade.
Systemic sclerosis (SSc) is characterized by microvascular damage, fibrosis of skin and visceral organs, and autoimmunity. Previous studies have shown that angiotensin II is involved in the synthesis of type I collagen. We investigated whether the blockade of angiotensin II receptor type I (AT1 ) by irbesartan reduces skin and lung fibrosis in 2 murine models of SSc. SSc was induced by daily intradermal injection of HOCl into the backs of BALB/c mice (HOCl-induced SSc). Mice were treated daily with irbesartan by oral gavage. Irbesartan reduced dermal thickness, collagen concentration, Smad2/3, and α-smooth muscle actin expression, as well as fibroblast proliferation and H-Ras expression in the skin of mice with HOCl-induced SSc. Mice treated with irbesartan also displayed less lung fibrosis, less inflammation, and a lower concentration of collagen in the lungs than untreated mice. Exhaled nitric oxide, inducible nitric oxide synthase, and 3-nitrotyrosine expression in the lungs were decreased following irbesartan treatment. Moreover, irbesartan reduced the number and the proliferation of splenic B and T cells and the serum levels of anti-DNA topoisomerase I autoantibodies. Irbesartan, an AT1 antagonist, prevents fibrosis and inflammation and inhibits nitric oxide production in HOCl-induced models of systemic fibrosis. Our findings extend the indication of an AT1 antagonist to SSc patients with diffuse fibrosis, especially those with lung involvement.


Degeneration secretion of amylase from the parotid gland of the rat.
In anaesthetized rats the parotid saliva secreted during degeneration of the auriculo-temporal nerve contains amylase in fairly constant concentration, the amylase output varying with the secretory rate. The amount of amylase was not reduced by adrenoceptor blocking agents; it was increased by sympathectomy carried out one week in advance. A sympathetic degeneration secretion of amylase could also be demonstrated while the post-ganglionic sympathetic nerves were degenerating; a simultaneous parasympathetic degeneration secretion provided the salivary flow needed for the transport of the amylase.


Parent proxy-report of their children's health-related quality of life: an analysis of 13,878 parents' reliability and validity across age subgroups using the PedsQL 4.0 Generic Core Scales.
Health-related quality of life (HRQOL) measurement has emerged as an important health outcome in clinical trials, clinical practice improvement strategies, and healthcare services research and evaluation. While pediatric patient self-report should be considered the standard for measuring perceived HRQOL, there are circumstances when children are too young, too cognitively impaired, too ill or fatigued to complete a HRQOL instrument, and reliable and valid parent proxy-report instruments are needed in such cases. Further, it is typically parents' perceptions of their children's HRQOL that influences healthcare utilization. Data from the PedsQL DatabaseSM were utilized to test the reliability and validity of parent proxy-report at the individual age subgroup level for ages 2-16 years as recommended by recent FDA guidelines. The sample analyzed represents parent proxy-report age data on 13,878 children ages 2 to 16 years from the PedsQL 4.0 Generic Core Scales DatabaseSM. Parents were recruited from general pediatric clinics, subspecialty clinics, and hospitals in which their children were being seen for well-child checks, mild acute illness, or chronic illness care (n = 3,718, 26.8%), and from a State Children's Health Insurance Program (SCHIP) in California (n = 10,160, 73.2%). The percentage of missing item responses for the parent proxy-report sample as a whole was 2.1%, supporting feasibility. The majority of the parent proxy-report scales across the age subgroups exceeded the minimum internal consistency reliability standard of 0.70 required for group comparisons, while the Total Scale Scores across the age subgroups approached or exceeded the reliability criterion of 0.90 recommended for analyzing individual patient scale scores. Construct validity was demonstrated utilizing the known groups approach. For each PedsQL scale and summary score, across age subgroups, healthy children demonstrated a statistically significant difference in HRQOL (better HRQOL) than children with a known chronic health condition, with most effect sizes in the medium to large effect size range. The results demonstrate the feasibility, reliability, and validity of parent proxy-report at the individual age subgroup for ages 2-16 years. These analyses are consistent with recent FDA guidelines which require instrument development and validation testing for children and adolescents within fairly narrow age groupings and which determine the lower age limit at which reliable and valid responses across age categories are achievable. Even as pediatric patient self-report is advocated, there remains a fundamental role for parent proxy-report in pediatric clinical trials and health services research.


"Central" auditory gap detection: a spatial case.
Normal listeners were tested for their temporal auditory gap detection thresholds using free-field presentation of white-noise stimuli delivered from the left (L) and right (R) poles of the interaural axis. The noise bursts serving as the leading and trailing markers for the silent period were presented in either the same (LL,RR) or different (LR,RL) auditory locations. The duration of the leading marker was a second independent variable. Gap thresholds for stimuli in which the markers had the same location were low, and usually were independent of the duration of the leading marker. Gap thresholds for the LR and RL conditions were longer. These gap thresholds were sensitive to the duration of the leading marker, and increased as the leading marker duration decreased. This finding is consistent with the hypothesis that a relative timing operation mediates gap detection when the markers activate different perceptual channels. The present data suggest that this timing process can operate on perceptual channels emerging from central nervous system processing.


CD155, an onco-immunologic molecule in human tumors.
CD155 is the fifth member in the nectin-like molecule family, and functions as the receptor of poliovirus; therefore, CD155 is also referred to as necl-5, or PVR. As an immunoglobulin-like adhesion molecule, CD155 is involved in cell motility, and natural killer and T cell-mediated immunity. CD155 is barely or weakly expressed in various normal human tissues, but frequently overexpressed in human malignant tumors. CD155 overexpression promotes tumor cell invasion and migration, and is associated with tumor progression and poor prognosis. As the ligand for both costimulatory receptor CD226 and coinhibitory receptor TIGIT and CD96 on natural killer and T cells, CD155 seems to play a dual role in oncoimmunity. However, some recent studies indicate that CD155 overexpression may induce tumor immune escape. Taken together, CD155 may be considered as a target for the treatment of tumors with CD155 overexpression.


Quantification of gammaH2AX foci in response to ionising radiation.
DNA double-strand breaks (DSBs), which are induced by either endogenous metabolic processes or by exogenous sources, are one of the most critical DNA lesions with respect to survival and preservation of genomic integrity. An early response to the induction of DSBs is phosphorylation of the H2A histone variant, H2AX, at the serine-139 residue, in the highly conserved C-terminal SQEY motif, forming gammaH2AX(1). Following induction of DSBs, H2AX is rapidly phosphorylated by the phosphatidyl-inosito 3-kinase (PIKK) family of proteins, ataxia telangiectasia mutated (ATM), DNA-protein kinase catalytic subunit and ATM and RAD3-related (ATR)(2). Typically, only a few base-pairs (bp) are implicated in a DSB, however, there is significant signal amplification, given the importance of chromatin modifications in DNA damage signalling and repair. Phosphorylation of H2AX mediated predominantly by ATM spreads to adjacent areas of chromatin, affecting approximately 0.03% of total cellular H2AX per DSB(2,3). This corresponds to phosphorylation of approximately 2000 H2AX molecules spanning approximately 2 Mbp regions of chromatin surrounding the site of the DSB and results in the formation of discrete gammaH2AX foci which can be easily visualized and quantitated by immunofluorescence microscopy(2). The loss of gammaH2AX at DSB reflects repair, however, there is some controversy as to what defines complete repair of DSBs; it has been proposed that rejoining of both strands of DNA is adequate however, it has also been suggested that re-instatement of the original chromatin state of compaction is necessary(4-8). The disappearence of gammaH2AX involves at least in part, dephosphorylation by phosphatases, phosphatase 2A and phosphatase 4C(5,6). Further, removal of gammaH2AX by redistribution involving histone exchange with H2A.Z has been implicated(7,8). Importantly, the quantitative analysis of gammaH2AX foci has led to a wide range of applications in medical and nuclear research. Here, we demonstrate the most commonly used immunofluorescence method for evaluation of initial DNA damage by detection and quantitation of gammaH2AX foci in gamma-irradiated adherent human keratinocytes(9).


Relapsing idiopathic scrotal calcinosis.
Idiopathic scrotal calcinosis is a rare and benign disease of the scrotum which is described in all age groups. It was initially first defined by Lewinski in 1883. Although many mechanisms have been proposed in the pathogenesis, underlying mechanisms are still controversial at the present time. Currently, the best therapeutic approach is the surgical removal of the scrotum without disrupting its integrity. Although it is indicated in literature that its recurrence is still controversial, we have observed relapse two times in our 41 year-old male patient following surgery at the 19th and 33rd months. We have confirmed recurrence with clinical and pathological assessments. Idiopathic scrotal calcinosis may recur both clinically and pathologically in the long-term follow up. Recurrence should be confirmed with post-surgical long-term follow up in larger series.


Morphofunctional studies on human labial salivary glands.
In this study, the first experimental investigation carried out at the ultrastructural level on mucous cells of human salivary glands, we have examined by light microscopy (LM), transmission electron microscopy (TEM), high resolution scanning electron microscopy (HRSEM), the secretory response of labial glands stimulated in vitro by the beta-adrenergic agent, D,L isoproterenol, and by the muscarinic agent carbachol. For comparison we have used identical methods to study samples of mixed portions of human submandibular glands. Morphological findings obtained here on both submandibular and labial glands mucous cells demonstrate that mucous droplets are released solely by muscarinic stimulation, and that cytological events occurring during secretory discharge are similar to those described by others, using TEM, on stimulated mucous cells of rat sublingual glands. Despite the fact that human labial glands are said to have a prominent cholinergic innervation with scanty adrenergic nerves, the response of seromucous cells in these organs to stimulation with carbachol and with isoproterenol was similar to that observed by us, (using LM, TEM and HRSEM), in serous cells of human major salivary glands.


Comparison of the left ventricular dyssynchrony between stylet-driven and lumen-less lead technique in left bundle branch area pacing using myocardial perfusion scintigraphy.
Left bundle branch area pacing (LBBAP) has emerged as a novel physiological pacing method to reduce left ventricular (LV) dyssynchrony due to ventricular pacing. Only lumen-less pacing leads (LLLs) with fixed helixes could achieve LBBAP previously, but recently, LBBAP has been performed using stylet-driven leads (SDLs). This study aimed to evaluate the LV dyssynchrony between SDLs and LLLs techniques in LBBAP. We retrospectively evaluated patients who underwent LBBAP with either SDLs or LLLs. We compared both groups' electrocardiogram (ECG) findings and LV dyssynchrony parameters derived from myocardial perfusion scintigraphy. LV dyssynchrony parameters consisted of phase analysis and regional wall motion analysis. We evaluated bandwidth, phase standard deviation (PSD), and entropy in the phase analysis. The time to the end-systolic frame (TES) was calculated in regional wall motion analysis using single-photon emission computed tomography (SPECT). We also evaluated the maximum differences between segmental TES (MDTES), the standard deviation of TES (SDTES), and the difference in the TES between the lateral wall and septum (DTES-LS). In total, 97 patients were enrolled. The success rate of LBBAP did not differ between the groups [SDLs: 47/48 patients (98%) vs. LLLs: 47/51 patients (92%), P=0.36]. The paced QRS duration and the stimulus to the peak LV activation time (stim-LVAT) also did not differ between SDL and LLL groups (122±10 vs. 119±12 ms, P=0.206; 69±12 vs. 66±13 ms, P=0.31, respectively). There were no differences in bandwidth, PSD, and entropy between SDL and LLL groups (73°±37° vs. 86°±47°, P=0.18; 19°±8.5° vs. 21°±9.7°, P=0.19; 0.57±0.08 vs. 0.59±0.08, P=0.17, respectively). The regional wall motion analysis parameters MDTES, SDTES, and DTES-LS also did not differ between SDL and LLL groups (19%±10% vs. 20%±10%, P=0.885; 5.0%±2.5% vs. 5.0%±2.5%, P=0.995; 5.0%±3.7% vs. 4.8%±4.2%, P=0.78, respectively). LBBAP using SDLs was comparable to LV electrical and mechanical synchrony with LLLs.


Sub-2 nm Single-Crystal Pt Nanoparticles via Sputtering onto a Liquid Polymer.
Matrix sputtering with the use of a low vapor pressure liquid as its matrix becomes a green technique to prepare nanoparticles dispersed in liquid. In the present study, we proposed using this method with polyethylene glycol (PEG, molecular weight = 600) as the liquid matrix to produce highly uniform Pt nanoparticles with a small size (below 2.0 nm) and a narrow size distribution. The results indicated that particle sizes were tailorable from 0.9 ± 0.3 to 1.4 ± 0.3 nm by varying the sputtering current (5-50 mA) with negligible particle aggregation that occurred in PEG during sputtering. The slight growth of the particle size observed after sputtering was attributed to the addition of free Pt atoms to the existing Pt nanoparticles. All samples formed stable dispersion in PEG for 5 month storage. This result suggested an advantage of using a liquid matrix to produce and stabilize nanoparticles.


Dubin-Johnson syndrome--a clinicopathologic study of twenty cases.
Dubin-Johnson syndrome (DJS) is a rare benign chronic disorder of bilirubin metabolism, characterized by conjugated hyperbilirubinemia, darkly pigmented liver and presence of abnormal pigment in hepatic parenchymal cells. This is a retrospective study of twenty cases of DJS highlighting their major clinical and pathological findings. Liver biopsies were available in all the cases, obtained during a fourteen-year period (January 1991 to March 2005). The patients' age ranged from 7-63 years (median 21 years). These twenty cases comprised 13 males and 7 females. Major clinical manifestations were recurrent or persistent jaundice, abdominal pain and fever. Duration of illness ranged from 9 months to 58 years (median 10 years). All of them had conjugated hyberbilirubinemia and total serum bilirubin levels ranged between 1.4-13 mg/dl (mean 4.4 mg/dl). Liver biopsies revealed presence of coarse granular brown pigment in the cytoplasm of hepatocytes more concentrated in the pericanalicular region and more prominent in centrilobular hepatocytes. Associated findings were presence of hepatitis B virus related chronic hepatitis (1), history of tubercular lymphadenitis (1), chronic cholecystitis in (2), coronary heart disease (1) and exacerbation during pregnancy (1).


Cortical reorganization in patients with facial palsy.
Possible changes in the organization of the cortex in patients with facial palsy, serving as a model of peripheral motor deefferentation, were investigated by using transcranial magnetic stimulation (TMS) and positron emission tomography (PET). With TMS, the size of the area producing muscle-evoked potentials (MEPs) of the abductor pollicis brevis muscle, the sum of MEP amplitudes within this area, and the volume over the mapping area were compared between both hemispheres in 8 patients. With PET, increases in regional cerebral blood flow, measured with the standard H2(15)O2 bolus injection technique, were compared between 6 patients and 6 healthy volunteers during sequential finger opposition. Patients moved the hand ipsilateral to the facial palsy, the control subjects the right hand. Of 9 patients in total, 5 participated in both experiments. With both methods, an enlargement of the hand field contralateral to the facial palsy was found, extending in a lateral direction, into the site of the presumed face area. The PET data showed that the enlargement of the hand field in the somatosensory cortex (SMC) is part of a widespread cortical reorganization, including the ipsilateral SMC and bilateral secondary motor and sensory areas. We report for the first time, using two different noninvasive methods, that peripheral, mere motor deefferentation is a sufficient stimulus for reorganizational changes in the healthy adult human cortex.


Current concepts in the pathogenesis and treatment of reflux esophagitis.
The etiology, pathogenesis, diagnosis, and treatment of reflux esophagitis are reviewed. Reflux esophagitis is the subjective or objective response to gastroesophageal reflux (GER), which is defined as the entrance of gastroduodenal contents into the esophagus not associated with vomiting or belching. The pathogenesis of reflux esophagitis may involve a number of mechanisms, including changes in lower esophageal sphincter pressure, gastric volume, composition of the refluxate, esophageal acid clearance, and esophageal tissue resistance. The most common symptom of reflux esophagitis is heartburn. Regurgitation of fluid into the mouth, usually after bending or during the night, is an unequivocal symptom of GER. Treatment can be divided into three phases. Phase 1 involves the avoidance of certain foods and habits, elevation of the bed head, antacid, and alginic acid-antacid therapy. Phase 2 involves drug therapy with agents not yet approved by the FDA for this indication: bethanechol chloride, cimetidine, and metoclopramide hydrochloride. Bethanechol chloride 25 mg is generally given four times daily. Cimetidine is given in doses of 300-400 mg after meals and at bedtime. Metoclopramide hydrochloride is administered in doses of 10 mg before meals and at bedtime. Phase 3 is antireflux surgery. Clinical experience has shown that phase 1 therapy is successful for about 75% of all patients. Of the 25% that do not respond to phase 1 therapy, about 90% will respond to phase 2 therapy, leaving only 5-10% of all patients with this disorder who will require phase 3 treatment. Current data favor cimetidine and bethanechol over metoclopramide. The least proof of efficacy and the most frequent adverse side effects are seen with metoclopramide. Cimetidine and bethanechol appear to have similar efficacy and relatively infrequent side effects. Evidence confirming the superiority of cimetidine over bethanechol is lacking. Further research is needed to determine the optimal pharmacologic combinations and treatment regimens.


Biosocial correlates of colorectal cancer in Greece.
One hundred consecutive patients with histologically confirmed colorectal cancer and an equal number of age- and sex-matched orthopaedic patients as hospital controls were interviewed about demographic, socioeconomic, biometric and medical variables. Cholecystectomy was significantly more frequent among cases than controls, but there was no side-predilection of the post-cholecystectomy tumours. The frequency of bowel evacuation was significantly higher among cases, particularly those with rectal cancer, an observation which appears contradictory to the 'prolonged bowel transit time--high colorectal cancer risk' hypothesis. No significant differences were found between cases and controls with respect to socioeconomic status, height and weight, smoking habits, use of laxatives and (for females) parity, age at first pregnancy, and age at menopause; however, cases appeared to be younger at menarche.


Elaboration of stable and antibody functionalized positively charged colloids by polyelectrolyte complexation between chitosan and hyaluronic acid.
In this study, we describe the elaboration of multifunctional positively charged polyelectrolyte complex (PEC) nanoparticles, designed to be stable at physiological salt concentration and pH, for effective targeted delivery. These nanoparticles were obtained by charge neutralization between chitosan (CS) as polycation and hyaluronic acid (HA) as polyanion. We showed that the course of the complexation process and the physico-chemical properties of the resulting colloids were impacted by (i) internal parameters such as the Degree of Acetylation (DA, i.e., the molar ration of acetyl glucosamine residues) and molar mass of CS, the HA molar mass and (ii) external parameters like the charge mixing ratio and the polymer concentrations. As a result, nonstoichiometric colloidal PECs were obtained in water or PBS (pH 7.4) and remained stable over one month. The polymer interactions were characterized by thermal analysis (DSC and TGA) and the morphology was studied by scanning electron microscopy. A model antibody, anti-ovalbumine (OVA) immunoglobulin A (IgA) was sorbed on the particle surface in water and PBS quantitatively in 4 h. The CS-HA/IgA nanoparticles average size was between 425-665 nm with a positive zeta potential. These results pointed out that CS-HA can be effective carriers for use in targeted drug delivery.


Applicability of the hodograph method for the problem of long-scale nonlinear dynamics of a thin vortex filament near a flat boundary.
Hamiltonian dynamics of a thin vortex filament in an ideal incompressible fluid near a flat fixed boundary is considered under the conditions that at any point of the curve, determining the shape of the filament, the angle between tangent vector and the boundary plane is small. Also the distance from a point on the curve to the plane is small in comparison with the curvature radius. The dynamics is shown to be effectively described by a nonlinear system of two (1+1)-dimensional partial differential equations. The hodograph transformation reduces this system to a single linear differential equation of the second order with separable variables. Simple solutions of the linear equation are investigated for real values of spectral parameter lambda, when the filament projection on the boundary plane has shape of a two-branch spiral or a smoothed angle, depending on the sign of lambda.


Comparative net cost impact of the utilization of panitumumab versus cetuximab for the treatment of patients with metastatic colorectal cancer in Canada.
Clinical practice guidelines support the use of the epidermal growth factor receptor (EGFR) inhibitors panitumumab and cetuximab for the treatment of metastatic colorectal cancer (mCRC) after failure of other chemotherapy regimens, based on significant clinical benefits in patients with wild-type KRAS. The purpose of the analysis was to compare provincial hospital costs when using panitumumab vs cetuximab with or without irinotecan in this patient population using a Net Impact Analysis (NIA) approach. The NIA determined the total per patient cost of the reimbursed regimens of panitumumab vs cetuximab in British Columbia, Alberta, Manitoba, Ontario, and Québec. Utilization of healthcare resources related to EGFR inhibitor infusions, follow-up monitoring, and treatment of adverse events (AEs) were also included. Healthcare resource use including drugs, medical supplies, laboratory testing, oncology infusion time, and healthcare professionals' time was obtained through expert consultation and the use was then multiplied by the province-specific cost of each resource. Numerous sensitivity analyses were conducted. Based on the dosing regimens in place in each province, the total annual per patient cost of panitumumab ranged from $22,203-$32,600, while the total annual per patient cost of cetuximab treatment varied from $30,321-$40,908. Treatment with panitumumab resulted in lower costs in all cost categories including drug acquisition, infusion preparation/administration, patient monitoring, and AE management. Per patient savings with panitumumab ranged from a low of $3815 in British Columbia to a high of $10,603 in Ontario. In sensitivity analyses, panitumumab remained cost saving in all scenarios where the savings ranged from $150-$16,006 per patient. Treating chemorefractory mCRC patients with panitumumab rather than cetuximab reduced healthcare resource costs. Provincial healthcare savings achieved with the use of panitumumab could potentially be re-allocated to other cancer treatments, although further study would be needed to validate this assumption.


Subacute proximal diabetic neuropathy.
The results of clinical, electrophysiologic, and histologic studies in three patients with a type of diabetic peripheral neuropathy, subacute proximal diabetic neuropathy (diabetic amyotrophy), are presented. On the basis of our findings, we suggest that diabetic amyotrophy is a clinical and pathologic entity separate from mononeuritis multiplex. These patients have a generalized neuropathy, and it is postulated that disordered neuron-axonal metabolism forms the basis for the pathologic and clinical changes. Histochemical changes in the muscle biopsy showed type 1 predominance. We suggest that this phenomenon represents a conversion of surviving fibers of whatever type, to a type 1 oxidative metabolism because of the change in use of these fibers.


Urticaria and angioedema. A simple approach to a complex problem.
Urticaria is a complex problem for both primary care practitioners and patients. Patients often present in considerable distress, with pruritus and uncomfortable lesions. They are frightened and frustrated about their condition and are searching for answers. Attempting to identify the cause by evaluating patient medications, contacts, and dietary history can be challenging. A multitude of laboratory tests can be performed, but they often do not provide a diagnosis. Skin allergy testing is frequently difficult at this stage. A working knowledge of the underlying pathology and causes of urticaria is essential during diagnosis. Astute evaluation can provide the clues necessary to accurately identify and treat the problem with available medications and modalities.


Impact of incomplete DNase I treatment on human macrophage proteome analysis.
The aim of our study was to analyze the proteomic pattern of human macrophages obtained over a 4 year period from blood donors. The purpose was to simulate a long-term clinical study to assess the application of 2-D DIGE technique for differential proteomic analysis of these scarce samples. Bioinformatic analysis of 2-D DIGE gels of 19 different cultures of macrophages assessed whether they did or did not contain at least specific five spots identified by MS as being or containing bovine deoxyribonuclease I (DNase I). Bovine DNase I was used during sample treatment to remove nucleic acids from protein extracts. Macrophages were classified in two groups, which appeared to be differentiated by the completeness of DNase I treatment. Further detailed analysis revealed a different proteomic pattern of macrophage protein samples according to the completeness of this treatment. The major group of proteins affected, accounting for one third of the differentially expressed proteins, included proteins involved in cell motion and actin cytoskeleton reorganization. The use of DNase I for the removal of nucleic acids from protein samples must be avoided in proteomic studies since it can generate bias in the analysis of protein expression patterns.


Macrophage solubilization and cytotoxicity of indium-containing particles as in vitro correlates to pulmonary toxicity in vivo.
Macrophage-solubilized indium-containing particles (ICPs) were previously shown in vitro to be cytotoxic. In this study, we compared macrophage solubilization and cytotoxicity of indium phosphide (InP) and indium-tin oxide (ITO) with similar particle diameters (∼ 1.5 µm) and then determined if relative differences in these in vitro parameters correlated with pulmonary toxicity in vivo. RAW 264.7 macrophages were treated with InP or ITO particles and cytotoxicity was assayed at 24 h. Ionic indium was measured in 24 h culture supernatants. Macrophage cytotoxicity and particle solubilization in vitro were much greater for InP compared with ITO. To correlate changes in vivo, B6C3F1 mice were treated with InP or ITO by oropharyngeal aspiration. On Days 14 and 28, bronchoalveolar lavage (BAL) and pleural lavage (PL) fluids were collected and assayed for total leukocytes. Cell differentials, lactate dehydrogenase activity, and protein levels were also measured in BAL. All lavage parameters were greatly increased in mice treated with InP compared with ITO. These data suggest that macrophage solubilization and cytotoxicity of some ICPs in vitro are capable of predicting pulmonary toxicity in vivo. In addition, these differences in toxicity were observed despite the two particulate compounds containing similar amounts of indium suggesting that solubilization, not total indium content, better reflects the toxic potential of some ICPs. Soluble InCl3 was shown to be more cytotoxic than InP to macrophages and lung epithelial cells in vitro further suggesting that ionic indium is the primary cytotoxic component of InP.


The impact of aviation-based teamwork training on the attitudes of health-care professionals.
Both the Institute of Medicine and the Agency for Healthcare Research and Quality suggest patient safety can be enhanced by implementing aviation Crew Resource Management (CRM) in health care. CRM emphasizes six key areas: managing fatigue, creating and managing teams, recognizing adverse situations (red flags), cross-checking and communication, decision making, and performance feedback. This study evaluates participant reactions and attitudes to CRM training. From April 22, 2003, to December 11, 2003, clinical teams from the trauma unit, emergency department, operative services, cardiac catheterization laboratory, and administration underwent an 8-hour training course. Participants completed an 11-question End-of-Course Critique (ECC), designed to assess the perceived need for training and usefulness of CRM skill sets. The Human Factors Attitude Survey contains 23 items and is administered on the same day both pre- and posttraining. It measures attitudinal shifts toward the six training modules and CRM. Of the 489 participants undergoing CRM training during the study period, 463 (95%) completed the ECC and 338 (69%) completed the Human Factors Attitude Survey. The demographics of the group included 288 (59%) nurses and technicians, 104 (21%) physicians, and 97 (20%) administrative personnel. Responses to the ECC were very positive for all questions, and 95% of respondents agreed or strongly agreed CRM training would reduce errors in their practice. Responses to the Human Factors Attitude Survey indicated that the training had a positive impact on 20 of the 23 items (p < 0.01). CRM training improves attitudes toward fatigue management, team building, communication, recognizing adverse events, team decision making, and performance feedback. Participants agreed that CRM training will reduce errors and improve patient safety.


Placement of umbilical artery catheters: high vs. low.
Placement of umbilical artery catheters was retrospectively reviewed in 181 newborns to evaluate random placement of catheter tip in the "high" position between T7 and T9 in the thoracic aorta of 127 infants and in the "low" position below L3 in the abdominal aorta of 54 infants. Group differences in gestational age, asphyxia, hypotension, respiratory disease, duration of catheterization, or infusate type were not significant. Cyanosis or blanching in the low extremities occurred in 67% of the "low" group and 21% of the "high" group (P less than .001). Hematuria occurred in 39% of the "low" group and 21% of the "high" group (P less than .05). High placement appears to have fewer complications. Prompt intervention by neonatal nurse practitioners can help reverse complications that occur during umbilical artery catheterizations.


The cumulative and sublethal effects of turbulence on erythrocytes in a stirred-tank model.
Mechanical forces generated by prosthetic heart devices (artificial valves, artificial hearts, ventricular assist devices) have been known to cause damage and destruction of erythrocytes. Turbulent flow within such devices generates shear stresses and can induce cell damage. Current models of cell damage rate utilize only the power input per unit mass as a modeling parameter. A stirred-tank reactor provides for a more extensive characterization of turbulence through eddy scale calculations. Through a simplified model, turbulence can be characterized by evaluating the Kolmogorov microscale. Our analysis of erythrocyte rupture in a stirred tank reactor suggests that parameters such as eddy wavelength and eddy velocity may better characterize and model the turbulent damage. Further, hemolysis of red blood cells by turbulent effects has been shown to have a fixed rate for constant levels of power input. Damage inflicted on the remaining, intact erythrocytes (sublethal damage) was evaluated by exposure to turbulence followed by osmotic fragility (OF) testing. Logistic models were fit to the OF data indicating a significant osmotic sensitivity in the sublethal damaged population between control and turbulence-exposed cells (chi(2) test; p < 0.001). This susceptibility indicates a significant cell population more susceptible to destruction as a result of turbulent exposure. This work has therefore helped identify optimization parameters for evaluating cell damage potential when engineering cardiovascular prosthetic devices.


Regulation of cholesterol side-chain cleavage enzyme activity by gonadotropin in rat corpus luteum.
The locus of gonadotropin-induced acute stimulation of pregnenolone production by cholesterol side-chain cleavage (CSCC) enzyme containing cytochrome P450 (cytP450scc) was examined in rat corpus luteum. Mitochondria were isolated from pseudopregnant rat ovaries after treatment with different doses of human CG (hCG) (25-200 IU) for 30 min; Electron Paramagnetic Resonance (EPR) spectra of high spin cholesterol complex of cyt P450scc (type I high spin EPR signal) and the cyt P450scc activity were determined. hCG treatment increased the formation of type I EPR spectra compared to that obtained with saline-treated controls, and pretreatment with cycloheximide (30 mg/kg BW) before hCG abolished this increase. The magnitude of type I EPR signal diminished with increasing pH over the range of 6.2-7.3. The type I EPR signal increased with doses of hCG and correlated well with the pregnenolone production. Aminoglutethimide treatment (competitive inhibitor of CSCC) before hCG injection led to an increased accumulation of cholesterol in inner mitochondrial membranes with a corresponding decrease in the outer membrane cholesterol, and cycloheximide treatment inhibited this accumulation. This suggests that the transport of cholesterol to inner mitochondrial membranes from outer membranes is regulated by hCG. In addition, gonadotropin also regulates the redistribution of cholesterol within the inner mitochondrial membranes.


Study on the Influence of Urban Built Environment Factors on the Social Behavior of ASD Children.
The use of urban space by vulnerable groups, especially ASD children with social anxiety, is an important part of building sustainable urban development. In this study, we focus on the play behavior of ASD children from the perspective of urban planning; then, we discussed how the urban built environmental factors affect the social behavior of ASD children. In this paper, 220 parents of ASD children were given questionnaires and 197 valid questionnaires were obtained after removing invalid ones. Stepwise regression was adopted to further accurately analyze the influence of each factor index in the built environment on children's social behavior. The results showed that multiple urban built environment factors had significant influence on the social behaviors (observation, participation, retreat, and concealment) of children with autism at three stages: before departure, during journey, and arrived at destination. The purpose of study is to fully consider the use of urban space by ASD children when urban researchers or urban planners construct sustainable urban forms, formulate urban design guidelines, and implement old city renewal strategies.


Composite scaffolds of mesoporous bioactive glass and polyamide for bone repair.
A bone-implanted porous scaffold of mesoporous bioglass/polyamide composite (m-BPC) was fabricated, and its biological properties were investigated. The results indicate that the m-BPC scaffold contained open and interconnected macropores ranging 400-500 μm, and exhibited a porosity of 76%. The attachment ratio of MG-63 cells on m-BPC was higher than polyamide scaffolds at 4 hours, and the cells with normal phenotype extended well when cultured with m-BPC and polyamide scaffolds. When the m-BPC scaffolds were implanted into bone defects of rabbit thighbone, histological evaluation confirmed that the m-BPC scaffolds exhibited excellent biocompatibility and osteoconductivity, and more effective osteogenesis than the polyamide scaffolds in vivo. The results indicate that the m-BPC scaffolds improved the efficiency of new bone regeneration and, thus, have clinical potential for bone repair.


Should compulsory admission to hospital be part of suicide prevention strategies?
The World Health Organization report Preventing Suicide: A Global Imperative provides governments with guidance for comprehensive suicide prevention strategies. However, it does not mention the role that compulsory admission to hospital of psychiatric patients should have in policies for suicide prevention. This was a missed opportunity for international discussion and guidance about a measure that, although widely used, is becoming increasingly controversial in light of the existing evidence and human rights norms.


Nonlinear effects on solvation dynamics in simple mixtures.
The authors applied the time dependent density functional method (TDDFM) and a linear model to solvation dynamics in simple binary solvents. Changing the solute-solvent interactions at t=0, the authors calculated the time evolution of density fields for solvent particles after the change (t>0) by the TDDFM and linear model. First, the authors changed the interaction of only one component of solvents. In this case, the TDDFM showed that the solvation time decreased monotonically with a mole fraction of the solvent strongly interacting with the solute. The monotonical decreases agreed with experimental results, while the linear model did not reproduce these results. The authors also calculated the solvation time by changing the interaction of both components. The calculation showed that the mole fraction dependence had the peak. The TDDFM presented a much higher peak than the linear model. The difference between the TDDFM and the linear model was caused by a nonlinear effect on an exchange process of solvent particles.


Whole-globe biomechanics using high-field MRI.
The eye is a complex structure composed of several interconnected tissues acting together, across the whole globe, to resist deformation due to intraocular pressure (IOP). However, most work in the ocular biomechanics field only examines the response to IOP over smaller regions of the eye. We used high-field MRI to measure IOP induced ocular displacements and deformations over the whole globe. Seven sheep eyes were obtained from a local abattoir and imaged within 48 h using MRI at multiple levels of IOP. IOP was controlled with a gravity perfusion system and a cannula inserted into the anterior chamber. T2-weighted imaging was performed to the eyes serially at 0 mmHg, 10 mmHg, 20 mmHg and 40 mmHg of IOP using a 9.4 T MRI scanner. Manual morphometry was conducted using 3D visualization software to quantify IOP-induced effects at the globe scale (e.g. axial length and equatorial diameters) or optic nerve head scale (e.g. canal diameter, peripapillary sclera bowing). Measurement sensitivity analysis was conducted to determine measurement precision. High-field MRI revealed an outward bowing of the posterior sclera and anterior bulging of the cornea due to IOP elevation. Increments in IOP from 10 to 40 mmHg caused measurable increases in axial length in 6 of 7 eyes of 7.9 ± 5.7% (mean ± SD). Changes in equatorial diameter were minimal, 0.4 ± 1.2% between 10 and 40 mmHg, and in all cases less than the measurement sensitivity. The effects were nonlinear, with larger deformations at normal IOPs (10-20 mmHg) than at elevated IOPs (20-40 mmHg). IOP also caused measurable increases in the nasal-temporal scleral canal diameter of 13.4 ± 9.7% between 0 and 20 mmHg, but not in the superior-inferior diameter. This study demonstrates that high-field MRI can be used to visualize and measure simultaneously the effects of IOP over the whole globe, including the effects on axial length and equatorial diameter, posterior sclera displacement and bowing, and even changes in scleral canal diameter. The fact that the equatorial diameter did not change with IOP, in agreement with previous studies, indicates that a fixed boundary condition is a reasonable assumption for half globe inflation tests and computational models. Our results demonstrate the potential of high-field MRI to contribute to understanding ocular biomechanics, and specifically of the effects of IOP in large animal models.


Novel missense mutation in cardiac troponin T gene found in Japanese patient with hypertrophic cardiomyopathy.
Familial hypertrophic cardiomyopathy (HCM) is a primary cardiomyopathy with an autosomal dominant pattern of inheritance. The disease bearing genes for HCM in HCM families have been identified as beta-myosin heavy chain, alpha-tropomyosin, cardiac troponin T (cTnT) and myosin binding protein-C genes. In the present study, we searched for the mutations in the cTnT gene in Japanese HCM patients. Single-strand conformation polymorphism gel analysis of polymerase chain reaction-amplified product was used to search for the mutations in the exons 8, 9 and 15 of the cTnT gene from 60 familial HCM patients. Clinical studies of the family members were performed and the incidence of sudden or disease-related deaths within the family was also examined. We have identified a novel missense mutation in exon 9 (Ala104Val) of the cTnT gene in a patient with familial HCM. Because the missense mutation was found at the residue conserved through chicken to humans and was not detected in the more than 50 normal controls, it was suggested that this missense mutation is the cause of HCM in this family. Although the affected family members presented moderate hypertrophy of the left ventricular wall, they were symptomatic and there was a high incidence of sudden death in her family members. Among Japanese patients with familial HCM, a novel missense mutation (Ala104Val) in the cTnT gene was identified. Familial HCM is genetically heterogeneous in Japanese HCM patients as observed in Caucasian kindreds. The disease in the kindred was severe and there was a high incidence of sudden or disease-related deaths in the kindred with this mutation.


Mechanism of action of migration inhibitory factor (MIF). I. Evidence for a receptor for MIF present on the peritoneal macrophage but not on the alveolar macrophage.
The initial interaction between migration inhibitory factor (MIF) and the guinea pig alveolar and peritoneal macrophage was studied. MIF-containing supernatants were generated from sensitized lymph node lymphocytes obtained from guinea pigs immunized with bovine gamma globulin in complete Freund's adjuvant. MIF-containing supernatants were markedly inhibitory for the migration of the peritoneal macrophage but had no effect on the alveolar macrophage. A linear relationship was observed between per cent inhibition of migration and serial twofold dilution of supernatant. Reexpressed in arbitrary MIF units, this relationship reflects a dose-response relationship with saturation characteristics. Pulse exposure of peritoneal macrophages to MIF resulted in adsorption of MIF onto both viable and nonviable cells with corresponding depletion of supernatant MIF. The alveolar macrophage did not adsorb MIF. Pulse adsorption of MIF onto the peritoneal macrophage is dependent on time, temperature, and cell number. Pretreatment of the cells with proteolytic enzyme prevents the adsorption of MIF while leaving migration unaffected. These observations support the existence of a specific cell surface receptor for MIF. The existence of such a receptor provides selectivity of immune modulation of macrophage populations by lymphocytes in delayed hypersensitivity reactions.


Factors influencing women's attitudes towards midwifery: Tool validation.
The purpose of this study was to validate a tool that explores the factors influencing women's opinion of and attitudes towards midwifery. A descriptive, cross-sectional design was used. The sample consisted of 526 Jordanian women. Cluster sampling was used to ensure a representative sample; then, convenience sampling was performed. The instrument asked non-identifying demographic questions and covered factors reported in literature to influence women's attitudes towards and views of the profession. The resulting instrument consisted of five factors explained by 29 items. These factors were women's general view of midwives, midwife duties, professional ethics, media influence and demotivating factors associated with working as a midwife. Although the instrument is valid and reliable, it needs further testing in other studies. Taking the factors reported on by the present study into account in public policy-making could promote better understanding of midwifery and improve its status in the community.


Reasons for attending a general emergency outpatient clinic versus a regular general practitioner - a survey among immigrant and native walk-in patients in Oslo, Norway.
To explore reasons for attending a general emergency outpatient clinic versus a regular general practitioner (RGP). Cross-sectional study using a multilingual anonymous questionnaire. Native and immigrant walk-in patients attending a general emergency outpatient clinic in Oslo (Monday-Friday, 08:00-23:00) during 2 weeks in September 2009. We included 1022 walk-in patients: 565 native Norwegians (55%) and 457 immigrants (45%). Patients' reasons for attending an emergency outpatient clinic versus their RGP. Among patients reporting an RGP affiliation, 49% tried to contact their RGP before this emergency encounter: 44% of native Norwegian and 58% of immigrant respondents. Immigrants from Africa [odds ratio (OR) = 2.55 (95% confidence interval [CI]: 1.46-4.46)] and Asia [OR = 2.32 (95% CI: 1.42-3.78)] were more likely to contact their RGP before attending the general emergency outpatient clinic compared with native Norwegians. The most frequent reason for attending the emergency clinic was difficulty making an immediate appointment with their RGP. A frequent reason for not contacting an RGP was lack of access: 21% of the native Norwegians versus 4% of the immigrants claimed their RGP was in another district/municipality, and 31% of the immigrants reported a lack of affiliation with the RGP scheme. Access to primary care provided by an RGP affects patients' use of emergency health care services. To facilitate continuity of health care, policymakers should emphasize initiatives to improve access to primary health care services. KEY POINTS Access to immediate primary health care provided by a regular general practitioner (RGP) can reduce patients' use of emergency health care services. The main reason for attending a general emergency outpatient clinic was difficulty obtaining an immediate appointment with an RGP. A frequent reason for native Norwegians attending a general emergency outpatient clinic during the daytime is having an RGP outside Oslo. Lack of affiliation with the RGP scheme is a frequent reason for attending a general emergency outpatient clinic among immigrants.


Cyclopropyl Group: An Excited-State Aromaticity Indicator?
The cyclopropyl (cPr) group, which is a well-known probe for detecting radical character at atoms to which it is connected, is tested as an indicator for aromaticity in the first ππ* triplet and singlet excited states (T1 and S1 ). Baird's rule says that the π-electron counts for aromaticity and antiaromaticity in the T1 and S1 states are opposite to Hückel's rule in the ground state (S0 ). Our hypothesis is that the cPr group, as a result of Baird's rule, will remain closed when attached to an excited-state aromatic ring, enabling it to be used as an indicator to distinguish excited-state aromatic rings from excited-state antiaromatic and nonaromatic rings. Quantum chemical calculations and photoreactivity experiments support our hypothesis; calculated aromaticity indices reveal that openings of cPr substituents on [4n]annulenes ruin the excited-state aromaticity in energetically unfavorable processes. Yet, polycyclic compounds influenced by excited-state aromaticity (e.g., biphenylene), as well as 4nπ-electron heterocycles with two or more heteroatoms represent limitations.


Discordant KCNQ1OT1 imprinting in sets of monozygotic twins discordant for Beckwith-Wiedemann syndrome.
Beckwith-Wiedemann syndrome (BWS) presents with visceromegaly, macroglossia, tumor predisposition and other congenital abnormalities, and is usually associated with abnormalities of chromosome 11p15. A number of identical twin pairs, mostly female, have been reported to be discordant for BWS. We show here that the incidence of female monozygotic twins among patients with BWS is dramatically increased over that of the general population. A cluster of imprinted genes within 11p15 is thought to be coordinately regulated via the imprinted expression of KCNQ1OT1, which encodes an untranslated RNA. In skin fibroblasts from five monozygotic twin pairs discordant for BWS, each affected twin had an imprinting defect at KCNQ1OT1 on 11p15, whereas the unaffected twin did not. Five additional monozygotic twin pairs, for whom only blood was available, also displayed an imprinting defect at KCNQ1OT1. It is possible that discordance for BWS in MZ twins is due to unequal splitting of the inner cell mass during twinning, thereby causing differential maintenance of imprinting at KCNQ1OT1. Alternatively, we propose that KCNQ1OT1 is especially vulnerable to a loss of imprinting event, caused by a lack of maintenance DNA methylation at a critical stage of preimplantation development, and that this loss of imprinting predisposes to twinning as well as to discordance for BWS. These data underscore the importance of continued surveillance of children born following assisted reproductive technologies that impact the preimplantation embryo.


Low clinical stage renal cell carcinoma: relevance of microvascular tumor invasion as a prognostic parameter.
Renal cell carcinoma is a tumor with unpredictable behavior and defining reliable prognostic factors would be extremely valuable in the clinical setting. Tumor stage, nuclear grade and tumor cell type are the main prognostic clinical parameters available. In this study we evaluated the role of microvascular involvement in the primary lesion for predicting tumor behavior in patients with low stage clinical disease. A total of 95 patients with clinically localized renal cell carcinoma (stages T1-T2 Nx M0) underwent radical nephrectomy and/or nephron sparing surgery, and were followed for a median of 45 months. The impact of microvascular tumor invasion on disease progression and its correlation with known pathological outcomes (tumor size, nuclear grade and cell type) were studied. Microvascular tumor invasion was observed in 24 patients (25%), of whom 50% had disease recurrence. Of the 71 patients without microvascular invasion only 4 (6%) showed tumor recurrence. When microvascular invasion was correlated with other histological parameters, a significant statistical association was noted with tumor diameter, perirenal fat invasion, macroscopic extension to the renal vein, nuclear grade, lymph node metastasis and sarcomatous elements in the tumor. Multivariate analysis showed that microvascular invasion and the involvement of regional lymph nodes were independent predictors of disease recurrence. Concerning cancer specific survival, microvascular invasion and perirenal fat infiltration were the only factors related to death. Microvascular invasion is an independent and relevant clinical prognostic parameter for low clinical stage renal cell carcinoma.


Measurement of respiratory morbidity in general practice in the United Kingdom during the acid transport event of January 1985.
The Weekly Returns System of the Royal College of General Practitioners was used to assess the effect on respiratory illness of the acid transport event that occurred during January 1985. The pollution event, as assessed by SO2 and smoke levels measured at pollution monitoring stations within and without the affected area showed only modest rises in SO2 levels, which were less than levels that occurred 4 years earlier. January is the peak time of year for reporting of acute respiratory episodes, and the minor increase in pollution was not reflected in any rise in respiratory morbidity, both for all ages and for different age bands. There was a rise in rates for children up to the age of 14, but this was seen each year and in both polluted and nonpolluted areas. This was probably due to children returning to school after the winter vacation and the subsequent spread of viral infections. The limitations of the two data sets in this analysis are discussed, including the relative insensitivity of weekly data in picking out a short-lived event, the distribution of the practices and pollution monitoring stations, and the effect of the extreme cold weather and the coal miners' strike on domestic coal burning during this event.


New graduate RNs in a float pool. An inner-city hospital experience.
Nurse managers and nurse educators alike have historically discouraged hiring new graduate RNs into a float pool and have preferred experienced nurses with multiple clinical skills. With a nursing shortage and changing marketplace, we need different strategies for recruitment and retention and ways to improve our clinical practice. A new graduate RN offers a nursing service an opportunity to employ a motivated, ready-to-learn, educationally prepared and intellectually stimulated nurse who happens to have limited clinical experience. The authors present a program for training new graduate RNs to practice nursing in a float pool. The training program focuses on their clinical practice needs and on transitioning them to the RN role. This program resulted in a 96% retention rate. The program offered our medical surgical units a strong clinical support float nurse, our managers a staffing solution in times of need, and the new graduate RN a broad range of clinical experiences making them more valuable members of the healthcare team. This training model is one approach to increasing recruitment and retention and can be replicated in other institutions.


Contribution of nucleophosmin overexpression to multidrug resistance in breast carcinoma.
Multidrug resistance (MDR) is a serious obstacle in breast cancer patients which limits chemotherapeutic drugs application. Our previous study confirmed that overexpression of nucleophosmin (NPM) was closely related to MDR in methotrexate-resistant breast cancer cells (MCF-7/MTX), and NPM could be a potential therapeutic target for chemoresistance. In this work, we aim to investigate NPM-mediated resistance mechanism in breast carcinoma. The NPM level was strongly positive in breast carcinoma tissues compared with adjacent normal samples, which was associated with lymph node metastasis. We found abnormal expression of NPM activated PI3K/Akt pathway and affected downstream apoptosis factors. Then, NPM level was attenuated by RNA interfering technology, the sensitivity of MCF-7/MTX cells to methotrexate was obviously increased, factor level of mitochondria apoptosis pathway was significantly augmented, and Akt phosphorylation was inhibited. Furthermore, examination of Akt and NPM level demonstrated that Akt inhibitor MK-2206 sensitised resistant cells to methotrexate and induced MCF-7/MTX cell apoptosis by PI3K/Akt pathway and mitochondria apoptosis pathway. These suggested NPM-induced resistance and anti-apoptosis were required for Akt activity. NPM has a crucial function in MDR of breast cancer through influencing Akt activity and resistant cell apoptosis, and it could be expected to become a therapeutic target for chemoresistance in breast cancer.


Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.
Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin). Mice were subjected to morphological analysis as well as gut microbiota and bile acid profiling. Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. In addition, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment. Only polymyxin B could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary bile acids as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation.


Heme oxygenase-1 protects against Alzheimer's amyloid-β(1-42)-induced toxicity via carbon monoxide production.
Heme oxygenase-1 (HO-1), an inducible enzyme up-regulated in Alzheimer's disease, catabolises heme to biliverdin, Fe2+ and carbon monoxide (CO). CO can protect neurones from oxidative stress-induced apoptosis by inhibiting Kv2.1 channels, which mediates cellular K+ efflux as an early step in the apoptotic cascade. Since apoptosis contributes to the neuronal loss associated with amyloid β peptide (Aβ) toxicity in AD, we investigated the protective effects of HO-1 and CO against Aβ(1-42) toxicity in SH-SY5Y cells, employing cells stably transfected with empty vector or expressing the cellular prion protein, PrP(c), and rat primary hippocampal neurons. Aβ(1-42) (containing protofibrils) caused a concentration-dependent decrease in cell viability, attributable at least in part to induction of apoptosis, with the PrP(c)-expressing cells showing greater susceptibility to Aβ(1-42) toxicity. Pharmacological induction or genetic over-expression of HO-1 significantly ameliorated the effects of Aβ(1-42). The CO-donor CORM-2 protected cells against Aβ(1-42) toxicity in a concentration-dependent manner. Electrophysiological studies revealed no differences in the outward current pre- and post-Aβ(1-42) treatment suggesting that K+ channel activity is unaffected in these cells. Instead, Aβ toxicity was reduced by the L-type Ca2+ channel blocker nifedipine, and by the CaMKKII inhibitor, STO-609. Aβ also activated the downstream kinase, AMP-dependent protein kinase (AMPK). CO prevented this activation of AMPK. Our findings indicate that HO-1 protects against Aβ toxicity via production of CO. Protection does not arise from inhibition of apoptosis-associated K+ efflux, but rather by inhibition of AMPK activation, which has been recently implicated in the toxic effects of Aβ. These data provide a novel, beneficial effect of CO which adds to its growing potential as a therapeutic agent.


Bleomycin-induced pulmonary fibrosis in rats: biochemical demonstration of increased rate of collagen synthesis.
The net rate of collagen synthesis in short-term lung explant cultures from rats was examined during a period of 4 wk after administration of a single intratracheal dose of bleomycin. After a delay of 3 to 4 days, the net rate of collagen synthesis was significantly increased over that in untreated control animals. This increase was sustained during approximately 10 days and subsequently returned to normal or below normal values. The increased rate of collagen synthesis could not be explained by increased free radioactive proline pools or by age differences among the animals. The period of increased rate of collagen synthesis preceded the detectable increases in lung collagen content, as we have reported previously.


Nuclear, Cytosolic, and Surface-Localized Poly(A)-Binding Proteins of Plasmodium yoelii.
Malaria is a devastating illness that causes approximately 500,000 deaths annually. The malaria-causing parasite (Plasmodium genus) uses the process of translational repression to regulate its growth, development, and transmission. As poly(A)-binding proteins (PABP) have been identified as critical components of RNA metabolism and translational repression in model eukaryotes and in Plasmodium, we have identified and investigated two PABPs in Plasmodium yoelii, PyPABP1 and PyPABP2. In contrast to most single-celled eukaryotes, Plasmodium closely resembles metazoans and encodes both a nuclear PABP and a cytosolic PABP; here, we provide multiple lines of evidence in support of this observation. The conserved domain architectures of PyPABP1 and PyPABP2 resemble those of yeast and metazoans, while multiple independent binding assays demonstrated their ability to bind very strongly and specifically to poly(A) sequences. Interestingly, we also observed that purified PyPABP1 forms homopolymeric chains despite exhaustive RNase treatment in vitro. Finally, we show by indirect immunofluorescence assays (IFAs) that PyPABP1 and PyPABP2 are cytoplasm- and nucleus-associated PABPs during the blood stages of the life cycle. Surprisingly, however, PyPABP1 was instead observed to also be localized on the surface of transmitted salivary gland sporozoites and to be deposited in trails when parasites glide on a substrate. This is the third RNA-binding protein verified to be found on the sporozoite surface, and the data may point to an unappreciated RNA-centered interface between the host and parasite. IMPORTANCE Malaria remains one of the great global health problems. The parasite that causes malaria (Plasmodium genus) relies upon exquisite control of its transmission between vertebrate hosts and mosquitoes. One crucial way that it does so is by proactively producing mRNAs needed to establish the new infection but by silencing and storing them until they are needed. One key protein in this process of translational repression in model eukaryotes is poly(A)-binding protein (PABP). Here we have shown that Plasmodium yoelii utilizes both a nuclear PABP and a cytosolic PABP, both of which bind specifically to polyadenylated RNA sequences. Moreover, we find that the cytosolic PABP forms chains in vitro, consistent with its appreciated role in coating the poly(A) tails of mRNA. Finally, we have also verified that, surprisingly, the cytosolic PABP is found on the surface of Plasmodium sporozoites. Taking the data together, we propose that Plasmodium utilizes a more metazoan-like strategy for RNA metabolism using specialized PABPs.


Our experience with chemotherapeutic agents in the treatment of breast cancer.
We are reporting about 300 female patients with progressive breast cancer and metastases. One hundred them had been treated by single agent in 5 sub-groups consisting each of 20 patients. Their medial survival was 18.5 month in complete response (CR) patient. One hundred of the patients had 5-drugs chemotherapy with median survival in complete responders of 26 months. One hundred patients had a 5-drug combination chemotherapy including adriblastina with median survival for complete responders of 34 months. In the present work it is apparent that adriblastina prolongs the life of the patients. Our findings and the data of other investigators urge us to consider future experimental pilot protocols which will allow us to individualize treatment by defining for each patient the optimal mix of modalities and agents. We emphasize the use of tumor cell markers and ER receptors.


The prevalence of posttraumatic stress disorder among American Indian Vietnam veterans: disparities and context.
This study employed data from two Congressionally mandated efforts (the American Indian Vietnam Veterans Project and the National Vietnam Veterans Readjustment Study) to examine differential prevalence of posttraumatic stress disorder (PTSD) among 5 ethnically defined samples of male Vietnam theater veterans. Lay interviews assessed individual experiences before, during, and after the war from 1,798 male Vietnam theater veterans. Clinical reinterviews using the SCID were conducted with subsamples (N = 487). The prevalence of both 1-month and lifetime PTSD was higher for the 2 American Indian samples than for Whites. Once logistic regressions controlled for differential exposure to war-zone stress, ethnicity was no longer a significant predictor of PTSD.


Simultaneous SNP selection and adjustment for population structure in high dimensional prediction models.
Complex traits are known to be influenced by a combination of environmental factors and rare and common genetic variants. However, detection of such multivariate associations can be compromised by low statistical power and confounding by population structure. Linear mixed effects models (LMM) can account for correlations due to relatedness but have not been applicable in high-dimensional (HD) settings where the number of fixed effect predictors greatly exceeds the number of samples. False positives or false negatives can result from two-stage approaches, where the residuals estimated from a null model adjusted for the subjects' relationship structure are subsequently used as the response in a standard penalized regression model. To overcome these challenges, we develop a general penalized LMM with a single random effect called ggmix for simultaneous SNP selection and adjustment for population structure in high dimensional prediction models. We develop a blockwise coordinate descent algorithm with automatic tuning parameter selection which is highly scalable, computationally efficient and has theoretical guarantees of convergence. Through simulations and three real data examples, we show that ggmix leads to more parsimonious models compared to the two-stage approach or principal component adjustment with better prediction accuracy. Our method performs well even in the presence of highly correlated markers, and when the causal SNPs are included in the kinship matrix. ggmix can be used to construct polygenic risk scores and select instrumental variables in Mendelian randomization studies. Our algorithms are available in an R package available on CRAN (https://cran.r-project.org/package=ggmix).


Human vault-associated non-coding RNAs bind to mitoxantrone, a chemotherapeutic compound.
Human vaults are the largest cytoplasmic ribonucleoprotein and are overexpressed in cancer cells. Vaults reportedly function in the extrusion of xenobiotics from the nuclei of resistant cells, but the interactions of xenobiotics with the vault-associated proteins or non-coding RNAs have never been directly observed. In the present study, we show that vault RNAs (vRNAs), specifically the hvg-1 and hvg-2 RNAs, bind to a chemotherapeutic compound, mitoxantrone. Using an in-line probing assay (spontaneous transesterification of RNA linkages), we have identified the mitoxantrone binding region within the vRNAs. In addition, we analyzed the interactions between vRNAs and mitoxantrone in the cellular milieu, using an in vitro translation inhibition assay. Taken together, our results clearly suggest that vRNAs have the ability to bind certain chemotherapeutic compounds and these interactions may play an important role in vault function, by participating in the export of toxic compounds.


Arabidopsis thaliana gamma-glutamylcysteine synthetase is structurally unrelated to mammalian, yeast, and Escherichia coli homologs.
A mutant of Escherichia coli, JTG10, deficient in gamma-glutamylcysteine synthetase (gamma-ECS; EC 126.96.36.199) is unable to synthesize glutathione (GSH) and is sensitive to 8-hydroxyquinoline. This phenotype was exploited for the isolation of Arabidopsis thaliana gamma-ECS cDNAs by expression cloning, and clones were selected through functional complementation by growth on 8-hydroxyquinoline. High levels of gamma-ECS activity were detectable in extracts derived from cultures of JTG10 expressing the Arabidopsis gamma-ECS open reading frame, although these complemented mutants accumulated GSH to only 10% of the wild-type level. The derived amino acid sequence constitutes a polypeptide of 59.9 kDa and shows only 44-48% similarity with previously published sequences of rat kidney, human liver, yeast, and E. coli gamma-ECS. When the gamma-ECS cDNA was used as a probe, Southern blot analysis of Arabidopsis genomic DNA revealed that it is present as a low copy number gene. Furthermore, the Arabidopsis gamma-ECS cDNA probe failed to hybridize to maize and tobacco genomic DNA at low stringency, suggesting that heterogeneity in gamma-ECS structure exists between plant species. The activity of recombinant Arabidopsis gamma-ECS was inhibited by buthionine sulfoximine and GSH, indicating that, while differences in the primary and secondary structure of gamma-ECS from different sources exist, the enzymes may have similar active site structures.


[Mapping mini-implant anatomic sites in the area of the maxillary first molar with the aid of the NewTom 3G® system].
The goal of our study was to construct a map of the implant sites in the region of the attached gingiva around the maxillary first molars that would be appropriate locations for placement of miniscrews to serve as orthodontic anchorage. We conducted 58 radiographic examinations with the NewTom 3G(®) cone beam technique. For each interdental space, between upper second bicuspids and first molars (5/6) and between upper first and second molars (6/7), we studied the mesio-distal width and depth of bucco-lingual bone at two different levels, L1 and L2, that corresponded to the lower and upper limits of the attached gingiva in the general population. The widths of the interdental spaces varied very little between L1 and L2 and their variances were comparable. At the level of the 5/6 space, the interdental widths displayed a Gaussian distribution, which made it possible for us to determine the confidence intervals at the two borders of attached gingiva as a function of age: IC(99%) of L1 = [2.045 ; 3.462] from 12 to 17 years or [1.594 ; 2.519] from 18 to 24 or [1.613 ; 2.5] from 25 to 48 years and IC(99%) of L2 = [2.37 ; 3.69] from 12 to 17 years or [1.5 ; 2.613] from 18 to 24 or [1.546 ; 2.619] from 25 to 48 ans. The interdental depths increased in an apical direction and their variance diminished. Even if the adequacy of the Gaussian law is less reliable in the sagittal plane, we find a greater consistency in depths in the spaces around 5/6 that allows us to establish very precise confidence levels: IC(99%) of L1 = [9.213; 10.575] and IC(99%) of L2 = [10.295; 11.593]. The mesial areas of the first molars constitute safe zones for implantation of miniscrews with a maximum of 2-2.3 mm for 12 to 17 years old or 1.5-1.6 mm for 18 to 48 year olds and of a maximum of 9-10 mm in length whether the attached gingival level is strong or feeble. The distal areas of the first molars, because of their great variability, require an individualized radiographic study before any mini/screw can be placed.


Can Gastric Cancer Patients with High Mandard Score Benefit from Neoadjuvant Chemotherapy?
A high Mandard score may indicate the tumor is insensitive to chemotherapy. We analyzed tumor regression and lymph node response under different Mandard scores to assess the impact of Mandard score on prognosis. Methods. Mandard scores and ypN stage of postoperative pathological reports were recorded. The results were reviewed by a professional pathologist. The radiologist compared the tumor regression before and after chemotherapy by computed tomography (CT). The survival of all patients was obtained by telephone follow-up. Multivariate Cox regression was used to assess the relationship between overall risk of death and Mandard score, imaging evaluation, and ypN stage. Results. In the Mandard score (4-5) group, the median survival time for PR and ypN0 patients was 68.5 and 76.7 months. While in the Mandard score (1-2) group, the median survival time for PD and ypN3a patients was 15.6 and 14.5 months. Imaging evaluation of tumor regression (PR 68.5 months, SD 27.8 months, and PD 10.2 months) and lymph node remission (ypN0 76.7 months, ypN1 61.6 months, ypN2 18.0 months, ypN3a 18.7 months, and ypN3b 18.3 months) showed improved survival. Mandard score, imaging evaluation, and ypN stage are important prognostic factors affecting prognosis. Conclusion. A high Mandard score does not mean neoadjuvant chemotherapy is ineffective in gastric cancer. Patients with imaging evaluation of tumor regression and ypN stage reduction may benefit from neoadjuvant chemotherapy.


Phenolic Metabolites Modulate Cardiomyocyte Beating in Response to Isoproterenol.
Cardiovascular disease (CVD) is a public health concern, and the third cause of death worldwide. Several epidemiological studies and experimental approaches have demonstrated that consumption of polyphenol-enriched fruits and vegetables can promote cardioprotection. Thus, diet plays a key role in CVD development and/or prevention. Physiological β-adrenergic stimulation promotes beneficial inotropic effects by increasing heart rate, contractility and relaxation speed of cardiomyocytes. Nevertheless, chronic activation of β-adrenergic receptors can cause arrhythmias, oxidative stress and cell death. Herein the cardioprotective effect of human metabolites derived from polyphenols present in berries was assessed in cardiomyocytes, in response to chronic β-adrenergic stimulation, to disclose some of the underlying molecular mechanisms. Ventricular cardiomyocytes derived from neonate rats were treated with three human bioavailable phenolic metabolites found in circulating human plasma, following berries' ingestion (catechol-O-sulphate, pyrogallol-O-sulphate, and 1-methylpyrogallol-O-sulphate). The experimental conditions mimic the physiological concentrations and circulating time of these metabolites in the human plasma (2 h). Cardiomyocytes were then challenged with the β-adrenergic agonist isoproterenol (ISO) for 24 h. The presence of phenolic metabolites limited ISO-induced mitochondrial oxidative stress. Likewise, phenolic metabolites increased cell beating rate and synchronized cardiomyocyte beating population, following prolonged β-adrenergic receptor activation. Finally, phenolic metabolites also prevented ISO-increased activation of PKA-cAMP pathway, modulating Ca2+ signalling and rescuing cells from an arrhythmogenic Ca2+ transients' phenotype. Unexpected cardioprotective properties of the recently identified human-circulating berry-derived polyphenol metabolites were identified. These metabolites modulate cardiomyocyte beating and Ca2+ transients following β-adrenergic prolonged stimulation.


Chlormadinone acetate and its effect on the hemostatic mechanism.
There is an apparent discrepancy between the effects on the hemostatic mechanism of synthetic progestins alone and synthetic progestins in combination with synthetic estrogens. Coagulation studies were carried out on 21 patients treated with chlormadinone acetate 0.5 mg. on a continuous daily basis for 12 weeks in order to determine its effects on hemostasis. Unlike the standard estrogen/progestin contraceptive agents, this synthetic progestin appears to have no effect on the coagulation system as determined by standard laboratory tests.


Electrochemical synthesis and surface characterization of poly(3,4-ethylenedioxythiophene) films grown in an ionic liquid.
We report a facile method to synthesize poly(3,4-ethylenedioxythiophene) (PEDOT) films at room temperature in a waterproof ionic liquid, 1-ethyl-3-methylimidazolium bis(perfluoroethylsulfonyl)imide (EMIPFSI), by electropolymerization. The ionic liquid leads to the formation of randomly oriented nanofibers and particles confined to submicrometer-sized domains in the film microstructure. X-ray photoelectron spectroscopy (XPS) and energy-dispersive X-ray (EDX) studies provide information about the intercalation of the cation apart from the reported anion in the polymer film, and on how the imidazolium ion controls the growth of PEDOT nanostructures.


A telepresence wheelchair using cellular network infrastructure in outdoor environments.
Mobile wireless network technology has grown rapidly over the past decade with emerging applications and services. Particularly, the fourth generation (4G) cellular network has acted as a bridge between telecommunication technology and daily life applications. In this paper, we present an investigation into a telepresence wheelchair in outdoor environments employing cellular network infrastructure instead of using local wireless networks in indoor environments. Experiments were carried out to demonstrate remote interaction and control from a long distance and across countries. A large amount of communication data based on real network measurements was collected and analyzed to evaluate the system performance. The experimental results show that a wheelchair system can be controlled remotely in real-time with the acceptable round trip time of less than 400 ms. The results reveal the feasibility of using the 4G network for a telepresence wheelchair in healthcare applications.


Assessing Changes in Ecosystem Service Values in Response to Land Cover Dynamics in Jiangxi Province, China.
This paper examines the ecosystem service values of Jiangxi province, China using the benefit transfer approach. The land cover dynamics results show that cropland and forest are the main land cover types in Jiangxi province. Urban land drastically increased after 2000, expanding from 846.54 km2 in 2000 to 2317.48 km2 in 2015. Forest and water obviously decreased across the study periods. Consequently, the total ecosystem service values decreased from 37.91 × 1010 Yuan in 1995 to 35.27 × 1010 Yuan in 2015. The values showed a declining trend, especially during the 1995-2000 period. The largest declines in ecosystem service values were caused by decreases in forest and water cover. Regulating services experienced the largest declines in ecosystem services value. Moreover, water supply showed the largest decline in ecosystem service value between 1995 and 2015. Not surprisingly, food production increased in the whole period, especially in the 1995-2000 period. Forest and cropland played the most important roles in the total ecosystem service values of Jiangxi province. We then discussed the relationship among ecosystem services based on the ecosystem service trade-off degree. The results show that the dominant relationship among ecosystem services in Jiangxi province was synergy; thus synergy mostly occurred in all ecosystem services except for food production from 1995 to 2015. However, during the 1995-2000 period, trade-offs mainly existed in both food production and waste treatment. The proportion of synergy greatly increased in the 2000-2015 period, and the synergistic relationship between waste treatment and other ecosystem services increased. However, the trade-off relationship between food production and other ecosystem services still has not improved, which should be concerned in the future. Changes in the percentage share of cropland showed a declining trend; thus, the potential risk of cropland loss should be monitored.


Cannabinoid receptor-regulated cyclic AMP accumulation in the rat striatum.
The present study demonstrates that desacetyllevonantradol, a synthetic cannabinoid analog, reduces cyclic AMP levels in rat striatal slices stimulated with vasoactive intestinal peptide or SKF 38393, a D1-dopamine agonist. Desacetyllevonantradol and the D2 agonist LY 171555 both inhibited D1-stimulated cyclic AMP accumulation in the striatum. Spiperone, a specific D2-dopamine antagonist, fully reversed the inhibitory effect of LY 171555 but not that of desacetyllevonantradol, indicating that this cannabinoid response is not occurring through a D2-dopaminergic mechanism. Morphine also inhibited cyclic AMP accumulation in striatal slices stimulated with either SKF 38393 or vasoactive intestinal peptide. Naloxone, an opioid antagonist, fully reversed the effect of morphine but not that of desacetyllevonantradol, indicating that cannabinoid drugs are not acting via a mechanism involving opioid receptors. The response to maximally effective concentrations of desacetyllevonantradol was not additive to that of maximally effective concentrations of either morphine or LY 171555, suggesting that dopaminergic, opioid, and cannabinoid receptors may be present on the same populations of cells.


Transferrin receptor-targeted vitamin E TPGS micelles for brain cancer therapy: preparation, characterization and brain distribution in rats.
The effective treatment of brain cancer is hindered by the poor transport across the blood-brain barrier (BBB) and the low penetration across the blood-tumor barrier (BTB). The objective of this work was to formulate transferrin-conjugated docetaxel (DTX)-loaded d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS or TPGS) micelles for targeted brain cancer therapy. The micelles with and without transferrin conjugation were prepared by the solvent casting method and characterized for their particle size, polydispersity, drug encapsulation efficiency, drug loading, in vitro release study and brain distribution study. Particle sizes of prepared micelles were determined at 25 °C by dynamic light scattering technique. The external surface morphology was determined by transmission electron microscopy analysis and atomic force microscopy. The encapsulation efficiency was determined by spectrophotometery. In vitro release studies of micelles and control formulations were carried out by dialysis bag diffusion method. The particle sizes of the non-targeted and targeted micelles were <20 nm. About 85% of drug encapsulation efficiency was achieved with micelles. The drug release from transferrin-conjugated micelles was sustained for >24 h with 50% of drug release. The in vivo results indicated that transferrin-targeted TPGS micelles could be a promising carrier for brain targeting due to nano-sized drug delivery, solubility enhancement and permeability which provided an improved and prolonged brain targeting of DTX in comparison to the non-targeted micelles and marketed formulation.