There is cumulative evidence that young people in an "atrisk mental state" (ARMS) for psychosis show structural brain abnormalities in frontolimbic areas, comparable to, but less extensive than those reported in established schizophrenia. However, most available data come from ARMS samples from Australia, Europe, and North America while large studies from other populations are missing. We conducted a structural brain magnetic resonance imaging study from a relatively large sample of 69 ARMS individuals and 32 matched healthy controls (HC) recruited from Singapore as part of the Longitudinal Youth At-Risk Study (LYRIKS). We used 2 complementary approaches: a voxel-based morphometry and a surface-based morphometry analysis to extract regional gray and white matter volumes (GMV and WMV) and cortical thickness (CT). At the whole-brain level, we did not find any statistically significant difference between ARMS and HC groups concerning total GMV and WMV or regional GMV, WMV, and CT. The additional comparison of 2 regions of interest, hippocampal, and ventricular volumes, did not return any significant difference either. Several characteristics of the LYRIKS sample like Asian origins or the absence of current illicit drug use could explain, alone or in conjunction, the negative findings and suggest that there may be no dramatic volumetric or CT abnormalities in ARMS.

BackgroundSalience network (SN) dysconnectivity has been hypothesized to contribute to schizophrenia. Nevertheless, little is known about the functional and structural dysconnectivity of SN in subjects at risk for psychosis. We hypothesized that SN functional and structural connectivity would be disrupted in subjects with At-Risk Mental State (ARMS) and would be associated with symptom severity and disease progression.MethodWe examined 87 ARMS and 37 healthy participants using both resting-state functional magnetic resonance imaging and diffusion tensor imaging. Group differences in SN functional and structural connectivity were examined using a seed-based approach and tract-based spatial statistics. Subject-level functional connectivity measures and diffusion indices of disrupted regions were correlated with CAARMS scores and compared between ARMS with and without transition to psychosis.ResultsARMS subjects exhibited reduced functional connectivity between the left ventral anterior insula and other SN regions. Reduced fractional anisotropy (FA) and axial diffusivity were also found along white-matter tracts in close proximity to regions of disrupted functional connectivity, including frontal-striatal-thalamic circuits and the cingulum. FA measures extracted from these disrupted white-matter regions correlated with individual symptom severity in the ARMS group. Furthermore, functional connectivity between the bilateral insula and FA at the forceps minor were further reduced in subjects who transitioned to psychosis after 2 years.ConclusionsOur findings support the insular dysconnectivity of the proximal SN hypothesis in the early stages of psychosis. Further developed, the combined structural and functional SN assays may inform the prognosis of persons at-risk for psychosis.

Aims and Objectives:The aim of the present study was to investigate systemic levels of inflammatory markers of cardiovascular diseases like C-reactive protein and interleukin-6 in patients with chronic periodontitis, in comparison to periodontally healthy individuals.Materials and Methods:A total of 42 individuals, both males and females above the age of 30 years, were included in the study. Healthy controls (Group I, n = 14), chronic localized periodontitis (Group II, n = 14), and chronic generalized periodontitis (Group III, n = 14), all without any medical disorder, were recruited. Peripheral blood samples were taken and C-reactive protein (CRP) levels were estimated in the serum samples by using the Particle-Enhanced Turbidimetric Immunoassay (PETIA) technique. Serum samples of Interleukin-6 (IL-6) were assayed by using the Chemiluminescent Immunoassay (IMMULITE) technique.Results:When mean CRP levels were compared between the groups, group III showed statistical significance when compared to group I (P = 0.04). Group III had a higher median IL-6 level (6.35 pg/mL) than Group II (< 5.0 pg/mL) and group I (< 5.0 pg/mL). Differences in median values of IL-6 were not statistically significant in any group (P = 0.29).Conclusion:Periodontitis results in higher systemic levels of CRP and IL-6. These elevated inflammatory factors may increase inflammatory activity in atherosclerotic lesions and potentially increasing the risk for cardiovascular events.

A brain-computer-interface (BCI)-based attention training game system has shown promise for treating attention deficit/hyperactivity disorder (ADHD) children with inattentive symptoms. However, little is known about brain network organizational changes underlying behavior improvement following BCI-based training. To cover this gap, we aimed to examine the topological alterations of large-scale brain functional networks induced by the 8-week BCI-based attention intervention in ADHD boys using resting-state functional magnetic resonance imaging method. Compared to the non-intervention (ADHD-NI) group, the intervention group (ADHD-I) showed greater reduction of inattention symptoms accompanied with differential brain network reorganizations after training. Specifically, the ADHD-NI group had increased functional connectivity (FC) within the salience/ventral attention network (SVN) and increased FC between task-positive networks (including the SVN, dorsal attention (DAN), somatomotor, and executive control network) and subcortical regions; in contrast ADHD-I group did not have this pattern. In parallel, ADHD-I group had reduced degree centrality and clustering coefficient as well as increased closeness in task-positive and the default mode networks (prefrontal regions) after the training. More importantly, these reduced local functional processing mainly in the SVN were associated with less inattentive/internalizing problems after 8-week BCI-based intervention across ADHD patients. Our findings suggest that the BCI-based attention training facilitates behavioral improvement in ADHD children by reorganizing brain functional network from more regular to more random configurations, particularly renormalizing salience network processing. Future long-term longitudinal neuroimaging studies are needed to develop the BCI-based intervention approach to promote brain maturation in ADHD.

Objective The use of brain-computer interface in neurofeedback therapy for attention deficit hyperactivity disorder (ADHD) is a relatively new approach. We conducted a randomized controlled trial (RCT) to determine whether an 8-week brain computer interface (BCI)-based attention training program improved inattentive symptoms in children with ADHD compared to a waitlist-control group, and the effects of a subsequent 12-week lower-intensity training. Study design We randomized 172 children aged 6–12 attending an outpatient child psychiatry clinic diagnosed with inattentive or combined subtypes of ADHD and not receiving concurrent pharmacotherapy or behavioral intervention to either the intervention or waitlist-control group. Intervention involved 3 sessions of BCI-based training for 8 weeks, followed by 3 training sessions per month over the subsequent 12 weeks. The waitlist-control group received similar 20-week intervention after a wait-time of 8 weeks. Results The participants’ mean age was 8.6 years (SD = 1.51), with 147 males (85.5%) and 25 females (14.5%). Modified intention to treat analyzes conducted on 163 participants with at least one follow-up rating showed that at 8 weeks, clinician-rated inattentive symptoms on the ADHD-Rating Scale (ADHD-RS) was reduced by 3.5 (SD 3.97) in the intervention group compared to 1.9 (SD 4.42) in the waitlist-control group (between-group difference of 1.6; 95% CI 0.3 to 2.9 p = 0.0177). At the end of the full 20-week treatment, the mean reduction (pre-post BCI) of the pooled group was 3.2 (95% CI 2.4 to 4.1). Conclusion The results suggest that the BCI-based attention training program can improve ADHD symptoms after a minimum of 24 sessions and maintenance training may sustain this improvement. This intervention may be an option for treating milder cases or as an adjunctive treatment.

Tissue engineering and nanotechnology have advanced a general strategy combining the cellular elements of living tissue with sophisticated functional biocomposites to produce living structures of sufficient size and function at a low cost for clinical relevance. Xylan, a natural polysaccharide was electrospun along with polyvinyl alcohol (PVA) to produce Xylan/PVA nanofibers for skin tissue engineering. The Xylan/PVA glutaraldehyde (Glu) vapor cross-linked nanofibers were characterized by SEM, FT-IR, tensile testing and water contact angle measurements to analyze the morphology, functional groups, mechanical properties and wettability of the fibers for skin tissue regeneration. The cell-biomaterial interactions were studied by culturing human foreskin fibroblasts on Xylan/PVA Glu vapor cross-linked and Xylan/PVA/Glu blend nanofibrous scaffolds. The observed results showed that the mechanical properties (72 %) and fibroblast proliferation significantly increased up to 23 % (P < 0.05) in 48 h Glu vapor cross-linked nanofibers compared to 24 h Glu vapor cross-linked Xylan/PVA nanofibers. The present study may prove that the natural biodegradable Xylan/PVA nanofibrous scaffolds have good potential for fibroblast adhesion, proliferation and cell matrix interactions relevant for skin tissue regeneration.

Full, persistent blockade of central neurokinin-1 (NK1) receptors may be a potential antidepressant mechanism. The selective NK1 antagonist orvepitant (GW823296) was used to test this hypothesis. A preliminary positron emission tomography study in eight male volunteers drove dose selection for two randomized six week studies in patients with major depressive disorder (MDD). Displacement of central [(11)C]GR205171 binding indicated that oral orvepitant doses of 30-60 mg/day provided >99% receptor occupancy for ≥24 h. Studies 733 and 833 randomized patients with MDD and 17-item Hamilton Depression Rating Scale (HAM-D)≥22 to double-blind treatment with orvepitant 30 mg/day, orvepitant 60 mg/day or placebo (1:1:1). Primary outcome measure was change from baseline in 17-item HAM-D total score at Week 6 analyzed using mixed models repeated measures. Study 733 (n=328) demonstrated efficacy on the primary endpoint (estimated drug-placebo differences of 30 mg: -2.41, 95% confidence interval (CI) (-4.50 to -0.31) p=0.0245; 60 mg: -2.86, 95% CI (-4.97 to -0.75) p=0.0082). Study 833 (n=345) did not show significance (estimated drug-placebo differences of 30 mg: -1.67, 95% CI (-3.73 to 0.39) p=0.1122; 60 mg: -0.76, 95% CI (-2.85 to 1.32) p=0.4713). The results support the hypothesis that full, long lasting blockade of central NK1 receptors may be an efficacious mechanism for the treatment of MDD.

Despite comparable behavioral performance, at-risk participants performing a verbal working memory task exhibited altered brain activation compared with healthy subjects. These findings demonstrate an altered pattern of brain activation in at-risk persons that contains elements of reduced function as well as compensation.