AHR2 knockdown prevents PAH-mediated cardiac toxicity and XRE- and ARE-associated gene induction in zebrafish (Danio rerio).
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants often present in aquatic systems as complex mixtures. Embryonic fish are sensitive to the developmental toxicity of some PAHs, but the exact mechanisms involved in this toxicity are still unknown. This study explored the role of the aryl hydrocarbon receptor (AHR) in the oxidative stress response of zebrafish to the embryotoxicity of select PAHs. Embryos were exposed to two PAHs, benzo[k]fluoranthene (BkF; a strong AHR agonist) and fluoranthene (FL; a cytochrome P4501A (CYP1A) inhibitor), alone and in combination. CYP1A, CYP1B1, CYP1C1, and redox-responsive genes glutathione s-transferase pi 2 (GSTp2), glutathione peroxidase 1 (GPx1), the glutamate-cysteine ligase catalytic subunit (GCLc), MnSOD and CuZnSOD mRNA expression was examined. CYP1 activity was measured via an in vivo ethoxyresorufin-O-deethlyase (EROD) activity assay, and the area of the pericardium was measured as an index of cardiotoxicity. BkF or FL alone caused no deformities whereas BkF+FL resulted in extreme pericardial effusion. BkF induced CYP activity above controls and co-exposure with FL inhibited this activity. BkF induced expression of all three CYPs, GSTp2, and GCLc. BkF+FL caused greater than additive induction of the three CYPs, GSTp2, GPx1, and GCLc but had no effect on MnSOD or CuZnSOD. AHR2 knockdown protected against the cardiac deformities caused by BkF+FL and significantly inhibited the induction of the CYPs, GSTp2, GPx1, and GCLc after BkF+FL compared to non-injected controls. These results further show the protective role of AHR2 knockdown against cardiotoxic PAHs and the role of AHR2 as a mediator of redox-responsive gene induction.


Ionic selectivity of low-affinity ratiometric calcium indicators: mag-Fura-2, Fura-2FF and BTC.
Accurate measurement of elevated intracellular calcium levels requires indicators with low calcium affinity and high selectivity. We examined fluorescence spectral properties and ionic specificity of three low-affinity, ratiometric indicators structurally related to Fura-2: mag-Fura-2 (furaptra), Fura-2FF, and BTC. The indicators differed in respect to their excitation wavelengths, affinity for Ca2+ (Kd approximately 20 microM, 6 microM and 12 microM respectively) and selectivity over Mg2+ (Kd approximately 2 mM for mag-Fura-2, > 10 mM for Fura-2FF and BTC). Among the tested indicators, BTC was limited by a modest dynamic range upon Ca2+ binding, susceptibility to photodamage, and sensitivity to alterations in pH. All three indicators bound other metal ions including Zn2+, Cd2+ and Gd3+. Interestingly, only in the case of BTC were spectral differences apparent between Ca2+ and other metal ions. For example, the presence of Zn2+ increased BTC fluorescence 6-fold at the Ca2+ isosbestic point, suggesting that this dye may be used as a fluorescent Zn2+ indicator. Fura-2FF has high specificity, wide dynamic range, and low pH sensitivity, and is an optimal low-affinity Ca2+ indicator for most imaging applications. BTC may be useful if experimental conditions require visible wavelength excitation or sensitivity to other metal ions including Zn2+.


P-selectin/ PSGL-1 inhibitors versus enoxaparin in the resolution of venous thrombosis: a meta-analysis.
P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT). To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis. Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects. Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77-70.96], p=0.001, I(2)=97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88-18.95], p=0.48, I(2)=41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98-(-8.30)], p<0.00001, I(2)=80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67-3.48], p=0.32, I(2)=66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36-0.11], p=0.07, I(2)=92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p<0.0001). P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.


Prediction of jaywalker-vehicle conflicts based on encoder-decoder framework utilizing multi-source data.
Jaywalker-vehicle (J-V) conflicts at mid-blocks without crossing facilities in China are frequent and hazardous. Due to the unexpected and sudden nature of jaywalking activity, it is crucial to develop predictive models for J-V conflicts to offer pre-conflict warnings for road users. This study introduces a novel encoder-decoder framework that utilizes multi-source data to predict J-V conflict severity. We define three encoders to represent three types of input data, (1) J-V interaction encoder (Bi-LSTM), (2) jaywalker motion encoder (Bi-LSTM) and (3) background information encoder (MLP). Subsequently, features extracted by these three encoders are concatenated and transferred to the conflict severity decoder (MLP) to obtain the predicted severity level. We further conduct a case study using the surveyed video data at three mid-blocks without crossing facilities in Nanjing, China. The experimental results indicate that, compared to classical models, our proposed encoder-decoder (Proposed ED) model exhibits the best and stable predictive metrics. Furthermore, the results of the ablation study suggest that the incorporation of background information significantly enhances the four evaluative metrics of the Proposed ED model, with an average improvement of 24.291%. Additionally, the results of transferability analysis suggest that, when the ratio of added samples from the new mid-block reaches 40% to 50%, the predictive metrics of the updated models could stabilize at around 80% to 95%, indicating a notably good performance. Eventually, we derive several practical suggestions from the above findings, in order to help with J-V conflict prediction and jaywalking safety improvement.


Epigenetic features of human mesenchymal stem cells determine their permissiveness for induction of relevant transcriptional changes by SYT-SSX1.
A characteristic SYT-SSX fusion gene resulting from the chromosomal translocation t(X;18)(p11;q11) is detectable in almost all synovial sarcomas, a malignant soft tissue tumor widely believed to originate from as yet unidentified pluripotent stem cells. The resulting fusion protein has no DNA binding motifs but possesses protein-protein interaction domains that are believed to mediate association with chromatin remodeling complexes. Despite recent advances in the identification of molecules that interact with SYT-SSX and with the corresponding wild type SYT and SSX proteins, the mechanisms whereby the SYT-SSX might contribute to neoplastic transformation remain unclear. Epigenetic deregulation has been suggested to be one possible mechanism. We addressed the effect of SYT/SSX expression on the transcriptome of four independent isolates of primary human bone marrow mesenchymal stem cells (hMSC). We observed transcriptional changes similar to the gene expression signature of synovial sarcoma, principally involving genes whose regulation is linked to epigenetic factors, including imprinted genes, genes with transcription start sites within a CpG island and chromatin related genes. Single population analysis revealed hMSC isolate-specific transcriptional changes involving genes that are important for biological functions of stem cells as well as genes that are considered to be molecular markers of synovial sarcoma including IGF2, EPHRINS, and BCL2. Methylation status analysis of sequences at the H19/IGF2 imprinted locus indicated that distinct epigenetic features characterize hMSC populations and condition the transcriptional effects of SYT-SSX expression. Our observations suggest that epigenetic features may define the cellular microenvironment in which SYT-SSX displays its functional effects.


Cardiac Conduction Disorders as Markers of Cardiac Events in Myotonic Dystrophy Type 1.
Background Myotonic dystrophy type 1 involves cardiac conduction disorders. Cardiac conduction disease can cause fatal arrhythmias or sudden death in patients with myotonic dystrophy type 1. Methods and Results This study enrolled 506 patients with myotonic dystrophy type 1 (aged ≥15 years; >50 cytosine-thymine-guanine repeats) and was treated in 9 Japanese hospitals for neuromuscular diseases from January 2006 to August 2016. We investigated genetic and clinical backgrounds including health care, activities of daily living, dietary intake, cardiac involvement, and respiratory involvement during follow-up. The cause of death or the occurrence of composite cardiac events (ie, ventricular arrhythmias, advanced atrioventricular blocks, and device implantations) were evaluated as significant outcomes. During a median follow-up period of 87 months (Q1-Q3, 37-138 months), 71 patients expired. In the univariate analysis, pacemaker implantations (hazard ratio [HR], 4.35; 95% CI, 1.22-15.50) were associated with sudden death. In contrast, PQ interval ≥240 ms, QRS duration ≥120 ms, nutrition, or respiratory failure were not associated with the incidence of sudden death. The multivariable analysis revealed that a PQ interval ≥240 ms (HR, 2.79; 95% CI, 1.9-7.19, P<0.05) or QRS duration ≥120 ms (HR, 9.41; 95% CI, 2.62-33.77, P < 0.01) were independent factors associated with a higher occurrence of cardiac events than those observed with a PQ interval <240 ms or QRS duration <120 ms; these cardiac conduction parameters were not related to sudden death. Conclusions Cardiac conduction disorders are independent markers associated with cardiac events. Further investigation on the prediction of occurrence of sudden death is warranted.


Endosome-mediated autophagy: an unconventional MIIC-driven autophagic pathway operational in dendritic cells.
Activation of TLR signaling has been shown to induce autophagy in antigen-presenting cells (APCs). Using high-resolution microscopy approaches, we show that in LPS-stimulated dendritic cells (DCs), autophagosomes emerge from MHC class II compartments (MIICs) and harbor both the molecular machinery for antigen processing and the autophagosome markers LC3 and ATG16L1. This ENdosome-Mediated Autophagy (ENMA) appears to be the major type of autophagy in DCs, as similar structures were observed upon established autophagy-inducing conditions (nutrient deprivation, rapamycin) and under basal conditions in the presence of bafilomycin A1. Autophagosome formation was not significantly affected in DCs expressing ATG4B (C74A) mutant and atg4b (-/-) bone marrow DCs, but the degradation of the autophagy substrate SQSTM1/p62 was largely impaired. Furthermore, we demonstrate that the previously described DC aggresome-like LPS-induced structures (DALIS) contain vesicular membranes, and in addition to SQSTM1 and ubiquitin, they are positive for LC3. LC3 localization on DALIS is independent of its lipidation. MIIC-driven autophagosomes preferentially engulf the LPS-induced SQSTM1-positive DALIS, which become later degraded in autolysosomes. DALIS-associated membranes also contain ATG16L1, ATG9 and the Q-SNARE VTI1B, suggesting that they may represent (at least in part) a membrane reservoir for autophagosome expansion. We propose that ENMA constitutes an unconventional, APC-specific type of autophagy, which mediates the processing and presentation of cytosolic antigens by MHC class II machinery, and/or the selective clearance of toxic by-products of elevated ROS/RNS production in activated DCs, thereby promoting their survival.


Selected characteristics of cervical cancer incidence cases.
Selected demographic characteristics associated with incidence cases of uterine cervical squamous severe dysplasia and carcinoma were determined. The mean age at histologic detection for all patients with Papanicolaou smears at not greater than three-year intervals was 31.0 years, with a range of 19 to 63. Invasive carcinomas were predominantly of the microinvasive type, and the mean age of patients was 34.1 years. The mean interval for conversion from cytologic negativity or mild dysplasia was 2.2 years, and two basic patterns of conversion were recognized: (1) continuously increasing atypia and (2) retrogressive cytologic findings. Most instances of the latter type probably were due to inadequacies of cellular sampling. No significant correlation was found between conversion interval and age of patient. A case-control comparison of gravidity and parity showed statistically significantly higher values among index cases for both measures for ages 20 to 29 but not for 30 years or older, implicating youthful pregnancy as an etiologic factor in cervical carcinogenesis.


Measurement of free-circulating cis-dichlorodiammineplatinum(II) in plasma.
Dichlorodiammineplatinum(II) is an anti-neoplastic agent that is currently undergoing clinical evaluation. We describe an analytical method for monitoring the free drug (or its breakdown products) in plasma. The method is able to distinguish between free and protein-bound drug. Plasma samples are deproteinized by centrifugal ultrafiltration. The platinum in the ultrafiltrate is converted to a cationic species by reaction with ethylenediamine and then collected on paper impregnated with cation-exchange resin. This process concentrates the samples, increases the stability of the platinum compounds (by removing the compound from solution), and places the sample in a uniform matrix of minimum thickness, which maximizes detection capabilities. Platinum was measured directly on the ion-exchange disks by X-ray fluorescence. The detection limit for free drug is 240 microgram/liter of plasma at the 3s level and fluorescence intensity is linearly related to drug concentration in the range from 570 to 5700 microgram/liter.


Ultrasound shear wave elasticity imaging quantifies coronary perfusion pressure effect on cardiac compliance.
Diastolic heart failure (DHF) is a major source of cardiac related morbidity and mortality in the world today. A major contributor to, or indicator of DHF is a change in cardiac compliance. Currently, there is no accepted clinical method to evaluate the compliance of cardiac tissue in diastolic dysfunction. Shear wave elasticity imaging (SWEI) is a novel ultrasound-based elastography technique that provides a measure of tissue stiffness. Coronary perfusion pressure affects cardiac stiffness during diastole; we sought to characterize the relationship between these two parameters using the SWEI technique. In this work, we demonstrate how changes in coronary perfusion pressure are reflected in a local SWEI measurement of stiffness during diastole. Eight Langendorff perfused isolated rabbit hearts were used in this study. Coronary perfusion pressure was changed in a randomized order (0-90 mmHg range) and SWEI measurements were recorded during diastole with each change. Coronary perfusion pressure and the SWEI measurement of stiffness had a positive linear correlation with the 95% confidence interval (CI) for the slope of 0.009-0.011 m/s/mmHg ( R(2) = 0.88 ). Furthermore, shear modulus was linearly correlated to the coronary perfusion pressure with the 95% CI of this slope of 0.035-0.042 kPa/mmHg ( R(2) = 0.83). In conclusion, diastolic SWEI measurements of stiffness can be used to characterize factors affecting cardiac compliance specifically the mechanical interaction (cross-talk) between perfusion pressure in the coronary vasculature and cardiac muscle. This relationship was found to be linear over the range of pressures tested.


The role of deleterious mutations in the stability of hybridogenetic water frog complexes.
Some species of water frogs originated from hybridization between different species. Such hybrid populations have a particular reproduction system called hybridogenesis. In this paper we consider the two species Pelophylax ridibundus and Pelophylax lessonae, and their hybrids Pelophylax esculentus. P. lessonae and P. esculentus form stable complexes (L-E complexes) in which P. esculentus are hemiclonal. In L-E complexes all the transmitted genomes by P. esculentus carry deleterious mutations which are lethal in homozygosity. We analyze, by means of an individual based computational model, L-E complexes. The results of simulations based on the model show that, by eliminating deleterious mutations, L-E complexes collapse. In addition, simulations show that particular female preferences can contribute to the diffusion of deleterious mutations among all P. esculentus frogs. Finally, simulations show how L-E complexes react to the introduction of translocated P. ridibundus. The conclusions are the following: (i) deleterious mutations (combined with sexual preferences) strongly contribute to the stability of L-E complexes; (ii) female sexual choice can contribute to the diffusion of deleterious mutations; and (iii) the introduction of P. ridibundus can destabilize L-E complexes.


Auditory epidermal cell migration. VII. Antigen expression of proliferating cell nuclear antigens, PCNA and Ki-67 in human tympanic membrane and external auditory canal.
A location of proliferating cells was investigated in eight human normal tympanic membranes (TMs) and external auditory canals (EACs) by an immunohistochemical method using two different types of antibodies for nuclear antigens in proliferating cells: anti-PCNA monoclonal antibody, and anti-Ki-67 polyclonal antibody. Four specimens prepared for cryostat sections were immunostained by both antibodies. Another four were fixed in 4% formaldehyde solution, embedded in paraffin wax and were reacted only with anti-PCNA antibodies. The expression pattern of Ki-67 was basically the same as of PCNA. In the pars tensa (PT), immunoreactivities were expressed in the nuclei of basal layer cells and cells just overlying the basal layer of epidermis both in the handle of the malleus (HM) and annular regions. In the intermediate region of the PT, no immunoreactivity was found basically, apart from a few labelled cells observed in the upper-third of the superior quadrant. In the pars flaccida (PF) and in both the osseous and cartilaginous regions of the EAC, positive cells were also situated in the basal layer and the deeper aspect of the suprabasal layers without any specific distributing pattern. It was certified that the generation centre of epidermal cells (keratinocytes) in the PT was located in both the HM and annular regions, and that stem cells in the PF and the EAC were uniformly scattered in the basal layer and the deeper aspect of the spinous layer. According to these findings, the migratory patterns of auditory epidermal cells in the human TM and EAC were discussed.


The experiences of non-operative treatment in patients with bacterial brain abscess.
Although treatment of brain abscess requires a combination of antimicrobials and surgical intervention for the infected foci, nonsurgical, empirical treatment is possible and efficient in selected groups of patients. A total of 31 patients were enrolled in this 22-year retrospective study. We describe our therapeutic experiences and attempt to analyze the risk factors that were predictive of therapeutic outcomes. Multiple logistic regression was used to evaluate the relationships between baseline clinical factors and therapeutic outcome during the study period. Of these 31 patients, 25 had community-acquired infections, whereas the other six had nosocomially-acquired infections. Thirteen cases (42%) had a single brain abscess and the other 18 cases (58%) had multiple brain abscesses. Furthermore, the association of bacterial meningitis and brain abscess was found in 81% (25/31) of cases. The overall case fatality rate was 48% (15/31). Significant risk factors for poor outcomes included Glasgow coma scale (GCS) at presentation, presence of septic shock and neck stiffness. In addition, each reduction of one point on the GCS increased the poor outcome rate by 28%. The findings of the study demonstrate that both a higher mortality rate (48%) and worse outcomes were found in this select group of patients. Among the significant prognostic factors, a lower mean GCS at presentation was a major determinant of poor outcome.


Associations between respiratory sinus arrhythmia reactivity and internalizing and externalizing symptoms are emotion specific.
Internalizing and externalizing disorders are often, though inconsistently in studies of young children, associated with low baseline levels of respiratory sinus arrhythmia (RSA). RSA is thus considered to reflect the capacity for flexible and regulated affective reactivity and a general propensity for psychopathology. However, studies assessing RSA reactivity to emotional challenges tend to report more consistent associations with internalizing than with externalizing disorders, although it is unclear whether this is a function of the type of emotion challenges used. In the present study, we examined whether baseline RSA was associated with internalizing and/or externalizing severity in a sample of 273 young children (ages 5-6) with elevated symptoms of psychopathology. Following motivation-based models of emotion, we also tested whether RSA reactivity during withdrawal-based (fear, sadness) and approach-based (happiness, anger) emotion inductions was differentially associated with internalizing and externalizing symptoms, respectively. Baseline RSA was not associated with externalizing or internalizing symptom severity. However, RSA reactivity to specific emotional challenges was associated differentially with each symptom domain. As expected, internalizing symptom severity was associated with greater RSA withdrawal (increased arousal) during fearful and sad film segments. Conversely, externalizing symptom severity was related to blunted RSA withdrawal during a happy film segment. The use of theoretically derived stimuli may be important in characterizing the nature of the deficits in emotion processing that differentiate the internalizing and externalizing domains of psychopathology.


Correlation of specific amyloid-β oligomers with tau in cerebrospinal fluid from cognitively normal older adults.
To improve the ability to develop treatments that prevent incipient Alzheimer disease (AD) from progressing to overt AD, it is important to understand the molecular basis of the earliest pathophysiological abnormalities and to determine how amyloid-β (Aβ) is involved very early in its pathogenesis. To investigate 2 specific Aβ oligomers, Aβ trimers and Aβ*56, in human cerebrospinal fluid (CSF); evaluate the effects of aging and AD; and obtain support for the hypothesis that they may be pathogenic by determining their relationships to CSF tau. A CSF sampling study. The University of Minnesota Medical School in Minneapolis, Minnesota, and the Salhgrenska University Hospital, Sweden. Forty-eight older adults with mild cognitive impairment or AD (impaired group); 49 age-matched cognitively intact control subjects (unimpaired group); and 10 younger, normal control subjects. Measurements of CSF Aβ trimers, Aβ*56, the 42-amino acid Aβ isoform (Aβ1-42), total tau (T-tau), and phospho-tau 181 (p-tau(181)). The hypothesis being tested was formulated after data collection. RESULTS We observed that Aβ trimers and Aβ*56 levels increased with age; within the unimpaired group, they were elevated in subjects with T-tau/Aβ1-42 ratios greater than a cutoff that distinguished the unimpaired group from subjects with AD. In the unimpaired group, T-tau and p-tau(181) were found to correlate strongly with Aβ trimers and Aβ*56 (r > 0.63), but not with Aβ1-42 (-0.10 < r < -0.01). The strong correlations were found to be attenuated in the impaired group. In cognitively intact older adults, CSF Aβ trimers and Aβ*56 were elevated in individuals at risk for AD, and they showed stronger relationships with tau than did Aβ1-42, a surrogate for Aβ fibril deposition. These findings suggest that prior to overt symptoms, 1 or both of the Aβ oligomers, but not fibrillar Aβ, is coupled to tau; however, this coupling is weakened or broken when AD advances to symptomatic stages. The uncoupling is interesting in light of the failure of experimental Aβ therapies to improve mild cognitive impairment/AD, which has prompted a shift in the timing of Aβ therapies to asymptomatic subjects. Knowing which Aβ species to target in asymptomatic subjects may enhance the success of future treatments for AD.


Restoration of mature etiolated cucumber hypocotyl cell wall susceptibility to expansin by pretreatment with fungal pectinases and EGTA in vitro.
Mature plant cell walls lose their ability to expand and become unresponsive to expansin. This phenomenon is believed to be due to cross-linking of hemicellulose, pectin, or phenolic groups in the wall. By screening various hydrolytic enzymes, we found that pretreatment of nongrowing, heat-inactivated, basal cucumber (Cucumis sativus) hypocotyls with pectin lyase (Pel1) from Aspergillus japonicus could restore reconstituted exogenous expansin-induced extension in mature cell walls in vitro. Recombinant pectate lyase A (PelA) and polygalacturonase (PG) from Aspergillus spp. exhibited similar capacity to Pel1. Pel1, PelA, and PG also enhanced the reconstituted expansin-induced extension of the apical (elongating) segments of cucumber hypocotyls. However, the effective concentrations of PelA and PG for enhancing the reconstituted expansin-induced extension were greater in the apical segments than in the basal segments, whereas Pel1 behaved in the opposite manner. These data are consistent with distribution of more methyl-esterified pectin in cell walls of the apical segments and less esterified pectin in the basal segments. Associated with the degree of esterification of pectin, more calcium was found in cell walls of basal segments compared to apical segments. Pretreatment of the calcium chelator EGTA could also restore mature cell walls' susceptibility to expansin by removing calcium from mature cell walls. Because recombinant pectinases do not hydrolyze other wall polysaccharides, and endoglucanase, xylanase, and protease cannot restore the mature wall's extensibility, we can conclude that the pectin network, especially calcium-pectate bridges, may be the primary factor that determines cucumber hypocotyl mature cell walls' unresponsiveness to expansin.


Identification of sites within gp41 that serve as targets for antibody-dependent cellular cytotoxicity by using human monoclonal antibodies.
In an effort to determine the functional activity of anti-HIV-1 human mAb and to define the epitopes against which they are directed, supernatants from 10 EBV-transformed lymphoblastoid cell lines producing mAb to HIV were tested. Five clones producing mAb to gp41 and five producing mAb to p24 were identified. The anti-HIV-1 human mAb were tested in neutralization and cell fusion assays in the form of cell culture supernatants at concentrations ranging from 1.7 to 22.0 micrograms/ml. None of the human mAb were found either to inhibit HIV-1-(IIIB or RF) associated cell fusion or to neutralize HIV-1 (IIIB) infection of AA5 cells. All human mAb were additionally tested in 6 h 51Cr release assays for their ability to direct HIV-1 specific antibody-dependent cellular cytotoxicity (ADCC). For ADCC assays, PBMC were isolated from healthy seronegative donors and used as effector cells. HIV-1 infected (IIIB, RF, and MN) CEM.NKR cells as well as CEM.NKR cells with purified gp120 adsorbed onto their surface served as targets. None of the anti-p24 mAb mediated ADCC. In contrast, three of the anti-gp41 mAb were able to direct a significant level of ADCC against each of the infected targets, but as expected, failed to lyse gp120 adsorbed cells. To define the specific epitopes against which the anti-gp41 mAb were directed, seven small peptides homologous to regions within the extracellular domain of gp41 were synthesized. Using RIA, two of the mAb could be mapped. The most effective ADCC-directing human mAb bound to a peptide comprising amino acids 644-663, whereas the least effective ADCC directing anti-gp41 human mAb bound to a region within the immunodominant portion of gp41 outlined by amino acids 579-604. Together, these results for the first time assign a functional activity to human mAb directed at specific regions within gp41 by demonstrating that areas within this molecule can serve as targets for ADCC.


Language Brain Representation in Bilinguals With Different Age of Appropriation and Proficiency of the Second Language: A Meta-Analysis of Functional Imaging Studies.
Language representation in the bilingual brain is the result of many factors, of which age of appropriation (AoA) and proficiency of the second language (L2) are probably the most studied. Many studies indeed compare early and late bilinguals, although it is not yet clear what the role of the so-called critical period in L2 appropriation is. In this study, we carried out coordinate-based meta-analyses to address this issue and to inspect the role of proficiency in addition to that of AoA. After the preliminary inspection of the early (also very early) and late bilinguals' language networks, we explored the specific activations associated with each language and compared them within and between the groups. Results confirmed that the L2 language brain representation was wider than that associated with L1. This was observed regardless of AoA, although differences were more relevant in the late bilinguals' group. In particular, L2 entailed a greater enrollment of the brain areas devoted to the executive functions, and this was also observed in proficient bilinguals. The early bilinguals displayed many activation clusters as well, which also included the areas involved in cognitive control. Interestingly, these regions activated even in L1 of both early and late bilingual groups, although less consistently. Overall, these findings suggest that bilinguals in general are constantly subjected to cognitive effort to monitor and regulate the language use, although early AoA and high proficiency are likely to reduce this.


Assessment of the activity of photocatalytic paint using a simple smart ink designed for high activity surfaces.
The use of an acid violet 7 (AV7) smart ink to assess the activity of photocatalytic paint is demonstrated. A linear correlation is established between the change in oxidized dye concentration, as measured by diffuse reflectance, and the change in the green component of the RGB color values, obtained using a portable hand-held scanner, suggesting that such tests can be monitored easily using an inexpensive piece of hand-held office equipment, as opposed to an expensive lab-based instrument, such as a diffuse reflectance UV/vis spectrophotometer. The bleaching of the AV7 follows first order kinetics, at a rate that is linearly dependent upon the UVA irradiance (0.30-3.26 mW cm(-2)). A comparison of relative rate of bleaching of the AV7 ink with the relative rate of removal of NOx, as determined using the ISO test (ISO 22197-1:2007), established a linear relationship between the two sets of results and the relevance of this correlation is discussed briefly.


Living and cadaver donor transplant programs in the Maghreb.
In the Maghreb, organ failure constitutes a major public health problem, especially given the increasing number of patients with chronic renal failure and the high cost of care. In this study, we attempted to seek the recommendations, through a questionnaire, of various officials related to organ transplantation as well as leaders of ethics committees and religious groups in different countries of the Maghreb. The objective was to improve the rate of organ donation and transplantation. We received 36 replies (62%) within the prescribed time limit. In our survey, 83% of the respondents felt that living donor transplantation should be promoted initially, followed gradually by measures to increase cadaver donor transplantation to achieve a target of about 30 transplants with cadaver kidney donors per million inhabitants. To expand the donor pool, 83% of the respondents proposed to expand the family circle to include the spouse and in laws. To improve the cadaver donation activity, one should improve the organizational aspects to ensure at least 50 renal transplantations per year (100%) and provide material motivation to the treatment team proportional to the activity of organ donation and transplantation. Finally, 93% of the respondents suggested suitable moral motivation of the donors.


[Study of the influence of raw material and processing conditions on acrylamide level in fried potato chips].
The aim of our study was to examine relation between the asparagine level in raw material and acrylamide concentration in chips made from different varieties of potato. Relation between colour of potato chips and acrylamide content was also examined. Acrylamide concentration in fried potato chips ranged from 376 to 2348 microg/kg. We found the lowest acrylamide content in potato chips made from the Plant Breeding and Acclimatization Institute Irga and the highest in Irga bought in the Warsaw market. We didn't find significant correlation between the asparagine content in raw material and the acrylamide level in potato chips (r = -0.13). The colour intensity of fried chips positively correlated with acrylamide concentration independently from the potato varieties and sequence of frying (r = 0.8045; p < 0.005).


Profile likelihood-based confidence interval of the intraclass correlation for binary outcome data sampled from clusters.
The intraclass correlation in binary outcome data sampled from clusters is an important and versatile measure in many biological and biomedical investigations. Properties of the different estimators of the intraclass correlation based on the parametric, semi-parametric, and nonparametric approaches have been studied extensively, mainly in terms of bias and efficiency [see, for example, Ridout et al., Biometrics 1999, 55:137-148; Paul et al., Journal of Statistical Computation and Simulation 2003, 73:507-523; and Lee, Statistical Modelling 2004, 4: 113-126], but little attention has been paid to extending these results to the problem of the confidence intervals. In this article, we generalize the results of the four point estimators by constructing asymptotic confidence intervals obtaining closed-form asymptotic and sandwich variance expressions of those four point estimators. It appears from simulation results that the asymptotic confidence intervals based on these four estimators have serious under-coverage. To remedy this, we introduce the Fisher's z-transformation approach on the intraclass correlation coefficient, the profile likelihood approach based on the beta-binomial model, and the hybrid profile variance approach based on the quadratic estimating equation for constructing the confidence intervals of the intraclass correlation for binary outcome data. As assessed by Monte Carlo simulations, these confidence interval approaches show significant improvement in the coverage probabilities. Moreover, the profile likelihood approach performs quite well by providing coverage levels close to nominal over a wide range of parameter combinations. We provide applications to biological data to illustrate the methods.


Multiple Ras signals pattern the Drosophila ovarian follicle cells.
During Drosophila oogenesis, spatially restricted activity of the TORPEDO receptor tyrosine kinase first recruits follicle cells adjacent to the oocyte to a posterior cell fate and then specifies dorsal follicle cells. Another receptor tyrosine kinase, BREATHLESS, stimulates migration of the anterior follicle cells known as border cells. Since Ras is known to mediate many receptor tyrosine kinase effects, we have investigated the role of Ras in follicle cell fate determination, differentiation, and migration throughout oogenesis. Early ectopic Ras activity induced transient expression of posterior follicle cell markers in anterior follicle cells, but did not inhibit anterior differentiation. Later ectopic Ras activity inhibited anterior follicle cell differentiation but did not induce posterior marker expression. Complete transformation of anterior follicle cells to posterior follicle cells required early ectopic Ras activity in egg chambers where terminal differentiation of anterior cells was inhibited. These results suggest that, in vivo as in vitro, Ras can have diverse effects on different cells, but, in addition, Ras activity can have different effects on the same cells at different stages in their development.


Fibroblast growth factor 21 is regulated by the IRE1α-XBP1 branch of the unfolded protein response and counteracts endoplasmic reticulum stress-induced hepatic steatosis.
Endoplasmic reticulum (ER) stress activates the adaptive unfolded protein response (UPR) and represents a critical mechanism that underlies metabolic dysfunctions. Fibroblast growth factor 21 (FGF21), a hormone that is predominantly secreted by the liver, exerts a broad range of effects upon the metabolism of carbohydrates and lipids. Although increased circulating levels of FGF21 have been documented in animal models and human subjects with obesity and nonalcoholic fatty liver disease, the functional interconnections between metabolic ER stress and FGF21 are incompletely understood. Here, we report that increased ER stress along with the simultaneous elevation of FGF21 expression were associated with the occurrence of nonalcoholic fatty liver disease both in diet-induced obese mice and human patients. Intraperitoneal administration of the ER stressor tunicamycin in mice resulted in hepatic steatosis, accompanied by activation of the three canonical UPR branches and increased the expression of FGF21. Furthermore, the IRE1α-XBP1 pathway of the UPR could directly activate the transcriptional expression of Fgf21. Administration of recombinant FGF21 in mice alleviated tunicamycin-induced liver steatosis, in parallel with reduced eIF2α-ATF4-CHOP signaling. Taken together, these results suggest that FGF21 is an integral physiological component of the cellular UPR program, which exerts beneficial feedback effects upon lipid metabolism through counteracting ER stress.


Production of potato (Solanum tuberosum, L.) microtubers using plastic culture bags.
We have developed a system using plastic culture bags with forced aeration system for both liquid medium and gaseous phase to produce microtubers of potato (Solanum tuberosum L.). The production of microtubers under sterile conditions is a good way to produce disease-free materials for crop production, and bioreactors have been used for this purpose. However, bioreactors are expensive and difficult to handle. The plastic culture bags are relatively inexpensive and are easy to store and sterilize because they can be flattened. Microtuber production involves two stages: plant proliferation in one medium, followed by microtuber production in a different medium. Both steps are carried out using the same culture bag. Using this system, we produced 100 to 300 microtubers per 8 l culture bag, depending on the potato cultivar. We varied the nutrient concentrations in the media and found that a lower sucrose concentration in the plant proliferation medium and lower nitrogen concentration in the microtuber production medium both increased the total numbers of microtubers per bag. Notably, a higher concentration of potassium phosphate increased the numbers of larger microtubers. This is beneficial because larger microtubers are much more tolerant to field conditions. We produced about 250,000 microtubers per year in a 66 m2 tissue culture room using the culture bag system. These microtubers have been planted directly in the field and utilized for seed potato production.


Discrimination of optical sources by use of adaptive blind source separation theory.
Optical systems based on rotating reticles were invented to determine the polar coordinates of a primarily IR optical source. Such systems fail when several optical sources are present in their field of view simultaneously. It is demonstrated experimentally that this drawback can be overcome by the application of a blind-signal-separation algorithm on the output signals of a modified optical system. The separation of the modified optical system responses into independent components yields modulating functions that carry information concerning the polar coordinates of the corresponding single optical sources.


An optimization algorithm for 3D real-time lung tumor tracking during arc therapy using kV projection images.
To develop a real-time markerless 3D tumor tracking using kilovoltage (kV) cone-beam CT (CBCT) projection images during volumetric modulated arc therapy (VMAT) treatment of lung tumors. The authors have developed a method to identify the position of lung tumors during VMAT treatment, where the current mean 3D position is detected and subsequently the real time 3D position is obtained. The mean position is evaluated by iteratively minimizing an observation error function between the tumor coordinate detected in the imaging plane and the coordinate of the corresponding projection of the estimated mean position. The 3D trajectory is reconstructed using the same optimization formalism, where an observation error function is minimized for tumor positions confined within a predefined amplitude bin as determined from the superior-inferior tumor motion. Dynamic phantom experiments were performed and image data acquired during patient treatment were analyzed to characterize the reconstruction ability of the proposed method. The proposed algorithm needs to acquire kV projection data until a certain gantry angle is passed through, termed the black-out angle, before accurate estimation mean 3D tumor position is possible. The black-out angle for the mean position method is approximately 20°, while for the 3D trajectory reconstruction an additional ≈ 15° is required. The mean 3D position and 3D trajectory reconstruction are accurate within ± 0.5 mm. The authors present a real-time tracking framework to locate lung tumors during VMAT treatment using an optimization algorithm applied to CBCT kV projection images taken concomitantly with the treatment delivery. The authors' technique does not introduce significant additional dose and can be used for real-time treatment monitoring.


Cluster-randomized trial of a German leisure-based alcohol peer education measure.
Because of scarce research, the effectiveness of substance abuse prevention in leisure settings remains unclear. In this study, we evaluated the effectiveness of a peer-led educational prevention measure with adolescent groups in unstructured leisure settings, which is a component of the complex German nationwide 'Na Toll!' campaign. Using a cluster-randomized two-group post-test-only design, we tested whether the measure influenced component-specific goals, namely risk and protective factors of alcohol use such as risk perception, group communication and resistance self-efficacy. The sample consisted of 738 adolescents aged 12-20 years who were recruited at recreational locations and completed an online questionnaire 1 week after the peer education or recruitment event. Sixty-three percent of the sample participated in the 3-month follow-up assessment. Data analysis revealed post-test effects on risk perception, perceived norm of alcohol communication in the peer group and resistance self-efficacy. Follow-up effects were not observed, with the exception of a significant effect on risk perception. In conclusion, the peer-led education measure in leisure settings might have supported the adolescents in this study to perceive alcohol-related risks, to feel accepted to talk about alcohol problems with their friends and to be more assertive in resisting alcohol use in the short term.


Telemetric Interventions Offer New Opportunities for Managing Type 1 Diabetes Mellitus: Systematic Meta-review.
The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide. Simultaneously, technological advances are offering new opportunities for better management of type 1 diabetes mellitus (T1DM). Telemetry, the remote acquisition of patient data via a telecommunication system, is a promising field of application in eHealth and is rapidly gaining importance. The aim of this study was to summarize the current evidences available on the effectiveness of telemetric approaches in T1DM management. This systematic meta-review examined different types of interventions of the technologies used in communication between health care professionals and patients as well as the key outcomes. We performed a systematic search in Web of Science Core Collection, EMBASE, Cochrane Library, MEDLINE via PubMed, and CINAHL databases in April 2020 with regard to the effectiveness of telemetric interventions for T1DM. We classified the interventions into 4 categories according to the technology used: (1) real-time video communication, (2) real-time audio communication, (3) asynchronous communication, and (4) combined forms of communication (real-time and asynchronous). We considered various study designs such as systematic reviews, clinical trials, meta-analyses, and randomized controlled trials and focused on the key outcomes. Additionally, a funnel plot based on hemoglobin A1c (HbA1c) values and different quality assessments were performed. We identified 17 (6 high quality and 9 moderate quality) eligible publications: randomized controlled trials (n=9), systematic reviews and meta-analyses (n=5), cohort studies (n=2), and qualitative publications (n=1). Of 12 studies, 8 (67%) indicated a (significant or nonsignificant) reduction in HbA1c levels; 65% (11/17) of the studies reported overall (mildly) positive effects of telemetric interventions by addressing all the measured outcomes. Asynchronous interventions were the most successful for patients diagnosed with T1DM, but no technology was clearly superior. However, there were many nonsignificant results and not sustained effects, and in some studies, the control group benefited from telemetric support or increased frequency of contacts. Based on the currently available literature, this systematic meta-review shows that telemetric interventions cause significant reduction in HbA1c levels and result in overall positive effects in T1DM management. However, more specified effects of telemetric approaches in T1DM management should be analyzed in detail in larger cohorts.


Influence of a child's race and the EMR label on initial impressions of regular-classroom teachers.
Regular-classroom elementary school teachers (n = 99) were shown a photograph of an 11-year-old black, Mexican-American, or white child and were told that the child was either EMR or attended a fifth-grade class. Three dependent measures were used to assess the teachers' initial impressions of the child's attractiveness and his academic and behavioral potential. Data indicated that the race of the child significantly influenced the teachers' initial expectations. The EMR label yielded significant results when the teachers assessed the child's intellectual potential. A significant interaction was found on the behavioral measure between race and label, indicating that the race and label of a child can differentially influence a teacher's initial impressions of his or her behavior. Implications and suggestions for further research were discussed.


Intake of high fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is associated with prevalent coronary heart disease, in U.S. adults, ages 45-59 y.
Intake of high excess free fructose (EFF) beverages, including high fructose corn syrup (HFCS), sweetened soft drinks, fruit drinks, and apple juice, may be associated with childhood asthma, adult idiopathic chronic bronchitis/ COPD, and autoimmune arthritis, possibly due to underlying fructose malabsorption. Fructose malabsorption may contribute to the intestinal in situ formation of advanced glycation end-products (enFruAGEs) that travel to other tissues and promote inflammation. Chronic respiratory conditions and arthritis are comorbidities of coronary heart disease (CHD). The objective of this study was to investigate the association between intake of high EFF beverages and CHD. In this cross sectional study (NHANES 2003-2006) of adults, aged 45-59 y, n = 1230, the exposure variables were non-diet soft drinks, and any combination of high EFF beverages including non-diet soft drinks, fruit drinks, and apple juice. Analyses of diet soft drinks, diet fruit drinks, and orange juice (non/low EFF beverages) were included for comparison. The outcome was self-reported history of coronary heart disease and/or angina (CHD). Rao Scott Ҳ2 was used for prevalence differences and logistic regression for associations, adjusted for age, sex, race-ethnicity, BMI, socio-economic status, health insurance coverage, smoking, physical activity level, hypertension, energy intake, fruit and vegetable intake, glycated hemoglobin, pre-diabetes, and diabetes. Intake of any combination of HFCS sweetened soft drinks, fruit drinks, and apple juice (tEFF) was significantly associated with CHD in adults aged 45-59 y. Adults consuming tEFF ≥5 times/wk. were 2.8 times more likely to report CHD than ≤3 times/mo consumers (OR 2.82; 95% CI 1.16-6.84; P = 0.023), independent of all covariates. HFCS sweetened soft drinks, fruit drinks, and apple juice may contribute to CHD, a common comorbidity of chronic respiratory conditions and autoimmune arthritis, possibly due to the high ratio of fructose to glucose in these beverages. Underlying fructose malabsorption may contribute to the intestinal in situ formation of pro-inflammatory enFruAGEs, that are eventually absorbed and induce inflammation of the coronary arteries. Additional research is needed.


Double-negative neuromyelitis optica spectrum disorder.
Most patients with neuromyelitis optica spectrum disorders (NMOSD) test positive for aquaporin-4 antibody (AQP4-IgG) or myelin oligodendrocyte glycoprotein antibodies (MOG-IgG). Those who are negative are termed double-negative (DN) NMOSD and may constitute a diagnostic and therapeutic challenge. DN NMOSD is a syndrome rather than a single disease, ranging from a (postinfectious) monophasic illness to a more chronic syndrome that can be indistinguishable from AQP4-IgG+ NMOSD or develop into other mimics such as multiple sclerosis. Thus, underlying disease mechanisms are likely to be heterogeneous. This topical review aims to (1) reappraise antibody-negative NMOSD definition as it has changed over time with the development of the AQP4 and MOG-IgG assays; (2) outline clinical characteristics and the pathophysiological nature of this rare entity by contrasting its differences and similarities with antibody-positive NMOSD; (3) summarize laboratory characteristics and magnetic resonance imaging findings of DN NMOSD; and (4) discuss the current treatment for DN NMOSD.


Protection from radiation-induced apoptosis by the radioprotector amifostine (WR-2721) is radiation dose dependent.
The radioprotective agent amifostine is a free radical scavenger that can protect cells from the damaging effects of ionising radiation when administered prior to radiation exposure. However, amifostine has also been shown to protect cells from chromosomal mutations when administered after radiation exposure. As apoptosis is a common mechanism by which cells with mutations are removed from the cell population, we investigated whether amifostine stimulates apoptosis when administered after radiation exposure. We chose to study a relatively low dose which is the maximum radiation dose for radiation emergency workers (0.25 Gy) and a high dose relevant to radiotherapy exposures (6 Gy). Mice were administered 400 mg/kg amifostine 30 min before, or 3 h after, whole-body irradiation with 0.25 or 6 Gy X-rays and apoptosis was analysed 3 or 7 h later in spleen and bone marrow. We observed a significant increase in radiation-induced apoptosis in the spleen of mice when amifostine was administered before or after 0.25 Gy X-rays. In contrast, when a high dose of radiation was used (6 Gy), amifostine caused a reduction in radiation-induced apoptosis 3 h post-irradiation in spleen and bone marrow similar to previously published studies. This is the first study to investigate the effect of amifostine on radiation-induced apoptosis at a relatively low radiation dose and the first to demonstrate that while amifostine can reduce apoptosis from high doses of radiation, it does not mediate the same effect in response to low-dose exposures. These results suggest that there may be a dose threshold at which amifostine protects from radiation-induced apoptosis and highlight the importance of examining a range of radiation doses and timepoints.


Sequence motifs of myelin membrane proteins: towards the molecular basis of diseases.
The shortest sequence of amino acids in protein containing functional and structural information is a "motif." To understand myelin protein functions, we intensively searched for motifs that can be found in myelin proteins. Some myelin proteins had several different motifs or repetition of the same motif. The most abundant motif found among myelin proteins was a myristoylation motif. Bovine MAG held 11 myristoylation motifs and human myelin basic protein held as many as eight such motifs. PMP22 had the fewest myristoylation motifs, which was only one; rat PMP22 contained no such motifs. Cholesterol recognition/interaction amino-acid consensus (CRAC) motif was not found in myelin basic protein. P2 protein of different species contained only one CRAC motif, except for P2 of horse, which had no such motifs. MAG, MOG, and P0 were very rich in CRAC, three to eight motifs per protein. The analysis of motifs in myelin proteins is expected to provide structural insight and refinement of predicted 3D models for which structures are as yet unknown. Analysis of motifs in mutant proteins associated with neurological diseases uncovered that some motifs disappeared in P0 with mutation found in neurological diseases. There are 2,500 motifs deposited in a databank, but 21 were found in myelin proteins, which is only 1% of the total known motifs. There was great variability in the number of motifs among proteins from different species. The appearance or disappearance of protein motifs after gaining point mutation in the protein related to neurological diseases was very interesting.


Long Noncoding RNA UCA1 Accelerates Nasopharyngeal Carcinoma Cell Progression By Modulating miR-124-3p/ITGB1 Axis.
Nasopharyngeal carcinoma (NPC) is a common malignant cancer that is distributed particularly in Southeastern Asia. Previous studies have manifested that long noncoding RNA urothelial carcinoma associated 1 (UCA1) was involved in NPC tumorigenesis and metastasis. However, the biological mechanism of UCA1 for NPC cell progression requires further investigation. The expression levels of UCA1, miR-124-3p, integrin beta-1 (ITGB1) were detected by qRT-PCR. Protein expression of ITGB1 was determined by Western blot assay. Cell proliferation, migration and invasion were evaluated by CCK8 and transwell assay, respectively. The interaction between miR-124-3p and UCA1 or ITGB1 was determined by luciferase reporter system, RIP and RNA pull-down assay. Mice model was established by subcutaneously injecting SUNE1 cells stably transfected with sh-UCA1 and sh-NC. The expression of UCA1 was up-regulated in NPC tissues and cells. However, UCA1 knockdown hindered NPC cell growth, migration and invasion. In addition, the interaction between miR-124-3p and UCA1 or ITGB1 was confirmed by luciferase reporter system, RIP and RNA pull-down assay. Besides, miR-124-3p inhibitor abrogated UCA1 silencing-mediated suppression on cell progression in NPC. Moreover, UCA1 accelerated NPC cell progression through modulating ITGB1 via sponging miR-124-3p. In vivo experiments revealed the interference of UCA1-inhibited tumor growth by regulating miR-124-3p/ITGB1 axis. UCA1 acts as an oncogene to promote NPC cell proliferation by up-regulating ITGB1 through suppressing miR-124-3p in vitro and in vivo, providing a potential target for NPC diagnosis and treatment.


The impact of eliminating the global illicit cigarette trade on health and revenue.
The purpose of this study was to update global estimates of the illicit cigarette trade, based on recent data, and estimate how many lives could be saved by eliminating it and how much revenue governments would gain. Our estimates of illicit market share are based on formal and informal sources. Our method for estimating the effect of eliminating the illicit trade on tobacco related deaths is based on West et al. with some minor modifications, and involves calculating the size of the illicit cigarette trade; the effect of eliminating it on the price of cigarettes and thus on consumption; the revenue governments are losing because of it; and the number of tobacco-related premature deaths that would be avoided if this illicit trade were eliminated. According to available estimates, the size of the illicit trade varies between countries from 1% to about 40-50% of the market, 11.6% globally, 16.8% in low-income and 9.8% in high-income countries. The total lost revenue is about $40.5 billion a year. If this illicit trade were eliminated governments would gain at least $31.3 billion a year, and from 2030 onwards more than 164,000 premature deaths a year would be avoided, the vast majority in middle- and low-income countries. The burden of deaths and lost revenue caused by the illicit cigarette trade falls disproportionately on low- and middle-income countries. Eliminating this trade would avoid millions of premature deaths, and recover billions of dollars for governments.


Theory and experimental verifications of the resonator Q and equivalent electrical parameters due to viscoelastic and mounting supports losses.
A novel analytical/numerical method for calculating the resonator Q and its equivalent electrical parameters due to viscoelastic, conductivity, and mounting supports losses is presented. The method presented will be quite useful for designing new resonators and reducing the time and costs of prototyping. There was also a necessity for better and more realistic modeling of the resonators because of miniaturization and the rapid advances in the frequency ranges of telecommunication. We present new 3-D finite elements models of quartz resonators with viscoelasticity, conductivity, and mounting support losses. The losses at the mounting supports were modeled by perfectly matched layers (PMLs). A previously published theory for dissipative anisotropic piezoelectric solids was formulated in a weak form for finite element (FE) applications. PMLs were placed at the base of the mounting supports to simulate the energy losses to a semi-infinite base substrate. FE simulations were carried out for free vibrations and forced vibrations of quartz tuning fork and AT-cut resonators. Results for quartz tuning fork and thickness shear AT-cut resonators were presented and compared with experimental data. Results for the resonator Q and the equivalent electrical parameters were compared with their measured values. Good equivalences were found. Results for both low- and high-Q AT-cut quartz resonators compared well with their experimental values. A method for estimating the Q directly from the frequency spectrum obtained for free vibrations was also presented. An important determinant of the quality factor Q of a quartz resonator is the loss of energy from the electrode area to the base via the mountings. The acoustical characteristics of the plate resonator are changed when the plate is mounted onto a base substrate. The base affects the frequency spectra of the plate resonator. A resonator with a high Q may not have a similarly high Q when mounted on a base. Hence, the base is an energy sink and the Q will be affected by the shape and size of this base. A lower-bound Q will be obtained if the base is a semi-infinite base because it will absorb all acoustical energies radiated from the resonator.


Plasmid-located extended-spectrum β-lactamase gene blaROB-2 in Mannheimia haemolytica.
To identify and analyse the first ESBL gene from Mannheimia haemolytica. Susceptibility testing was performed according to CLSI. Plasmids were extracted via alkaline lysis and transferred by electrotransformation. The sequence was determined by WGS and confirmed by Sanger sequencing. The M. haemolytica strain 48 showed high cephalosporin MICs. A single plasmid, designated pKKM48, with a size of 4323 bp, was isolated. Plasmid pKKM48 harboured a novel blaROB gene, tentatively designated blaROB-2, and was transferred to Pasteurella multocida B130 and to Escherichia coli JM107. PCR assays and susceptibility testing confirmed the presence and activity of the blaROB-2 gene in the P. multocida and in the E. coli recipient carrying plasmid pKKM48. The transformants had high MICs of all β-lactam antibiotics. An ESBL phenotype was seen in the E. coli transformant when applying the CLSI double-disc confirmatory test for E. coli. The blaROB-2 gene from plasmid pKKM48 differed in three positions from blaROB-1, resulting in two amino acid exchanges and one additional amino acid in the deduced β-lactamase protein. In addition to blaROB-2, pKKM48 harboured mob genes and showed high similarity to other plasmids from Pasteurellaceae. This study described the first ESBL gene in Pasteurellaceae, which may limit the therapeutic options for veterinarians. The transferability to Enterobacteriaceae with the functional activity of the gene in the new host underlines the possibility of the spread of this gene across species or genus boundaries.


Neutralization studies with Marek's disease virus and turkey herpesvirus.
Use of Marek's disease virus (MDV) in a neutralization test presents several problems, which are described, making this potentially useful test difficult. To obviate these difficulties, a plaque reduction test has been designed based on cross-neutralization of turkey herpesvirus (HVT) by serum-neutralizing MDV. The technique for such a neutralization test is outlined. Kinetics of development of neutralizing antibodies in chickens inoculated with HVT and MDV are described. The neutralization test can be used to evaluate viability of HVT vaccines and the possible role of neutralizing antibodies in the protection afforded by vaccination against MDV-induced tumors.


Influence of cell position relative to planar alpha-particle sources on survival and preneoplastic transformation of primary rat tracheal epithelial cells.
Rat tracheal epithelial cells exposed directly on planar 210Po sources exhibited exponential cell killing; however, no significant increase in induction of preneoplastic transformation was observed over a range of alpha-particle fluences (0.017-0.050 micron-2). In contrast, up to 10-fold increases in frequencies of preneoplastic transformants, above control levels, were observed after exposure of rat tracheal epithelial cells to similar alpha-particle fluences on 238Pu and 241Am sources. Two alternative hypotheses are evaluated as an explanation for this apparent difference in the biological effect of alpha particles emitted from different sources: (a) possible interactions between effects produced by alpha particles and by low-energy photons, which occur with 238Pu and 241Am but not with 210Po; and (b) the influence of spatial relationships between exposed cells and the surface of the planar source. The data suggest that cell-to-source spatial relationships affect both survival and transformation markedly.


Increased waist size and weight in relation to consumption of Areca catechu (betel-nut); a risk factor for increased glycaemia in Asians in east London.
Type 2 diabetes is commoner in Asians than Caucasians. Many nitrosamines are diabetogenic, causing both type 2 and type 1 diabetes. Of CD1 mice fed with betel-nut or associated nitrosamines 8.5% develop glucose intolerance with marked obesity. Glycaemia and anthropometric risk markers for type 2 diabetes were therefore examined in relation to betel usage in 993 'healthy' Bangladeshis by one bilingual research-worker (N.M.). Of these, 12% had known diabetes. A further 145 of 187 subjects 'at-risk' of diabetes (spot glucose > 6.5 mmol/l < 2 h after food, or > 4.5 mmol/l > 2 h after food) had a second blood glucose sample taken; sixty-one were confirmed as 'at-risk', and had an oral glucose tolerance test; nine new diabetics were identified. Multiple regression analysis showed that spot blood glucose values decreased with time after eating (P = 0.0005) and increased independently with waist size (P = 0.0005) and age (P = 0.0005) without relationships to other aspects of the diet, season or smoking. Waist size was strongly related to betel usage independent of other factors such as age. Betel use interacted with sex, relating to increasing glycaemia only in females. Since waist and age were the major markers of increasing glycaemia we suggest that betel chewing, a habit common to about 10% of the world population (more than 200 million people) may contribute to the risk of developing type 2 diabetes mellitus.


Expression of class I O-methyltransferase in healthy and TMV-infected tobacco.
Tobacco possesses two distinct classes of O-methyltransferases (OMTs; S-adenosyl-L-methionine:o-diphenol O-methyltransferases; EC 220.127.116.11). Here we report on the cloning and the expression pattern of the class I OMT that is specifically involved in lignin biosynthesis. Near-full-length cDNAs have been isolated from tobacco libraries constructed from leaf and stem poly(A)+ RNA. Sequence analysis demonstrated that the OMT I clones derived from two different mRNA species. The two types of OMT I mRNA were reverse transcribed from total RNA and the cDNAs were amplified by polymerase chain reaction and characterized by restriction analysis. The same proportion of the two transcripts was measured in stem tissue of healthy plants and in leaves reacting hypersensitively to tobacco mosaic virus, indicating a coordinate expression of the two OMT I genes. Consistently, genomic hybridization indicated the presence of two OMT I genes in the amphidiploid genome of tobacco. The pattern of expression of OMT I genes was studied by in situ mRNA hybridization. In stem, petiole, and root tissues, OMT I genes were found to be specifically expressed in vascular cells and epidermis. In healthy leaves OMT I mRNA was only detected in vascular strands, whereas, in leaves bearing tobacco mosaic virus-induced necrotic lesions, a particularly strong accumulation of the labeling was also localized in the upper and lower epidermis.


Initial clinical evaluation of a new Rocky Mountain spotted fever vaccine of tissue culture origin.
Currently available Rocky Mountain spotted fever (RMSF) vaccines are relatively ineffective in preventing infections in humans and contain considerable amounts of contaminating egg protein. A new formalin-inactivated vaccine was prepared by sucrose density gradient centrifugation of the Sheila Smith strain of Rickettsia rickettsii grown in chick embryo cell tissue culture. The new product has greater protective immunogenicity in rheusus monkeys and guinea pigs than commercial vaccines. Six volunteers without immunologic evidence of prior exposure to RMSF received from one to three inoculations of the vaccine diluted 1:10, and there were two benign local reactions. Titers of antibody (determined by microagglutination and indirect fluorescence techniques) increased in all recipients as did lymphocyte tranformation responses to specific rickettsial antigen. Ten volunteers were immunized twice with vaccine diluted 1:3; there were no local reactions, and immunologic responses were similar to those in the six volunteers in the first group. The proper dosage and immunization schedule for the vaccine must be determined in further studies.


Triple Immunofluorescence Evidence for the Coexistence of Acetylcholine, Enkephalins and Calcitonin Gene-related Peptide Within Efferent (Olivocochlear) Neurons of Rats and Guinea-pigs.
The efferent (olivocochlear) nerve supply to the cochlea is subdivided into a lateral and a medial innervation according to several criteria, e.g. locus of origin in the superior olivary complex and type of synaptic connections established in the organ of Corti. We have used a triple immunofluorescence colocalization approach to determine whether putative cholinergic neurons from the lateral innervation contain both metenkephalin and calcitonin gene-related peptide (CGRP), and whether those from the medial innervation also contain CGRP. About 80% of the choline acetyltransferase (ChAT)-like immunostained lateral efferent neurons within the lateral superior olive were CGRP- and metenkephalin-like immunostained. In the organ of Corti, colocalization of the three antigens within the inner spiral bundle was also found. This bundle contains the lateral efferent synapses, with the dendrites of the primary auditory neurons innervating the sensory inner hair cells. Most of the medial efferent neurons in the ventral nucleus of the trapezoid body were only immunoreactive for ChAT. However, in the rostral part of the nucleus, a minority of ChAT-like immunostained neurons were also CGRP-like immunostained. None of the ChAT-like immunostained medial efferent neurons presented metenkephalin-like immunostaining. In agreement with these brainstem data, partial colocalization of the ChAT- and CGRP-like immunostaining and a lack of metenkephalin immunoreactivity was noted below the sensory outer hair cells, which are the synaptic targets of medial efferent terminals in the organ of Corti. This distinction in the coexistence pattern of the two efferent innervations probably reflects distinct modes of action for acetylcholine in the cochlea. In one case, the effects of acetylcholine on the primary auditory neurons innervating the inner hair cells may require balanced modulation by metenkephalin and CGRP. In the other case, modulation of the effects of acetylcholine on the outer hair cells by neuropeptides would be less critical.


Glucocorticoid receptor expression in the spinal cord after traumatic injury in adult rats.
Methylprednisolone (MP), a glucocorticoid, is the only effective therapeutic agent used in the clinical treatment of acute spinal cord injury (SCI). MP given within 8 hr after SCI significantly improves neurological function. Although the glucocorticoid receptor (GR) is suggested to mediate MP actions, limited knowledge is available on its expression and possible function after SCI. Presently, the expression of GR was studied in a weight-drop SCI model in adult rats. Immunohistochemistry and Western blot analysis revealed an increase in GR protein expression as early as 15 min after injury. GR expression sharply increased at 4 hr (22-fold), peaked at 8 hr (56-fold), rapidly declined at 1 d, and returned to the baseline level at and after 3 d. During its peak expression, GR was localized in neural somata and dendrites but not in axons and their terminals. GR immunoreactivity was also found in oligodendrocytes and astrocytes. Interestingly, other cell types, such as endothelial cells, were GR-negative. An increase in the binding activity of nuclear proteins to the glucocorticoid responsive element was also observed after SCI, demonstrating a functional element of GR activation. Finally, colocalization of GR and tumor necrosis factor alpha (TNF-alpha), an inflammatory cytokine, was observed in neurons and glial cells, consistent with MP regulation of TNF-alpha in this model. Thus, the transient expression of high levels of GR after SCI may provide new insights into the anti-inflammatory action of MP.


Euclid's Random Walk: Developmental Changes in the Use of Simulation for Geometric Reasoning.
Euclidean geometry has formed the foundation of architecture, science, and technology for millennia, yet the development of human's intuitive reasoning about Euclidean geometry is not well understood. The present study explores the cognitive processes and representations that support the development of humans' intuitive reasoning about Euclidean geometry. One-hundred-twenty-five 7- to 12-year-old children and 30 adults completed a localization task in which they visually extrapolated missing parts of fragmented planar triangles and a reasoning task in which they answered verbal questions about the general properties of planar triangles. While basic Euclidean principles guided even young children's visual extrapolations, only older children and adults reasoned about triangles in ways that were consistent with Euclidean geometry. Moreover, a relation beteen visual extrapolation and reasoning appeared only in older children and adults. Reasoning consistent with Euclidean geometry may thus emerge when children abandon incorrect, axiomatic-based reasoning strategies and come to reason using mental simulations of visual extrapolations.


Human GABA, Receptor αl and α3 Subunits Genes and Alcoholism.
γ-Aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the brain. GABA effects are largely mediated by binding to the postsynaptic GABAA receptor, causing the opening of an integral chloride-ion channel. The GABAA antagonists picrotoxin and bicuculline reduce some ethanol-induced behaviors, such as motor impairment, sedation, and hypnosis. The role of this receptor in alcoholism is further supported by effective alleviation of alcohol withdrawal symptoms by GABAA agonists. To determine the role of the GABA, receptor (GABR) genes in the development of alcoholism, we have used α1 and α3 simple sequence repeat polymorphisms in a sample of unrelated alcoholics, alcoholic probands with both parents, and psychiatrically normal controls. For the GABRα1 gene, the differences between allele frequencies, when all alleles were compared together, were not significant between total alcoholics, subtypes of alcoholics, and normal controls. However, for GABRα3 , the differences between total alcoholics and normal controls were significant when all alleles were compared together. The differences between subtypes of alcoholics and normal controls were not significant. The results of haplotype relative risk analysis for both genes, GABRα1 and GABRα3 , were also negative. It is possible that the sample size in the haplotype relative risk is too small to have power to detect the differences in transmitted versus nontransmitted alleles. There is a need for a replication study in a large family sample, that will allow haplotype relative risk or affected sib-pair analysis.


High remnant lipoprotein predicts recurrent cardiovascular events on statin treatment after acute coronary syndrome.
After acute coronary syndrome (ACS), there is a high risk of recurrent cardiovascular events. Triglyceride-rich lipoproteins influence residual cardiovascular risk in patients taking statin. This study examined the predictive value of remnant lipoprotein level for secondary cardiovascular events in patients treated with statins after ACS. A total of 190 patients treated with statins after ACS were enrolled in the study. The serum level of remnant lipoproteins (remnant-like lipoprotein particle cholesterol; RLP-C) was measured using an immunoseparation method. All the patients were followed prospectively for a maximum period of 70 months or until the occurrence of one of the following events: cardiac death, non-fatal myocardial infarction, unstable angina requiring unplanned coronary revascularization, or ischemic stroke. During the follow-up period, 42 patients had a secondary event. Multivariate Cox analysis showed that a high level of RLP-C (≥5.4 mg/dl; determined on receiver operating characteristic curve analysis) was a significant risk factor for secondary events, independent of conventional risk factors (hazard ratio, 2.94; 95% confidence interval: 1.40-6.18; P<0.01). The addition of high RLP-C to traditional risk factors enhanced net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI, 0.66, P=0.0003; and IDI, 0.08, P=0.0002). RLP-C is useful for risk assessment of secondary cardiovascular events in patients treated with statins after ACS.


Relationship of active trigger points with related disability and anxiety in people with tension-type headache.
To investigate the differences in the presence of trigger points (TrPs) and their association with headache-related disability and mood disorders in people with frequent episodic tension-type headache (TTH) (FETTH) and chronic TTH (CTTH). One hundred twenty-two individuals with TTH participated. Clinical features of headache (i.e., intensity, duration, and frequency) were recorded on a headache diary. Headache-related disability was assessed with the Headache Disability Inventory, trait and state anxiety levels with State-Trait Anxiety Inventory, and depression with the Hospital Anxiety and Depression Scale. TrPs were bilaterally explored in the temporalis, masseter, suboccipital, upper trapezius, splenius capitis, and sternocleidomastoid muscles. Sixty-two (51%) patients were classified as FETTH, whereas 60 (49%) were classified as CTTH. Individuals with CTTH showed higher burden of headache and depression than FETTH (P < 0.001). Subjects with FETTH showed similar number of TrPs (total number: 5.9 ± 3.1, active TrPs: 4.7 ± 2.5, and latent TrPs: 1.2 ± 1.9) than those with CTTH (total number: 5.7 ± 3.2, active TrPs: 4.2 ± 3.0, and latent TrPs: 1.5 ± 1.8). The number of active TrPs was significantly associated with the burden of headache (r = 0.189; P = 0.037) and trait anxiety (r = 0.273; P = 0.005): the higher the number of active TrPs, the greater the physical burden of headache or the more the trait anxiety level. No association with the depression was observed. The presence of active TrPs in head and neck/shoulder muscles was similar between individuals with FETTH and CTTH and associated with the physical burden of headache and trait anxiety levels independently of the subgroup of TTH.


Regulation and legislation of the dying process: views of health care professionals.
Because of radical changes that have been effected by medical advances in the process of dying, it is now frequently necessary for patients to make an explicit decision on whether to forego life-prolonging medical therapies. We report physicians' and nurses' perceptions of the need for, feasibility of, and value of regulations and legislation to govern the dying process. In-depth, semistructured interviews were conducted with a sample of 20 physicians and 20 nurses at a large teaching hospital. There was little unanimity in their attitudes toward whether it is advisable or feasible to devise adequate legal safeguards for physicians and nurses who assist patients to hasten their deaths. Some believed such regulations were needed, but others believed they would seriously compromise good patient care. There was also disagreement as to who should develop guidelines. There was, however, clear opposition among most participants to the involvement of lawyers in the process of clarifying the content of regulations and legislation on the dying process.


[Calculation of the dose of sodium bicarbonate for correcting metabolic acidosis in surgery with circulation arrest and deep hypothermia].
The study was aimed at detecting the factors which determine the amount of 7% sodium bicarbonate solution needed to correct metabolic acidosis in patients subjected to repair surgery on the aorta involving long arrest of circulation under conditions of deep hypothermia. The total dose of 7% sodium bicarbonate solution was calculated as the sum of volumes of this solution needed to neutralize certain concentrations of underoxidized metabolites and BE. Accumulation of acid metabolites in tissues is caused by ineffective compensation of energy expenditure during warming of a patient after circulation arrest and deep hypothermia. After reperfusion injury to tissues, the release of these metabolites into the blood and further neutralization are appreciably slower during such operations than during other cardiovascular bypass interventions. That is why the routine method for calculating the dose of 7% sodium bicarbonate solution for correcting metabolic acidosis is not adequate in cases with abnormal body temperature. Estimation of the dose with consideration for venous blood temperature and pO2 is more correct. An algorithm of calculation is proposed.


Polymer monoliths with exchangeable chemistries: use of gold nanoparticles as intermediate ligands for capillary columns with varying surface functionalities.
Newly developed porous polymer monolithic capillary columns modified with gold nanoparticles coated with exchangeable functionalities allow easy switching of separation modes by a simple ligand exchange process. These columns are prepared from a poly(glycidyl methacrylate-co-ethylene dimethacrylate) monolith through reaction of its epoxide moieties with cysteamine to afford a monolith rich in surface thiol groups. Gold nanoparticles prepared via in situ reduction of chloroauric acid within the column become attached to the surface of the pores of the monolith. Alternatively, a solution of colloidal gold nanoparticles can be pumped through the thiol modified column to achieve their attachment. While the first approach is faster, it affords a lower coverage of nanoparticles than the second method, while both methods preserve the excellent hydrodynamic properties that are typical of the monolithic columns. Functionalization of the surface of the bound gold nanoparticles is then carried out using low molecular weight thiol-containing surface ligands. The dynamic nature of the bond between gold and these surface ligands enables the replacement of one surface ligand by another through a simple solution exchange process. This novel approach expands the application range of monoliths as a single column can now be used in different separations modes. Applications of the columns with exchangeable chemistries are demonstrated with the capillary electrochromatographic separation of peptides and the nano-high-pressure liquid chromatography (HPLC) separation of proteins in both reversed phase and ion exchange modes.


Relationships between obsessive-compulsive symptomatology and severity of psychosis in schizophrenia: a systematic review and meta-analysis.
The presence of obsessive-compulsive symptoms (OCS) or obsessive-compulsive disorder (OCD) is common in patients with schizophrenia. The impact of OCS and OCD on severity of psychotic symptoms has been assessed in several past studies yielding inconclusive results. In this report, we aim to integrate the findings of prior studies by means of a systematic review followed by a meta-analysis. A search of studies in PubMed (from 1950 to September 2006) and PsycINFO (from 1966 to September 2006) databases was performed to assess the influence of OCS and OCD on severity of psychotic symptoms in patients with schizophrenia using as syntax ("schizophrenia" OR "psychosis" OR "psychotic") AND ("obsessive-compulsive disorder" OR "OCD" OR "obsession*" OR "compulsion*" OR "obsessiv*" OR "compulsiv*"). Reference lists of all retrieved articles were also hand-searched. Twenty-three studies were included in the systematic review, and 18 articles provided usable data for the meta-analysis. All relevant data were extracted using a standardized report form by 2 investigators. Effect sizes and pooled estimates were calculated. Data were analyzed separately for studies using an OCS or OCD definition. The presence of OCS was significantly associated with greater severity of global psychotic symptoms (standardized mean difference [95% CI], 0.39 [0.14 to 0.64]), positive psychotic symptoms (0.28 [0.00 to 0.56]), and negative psychotic symptoms (0.36 [0.11 to 0.62]). In contrast, no differences in the severity of global psychotic symptoms (0.19 [-0.14 to 0.51]), positive psychotic symptoms (-0.01 [-0.20 to 0.19]), or negative psychotic symptoms (-0.11 [-0.30 to 0.08]) were found for the OCD versus non-OCD subgroups. This first meta-analysis revealed that the presence of obsessive-compulsive symptoms in schizophrenia is associated with higher global, positive, and negative psychotic symptoms. This association was not found when a categorical definition of obsessive-compulsive disorder was used.


Amphotropic proviral envelope sequences are absent from the Mus germ line.
We derived an amphotropic murine leukemia virus (MuLV) type-specific probe for use in Southern blot hybridizations with cloned and genomic DNAs. A 133-base-pair RsaI-RsaI fragment from the 5' env region of the amphotropic viral isolate 4070A was subcloned into M13mp18 and radiolabeled in vitro. The probe detected the proviral DNAs in mink cells infected with seven different amphotropic MuLV isolates. The probe did not cross hybridize with the DNAs of molecular clones of ecotropic, mink cell focus-forming, or xenotropic MuLVs; nor did it anneal to the proviral DNAs of four xenotropic or six mink cell focus-forming viral isolates grown in mink cells. DNAs of 12 inbred laboratory mouse strains and more than 15 different wild mouse species and subspecies were examined for the presence of endogenous amphotropic env-related fragments. Amphotropic env-related sequences were found only in the DNAs of wild mice trapped in southern California in an area previously shown to harbor mice producing infectious amphotropic virus. Restriction enzyme analyses of DNAs from these mice showed that amphotropic sequences were not present as germ line copies but were the result of congenital or horizontal infection or both in this population. The DNAs of 11 various mammalian and avian species, including both natural predators of mice and squabs from the farms with virus-positive mice, lacked amphotropic envelope-related sequences.


Neuromuscular and psychomotor function in elderly subjects who fall and the relationship with vitamin D status.
Vitamin D and calcium supplementation significantly reduces the incidence of fractures. Evidence suggests vitamin D deficiency impairs neuromuscular function, causing an increase in falls and thereby fractures. The relationship between vitamin D, functional performance, and psychomotor function in elderly people who fall was examined in a prospective cross-sectional study. Patients were recruited from a falls clinic and stratified according to serum 25-hydroxyvitamin-D levels (25OHD): group 1, 25OHD < 12 microg/liter; group 2 25OHD, 12-17 microg/liter; and group 3, 25OHD > 17 microg/liter. Healthy elderly volunteers with 25OHD > 17 microg/liter comprised group 4 (n = 20/group). Measures included aggregate functional performance time (AFPT, seconds), isometric quadriceps strength (Newtons), postural sway (degrees), and choice reaction time (CRT, seconds). Serum bone biochemistry, 25OHD, and parathyroid hormone levels were measured. Patients who fell had significantly impaired functional performance, psychomotor function, and quadriceps strength compared with healthy subjects (AFPT: 51.0 s vs. 32.8 s,p < 0.05; CRT: 1.66 s vs. 0.98 s,p < 0.05; strength: 223N vs. 271N, t = 2.35, p = 0.02). Group 1 had significantly slower AFPT (66.0 s vs. 44.8 s, t = 4.15, p < 0.05) and CRT (2.37 s vs. 0.98 s, t = 3.59, p < 0.05) than groups 2 and 3. Group 1 had the greatest degree of postural sway and the weakest quadriceps strength, although this did not reach significance. Multivariate analysis revealed 25OHD as an independent variable for AFPT, CRT, and postural sway. PTH was an independent variable for muscle strength. Older people who fall have impaired functional performance, psychomotor function, and muscle strength. Within this group, those with 25OHD < 12 microg/liter are the most significantly affected.


A metabonomic study of transgenic maize (Zea mays) seeds revealed variations in osmolytes and branched amino acids.
The aim of the research was to investigate metabolic variations associated with genetic modifications in the grains of Zea mays using metabonomic techniques. With this in mind, the non-targeted characteristic of the technique is useful to identify metabolites peculiar to the genetic modification and initially undefined. The results obtained showed that the genetic modification, introducing Cry1Ab gene expression, induces metabolic variations involving the primary nitrogen pathway. Concerning the methodological aspects, the experimental protocol used has been applied in this field for the first time. It consists of a combination of partial least square-discriminant analysis and principal component analysis. The most important metabolites for discrimination were selected and the metabolic correlations linking them are identified. Principal component analysis on selected signals confirms metabolic variations, highlighting important details about the changes induced on the metabolic network by the presence of a Bt transgene in the maize genome.


Magnesium Fertilizer-Induced Increase of Symbiotic Microorganisms Improves Forage Growth and Quality.
Magnesium (Mg) plays important roles in photosynthesis and protein synthesis; however, latent Mg deficiencies are common phenomena that can influence food quality. Nevertheless, the effects of Mg fertilizer additions on plant carbon (C):nitrogen (N):phosphorus (P) stoichiometry, an important index of food quality, are unclear and the underlying mechanisms unexplored. We conducted a greenhouse experiment using low-Mg in situ soil without and with a gradient of Mg additions to investigate the effect of Mg fertilizer on growth and stoichiometry of maize and soybean and also measure these plants' main symbiotic microorganisms: arbuscular mycorrhizal fungi (AMF) and rhizobium, respectively. Our results showed that Mg addition significantly improved both plant species' growth and also increased N and P concentrations in soybean and maize, respectively, resulting in low C:N ratio and high N:P ratio in soybean and low C:P and N:P ratios in maize. These results presumably stemmed from the increase of nutrients supplied by activation-enhanced plant symbiotic microorganisms, an explanation supported by statistically significant positive correlations between plant stoichiometry and plants' symbiotic microorganisms' increased growth with Mg addition. We conclude that Mg supply can improve plant growth and alter plant stoichiometry via enhanced activity of plant symbiotic microorganisms. Possible mechanisms underlying this positive plant-soil feedback include an enhanced photosynthetic product flow to roots caused by adequate Mg supply.


Glioma: Novel considerations and treatment modalities.
Glioma tumors often evade traditional cancer treatments and quickly invade healthy brain tissue. Current clinical perspective focuses on the invasiveness of glioma cells which follow distinct anatomic structures within the central nervous system. Advances in magnetic resonance imaging have made it the procedure of choice for identifying brainstem gliomas and classifying them anatomically. Etiologic considerations include adhesion, migration, invasiveness, cell proliferation, angiogenesis and neurotoxin release. This review examines various novel interventions used in treating these deadly growths to prolong life. Recent interventional studies, detecting the cancer's unique characteristics, include the mechanisms that help it survive and spread throughout the brain. Current therapies include those that target glioma cells only, limit the spread of the cancer or block molecules which sustain the tumor. A variety of specific agents, general chemotherapy, radiotherapy and surgery are discussed.


Implementation outcomes of the national scale up of chlorhexidine cord cleansing in Bangladesh's public health system.
Chlorhexidine (CHX) cleansing of the umbilical cord stump is an evidence-based intervention that reduces newborn infections and is recommended for high-mortality settings. Bangladesh is one of the first countries to adopt and scale up CHX nationally. This study evaluates the implementation outcomes for the CHX scale up in Bangladesh and identifies and describes key milestones and processes for the scale up. We adapted the RE-AIM framework for this study, incorporating the WHO/ExpandNet model of Scale Up. Adoption and incorporation milestones were assessed through program documents and interviews with national stakeholders (n = 25). Provider training records served as a measure of reach. Implementation was assessed through a survey of readiness to provide CHX at public facilities (n = 4479) and routine data on the proportion of all live births at public facilities (n = 813 607) that received CHX from December 2016 to November 2017. Six rounds of a rolling household survey with recently-delivered women in four districts (n = 6000 to 8000 per round) measured the effectiveness and maintenance of the scale up in increasing population-level coverage of CHX in those districts. More than 80 000 providers, supervisors, and managers across all 64 districts received a half-day training on CHX and essential newborn care between July 2015 and September 2016. Seventy-four percent of facilities had at least 70% of maternal and newborn health providers with CHX training, while only 46% had CHX in stock on the day of the assessment. The provision of CHX to newborns delivered at facilities steadily increased from 15 059 newborns (24%) in December 2016 to 71 704 (72%) in November 2017. In the final household survey of four districts, 33% of newborns were reported to receive CHX, and babies delivered at public facilities had 5.04 times greater odds (95% CI = 4.45, 5.72) of receiving CHX than those delivered at home. The scale up of CHX in Bangladesh achieved sustained national implementation in public health facilities. Institutionalization barriers, such as changes to supply logistics systems, had to be addressed before expansion was achieved. For greater public health impact, implementation must reach deliveries that take place at home and in the private sector.


Clinical characteristics and outcomes of obstetric patients admitted to the Intensive Care Unit: a 10-year retrospective review.
To review the characteristics and health-related quality-of-life outcomes of obstetric patients admitted to the Intensive Care Unit. Retrospective cohort study. A regional hospital in Hong Kong. Consecutive obstetric patients admitted to the Intensive Care Unit of Pamela Youde Nethersole Eastern Hospital from January 1998 to December 2007. Fifty obstetric patients (mean [standard deviation] age, 31 [6] years; mean gestational age, 34 [9] weeks) were analysed. The most common obstetric cause of admission was postpartum haemorrhage (n=19, 38%), followed by pregnancy-associated hypertension (n=7, 14%). The commonest non-obstetric cause of admission was sepsis (n=7, 14%). The commonest intervention was arterial line insertion (n=33, 66%) and mechanical ventilation (n=29, 58%). Maternal mortality was 6% (n=3), while the perinatal mortality rate was 8% (n=4). The average Short Form-36 Health Survey scores of our patients were lower than the norm for the Hong Kong population of the same age and gender. Postpartum haemorrhage and pregnancy-associated hypertension were the most common causes of admission to our Intensive Care Unit. Overall mortality was low. Long-term health-related quality of life in discharged patients was lower than the norm of the Hong Kong population. Appropriate antenatal care is important in preventing obstetric complications. Continued psychosocial follow-up of discharged patients has to be implemented.


Correlates of engaging in survival sex among homeless youth and young adults.
Using a sample of 1,625 homeless youth and young adults aged 10 to 25 from 28 different states in the United States, this study examines the correlates of having engaged in survival sex. Findings suggest that differences exist based on demographic variables (gender, age, race, and sexual orientation), lifetime drug use (inhalants, Valium™, crack cocaine, alcohol, Coricidin™, and morphine), recent drug use (alcohol, ecstasy, heroin, and methamphetamine), mental health variables (suicide attempts, familial history of substance use, and having been in substance abuse treatment), and health variables (sharing needles and having been tested for HIV). In addition to replicating previous findings, this study's findings suggest that African American youth; gay, lesbian, or bisexual youth; and youth who had been tested for HIV were significantly more likely to have engaged in survival sex than White, heterosexual youth, and youth who had not been tested for HIV, respectively. Implications for interventions with youth and suggestions for future research are discussed.