A critical role of brain network architecture in a continuum model of autism spectrum disorders spanning from healthy individuals with genetic liability to individuals with ASD.

Studies have shown cortical alterations in individuals with autism spectrum disorders (ASD) as well as in individuals with high polygenic risk for ASD. An important addition to the study of altered cortical anatomy is the investigation of the underlying brain network architecture that may reveal brain-wide mechanisms in ASD and in polygenic risk for ASD. Such an approach has been proven useful in other psychiatric disorders by revealing that brain network architecture shapes (to an extent) the disorder-related cortical alterations. This study uses data from a clinical dataset-560 male subjects (266 individuals with ASD and 294 healthy individuals, CTL, mean age at 17.2 years) from the Autism Brain Imaging Data Exchange database, and data of 391 healthy individuals (207 males, mean age at 12.1 years) from the Pediatric Imaging, Neurocognition and Genetics database. ASD-related cortical alterations (group difference, ASD-CTL, in cortical thickness) and cortical correlates of polygenic risk for ASD were assessed, and then statistically compared with structural connectome-based network measures (such as hubs) using spin permutation tests. Next, we investigated whether polygenic risk for ASD could be predicted by network architecture by building machine-learning based prediction models, and whether the top predictors of the model were identified as disease epicenters of ASD. We observed that ASD-related cortical alterations as well as cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. We also observed that age progression of ASD-related cortical alterations and cortical correlates of polygenic risk for ASD implicated cortical hubs more strongly than non-hub regions. Further investigation revealed that structural connectomes predicted polygenic risk for ASD (r = 0.30, p < 0.0001), and two brain regions (the left inferior parietal and left suparmarginal) with top predictive connections were identified as disease epicenters of ASD. Our study highlights a critical role of network architecture in a continuum model of ASD spanning from healthy individuals with genetic risk to individuals with ASD. Our study also highlights the strength of investigating polygenic risk scores in addition to multi-modal neuroimaging measures to better understand the interplay between genetic risk and brain alterations associated with ASD.

Effects of Probiotics Mouthwash on Levels of Red Complex Bacteria in Chronic Periodontitis Patients: A Clinico-microbiological Study.

AIM: The red complex includes Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia, which are recognized as the most important pathogens and are the indicators of infection in chronic periodontal disease. This study was to assess the levels of red complex bacteria in chronic periodontitis patients following treatment with probiotic mouthwash. MATERIALS AND METHODS: Twenty chronic periodontitis patients with ages ranging from 18 to 55 years were recruited for the study. The control group was given placebo mouthwash and the study group was given probiotic mouthwash. After clinical monitoring and scaling and root planing, the collected plaque samples at baseline and 14th day were transferred for microbiological analysis by transport media for Conventional Multiplex Polymerase Chain Reaction. RESULTS: On the 14th day, all the clinical parameters were significantly reduced in the study group with gingival index (p = 0.003 HS) and plaque index (p = 0.001 VHS). In the study group, there was significant bacterial cell reduction with T. denticola (p = 0.041 S) and T. forsythia (p = 0.037 S). CONCLUSION: In patients with chronic periodontitis, treatment with probiotic mouthwash significantly reduces the levels of red complex bacteria. CLINICAL SIGNIFICANCE: The use of probiotic mouthwash could be a useful adjunct to scaling and root planing in chronic periodontitis.

Esthetic Evaluation of Maxillary Anterior Immediate Implant with Provisionalization with or without Bone Grafting.

AIM: Immediate implant in the esthetic zone is a treatment of choice. However, much research regarding immediate implant provisionalization lacked in the literature. Hence, our study was conducted with an aim to assess the changes in the soft tissue, hard tissue, and esthetic outcomes following immediate implants with provisionalization with or without bone grafting. MATERIALS AND METHODS: Twenty patients with a mean age between 18 and 55 years referred to the department of periodontology, for immediate implant placement in maxillary anterior region were included in the study. Patients were enrolled into two groups. Group I (test group) included patients with immediate implant placement with provisionalization with bone grafting. Group II (control group) included patients with immediate implant placement with provisionalization without bone grafting. Cement-retained provisional restoration was fitted over temporary abutment for 6 months of healing period. After 6 months of implant placement, definite crown was delivered. RESULTS: The results of our study showed the least resorption of buccal cortical plate and good amount of bone gain in both the groups in terms of horizontal alveolar dimensional changes. The mean amount of horizontal alveolar gain in group I was 1.12 mm at 2 mm, 1.08 mm at 4 mm, and 0.85 mm at 6 mm; in group II, it was 0.97 mm at 2 mm, 1.4 mm at 4 mm, and 0.93 mm at 6 mm. CONCLUSION: This study showed a significantly better outcome in both the groups in terms of all the parameters when compared from baseline but the mean differences between the two groups were not very significant. The study concluded that immediate implant with provisionalization with or without bone grafting has maintained stability of soft tissues as well as hard tissues and has also given better esthetic outcomes. CLINICAL SIGNIFICANCE: The findings of this study proved that immediate implant placement with provisionalization with bone grafting is a predictable treatment modality that maintains the three-dimensional stability of alveolar bone and integrity of soft tissue and gives acceptable esthetics. Hence, this technique promises to fulfill both functional and esthetic concerns of the patient.

Distinct influence of parental occupation on cortical thickness and surface area in children and adolescents: Relation to self-esteem.

Studies of socioeconomic disparities have largely focused on correlating brain measures with either composite measure of socioeconomic status (SES), or its components-family income or parental education, giving little attention to the component of parental occupation. Emerging evidence suggests that parental occupation may be an important and neglected indicator of childhood and adolescent SES compared to absolute measures of material resources or academic attainment because, while related, it may more precisely capture position in social hierarchy and related health outcomes. On the other hand, although cortical thickness and surface area are brain measures with distinct genetic and developmental origins, large-scale neuroimaging studies investigating regional differences in interaction of the composite measure of SES or its components with cortical thickness and surface area are missing. We set out to fill this gap, focusing specifically on the role of parental occupation on cortical thickness and surface area by analyzing magnetic resonance imaging scans from 704 healthy individuals (age = 3-21 years). We observed spatially distributed patterns of (parental occupation × age2 ) interaction with cortical thickness (localized at the left caudal middle frontal, the left inferior parietal and the right superior parietal) and surface area (localized at the left orbitofrontal cortex), indicating independent sources of variability. Further, with decreased cortical thickness, children from families with lower parental occupation exhibited lower self-esteem. Our findings demonstrate distinct influence of parental occupation on cortical thickness and surface area in children and adolescents, potentially reflecting different neurobiological mechanisms by which parental occupation may impact brain development.

Sublingual Piroxicam as Preemptive Analgesia in Single Implant Surgery.

AIM: The aim of this study is to evaluate the efficacy of sublingual piroxicam as a preemptive analgesic agent in patients undergoing single implant surgery. MATERIALS AND METHODS: This was a prospective triple-blind placebo-controlled trial that involved 40 patients presented for the placement of a single endosteal implant in the posterior maxillary arch. Patients were randomly allocated to one of the following groups. Group I (study) who received sublingual piroxicam 40 mg 1 hour prior to the surgical procedure and group II (control) received placebo 1 hour before the surgery, both the groups received sublingual piroxicam 20 mg tablet twice a day on the first and the second postoperative day and once a day on the postoperative day 3. Visual analog scores for measuring pain intensity were assessed at postoperative 1 hour, 6 hours, days 1, 3, and 5. Facial swelling was measured and evaluated during the first, third, and fifth postoperative days using the digital vernier caliper. The Mann-Whitney U test was used to make between-group comparisons. The Wilcoxon-signed rank test was used to make within-group comparisons. RESULTS: At all-time intervals, both mean pain and mean swelling scores were higher in controls as compared with those of cases. The difference between the two groups was also statistically significant at all-time intervals for both parameters except for pain at 1 hour. CONCLUSION: Our findings suggest that preoperative sublingual piroxicam is more effective for controlling postoperative pain and swelling after surgical implant placement than only postoperative administration.

Parallel activation of prospective motor plans during visually-guided sequential saccades.

Behavioural evidences suggest that sequential saccades to multiple stimuli are planned in parallel. However, it remains unclear whether such parallel programming reflects concurrent processing of goals or whether multiple motor plans coexist, unfolding subsequently during execution. Here we use midway saccades, directed at intermediate locations between two targets, as a probe to address this question in a novel double-step adaptation task. The task consisted of trials where subjects had to follow the appearance of two targets presented in succession with two sequential saccades. In some trials, the second target predictably jumped to a new location during the second saccade. Initially, the second saccade was aimed at the final target's location before the jump. As subjects adapted to the target jump, saccades were aimed to the second target's new location. We tested whether the spatial distribution of midway saccades could be explained as an interaction between two concurrent saccade goals, each directed at the two target locations, or between the initial motor plan to the first target location and a prospective motor plan directed from the initial to the final target location. A shift in the midway saccades' distribution towards the jumped location of the second target following adaptation indicated that the brain can make use of prospective motor plans to guide sequential eye movements. Furthermore, we observed that the spatiotemporal pattern of endpoints of midway saccades can be well explained by a motor addition model. These results provide strong evidence of parallel activation of prospective motor plans during sequential saccades.

Queuing of concurrent movement plans by basal ganglia.

How the brain converts parallel representations of movement goals into sequential movements is not known. We tested the role of basal ganglia (BG) in the temporal control of movement sequences by a convergent approach involving inactivation of the BG by muscimol injections into the caudate nucleus of monkeys and assessing behavior of Parkinson's disease patients, performing a modified double-step saccade task. We tested a critical prediction of a class of competitive queuing models that explains serial behavior as the outcome of a selection of concurrently activated goals. In congruence with these models, we found that inactivation or impairment of the BG unmasked the parallel nature of goal representations such that a significantly greater extent of averaged saccades, curved saccades, and saccade sequence errors were observed. These results suggest that the BG perform a form of competitive queuing, holding the second movement plan in abeyance while the first movement is being executed, allowing the proper temporal control of movement sequences.

A Comparative Evaluation of Efficacy of Root Surface Biomodification using MTAD, MTAD+I-PRF on Adhesion of Fibrin Clot to Dentin Sem Study.

Root biomodifiers help in removing the smear layer following mechanical debridement. In this context, we evaluated and compared the in vitro efficacy of MTAD, MTAD+I-PRF, and phosphate-buffered saline-conditioned dentin surfaces by examining the distribution of the fibrin network using scanning electron microscopy. It was concluded that MTAD can serve as a potentially useful root conditioner/biomodifier. Further, the adjunct of MTAD+I-P resulted in more fibrin network linkage on the dentinal surface when compared to MTAD alone which can be of great utility in Advanced Regenerative Therapy.

Schizophrenia Polygenic Risk During Typical Development Reflects Multiscale Cortical Organization.

Background: Schizophrenia is widely recognized as a neurodevelopmental disorder. Abnormal cortical development in otherwise typically developing children and adolescents may be revealed using polygenic risk scores for schizophrenia (PRS-SCZ). Methods: We assessed PRS-SCZ and cortical morphometry in typically developing children and adolescents (3-21 years, 46.8% female) using whole-genome genotyping and T1-weighted magnetic resonance imaging (n = 390) from the PING (Pediatric Imaging, Neurocognition, and Genetics) cohort. We contextualized the findings using 1) age-matched transcriptomics, 2) histologically defined cytoarchitectural types and functionally defined networks, and 3) case-control differences of schizophrenia and other major psychiatric disorders derived from meta-analytic data of 6 ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) working groups, including a total of 12,876 patients and 15,670 control participants. Results: Higher PRS-SCZ was associated with greater cortical thickness, which was most prominent in areas with heightened gene expression of dendrites and synapses. PRS-SCZ-related increases in vertexwise cortical thickness were mainly distributed in association cortical areas, particularly the ventral attention network, while relatively sparing koniocortical type cortex (i.e., primary sensory areas). The large-scale pattern of cortical thickness increases related to PRS-SCZ mirrored the pattern of cortical thinning in schizophrenia and mood-related psychiatric disorders derived from the ENIGMA consortium. Age group models illustrate a possible trajectory from PRS-SCZ-associated cortical thickness increases in early childhood toward thinning in late adolescence, with the latter resembling the adult brain phenotype of schizophrenia. Conclusions: Collectively, combining imaging genetics with multiscale mapping, our work provides novel insight into how genetic risk for schizophrenia affects the cortex early in life.

Is saccade averaging determined by visual processing or movement planning?

Saccadic averaging that causes subjects' gaze to land between the location of two targets when faced with simultaneously or sequentially presented stimuli has been often used as a probe to investigate the nature of computations that transform sensory representations into an oculomotor plan. Since saccadic movements involve at least two processing stages-a visual stage that selects a target and a movement stage that prepares the response-saccade averaging can either occur due to interference in visual processing or movement planning. By having human subjects perform two versions of a saccadic double-step task, in which the stimuli remained the same, but different instructions were provided (REDIRECT gaze to the later-appearing target vs. FOLLOW the sequence of targets in their order of appearance), we tested two alternative hypotheses. If saccade averaging were due to visual processing alone, the pattern of saccade averaging is expected to remain the same across task conditions. However, whereas subjects produced averaged saccades between two targets in the FOLLOW condition, they produced hypometric saccades in the direction of the initial target in the REDIRECT condition, suggesting that the interaction between competing movement plans produces saccade averaging.

Mutual inhibition and capacity sharing during parallel preparation of serial eye movements.

Many common activities, like reading, scanning scenes, or searching for an inconspicuous item in a cluttered environment, entail serial movements of the eyes that shift the gaze from one object to another. Previous studies have shown that the primate brain is capable of programming sequential saccadic eye movements in parallel. Given that the onset of saccades directed to a target are unpredictable in individual trials, what prevents a saccade during parallel programming from being executed in the direction of the second target before execution of another saccade in the direction of the first target remains unclear. Using a computational model, here we demonstrate that sequential saccades inhibit each other and share the brain's limited processing resources (capacity) so that the planning of a saccade in the direction of the first target always finishes first. In this framework, the latency of a saccade increases linearly with the fraction of capacity allocated to the other saccade in the sequence, and exponentially with the duration of capacity sharing. Our study establishes a link between the dual-task paradigm and the ramp-to-threshold model of response time to identify a physiologically viable mechanism that preserves the serial order of saccades without compromising the speed of performance.

Trans-saccadic processing of visual and motor planning during sequential eye movements.

How the brain maintains perceptual continuity across eye movements that yield discontinuous snapshots of the world is still poorly understood. In this study, we adapted a framework from the dual-task paradigm, well suited to reveal bottlenecks in mental processing, to study how information is processed across sequential saccades. The pattern of RTs allowed us to distinguish among three forms of trans-saccadic processing (no trans-saccadic processing, trans-saccadic visual processing and trans-saccadic visual processing and saccade planning models). Using a cued double-step saccade task, we show that even though saccade execution is a processing bottleneck, limiting access to incoming visual information, partial visual and motor processing that occur prior to saccade execution is used to guide the next eye movement. These results provide insights into how the oculomotor system is designed to process information across multiple fixations that occur during natural scanning.

Impaired conflict monitoring in Parkinson's disease patients during an oculomotor redirect task.

Fallibility is inherent in human cognition and so a system that will monitor performance is indispensable. While behavioral evidence for such a system derives from the finding that subjects slow down after trials that are likely to produce errors, the neural and behavioral characterization that enables such control is incomplete. Here, we report a specific role for dopamine/basal ganglia in response conflict by accessing deficits in performance monitoring in patients with Parkinson's disease. To characterize such a deficit, we used a modification of the oculomotor countermanding task to show that slowing down of responses that generate robust response conflict, and not post-error per se, is deficient in Parkinson's disease patients. Poor performance adjustment could be either due to impaired ability to slow RT subsequent to conflicts or due to impaired response conflict recognition. If the latter hypothesis was true, then PD subjects should show evidence of impaired error detection/correction, which was found to be the case. These results make a strong case for impaired performance monitoring in Parkinson's patients.

Neural correlates of polygenic risk score for autism spectrum disorders in general population.

Autism spectrum disorder is a highly prevalent and highly heritable neurodevelopmental condition, but studies have mostly taken traditional categorical diagnosis approach (yes/no for autism spectrum disorder). In contrast, an emerging notion suggests a continuum model of autism spectrum disorder with a normal distribution of autistic tendencies in the general population, where a full diagnosis is at the severe tail of the distribution. We set out to investigate such a viewpoint by investigating the interaction of polygenic risk scores for autism spectrum disorder and Age2 on neuroimaging measures (cortical thickness and white matter connectivity) in a general population (n = 391, with age ranging from 3 to 21 years from the Pediatric Imaging, Neurocognition and Genetics study). We observed that children with higher polygenic risk for autism spectrum disorder exhibited greater cortical thickness for a large age span starting from 3 years up to ∼14 years in several cortical regions localized in bilateral precentral gyri and the left hemispheric postcentral gyrus and precuneus. In an independent case-control dataset from the Autism Brain Imaging Data Exchange (n = 560), we observed a similar pattern: children with autism spectrum disorder exhibited greater cortical thickness starting from 6 years onwards till ∼14 years in wide-spread cortical regions including (the ones identified using the general population). We also observed statistically significant regional overlap between the two maps, suggesting that some of the cortical abnormalities associated with autism spectrum disorder overlapped with brain changes associated with genetic vulnerability for autism spectrum disorder in healthy individuals. Lastly, we observed that white matter connectivity between the frontal and parietal regions showed significant association with polygenic risk for autism spectrum disorder, indicating that not only the brain structure, but the white matter connectivity might also show a predisposition for the risk of autism spectrum disorder. Our findings showed that the fronto-parietal thickness and connectivity are dimensionally related to genetic risk for autism spectrum disorder in general population and are also part of the cortical abnormalities associated with autism spectrum disorder. This highlights the necessity of considering continuum models in studying the aetiology of autism spectrum disorder using polygenic risk scores and multimodal neuroimaging.

Evaluation of bleaching efficacy of 37.5% hydrogen peroxide on human teeth using different modes of activations: An in vitro study.

INTRODUCTION: The aim of this in vitro study is to evaluate the role of light and laser sources in the bleaching ability of 37.5% H2 O2 on extracted human teeth. MATERIALS AND METHODS: About 30 caries-free single-rooted maxillary central incisors were used for the study. Specimens were prepared by sectioning the crown portion of teeth mesiodistally, and labial surface was used for the study. Specimens were then immersed in coffee solution for staining. Color of each tooth was analyzed using Shadestar, a digital shademeter. Specimens were then divided into three groups of 10 each and were subjected to bleaching with 37.5% H2 O2, 37.5% H2 O2 + light activation, and 37.5% H2 O2 + laser activation, respectively. Postbleaching, the color was analyzed for all the specimens immediately and then after 1, 2, and 3 weeks intervals, respectively. RESULTS: All the statistical analyses were done using SPSS version 17. Intra- and inter-group comparisons were done with Friedman test and Kruskal-Wallis ANOVA, respectively. Statistical analysis concluded with a significant improvement in their shade values from baseline in all the three groups. Halogen light activation and laser-activated groups showed comparatively enhanced bleaching results over no-activation group, though the difference was not statistically significant. CONCLUSION: The results of the present study show that bleaching assisted with halogen light and laser showed increased lightness than nonlight activated group. Durability of bleaching results obtained postbleaching was maintained throughout the experimental trail period of 3 weeks for both halogen light and laser activation group, whereas no-light activation group presented with shade rebound after 2 weeks postbleaching.

Effect of Diode Laser on Bacteria Beyond the Apex in Relation to the Size of the Apical Preparation - An In-Vitro Study.

INTRODUCTION: Microorganisms causing periapical infection are usually difficult to eradicate after conventional endodontic treatment or even in retreatment resulting in poor outcomes. So the purpose of the study was to assess whether disinfection of root canal with laser had any effect on bacteria in the periapex region. AIM: The aim of the present study was to evaluate the effects of a diode laser when activated in root canals with varying apical diameters, on the bacteria present beyond the apex of the teeth. MATERIALS AND METHODS: Total 30 intact single rooted teeth were taken and decoronated to standardize the root to a length of 12mm. They were divided into three groups depending on last file size used for instrumentation at apex i.e., size 30, 40 and 50 respectively. The samples were then mounted on test tubes such that roots of teeth were in contact with fresh broth of Escherichia coli (ATCC 25922) and left for incubation. Later a diode laser (Ezlase 940, Biolase) was used for disinfection of root canals of the samples. Following this the bacterial inoculums from each test tube were cultured and CFU were obtained from which the mean log values were obtained. Statistical analysis was done using Kruskal Wallis ANOVA test to compare mean CFU in three groups. Mann-Whitney U test with Bonferroni correction was used to compare inter-group differences. RESULTS: There was statistically significant difference in mean log values of CFU in all the three study groups. Inter-group comparisons showed that, Group A had significantly lower mean CFUs than Group B and C respectively. CONCLUSION: The study showed that intracanal irradiation with diode laser had an effect on the bacteria present beyond the apex, and it was influenced by the size of the apical preparation i.e., smaller apical size led to a greater reduction in the bacterial count.

Comparison of Effect of C-Factor on Bond Strength to Human Dentin Using Different Composite Resin Materials.

BACKGROUND: The study was planned to assess the use of low shrinkage composites for restoring cavities with high configuration factor (C-factor) which are subjected to high stresses. AIM: The aim of the study was to evaluate the effect of C- factor on tensile bond strength to human dentin using methacrylate based nanohybrid and low shrinkage silorane composite. MATERIALS AND METHODS: In this study 40 non carious human molar teeth were selected and assigned into two main groups - cavity (Class I cavity with high C-factor) and flat group (flat surface with low C-factor). Two different composite materials- methacrylate based and silorane low shrinkage composite were used to restore the teeth. Dentin surface was treated, adhesive application was done and composite was applied as per manufacturer's instructions. Samples were stored in distilled water then subjected to tensile bond strength measurement using universal testing machine. RESULTS: Statistical analysis was done using Independent sample t-test. The mean bond strength in methacrylate based and silorane composite was significantly higher in flat preparation (Low C-factor) than cavity preparation. The mean bond strength in both cavity (High C-factor) and flat preparation(Low C-factor) was significantly higher in silorane than in conventional methacrylate based composite. CONCLUSION: The bond strength of composites to dentin is strongly influenced by C-factor and type of composite resin material used.