Which, who and when? Therapeutic processes in group cognitive behaviour therapy for anxiety disorders.

The evidence for the effect of therapeutic alliance in group cognitive behaviour therapy (CBT) for anxiety disorders is unclear. Identifying whether the alliance-outcome relationship depends on (1) which components are assessed, (2) who is measuring the alliance and (3) when the alliance is measured will help to clarify the role of the client-therapist relationship in therapy. The present study explored the effects of alliance component (agreement vs. bond), rater perspective (client vs. therapist) and timing (early vs. late therapy) on the alliance-outcome relationship. Individuals with an anxiety disorder enrolled into transdiagnostic group CBT were studied, with n = 78 at early therapy and n = 57 at late therapy. Results showed that greater client-rated agreement significantly predicted improved post-treatment outcomes throughout the course of therapy, while stronger client-rated bond in late therapy predicted reduced treatment gains. In contrast, therapist perceptions of agreement and bond were not associated with post-treatment outcomes at any point in therapy. Client-reported group cohesion also was not associated with additional variance in outcome after accounting for client-rated alliance. Overall, the findings highlight the importance of prioritizing the client's perception of the client-therapist relationship in CBT for anxiety disorders, as well as distinguishing the effects of component, rater and timing in future process-outcome studies.

Can you see what I see? A comparison of client and observer perspectives of the alliance and group cohesion in CBT.

Both therapeutic alliance and group cohesion have been identified as "demonstrably effective" relationship elements in therapy. However, the overwhelming majority of process-outcome research has relied on clients as raters of the therapeutic relationship. A lack of convergence between client, therapist, and observer perspectives has raised questions regarding how best to measure relationships in therapy. Interest in observational measures has grown, as they may offer more objective and reliable measurements of process. This study compared the predictive validity of client and observer ratings of the alliance (Agreement and Bond) and group cohesion in the context of group cognitive behaviour therapy (CBT) for anxiety disorders. Results showed that client and observer ratings of process were not significantly correlated, and regarding the alliance, only client-rated Agreement predicted client-rated treatment gains. In contrast, both client and observer-ratings of group cohesion were found to uniquely contribute to treatment outcomes. If replicated, the findings from the present study suggest that (1) while client ratings of alliance consistently predict client-rated outcomes, the predictive validity of observer measures has yet to be established, and (2) both clients and observers provide meaningful and distinct information about group cohesion in therapy.

Elements of the therapeutic relationship in CBT for anxiety disorders: A systematic review.

To optimise the effects of cognitive behaviour therapy (CBT) for anxiety disorders, research has increasingly focussed on understanding mechanisms of change. Specifically, the therapeutic relationship has been identified as a potential "active ingredient" of therapy. The evidence for the effects of eleven elements of the therapeutic relationship (alliance, collaboration, goal consensus, group cohesion, empathy, positive regard, feedback, emotional expression, outcome expectations, treatment credibility, alliance rupture-repair) on treatment outcomes in CBT for anxiety disorders was systematically reviewed. Fifty unique studies were included, and findings were qualitatively reviewed and summarised. Results revealed consistent and sizeable evidence for the cohesion-outcome and expectation-outcome relationships. There was emerging evidence for the effects of collaboration, empathy, and alliance rupture-repair on outcomes. However, the evidence for goal consensus and credibility on outcomes was limited. Notably, review of the alliance literature revealed substantial inconsistencies across studies. No studies were identified for positive regard, feedback, and emotional expression. Overall, further research is needed to clarify the role of the therapeutic relationship in CBT for anxiety disorders. These findings will contribute to the conceptual integration of therapeutic relationship constructs in cognitive behavioural models, and help to improve treatments and outcomes for individuals.

Purified Inactivated Zika Vaccine Candidates Afford Protection against Lethal Challenge in Mice.

In response to the 2016 global public health emergency of international concern announced by the World Health Organization surrounding Zika virus (ZIKV) outbreaks, we developed a purified inactivated Zika virus vaccine (PIZV) candidate from ZIKV strain PRVABC59, isolated during the outbreak in 2015. The virus isolate was plaque purified, creating six sub-isolated virus stocks, two of which were selected to generate PIZV candidates for preclinical immunogenicity and efficacy evaluation in mice. The alum-adjuvanted PIZV candidates were highly immunogenic in both CD-1 and AG129 mice after a 2-dose immunization. Further, AG129 mice receiving 2 doses of PIZV formulated with alum were fully protected against lethal ZIKV challenge and mouse immune sera elicited by the PIZV candidates were capable of neutralizing ZIKVs of both African and Asian genetic lineages in vitro. Additionally, passive immunization of naïve mice with ZIKV-immune serum showed strong positive correlation between neutralizing ZIKV antibody (NAb) titers and protection against lethal challenge. This study supported advancement of the PIZV candidate toward clinical development.

Contrast-enhanced ultrasound in gallbladder disease: a pictorial review.

With its excellent contrast and spatial resolution, and the ability to image in real-time, ultrasound is the main imaging modality for assessing the gallbladder (GB). The application of contrast-enhanced ultrasound (CEUS) of the GB is now increasingly recognized as a useful addition to ultrasound and other cross-sectional imaging in the assessment of neoplastic and non-neoplastic GB disease. With the ability to image microcirculation and optimal contrast resolution, CEUS allows high-quality delineation in real-time, allowing for increased diagnostic confidence. In addition, ultrasound contrast agents have a favorable safety profile and can be used if CT or MR contrast agents are contraindicated or undesired. In this review, the CEUS appearances of a range of GB diseases encountered are presented, including adenomyomatosis, polyps, carcinoma, sludge, and cholecystitis with mural ulceration or perforation.

A comparison of independent component analysis algorithms and measures to discriminate between EEG and artifact components.

Independent Component Analysis (ICA) is a powerful statistical tool capable of separating multivariate scalp electrical signals into their additive independent or source components, specifically EEG or electroencephalogram and artifacts. Although ICA is a widely accepted EEG signal processing technique, classification of the recovered independent components (ICs) is still flawed, as current practice still requires subjective human decisions. Here we build on the results from Fitzgibbon et al. [1] to compare three measures and three ICA algorithms. Using EEG data acquired during neuromuscular paralysis, we tested the ability of the measures (spectral slope, peripherality and spatial smoothness) and algorithms (FastICA, Infomax and JADE) to identify components containing EMG. Spatial smoothness showed differentiation between paralysis and pre-paralysis ICs comparable to spectral slope, whereas peripherality showed less differentiation. A combination of the measures showed better differentiation than any measure alone. Furthermore, FastICA provided the best discrimination between muscle-free and muscle-contaminated recordings in the shortest time, suggesting it may be the most suited to EEG applications of the considered algorithms. Spatial smoothness results suggest that a significant number of ICs are mixed, i.e. contain signals from more than one biological source, and so the development of an ICA algorithm that is optimised to produce ICs that are easily classifiable is warranted.

Molecular evolution of candidate genes involved in post-mating-prezygotic reproductive isolation.

Traits involved in post-copulatory interactions between the sexes may evolve rapidly as a result of sexual selection and/or sexual conflict, leading to post-mating-prezygotic (PMPZ) reproductive isolating barriers between diverging lineages. Although the importance of PMPZ isolation is recognized, the molecular basis of such incompatibilities is not well understood. Here, we investigate molecular evolution of a subset of Drosophila mojavensis and Drosophila arizonae reproductive tract genes. These include genes that are transcriptionally regulated by conspecific mating in females, many of which are misregulated in heterospecific crosses, and a set of male genes whose transcripts are transferred to females during mating. As a group, misregulated female genes are not more divergent and do not appear to evolve under different selection pressures than other female reproductive genes. Male transferred genes evolve at a higher rate than testis-expressed genes, and at a similar rate compared to accessory gland protein genes, which are known to evolve rapidly. Four of the individual male transferred genes show patterns of divergent positive selection between D. mojavensis and D. arizonae. Three of the four genes belong to the sperm-coating protein-like family, including an ortholog of antares, which influences female fertility and receptivity in Drosophila melanogaster. Synthesis of these molecular evolutionary analyses with transcriptomics and predicted functional information makes these genes candidates for involvement in PMPZ reproductive incompatibilities between D. mojavensis and D. arizonae.

Unraveling the interfacial electron transfer dynamics of electroactive microbial biofilms using surface-enhanced Raman spectroscopy.

The electron transfer (ET) processes of electroactive microbial biofilms have been investigated by combining electrochemistry and time-resolved surface-enhanced resonance Raman (TR-SERR) spectroscopy. This experimental approach provides selective information on the ET process across the biofilm-electrode interface by monitoring the redox-state changes of heme cofactors in outer membrane cytochromes (OMCs) that are in close vicinity (i.e., within 7 nm) to the Ag working electrode. The rate constant for heterogeneous ET of the surface-confined OMCs (sc-OMCs) of a mixed culture derived electroactive microbial biofilm has been determined to be 0.03 s(-1) . In contrast, according to kinetic simulations the ET between sc-OMCs and their redox partners, embedded within the biofilm, is a much faster process with an estimated rate constant greater than 1.2 s(-1) . The slow rate of heterogeneous ET and the lack of high-spin species in the SERR spectra rule out the direct attachment of the sc-OMCs to the electrode surface.

Immune system phenotyping of radiation and radiation combined injury in outbred mice.

The complexity of a radionuclear event would be immense due to varying levels of radiation exposures and injuries caused by blast-associated trauma. With this scenario in mind, we developed a mouse model to mimic as closely as possible the potential consequences of radiation injury and radiation combined injury (RCI) on survival, immune system phenotype, and immune function. Using a mouse burn injury model and a (137)CsCl source irradiator to induce injuries, we report that the immunological response to radiation combined injury differs significantly from radiation or burn injury alone. Mice that underwent radiation combined injury showed lower injury survival and cecal ligation and puncture (CLP) induced polymicrobial sepsis survival rates than mice with single injuries. As anticipated, radiation exposure caused dose-dependent losses of immune cell subsets. We found B and T cells to be more radiation sensitive, while macrophages, dendritic cells and NK cells were relatively more resistant. However, radiation and radiation combined injury did induce significant increases in the percentages of CD4(+) regulatory T cells (Tregs) and a subset of macrophages that express cell-surface GR-1 (GR-1(+) macrophages). Immune system phenotyping analysis indicated that spleen cells from radiation combined injury mice produced higher levels of proinflammatory cytokines than cells from mice with radiation or burn injury alone, especially at lower dose radiation exposure levels. Interestingly, this enhanced proinflammatory phenotype induced by radiation combined injury persisted for at least 28 days after injury. In total, our data provide baseline information on differences in immune phenotype and function between radiation injury and radiation combined injury in mice. The establishment of this animal model will aid in future testing for therapeutic strategies to mitigate the immune and pathophysiological consequences of radionuclear events.

Development and stability of bacteriocin resistance in Campylobacter spp.

AIMS: Several bacteriocins (BCNs) that were identified from chicken commensal bacteria dramatically reduced Campylobacter colonization in poultry and are being directed toward on-farm control of this important foodborne human pathogen. A recent study has shown that BCN resistance in Campylobacter jejuni is very difficult to develop in vitro. In this study, in vivo development and stability of BCN resistance in Campylobacter was examined. METHODS AND RESULTS: Chickens infected with Camp. jejuni NCTC 11168 were treated with BCN E-760 at the dose of 5 mg kg(-1) body weight day(-1) via oral gavages for three consecutive days, which selected BCN-resistant (BCN(r)) mutants in the treated birds. However, all the in vivo-selected mutants only displayed low levels of resistance to BCN (MIC = 2-8 mg l(-1)) when compared to parent strain (MIC = 0.5 mg l(-1)). Inactivation of CmeABC efflux pump of the BCN(r) mutants led to increased susceptibility to BCN (8-32 fold MIC reduction). Three different BCN(r) Campylobacter strains (in vitro- or in vivo-derived) were examined for the stability of BCN resistance using both in vitro and in vivo systems. The low level of BCN resistance in these strains was not stable in vitro or in vivo in the absence of BCN selection pressure. CONCLUSIONS: Usage of BCN E-760 only selected low-level BCN(r) Camp. jejuni mutants in vivo, and the low-level BCN resistance was not stable in vitro and in vivo. SIGNIFICANCE AND IMPACT OF THE STUDY: The study provides helpful information for risk assessment of the future practical application of the anti-Campylobacter BCNs in animals.

The pro-longevity gene FoxO3 is a direct target of the p53 tumor suppressor.

FoxO transcription factors have a conserved role in longevity, and act as tissue-specific tumor suppressors in mammals. Several nodes of interaction have been identified between FoxO transcription factors and p53, a major tumor suppressor in humans and mice. However, the extent and importance of the functional interaction between FoxO and p53 have not been fully explored. Here, we show that p53 regulates the expression of FoxO3, one of the four mammalian FoxO genes, in response to DNA damaging agents in both mouse embryonic fibroblasts and thymocytes. We find that p53 transactivates FoxO3 in cells by binding to a site in the second intron of the FoxO3 gene, a genomic region recently found to be associated with extreme longevity in humans. While FoxO3 is not necessary for p53-dependent cell cycle arrest, FoxO3 appears to modulate p53-dependent apoptosis. We also find that FoxO3 loss does not interact with p53 loss for tumor development in vivo, although the tumor spectrum of p53-deficient mice appears to be affected by FoxO3 loss. Our findings indicate that FoxO3 is a p53 target gene, and suggest that FoxO3 and p53 are part of a regulatory transcriptional network that may have an important role during aging and cancer.

Smoking media literacy in Vietnamese adolescents.

BACKGROUND: Smoking media literacy (SML) has been found to be independently associated with reduced current smoking and reduced susceptibility to future smoking in a sample of American adolescents, but not in other populations of adolescents. Thus, the purpose of this study was to assess SML in Vietnamese adolescents and to determine the association with smoking behavior and susceptibility to future smoking. METHODS: A cross-sectional survey of 2000 high school students completed the SML scale, which is based on an integrated theoretical framework of media literacy, and items assessing cigarette use. Ordinal logistic regression was used to determine the association of SML with smoking and susceptibility to future smoking. Ordinal logistic regression was also to determine whether smoking in the past 30 days was associated with the 8 domains/core concepts of media literacy which comprise the SML. RESULTS: Smoking media literacy was lower among the Vietnamese adolescents than what has been previously reported in American adolescents. Ordinal logistic regression analysis results showed that in the total sample SML was associated with reduced smoking, but there was no association with susceptibility to future smoking. Further analysis showed that results differed according to school and grade level. There did not appear to be association of smoking with the specific domains/concepts that comprise the SML. CONCLUSIONS: The association of SML with reduced smoking suggests the need for further research involving SML, including the testing of media literacy training interventions, in Vietnamese adolescents and also other populations of adolescents.

Identifiable range of osseointegration of dental implants through resonance frequency analysis.

This paper aims to determine the identifiable stiffness range of interfacial tissue of dental implants by means of resonance frequency analysis. Two structural models of the Implant-Tissue-Bone system are built and the lowest two resonance frequencies of these two models are analyzed by Finite Element Method in the software Abaqus. The effects of four key parameters, i.e. the geometry, boundary constrain, material property of the bone and the interfacial tissue, to the resonance frequencies are examined in great detail. An intensive parametric study is conducted to reveal quantitative relationships between the resonance frequencies and these parameters. It is found that when the Young's modulus of the interfacial tissue is less than 15MPa, the resonance frequencies are dominantly affected by the interfacial tissue but not the other three parameters. This finding is extremely important to imply that the lowest two resonance frequencies of the Implant-Tissue-Bone system can be accurately determining the osseointegration of dental implants without worrying about all the other factors, as long as the Young's modulus of the interfacial tissue is in the range of 1-15MPa. However, beyond this range the measured resonance frequencies are affected by all these parameters, and need to be properly interpreted.

Immune activation by life-shortening Wolbachia and reduced filarial competence in mosquitoes.

Wolbachia strain wMelPop reduces the longevity of its Drosophila melanogaster host and, when introduced into the mosquito Aedes aegypti, halves its life span. We show that wMelPop induces up-regulation of the mosquito's innate immune system and that its presence inhibits the development of filarial nematodes in the mosquito. These data suggest that wMelPop could be used in the global effort to eliminate lymphatic filariasis and possibly for the control of other mosquito-borne parasites where immune preactivation inhibits their development. The cost of constitutive immune up-regulation may contribute to the life-shortening phenotype.

Actinomadura miaoliensis sp. nov., a thermotolerant polyester-degrading actinomycete.

An actinomycete, strain BC 44T-5(T), with the ability to degrade poly(d-3-hydroxybutyrate) was isolated from a soil sample collected from Miaoli County, Taiwan. The isolate displayed substrate mycelia and short spore chains were borne on the aerial mycelia. Spores were non-motile, round, 1 mum in diameter and spiny. The aerial spore mass was blue. Strain BC 44T-5(T) had meso-diaminopimelic acid as the diagnostic diamino acid of the cell-wall peptidoglycan. Whole-cell sugars of the novel strain were identified as glucose, galactose and madurose. Diphosphatidylglycerol and phosphatidylinositol were detected. The predominant menaquinones were MK-9(H(4)) and MK-9(H(2)). Mycolic acids were not detected. Major cellular fatty acids were iso-C(16 : 0) (14.82 %), C(16 : 0) (14.63 %), C(17 : 0) (13.79 %) and 10-methyl-C(17 : 0) (23.77 %.) The DNA G+C content of strain BC 44T-5(T) was 70.6 mol%. On the basis of phenotypic and genotypic data, it is proposed that strain BC 44T-5(T) (=FIRDI 002(T)=BCRC 16873(T)=LMG 24335(T)) should be classified as the type strain of a novel species of the genus Actinomadura, Actinomadura miaoliensis sp. nov.

Dexamethasone protects organ of corti explants against tumor necrosis factor-alpha-induced loss of auditory hair cells and alters the expression levels of apoptosis-related genes.

OBJECTIVE: Determine the molecular mechanism(s) behind tumor necrosis factor-alpha (TNFalpha)-induced loss of auditory hair cells and the ability of dexamethasone base (DXMb) to protect against TNFalpha ototoxicity. METHODS: Hair cell counts: Three-day-old rat organ of Corti explants were cultured under three different conditions: 1) untreated-control; 2) TNFalpha (2 mug/ml); and 3) TNFalpha (2 mug/ml)+DXMb (70 mug/ml) for 4 days, fixed, and stained with FITC-phalloidin. Hair cells were counted in the basal and middle turns. Gene expression: total RNA was extracted from the three different groups of explants at 0, 12, 24 and 48 h. Using quantitative real-time RT-PCR, mRNAs were transcribed into cDNAs and amplification was performed using primers for rat ss-actin (housekeeping gene), TNFR1, Bcl-2, Bax, and Bcl-xl. RESULTS: DXMb protected explant hair cells from TNFalpha-induced loss. Bax gene expression was greater in TNFalpha-exposed explants compared with TNFalpha+DXMb-treated explants at 48 h (P=0.023), confirmed by the increase in the Bax/Bcl-2 ratio at 48 h (P<0.001). These results correlated with increased TNFR1 expression at 24 h (P=0.038). DXMb otoprotection in TNFalpha-exposed cultures was accompanied by an up-regulation of Bcl-xl at both the 24 (P<0.001) and 48 h time points (P=0.030) and up-regulation of Bcl-2 expression at 24 h (P=0.018). DXMb treatment also prevented increases in the expression levels of Bax, TNFR1, and the Bax/Bcl-2 ratio that occurred in untreated TNFalpha-exposed explants. CONCLUSIONS: TNFalpha's ototoxicity may be mediated through an up-regulation of Bax and TNFR1 expression as well as an increase in the Bax/Bcl-2 ratio. DXMb protects the organ of Corti against TNFalpha ototoxicity by up-regulating Bcl-2 and Bcl-xl expression and by inhibiting TNFalpha-induced increases in Bax, TNFR1, and the Bax/Bcl-2 ratio. These results support the use of local dexamethasone treatment to conserve hearing following a trauma.

Use of sequence analysis of the VP4 gene to classify recent Vietnamese rotavirus isolates.

Twenty-eight strains of P(8), four of P(4) and one of P(19) rotavirus, isolated in Ho Chi Minh City, Vietnam, during 2002-2003, were investigated by sequence analysis of the VP4 gene. Seven of the 28 P(8) rotavirus VP4 sequences clustered in the P(8)-3 lineage, or the rare, so-called OP354-like lineage. Amino-acid sequence comparison revealed that Vietnamese P(8)-3 rotaviruses were generally very similar to Malawian strains, including the prototype OP354 strain. The numerical severity scores of diarrhoeal disease caused by the Vietnamese P(8)-3 rotaviruses were statistically higher than those of diarrhoeal disease caused by rotaviruses in the more common P(8)-2 lineage. Sequence and phylogenetic analysis of the VP4 gene of a Vietnamese G9P(19) rotavirus isolate showed a high degree of homology with the cognate genes of other human and porcine rotaviruses, including the prototype 4F strain.

The relationship between calcium, MAP kinase, and DNA synthesis in the sea urchin egg at fertilization.

Fertilization releases the brake on the cell cycle and the egg completes meiosis and enters into S phase of the mitotic cell cycle. The MAP kinase pathway has been implicated in this process, but the precise role of MAP kinase in meiosis and the first mitotic cell cycle remains unknown and may differ according to species. Unlike the eggs of most animals, sea urchin eggs have completed meiosis prior to fertilization and are arrested at the pronuclear stage. Using both phosphorylation-state-specific antibodies and a MAP kinase activity assay, we observe that MAP kinase is phosphorylated and active in unfertilized sea urchin eggs and then dephosphorylated and inactivated by 15 min postinsemination. Further, Ca(2+) was both sufficient and necessary for this MAP kinase inactivation. Treatment of eggs with the Ca(2+) ionophore A23187 caused MAP kinase inactivation and triggered DNA synthesis. When the rise in intracellular Ca(2+) was inhibited by injection of a chelator, BAPTA or EGTA, the activity of MAP kinase remained high. Finally, inhibition of the MAP kinase signaling pathway by the specific MEK inhibitor PD98059 triggered DNA synthesis in unfertilized eggs. Thus, whenever MAP kinase activity is retained, DNA synthesis is inhibited while inactivation of MAP kinase correlates with initiation of DNA synthesis.