Dynamics of temporally interleaved percept-choice sequences: interaction via adaptation in shared neural populations

At the onset of visually ambiguous or conflicting stimuli, our visual system quickly ‘chooses’ one of the possible percepts. Interrupted presentation of the same stimuli has revealed that each percept-choice depends strongly on the history of previous choices and the duration of the interruptions. Recent psychophysics and modeling has discovered increasingly rich dynamical structure in such percept-choice sequences, and explained or predicted these patterns in terms of simple neural mechanisms: fast cross-inhibition and slow shunting adaptation that also causes a near-threshold facilitatory effect. However, we still lack a clear understanding of the dynamical interactions between two distinct, temporally interleaved, percept-choice sequences—a type of experiment that probes which feature-level neural network connectivity and dynamics allow the visual system to resolve the vast ambiguity of everyday vision. Here, we fill this gap. We first show that a simple column-structured neural network captures the known phenomenology, and then identify and analyze the crucial underlying mechanism via two stages of model-reduction: A 6-population reduction shows how temporally well-separated sequences become coupled via adaptation in neurons that are shared between the populations driven by either of the two sequences. The essential dynamics can then be reduced further, to a set of iterated adaptation-maps. This enables detailed analysis, resulting in the prediction of phase-diagrams of possible sequence-pair patterns and their response to perturbations. These predictions invite a variety of future experiments

Opposite Influence of Perceptual Memory on Initial and Prolonged Perception of Sensory Ambiguity

Observers continually make unconscious inferences about the state of the world based on ambiguous sensory information. This process of perceptual decision-making may be optimized by learning from experience. We investigated the influence of previous perceptual experience on the interpretation of ambiguous visual information. Observers were pre-exposed to a perceptually stabilized sequence of an ambiguous structure-from-motion stimulus by means of intermittent presentation. At the subsequent re-appearance of the same ambiguous stimulus perception was initially biased toward the previously stabilized perceptual interpretation. However, prolonged viewing revealed a bias toward the alternative perceptual interpretation. The prevalence of the alternative percept during ongoing viewing was largely due to increased durations of this percept, as there was no reliable decrease in the durations of the pre-exposed percept. Moreover, the duration of the alternative percept was modulated by the specific characteristics of the pre-exposure, whereas the durations of the pre-exposed percept were not. The increase in duration of the alternative percept was larger when the pre-exposure had lasted longer and was larger after ambiguous pre-exposure than after unambiguous pre-exposure. Using a binocular rivalry stimulus we found analogous perceptual biases, while pre-exposure did not affect eye-bias. We conclude that previously perceived interpretations dominate at the onset of ambiguous sensory information, whereas alternative interpretations dominate prolonged viewing. Thus, at first instance ambiguous information seems to be judged using familiar percepts, while re-evaluation later on allows for alternative interpretations

Behavioral determinants as predictors of return to work after long-term sickness absence: an application of the theory of planned behavior

Background The aim of this prospective, longitudinal cohort study was to analyze the association between the three behavioral determinants of the theory of planned behavior (TPB) model-attitude, subjective norm and self-efficacy-and the time to return-to-work (RTW) in employees on long-term sick leave. Methods The study was based on a sample of 926 employees on sickness absence (maximum duration of 12 weeks). The employees filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. The TPB-determinants were measured at baseline. Work attitude was measured with a Dutch language version of the Work Involvement Scale. Subjective norm was measured with a self-structured scale reflecting a person's perception of social support and social pressure. Self-efficacy was measured with the three subscales of a standardised Dutch version of the general self-efficacy scale (ALCOS): willingness to expend effort in completing the behavior, persistence in the face of adversity, and willingness to initiate behavior. Cox proportional hazards regression analyses were used to identify behavioral determinants of the time to RTW. Results Median time to RTW was 160 days. In the univariate analysis, all potential prognostic factors were significantly associated (P < 0.15) with time to RTW: work attitude, social support, and the three subscales of self-efficacy. The final multivariate model with time to RTW as the predicted outcome included work attitude, social support and willingness to expend effort in completing the behavior as significant predictive factors. Conclusions This prospective, longitudinal cohort-study showed that work attitude, social support and willingness to expend effort in completing the behavior are significantly associated with a shorter time to RTW in employees on long-term sickness absence. This provides suggestive evidence for the relevance of behavioral characteristics in the prediction of duration of sickness absence. It may be a promising approach to address the behavioral determinants in the development of interventions focusing on RTW in employees on long-term sick leave

A Prospective Study of Return to Work Across Health Conditions: Perceived Work Attitude, Self-efficacy and Perceived Social Support

Background The aim of the present study was to conduct subgroup-analyses in a prospective cohort of workers on long-term sickness absence to investigate whether associations between perceived work attitude, self-efficacy and perceived social support and time to RTW differ across different health conditions. Methods The study was based on a sample of 926 workers on sickness absence (6–12 weeks). The participants filled out a baseline questionnaire and were subsequently followed until the tenth month after listing sick. Perceived work attitude was measured with a Dutch language version of the Work Involvement Scale. Perceived social support was measured with a self-constructed standardized scale reflecting a person’s perception of social support regarding RTW. Self-efficacy was measured with the standardised Dutch version of the General self-efficacy scale, assessing the subjects’ expectations of their general capacities. The sample was divided into three subgroups: musculoskeletal health conditions, other physical health conditions and mental health conditions. Anova analyses and Cox proportional hazards regression analyses were used to identify differences in association between the three factors and the time to RTW between different subgroups. Results The associations between the perceived work attitude, self-efficacy and perceived social support and the time to RTW vary across different health condition subgroups, not only with regard to the strength of the association but also for the type of factor. In the multivariate model, hazard ratios (HRs) of 1.33 (95% CI 1.01–1.75) in the musculoskeletal subgroup, and 1.26 (95% CI 0.89–1.78) in the other physical subgroup were found in perceived work attitude. With regard to perceived social support HRs of 1.39 (95% CI 1.12–1.99) respectively 1.51 (1.05–2.17) in the same subgroups were found. Only self-efficacy remained in the multivariate model in all subgroups with HRs of 1.49 (95% CI 1.12–1.99) in the musculoskeletal subgroup, 1.53 (95% CI 1.07–2.18) in the other physical subgroup and 1.60 (1.07–2.40) in the mental subgroup. Conclusions The results of this study show that perceived work attitude, self-efficacy and perceived social support are relevant predictors with regard to the time to RTW in all types of health conditions, but that important differences are observed in type of factor and strengths of the relationships between physical and mental health conditions

Development of a workplace intervention for sick-listed employees with stress-related mental disorders: Intervention Mapping as a useful tool

Background. To date, mental health problems and mental workload have been increasingly related to long-term sick leave and disability. However, there is, as yet, no structured protocol available for the identification and application of an intervention for stress-related mental health problems at the workplace. This paper describes the structured development, implementation and planning for the evaluation of a return-to-work intervention for sick-listed employees with stress-related mental disorders (SMDs). The intervention is based on an existing successful return-to-work intervention for sick-listed employees with low back pain. Methods. The principles of Intervention Mapping were applied to combine theory and evidence in the development, implementation and planning for the evaluation of a participatory workplace intervention, aimed at an early return-to-work for sick-listed employees with SMDs. All stakeholders were involved in focus group interviews: i.e. employees recently sick-listed with SMDs, supervisors and occupational health professionals. Results. The development of the participatory workplace intervention according to the Intervention Mapping principles resulted in a structured return-to-work intervention, specifically tailored to the needs of sick-listed employees with SMDs. Return-to-work was proposed as a behavioural change, and the Attitude - Social influence - self-Efficacy model was identified as a theoretical framework. Stakeholder involvement in focus group interviews served to enhance the implementation. The cost-effectiveness of the intervention will be evaluated in a randomised controlled trial. Conclusion. Intervention Mapping was found to be a promising method to develop interventions tailored to a specific target group in the field of occupational health. Trial registration. ISRCTN92307123. © 2007 van Oostrom et al; licensee BioMed Central Ltd

5-HT2C Receptors Localize to Dopamine and GABA Neurons in the Rat Mesoaccumbens Pathway

The serotonin 5-HT2C receptor (5-HT2CR) is localized to the limbic-corticostriatal circuit, which plays an integral role in mediating attention, motivation, cognition, and reward processes. The 5-HT2CR is linked to modulation of mesoaccumbens dopamine neurotransmission via an activation of γ-aminobutyric acid (GABA) neurons in the ventral tegmental area (VTA). However, we recently demonstrated the expression of the 5-HT2CR within dopamine VTA neurons suggesting the possibility of a direct influence of the 5-HT2CR upon mesoaccumbens dopamine output. Here, we employed double-label fluorescence immunochemistry with the synthetic enzymes for dopamine (tyrosine hydroxylase; TH) and GABA (glutamic acid decarboxylase isoform 67; GAD-67) and retrograde tract tracing with FluoroGold (FG) to uncover whether dopamine and GABA VTA neurons that possess 5-HT2CR innervate the nucleus accumbens (NAc). The highest numbers of FG-labeled cells were detected in the middle versus rostral and caudal levels of the VTA, and included a subset of TH- and GAD-67 immunoreactive cells, of which >50% also contained 5-HT2CR immunoreactivity. Thus, we demonstrate for the first time that the 5-HT2CR colocalizes in DA and GABA VTA neurons which project to the NAc, describe in detail the distribution of NAc-projecting GABA VTA neurons, and identify the colocalization of TH and GAD-67 in the same NAc-projecting VTA neurons. These data suggest that the 5-HT2CR may exert direct influence upon both dopamine and GABA VTA output to the NAc. Further, the indication that a proportion of NAc-projecting VTA neurons synthesize and potentially release both dopamine and GABA adds intriguing complexity to the framework of the VTA and its postulated neuroanatomical roles

Sulfhydryl Modification Induces Calcium Entry through IP3-Sensitive Store-Operated Pathway in Activation-Dependent Human Neutrophils

As the first line of host defense, neutrophils are stimulated by pro-inflammatory cytokines from resting state, facilitating the execution of immunomodulatory functions in activation state. Sulfhydryl modification has a regulatory role in a wide variety of physiological functions through mediation of signaling transductions in various cell types. Recent research suggested that two kinds of sulfhydryl modification, S-nitrosylation by exogenous nitric oxide (NO) and alkylation by N-ethylmaleimide (NEM), could induce calcium entry through a non-store-operated pathway in resting rat neutrophils and DDT1MF-2 cells, while in active human neutrophils a different process has been observed by us. In the present work, data showed that NEM induced a sharp rising of cytosolic calcium concentration ([Ca2+]c) without external calcium, followed by a second [Ca2+]c increase with readdition of external calcium in phorbol 12-myristate 13-acetate (PMA)-activated human neutrophils. Meanwhile, addition of external calcium did not cause [Ca2+]c change of Ca2+-free PMA-activated neutrophils before application of NEM. These data indicated that NEM could induce believable store-operated calcium entry (SOCE) in PMA-activated neutrophils. Besides, we found that sodium nitroprusside (SNP), a donor of exogenous NO, resulted in believable SOCE in PMA-activated human neutrophils via S-nitrosylation modification. In contrast, NEM and SNP have no effect on [Ca2+]c of resting neutrophils which were performed in suspension. Furthermore, 2-Aminoethoxydiphenyl borate, a reliable blocker of SOCE and an inhibitor of inositol 1,4,5-trisphosphate (IP3) receptor, evidently abolished SNP and NEM-induced calcium entry at 75 µM, while preventing calcium release in a concentration-dependent manner. Considered together, these results demonstrated that NEM and SNP induced calcium entry through an IP3-sensitive store-operated pathway of human neutrophils via sulfhydryl modification in a PMA-induced activation-dependent manner

Current therapy of granulomatosis with polyangiitis and microscopic polyangiitis: the role of rituximab.

Granulomatosis with polyangiitis and microscopic polyangiitis are anti-neutrophil cytoplasmic antibody-associated vasculitides (AAVs) that are prone to cycles of remission and relapse. The introduction of cytotoxic therapy has changed the prognosis for these diseases from typically fatal to manageable chronic illnesses with a relapsing course. Despite improvements in outcomes, recurrence of disease and drug-related toxicity continue to produce significant morbidity and mortality. Better understanding of the pathogenesis of AAV and the mechanism of action of cyclophosphamide has led to investigation of therapies that target B cells. Two randomized controlled trials have shown that rituximab is not inferior to cyclophosphamide for induction of remission in severe AAV, with no significant difference in the incidence of overall adverse events in rituximab- versus cyclophosphamide-treated patients. Data from ongoing clinical trials will determine the role of rituximab in the maintenance of remission

Promotion, prevention and protection: interventions at the population- and community-levels for mental, neurological and substance use disorders in low- and middle-income countries

Background In addition to services within the health system, interventions at the population and community levels are also important for the promotion of mental health, primary prevention of mental, neurological and substance use (MNS) disorders, identification and case detection of MNS disorders; and to a lesser degree treatment, care and rehabilitation. This study aims to identify “best practice” and “good practice” interventions that can feasibly be delivered at these population- and community-levels in low- and middle-income countries (LMICs), to aid the identification of resource efficiencies and allocation in LMICs. Methods A narrative review was conducted given the wide range of relevant interventions. Expert consensus was used to identify “best practice” at the population-level on the basis of existing quasi-experimental natural experiments and cost effectiveness, with small scale emerging and promising evidence comprising “good practice”. At the community-level, using expert consensus, the ACE (Assessing Cost-Effectiveness in Prevention Project) grading system was used to differentiate “best practice” interventions with sufficient evidence from “good practice” interventions with limited but promising evidence. ResultsAt the population-level, laws and regulations to control alcohol demand and restrict access to lethal means of suicide were considered “best practice”. Child protection laws, improved control of neurocysticercosis and mass awareness campaigns were identified as “good practice”. At the community level, socio-emotional learning programmes in schools and parenting programmes during infancy were identified as “best practice”. The following were all identified as “good practice”: Integrating mental health promotion strategies into workplace occupational health and safety policies; mental health information and awareness programmes as well as detection of MNS disorders in schools; early child enrichment/preschool educational programs and parenting programs for children aged 2–14 years; gender equity and/or economic empowerment programs for vulnerable groups; training of gatekeepers to identify people with MNS disorders in the community; and training non-specialist community members at a neighbourhood level to assist with community-based support and rehabilitation of people with mental disorders. Conclusion Interventions provided at the population- and community-levels have an important role to play in promoting mental health, preventing the onset, and protecting those with MNS disorders. The importance of inter-sectoral enga