Search

The appearance of a salient stimulus evokes a series of orienting responses including saccades and pupil size to prepare the body for appropriate action. The midbrain superior colliculus (SC) that receives critical control signals from the frontal eye field (FEF) is hypothesized to coordinate all components of orienting. It has shown recently that the FEF, together with the SC, is also importantly involved in the control of pupil size, in addition to its well-documented role in eye movements. Although the role of the FEF in pupil size is demonstrated in monkeys, its role in human pupil responses and the coordination between pupil size and saccades remains to be established. Through applying continuous theta-burst stimulation over the right FEF and vertex, we investigated the role of the FEF in human pupil and saccade responses evoked by a salient stimulus, and the coordination between pupil size and saccades. Our results showed that neither saccade reaction times (SRT) nor pupil responses evoked by salient stimuli were modulated by FEF stimulation. In contrast, the correlation between pupil size and SRTs in the contralateral stimulus condition was diminished with FEF stimulation, but intact with vertex stimulation. Moreover, FEF stimulation effects between saccade and pupil responses associated with salient stimuli correlated across participants. This is the first transcranial magnetic stimulation (TMS) study on the pupil orienting response, and our findings suggest that human FEF was involved in coordinating pupil size and saccades, but not involved in the control of pupil orienting responses., (© 2021 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

The brain's intrinsic activity plays a fundamental role in its function. In normal conditions this activity is responsive to behavioural context, changing as an individual switches between directed tasks and task-free conditions. A key feature of such changes is the movement of the brain between corresponding critical and sub-critical states, with these dynamics supporting efficient cognitive processing. Breakdowns in processing efficiency can occur, however, in brain disorders such as depression. It was therefore hypothesised that depressive symptoms would be related to reduced intrinsic activity responsiveness to changes in behavioural state. This was tested in a mixed group of major depressive disorder patients (n = 26) and healthy participants (n = 37) by measuring intrinsic EEG activity temporal structure, quantified with detrended fluctuation analysis (DFA), in eyes-closed (EC) and eyes-open task-free states and contrasting between the conditions. The degree to which DFA values changed between the states was found to correlate negatively with depressive symptoms. DFA values did not differ between states in those with higher symptom levels, meaning that the brain remained in a less flexible sub-critical condition. This sub-critical condition in the EC state was further found to correlate with levels of maladaptive rumination. This may reflect a general cognitive inflexibility resulting from a lack in neural activity reactivity that may predispose people to overly engage in self-directed attention. These results provide an initial link between intrinsic activity reactivity and psychological features found in psychiatric disorders., (© 2020 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Objective: To examine the epidemiological and economic impact of a nine-valent (nonavalent) human papillomavirus (HPV) 6/11/16/18/31/33/45/52/58 vaccine programme for young teenagers in Singapore., Design: Mathematical modelling., Setting: Pharmaco-economic simulation projection., Population: Singapore demography., Methods: Clinical, epidemiological and financial data from Singapore were used in a validated HPV transmission dynamic mathematical model to analyse the impact of nonavalent HPV vaccination over quadrivalent and bivalent vaccines in a school-based 2-dose vaccination for 11- to 12-year-old girls in the country. The model assumed routine cytology screening in the current rate (50%) and vaccine coverage rate of 80%., Main Outcome Measures: Changes over a 100-year time period in the incidence and mortality rates of cervical cancer, case load of genital warts, and incremental cost-effectiveness ratio (ICER)., Results: Compared with bivalent and quadrivalent HPV vaccination programmes, nonavalent HPV universal vaccination resulted in an additional reduction of HPV31/33/45/52/58 related CIN1 of 40.5%, CIN 2/3 of 35.4%, cervical cancer of 23.5%, and cervical cancer mortality of 20.2%. Compared with bivalent HPV vaccination, there was an additional reduction in HPV-6/11 related CIN1 of 75.7%, and genital warts of 78.9% in women and 73.4% in men. Over the 100 years, after applying a discount of 3%, disease management cost will be reduced by 32.5% (versus bivalent) and 7.5% (versus quadrivalent). The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year gained was SGD 929 compared with bivalent vaccination and SGD 9864 compared with quadrivalent vaccination., Conclusion: Universal two-dose nonavalent HPV vaccination for 11- to 12-year-old adolescent women is very cost-effective in Singapore., Tweetable Abstract: Nonavalent HPV vaccination of 11- to 12-year-old girls is cost-effective in Singapore., (© 2017 Royal College of Obstetricians and Gynaecologists.)

Background: Atopic dermatitis affects 15-30% of children worldwide. Onset of disease usually occurs within the first year of life, over half of which regress by 6 years of age. The aim of this study was to investigate the risk factors related to the persistence of infantile atopic dermatitis., Methods: In this birth cohort study, patients were enrolled prenatally and followed until 6 years of age; 246 patients had infantile atopic dermatitis at 6 months of age. Family history, maternal and paternal total and specific Immunoglobulin E (IgE) levels, and cord blood IgE were recorded. Clinical examination, questionnaire survey, and blood samples for total and specific IgE of the children were collected at each follow-up visit., Results: Of the 246 patients with infantile atopic dermatitis at 6 months of age, 48 patients had persisted atopic dermatitis at 6 years of age (19.5%). Risk factors associated with persistent infantile atopic dermatitis included egg white sensitization (odds ratio: 3.801, P = 0.020), and atopic dermatitis involving two or more areas at 6 months old (odds ratio: 2.921, P = 0.018) after multivariate analysis with logistic regression. Patients with persistent infantile atopic dermatitis had a higher risk of asthma before 6 years old (39.6% vs 24.2%, P = 0.032)., Conclusion: Egg white sensitization and the initial involvement of two or more areas at 6 months of age were associated with the persistent infantile atopic dermatitis. Patients with persistent infantile atopic dermatitis are more likely to develop asthma by 6 years of age., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives/hypothesis: To explore the possible determinants of bilateral audiometric notches in noise-induced hearing loss (NIHL)., Study Design: Prospectively enrolled cohort with cross-sectional analysis., Methods: Male workers (n = 412) with exposure to continuous loud noise (noise exposure level normalized to a nominal 8-hour working day >75 dBA) during work were included in this cohort study. The relationship between the presence of bilateral audiometric notches and age, noise exposure duration, noise exposure level, and shift from the predicted thresholds over different frequencies were determined by regression model analysis, receiver operating characteristic analysis, and area under the curve analysis., Results: The presence of bilateral audiometric notches was closely associated with the shifts from the predicted thresholds over 1, 2, 3, 4, and 6 kHz. The shift pattern was somewhat different between those who used hearing protection devices and those who did not. The shifts from the predicted thresholds demonstrated a stronger association with bilateral audiometric notches than did age, gender, noise exposure level, or noise exposure duration., Conclusions: The bilateral audiometric notches in NIHL could not be determined only on the basis of age, gender, noise exposure level, or noise exposure duration. The importance of other factors associated with bilateral audiometric notches should be recognized. Elucidation of the factors of formation of bilateral audiometric notches would help us to develop a more comprehensive protection strategy to prevent further NIHL., (Copyright © 2013 The American Laryngological, Rhinological, and Otological Society, Inc.)

Background: Prevalence of allergic diseases in children has increased worldwide over the past decades. Allergy sensitization may occur in fetal life. This study investigated whether gene-gene and gene-environment interactions affected cord blood IgE (CBIgE) levels., Methods: A total of 575 cord blood DNA samples were subjected to a multiplex microarray for 384 single nucleotide polymorphisms (SNPs) in 159 allergy candidate genes. Genetic association was initially assessed by univariate and multivariate analyses. Multifactor dimensionality reduction (MDR) was used to identify gene-gene and gene-environment interactions. Environmental factors for analysis included maternal atopy, paternal atopy, parental smoking, gender, and prematurity., Results: Twenty-one SNPs in 14 genes were associated with CBIgE elevation (>or =0.5 KU/l) in univariate analysis. Multivariate analysis identified eleven genes (IL13, IL17A, IL2RA, CCL17, CXCL1, PDGFRA, FGF1, HAVCR1, GNAQ, C11orf72, and ADAM33) which were significantly associated with CBIgE elevation. MDR analyses of gene-gene interactions identified IL13 interacted with IL17A and/or redox genes on CBIgE elevation with the prediction accuracy of 62.52%. Analyses of gene-environment interactions identified that maternal atopy combined with IL13, rs1800925 and CCL22, rs170359 SNPs had the highest prediction accuracy of 67.15%. All the high and low risk classifications on gene-gene and gene-environment interactions by MDR analyses could be validated by Chi-square test., Conclusions: Gene-gene (e.g. immune and redox genes) and gene-environment (e.g. maternal atopy and FGF1or redox genes) interactions on IgE production begin in prenatal stage, suggesting that prevention of IgE-mediated diseases may be made possible by control of maternal atopy and redox responses in prenatal stage.

Cord blood T cells are much more likely to be induced to apoptosis in vitro than adult T cells. Nevertheless, the expression of Fas is markedly lower on cord blood lymphocytes than on peripheral blood lymphocytes. In the current investigation, we determined the capacity of tumour necrosis factor-alpha (TNF-alpha) to induce apoptosis in human naïve T cells in cord blood, and assessed the roles of two distinct TNF receptors (TNFRs) in mediating death signals. After activation, cord blood T cells were sensitive to TNF-alpha-induced apoptosis, and interleukin 2 (IL-2) could prevent this apoptotic response. Both TNFR1 (p55) and TNFR2 (p75) expressed on activated cord blood T cells were able to transmit apoptotic signals. Moreover, a synergistic effect was observed by a combination of TNFR1- and TNFR2-signals. Additionally, CD4(+) T cells showed higher sensitivity to TNFR-mediated apoptosis than CD8(+) T cells. These data suggest that TNF-alpha probably is a mediator of apoptosis in cord blood T cells in vivo and may contribute to the low incidence of graft-versus-host disease in cord blood transplantation.