Intergroup contact, attitudes toward homosexuality, and the role of acceptance of gender non-conformity in young adolescents.
This study explored how contact with gay and lesbian persons affects adolescents' attitudes toward them, and whether this association is mediated or moderated by one's acceptance of gender non-conformity. We analyzed survey responses from 456 Dutch adolescents aged 12-15 who reported having no same-sex attractions. Data were collected in 2008 at 8 schools in Amsterdam, the Netherlands. Preliminary analyses showed that contact with lesbian/gay persons outside of school was positively associated with attitudes toward lesbians and gay men. Multilevel analyses showed that acceptance of gender non-conformity mediated rather than moderated the relationship between intergroup contact and sexual prejudice in males. The effect of intergroup contact on females' attitudes toward lesbian women was no longer significant in multilevel analyses. The findings suggest that attention to both intergroup contact and acceptance of gender non-conformity would enhance our understanding of attitudes toward homosexuality in adolescents.


Biogeography of the large intestinal mucosal and luminal microbiome in cynomolgus macaques with depressive-like behavior.
Most previous studies in the pathophysiology of major depressive disorder (MDD) focused on fecal samples, which limit the identification of the gut mucosal and luminal microbiome in depression. Here, we address this knowledge gap. Male cynomolgus macaques (Macaca fascicularis) were randomly assigned to a chronic unpredictable mild stress (CUMS) group, or to an unstressed control group. Behavioral tests were completed in both groups. At endpoint, microbe composition of paired mucosal and luminal samples from cecum, ascending, transverse, and descending colons were determined by 16S ribosomal RNA gene sequencing. The levels of 34 metabolites involved in carbohydrate or energy metabolism in luminal samples were measured by targeted metabolomics profiling. CUMS macaques demonstrated significantly more depressive-like behaviors than controls. We found differences in mucosal and luminal microbial composition between the two groups, which were characterized by Firmicutes and Bacteriodetes at the phylum level, as well as Prevotellaceae and Lachnospiraceae at the family level. The majority of discriminative microbes correlated with the depressive-like behavioral phenotype. In addition, we found 27 significantly different microbiome community functions between the two groups in mucosa, and one in lumen, which were mainly involved in carbohydrate and energy metabolism. A total of nine metabolites involved in these pathways were depleted in CUMS animals. Together, CUMS macaques with depressive-like behaviors associated with distinct alterations of covarying microbiota, carbohydrate and energy metabolism in mucosa and lumen. Further studies should focus on the mucosal and luminal microbiome to provide a deeper spatiotemporal perspective of microbial alterations in the pathogenesis of MDD.


Unique morphology of HeLa cell attachment, spreading and detachment from microcarrier beads covalently coated with a specific and non-specific substratum.
A SEM and TEM evaluation of adhesion of HeLa-S3 cells to suspensions of culture microcarriers coated with various substrata revealed two unique cell morphologies. One is similar to that for cells attaching to culture dishes and the other one only appeared with microcarriers stirred under high shear conditions. The usual appearance of a spreading cell is to change from a sphere to the shape of a 'fried egg'. This proceeded in HeLa cells by a radial extension of the filopodia in between which the cytoplasm subsequently filled. Fluorescent antibody staining of actin suggested that more actin was present at the periphery of the spreading edges of the cell than inwards. The above morphology was characteristic of HeLa cell attachment to gelatin-coated microcarriers. However, the morphology of the attachment to microcarriers coated with non-biological substances such as negatively charged sulfonate groups or positively charged polyethyleneimine or even with the attachment protein laminin was quite different. Here the cells attached and began to spread as with gelatin-microcarriers, however, the spreading was not radial but occurred from one or two major regions of the cell periphery. The cell then appeared to constrict with the formation of a substratum attached pedestal upon which the cell body was perched. With time the cell pinched-off from pedestal. Evidence indicated that the pedestal was quite fragile. Furthermore, fluorescent antiactin staining indicated that the initial spreading region contained abundant actin which was depleted upon pedestal formation and detachment. The above in addition to previous kinetic measurements provided the information to classify cell substrate attachment materials into two distinct types. One is specific substrata which promote normal attachment and spreading and appear to interact with specific cell surface proteins. The other is non-specific substrata which in high shear conditions induces pedestal formation followed by pinching-off of the cells. Had previous attachment assays been done under high shear as done with the microcarriers and HeLa cells it is likely that substrata classified as specific might be reclassified into non-specific.


REVascularization with paclitaxEL-coated balloon angioplasty versus drug-eluting stenting in acute myocardial infarcTION-A randomized controlled trial: Rationale and design of the REVELATION trial.
In primary percutaneous coronary intervention (PPCI) for ST-elevation myocardial infarction (STEMI), stenting has proved to reduce the need for repeat revascularization compared with balloon angioplasty alone. The incidence of cardiac death or recurrent myocardial infarction, though, is not reduced by stenting. This is in part attributable to stent-related complications like stent thrombosis which may occur even years after implantation. A strategy of drug coated balloon (DCB) angioplasty without stenting would abolish the potential disadvantages of stent implantation while reducing the probability of restenosis observed in plain old balloon angioplasty. Our aim is to evaluate the efficacy and safety of a DCB only strategy versus drug-eluting stents (DES) in PPCI for STEMI. The REVELATION trial is a prospective, single center, randomized study, in which 120 patients presenting with STEMI will be allocated to treatment with a DCB versus DES. Appertaining to the established prognostic value of fractional flow reserve (FFR) rather than angiographic lesion severity, the functional assessment of the infarct-related lesion by FFR at 9 months after initial treatment is the primary end point. Assuming an FFR value of 0.90 after stenting and an increased risk of adverse events if post-PCI FFR <0.85, we decided to accept an FFR value of ≥0.85 after DCB only at follow-up as noninferiority margin. Secondary end points include major adverse cardiac events up to 5-year follow-up. Our trial will address the efficacy and safety of DCB angioplasty versus DES in the setting of PPCI for STEMI. The REVELATION trial will introduce the recognized prognostic significance of physiologic assessment of the infarct-related lesion by FFR at 9 months follow-up as primary end point. © 2015 Wiley Periodicals, Inc.


Brief communication: the ecosystem perspective in ecotoxicology as a way forward for the ecological risk assessment of chemicals.
One of the objectives of the European Union (EU) ecological risk assessment of chemicals (ERA) is to derive maximum environmental concentrations that are not expected to cause adverse ecological effects. To this end, related EU directives list protection goals as well as guidelines that should be used to reach these goals. It is generally accepted that the individual-level endpoints on which these guidelines are based do not correspond to the listed population- and ecosystem-level protection goals. In this article, we identify 5 research topics that are key to bridging this gap: 1) the refinement of population-level effects and recovery rates by explicitly taking into account competition and 2) predation, 3) the assessment of chemical effects on biodiversity, 4) the assessment of chemical stress on ecosystem functions and services, and 5) the quantification of the effects of chemical mixtures. In addition, we illustrate why an ecosystem perspective is needed to address these topics and to inform the risk assessment process. We propose the use of existing ecotoxicological community, food web, and ecosystem models to tackle these issues and discuss why new models are needed to predict chemical effects on biodiversity.


Prognostic impact of number of examined lymph nodes on survival of patients with appendiceal neuroendocrine tumors.
The prognosis of patients with appendiceal neuroendocrine tumors (ANETs) is related to lymph node (LN) metastasis and other factors. However, it is unclear how the number of examined LNs (ELNs) impact on survival. To determine the factors affecting the cancer-specific survival (CSS) of patients with ANET and to evaluate the impact of the number of ELNs on survival. A total of 4583 ANET patients were analyzed in the Surveillance, Epidemiology, and End Results database. Univariate survival analysis was used to identify factors related to survival and the optimal number of ELNs and lymph node ratio (LNR) were determined by the Kaplan-Meier method. The survival difference was determined by CSS. Except for sex, the other factors, such as age, year, race, grade, histological type, stage, tumor size, ELNs, LNR, and surgery type, were associated with prognosis. The 3-, 5-, and 10-year CSS rates of ANET patients were 91.2%, 87.5, and 81.7%, respectively (median follow-up period of 31 mo and range of 0-499 mo). There was no survival difference between the two surgery types, namely, local resection and colectomy or greater, in both stratifications of tumor size ≥ 2 cm (P = 0.523) and < 2 cm (P = 0.068). In contrast to patients with a tumor size < 2 cm, those with a tumor size ≥ 2 cm were more likely to have LN metastasis (χ 2 = 378.16, P < 0.001). The optimal number of ELNs was more than 11, 7, and 18 for all patients, node-negative patients, and node-positive patients, respectively. CSS rates of patients with a larger number of ELNs were significantly improved (≤ 10 vs ≥ 11, χ 2 = 20.303, P < 0.001; ≤ 6 vs ≥ 7, χ 2 = 11.569, P < 0.001; ≤ 17 vs ≥ 18, χ 2 = 21.990, P < 0.001; respectively). ANET patients with an LNR value ≤ 0.16 were more likely to have better survival than those with values of 0.17-0.48 (χ 2 = 48.243, P < 0.001) and 0.49-1 (χ 2 = 168.485, P < 0.001). ANET ≥ 2 cm are more likely to develop LN metastasis. At least 11 ELNs are required to better evaluate the prognosis. For patients with positive LN metastasis, 18 or more LNs need to be detected and lower LNR values (LNR ≤ 0.16) indicate a better survival prognosis.


Multi-SNP Haplotype Analysis Methods for Association Analysis.
Haplotype analysis forms the basis of much of genetic association analysis using both related and unrelated individuals (we concentrate on unrelated). For example, haplotype analysis indirectly underlies the SNP imputation methods that are used for testing trait associations with known but unmeasured variants and for performing collaborative post-GWAS meta-analysis. This chapter is focused on the direct use of haplotypes in association testing. It reviews the rationale for haplotype-based association testing, discusses statistical issues related to haplotype uncertainty that affect the analysis, then gives practical guidance for testing haplotype-based associations with phenotype or outcome trait, first of candidate gene regions and then for the genome as a whole. Haplotypes are interesting for two reasons, first they may be in closer LD with a causal variant than any single measured SNP, and therefore may enhance the coverage value of the genotypes over single SNP analysis. Second, haplotypes may themselves be the causal variants of interest and some solid examples of this have appeared in the literature.This chapter discusses three possible approaches to incorporation of SNP haplotype analysis into generalized linear regression models: (1) a simple substitution method involving imputed haplotypes, (2) simultaneous maximum likelihood (ML) estimation of all parameters, including haplotype frequencies and regression parameters, and (3) a simplified approximation to full ML for case-control data.Examples of the various approaches for a haplotype analysis of a candidate gene are provided. We compare the behavior of the approximation-based methods and argue that in most instances the simpler methods hold up well in practice. We also describe the practical implementation of haplotype risk estimation genome-wide and discuss several shortcuts that can be used to speed up otherwise potentially very intensive computational requirements.


Valuing adaptive programming: A study of resilience processes and outcomes.
Recent decades have seen a growth in theoretical frameworks focusing on systems, context and the dynamic interplay of multiple variables, stimulating interest in complementary research and programme evaluation methods. With resilience theory now emphasising the complex and dynamic nature of resilience capacities, processes and outcomes, resilience programming stands to benefit from approaches such as design-based research and realist research/evaluation. The aim of this collaborative (researcher/practitioner) study was to explore how such benefits can be achieved when programme theory spans individual, community and institutional outcomes, with a focus on the reciprocal processes involved in effecting change across the social system. The context of the research was a regional (Middle East and North Africa) project operating in contexts with an escalated risk of marginalised young people being drawn into illegal/harmful activity. The project's youth engagement and development approach combined participatory learning, skills training, and collective social action, adapted for diverse localities and during the COVID-19 crisis. Quantitative measures of individual and collective resilience were at the centre of a set of realist analyses evidencing systemic connections in changes to individual, collective and community resilience. Findings demonstrated the value, challenges and limitations of the applied research approach for adaptive, contextualised programming.


Infection by the parasitic helminth Trichinella spiralis activates a Tas2r-mediated signaling pathway in intestinal tuft cells.
The parasitic helminth Trichinella spiralis, which poses a serious health risk to animals and humans, can be found worldwide. Recent findings indicate that a rare type of gut epithelial cell, tuft cells, can detect the helminth, triggering type 2 immune responses. However, the underlying molecular mechanisms remain to be fully understood. Here we show that both excretory-secretory products (E-S) and extract of T. spiralis can stimulate the release of the cytokine interleukin 25 (IL-25) from the mouse small intestinal villi and evoke calcium responses from tuft cells in the intestinal organoids, which can be blocked by a bitter-taste receptor inhibitor, allyl isothiocyanate. Heterologously expressed mouse Tas2r bitter-taste receptors, the expression of which is augmented during tuft-cell hyperplasia, can respond to the E-S and extract as well as to the bitter compound salicin whereas salicin in turn can induce IL-25 release from tuft cells. Furthermore, abolishment of the G-protein γ13 subunit, application of the inhibitors for G-protein αo/i, Gβγ subunits, and phospholipase Cβ2 dramatically reduces the IL-25 release. Finally, tuft cells are found to utilize the inositol triphosphate receptor type 2 (Ip3r2) to regulate cytosolic calcium and thus Trpm5 activity, while potentiation of Trpm5 by a sweet-tasting compound, stevioside, enhances tuft cell IL-25 release and hyperplasia in vivo. Taken together, T. spiralis infection activates a signaling pathway in intestinal tuft cells similar to that of taste-bud cells, but with some key differences, to initiate type 2 immunity.


Recombinant goose-type lysozyme in channel catfish: lysozyme activity and efficacy as plasmid DNA immunostimulant against Aeromonas hydrophila infection.
The objectives of this study were: 1) to investigate whether recombinant channel catfish lysozyme-g (CC-Lys-g) produced in Escherichia coli expression system possesses any lysozyme activity; and 2) to evaluate whether channel catfish lysozyme-g plasmid DNA could be used as an immunostimulant to protect channel catfish against Aeromonas hydrophila infection. Recombinant CC-Lys-g produced in E. coli expression system exhibited significant (P < 0.05) lytic activity against Gram-positive Micrococcus lysodeikticus and Gram-negative A. hydrophila. When pcDNA3.2-vectored recombinant channel catfish lysozyme-g (pcDNA-Lys-g) was transfected in channel catfish gill cells G1B, the over-expression of pcDNA-Lys-g offered significant (P < 0.05) protection to G1B cells against A. hydrophila infection. When channel catfish were intraperitoneally injected with pcDNA-Lys-g along with an adjuvant QCDCR, the transcriptional level of Lys-g was significantly (P < 0.05) increased. When pcDNA-Lys-g injected fish was challenged with a highly virulent A. hydrophila strain AL-09-71, pcDNA-Lys-g offered 100% protection to channel catfish at two days post DNA injection. Macrophages of fish injected with pcDNA-Lys-g produced significantly (P < 0.05) higher amounts of reactive oxygen species and nitric oxide than that of fish injected with pcDNA vector alone at two days post DNA injection. Taken together, our results suggest that pcDNA-Lys-g could be used as a novel immunostimulant to offer immediate protection to channel catfish against A. hydrophila infection.


Plasma proline kinetics and the regulation of proline synthesis in man.
A quantitative exploration of the regulation of plasma proline concentration, proline oxidation, and proline endogenous biosynthesis was undertaken utilizing a 360-minute primed continuous infusion of L-[1-13C]proline and L-[methyl-2H3]leucine in healthy, postabsorptive young men. The response of proline metabolism to the intravenous administration of two physiologic rates of L-proline, as well as the withdrawal of an L-proline infusion, were examined. The administration of L-proline at 20 mumol.kg-1.h-1 after an overnight fast resulted in a higher steady state plasma proline concentration, attained within 100 minutes, and this was associated with an increase in proline oxidation, from a baseline value of 10.9 to 16.1 mumol.kg-1.h-1 (P less than .01). Additionally, there was a decrease in proline endogenous synthesis from 15.8 (baseline) to 5.3 mumol.kg-1.h-1 (P less than .01). Administration of L-proline at 40 mumol.kg-1.h-1 after an overnight fast resulted again in a higher plasma steady state proline concentration, attained within 100 minutes and with an associated increase in proline oxidation from 13.1 to 20.0 mumol.kg-1.h-1 (P less than .01) and with a decrease in proline endogenous synthesis from 12.2 to -0.6 mumol.kg-1.h-1 (P less than 0.01). The withdrawal of L-proline after a 20 mumol.kg-1.h-1 infusion resulted in a lower plasma steady state proline level and this was accompanied by a decrease in proline oxidation from 21.2 to 18.2 mumol.kg-1.h-1 (P less than .05) and an increase in endogenous synthesis from 22.2 to 29.7 mumol.kg-1.h-1 (P less than .01).(ABSTRACT TRUNCATED AT 250 WORDS)


Ipecac root extracts and isolated circular peptides differentially suppress inflammatory immune response characterised by proliferation, activation and degranulation capacity of human lymphocytes in vitro.
Circular peptides are attractive lead compounds for drug development; this study investigates the immunomodulatory effects of defined root powder extracts and isolated peptides (called cyclotides) from Carapichea ipecacuanha (Brot.) L. Andersson ('ipecac'). Changes in the viability, proliferation and function of activated human primary T cells were analysed using flow cytometry-based assays. Three distinct peptide-enriched extracts of pulverised ipecac root material were prepared via C18 solid-phase extraction and analysed by reversed-phase HPLC and mass spectrometry. These extracts induced caspase 3/7 dependent apoptosis, thus leading to a suppressed proliferation of activated T cells and a reduction of the number of cells in the G2 phase. Furthermore, the stimulated T cells had a lower activation potential and a reduced degranulation capacity after treatment with ipecac extracts. Six different cyclotides were isolated from C. ipecacuanha and an T cell proliferation inhibiting effect was determined. Furthermore, the degranulation capacity of the T cells was diminished specifically by some cyclotides. In contrast to kalata B1 and its analog T20K, secretion of IL-2 and IFN- γ was not affected by any of the caripe cyclotides. The findings add to our increased understanding of the immunomodulating effects of cyclotides, and may provide a basis for the use of ipecac extracts for immunomodulation in conditions associated with an exessive immune responses.


Evidence of artificial habitat use by a recovering marine predator in southern California.
The giant sea bass Stereolepis gigas Ayres 1859 (GSB) is a critically endangered top marine predator in California. Since protection in 1982 and 1994, the population has appeared to increase, and individuals within a growing population may expand their ranges to new habitats to reduce intraspecific competition and increase foraging opportunities. In 2016-2018, two GSB tagged with acoustic transmitters were detected at artificial reefs for periods of up to 3 months during October-March, and one individual travelled 53 km from an offshore island to mainland California in 56 h. Artificial reefs may provide important foraging opportunities for these protected marine predators as they recover from exploitation.


Evaluation of FlaB1, FlaB2, FlaB3, and Tp0463 of Treponema pallidum for serodiagnosis of syphilis.
Syphilis is a multistage disease caused by the invasive spirochete Treponema pallidum subsp. pallidum, and accurate diagnosis is important for the prevention and treatment of syphilis. Here, to identify appropriate diagnostic antigens for serodiagnosis of syphilis, 6 recombinant proteins were expressed in Escherichia coli and purified, including flagellins (FlaB1 [Tp0868], FlaB2 [Tp0792], and FlaB3 [Tp0870]), Tp0463, Tp0751, and Tp1038. The sensitivities were determined by screening sera from individuals with primary (n=82), secondary (n=115), latent (n=105), and congenital (n=65) syphilis. The specificities were determined by screening sera from uninfected controls (n=30) and potentially cross-reactive infections including Lyme disease (n=30), leptospirosis (n=5), and hepatitis B (n=30). Our data showed that FlaB1, FlaB2, FlaB3, Tp0463, and Tp1038 exhibited higher overall sensitivities and specificities for detecting IgG antibody, with 95.4% and 98.9%, 92.6% and 95.8%, 95.1% and 95.8%, 92.6% and 97.9%, and 95.9% and 98.9%, respectively. In contrast, Tp0751 demonstrated only an overall sensitivity of 39.2%. For comparison, the sensitivity and specificity of Architect Syphilis TP were determined to be 98.1% and 93.7%, respectively. In addition, FlaB1, FlaB2, FlaB3, and Tp0463 demonstrated excellent performance for detecting IgM antibody in primary and congenital syphilis, with sensitivities of 76.8% and 83.1%, 72.0% and 87.7%, 74.4% and 89.2%, and 64.6% and 75.3%, respectively. These results indicate that FlaB1, FlaB2, FlaB3, and Tp0463 could be as novel diagnostic candidates for serodiagnosis of syphilis.


Retracted: Multifactor Analysis and Intervention Study on Menstrual Disorders of Female Athletes in the Context of the Winter Olympic Games: A Case-Control Study Based on a Large Sample.
[This retracts the article DOI: 10.1155/2022/2985557.].


Retrospective economic evaluation of the Hellenic Air Force Teleconsultation Project.
Hellenic Air Force introduced its teleconsultation project in 2002 by the establishment of PC-based videoconference links between the Central Air Force Hospital in Athens, Greece and several remote camps in order to serve the personnel and their dependants. A retrospective cost-minimization analysis was conducted for 38 remote subjects that were telemedically examined, instead of being referred to the hospital. For the evaluation of the annual cost of both procedures (telemedicine and referral), the fixed and variable costs were estimated. Furthermore, a simplified sensitivity analysis was conducted. The telemedical system proved to be cost-effective even for the limited number of 38 enrollees. Sensitivity analysis suggested that upon upgrade of the service as an integral component of daily care with subsequent higher number of beneficiaries and users of the system, the cost of each session would decrease dramatically. Current technology indicates that telemedical systems could provide efficient and cost-effective care to eligible enrollees.


Axial length measurement techniques in pediatric eyes with cataract.
Globe axial length (AL) in children is commonly measured using either contact or immersion technique. Office measurement of AL can be difficult in young children and infants and must often be done under anesthesia in an eye that is unable to cooperate with precise fixation and centration. Contact A-scan measurements yield shorter AL, on average, than immersion A-scan measurements in pediatric eyes. This difference is mainly the result of the anterior chamber depth rather than the lens thickness value. During intraocular lens power calculation, if globe axial length is measured by the contact technique, it will result in the use of an average 1-D stronger IOL power than is actually required. This can lead to induced myopia in the postoperative refraction. In our studied patients, there was a significant difference in prediction error between contact A-scan biometry and immersion A-scan biometry. The immersion A-scan technique is recommended for pediatric IOL power calculation. We also provide a review of biometry in pediatric eyes. The overall mean AL of pediatric cataractous eyes is significantly different than the mean AL of non cataractous eyes. More importantly, the standard deviation is higher in eyes with cataract than in those without. Three phases of eye growth in children have been documented: A rapid, postnatal phase from birth to 6 months of age, followed by a slower, infantile phase from 6 to 18 months of age, and finally a slow, juvenile phase from 18 months forward. In our study, girls had shorter ALs than boys and African-American subjects had longer ALs than Caucasians. Eyes with unilateral cataract had shorter ALs than eyes with bilateral cataract during the earlier years, but had longer ALs during later childhood.


Comparative analysis of the complete mitochondrial genomes of Aspergillus niger mtDNA type 1a and Aspergillus tubingensis mtDNA type 2b.
To understand the differences in the organization of mitochondrial genomes of the very closely related Aspergillus niger and Aspergillus tubingensis species, we determined the complete genome sequence of the 1a mtDNA type of A. niger and 2b mtDNA type of A. tubingensis and now we provide a comparative analysis of the two mtDNAs. We found that (1) the organization (gene content and order) of the two genomes is almost identical and (2) the size difference between them is principally attributed to the different intron content of their cox1, atp9 and ndh4L genes.


Longitudinal study of appraisal at Three Mile Island: implications for life event research.
This study tests a path model which indicates the occurrence of appraisal following the accident at Three Mile Island (TMI). The model posits a causal relationship between trust in TMI-related authorities, perceived danger, perceived harm to health, and psychological distress. The implications of the findings for life event research are discussed in terms of the etiological significance of meaning, event consequences, and control.


The effects of a brief mindfulness exercise on state mindfulness and affective outcomes among adult daily smokers.
Brief, single session mindfulness training has been shown to reduce emotional distress, craving, and withdrawal symptoms among smokers when they are nicotine-deprived. However, no research has examined the efficacy of brief mindfulness training for non-nicotine-deprived smokers, or explored its effects on smokers' ability to tolerate emotional distress. Smokers progress differently through various stages as they attempt to change their smoking behavior and evidence-based strategies are needed for smokers at all levels of nicotine deprivation. Therefore, the purpose of the current study was to examine the effects of a brief mindfulness exercise on state mindfulness, distress, distress tolerance, and smoking urges following a distressing laboratory task among 86 non-nicotine-deprived adult daily smokers (Mage=46years, 55% male, 74% African-American) who completed behavioral tasks and self-report measures before and after randomization to a 10-min mindfulness or control exercise. As hypothesized, the mindfulness exercise significantly increased state mindfulness [F=14.24, p=0.00, η2partial=0.15] and demonstrated a non-significant small to medium effect on decreased distress levels [F=3.22, p=0.08, η2partial=0.04]. Contrary to prediction, it was not associated with improvements in self-reported [F=2.68, p=0.11, η2partial=0.03] or behavioral distress tolerance [F(1)=0.75, p=0.39, η2partial=0.01], or smoking urges following a stressor [F=0.22, p=0.64, η2partial=0.00.] These findings suggest that brief mindfulness exercises successfully induce states of mindfulness in non-nicotine-deprived smokers. These exercises might also improve current moment levels of distress, but they do not appear to improve self-report or behavioral indices of distress tolerance.


A double mutant of highly purified Geobacillus stearothermophilus lactate dehydrogenase recognises l-mandelic acid as a substrate.
Lactate dehydrogenase from the thermophilic organism Geobacillus stearothermophilus (formerly Bacillus stearothermophilus) (bsLDH) has a crucial role in producing chirally pure hydroxyl compounds. α-Hydroxy acids are used in many industrial situations, ranging from pharmaceutical to cosmetic dermatology products. One drawback of this enzyme is its limited substrate specificity. For instance, l-lactate dehydrogenase exhibits no detectable activity towards the large side chain of 2-hydroxy acid l-mandelic acid, an α-hydroxy acid with anti-bacterial activity. Despite many attempts to engineer bsLDH to accept α-hydroxy acid substrates, there have been no attempts to introduce the industrially important l-mandelic acid to bsLDH. Herein, we describe attempts to change the reactivity of bsLDH towards l-mandelic acid. Using the Insight II molecular modelling programme (except 'program' in computers) and protein engineering techniques, we have successfully introduced substantial mandelate dehydrogenase activity to the enzyme. Energy minimisation modelling studies suggested that two mutations, T246G and I240A, would allow the enzyme to utilise l-mandelic acid as a substrate. Genes encoding for the wild-type and mutant enzymes were constructed, and the resulting bsLDH proteins were overexpressed in Escherichia coli and purified using the TAGZyme system. Enzyme assays showed that insertion of this double mutation into highly purified bsLDH switched the substrate specificity from lactate to l-mandelic acid.


Seroprevalence of hepatitis B and C and HIV in Malawian pregnant women.
to describe the seroprevalence of hepatitis B (HBV) and C (HCV) infection in HIV-positive and HIV-negative pregnant women from rural Malawi. descriptive study using serum samples collected between 1993-1995 in the Shire valley in rural Malawi. Fifty HIV-positive and 100 HIV-negative samples were selected randomly from 153 HIV-positive and 443 HIV-negative women delivering in the hospital. evidence of HBV and HCV infection was found in 71.7 and 16.5% of women, respectively. Chronic carriage of HBV (HBsAg positive) is high (13%) and in agreement with prevalences reported from highly endemic areas. Exposure to HBV and HCV probably occurred well before adulthood as the prevalence of anti-HBc antibody was high in young mothers <20 years of age (22/27; 81%). HBV and HCV infections are highly endemic in rural Malawi. There was no statistical evidence to suggest that HIV positivity was associated with an increased prevalence of HBV or HCV markers. Infection with HBV or HCV was not statistically associated.


Motor preparation in a memorised delay task.
The effect on reaction time (RT) and movement time (MT) of remembering which one of several targets to move to was investigated in 18 participants who completed 416 trials in each task. On each trial, participants moved their index finger from a central, illuminated switch (the stimulus) to one of eight targets located on the circumference of a 6 cm radius circle. A visual cue (illumination of the target) informed the participant of the appropriate target. In the memorised delay task, the cued target was lit for 300 ms followed by a variable (450-750 ms) foreperiod during which the participant was required to remember the location of the target until the stimulus light was extinguished. In the non-memorised delay task, the target remained lit during the entire foreperiod (750-1050 ms) until the response was completed. At the "go" signal (stimulus light extinguished) participants moved as quickly and accurately as possible to the cued target. Both RT and MT were significantly (p<0.05) longer in the memorised delay task. The increase in RT shows that remembering which target imposed a greater load on motor preparation even though all the information needed for preparing the response was presented in the cue at the beginning of each trial. The increase in MT raises the possibility that movement execution was also programmed during motor preparation.


Reproductive and Somatic Senescence in the European Badger (Meles meles): Evidence from Lifetime Sex-Steroid Profiles.
Among the Carnivora, there is sparse evidence for any substantive fitness benefits of post reproductive lifespan (PRLS, survival after reproductive cessation, RC). Using the European badger (Meles meles) as a model species, we analyzed sex-specific cross-sectional endocrinological and morphological data to investigate: 1) age-dependent reproductive decline in sex-steroid levels versus prime reproductive age; 2) age-dependent declines in somatic condition and reproductive advertisement (from subcaudal scent gland secretion); 3) changes in reproductive success with age due to somatic and endocrinological decline; 4) occurrence of RC, PRLS, and post reproductive representation (PrR) in the population with reference to pre-pubescent hormone levels and evidenced by fewer cub assignments from pedigree. We provide strong evidence for a gradual, not abrupt, decline in sex-steroid levels with age, with both sexes following a concave (down) quadratic trend. For both sexes, the onset of decline in somatic condition commenced at the age of 3 years. In contrast, decline in reproductive hormones started at age ca. 5.5 years in females and 6 years in males, with similar rates of decline thereafter. Subcaudal gland secretion volume also decreased in both sexes, especially after age 5, suggesting less investment in reproductive advertisement. After age 3, fewer (surviving) females were assigned cubs. This coincided with the onset of somatic decline but came earlier than hormonal decline (5.5 years onwards). The decrease in offspring assignments commenced later in males at age 5-6 years; concomitant with onset of testosterone decline at 6 years. This suggests that, contrary to females, in males declining body condition does not preclude reproductive success (no 'restraint') in advance of hormonal senescence ('constraint'). There was evidence of female PRLS, with very old adults living up to 2.59 ± 1.29 years after RC; although in males this evidence was weaker. We discuss the implications of these findings for RC and PRLS in the context of adaptive and non-adaptive hypotheses. There was evidence of over 2 years of Post Reproductive Life Span in both sexes.


Novel function of the human presqualene diphosphate phosphatase as a type II phosphatidate phosphatase in phosphatidylcholine and triacylglyceride biosynthesis pathways.
Phosphatidate phosphatases, PAPs, are key enzymes in lipid biosynthesis and signaling. Type I PAP enzymes participate in de-novo phospholipid biosynthesis, whereas type II PAP enzymes have an established role in lipid signaling. To identify novel human type II PAPs potentially involved in de-novo phospholipid synthesis we used bioinformatics to screen for enzymes with an active site exposed to the cytosolic side of membranes. Two related enzymes, a novel lipid phosphatase related protein (LPRP-A) and a presqualene diphosphate phosphatase (PA-PSP) met this criterion. PA-PSP and LPRP-A have differential tissue and subcellular distribution, and novel yet differential roles in lipid metabolism. Specifically, PA-PSP, but not LPRP-A, was a potent Mg(2+)-independent, NEM-insensitive type II PAP. Subcellular fractionation detection indicated that both proteins were associated with membranes, while immunofluorescent deconvolution imaging revealed that these membranes were exclusively from the nuclear envelope and the endoplasmic reticulum. PA-PSP overexpression, but not LPRP-A, accelerated the synthesis of phosphatidylcholine and caused accumulation of triacylglycerol with concomitant decrease in the rate of phosphatidylinositol synthesis. Coexpression of human CTP:phosphocholine cytidylyltransferase-alpha with PA-PSP enhanced the effect of PA-PSP on phosphatidylcholine levels, yet attenuated its effect on triacylglycerol. Taken together, our studies provide the first evidence that the eukaryotic, ER-resident PA-PSP is a bifunctional enzyme with specific type II PAP activity, and regulates, in addition to type I PAPs, the de-novo biosynthesis of phospholipids and triacylglycerols.


Ballistic carbon nanotube field-effect transistors.
A common feature of the single-walled carbon-nanotube field-effect transistors fabricated to date has been the presence of a Schottky barrier at the nanotube--metal junctions. These energy barriers severely limit transistor conductance in the 'ON' state, and reduce the current delivery capability--a key determinant of device performance. Here we show that contacting semiconducting single-walled nanotubes by palladium, a noble metal with high work function and good wetting interactions with nanotubes, greatly reduces or eliminates the barriers for transport through the valence band of nanotubes. In situ modification of the electrode work function by hydrogen is carried out to shed light on the nature of the contacts. With Pd contacts, the 'ON' states of semiconducting nanotubes can behave like ohmically contacted ballistic metallic tubes, exhibiting room-temperature conductance near the ballistic transport limit of 4e(2)/h (refs 4-6), high current-carrying capability (approximately 25 micro A per tube), and Fabry-Perot interferences at low temperatures. Under high voltage operation, the current saturation appears to be set by backscattering of the charge carriers by optical phonons. High-performance ballistic nanotube field-effect transistors with zero or slightly negative Schottky barriers are thus realized.


The promise of CAR T-cell therapy in aggressive B-cell lymphoma.
Relapsed or refractory aggressive B-cell lymphoma has an extremely poor prognosis and efforts to develop novel therapies for these patients have failed for almost four decades until the advent of chimeric antigen receptor (CAR) T-cell therapy. Within the last one year, two anti-CD19 CAR T-cell therapy products, axicabtagene ciloleucel and tisagenlecleucel, were approved by the United States Food and Drug Administration for the treatment of relapsed or refractory large B-cell lymphoma after at least two lines of systemic therapy based on multicenter single-arm phase two clinical trials. Here, we will discuss the different components of the CAR construct and their mechanisms of action, the role of conditioning chemotherapy, the efficacy and toxicity observed with anti-CD19 CAR T-cell therapies in aggressive B-cell lymphomas, and emerging strategies to further improve the safety and efficacy of these highly promising approaches.


Light People: Academician Junhao Chu.
The industrial revolutions of steam power, electric power and digital power have been three key steps in the development of science and technology. Now, the fourth industrial revolution has quietly begun, a revolution which will combine the powers of modern technologies such as the Internet, industrial digitalization and virtual reality to trigger a major change of science and technology, and sensor technology is of vital importance to this process.A famous physicist specialized in infrared and semiconductors, our featured guest not only discovered the intrinsic absorption spectra of the optical transition between narrow gap semiconductor mercury cadmium telluride bands, but also developed the theory of the band structure of mercury cadmium telluride and the theory of optical transition, put forward a series of expressions such as the gap width of mercury cadmium telluride bands, making outstanding contributions.Born into a scholarly family, he inherited a love for knowledge, especially physics and enjoyed all the challenges it presented. In research, he believes that technological development should be guided by the laws of physics. As a teacher, he asks his students to focus on the depth and breadth of learning. In life, he is famed for being easygoing, modest, well-mannered and meticulous.He is Academician Junhao Chu of the Shanghai Institute of Technical Physics (SITP), Chinese Academy of Sciences (CAS). Please follow Light People and discover what challenges Prof. Chu had to overcome in the study of mercury cadmium telluride.


Modeling, optimization and understanding of adsorption process for pollutant removal via machine learning: Recent progress and future perspectives.
It is crucial to reduce the concentration of pollutants in water environment to below safe levels. Some cost-effective pollutant removal technologies have been developed, among which adsorption technology is considered as a promising solution. However, the batch experiments and adsorption isotherms widely employed at present are inefficient and time-consuming to some extent, which limits the development of adsorption technology. As a new research paradigm, machine learning (ML) is expected to innovate traditional adsorption models. This reviews summarized the general workflow of ML and commonly employed ML algorithms for pollutant adsorption. Then, the latest progress of ML for pollutant adsorption was reviewed from the perspective of all-round regulation of adsorption process, including adsorption efficiency, operating conditions and adsorption mechanism. General guidelines of ML for pollutant adsorption were presented. Finally, the existing problems and future perspectives of ML for pollutant adsorption were put forward. We highly expect that this review will promote the application of ML in pollutant adsorption and improve the interpretability of ML.


1st MRC Human Genetics Symposium: maintenance of genomic stability.
This meeting served to juxtapose the fundamental studies on the distinct pathways which maintain genomic stability with work that addresses the phenotypic consequences of loss of genomic stability in humans. This created an exciting environment where we were prompted to think about the links between fundamental and applied research. It was also a forum where new ideas could be formed that will hopefully fuel interesting research in human disease. As we place the genome projects into perspective, the ideas arising from meetings such as the 1st MRC Human Genetics Symposium might be expected to guide studies that will reveal the molecular defects which underlie some of the more impenetrable phenotypes of human diseases.


Clinical features of depressed patients with or without a family history of alcoholism.
To compare clinical features of depressed subjects without alcoholism but with a family history of alcoholism to a depressed group without alcoholism and without a family history of alcoholism. Clinical and demographic data of 209 depressed subjects without a history of alcoholism in first-degree relatives and 73 depressed individuals with a history of alcoholism in first-degree relatives were compared. Subjects with a personal history of alcoholism were excluded. Depressed subjects with a family history of alcoholism have a significantly higher prevalence of reported childhood physical and sexual abuse and post-traumatic stress disorder (PTSD), make more suicide attempts, and have greater intent to die at the time of their most lethal suicide attempt, compared to depressed subjects without a family history of alcoholism. Depressed patients with a family history of alcoholism are at greater risk for suicidal behavior and PTSD and may require more careful management.


Transmission disequilibrium suggests a role for the sulfotransferase-4A1 gene in schizophrenia.
Previous studies suggest a role for chromosome 22q13 in schizophrenia. This segment of chromosome 22 contains the sulfotransferase-4A1 (Sult4A1) gene, which encodes an enzyme thought to be involved in neurotransmitter metabolism in the central nervous system. To evaluate this candidate, we developed a microsatellite marker targeting a polymorphism in its 5' nontranslated region (D22s1749E). Using samples obtained from the National Institutes of Mental Health Schizophrenia Genetics Initiative, we evaluated 27 families having multiple siblings with schizophrenia and schizophrenia-spectrum disorders for transmission disequilibrium (TDT) of this marker along with three single nucleotide polymorphisms (SNPs) spanning a 37 kb segment containing the Sult4A1 gene. TDT for D22s1749E was significant (P < 0.05), with a tendency for the 213 nt allele to be preferentially transferred to affected children (P = 0.0079). Global chi-square values for haplotypes involving the SNPs (ss146366, ss146407, and ss146420) and D22s1749E, also showed significant TDT values (P = 0.0006-0.0016). Consequently, we proposed that Sult4A merited more careful scrutiny as a candidate gene for schizophrenia susceptibility.


Nanomolar detection of food additive tert-butylhydroquinone in edible oils based on novel ternary metal oxide embedded β-cyclodextrin functionalized carbon black.
It is pivotal to precisely detect food preservatives to ascertain food quality and safety. In this work, we report the sensitive electrochemical detection of widely used cytotoxic food preservative tert-butylhydroquinone (TBHQ). A novel nanocomposite was sonochemically prepared by embedding ternary metal oxide (TMO) comprising ZnO, CuO, and MgO in β-cyclodextrin (β-CD) functionalized carbon black (CB). The properties of the prepared nanocomposite were evaluated by employing multiple characterization methods. The nanocomposite fabricated on a screen printed carbon electrode exhibited exceptional electrocatalytic activity towards TBHQ detection, evident from the resultant very low detection limit of 1 nM and high sensitivity of 22.67 μA μM-1 cm-2. Moreover, the developed TBHQ sensor evinced all the important traits of a good electrochemical sensor including excellent selectivity, stability, reproducibility, and repeatability. Furthermore, for validating practical feasibility of TBHQ detection, we successfully determined this food additive in edible oils.


Endocrine disruptor effect of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) on porcine ovarian cell steroidogenesis.
Previous studies with perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) indicate that they act as endocrine disruptors, in addition to inducing alterations and damaging reproductive health; however, the biological mechanisms by which these disorders are produced are not yet understood. The aim of this study was to analyze the effect of PFOS and PFOA on in vitro steroidogenic secretion in porcine theca and granulosa cells, with or without gonadotropic stimulation. Granulosa and theca cells were isolated and cultured. Cell nature was performed by immunocytochemistry. PFOS and PFOA effect on steroid secretion was analyzed by chemiluminescence. In the present study, alterations in steroidogenic secretion were found when administering PFOS (0.12, 1.2, 12, 120 or 240μM) or PFOA (0.012, 0.12, 1.2, 12 or 24μM) to theca and granulosa cells. When theca and granulosa cells were stimulated with 500ng/mL LH or 500ng/mL FHS, respectively and immediately followed with 1.2μM of PFOS or PFOA, the perfluorinated compounds inhibited the secretion of steroid hormones in both stimulated cell types. The results indicate that PFOS and PFOA act on steroidogenic ovarian cells as endocrine disruptors, which could affect the dependent functions of sexual steroids.


Feasibility of fast ventricular tachycardia mapping using the Rhythmia ™ system in a patient with an Impella ™.
Use of 3D navigation systems may be sometimes impossible in patients with left ventricular assist devices because of major electromagnetical interferences with some 3D systems based on magnetic localization. Mapping with the Rhythmia ™ system in patients implanted with an Impella ™ is described to be non feasible. We relate how to overcome this technical issues in this case.


CON4EI: Development of testing strategies for hazard identification and labelling for serious eye damage and eye irritation of chemicals.
Assessment of acute eye irritation potential is part of the international regulatory requirements for safety testing of chemicals. In the last decades, many efforts have been made in the search for alternative methods to replace the regulatory in vivo Draize rabbit eye test (OECD TG 405). Success in terms of complete replacement of the regulatory in vivo Draize rabbit eye test has not yet been achieved. The main objective of the CEFIC-LRI-AIMT6-VITO CON4EI (CONsortium for in vitro Eye Irritation testing strategy) project was to develop tiered testing strategies for serious eye damage and eye irritation assessment that can lead to complete replacement of OECD TG 405. A set of 80 reference chemicals (e.g. balanced by important driver of classification and physical state), was tested with seven test methods. Based on the results of this project, three different strategies were suggested. We have provided a standalone (EpiOcular ET-50), a two-tiered and three-tiered strategy, that can be used to distinguish between Cat 1 and Cat 2 chemicals and chemicals that do not require classification (No Cat). The two-tiered and three-tiered strategies use an RhCE test method (EpiOcular EIT or SkinEthic™ EIT) at the bottom (identification No Cat) in combination with the BCOP LLBO (two-tiered strategy) or BCOP OP-KIT and SMI (three-tiered strategy) at the top (identification Cat 1). For our proposed strategies, 71.1% - 82.9% Cat 1, 64.2% - 68.5% Cat 2 and ≥80% No Cat chemicals were correctly identified. Also, similar results were obtained for the Top-Down and Bottom-Up approach.


Emotion regulation and decision-making in persons with dementia: A scoping review.
Emotion is integral to decision-making, and emotion regulation is associated with improved well-being in older age. Persons with dementia are likely to experience impairments in emotion regulation processes that can potentially contribute to differential decision-making and well-being outcomes. To promote the development of theoretical models of well-being in dementia, we review the quantitative evidence concerning the associations between emotion regulation and decision-making in dementia. Scoping review. Seven studies of persons with dementia met our criteria. In persons with frontotemporal lobar degeneration, emotion regulation processes that precede the emotional experience were associated with decision-making in a moral (but not uncertainty) context. Independent of type of dementia, evidence concerning the associations between emotion regulation processes that occur after emotion is experienced and decision-making was mixed and drew on different methodologies. No studies relating to the associations between decision-making in dementia and several emotion regulation processes and strategies were found. In this review, we sought to clarify the concept of everyday decision-making in dementia and map the current state of evidence concerning its associations with emotion regulation. Our findings show that emotion regulation processes are associated with decision-making in dementia, depending on type of decision-making assessment and emotional experience. We outline the gaps in the literature to set a research agenda for promoting our understanding of how emotion regulation processes can shape the various decisions that are made by persons with dementia on a daily basis.


A solid-state electrochemiluminescence sensing platform for detection of catechol based on novel luminescent composite nanofibers.
A solid-state electrochemiluminescence (ECL) sensing platform based on the novel luminescent composite nanofibers for detection of catechol has been developed. The carboxylated multi-walled carbon nanotubes (MWNTs) and ruthenium(II) tris-(bipyridine) (Ru(bpy)3(2+)) doped nylon 6 (PA6) luminescent composite nanofibers (Ru-MWNTs-PA6) were successfully fabricated by a one-step electrospinning technique. The Ru-MWNTs-PA6 nanofibers, with unique 3D nanostructure, large specific surface area and a larger amount of immobilized-Ru(bpy)3(2+), maintained the photoelectric properties of the Ru(bpy)3(2+) ions and exhibited excellent ECL behaviors on glassy carbon (GC) electrode. As a solid-state ECL sensing platform, the Ru-MWNTs-PA6 nanofibers can sensitively detect low concentration catechol by monitoring the phenol-dependent ECL intensity change. The detection limit for catechol is 1.0 nM, which is comparable or better than that in the reported assays. The solid-state ECL sensor displayed wide linear range, high sensitivity and good stability. It holds promise for the electrospun nanofibers-based ECL sensors have a great potential for routine analyses.


Characterization of neutral blood group B-active glycosphingolipids of rat gastric mucosa. A novel type of blood group active glycosphingolipid based on isogloboside.
The blood group active glycosphingolipids of rat gastric mucosa have been investigated. Only blood group B active structures were found, two of which have been structurally characterized by monoclonal antibodies, mass spectrometry, permethylation analyses, proton NMR spectroscopy, and exoglycosidase digestions. A six-sugar compound based on a gangliotetraosylceramide core was isolated and shown to have the following structure: (Formula: see text). The same compound was recently isolated from rat bone marrow cells and characterized by Taki et al. (Taki, T., Kimura, H., Gasa, S., Nakamura, M., and Matsumoto, M. (1985) J. Biol. Chem. 260, 6219-6225). The possible precursor compounds of this structure, gangliotriaosylceramide and gangliotetraosylceramide, were also found in the gastric mucosa. A seven sugar compound, based on isogloboside, was isolated from the gastric mucosa and shown to have the following structure: (formula; see text) The latter compound is novel and extends the list of different types of core structures found for blood group glycolipids. The epithelial cells of the stomach are unique among the cells lining the gastrointestinal tract in having blood group active glycolipids based on ganglio- and isogloboseries core structures.


Epidemiology of hearing impairment at three Flemish Institutes for Deaf and Speech Defective Children.
A retrospective analysis of 190 records of hearing impaired children up to the age of 14, all educated at one of three Flemish Institutes for Deaf and Speech Defective Children in Belgium, was performed. Until 1999, the well-known behavioral test (Ewing test) was used in the Flemish national screening program for hearing losses. Because it presented a lot of disadvantages, it has been replaced by Automated Auditory Brainstem Responses (AABR), enabling the Flemish national neonatal screening program to commence. This study is an extension of the preliminary results of a recently performed retrospective analysis in one Flemish institute of the hearing loss of patients that were diagnosed in the pre-AABR era. The authors analyzed the following data: etiology, risk factors of congenital hearing impairment, the patient's history from the moment of the first suspicion to diagnosis and treatment. The median age of the children was 8.5 years (2-14 year). In 66.5% the parents and/or grandparents were the first to raise suspicion, this was at a median age of approximately 9 months. The diagnosis was often made late, at a median age of 15 months (0-88 months). The etiology was unknown in 32.6% of the cases. The only cast-iron certain diagnoses were pre- and perinatal infections, syndromal and genetic hearing loss, and acquired infections (meningitis and measles). No risk factors of hearing loss, as they are stated by the Joint Committee on Infant Hearing, were found in more than 50% of the cases. Audiometry was performed in all cases, often supplemented with Auditory Brainstem Responses and/or click-evoked otoacoustic emissions, while other diagnostic investigations (imaging, genetics, etc.) were only variably performed. Finally, the authors confirm the need for universal neonatal screening, which only recently started in Belgium, and suggest that a detailed protocol should be established to pursue a coherent diagnostic policy.


Modeling the Kinetics of Integrin Receptor Binding to Hepatic Extracellular Matrix Proteins.
The composition of the extracellular matrix (ECM) proteins and the expression of their cognate receptors dictate cell behavior and dynamics. In particular, the interactions of ECM proteins with integrin receptors are key mediators of these cellular processes, playing a crucial role in the progression of several diseases of the liver, including inflammation, fibrosis/cirrhosis and cancer. This study establishes a modeling approach combining computation and experiments to evaluate the kinetics of integrin receptor binding to hepatic ECM proteins. ECM ligand concentration was derived from LC-MS/MS quantification of the hepatic ECM from mice exposed to chronic carbon tetrachloride (CCl4); receptor density was derived from published literature. Mathematical models for ECM-integrin binding kinetics that were developed incorporate receptor divalence and an aggregation scheme to represent clustering. The computer simulations reproduced positive cooperativity in the receptor aggregation model when the aggregation equilibrium constant (Ka) was positive and greater than Keq for divalent complex formation. Importantly, the modeling projected an increase in integrin binding for several receptors for which signaling is known to be increased after CCl4 exposure in the liver. The proposed modeling approach may be of use to elucidate the kinetics of integrin receptor binding to ECM proteins for homeostatic and diseased livers.


Are women with gestational diabetes being screened for type 2 diabetes following pregnancy? A nationwide retrospective cohort study in Aotearoa New Zealand.
To estimate the proportion of women with a first episode of gestational diabetes mellitus (GDM) in Aotearoa (New Zealand) who received postpartum screening for type 2 diabetes mellitus (T2DM). Data from 941,468 pregnancies occurring between 2005 and 2015 were linked with laboratory, community pharmacy, and hospital discharge data from the Ministry of Health's National Collections to identify a cohort of women who had a first episode of GDM (n = 14,443). Proportions receiving a glycated haemoglobin (HbA1c) test or oral glucose tolerance test (OGTT) during the first year postpartum were estimated overall, and by calendar year, ethnic group, age, deprivation, and region. Overall, 40.9% (95% CI 40.1-41.7%) received an HbA1c test or OGTT within 3 months, 53.3% (52.5-54.1%) within 6 months, and 61.0% (60.2-61.8%) within 12 months postpartum. Screening proportions within 12 months were stable over time. Indigenous Māori were less likely to receive screening within 6 months postpartum (35.0% [33.1-37.0%]) than other ethnic groups, as were younger women and those with higher deprivation. There were marked variations by region (between 15.3% and 67.5%). Postpartum T2DM screening was low over the period studied, with substantial ethnic and regional inequities across New Zealand.


Modeling and simulation of anion exchange chromatography for purification of proteins in complex mixtures.
Ion exchange chromatography is extensively used in the purification of biological compounds. Reliable mathematical models describing this chromatographic technique are available and can be used to improve the performance of this separation step. However, the use of synthetic mixtures for model development hampers the application of this approach with real cell extracts processed in downstream operations. This work presents an original approach for handling non-synthetic genuine mixtures of proteins, which was applied in the purification of an untagged recombinant pneumococcal surface protein A (PspA4Pro). First, evaluation was made of the efficiency of steric mass action (SMA) and modified Langmuir isotherms, which were separately used together with the equilibrium dispersive model (EDM). The data used for parameter estimation and model validation were obtained from anion exchange chromatography runs (employing Q-Sepharose FF), applied to real cell extracts produced by different cultivation strategies. Simulations showed that the models were able to describe the complex mixtures of unknown proteins. Next, the EDM and SMA approaches were used to separately describe the profile of PspA4Pro and the pool of protein impurities eluted together. The simulations showed that PspA4Pro tended to elute at the beginning of the peak, enabling the establishment of an alternative elution schedule that provided a 34% increase in the purity achieved using the anion exchange chromatography.


Hepatitis B transmission in school contacts of retarded HBsAg carrier students.
A prospective study was performed to assess the rate of transmission of hepatitis B from mentally retarded carrier students to susceptible mentally retarded peer students or school staff. Eighteen hepatitis B carriers were integrated into a public school program for the developmentally disabled, and serum hepatitis B markers were monitored in staff and students over 14 months. During this time no susceptible staff acquired hepatitis B serologic markers. Of susceptible students, 1.8% demonstrated seroconversion, but the route of infection is likely to have been outside the classroom environment. The results indicate that the risk of hepatitis B transmission is low in this particular school program.


Existence in Escherichia coli of a mechanism that generates 'staggered' head-to-head dimers of plasmid DNA; possible involvement of the Tn3 transposase.
The structures of two plasmids, one found in one of the transformants with putative products of an in vitro DNA rearrangement reaction containing the Tn3 transposase, and another found as a spontaneous tnpA negative derivative of an overproducer of the Tn3 transposase, have been elucidated. They both had shown non-conventional results in restriction enzyme analysis. For the determination of the structures, we used restriction enzyme analysis, denaturation and renaturation experiments, and DNA nucleotide sequencing. The structures turned out to be 'staggered' head-to-head dimers of the original monomer plasmids, containing gigantic inverted repeats separated by two identical spacers which are also in inverted orientations themselves. Two alternative models for the mode of origin of such a structure, a bimolecular model and a unimolecular one, are discussed. The circumstances in which these two plasmids occurred suggest possible involvement of the Tn3 transposase in their generation.


Current knowledge and interest of French Canadians regarding nutrigenetics.
The purpose of this study was to draw a global portrait of the current knowledge and interest regarding nutrigenetics in a population of French Canadians from the province of Quebec (Canada). A total of 2238 residents from the province of Quebec, Canada, were recruited via social networks and from the Laval University employee/student lists to participate in a 37-question online survey on nutrigenetics. Most participants were not familiar with the term "nutrigenetics" (82.7%). Participants with good genetic literacy (26.8%) were less interested in nutrigenetic testing (p < 0.0001). The vast majority of participants (90.7%) reported to be willing to follow a personalised diet based on nutrigenetic testing, especially if they came to know themselves as carriers of a polymorphism increasing the risk of certain diseases. Participants had a higher interest in testing related to metabolic response to macronutrients (types of sugars, fats and proteins) than to micronutrients or other nutrients related to food intolerance. The attitude of French Canadians about nutrigenetics is very consistent with the results from other surveys published in the literature. Although few individuals are familiar with nutrigenetics, the public's attitude towards nutrigenetics is globally favourable.


CD26/dipeptidyl peptidase IV: a comparative study of healthy persons and kidney transplant recipients before and early after transplantation.
Human CD26 is co-stimulatory for lymphocytes, circulates in a soluble form in blood (sCD26), and has intrinsic dipeptidyl peptidase IV (DPPIV) activity. Associations between CD26 expression on the surface of T cells (CD26+/CD3+) and acute rejection and between (CD26+/CD3+)/DPPIV and clinical immunosuppression have been reported. These results encouraged the investigation of CD26 as a potential biomarker to optimize immunosuppressive therapy. To better understand the significance of CD26, a comparative study of CD26 expression on CD3+ cells, sCD26 concentration, and DPPIV activity in healthy persons (HP) and kidney transplant recipients (KTR) was performed. Thirty-one HP and 34 KTR were included in the study. CD26+/CD3+ was determined by FACS, sCD26 concentration was determined by ELISA, and DPP activity was determined by spectrophotometry. For KTR, these parameters were studied on the day before transplantation (preTx) and 7±1days after transplantation (postTx). There was no significant difference in the CD26+/CD3+, sCD26, and DPPIV data regarding gender, donor type (16 living donors), delayed graft function (n=8), or presence of ≥4HLA mismatches (n=16). Compared to the HP data, preTx CD26+/CD3+ was 4.5-fold higher, sCD26 was 1.2-fold higher, and DPPIV showed no significant difference. PostTx, CD26+/CD3+ was 3.8-fold higher, and sCD26 and DPPIV decreased significantly, reaching lower values than that observed in HP. Re-transplanted patients (n=5) showed significantly lower preTx CD26+/CD3+ expression than patients receiving their first transplant. Patients with preemptive transplantation (n=7) showed higher postTx CD26+/CD3+ expression than patients on dialysis. CD26 expression on CD3+ cells was strongly increased in patients with end stage kidney disease compared to HP and remained high early postTx. The differences in sCD26 and DPPIV behavior compared to that of CD26+/CD3+ postTx may reflect a regulatory response to the new immunological situation and the effects of therapy.


Association with the nonparoxysmal atrial fibrillation duration and outcome of ExTRa Mapping-guided rotor ablation.
Additional ablation strategies after pulmonary vein isolation (PVI) for patients with nonparoxysmal atrial fibrillation (non-PAF) lasting ≥2 years have not been fully effective. This is presumably because of insufficient identification of non-PAF maintenance mechanisms. In this study, we employed a novel online and real-time phase mapping system, ExTRa Mapping, to identify and modulate rotors as one of the non-PAF maintenance mechanisms in patients with non-PAF sustained after PVI. We investigated the relationship between outcomes of ExTRa Mapping-guided rotor ablation (ExTRa-ABL) and non-PAF duration prior to this procedure. This study consisted of 73 non-PAF patients (63 ± 8 years, non-PAF duration 31 ± 37 months) who underwent the first ExTRa-ABL in patients with non-PAF sustained after completion of PVI. Freedom from non-PAF/atrial tachycardia (AT) recurrence at 12 months after ExTRa-ABL was achieved in 50 (69%) of patients. The non-PAF duration prior to ExTRa-ABL was significantly longer in patients with non-PAF/AT recurrence after ExTRa-ABL compared with those without (56 ± 50 vs. 19 ± 22 months, p = .001). In patients with non-PAF duration of ≤60 months prior to ExTRa-ABL, compared with >60 months, non-PAF/AT-free rate was significantly higher (68.9% vs. 23.1%, p < .001), during the follow-up of 36 ± 18 months. A non-PAF duration of ≤60 months prior to ExTRa-ABL was associated with a better outcome. The effect of ExTRa-ABL was considered to be limited in patients with >60 months of non-PAF duration.


Plasma cytokine profiles in patients with celiac disease and selective IgA deficiency.
Celiac disease (CD) and selective IgA deficiency (IgAD) are frequently associated, and share the same genetic background. The aim of the present study was to evaluate both Type 1 and 2 plasma cytokine levels in CD and in CD-IgAD. IL-2, TNF-alpha, IL-10, IL-4 and IL-13 plasma levels were measured both at diagnosis and after a gluten-free diet (GFD) in 32 CD patients, in 27 CD-IgAD patients and in 30 healthy controls. IFN-gamma levels were significantly higher in CD and CD-IgAD than in controls, TNF-alpha displayed significantly higher levels in CD-IgAD when compared both with controls and with CD, and IL-2 was in CD-IgAD significantly increased respect to controls. Kinetics of the Type 1 cytokine plasma levels did not show a clear relationship with the GFD in both groups of CD patients, and particularly in those with IgAD. IL-4 and IL-13, both at diagnosis and after a GFD, were not significantly different in controls and in celiac patients (with and without IgAD). IL-10, whose production is stimulated by the TNF-alpha, had significantly higher plasma levels in CD-IgAD, but not in CD patients, with a significant decrease after a GFD. CD and especially CD-IgAD patients display persistently higher pro-inflammatory cytokine levels, suggesting a persistent state of activation of pro-phlogistic signals in CD, particularly when IgAD coexists. Serial measurement of serum IL-10 may be an adjunctive evaluating criterion in the follow-up of CD-IgAD patients.


In vivo efficacy of silver-impregnated barrel contact lens storage cases.
This study examined the rate and level of microbial contamination of silver and non-silver (control) barrel contact lens storage cases in vivo. A prospective, single-centre, randomized, double blinded, crossover study was conducted to evaluate the efficacy of silver and control barrel cases used with an Oxipol™-based disinfecting solution over a two-month period. Lens cases were collected, and the frequency, type and level of microbial contamination evaluated using viable culture and standard identification methods. Questionnaires were used to assess the contact lens-related hygiene compliance of the participants. Forty eight daily contact lens wearers completed the study. Overall, 27 % of silver and 35 % control lens cases (P > 0.05) were contaminated, predominantly with Gram-positive bacteria. Only, 12 % of participants had good compliance, with 46 % having average compliance and 43 % poor compliance. Compliance score was not associated with level of microbial contamination. However, the use of hydrogel lenses in combination with silver cases compared to non-silver barrel cases resulted significantly greater numbers of bacteria colonising cases. The present investigation demonstrated that the use of silver barrel cases does not reduce the overall rate and level of bacterial contamination, but that using hydrogel lenses in combination with silver cases resulted in higher numbers of bacteria isolated from cases.


Fine structure and sporogonic development of a Vavraia sp. (Microsporida: Pleistophoridae) in the biting midge Culicoides edeni (Diptera: Ceratopogonidae).
A microsporidium with ultrastructural characteristics of the genus Vavraia was found in the fat body of an adult specimen of Culicoides edeni (Diptera: Ceratopogonidae) collected in northern Florida. The sporogonial stages developed within sporophorous vesicles, which contained variable numbers of oval spores at maturity. The wall of the sporophorous vesicle was composed of two electron-dense outer layers and an electron-lucent intermediate layer. Sporonts contained haplokaryotic nuclei and divided by rosette formation. Mature spores had anisofilar polar filaments and measured 3.8 +/- 0.28 microns in length and 2.2 +/- 0.16 microns in width in thick sections of resin-embedded material. This is the first report of a Vavraia sp. from a species of Culicodes.


Intracranial hemorrhage with concurrent aortic dissection.
Aortic dissection is a rare yet lethal condition that is often missed. Presenting symptoms often include chest pain, abdominal pain, or loss of consciousness. Rarely is it asymptomatic, and the concurring symptoms may draw attention away from the dissection. We present a case of a 51-year-old male who presented to the emergency department with sudden onset of slurred speech and right-sided weakness. The CT scan showed a basal ganglia hemorrhage. However, during the scan, the radiologist incidentally found some aortic changes and recommended an ECG-gated CT scan of the thorax, which revealed a Stanford type B aortic dissection. We aim to shed light on patients presenting with neurological findings and conclude to have aortic dissection to increase awareness and facilitate rapid diagnosis and treatment.


In vitro effects of N-acetyl cysteine alone and in combination with antibiotics on Prevotella intermedia.
N-acetyl cysteine (NAC) is an antioxidant that possesses anti-inflammatory activities in tissues. In the field of dentistry, NAC was demonstrated to prevent the expression of LPS-induced inflammatory mediators in phagocytic cells and gingival fibroblasts during the inflammatory process, but the effect of NAC on oral pathogens has been rarely studied. Here, we examined the effect of NAC against planktonic and biofilm cells of Prevotella intermedia, a major oral pathogen. NAC showed antibacterial activity against the planktonic P. intermedia with MIC value of 3 mg/ml and significantly decreased biofilm formation by the bacterium even at sub MIC. NAC did not affect the antibiotic susceptibility of planktonic P. intermedia, showing indifference (fractional inhibitory concentration index of 0.5-4) results against the bacterium in combination with ampicillin, ciprofloxacin, tetracycline or metronidazole. On the other hand, viability of the pre-established bacterial biofilm exposed to the antibiotics except metronidazole was increased in the presence of NAC. Collectively, NAC may be used for prevention of the biofilm formation by P. intermedia rather than eradication of the pre-established bacterial biofilm. Further studies are required to explore antibacterial and anti-biofilm activity of NAC against mixed population of oral bacteria and its modulatory effect on antibiotics used for oral infectious diseases.


An assessment tool translation study.
Policymakers hoped to substitute a new, multi-purpose, functional assessment instrument, the minimum data set post-acute care (MDS-PAC), into the planned prospective payment system (PPS) for inpatient rehabilitation hospitals. PPS design requires a large database linking treatment costs with measures of the need for care, so the PPS was designed using the functional independence measure (FIM) database linked to Medicare hospital claims. An accurate translation from the MDS-PAC items to FIM--like items was needed to ensure payment equity under the substitution. This article describes the translation efforts and some of the problems that led policymakers to abandon the effort.


Management of the smashed distal humerus.
The purpose of this article is to present a principle-based approach to treating the smashed distal humerus. These injuries are challenging to even the most experienced surgeons. The four goals, in order of priority, are soft tissue healing without infection, restoration of diaphyseal bone stock, union between the distal fragments and the shaft, and a stable and mobile articulation.


Procoagulant property of platelet activating factor (PAF).
Platelet-activating factor (PAF) is known to activate platelets and thus promote clot formation in most mammalian species including humans. In this communication, the ability of PAF to hasten the overall coagulation process by measuring the recalcification time (RT) is described. Assessment of the RT in vitro indicated that the RT was significantly reduced by PAF (p < 0.001). This information adds a new dimension to the role of PAF in coagulation and also provides an exciting lead to the development of drugs for controlling the state of accelerated coagulation by pharmacologic means.


Poly(I:C) is an effective adjuvant for antibody and multi-functional CD4+ T cell responses to Plasmodium falciparum circumsporozoite protein (CSP) and αDEC-CSP in non human primates.
Development of a fully effective vaccine against the pre-erythrocytic stage of malaria infection will likely require induction of both humoral and cellular immune responses. Protein based vaccines can elicit such broad-based immunity depending on the adjuvant and how the protein is formulated. Here to assess these variables, non human primates (NHP) were immunized three times with Plasmodium falciparum (Pf) circumsporozoite protein (CSP) or CSP cloned into MG38, a monoclonal antibody that targets DEC-205 (αDEC-CSP), an endocytic receptor on dendritic cells (DCs). Both vaccines were administered with or without poly(I:C) as adjuvant. Following three immunizations, the magnitude and quality of cytokine secreting CD4+ T cells were comparable between CSP+poly(I:C) and αDEC-CSP+poly(I:C) groups with both regimens eliciting multi-functional cytokine responses. However, NHP immunized with CSP+poly(I:C) had significantly higher serum titers of CSP-specific IgG antibodies and indirect immunofluorescent antibody (IFA) titers against Pf sporozoites. Furthermore, sera from both CSP or αDEC-CSP+poly(I:C) immunized animals limited sporozoite invasion of a hepatocyte cell line (HC04) in vitro. To determine whether CSP-specific responses could be enhanced, all NHP primed with CSP or αDEC-CSP+poly(I:C) were boosted with a single dose of 150,000 irradiated Pf sporozoites (PfSPZ) intravenously. Remarkably, boosting had no effect on the CSP-specific immunity. Finally, immunization with CSP+poly-ICLC reduced malaria parasite burden in the liver in an experimental mouse model. Taken together, these data showing that poly(I:C) is an effective adjuvant for inducing potent antibody and Th1 immunity with CSP based vaccines offers a potential alternative to the existing protein based pre-erythrocytic vaccines.


Challenges to nurse prescribers of a no-antibiotic prescribing strategy for managing self-limiting respiratory tract infections.
To report a qualitative study of the experiences of nurse prescribers in managing patients with self-limiting respiratory tract infections. Patients frequently attend primary care with respiratory tract infections. Although a no-prescribing strategy is recommended for these consultations, general practitioners frequently prescribe antibiotics, citing non-clinical reasons such as patient pressure. Nurses increasingly manage people with respiratory tract infections, but research has not yet explored their experiences within such consultations. Semi-structured interviews and focus groups. Fifteen semi-structured interviews and three focus groups (n=5, n=4, and n=12) with a purposive sample of nurse prescribers (n=34) and other non-medical prescribers (n=2) were conducted between November 2009-November 2010. A qualitative approach was used to develop conceptual categories from the dataset, and emerging themes were explored in subsequent interviews/focus groups. Although participants reported experiencing numerous challenges within these consultations, they believed that they possessed some of the communication skills to deal effectively with patients without prescribing antibiotics. Participants reported that protocols supported their decision-making and welcomed the benefits of peer support in dealing with 'demanding' patients. However, the newness of nurses and other non-medical prescribers to the prescribing role meant that some were cautious in dealing with patients with respiratory tract infections. Training for nurses and other non-medical prescribers should focus on building their confidence and skills to manage people with respiratory tract infections without recourse to antibiotics. Further work should seek to explore which strategies are most effective in managing respiratory tract infections while maintaining patient satisfaction with care.


The effect of different prosthetic restorations on the dietary selection in edentulous patients. A longitudinal study of patients initially treated with optimal complete dentures and finally with tissue-integrated prostheses.
The effect of prosthetic restoration of masticatory ability on dietary selection was evaluated in 23 edentulous patients with denture adaptation problems. The patients were first given optimal complete dentures and then a fixed prosthesis on tissue-integrated implants in the lower jaw. Changes in dietary selection were evaluated from 4-day records obtained before prosthetic treatment and on six occasions up to 78 months after treatment. With the method used, no significant changes in food selection were recorded during the rehabilitation period, except for a slight increase in intake of crisp bread and fresh fruit after treatment with fixed tissue-integrated prostheses in the mandibular jaw. It is concluded that an improved oral function will not in itself lead to a change in dietary selection and that dietary changes probably require professional and individually given dietary advice by a trained dietitian.


Post-tonsillectomy bleeding: a regional hospital experience.
Post-tonsillectomy bleeding (PTB) is still one of the most common complications of tonsillectomy. The rate of PTB varies with different methods. We retrospectively reviewed all charts of patients who underwent tonsillectomy in a regional hospital. Post-tonsillectomy bleeding occurred in 33 patients (6.68%); 3 experienced primary haemorrhage and 30 had secondary haemorrhage. The rate of PTB was higher in males and in the over 15-year group (9.41%). The commonest surgical techniques used were cold steel dissection with bipolar diathermy for haemostasis (55.87%). The lowest PTB was observed with 'cold steel and ties technique' (3.14%). Operations which used bipolar diathermy throughout had the highest level of haemorrhage (8.47%). In conclusion, the overall risk of bleeding is related to surgical technique. A 'hot' technique had a higher risk of bleeding than 'cold' technique.


Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial.
Neutrophilic inflammation plays a causal role in Chronic Obstructive Pulmonary Disease (COPD). Neutrophil derived myeloperoxidase(MPO) matrix metalloproteinases(MMP's), and elastases are thought to contribute to the perpetuation of the disease. The tetracycline analogue doxycycline has been shown to inhibit neutrophil-mediated inflammation. It was thus reasoned that doxycycline may attenuate neutrophil-mediated inflammation in COPD. In this double blind randomized controlled trial the effect of a 3-week course of doxycycline on sputum and systemic inflammatory parameters was evaluated in stable COPD patients. In order to exclude inflammation by bacterial colonisation patients must have 2 negative sputum cultures in the previous year. The effect of doxycycline treatment on inflammatory markers (TNF-α, IL-1β and IL-6) and neutrophil specific markers in sputum (MPO, MMP's, and IL-8) and serum C-reactive protein was evaluated. Sputum was obtained by sputum induction with hypertonic saline. A total of 41 patients were included. Ten patients were excluded as they were not able to produce sputum at the first or second visit. Baseline characteristics were similar in the two groups. In the remaining patients doxycycline did not influence sputum MPO concentrations. Also MMP-8 and 9, IL-6 and IL-8 concentrations as well as lung function parameters were not affected by doxycycline. Systemic inflammation by means of CRP was also not influenced by doxycycline. A three week course of doxycycline did not influence MPO sputum levels nor any of the other inflammatory sputum and systemic markers. ClinicalTrials.gov; No.: NCT00857038 URL: clinicaltrials.gov.


[Role of GABA in the modulation of Na, K-pump activity in nerve cells after irradiation and experimental modification of membrane lipid component].
After irradiation acute (12 Gy, 600 mGy/min), single prolonged (0.25 Gy, 1.75 mG/min), chronic (0.01 Gy/day, 0.25 Gy, 0.50 Gy, 1.75 mGy/min), and experimental disturbances of cell membranes with phospholipases-A2, -D, and arachidonic acid administration the considerable changes in Na,K-pump function were found in rat brain cortex slices, with their reduction almost to the control level in presence of gamma-aminobutyric acid (0.1-10.0 mcM). It had been supposed existing of the GABA-ergic "homeostasis control" mechanism, which restores the intracellular potassium homeostasis via GABA-modulation of the Na,K-pump activity by principles of receptor-mediated structural-membrane regulation under extreme factor influence.


Disruption of the BLM gene in ATM-null DT40 cells does not exacerbate either phenotype.
Bloom syndrome and ataxia-telangiectasia are autosomal recessive human disorders characterized by immunodeficiency, genome instability and predisposition to develop cancer. Recent data reveal that the products of these two genes, BLM and ATM, interact and function together in recognizing abnormal DNA structures. To investigate the function of these two molecules in DNA damage recognition, we generated double knockouts of ATM(-/-) BLM(-/-) in the DT40 chicken B-lymphocyte cell line. The double mutant cells were viable and exhibited a variety of characteristics of both ATM(-/-) and BLM(-/-) cells. There was no evidence for exacerbation of either phenotype; however, the more extreme radiosensitivity seen in ATM(-/-) and the elevated sister chromatid exchange seen in BLM(-/-) cells were retained in the double mutants. These results suggest that ATM and BLM have largely distinct roles in recognizing different forms of damage in DNA, but are also compatible with partially overlapping functions in recognizing breaks in radiation-damaged DNA.


Desensitization of the histamine H1-receptor and transcriptional down-regulation of histamine H1-receptor gene expression in bovine tracheal smooth muscle.
We have investigated the role of protein kinase C (PKC) in the desensitization of histamine H1-receptors and in the expression of the histamine H1-receptor gene in airway smooth muscle. Prolonged 4beta-phorbol 12,13 dibutyrate (PDBu) pretreatment (4 h, 100 nM-1 microM) of bovine trachealis caused a concentration-dependent loss of contraction in response to histamine H1-receptor stimulation, which was associated with a concentration-dependent decrease in histamine-induced total [3H]-inositol phosphates accumulation. In contrast, the responses to sodium fluoride, a direct G-protein activator, were unalterd by PDBu (100-300 nM) pre-incubation and only slightly reduced following incubation with 1 microM PDBu. A selective PKC inhibitor, GF 109203X, partially blocked the PDBu (1 microM)-induced desensitization and completely blocked the effect of 100 nM PDBu, confirming the involvement of PKC. Binding experiments using [3H]-pyrilamine revealed a class of high-affinity binding sites within the range for the histamine H1 receptor in airway smooth muscle. PDBu (1 microM) pretreatment for 4 h did not change the number of histamine H1 receptors. PDBu (1 microM) exposure caused a time-dependent reduction in the steady-state levels of histamine H1-receptor mRNA, which was inhibited by pre-incubation with GF 109203X and by cycloheximide, a protein synthesis inhibitor. Nuclear run-on assays revealed a 50% reduction in the rate of histamine H1-receptor gene transcription after 17 h PDBu pretreatment, whereas mRNA stability was not affected by PDBu pretreatment (17 h). In conclusion, we have shown a PKC-mediated desensitization of the histamine H1-receptor in BTSM and a transcriptional down-regulation of the histamine H1-receptor gene expression, which requires new protein synthesis.


[Multi-systemic toxicity of colchicine and renal failure: apropos of a case].
The use of colchicine can produce various side effects, but multiorgan toxicity is rare. We report the first Swiss case of multiorgan toxicity involving typical neuromuscular lesions. Muscular biopsy is a valuable tool in confirming the diagnosis. Renal insufficiency and hepatobiliary diseases are predisposing factors for such complications. Colchicine pharmacology in the case of renal insufficiency is discussed.


Influence of bacterial biopolymers on physical properties of experimental limestone blocks.
This article describes the consolidation effects of bacterial biopolymers synthesized by biofilm bacteria colonizing Mayan limestone buildings on the surface properties of limestone blocks, including disaggregation, hardness, and total color change at the laboratory level. The biopolymers evaluated, produced by bacterial isolates TM1B-488, TM1B-489, TM1B-349, and TM1B-464, influenced surface properties at different levels. 16S rRNA gene sequences analysis showed that isolate TM1B-349 was related with Psychrobacter sp. strain Marseille P-5312, TM1B-464 was related with Agrococcus terreus strain BT116, and isolates TM1B-488 and TM1B-489 were related with Xanthomonas citri pv. mangiferaeindicae strain XC01. Biopolymer A reduced the surface disaggregation of the material (26%) compared to the untreated control, as revealed by the peeling test, followed by biopolymer B (10%), while the remaining biopolymers had a negligible effect. The cactus biopolymer reduced disaggregation at higher levels (37%). On the other hand, there was a similar concomitant increase in surface hardness of limestone samples coated with biopolymer A (34%) and biopolymer B (32%), higher than biopolymers C (10%) and D (19%). Total color change for all treatments was below the threshold value of 5, indicating a non-significant color alteration. Partial chemical characterization of best-performing biopolymer (A) suggests its probable glycoprotein nature, whose constitutive acidic monosaccharides probably contributed to higher adherence to the limestone surfaces, contributing to surface stabilization, hardening the surface, and decreasing surface decohesion. These preliminary findings suggest its potential application in bioconsolidants, but further studies are required.


Synthesis of 14 C-radiolabeled oligonucleotides with a novel phosphoramidite reagent.
A novel solid-phase synthesis of 5'-radiolabeled oligonucleotides is described. The labeling reaction is carried out by the phosphoramidite method with the aid of [4,6-di-14C]-5'-dimethoxytritylthymidine building block 1. The feasibility of the method is demonstrated by preparation of 3'-phosphorylated dodecathymidylate phosphorothioate containing radiolabeled nucleoside at the 5'-terminus.


Association of sleep duration and risk of mental disorder: a systematic review and meta-analysis.
The effects of sleep duration on the development of mental illness remain controversial. Therefore, it is necessary to identify the effects of long or short sleep duration on psychological disorders, which could reveal new ways for preventing and treating mental health conditions cheaply. Identifying published papers was accomplished by using the following five English databases on March 16, 2022: PubMed, MEDLINE, Embase, Web of Science databases, and Scopus. Cross-sectional and cohort studies were considered if they evaluated the association of sleep duration with all kinds of mental illness in adults. We excluded case reports, editorials, narrative reviews, and studies without detailed information on sleep duration. Summary effect-size estimates were expressed as risk ratios (RRs) or odds ratios (ORs) with 95% confidence intervals and were evaluated using random-effect models. Mantel-Haenszel's random-effects model was used to estimate the inconsistency index (I2) and Tau2 index (measurement of heterogeneity). A total of 52 studies were included in this analysis, consisting of 14 cohort studies and 38 cross-sectional studies. These studies involved a combined sample size of 1,407,891 participants who met the inclusion criteria. Cohort (adjusted RR = 1.42, 95% CI: 1.26-1.60, P < .001, I2 = 37.6%, Tau2 = 0.014) and cross-sectional studies (adjusted OR = 1.67, 95% CI: 1.57-1.77, P < .001, I2 = 79.7%, Tau2 = 0.060) concluded that short sleep duration increased mental disorder risks. The same conclusions were acquired in the subgroup analysis, especially for depression (adjusted RR = 1.43, 95% CI: 1.24-1.65, P < .001, I2 = 80.4%, Tau2 = 0.082), anxiety (adjusted RR = 1.30, 95% CI: 1.04-1.63, P = .002, I2 = 0.0%, Tau2 = 0.000), and PTSD (adjusted RR = 1.35, 95% CI: 1.04-1.76, P = .022, I2 = 24.1%, Tau2 = 0.013) in cohort studies. The results of subgroup analysis indicated that long sleep duration was not a risk factor for depression (adjusted RR = 1.15, 95% CI: 0.98-1.34, P = .088, I2 = 63.4%, Tau2 = 0.045) and anxiety (adjusted RR = 1.37, 95% CI: 0.93-2.03, P = .114, I2 = 0.0%, Tau2 = 0.000). Short sleep duration, not long sleep duration, is an independent predictor of developing mental disorders, particularly anxiety and depression.


Tumor budding and evidence-based treatment of T2 rectal carcinomas.
The validity of the histological criteria in deciding additional bowel resection after local excision of T2 rectal carcinomas is questioned. In 72 T2 colorectal carcinomas resected by major surgery, the associations between lymph node metastasis (LNM) and clinicopathologic parameters were examined statistically, a prediction formula for LNM was constructed and decision analysis was attempted. Multivariate analysis showed that female gender and a greater number of tumor budding were significantly associated with LNM. The probability of LNM can be calculated as follows; Z = 0.037 x (budding number) + 2.08 x (SEX; male, 1; female, 2) - 5.736; Probability = 1/1 + e(-Z). When a 75-year-old patient has pulmonary complications, the operative risk is assumed to be over 2%. If a number of tumor budding is 0, the risk of LNM is calculated as 2.4% in a male and 17.1% in a female patient. On the assumption that the risk of liver metastasis is half of that of LNM, and the salvageabilities after LNM and liver metastasis are 20% and 50%, respectively, observation policy is justified for a male patient, whereas additional surgery should be undertaken for a female patient. A number of tumor budding may be useful for determining the individualized treatment of T2 rectal carcinomas.


Integrating transcription factor occupancy with transcriptome-wide association analysis identifies susceptibility genes in human cancers.
Transcriptome-wide association studies (TWAS) have successfully discovered many putative disease susceptibility genes. However, TWAS may suffer from inaccuracy of gene expression predictions due to inclusion of non-regulatory variants. By integrating prior knowledge of susceptible transcription factor occupied elements, we develop sTF-TWAS and demonstrate that it outperforms existing TWAS approaches in both simulation and real data analyses. Under the sTF-TWAS framework, we build genetic models to predict alternative splicing and gene expression in normal breast, prostate and lung tissues from the Genotype-Tissue Expression project and apply these models to data from large genome-wide association studies (GWAS) conducted among European-ancestry populations. At Bonferroni-corrected P < 0.05, we identify 354 putative susceptibility genes for these cancers, including 189 previously unreported in GWAS loci and 45 in loci unreported by GWAS. These findings provide additional insight into the genetic susceptibility of human cancers. Additionally, we show the generalizability of the sTF-TWAS on non-cancer diseases.


Proteomic Analysis after Sequential Extraction of Matrix Proteins in Urinary Stones Composed of Calcium Oxalate Monohydrate and Calcium Oxalate Dihydrate.
In this study, we performed proteomic analysis following sequential protein extraction on calcium oxalate monohydrate (COM) and calcium oxalate dihydrate (COD) urinary stones to determine the specific matrix proteins according to the crystal components of the stones. After X-ray and IR analysis of 13 urinary stones, matrix proteins were sequentially extracted with KCl, formic acid, guanidine-HCl, and EDTA, before SDS-electrophoresis followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The electrophoretic patterns of the extracted proteins differed from that of COM and COD stones. LC-MS/MS identified 65 proteins, of which many were cellular plasma proteins, and were frequently detected regardless of the crystal components. However, 6 proteins (protein Z, protein S, prothrombin, osteopontin, fatty acid binding protein 5, and ubiquitin) were detected in the final EDTA fractions of COM stones. These proteins are involved in the coagulation process or osteometabolism, and thus the roles they play are of particular interest.