MMDiff: quantitative testing for shape changes in ChIP-Seq data sets.
Cell-specific gene expression is controlled by epigenetic modifications and transcription factor binding. While genome-wide maps for these protein-DNA interactions have become widely available, quantitative comparison of the resulting ChIP-Seq data sets remains challenging. Current approaches to detect differentially bound or modified regions are mainly borrowed from RNA-Seq data analysis, thus focusing on total counts of fragments mapped to a region, ignoring any information encoded in the shape of the peaks. Here, we present MMDiff, a robust, broadly applicable method for detecting differences between sequence count data sets. Based on quantifying shape changes in signal profiles, it overcomes challenges imposed by the highly structured nature of the data and the paucity of replicates.We first use a simulated data set to compare the performance of MMDiff with results obtained by four alternative methods. We demonstrate that MMDiff excels when peak profiles change between samples. We next use MMDiff to re-analyse a recent data set of the histone modification H3K4me3 elucidating the establishment of this prominent epigenomic marker. Our empirical analysis shows that the method yields reproducible results across experiments, and is able to detect functional important changes in histone modifications. To further explore the broader applicability of MMDiff, we apply it to two ENCODE data sets: one investigating the histone modification H3K27ac and one measuring the genome-wide binding of the transcription factor CTCF. In both cases, MMDiff proves to be complementary to count-based methods. In addition, we can show that MMDiff is capable of directly detecting changes of homotypic binding events at neighbouring binding sites. MMDiff is readily available as a Bioconductor package. Our results demonstrate that higher order features of ChIP-Seq peaks carry relevant and often complementary information to total counts, and hence are important in assessing differential histone modifications and transcription factor binding. We have developed a new computational method, MMDiff, that is capable of exploring these features and therefore closes an existing gap in the analysis of ChIP-Seq data sets.


Mapping of genomic segments of influenza B virus strains by an oligonucleotide microarray method.
Similar to other segmented RNA viruses, influenza viruses can exchange genome segments and form a wide variety of reassortant strains upon coreplication within a host cell. Therefore, the mapping of genome segments of influenza viruses is essential for understanding their phenotypes. In this work, we have developed an oligonucleotide microarray hybridization method for simultaneous genotyping of all genomic segments of two highly homologous strains of influenza B virus. A few strain-specific oligonucleotide probes matching each of the eight segments of the viral genomes of the B/Beijing/184/93 and B/Shangdong/7/97 strains were hybridized with PCR-amplified fluorescently labeled single-stranded DNA. Even though there were a few mismatches among the genomes of the studied virus strains, microarray hybridization showed highly significant and reproducible discrimination ability and allowed us to determine the origins of individual genomic segments in a series of reassortant strains prepared as vaccine candidates. Additionally, we were able to detect the presence of at least 5% of mixed genotypes in virus stocks even when conventional sequencing methods failed, for example, for the NS segment. Thus, the proposed microarray method can be used for (i) rapid and reliable genome mapping of highly homologous influenza B viruses and (ii) extensive monitoring of influenza B virus reassortants and the mixed genotypes. The array can be expanded by adding new oligoprobes and using more quantitative assays to determine the origin of individual genomic segments in series of reassortant strains prepared as vaccine candidates or in mixed virus populations.


Prognostic and Genomic Analysis of Proteasome 20S Subunit Alpha (PSMA) Family Members in Breast Cancer.
The complexity of breast cancer includes many interacting biological processes, and proteasome alpha (PSMA) subunits are reported to be involved in many cancerous diseases, although the transcriptomic expression of this gene family in breast cancer still needs to be more thoroughly investigated. Consequently, we used a holistic bioinformatics approach to study the PSMA genes involved in breast cancer by integrating several well-established high-throughput databases and tools, such as cBioPortal, Oncomine, and the Kaplan-Meier plotter. Additionally, correlations of breast cancer patient survival and PSMA messenger RNA expressions were also studied. The results demonstrated that breast cancer tissues had higher expression levels of PSMA genes compared to normal breast tissues. Furthermore, PSMA2, PSMA3, PSMA4, PSMA6, and PSMA7 showed high expression levels, which were correlated with poor survival of breast cancer patients. In contrast, PSMA5 and PSMA8 had high expression levels, which were associated with good prognoses. We also found that PSMA family genes were positively correlated with the cell cycle, ubiquinone metabolism, oxidative stress, and immune response signaling, including antigen presentation by major histocompatibility class, interferon-gamma, and the cluster of differentiation signaling. Collectively, these findings suggest that PSMA genes have the potential to serve as novel biomarkers and therapeutic targets for breast cancer. Nevertheless, the bioinformatic results from the present study would be strengthened with experimental validation in the future by prospective studies on the underlying biological mechanisms of PSMA genes and breast cancer.


The effects of gender difference on monocrotaline-induced pulmonary hypertension in rats.
The present study aimed to compare the effect of gender difference on hemodynamic consequences in the development of monocrotaline (MCT)-induced pulmonary hypertension in rat. The effect of antioxidant enzyme systems on the development of pulmonary hypertension mediated by the phytotoxin MCT and the effect of gender on these antioxidant systems were also investigated. For this purpose, the right ventricular pressures (RVPs) and right ventricular/heart weight (HW) ratios were compared between groups and the glutathione (GSH) level and superoxide dismutase (SOD), catalase (CAT) and glutathione-S-transferase (GST) activities were determined in lung and liver tissue samples of rats. RVP and right ventricular/HW ratios significantly increased in the MCT group compared to the control group. In the MCT group, RVP was significantly higher in males than females. MCT-induced pulmonary hypertension resulted in decreased GSH level, decreased GST and SOD activities and increased CAT activity in lung and liver tissues of both male and female rats. In addition, the lung and liver GSH level and GST and SOD levels were higher in female control rats compared to male control rats. The results of the present study, that antioxidant enzyme activities were different between the groups, highlight the possible role of oxidative stress in the pathogenesis of MCT-induced pulmonary hypertension in rats. Moreover, the lower antioxidant defense capacity of male rats than female rats may be considered as a cause of more aggressive course of MCT-induced pulmonary hypertension in males compared to females.


Prediction of plant-derived xenomiRs from plant miRNA sequences using random forest and one-dimensional convolutional neural network models.
An increasing number of studies reported that exogenous miRNAs (xenomiRs) can be detected in animal bodies, however, some others reported negative results. Some attributed this divergence to the selective absorption of plant-derived xenomiRs by animals. Here, we analyzed 166 plant-derived xenomiRs reported in our previous study and 942 non-xenomiRs extracted from miRNA expression profiles of four species of commonly consumed plants. Employing statistics analysis and cluster analysis, our study revealed the potential sequence specificity of plant-derived xenomiRs. Furthermore, a random forest model and a one-dimensional convolutional neural network model were trained using miRNA sequence features and raw miRNA sequences respectively and then employed to predict unlabeled plant miRNAs in miRBase. A total of 241 possible plant-derived xenomiRs were predicted by both models. Finally, the potential functions of these possible plant-derived xenomiRs along with our previously reported ones in human body were analyzed. Our study, for the first time, presents the systematic plant-derived xenomiR sequences analysis and provides evidence for selective absorption of plant miRNA by human body, which could facilitate the future investigation about the mechanisms underlying the transference of plant-derived xenomiR.


Polymorphic variants in VAX1 and the risk of nonsyndromic cleft lip with or without cleft palate in a population from northern China.
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is one of the most common craniofacial birth defects, and the etiology of NSCL/P involves both genetic and environmental factors. Genome-wide association study (GWAS) identified a novel susceptibility locus of ventral anterior homeobox 1 (VAX1) in patients with NSCL/P. However, the association of single nucleotide polymorphisms (SNPs) of VAX1 with NSCL/P is inconclusive due to the differences in the racial and ethnic populations. The aim of this study was to replicate the association between VAX1 and NSCL/P in a northern Chinese Han population. Our study included 186 patients with NSCL/P and 223 healthy individuals from northern China. Five SNPs (rs4752028, rs10787760, rs7078160, rs6585429, and rs1871345) on VAX1 were genotyped using the SNaPshot method. Recessive genetic model analysis revealed that homozygous genotype CC of VAX1 rs4752028 was associated with an increased risk of NSCL/P (odds ratio = 1.89, 95% confidence interval = 1.12-3.19, P = 0.017), but the results were not significant after the Bonferroni correction for multiple comparisons. The allele and genotype frequencies of rs10787760, rs7078160, rs6585429, and rs1871345 and the allele frequencies of rs4752028 showed no significant differences between cases and controls. Haplotype and SNP-SNP interaction analyses did not detect any significant association of VAX1 with the occurrence of NSCL/P. VAX1 rs4752028 was weakly associated with NSCL/P development in the studied northern Chinese Han population.


Myxoid liposarcoma with t(12;16) (q13;p11) contains site-specific differences in methylation patterns surrounding a zinc-finger gene mapped to the breakpoint region on chromosome 12.
The q13 to q15 region of human chromosome 12 is frequently and consistently rearranged in malignant and benign adipose tissue tumors as well as benign tumors of smooth muscle and salivary glands. A reciprocal translocation, (12;16) (q13;p11), is characteristic of the myxoid subtype of liposarcoma, whereas translocations within 12q13-14 are frequently observed in benign lipomas. We are using pulsed-field gel electrophoresis to study the 12q13-q14 region in order to detect and clone the respective translocation breakpoints in these tumors. The locus GLI, which encodes a zinc-finger protein, has been mapped to the same region as the myxoid liposarcoma breakpoint. Pulsed-field analysis of myxoid liposarcoma and lipoma DNA has allowed us to construct a 600-kilobase physical map surrounding the GLI locus, which shows that breakpoints in both types of tumor are outside this region. However, myxoid liposarcoma DNA samples contained altered restriction fragments detectable with GLI probes that were highly specific and reproducible from case to case. These altered fragments are due to highly specific and reproducible methylation differences that are unique to myxoid liposarcoma DNA. These methylation changes may prove to be useful clinically as a diagnostic tool to differentiate subtypes of liposarcoma.


Structural, electronic and energetic properties of giant icosahedral fullerenes up to C6000: insights from an ab initio hybrid DFT study.
The properties of the (n,n) icosahedral family of carbon fullerenes up to n = 10 (6000 atoms) have been investigated through ab initio quantum-mechanical simulation by using a Gaussian type basis set of double zeta quality with polarization functions (84,000 atomic orbitals for the largest case), the hybrid B3LYP functional and the CRYSTAL14 code featuring generalization of symmetry treatment. The geometry of giant fullerenes shows hybrid features, between a polyhedron and a sphere; as n increases, it approaches the former. Hexagon rings at face centres take a planar, graphene-like configuration; the 12 pentagon rings at vertices impose, however, a severe structural constraint to which hexagon rings at the edges must adapt smoothly, adopting a bent (rather than sharp) transversal profile and an inward longitudinal curvature. The HOMO and LUMO electronic levels, as well as the band gap, are well described using power laws. The gap is predicted to become zero for n ≥ 34 (69,360 atoms). The atomic excess energy with respect to the ideal graphene sheet goes to zero following the log(Nat)/Nat law, which is well described through the continuum elastic theory applied to graphene; the limits for the adopted model are briefly outlined. Compared to larger fullerenes of the series, C60 shows unique features with respect to all the considered properties; C240 presents minor structural and energetic peculiarities, too.


Effectiveness of a breastfeeding program for mothers returning to work in Japan: a quasi-experimental study.
Maternal employment has been described as a barrier to breastfeeding in many countries. In Japan, many mothers quit breastfeeding after returning to work because they do not know how to continue breastfeeding. The primary objective of this study was to investigate the effectiveness of a breastfeeding support program for mothers. The secondary objective was to explore the effectiveness of a pamphlet for mothers returning to work. This was a quasi-experimental design study with a program group (n = 48), pamphlet group (n = 46) and comparison group (n = 47) that took place from February 2017 to August 2018. Participants in the program and pamphlet groups were women who planned to return to work within 4-12 months after giving birth, while the comparison group included women who had been back at work for at least 3 months. The program involved a 90-min breastfeeding class, a pamphlet, a newsletter, and email consultation. The pamphlet group was sent only the pamphlet, while the comparison group received no intervention. The outcome was breastfeeding continuation rate at 3 months after returning to work. The breastfeeding continuation rate 3 months after returning to work was significantly higher in the program group than in the comparison group (79.2% vs. 51.1%, p = 0.004). After adjusting for background factors, the program intervention had an effect on breastfeeding rates (adjusted odds ratio = 4.68, 95% confidence interval: 1.57, 13.96; p = 0.006). However, comparing the pamphlet and comparison groups revealed no significant differences in breastfeeding continuation rates at 3 months after returning to work (69.6% vs. 51.1%, p = 0.07). Program intervention was associated with a significant increase in breastfeeding continuation rates 3 months after returning to work. Randomized controlled trials are needed to make this program applicable in practice. Pamphlet intervention resulted in no significant difference. Further study is necessary after examining the contents of the pamphlet.


Cariogenic Biofilms: Development, Properties, and Biomimetic Preventive Agents.
Oral biofilms will build up within minutes after cleaning of the dental hard tissues. While the application of remineralizing agents is a well-known approach to prevent dental caries, modern oral care products offer also additional active agents to maintain oral health. Human saliva contains many different organic and inorganic compounds that help to buffer organic acids produced by cariogenic microorganisms. However, most oral care products only contain remineralizing agents. To improve the benefit of those products, further active ingredients are needed. Books, review articles, and original research papers were included in this narrative review. Putting all these data together, we give an overview of oral biofilms and active compounds used in modern oral care products to interact with them. The special focus is on inorganic compounds and their interaction with oral biofilms. While organic compounds have several limitations (e.g., cell toxicity), inorganic compounds based on calcium and/or phosphate (e.g., sodium bicarbonate, hydroxyapatite, calcium carbonate) offer several advantages when used in oral care products. Calcium release can inhibit demineralization, and the release of hydroxide and phosphate ions might help in the buffering of acids. Therefore, the focus of this review is to summarize the scientific background of further active ingredients that can be used for oral care formulations.


Contamination of a high-cell-density continuous bioreactor.
Continuous fermentations were carried out with a recombinant flocculent Saccharomyces cerevisiae strain in an airlift bioreactor. Once operating under steady state at a dilution rate of 0.45 h(-1), the bioreactor was contaminated with Escherichia coli cells. The faster growing E. coli strain was washed out of the bioreactor and the recombinant, slower growing flocculating S. cerevisiae strain remained as the only species detected in the bioreactor. Flocculation, besides allowing for the realization of high-cell-density systems with corresponding unusual high productivity, may be used as a selective property for controlling some contamination problems associated with prolonged continuous operation.


[Primary meningioma of the ventricle IV].
A clinical observation of a rare neurosurgical pathology, i.e. meningioma growing in the cavity of ventricle IV, is reported. The female patient underwent a surgery of tumor eradication. Issues related with diagnostics, treatment tactics and disease prognostication are discussed on the basis of literature survey. Practical recommendations on treatment tactics are provided with regard for the discussed published data and the mentioned clinical case.


The severity and extent of the Australia 2019-20 Eucalyptus forest fires are not the legacy of forest management.
The 2019-20 wildfires in eastern Australia presented a globally important opportunity to evaluate the respective roles of climatic drivers and natural and anthropogenic disturbances in causing high-severity fires. Here, we show the overwhelming dominance of fire weather in causing complete scorch or consumption of forest canopies in natural and plantation forests in three regions across the geographic range of these fires. Sampling 32% (2.35 Mha) of the area burnt we found that >44% of the native forests suffered severe canopy damage. Past logging and wildfire disturbance in natural forests had a very low effect on severe canopy damage, reflecting the limited extent logged in the last 25 years (4.5% in eastern Victoria, 5.3% in southern New South Wales (NSW) and 7.8% in northern NSW). The most important variables determining severe canopy damage were broad spatial factors (mostly topographic) followed by fire weather. Timber plantations affected by fire were concentrated in NSW and 26% were burnt by the fires and >70% of the NSW plantations suffered severe canopy damage showing that this intensive means of wood production is extremely vulnerable to wildfire. The massive geographic scale and severity of these Australian fires is best explained by extrinsic factors: an historically anomalous drought coupled with strong, hot dry westerly winds that caused uninterrupted, and often dangerous, fire weather over the entire fire season.


Dynamic links between memory and functional limitations in old age: longitudinal evidence for age-based structural dynamics from the AHEAD study.
This study examined competing substantive hypotheses about dynamic (i.e., time-ordered) links between memory and functional limitations in old age. We applied the Bivariate Dual Change Score Model to 13-year longitudinal data from the Asset and Health Dynamics Among the Oldest Old Study (AHEAD; N = 6,990; ages 70 - 95). Results revealed that better memory predicted shallower increases in functional limitations. Little evidence was found for the opposite direction that functional limitations predict ensuing changes in memory. Spline models indicated that dynamic associations between memory and functional limitations were substantively similar between participants aged 70-79 and those aged 80-95. Potential covariates (gender, education, health conditions, and depressive symptoms) did not account for these differential lead-lag associations. Applying a multivariate approach, our results suggest that late-life developments in two key components of successful aging are intrinsically interrelated. Our discussion focuses on possible mechanisms why cognitive functioning may serve as a source of age-related changes in health both among the young-old and the old-old.


Establishment of a genome-wide and quantitative protocol for assessment of transcriptional activity at human retrotransposon L1 antisense promoters.
Long interspersed element 1 (L1) retrotransposon sequences are widespread in the human genome, occupying ~500,000 locations. The majority of L1s have lost their retrotransposition capability, although a significant population of human L1s maintains bidirectional transcriptional activity from the internal promoter. While the sense promoter drives transcription of the entire L1 mRNA and leads to L1 retrotransposition, the antisense promoter (ASP) transcribes L1-gene chimeric RNAs that include neighboring exon sequences. Activation mechanisms and functional impacts of L1ASP transcription are thought to vary at every L1ASP location. To explore the locus-specific regulation and function of L1ASP transcription, quantitative methodology is necessary for identifying the genomic positions of highly active L1ASPs on a genome-wide scale. Here, we employed deep-sequencing techniques and built a 3' RACE-based experimental and bioinformatics protocol, named the L1 antisense transcriptome protocol (LATRAP). In LATRAP, the PCR primer and the read mapping scheme were designed to reduce false positives and negatives, which may have been included as hits in previous cloning studies. LATRAP was here applied to the A549 human lung cancer cell line, and 313 L1ASP loci were detected to have transcriptional activity but differed in the number of mapped reads by four orders of magnitude. This indicates that transcriptional activities of the individual L1ASPs can vary greatly and that only a small population of L1ASP loci is active within individual nuclei. LATRAP is the first experimental method for ranking L1ASPs according to their transcriptional activity and will thus open a new avenue to unveiling the locus-specific biology of L1ASPs.


Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial.
Chikungunya is an emerging arthropod-borne disease that has spread from tropical endemic areas to more temperate climates of the USA and Europe. However, no specific treatment or preventive measure is yet available. We aimed to investigate the immunogenicity and safety of a live recombinant measles-virus-based chikungunya vaccine. We did a randomised, double-blind, placebo-controlled, active-comparator, phase 1, dose-escalation study at one centre in Vienna, Austria. Healthy men and women aged 18-45 years with no comorbidities were randomly assigned, by computer-generated block randomisation (block size of 14), to receive either one of three escalating doses of the measles-virus-based candidate vaccine (low dose [1·5 × 10(4) median tissue culture infection doses (TCID50) per 0·05 mL], medium dose [7·5 × 10(4) TCID50 per 0·25 mL], or high dose [3·0 × 10(5) TCID50 per 1·0 mL]), or the active comparator-Priorix. Participants were additionally block-randomised to receive a booster injection on either day 28 or day 90 after the first vaccination. Participants and study investigators were masked to group allocation. The primary endpoint was the presence of neutralising anti-chikungunya antibodies on day 28, as assessed by 50% plaque reduction neutralisation test. Analysis was by intention to treat and per protocol. This trial is registered with EudraCT, number 2013-001084-23. Between Nov 22, 2013, and Feb 25, 2014, we randomly assigned 42 participants to receive the low dose (n=12), the medium dose (n=12), or the high dose (n=12) of the measles-virus-based candidate vaccine, or Priorix (n=6), of whom 36 participants (86%; n=9, n=12, n=10, n=5, respectively) were included in the per-protocol population. The candidate vaccine raised neutralising antibodies in all dose cohorts after one immunisation, with seroconversion rates of 44% (n=4) in the low-dose group, 92% (n=11) in the medium-dose group, and 90% (n=10) in the high-dose group. The immunogenicity of the candidate vaccine was not affected by pre-existing anti-measles immunity. The second vaccination resulted in a 100% seroconversion for all participants in the candidate vaccine groups. The candidate vaccine had an overall good safety profile, and the rate of adverse events increased with vaccine dose and volume. No vaccination-related serious adverse events were recorded. The live recombinant measles-virus-based chikungunya vaccine had good immunogenicity, even in the presence of anti-vector immunity, was safe, and had a generally acceptable tolerability profile. This vaccine is the first promising measles-virus-based candidate vaccine for use in human beings. Themis Bioscience GmBH.


Effectiveness of a Bystander Intervention Program to Increase Bystander Behaviors Across Latent Risk Groups of High Schoolers.
Bystander intervention programs have established efficacy to increase bystander behaviors to prevent interpersonal violence (IPV). Little research has investigated intervention efficacy among latent risk classes among high school students. Data from a five-year randomized control trial were used to conduct multigroup path analyses to assess the association between type of training received and bystander outcomes moderated by risk groups identified via latent profile analysis (LPA). LPA was used to identify risk based on six indicators related to violence exposure, association with aggressive friends, and alcohol use. Bystander training received was the primary independent variable characterized as: no training, overview speech alone, or skills training. Outcomes included (a) observed bystander behaviors; (b) reactive bystander behaviors; or (c) proactive bystander behaviors. Three risk groups were identified via LPA: low risk, moderate risk witnesses of IPV, and highest risk victims and perpetrators. Of the bystander trainings received, overview speeches only increased reactive bystander behaviors among low risk students. The skills training was effective at increasing most bystander outcomes among all risk groups, with the largest effect sizes observed among the highest risk victims and perpetrators profile. Findings suggest that tailoring or modifying bystander training based on the risk profiles of youth may lead to greater potential to increase bystander behaviors to reduce risk of violence. Specifically, overview speech trainings should be targeted to low risk youth, while skills training primarily delivered to higher risk youth. These skills trainings could incorporate content related to trauma-informed care as well as associations with alcohol use, which may enhance their effectiveness further.


A "toxic window" study on the hippocampal development of mice offspring exposed to azithromycin at different doses, courses, and time during pregnancy.
Azithromycin, one of the new-generation macrolides, is an effective medicine for the treatment of mycoplasma infection during pregnancy. Epidemiological studies have reported adverse pregnancy outcomes with prenatal azithromycin exposure (PAzE). However, the effect of PAzE on fetal hippocampal development is unclear. This study aimed to explore the effects and potential mechanism of PAzE-induced fetal hippocampal development at different doses, courses, and time. Pregnant mice were administered azithromycin by gavage at different doses (50, 100 or 200 mg/kg.d), different courses (gestational day (GD)15-17 for three consecutive days, or GD17 once a day) and different time (GD10-12, GD15-17). Compared with the control group, morphological development damage of the fetal hippocampus was observed in the PAzE group, with a dysbalance in neuronal proliferation and apoptosis, decreased expression of the neuronal-specific marker Snap25, NeuN, PSD95 and Map2, increased expression of the glial-specific marker Iba1, GFAP, and S-100β, and decreased expression of P2ry12. The PAzE-induced hippocampal developmental deficiency varied based on different doses, courses, and time, and the developmental toxicity was most significant in the late pregnancy, high dose, multi-course group (AZHT). The significant reduction of SOX2 and Wnt, which were related to regulation of neural progenitor cells (NPCs) proliferation in PAzE fetus compared with the control group indicated that the SOX2/Wnt signaling may be involved in PAzE-induced hippocampal developmental toxicity. In this study, PAzE was associated with hippocampal developmental toxicity in a variety of nerve cells. Hippocampal developmental toxicity due to azithromycin was most significant in the late pregnancy, high-dose (equivalent to maximum clinical dose) and multi-course group (AZHT). The findings provide an experimental and theoretical foundation for guiding the sensible use of medications during pregnancy and effectively assessing the risk of fetal hippocampal developmental toxicity.


Hemispheric Lateralization of Visuospatial Attention Is Independent of Language Production on Right-Handers: Evidence From Functional Near-Infrared Spectroscopy.
It is well-established that visuospatial attention is mainly lateralized to the right hemisphere, whereas language production is mainly left-lateralized. However, there is a significant controversy regarding how these two kinds of lateralization interact with each other. The present research used functional near-infrared spectroscopy (fNIRS) to examine whether visuospatial attention is indeed right-lateralized, whereas language production is left-lateralized, and more importantly, whether the extent of lateralization in the visuospatial task is correlated with that in the task involving language. Specifically, fifty-two healthy right-handed participants participated in this study. Multiple-channel fNIRS technique was utilized to record the cerebral hemodynamic changes when participants were engaged in naming objects depicted in pictures (the picture naming task) or judging whether a presented line was bisected correctly (the landmark task). The degree of hemispheric lateralization was quantified according to the activation difference between the left and right hemispheres. We found that the picture-naming task predominantly activated the inferior frontal gyrus (IFG) of the left hemisphere. In contrast, the landmark task predominantly activated the inferior parietal sulcus (IPS) and superior parietal lobule (SPL) of the right hemisphere. The quantitative calculation of the laterality index also showed a left-lateralized distribution for the picture-naming task and a right-lateralized distribution for the landmark task. Intriguingly, the correlation analysis revealed no significant correlation between the laterality indices of these two tasks. Our findings support the independent hypothesis, suggesting that different cognitive tasks may engender lateralized processing in the brain, but these lateralized activities may be independent of each other. Meanwhile, we stress the importance of handedness in understanding the relationship between functional asymmetries. Methodologically, we demonstrated the effectiveness of using the multichannel fNIRS technique to investigate the hemispheric specialization of different cognitive tasks and their lateralization relations between different tasks. Our findings and methods may have important implications for future research to explore lateralization-related issues in individuals with neural pathologies.


The Chemical Profile, Antioxidant, and Anti-Lipid Droplet Activity of Fluid Extracts from Romanian Cultivars of Haskap Berries, Bitter Cherries, and Red Grape Pomace for the Management of Liver Steatosis.
This study aimed to investigate, for the first time, the chemical composition and antioxidant activity of fluid extracts obtained from three Romanian cultivars of haskap berries (Lonicera caerulea L.) var. Loni, bitter cherries (Prunus avium var. sylvestris Ser.) var. Silva, and pomace from red grapes (Vitis vinifera L.) var. Mamaia, and their capacity to modulate in vitro steatosis, in view of developing novel anti-obesity products. Total phenolic, flavonoid, anthocyanin, and ascorbic acid content of fluid extracts was spectrophotometrically assessed and their free radical scavenging capacity was evaluated using Trolox Equivalent Antioxidant Capacity (TEAC) and free 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical inhibition assays. The Pearson coefficients showed a moderate correlation between the antioxidant activity of fluid extracts and their phenolic content, but a strong correlation between anthocyanin and ascorbic acid content. HPLC analysis identified and quantified the main phenolic compounds of chlorogenic and syringic acid, catechin, and glycosylated kaempferol, apigenin, and quercetin, in variable proportions. An in vitro experimental model of steatosis was developed in HepG2 hepatocytes treated with a mixture of free fatty acids. Cell culture analyses showed that cytocompatible concentrations of fluid extracts could significantly reduce the lipid accumulation and inhibit the reactive oxygen species, malondialdehyde, and nitric oxide secretion in stressed hepatocytes. In conclusion, these results put an emphasis on the chemical compounds' high antioxidant and liver protection capacity of unstudied fluid extracts obtained from Romanian cultivars of bitter cherries var. Silva and pomace of red grapes var. Mamaia, similar to the fluid extract of haskap berries var. Loni, in particular, the positive modulation of fat deposition next to oxidative stress and the lipid peroxidation process triggered by fatty acids in HepG2 hepatocytes. Consequently, this study indicated that these fluid extracts could be further exploited as hepatoprotective agents in liver steatosis, which provides a basis for the further development of novel extract mixtures with synergistic activity as anti-obesity products.


Does heart transplantation confer survival benefit in all risk groups?
Over 50,000 heart transplants have been performed in the last 3 decades. The global shortage of donor organs and the relaxation of candidate selection criteria over time has resulted in recent controversy about the benefits of heart transplantation for some risk groups. We assessed the survival benefit acquired in the Papworth Hospital heart transplant population overall, taking into account resuscitated marginal donors and high-risk recipients. All heart transplant patients listed between 1979 and June 2002 were analyzed (n = 1,212). Of these, 931 cardiac transplantations were done, including the use of 126 marginal donors. High-risk recipients (n = 163) were defined as patients being in the hospital, on intravenous inotropic drugs, and/or with a high transpulmonary gradient (>15 mm Hg). Using Cox regression with transplantation as a time-dependent covariate, we assessed the survival benefit of transplantation. In our model we assumed that after transplantation the initial risk of death is high relative to continued waiting, followed by an exponential decline in risk. The crossover point (COP) is the time at which the risk of death after transplantation is equal to that of continued waiting (i.e., the relative risk is 1). The equity point (EP) determines the time at which the early post-operative risk is offset by the later period of lower risk and, therefore, the time at which transplantation has a survival advantage. Overall, the COP was at 54 days and EP at 141 days. In the marginal donor sub-group, COP was achieved at 32 days with EP at 72 days, indicating a survival benefit. The difference in the COP and EP between the borderline donor and normal donor sub-groups was not statistically significant. Post-transplant survival was not significantly different from recipients of normal cardiac allografts (p = .43). Likewise, for the high-risk recipient group, the COP and EP were at 72 and 203 days. Although post-op survival was significantly shorter than the normal-risk group, both groups achieved survival benefits. Heart transplantation provides survival benefit in these risk groups of recipients in our population. This is a reflection of our active donor management protocol and rigorous donor and recipient selection process.


Report of 16 kindreds and one kindred with hMLH1 germline mutation.
To analyze the diagnosis and treatment of 16 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, and to report the first kindred with hMLH1 germline mutation in Mainland China. The diagnosis, treatment and follow-up study of 16 HNPCC kindreds were retrospectively reviewed. Data concerning site of the malignant tumor, age at the diagnosis, history of synchronous and/or metachronous cancer, and histopathology of tumors were recorded. All treatments had won formal consent. PCR and SSCP were used to screen the coding region of hMLH1 and hMSH2 genes. Variant bands were sequenced by a 377 DNA sequencer. Among sixteen kindreds, sixty-eight patients had a mean age of 50.8 years, including twenty-one multiple cancer patients and forty-six colorectal cancer patients (metachronous colorectal cancers in sixteen). A total of one hundred and one malignant neoplasms were found in these sixty-eight patients, including 50 colonic, 17 rectal, 11 gastric, 7 endometrial, and 4 esophageal cancers. 39.5% colorectal patients had metachronous cancers within ten years who needed reoperations. A germline G265T nonsense mutation was found in the third exon of hMLH1, resulting in a stop codon and truncated protein. Three phenotypically normal family members were also found to carry the mutated gene. HNPCC is a typical auto-dominant hereditary disease, the main characteristics include early onset and frequency of cancers; predominance of colorectal, especially right-sided colon cancers; frequency of multiple primary cancers (especially colorectal cancers). Segmental resection for colorectal cancers is not eligible for colorectal cancer patient in HNPCC kindreds. Intensive follow-up is essential for all patients and possible gene carriers. The first HNPCC kindred with hMLH1 gene germline mutation was identified in Mainland China, and three phenotypically normal family members were found to be carriers of the mutated gene. The G265T germline (nonsense) mutation in the third exon of hMLH1 found here had not been reported previously in the literature.


Tail-flick test response in 3×Tg-AD mice at early and advanced stages of disease.
Despite the impact of pain in cognitive dysfunctions and affective disorders has been largely studied, the research that examines pain dimensions in cognitive impairment or dementia is still scarce. In patients with Alzheimer's disease (AD) and related dementias, management of pain is challenging. While the sensory-discriminative dimension of pain is preserved, the cognitive-evaluative and the affective-motivational pain dimensions are affected. Due to the complexity of the disease and the poor self-reports, pain is underdiagnosed and undertreated. In confluence with an impaired thermoregulatory behavior, the patients' ability to confront environmental stressors such as cold temperature can put them at risk of fatal accidental hypothermia. Here, 3xTg-AD mice demonstrate that the sensorial-discriminative threshold to a noxious cold stimulus, as measured by the latency of tail-flicking, was preserved at early and advances stages of disease (7 and 11 month-old, respectively) as compared to age-matched (adulthood and middle aged, respectively) non-transgenic mice (NTg). In both genotypes, the sensory deterioration and poor thermoregulatory behavior associated to age was observed as an increase of tail-flick response and poor sensorimotor performance. At both stages studied, 3xTg-AD mice exhibited BPSD (Behavioral and Psychological Symptoms of Dementia)-like alterations in the corner, open-field, dark-light box and the T-maze tests. In the adult NTg mice, this nociceptive withdrawal response was correlated with copying with stress-related behaviors. This integrative behavioral profile was lost in both groups of 3xTg-AD mice and middle aged controls, suggesting derangements in their subjacent networks and the complex interplay between the pain dimensions in the elderly with dementia.


[Inguinal hernia. The Shouldice parietal repair].
Parietal repair according to the Shouldice technique consists of a double line of sutures on each of three musculo-aponeurotic layers of the groin, i.e. successively: plicature of the transverse muscle and attachments; aponeuroplasty by back-to-back suture of the internal and external oblique muscles, and plicature of the aponeurosis of the external oblique muscle. Parietal repair of this kind is only possible after wide dissection of the inguinal region. It can be performed under local anaesthesia during a short hospitalization period. Normal activity is rapidly resumed, and in the experience of those who favour this technique, the recurrence rate is a mere 1%.


Reconstitution of human corporal smooth muscle and endothelial cells in vivo.
The availability of autologous erectile tissue composed of corporal smooth muscle and endothelial cells would be beneficial in patients undergoing penile reconstruction. We previously showed that cultured cavernous cells seeded on polymer scaffolds form corporal muscle when implanted in vivo. However, to reconstruct corporal tissue endothelial and corporal muscle cells are necessary. In this study we investigated the possibility of developing tissue composed of corporal cells in vivo by combining smooth muscle and endothelial cells. Human corporal smooth muscle and endothelial cells were seeded on biodegradable polyglycolic acid polymer scaffolds at concentrations of 20 x 10(6) and 10 x 10(6) cells per cm3, respectively. A total of 60 polymer scaffolds seeded with cells and 20 control polymers without cells were implanted in the subcutaneous space of 20 athymic mice. Mice were sacrificed 1, 3, 5, 7, 14, 21, 28 and 42 days, respectively, after implantation. Immunocytochemical and histochemical analyses were performed with antifactor VIII, antipancytokeratins and anti-alpha actin antibodies. Histologically the retrieved polymers seeded with corporal smooth muscle and endothelial cells showed the formation of multilayered smooth muscle strips adjacent to endothelial cells 7 days after implantation. Increased organization of the smooth muscle tissue and accumulation of endothelium lining the luminal structures were evident by 14 days. A well organized tissue construct was noted 28 and 42 days after implantation. There was no evidence of tissue formation in controls. Immunocytochemical analysis using antifactor VIII to identify native vasculature only and antipancytokeratins to identify ECV 304 endothelial cells only distinguished the origin of the vascular structures in each construct. Anti-alpha-actin confirmed the smooth muscle phenotype. Human corporal smooth muscle and endothelial cells seeded on biodegradable polymer scaffolds formed vascularized corpus cavernosum muscle when implanted in vivo. To our knowledge this is the first demonstration in tissue engineering in which capillary formation was facilitated by the addition of endothelial cells in composite tissue in vivo.


Can Weakness in End-Range Plantar Flexion After Achilles Tendon Repair Be Prevented?
Disproportionate end-range plantar flexion weakness, decreased passive stiffness, and inability to perform a heel rise on a decline after Achilles tendon repair are thought to reflect increased tendon compliance or tendon lengthening. Since this was first noted, we have performed stronger repairs and avoided stretching into dorsiflexion for the first 12 weeks after surgery. Using stronger repairs and avoiding stretching into dorsiflexion would eliminate end-range plantar flexion weakness and normalize passive stiffness. Case series; Level of evidence, 4. Achilles repairs with epitendinous augmentation were performed on 18 patients. Plantar flexion torque, dorsiflexion range of motion (ROM), passive joint stiffness, and standing single-legged heel rise on a decline were assessed at 43 ± 24 months after surgery (range, 9 months to 8 years). Maximum isometric plantar flexion torque was measured at 20° and 10° of dorsiflexion, neutral position, and 10° and 20° of plantar flexion. Passive dorsiflexion ROM was measured with a goniometer. Passive joint stiffness was computed from the increase in passive torque from 10° to 20° of dorsiflexion. Tendon thickness was measured by use of digital calipers. Plantar flexion electromyographic (EMG) data were recorded during strength and functional tests. Analysis of variance and chi-square tests were used to assess weakness and function. Marked weakness was evident on the involved side at 20° of plantar flexion (deficit, 26% ± 18%; P < .001), with no weakness at 20° of dorsiflexion (deficit, 6% ± 17%; P = .390). Dorsiflexion ROM was decreased 5.5° ± 8° (P = .015), and tendon width was 8 ± 3 mm greater on the involved side (P < .001). Passive joint stiffness was similar between the involved and noninvolved sides. Only 2 of 18 patients could perform a decline heel rise on the involved side compared with 18 of 18 on the noninvolved side (P = .01). No difference in EMG amplitude was found between the involved and noninvolved sides during the strength or heel rise tests. The use of stronger repair techniques and attempts to limit tendon elongation by avoiding dorsiflexion stretching did not eliminate weakness in end-range plantar flexion. EMG data confirmed that end-range weakness was not due to neural inhibition. Physiological changes that alter the force transmission capability of the healing tendon may be responsible for this continued impairment. This weakness has implications for high-demand jumping and sprinting after Achilles tendon repair.


Spirometry to increase smoking cessation rate: A systematic review.
Addressing tobacco use is an important issue in general health care. In order to improve smoking cessation advice, spirometry values can be displayed to the smoker to demonstrate possible lung function impairment. The estimate of so-called lung age may show a decrease in lung function associated with smoking. It has been suggested that performing spirometry on patients who smoke but are asymptomatic can be a useful way to show the adverse effects of smoking. The aim of this systematic review was to determine if providing spirometry results in combination with smoking cessation counselling can increase smoking cessation rates compared to what is achieved through counselling alone. In this systematic review, we included randomized controlled trials (RCTs) evaluating smoking cessation interventions for adult smokers. The systematic search was performed in PubMed, Medline, Cochrane Library, Cinahl, Embase, Amed and PsycInfo. The literature search resulted in 946 studies, which, after reading by two independent reviewers, were reduced to seven trials that matched the inclusion criteria. Two RCTs showed significant improvement in smoking cessation when giving patients feedback on spirometry results in combination with smoking cessation counselling, compared to patients who received only smoking cessation counselling. In both studies, the spirometry results were expressed as lung age. In the other five studies no difference was found. Five further published study protocols for ongoing RCT studies in the field have been found, and therefore this systematic overview will likely need to be updated within a few years. Few studies have been undertaken to examine the efficacy of spirometry in increasing smoking quit rates. Studies conducted to date have shown mixed results, and there is currently limited evidence in the literature that smoking cessation counselling that includes feedback from spirometry and a demonstration of lung age promotes quit rates.


Abiraterone acetate in metastatic castration-resistant prostate cancer - the unanticipated real-world clinical experience.
There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice. The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed. The treatment efficacy and its determinants, and toxicities were determined. A total of 110 patients with mCRPC were treated with AA in the review period, of whom 58 were chemo-naive and 52 had received prior chemotherapy (post-chemo). The median follow-up time was 7.5/11.4 months for chemo-naive/post-chemo patients. 6.9/15.4 % of chemo-naive/post-chemo patients had visceral metastases. The median overall survival (OS) and progression-free survival (PFS) were 18.1/15.5 months and 6.7/6.4 months for chemo-naive/post-chemo patients, respectively. Among chemo-naive patients, those with visceral diseases had significantly inferior OS (2.8 vs 18.0 p = 0.0007) and PFS (2.8 vs 6.8 months, p = 0.0088) than those without. Pain control was comparable in both groups of patients. The most common grade 3 or above toxicities were hypertension (6.9/5.8 %) and hypokalemia (3.4/3.8 %) in chemo-naive/post-chemo patients. In multivariate analysis, the presence of prostate-specific antigen (PSA) response (≥50 % drop of PSA from baseline) within the first 3 months of therapy was associated with favorable OS and PFS in both chemo-naive and post-chemo group. In clinical practice outside the trial setting, OS after AA in our chemo-naive patient cohort (18.1 months) was considerably shorter than that reported in the COU-AA-302 trial (34.7 months), and the OS was particularly short in those with visceral metastases (2.8 months). Conversely, AA was efficacious in post-chemo patients. AA resulted in comparable pain control in both groups of patients. The presence of PSA response within the first 3 months of treatment was a significant determinant of survival.


Baicalin Protects against TNF-α-Induced Injury by Down-Regulating miR-191a That Targets the Tight Junction Protein ZO-1 in IEC-6 Cells.
Tumor necrosis factor-alpha (TNF-α) plays an important role in the developing process of inflammatory bowel disease. Tight junction protein zonula occludens-1 (ZO-1), one of epithelial junctional proteins, maintains the permeability of intestinal barrier. The objective of this study was to investigate the mechanism of the protective effect of baicalin on TNF-α-induced injury and ZO-1 expression in intestinal epithelial cells (IECs). We found that baicalin pretreatment significantly improved cell viability and cell migration following TNF-α stimulation. miR-191a inhibitor increased the protective effect of baicalin on cell motility injured by TNF-α. In addition, miR-191a down-regulated the mRNA and protein level of its target gene ZO-1. TNF-α stimulation increased miR-191a expression, leading to the decline of ZO-1 mRNA and protein. Moreover, pretreatment with baicalin reversed TNF-α induced decrease of ZO-1 and increase of miR-191a, miR-191a inhibitor significantly enhanced ZO-1 protein expression restored by baicalin. These results indicate that baicalin exerts a protective effect on IEC-6 (rat small intestinal epithelial cells) cells against TNF-α-induced injury, which is at least partly via inhibiting the expression of miR-191a, thus increasing ZO-1 mRNA and protein levels.


Coupled near- and far-field scattering in silver nanoparticles for high-efficiency, stable, and thin plasmonic dye-sensitized solar cells.
Here, we report plasmonically enhanced thin dye-sensitized solar cells (DSSCs) in an imidazolium-dicyanamide based ionic liquid, in which size-controlled metal (silver) nanoparticles (AgNPs) with passivation layers of a few nanometers are arranged into the electrolyte and photo-electrodes. It was revealed that the AgNPs in the electrolyte and the photo-electrode have distinct effects on device performance via different coupling mechanisms. Strong far-field scattering is critical in the electrolyte while near-field scattering is efficient in the photo-electrode. Indeed, we find that the power conversion efficiency of the DSSC can be substantially improved by a synergistic arrangement of the AgNPs in the electrolyte and the photo-electrode. Furthermore, an imidazolium-dicyanamide based nonvolatile ionic liquid electrolyte for MNPs is demonstrated to provide thin plasmonic DSSCs with good stability.


Study on the expression of Toll-like receptor 4 and matrix metalloproteinase-9 in patients with chronic obstructive pulmonary disease and their clinical significance.
To investigate the expression of Toll-like receptor 4 (TLR4) and matrix metalloproteinase-9 (MMP-9) in patients with chronic obstructive pulmonary disease (COPD) and their clinical significance. Paracancerous tissues from 48 patients with lung squamous cell carcinoma harvested during pulmonary lobectomy were studied. Twenty-four cases of COPD were chosen as the observation group and 24 cases of non-COPD as the control group. The degree of lung inflammation was observed; the ratio of the thickness of the wall to the external diameter of the pulmonary arterioles (WT%), and the ratio of the area of the wall to that of the pulmonary arterioles (WA%) were calculated. Immunohistochemistry was used to evaluate the expression of TLR4, MMP-9, and proliferating cell nuclear antigen (PCNA) in vascular smooth muscle cells, and the expressions were correlated with lung revascularization. (1) Compared with the non-COPD group, the degree of inflammatory cell infiltration, WA%, and WT% of the COPD group were significantly increased (p<0.05). Additionally, the expression of TLR4, MMP-9, and PCNA in vascular smooth muscle cells was significantly increased (p<0.05). (2) Correlative analysis revealed that the expression of TLR4 and MMP-9 had significant positive correlation with the degree of inflammatory cell infiltration, WA%, WT%, and PCNA expression (p<0.05). Multivariate regression analysis showed that, compared with the smoking index and inflammation score, TLR4 and MMP-9 expression were the strongest factors affecting the parameters of lung revascularization (WA% and WT%) (p<0.05). High expression of MMP-9 and TLR4 in patients with COPD may promote inflammatory cell infiltration, induce proliferation of smooth muscle cells, degrade extracellular matrix, and play an important role in lung revascularization.


Pioglitazone versus metformin in two rat models of glucose intolerance and diabetes.
Insulin resistance has been implicated in the pathogenesis of type 2 diabetes. High fat diets cause insulin resistance. Both metformin and pioglitazone are considered "insulin sensitizers" and used as antihyperglycemic agents for type 2 diabetes treatment. The aim of this study is to Compare pioglitazone and metformin effects on carbohydrate metabolism and insulin sensitivity in diabetic and glucose intolerant rats on high fat diet. Male albino rats were randomized to seven groups. The 1st group received high carbohydrate diet (control). The 2nd, 3rd and 4th groups received high sunflower oil diets for 6 weeks and either left untreated, or given pioglitazone or metformin during the last 3 weeks. The 5th, 6th, and 7th groups were made diabetic by STZ injection on day 15 of the 6 weeks-high fat diet regimen. They were either left untreated, or given pioglitazone or metformin during the last 3 weeks. High-fat diet induced glucose intolerance; represented by increase of serum glucose associated with increase in liver glucose-6-phosphatase and decreases in liver glucose-6-phosphate dehydrogenase and glucokinase activities. No significant differences were observed between pioglitazone and metformin. In diabetic rats, both pioglitazone and metformin decreased elevated serum glucose by approximately 30%. Only metformin increased hepatic glycogen, and normalized glucose-6-phosphatase activity. On the other hand, pioglitazone normalized elevated renal glycogen content and increased glucose-6-phosphate dehydrogenase activity. High sunflower oil diet impaired glucose tolerance. Pioglitazone and metformin had comparable effects on estimates of carbohydrate metabolism and insulin sensitivity in high-fat fed rats, but different effects in diabetic rats.


STEP inhibition reverses behavioral, electrophysiologic, and synaptic abnormalities in Fmr1 KO mice.
Fragile X syndrome (FXS) is the leading cause of inherited intellectual disability, with additional symptoms including attention deficit and hyperactivity, anxiety, impulsivity, and repetitive movements or actions. The majority of FXS cases are attributed to a CGG expansion that leads to transcriptional silencing and diminished expression of fragile X mental retardation protein (FMRP). FMRP, an RNA binding protein, regulates the synthesis of dendritically-translated mRNAs by stalling ribosomal translation. Loss of FMRP leads to increased translation of some of these mRNAs, including the CNS-specific tyrosine phosphatase STEP (STriatal-Enriched protein tyrosine Phosphatase). Genetic reduction of STEP in Fmr1 KO mice have diminished audiogenic seizures and a reversal of social and non-social anxiety-related abnormalities. This study investigates whether a newly discovered STEP inhibitor (TC-2153) could attenuate the behavioral and synaptic abnormalities in Fmr1 KO mice. TC-2153 reversed audiogenic seizure incidences, reduced hyperactivity, normalized anxiety states, and increased sociability in Fmr1 KO mice. Moreover, TC-2153 reduced dendritic spine density and improved synaptic aberrations in Fmr1 KO neuronal cultures as well as in vivo. TC-2153 also reversed the mGluR-mediated exaggerated LTD in brain slices derived from Fmr1 KO mice. These studies suggest that STEP inhibition may have therapeutic benefit in FXS.


Degradation mechanism of small molecule-based organic light-emitting devices
Studies on the long-term degradation of organic light-emitting devices (OLEDs) based on tris(8-hydroxyquinoline) aluminum (AlQ3), the most widely used electroluminescent molecule, reveal that injection of holes in AlQ3 is the main cause of device degradation. The transport of holes into AlQ3 caused a decrease in its fluorescence quantum efficiency, thus showing that cationic AlQ3 species are unstable and that their degradation products are fluorescence quenchers. These findings explain the success of different approaches to stabilizing OLEDs, such as doping of the hole transport layer, introducing a buffer layer at the hole-injecting contact, and using mixed emitting layers of hole and electron transporting molecules.


Determining the Site of Action of Strigolactones during Nodulation.
Strigolactones (SLs) influence the ability of legumes to associate with nitrogen-fixing bacteria. In this study, we determine the precise stage at which SLs influence nodulation. We show that SLs promote infection thread formation, as a null SL-deficient pea (Pisum sativum) mutant forms significantly fewer infection threads than wild-type plants, and this reduction can be overcome by the application of the synthetic SL GR24. We found no evidence that SLs influence physical events in the plant before or after infection thread formation, since SL-deficient plants displayed a similar ability to induce root hair curling in response to rhizobia or Nod lipochitooligosaccharides (LCOs) and SL-deficient nodules appear to fix nitrogen at a similar rate to those of wild-type plants. In contrast, an SL receptor mutant displayed no decrease in infection thread formation or nodule number, suggesting that SL deficiency may influence the bacterial partner. We found that this influence of SL deficiency was not due to altered flavonoid exudation or the ability of root exudates to stimulate bacterial growth. The influence of SL deficiency on infection thread formation was accompanied by reduced expression of some early nodulation genes. Importantly, SL synthesis is down-regulated by mutations in genes of the Nod LCO signaling pathway, and this requires the downstream transcription factor NSP2 but not NIN This, together with the fact that the expression of certain SL biosynthesis genes can be elevated in response to rhizobia/Nod LCOs, suggests that Nod LCOs may induce SL biosynthesis. SLs appear to influence nodulation independently of ethylene action, as SL-deficient and ethylene-insensitive double mutant plants display essentially additive phenotypes, and we found no evidence that SLs influence ethylene synthesis or vice versa.


Knee extensor strength differences in obese and healthy-weight 10-to 13-year-olds.
The purpose of this study was to investigate if obese children have reduced knee extensor (KE) strength and to explore the relationship between adiposity and KE strength. An observational case-control study was conducted in three Australian states, recruiting obese [N = 107 (51 female, 56 male)] and healthy-weight [N = 132 (56 female, 76 male)] 10- to 13-year-old children. Body mass index, body composition (dual energy X-ray absorptiometry), isokinetic/isometric peak KE torques (dynamometry) and physical activity (accelerometry) were assessed. Results revealed that compared with their healthy-weight peers, obese children had higher absolute KE torques (P ≤ 0.005), equivocal KE torques when allometrically normalized for fat-free mass (FFM) (P ≥ 0.448) but lower relative KE torques when allometrically normalized for body mass (P ≤ 0.008). Adjustments for maternal education, income and accelerometry had little impact on group differences, except for isometric KE torques relative to body mass which were no longer significantly lower in obese children (P ≥ 0.013, not significant after controlling for multiple comparisons). Percent body fat was inversely related to KE torques relative to body mass (r = -0.22 to -0.35, P ≤ 0.002), irrespective of maternal education, income or accelerometry. In conclusion, while obese children have higher absolute KE strength and FFM, they have less functional KE strength (relative to mass) available for weight-bearing activities than healthy-weight children. The finding that FFM-normalized KE torques did not differ suggests that the intrinsic contractile properties of the KE muscles are unaffected by obesity. Future research is needed to see if deficits in KE strength relative to mass translate into functional limitations in weight-bearing activities.


Stability of purple membranes from Halobacterium salinarum toward surfactants: inkjet printing of a retinal protein.
Inkjet printing is a versatile technique widely applied in biological microarray technology. Because of its photochemical and photophysical properties, bacteriorhodopsin (BR) from Halobacterium salinarum holds promise for applications in nanotechnology, and inkjet printing would simplify the transfer of BR to suitable substrates. Surfactants are essential parts of inkjet formulations tuning viscosity, rheology, and spreading behavior of the solution. However, many surfactants destabilize the structure of proteins and often cause denaturation accompanied by a complete loss of function. Inkjet printing of membrane proteins is particularly challenging and special care must be taken in the choice of the surfactant. For BR, the situation is complicated by the fact that the structural integrity of BR depends on its native membrane environment, the so-called purple membrane (PM). PM contains 10 lipid molecules per BR monomer and is very sensitive toward surfactants. In this work, we identified surfactants suitable for inkjet formulations containing PM. Initially, we screened a variety of technically relevant surfactants for compatibility with PM using the UV-vis absorption of the retinal chromophore as a natural probe. Promising candidates were selected, and their impact on the structure of PM and BR was analyzed using UV-vis spectroscopy, CD spectroscopy, and small-angle X-ray scattering (SAXS). We identified two surfactants compatible with PM and suitable for inkjet formulations. An inkjet formulation containing PM as dye component was developed. We demonstrate that the photochromic properties of BR are maintained upon inkjet printing.


Automated intracranial hemorrhage detection in traumatic brain injury using 3D CNN.
Intracranial hemorrhage (ICH) is a prevalent and potentially fatal consequence of traumatic brain injury (TBI). Timely identification of ICH is crucial to ensure timely intervention and to optimize better patient outcomes. However, the current methods for diagnosing ICH from head computed tomography (CT) scans require skilled personnel (Radiologists and/or Neurosurgeons) who may be unavailable in all centers, especially in rural areas. The aim of this study is to develop a neurotrauma screening tool for identifying ICH from head CT scans of TBI patients. We prospectively collected head CT scans from the Department of Neurosurgery, All India Institute of Medical Sciences, New Delhi. Approximately 738 consecutive head CT scans from patients enrolled in the department were collected for this study spanning a duration of 9 months, that is, January 2020 to September 2020. The metadata collected along with the head CT scans consisted of demographic and clinical details and the radiologist's report which was used as the gold standard. A deep learning-based 3D convolutional neural network (CNN) model was trained on the dataset. The pre-processing, hyperparameters, and augmentation were common for training the 3D CNN model whereas the training modules were set differently. The model was trained along with the save best model option and was monitored by validation metrics. The Institute Ethics Committee permission was taken before starting the study. We developed a 3D CNN model for automatically detecting the ICH from head CT scans. The screening tool was tested in 20 cases and trained on 200 head CT scans, with 99 normal head CT and 101 CT scans with some type of ICH. The final model performed with 90% sensitivity, 70% specificity, and 80% accuracy. Our study reveals that the automated screening tool exhibits a commendable level of accuracy and sensitivity in detecting ICH from the head CT scans. The results indicate that the 3D CNN approach has a potential for further exploring the TBI-related pathologies.


Viral distribution and life strategies in the Bach Dang Estuary, Vietnam.
Although the structure and dynamics of planktonic viruses in freshwater and seawater environments are relatively well documented, little is known about the occurrence and activity of these viruses in estuaries, especially in the tropics. Viral abundance, life strategies, and morphotype distribution were examined in the Bach Dang Estuary (Vietnam) during the dry season in 2009. The abundance of both viruses and their prokaryotic hosts decreased significantly from upstream to downstream, probably as the result of nutrient dilution and osmotic stress faced by the freshwater communities. The antibiotic mitomycin-C revealed that the fraction of lysogenic cells was substantially higher in the lower seawater part of the estuary (max 27.1%) than in the upper freshwater area where no inducible lysogens were observed. The question of whether there is a massive, continuous induction of marine lysogens caused by the mixing with freshwater is considered. Conversely, the production of lytic viruses declined as salinity increased, indicating a spatial succession of viral life strategies in this tropical estuary. Icosahedral tailless viruses with capsids smaller than 60 nm dominated the viral assemblage throughout the estuary (63.0% to 72.1% of the total viral counts), and their distribution was positively correlated with that of viral lytic production. Interestingly, the gamma-proteobacteria explained a significant portion of the variance in the <60 nm and 60 to 90 nm tailless viruses (92% and 80%, respectively), and in the Myoviridae (73%). Also, 60% of the variance of the tailless larger viruses (>90 nm) was explained by the beta-proteobacteria. Overall, these results support the view that the environment, through selection mechanisms, probably shapes the structure of the prokaryotic community. This might be in turn a source of selection for the virioplankton community via specific affiliation favoring particular morphotypes and life strategies.


Integrated Quantum-Classical Protocol for the Realistic Description of Solvated Multinuclear Mixed-Valence Transition-Metal Complexes and Their Solvatochromic Properties.
Linear cyanide-bridged polymetallic complexes, which undergo photoinduced metal-to-metal charge transfer, represent prototypical systems for studying long-range electron-transfer reactions and understanding the role played by specific solute-solvent interactions in modulating the excited-state dynamics. To tackle this problem, while achieving a statistically meaningful description of the solvent and of its relaxation, one needs a computational approach capable of handling large polynuclear transition-metal complexes, both in their ground and excited states, as well as the ability to follow their dynamics in several environments up to nanosecond time scales. Here, we present a mixed quantum classical approach, which combines large-scale molecular dynamics (MD) simulations based on an accurate quantum mechanically derived force field (QMD-FF) and self-consistent QMD polarized point charges, with IR and UV-vis spectral calculations to model the solvation dynamics and optical properties of a cyano-bridged trinuclear mixed-valence compound (trans-[(NC)5FeIII(μ-CN)RuII(pyridine)4(μ-NC)FeIII(CN)5]4-). We demonstrate the reliability of the QMD-FF/MD approach in sampling the solute conformational space and capturing the local solute-solvent interactions by comparing the results with higher-level quantum mechanics/molecular mechanics (QM/MM) MD reference data. The IR spectra calculated along the classical MD trajectories in different solvents correctly predict the red shift of the CN stretching band in the aprotic medium (acetonitrile) and the subtle differences measured in water and methanol, respectively. By explicitly including the solvent molecules around the cyanide ligands and calculating the thermal averaged absorption spectra using time-dependent density functional theory calculations within the Tamm-Dancoff approximation, the experimental solvatochromic shift is quantitatively reproduced going from water to methanol, while it is overestimated for acetonitrile. This discrepancy can likely be traced back to the lack of important dispersion interactions between the solvent cyano groups and the pyridine substituents in our micro solvation model. The proposed protocol is applied to the ground state in water, methanol, and acetonitrile and can be flexibly generalized to study excited-state nonequilibrium solvation dynamics.


Event-based prospective memory is independently associated with self-report of medication management in older adults.
Identifying potentially modifiable risk factors for medication non-adherence in older adults is important in order to enhance screening and intervention efforts designed to improve medication-taking behavior and health outcomes. The current study sought to determine the unique contribution of prospective memory (PM) (i.e. 'remembering to remember') to successful self-reported medication management in older adults. Sixty-five older adults with current medication prescriptions completed a comprehensive research evaluation of sociodemographic, psychiatric, and neurocognitive functioning, which included the memory for adherence to medication scale (MAMS), prospective and retrospective memory questionnaire (PRMQ), and a performance-based measure of PM that measured both semantically related and semantically unrelated cue-intention (i.e. when-what) pairings. A series of hierarchical regressions controlling for biopsychosocial, other neurocognitive, and medication-related factors showed that elevated complaints on the PM scale of the PRMQ and worse performance on an objective semantically unrelated event-based PM task were independent predictors of poorer medication adherence as measured by the MAMS. PM plays an important role in self-report of successful medication management among older adults. Findings may have implications for screening for older individuals 'at risk' of non-adherence, as well as the development of PM-based interventions to improve medication adherence and, ultimately, long-term health outcomes in older adults.


Energy and water use by invasive goats (Capra hircus) in an Australian rangeland, and a caution against using broad-scale allometry to predict species-specific requirements.
Feral goats (Capra hircus) are ubiquitous across much of Australia's arid and semi-arid rangelands, where they compete with domestic stock, contribute to grazing pressure on fragile ecosystems, and have been implicated in the decline of several native marsupial herbivores. Understanding the success of feral goats in Australia may provide insights into management strategies for this and other invasive herbivores. It has been suggested that frugal use of energy and water contributes to the success of feral goats in Australia, but data on the energy and water use of free-ranging animals are lacking. We measured the field metabolic rate and water turnover rate of pregnant and non-pregnant feral goats in an Australian rangeland during late summer (dry season). Field metabolic rate of pregnant goats (601 ± 37 kJ kg(-0.73)d(-1)) was 1.3 times that of non-pregnant goats (456 ± 24 kJ kg(-0.73)d(-1)). The water turnover rate of pregnant goats (228 ± 18 mL kg(-0.79)d(-1)) was also 1.3 times that of non-pregnant goats (173 ± 18 kg(-0.79)d(-1)), but the difference was not significant (P=0.07). There was no significant difference in estimated dry matter digestibility between pregnant and non-pregnant goats (mean ca. 58%), blood or urine osmolality, or urine electrolyte concentrations, indicating they were probably eating similar diets and were able to maintain osmohomeostasis. Overall, the metabolic and hygric physiology of non-pregnant goats conformed statistically to the predictions for non-marine, non-reproductive placental mammals according to both conventional and phylogenetically independent analyses. That was despite the field metabolic rate and estimated dry matter intake of non-pregnant goats being only 60% of the predicted level. We suggest that general allometric analyses predict the range of adaptive possibilities for mammals, but that specific adaptations, as present in goats, result in ecologically significant departures from the average allometric curve. In the case of goats in the arid Australian rangelands, predictions from the allometric regression would overestimate their grazing pressure by about 40% with implications for the predicted impact on their local ecology.


Quantification of coronary artery calcium on the basis of dual-energy coronary CT angiography.
To evaluate the feasibility of using virtual noncontrast material-enhanced (VNC) computed tomographic (CT) series derived from dual-energy CT imaging studies for coronary artery calcium quantification. This HIPAA-compliant study was institutional review board approved; all patients provided written informed consent. Thirty-six patients prospectively underwent noncontrast-enhanced CT calcium scoring followed by coronary CT angiography performed in dual-energy mode. By using different reconstruction algorithms, three VNC series were generated and evaluated for noise and efficiency of virtual iodine removal. Two readers independently quantified calcium on VNC images and true noncontrast-enhanced conventional calcium scoring series. A leave-one-out cross validation was used to assess the accuracy of calcium score prediction from VNC series by means of linear regression. CT value histograms of the VNC series closely resembled the profile in the true noncontrast-enhanced series. There was excellent correlation between calcium volumes on the VNC series and true noncontrast-enhanced series on a per-patient (r = 0.94, P < .001, n = 36) and per-vessel (r = 0.94, 0.91, and 0.92 for the three coronary arteries, all P < .001, n = 36 each) level. The ability of a linear regression model to predict actual calcium scores from calcium volumes on VNC series was excellent (r = 0.82). Multiethnic Study of Atherosclerosis rankings that were derived from the predicted calcium scores also showed excellent agreement (intraclass correlation coefficient = 0.909). Coronary artery calcium identification and quantification based on dual-energy coronary CT angiographic studies may obviate the need for dedicated CT calcium scoring studies.


Synoviocyte innate immune responses: II. Pivotal role of IFN regulatory factor 3.
Innate immune responses contribute to synovial inflammation in rheumatoid arthritis. The present study was designed to investigate the contribution of IFN regulatory factor (IRF)3 and IRF7 to type I IFN-regulated gene expression in synoviocytes. Fibroblast-like synoviocytes were stimulated with polyinosinic-polycytidylic acid (poly [I-C]) after transfection with IRF3 or IRF7 small interfering RNA to knockdown transcription factor expression. Western blots, luciferase assay after transfection with reporter constructs, quantitative PCR, and AP-1 DNA binding ELISA were performed to evaluate the role of IRF3 and IRF7 in poly (I-C)-induced signaling and synoviocyte gene expression. IRF3 regulates IFN-stimulated response element (ISRE) promoter activity as well as IFN-beta, IRF5, IRF7, RANTES, IFN-inducible protein-10, MCP-1, and MIP1alpha gene expression in response to poly (I-C). IRF7 knockdown modestly decreased a subset of genes and ISRE activity, although the results were not statistically significant. Surprisingly, IRF3 knockdown almost completely blocked expression of additional genes in which the ISRE is not traditionally considered a dominant promoter site in fibroblast-like synoviocytes, including matrix metalloproteinase (MMP)3, MMP9, IL-6, and IL-8. Transcription factor activation studies demonstrated a role for IRF3 in regulation of c-Jun phosphorylation and AP-1 binding. IRF3 rather than IRF7 regulates poly (I-C)-induced type I IFN responses in human synoviocytes by increasing ISRE promoter activity. IRF3 also partially regulates expression of other cytokines and MMP through activation of c-Jun and the AP-1 promoter site. Targeting synoviocyte IRF3 represents a potential approach to suppress diverse mediators while limiting suppression of IRF7-mediated immune responses.


Poly[[(μ2-benzene-1,3-di-carboxyl-ato){μ2-1,4-bis-[(1H-imidazol-1-yl)meth-yl]benzene}-cadmium] di-methyl-formamide monosolvate].
The title coordination polymer, {[Cd(C8H4O4)(C14H14N4)]·C3H7NO} n , was synthesized by solvothermal reaction of metallic cadmium with the semi-rigid neutral ligand 1,4-bis-[(1H-imidazol-1-yl)meth-yl]benzene (bix) and the V-shaped benzene-1,3-di-carb-oxy-lic acid (m-H2bdc). The structure exhibits a pseudo-C-centring which is almost fulfilled by the polymeric metal complex but not by the solvent dimethylform-amide (DMF) mol-ecules. The asymmetric unit contains two independent Cd(II) ions, two m-bdc(2-) ligands, one and two half bix ligands, and two solvent DMF mol-ecules. The Cd(II) ions are both five-coordinated by three O atoms from two different m-bdc(2-) ligands and two N atoms from two different bix ligands in a distorted square-pyramidal geometry. The m-bdc(2-) ligands adopt a chelate-monodentate coordination mode, connecting neighboring Cd(II) ions into a zigzag chain parallel to [110]. Adjacent chains are further cross-linked by bix ligands, giving rise to a puckered sheet nearly perpendicular to the chain direction. Thus, each Cd(II) ion is connected to four neighboring Cd(II) ions through two m-bdc(2-) anions and two bix ligands, giving rise to the final non-inter-penetrating uninodal layer with sql (4,4) topology.


Rapid enzyme analysis of amniotic fluid phospholipids containing choline: a comparison with the lecithin to sphingomyelin ratio in prenatal assessment of fetal lung maturity.
The relation between the choline containing surfactant phospholipids lecithin and sphingomyelin in amniotic fluid and fetal lung maturity is well established. An enzymatic method that had been automated and optimised for use on a centrifugal analyser was used to measure the total choline containing phospholipids in amniotic fluid. The total time taken for this assay was 10 minutes. The results obtained from 100 patient samples, using this procedure, compared favourably with the results obtained by the thin layer chromatography procedure used to determine the lecithin to sphingomyelin ratio (r = 0.93). A clinical study of 60 patients showed that this assay predicted prenatal respiratory distress syndrome as well as the lecithin to sphingomyelin ratios. The advantage of this assay over existing procedures is that it requires minimum preparation of the specimen and no extraction, is quick, and shows a high degree of precision.


Kin selection-mutation balance: a model for the origin, maintenance, and consequences of social cheating.
Social conflict, in the form of intraspecific selfish "cheating," has been observed in a number of natural systems. However, a formal, evolutionary genetic theory of social cheating that provides an explanatory, predictive framework for these observations is lacking. Here we derive the kin selection-mutation balance, which provides an evolutionary null hypothesis for the statics and dynamics of cheating. When social interactions have linear fitness effects and Hamilton's rule is satisfied, selection is never strong enough to eliminate recurrent cheater mutants from a population, but cheater lineages are transient and do not invade. Instead, cheating lineages are eliminated by kin selection but are constantly reintroduced by mutation, maintaining a stable equilibrium frequency of cheaters. The presence of cheaters at equilibrium creates a "cheater load" that selects for mechanisms of cheater control, such as policing. We find that increasing relatedness reduces the cheater load more efficiently than does policing the costs and benefits of cooperation. Our results provide new insight into the effects of genetic systems, mating systems, ecology, and patterns of sex-limited expression on social evolution. We offer an explanation for the widespread cheater/altruist polymorphism found in nature and suggest that the common fear of conflict-induced social collapse is unwarranted.


Rapid changes in shape and cell architecture of isolated fragments of amphibian embryonic tissues as an experimental model of morphogenesis.
Changes in the shape and cell architecture of pieces of epithelial and neural ectoderm, mesoderm, neural tube, and combined ectomesodermal fragments from embryos of Rana temporaria 0-60 min after isolation were studied. The fragments were capable of changing their shape quickly (actually during separation) or after a latent period of several minutes. Rapid deformations were not prevented by cooling or by moderate doses of cyanide; as a rule they were connected with contraction of the surface area of the cells of the fragment and they can be regarded as relaxation to forms with lower mechanical energy. The direction of the deformation usually coincides with the subsequent normal morphogenesis of the particular anlage. Deformations with a latent period are suppressed by cooling and by the addition of cyanide, which lead to an increase in the surface area of individual cells, but they reduce the total surface area of the fragment. The shape of the fragments becomes more complex: they become irregularly twisted, they form folds, and they separate into spherical regions with stretched surfaces ("drops"). These processes are connected with the performance of positive mechanical work by the intracellular contractile systems. The reasons why the fragments become more complex in shape are discussed.


Non-Canonical and Sexually Dimorphic X Dosage Compensation States in the Mouse and Human Germline.
Somatic X dosage compensation requires two mechanisms: X inactivation balances X gene output between males (XY) and females (XX), while X upregulation, hypothesized by Ohno and documented in vivo, balances X gene with autosomal gene output. Whether X dosage compensation occurs in germ cells is unclear. We show that mouse and human germ cells exhibit non-canonical X dosage states that differ from the soma and between the sexes. Prior to genome-wide reprogramming, X upregulation is present, consistent with Ohno's hypothesis. Subsequently, however, it is erased. In females, erasure follows loss of X inactivation, causing X dosage excess. Conversely, in males, erasure leads to permanent X dosage decompensation. Sex chromosomally abnormal models exhibit a "sex-reversed" X dosage state: XX males, like XX females, develop X dosage excess, while XO females, like XY males, develop X dosage decompensation. Thus, germline X dosage compensation states are determined by X chromosome number, not phenotypic sex. These unexpected differences in X dosage compensation states between germline and soma offer unique perspectives on sex chromosome infertility.


Microscopy outperformed in a comparison of five methods for detecting Trichomonas vaginalis in symptomatic women.
In the UK, despite its low sensitivity, wet mount microscopy is often the only method of detecting Trichomonas vaginalis infection. A study was conducted in symptomatic women to compare the performance of five methods for detecting T. vaginalis: an in-house polymerase chain reaction (PCR); Aptima T. vaginalis kit; OSOM ®Trichomonas Rapid Test; culture and microscopy. Symptomatic women underwent routine testing; microscopy and further swabs were taken for molecular testing, OSOM and culture. A true positive was defined as a sample that was positive for T. vaginalis by two or more different methods. Two hundred and forty-six women were recruited: 24 patients were positive for T. vaginalis by two or more different methods. Of these 24 patients, 21 patients were detected by real-time PCR (sensitivity 88%); 22 patients were detected by the Aptima T. vaginalis kit (sensitivity 92%); 22 patients were detected by OSOM (sensitivity 92%); nine were detected by wet mount microscopy (sensitivity 38%); and 21 were detected by culture (sensitivity 88%). Two patients were positive by just one method and were not considered true positives. All the other detection methods had a sensitivity to detect T. vaginalis that was significantly greater than wet mount microscopy, highlighting the number of cases that are routinely missed even in symptomatic women if microscopy is the only diagnostic method available.


Incidence of venous thromboembolism in young Swedish women and possibly preventable cases among combined oral contraceptive users.
We wanted to study the incidence of venous thromboembolism (VTE), acquired risk factors of VTE and preventable cases among users of combined oral contraceptives (COCs). All women aged 15-44 years, (n = 24 373) living in the county of Jämtland, Sweden, between 1991 and 2000, constituted the study base in a retrospective case-reference study. Women with VTE were identified through hospital registers and interviewed by telephone. The utilization of COCs according to age was obtained from a prospective prescription database, and data from national health databases were used. Of 88 women with first-time VTE, 43 (49%) were COC users and 13 (15%) were pregnant. All women had at least one known risk factor, and 51 (58%) women had combinations of risk factors. The total incidence rate of VTE per 100,000 women-years for all women were 36 (29-44), for nonusers 19 (12-25) for women using third generation COCs 115 (67-184), for women using other COCs 60 (37-83), and for women during pregnancy and postpartum 103 (55-177). Of the total 244,000 women-years represented, COC users constituted 24%, pregnant women 5%, and women with other acquired risk factors 5%. The corresponding incidence rates after excluding VTE cases with other acquired risk factors were 10 (6-14), 1.2 (0.14-4.4), 64 (29-121), 27 (13-48), and 59 (24-121), per 100,000 women-years. In 11 (26%) of the COC-related VTE cases, there were relative contraindications for use of COCs or lack of thromboprophylaxis in relation to surgery. CONCLUSION. We found a very low incidence of idiopathic VTE among young non-OC users. The incidence of VTE during pregnancy was only slightly higher than during COC use. It was considered that a significant part of COC-related VTE might have been avoided.


A health risk assessment for exposure to trace metals via drinking water ingestion pathway.
A health risk assessment was conducted for exposure to trace metals via drinking water ingestion pathway for Province of Izmir, Turkey. Concentrations of 11 trace metals were measured in drinking waters collected from 100 population weighted random sampling units (houses). The samples were analyzed in atomic absorption spectrometry for arsenic, and inductively coupled plasma-optical emission spectrometry for Be, Cd, Co, Cr, Cu, Mn, Ni, Pb, V, and Zn. Questionnaires were administered to a participant from each sampling unit to determine drinking water consumption related information and demographics. Exposure and risks were estimated for each individual by direct calculation, and for Izmir population by Monte Carlo simulation. Six trace metals (As, Cr, Cu, Mn, Ni, and Zn) were detected in >50% of the samples. Concentrations of As and Ni exceeded the corresponding standards in 20% and 58% of the samples, respectively. As a result, arsenic noncarcinogenic risks were higher than the level of concern for 19% of the population, whereas carcinogenic risks were >10(-4) for 46%, and >10(-6) for 90% of the population.


Low-dose topiramate plus sodium divalproate for positive responders intolerant to full-dose monotherapy.
Neuromodulators such as topiramate (TPM) and divalproex sodium (DVS) are effective in the preventive treatment of migraine. Nonetheless, patients often discontinue their use due to side effects. The study aims to determine whether the combination of lower doses of TPM and DVS may be useful for patients responsive to higher doses of the individual drugs but experiencing intolerable side effects. This clinic-based study was conducted to evaluate a series of patients who experienced at least a 50% reduction in headache frequency after 6 weeks of treatment with either TPM 100 mg/day or DVS 750 mg/day, but suffered intolerable drug-related side effects. At that point, patients were switched to TPM (50 mg in the morning and 25 mg at night) plus DVS 500 mg/day (single dose) and reevaluated after 6 further weeks. Thirty-eight patients were evaluated. Mean age was 37 years, and 84% were female. Of the 38, 17 (77.3%) initially were using TPM only, and 10 (62.5%) initially were using DVS only. After 6 weeks on combination therapy, 27 (62.9%) reported improved tolerability without any decrease in efficacy. Five patients who initially were using TPM only and six using DVS only failed to return for follow-up or were noncompliant with treatment due to persistent or worsening side effects. This small, open-label study suggests that the combination of TPM and DVS in doses lower than those typically used for migraine prophylaxis may be an effective option for patients who benefited from higher doses of these same medications used as monotherapy but were unable to tolerate such treatment due to side effects.


[Analysis of proxemic factors in the communication with laryngectomized patients].
The present study analyzed the proxemic factors of interactions between health professionals and laryngotomized patients in mediate post-surgery. We used the non-participant observation technique with pre-established guidelines. Data were analyzed according to Hall's theoretical framework. The speakers' sex or color did not influence the distance maintained in the interactions; the nursing technical care category was predominant; the attitude adopted was compatible with the meeting goals; instrumental touch with visual contact was predominant, voice tone was adequate to the distances maintained and the authors observed the presence of obstacles in some interactions, which demonstrated that communication was impaired.


Retrograde horseradish peroxidase transport after oculomotor nerve injury.
We studied the distribution of somatic motor neurons innervating the cat superior rectus 3-6 months after oculomotor nerve injury using intramuscular horseradish peroxidase (HRP). In normal cats, 98% or more of the labelled superior rectus motoneurons were in the contralateral oculomotor subnucleus. Two experimental cats who exhibited little or no evidence of recovery showed few labelled cells (4% of controls) which were distributed in both the ipsilateral and contralateral oculomotor nucleus. The other three experimental cats demonstrated definite signs of recovery, and HRP injections labelled more cells (20% of controls) also distributed in the ipsilateral and contralateral oculomotor subnuclei. This study shows that, after sectioning, the oculomotor nerve regenerates and anomalous connections develop between the somatic motoneurons of the ipsilateral oculomotor nucleus and the superior rectus. These findings support the hypothesis that acquired oculomotor synkinesis developing after third nerve injury results from misdirection of regenerating axons.


Reshapable hydrogel tissue expander for ridge augmentation: Results of a series of successive insertions at the same intraoral site.
Oral mucosa expansion before ridge augmentation is a procedure to reduce soft tissue exposure and to improve bone graft density and volume after augmentation. This study explored a novel, shapeable hydrogel tissue expander (HTE) in intraoral sites that had undergone previous expansion and surgery. Nine beagle dogs had all premolar teeth extracted and adjacent alveolar bone reduced. After at least 3 months healing hydrogels were placed at 4 sites in each dog: maxilla and mandible, right and left. After 6 weeks of expansion, the hydrogels were removed and measured for volume expansion and physical condition. Punch biopsies were taken of the expanded oral mucosa. After 3 months, a second hydrogel insertion was performed at each of the same sites. After this second expansion cycle, volume and hydrogel condition were recorded. Three dogs received ultrasound imaging of the hydrogels during the second expansion. Necropsy specimens were taken of both expanded and non-expanded oral mucosa. Within 2 weeks after HTE insertion in both first and second insertions, blood flow returned to the pre-insertion level. The first and second insertions resulted in linear oral mucosa gain of 8.13 mm, and 6.44 mm, respectively. First and second insertion hydrogels erupted from 4% of the first expansion sites, and 3% of the second expansion sites. There was no directional migration of the expanding hydrogel at any site. Histology found little inflammatory reaction to any hydrogel implant. Oral mucosa can be consistently and successfully expanded before bone graft for ridge augmentation even at sites with a history of prior surgeries.


[Isolation of a field strain of Babesia bigemina (Piroplasma: Babesiidae) and establishment of in vitro culture for antigen production].
Isolation of a field strain of Babesia bigemina (Piroplasma: Babesiidae) and establishment of in vitro culture for antigen production. Bovine b abesiosis, caused by Babesia bigemina, is a barrier for livestock development; it results in high economic loss to Mexican livestock. Control requires adequate antigens for diagnosis and vaccination programs. However, because of antigenic variation among Babesia strains, it is necessary to use antigens prepared from local strains. The purpose of the present study was to isolate a local field strain and to establish the in vitro culture of B. bigemina by the evaluation of the constituent's concentration of culture media. Thirty engorged female Boophilus microplus were collected from cattle suffering clinical babesiosis (B. bigemina) in Yucatan state, Mexico. These ticks were sent to the laboratory for detection of Babesia sp. vermicules. Eggs were kept at 83-85 % humidity and 27 degrees C until hatching. Larvae were transferred to an esplenectomized calf (B-1). The resulting nymphs were transferred to an esplenectomized calf (B-2). Twelve days later, B. bigemina (local strain) was detected in calf B-2 and its infected blood was frozen in liquid nitrogen to initiate the in vitro culture. The Microaerophilus Stationary Phase (MASP) in vitro culture method was used to reactivate the parasite. Three different concentrations of culture media (70, 60 and 50%), serum (30, 40 and 50%) and uninfected red blood cells (5, 10 and 15 %) were used in order to know the convenient concentrations to obtain the highest percentage of infected red blood cells (PEI). The cultured strain was used to prepare antigens for the Immunofluorescence Antibody Test (IFAT) and several concentrations of serum and conjugate were tested. Strain isolation was successful; 30 days were needed to obtain a PEI of 1.5%. The isolated strain was frozen in liquid nitrogen and the parasites were reactivated with the in vitro culture MASP method. The concentration of culture media that produced the highest PEI (14%) (p < 0.05) was 30% serum, 70% M199 and 5%. Uninfected Red Blood cells antigens were successfully used in the IFAT and the best dilutions to differentiate between positive and negative controls were serum 1:80 and conjugate 1:80. The isolated B. bigemina local strain requires particular conditions of in vitro culture by the MASP method to reach high numbers of infected red blood cells, needed to prepare and provide high quality antigens for serological diagnosis of B. bigemina.