Building a sustainable model of integrated stem education: investigating secondary school STEM classes after an integrated STEM project.

This study investigated the sustainability of an integrated STEM education program. Two US high school science teachers and an engineering technology teacher sustained implementation of an integrated STEM curriculum after the conclusion of the funded program, TRAILS. Class observations were conducted to examine how the teachers implemented the integrated STEM curriculum and how they maintained integrated STEM teaching in a science and engineering technology education (ETE) teacher pair using science and engineering technology shared practices. After the integrated STEM lesson, their students' academic achievements were compared to those of the students who previously participated in the project. The results reveal that the students showed no difference from the previous TRAILS students in terms of academic achievements as measured by STEM knowledge test scores, which may indicate that the teachers successfully maintained consistency and effectiveness of the implementation. Additionally, a twenty-first century skills survey was newly conducted to examine students' growth in confidence in twenty-first century skills after they were taught the integrated STEM lesson. The students showed increased confidence in critical thinking, which indicates that the students benefitted from the teachers' instructions even after the conclusion of the funded program and the absence of support. Based on the findings from the teachers' experiences of multiple years of integrated STEM teaching, the study discusses how to better support teachers for the successful implementation of an integrated STEM curriculum as a sustainable education program in secondary schools.

Effects of gonadotropin-releasing hormone agonist administered in microparticles on sperm quality and quantity, and plasma sex steroid levels in northern pike.

Artificial reproduction of northern pike Esox lucius is impeded by the likelihood of obtaining only a small volume of sperm of inconsistent quality. A controlled-release hormone delivery system has the potential to enhance sperm production while avoiding multiple injections The objective of this study was to investigate the effects of mammalian gonadotropin-releasing hormone agonist (mGnRHa) incorporated into poly(lactic-co-glycolic acid) (PLGA) microparticles on milt production, spermatozoon characteristics, and secretion of 17ß-estradiol (E2), 11-keto testosterone (11-KT), and testosterone in northern pike. Fish were divided into four groups and injected with 2 mg/kg BW carp pituitary extract (CPE), 20 µg/kg BW mGnRHa in PLGA microparticles, or 20 µg/kg BW mGnRHa plus 20 mg/kg BW metoclopramide (MET) in PLGA microparticles (PLGA + MET), along with a control group injected with 1 ml/kg 0.9% NaCl. At 48 h postinjection, the volume of milt produced was significantly greater in groups treated with CPE and PLGA + MET than in other groups. At 96 h postinjection, all hormone-treated groups exhibited significantly higher spermatozoon average velocity than recorded in the control group. Spermatozoon motility was significantly increased (P < 0.05) in the CPE and PLGA groups compared to baseline values. All treated groups showed significantly lower levels of 11-KT after the hormone injection compared to baseline values and to controls. Plasma testosterone levels increased in all hormone-treated groups. The use of PLGA microparticles, with or without metoclopramide, is suitable for use as a carrier of hormone treatments to regulate spermiation in mature northern pike.

Effect of root canal irrigant (sodium hypochlorite & saline) delivery at different temperatures and durations on pre-load and cyclic-loading surface-strain of anatomically different premolars.

AIM: To evaluate the effect of NaOCl (5%) and saline (control) irrigant delivery at different temperatures and durations on pre-load and cyclic-loading tooth-surface-strain (TSS) on anatomically different premolars. METHODOLOGY: Single-rooted premolars (n = 36), root-canal-prepared in standard manner, were randomly allocated to six irrigation groups: (A1) NaOCl-21 °C; (A2) NaOCl-60 °C; (A3) saline-21 °C then NaOCl-21 °C; (A4) saline-60 °C then NaOCl-21 °C; (A5) saline-21 °C then NaOCl-60 °C; (A6) saline-60 °C then NaOCl-60 °C. A1-2 received nine 10-min irrigation periods (IP) with NaOCl; A3-6 received nine 10-min IP with saline, followed by 9 IP with NaOCl at different temperature combinations. Premolars (n = 56) with single, fused or double roots prepared by standard protocol, were stratified and randomly allocated to: (B1) saline-21 °C; (B2) saline-80 °C; (B3) NaOCl-21 °C; (B4) NaOCl-80 °C. TSS (µÑ”) was recorded pre-irrigation, post-irrigation and pre-load for each IP and during cyclic loading 2 min after each IP, over 30-274 min, using strain-gauges. Generalised linear mixed models were used for analysis. RESULTS: Baseline TSS in double-rooted premolars was significantly (p=0.001) lower than in single/fused-rooted-premolars; and affected by mesial-wall-thickness (p=0.005). There was significant increase in loading-TSS (µÑ”) after NaOCl-21 °C irrigation (p=0.01) but decrease after NaOCl-60 °C irrigation (p=0.001). TSS also increased significantly (p = 0.005) after Saline-80 °C irrigation. Pre-load "strain-shift" was noted only upon first saline delivery but every-time with NaOCl. Strain-shift negatively influenced loading-TSS after saline or NaOCl irrigation (A3-6) but was only significant for saline-21 °C. CONCLUSIONS: Tooth anatomy significantly affected its strain characteristics, exhibiting limits within which strain changes occurred. Intra-canal introduction of saline or NaOCl caused non-random strain shifts without loading. Irrigation with NaOCl-21 °C increased loading tooth strain, as did saline-80 °C or NaOCl-80 °C but NaOCl-60 °C decreased it. A "chain-link" model was proposed to explain the findings and tooth biomechanics.

Digital image correlation in dental materials and related research: A review.

OBJECTIVE: Digital image correlation (DIC) is a non-contact image processing technique for full-field strain measurement. Although DIC has been widely used in engineering and biomechanical fields, it is in the spotlight only recently in dental materials. Therefore, the purpose of this review paper is introducing the working principle of the DIC technique with some modifications and providing further potential applications in various dental materials and related fields. METHODS: The accuracy of the algorithm depending on the environmental characteristics of the DIC technique, as well as the advantages and disadvantages of strain measurement using optical measurements, have been elaborated in dental materials and related fields. Applications to those researches have been classified into the following categories: shrinkage behavior of light-cured resin composite, resin-tooth interface, mechanical properties of tooth structure, crack extension and elastic properties of dental materials, and deformation of dental restoration and prosthesis. This classification and discussion were performed using literature survey and review based on numerous papers in the international journals published over the past 20 years. The future directions for predicting the precise deformation of dental materials under various environments, as well as limitations of the DIC technique, was presented in this review. RESULTS: The DIC technique was demonstrated as a more effective tool to measure full-field polymerization shrinkage of composite resin, even in a simulated clinical condition over the existing methods. Moreover, the DIC combined with other technologies can be useful to evaluate the mechanical behavior of material-tooth interface, dentine structure and restorative and prosthetic materials with high accuracy. Three-dimensional DIC using two cameras extended the measurement range in-plane to out-of-plane, enabling measure of the strain directly on the surface of dental restorations or prosthesis. SIGNIFICANCE: DIC technique is a potential tool for measuring and predicting the full-field deformation/strain of dental materials and actual prostheses in diverse clinical conditions. The versatility of DIC can replace the existing complex sensor devices in those studies.

Enhanced efficacy in drug-resistant cancer cells through synergistic nanoparticle mediated delivery of cisplatin and decitabine.

There are several limitations with monodrug cancer therapy, including poor bioavailability, rapid clearance and drug resistance. Combination therapy addresses these by exploiting synergism between different drugs against cancer cells. In particular, the combination of epigenetic therapies with conventional chemotherapeutic agents can improve the initial tumour response and overcome acquired drug resistance. Co-encapsulation of multiple therapeutic agents into a single polymeric nanoparticle is one of the many approaches taken to enhance therapeutic effect and improve the pharmacokinetic profile. In this study, different types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), matrix and core-shell (CS), were investigated for simultaneous encapsulation of a demethylating drug, decitabine, and a potent anticancer agent, cisplatin. It was shown that by altering the configuration of the CS structure, the release profile could be tuned. In order to investigate whether this could enhance the anticancer effect compared to cisplatin, human ovarian carcinoma cell line (A2780) and its cisplatin resistant variant (A2780cis) were exposed to free cisplatin and the CS-NPs. A better response was obtained in both cell lines (11% and 51% viability of A2780 and A2780cis, respectively) using CS-NPs than cisplatin alone (27%, 82% viability of A2780 and A2780cis, respectively) or in combination with decitabine (22%, 96% viability of A2780 and A2780cis, respectively) at equivalent doses (10 µM).

The effect of NaOCl and heat treatment on static and dynamic mechanical properties and chemical changes of dentine.

OBJECTIVES: To determine the effect of heat on flexural strength (FS), maximum strain (MS), storage modulus (SM), tan delta (TD) and chemical changes through micro-Raman spectroscopy of dentine exposed to 2.5% NaOCl or saline. METHOD: ology: Dentine bars were randomly allocated to 8 test groups. Half (groups 2,4,6,8) were treated with NaOCl for 20 min; the rest (groups 1,3,5,7) remained in saline. FS/MS were measured in groups 1-4 (n = 15) (3/4 were also heated to 200 °C & re-hydrated in saline). Micro-Raman spectroscopy was performed on bars from groups 1-4. SM/TD were measured in 5-8: in 5/6 (n = 10), repeated after heating (200 °C), then following re-hydration; in 7/8 (n = 3) after heating to 25-185 °C. RESULTS: Increase in MS on heat and FS/MS on heat + NaOCl was not significant (P > 0.05). SM increased (P = 0.06) after heat treatment but reduced to initial state after rehydration (P = 0.03). TD did not change (P = 0.4) after heat (200 °C) treatment but rehydration increased it compared with pre-treatment state (P = 0.001). For dentine bars pre-treated with NaOCl, SM did not change (P = 0.6) after heat (200 °C) treatment or rehydration but TD significantly increased (P = 0.02) upon re-hydration compared with pre- (P=0.007), or post- (P = 0.03) heat-treatment states. SM and TD varied between 25-185 °C with no consistent trend amongst the NaOCl pre-treated bars. Micro-Raman only detected chemical changes following NaOCl treatment in the mineral phase. CONCLUSIONS: Exposure of dentine bars to heat and NaOCl produced only moderate changes to quasi-static but marked changes to viscoelastic properties, which may be explained by chemical alterations.

Distance to treatment as a factor for loss to follow up of hepatitis C patients in North East England.

BACKGROUND: A large proportion of the 200 000 HCV-infected individuals in the UK are undiagnosed or lost to follow-up. Engaging known infected individuals in treatment is essential for elimination. METHODS: Using PHE surveillance data and HCV treatment registers from North East of England (NE) treatment centres for 1997-2016, we estimated the number of HCV cases not linked to treatment and the proportion with active infection. We compared distances of treated and untreated cases to treatment services, and assessed the effect of expanding HCV treatment into existing drug and alcohol treatment centres in the NEE on treatment accessibility. RESULTS: The odds of being treated was associated with distance to treatment services. Confirmatory results for ~50% were not reported to PHE NE. Overall, 3385 patients reported to PHE NE had no record of treatment; we estimated 1621 of these may have been lost to follow-up after confirmation of active infection. CONCLUSIONS: Poor access to healthcare services may contribute to under-diagnosis or loss to follow-up. Expanding HCV treatment delivery into NEE drug and alcohol treatment centres would improve the accessibility of treatment services to people infected with/at risk of HCV. This may increase the proportion receiving treatment and support progress towards elimination.

Reduction of Tribocorrosion Products When Using the Platform-Switching Concept.

The reduced marginal bone loss observed when using the platform-switching concept may be the result of reduced amounts of tribocorrosion products released to the peri-implant tissues. Therefore, the purpose of this study was to compare the tribocorrosion product release from various platform-matched and platform-switched implant-abutment couplings under cyclic loading. Forty-eight titanium implants were coupled with pure titanium, gold alloy, cobalt-chrome alloy, and zirconia abutments forming either platform-switched or platform-matched groups ( n = 6). The specimens were subjected to cyclic occlusal forces in a wet acidic environment for 24 h followed by static aqueous immersion for 6 d. The amount of metal ions released was measured using inductively coupled plasma mass spectrometry. Microscopic evaluations were performed pre- and postimmersion under scanning electron microscope (SEM) equipped with energy-dispersive spectroscopy X-ray for corrosion assessment at the interface and wear particle characterization. All platform-switched groups showed less metal ion release compared with their platform-matched counterparts within each abutment material group ( P < 0.001). Implants connected to platform-matched cobalt-chrome abutments demonstrated the highest total mean metal ion release (218 ppb), while the least total mean ion release (11 ppb) was observed in the implants connected to platform-switched titanium abutments ( P ≤ 0.001). Titanium was released from all test groups, with its highest mean release (108 ppb) observed in the implants connected to platform-matched gold abutments ( P < 0.001). SEM images showed surface tribocorrosion features such as pitting and bands of fretting scars. Wear particles were mostly titanium, ranging from submicron to 48 µm in length. The platform-matched groups demonstrated a higher amount of metal ion release and more surface damage. These findings highlight the positive effect of the platform-switching concept in the reduction of tribocorrosion products released from dental implants, which consequently may minimize the adverse tissue reactions that lead to peri-implant bone loss.

Dlgap1 knockout mice exhibit alterations of the postsynaptic density and selective reductions in sociability.

The scaffold protein DLGAP1 is localized at the post-synaptic density (PSD) of glutamatergic neurons and is a component of supramolecular protein complexes organized by PSD95. Gain-of-function variants of DLGAP1 have been associated with obsessive-compulsive disorder (OCD), while haploinsufficient variants have been linked to autism spectrum disorder (ASD) and schizophrenia in human genetic studies. We tested male and female Dlgap1 wild type (WT), heterozygous (HT), and knockout (KO) mice in a battery of behavioral tests: open field, dig, splash, prepulse inhibition, forced swim, nest building, social approach, and sucrose preference. We also used biochemical approaches to examine the role of DLGAP1 in the organization of PSD protein complexes. Dlgap1 KO mice were most notable for disruption of protein interactions in the PSD, and deficits in sociability. Other behavioral measures were largely unaffected. Our data suggest that Dlgap1 knockout leads to PSD disruption and reduced sociability, consistent with reports of DLGAP1 haploinsufficient variants in schizophrenia and ASD.

Investigations into in situ Enterococcus faecalis biofilm removal by passive and active sodium hypochlorite irrigation delivered into the lateral canal of a simulated root canal model.

AIM: To investigate in situ Enterococcus faecalis biofilm removal from the lateral canal of a simulated root canal system using passive or active irrigation protocols. METHODOLOGY: Root canal models (n = 43) were manufactured from transparent resin materials using 3D printing. Each canal was created with an 18 mm length, apical size 30, a .06 taper and a lateral canal of 3 mm length, with 0.3 mm diameter. Biofilms were grown in the lateral canal and apical 3 mm of the main canal for 10 days. Three models from each group were examined for residual biofilm using SEM. The other forty models were divided into four groups (n = 10). The models were observed under a fluorescence microscope. Following 60 s of 9 mL of 2.5% NaOCl irrigation using syringe and needle, the irrigant was either left stagnant in the canal or activated using gutta-percha, sonic or ultrasonic methods for 30 s. Images were then captured every second using an external camera. The residual biofilm percentages were measured using image analysis software. The data were analysed using generalized linear mixed models. A significance level of 0.05 was used throughout. RESULTS: The greatest level of biofilm removal was obtained with ultrasonic agitation (66.76%) followed by sonic (45.49%), manual agitation (43.97%) and passive irrigation groups (38.67%), respectively. The differences were significant between the residual biofilm in the passive irrigation and both sonic and ultrasonic groups (P = 0.001). CONCLUSION: Agitation resulted in better penetration of 2.5% NaOCl into the lateral canal of an artificial root canal model. Ultrasonic agitation of NaOCl improved the removal of biofilm.

Polygenic risk score and heritability estimates reveals a genetic relationship between ASD and OCD.

Obsessive-compulsive disorder (OCD) and Autism spectrum disorder (ASD) are both highly heritable neurodevelopmental disorders that conceivably share genetic risk factors. However, the underlying genetic determinants remain largely unknown. In this work, the authors describe a combined genome-wide association study (GWAS) of ASD and OCD. The OCD dataset includes 2998 individuals in nuclear families. The ASD dataset includes 6898 individuals in case-parents trios. GWAS summary statistics were examined for potential enrichment of functional variants associated with gene expression levels in brain regions. The top ranked SNP is rs4785741 (chromosome 16) with P value=6.9×10-7 in our re-analysis. Polygenic risk score analyses were conducted to investigate the genetic relationship within and across the two disorders. These analyses identified a significant polygenic component of ASD, predicting 0.11% of the phenotypic variance in an independent OCD data set. In addition, we examined the genomic architecture of ASD and OCD by estimating heritability on different chromosomes and different allele frequencies, analyzing genome-wide common variant data by using the Genome-wide Complex Trait Analysis (GCTA) program. The estimated global heritability of OCD is 0.427 (se=0.093) and 0.174 (se=0.053) for ASD in these imputed data.

Genetic effects influencing risk for major depressive disorder in China and Europe.

Major depressive disorder (MDD) is a common, complex psychiatric disorder and a leading cause of disability worldwide. Despite twin studies indicating its modest heritability (~30-40%), extensive heterogeneity and a complex genetic architecture have complicated efforts to detect associated genetic risk variants. We combined single-nucleotide polymorphism (SNP) summary statistics from the CONVERGE and PGC studies of MDD, representing 10 502 Chinese (5282 cases and 5220 controls) and 18 663 European (9447 cases and 9215 controls) subjects. We determined the fraction of SNPs displaying consistent directions of effect, assessed the significance of polygenic risk scores and estimated the genetic correlation of MDD across ancestries. Subsequent trans-ancestry meta-analyses combined SNP-level evidence of association. Sign tests and polygenic score profiling weakly support an overlap of SNP effects between East Asian and European populations. We estimated the trans-ancestry genetic correlation of lifetime MDD as 0.33; female-only and recurrent MDD yielded estimates of 0.40 and 0.41, respectively. Common variants downstream of GPHN achieved genome-wide significance by Bayesian trans-ancestry meta-analysis (rs9323497; log10 Bayes Factor=8.08) but failed to replicate in an independent European sample (P=0.911). Gene-set enrichment analyses indicate enrichment of genes involved in neuronal development and axonal trafficking. We successfully demonstrate a partially shared polygenic basis of MDD in East Asian and European populations. Taken together, these findings support a complex etiology for MDD and possible population differences in predisposing genetic factors, with important implications for future genetic studies.

Evidence for genetic heterogeneity between clinical subtypes of bipolar disorder.

We performed a genome-wide association study of 6447 bipolar disorder (BD) cases and 12 639 controls from the International Cohort Collection for Bipolar Disorder (ICCBD). Meta-analysis was performed with prior results from the Psychiatric Genomics Consortium Bipolar Disorder Working Group for a combined sample of 13 902 cases and 19 279 controls. We identified eight genome-wide significant, associated regions, including a novel associated region on chromosome 10 (rs10884920; P=3.28 × 10-8) that includes the brain-enriched cytoskeleton protein adducin 3 (ADD3), a non-coding RNA, and a neuropeptide-specific aminopeptidase P (XPNPEP1). Our large sample size allowed us to test the heritability and genetic correlation of BD subtypes and investigate their genetic overlap with schizophrenia and major depressive disorder. We found a significant difference in heritability of the two most common forms of BD (BD I SNP-h2=0.35; BD II SNP-h2=0.25; P=0.02). The genetic correlation between BD I and BD II was 0.78, whereas the genetic correlation was 0.97 when BD cohorts containing both types were compared. In addition, we demonstrated a significantly greater load of polygenic risk alleles for schizophrenia and BD in patients with BD I compared with patients with BD II, and a greater load of schizophrenia risk alleles in patients with the bipolar type of schizoaffective disorder compared with patients with either BD I or BD II. These results point to a partial difference in the genetic architecture of BD subtypes as currently defined.

Dissolution and drug release profiles of phosphate glasses doped with high valency oxides.

This paper investigates phosphate glasses incorporating vanadium and molybdenum oxides for effective management of dissolution and drug release. These glass formulations are found to reduce the rate of dissolution from the glass surfaces. The drug functional groups of vancomycin molecules loaded by immersion showed stronger hydrogen bonding with Vanadium doped glasses and consequently lower rate of drug release over 2 weeks indicating better surface attachment with the drug molecules and slow drug release profiles. This can be explained by the strong adherence of drug molecules to glass surfaces compared with the molybdenum containing glasses (PM5 and PM10). The strong attachment relates to hydrogen bonding between the amino-functional groups of vancomycin and the hydrated P-O-H groups in the glass network. In conclusion, the rate of dissolution of doped glasses and the rate of drug release can be administered to deliver the drug molecules over weeks.

Effectiveness of the Kids in Control of Food (KICk-OFF) structured education course for 11-16 year olds with Type 1 diabetes.

AIM: To assess the effect of a 5-day structured education course (Kids in Control of Food; KICk-OFF) on biomedical and psychological outcomes in young people with Type 1 diabetes. METHODS: This was a cluster-randomized trial involving 31 UK paediatric centres. Participants were recruited prior to stratified centre randomization. Intervention centres delivered KICk-OFF courses, whereas control centres delivered usual care. Participants were 11-16 years of age and had Type 1 diabetes for at least one year. The KICk-OFF course was delivered by trained educators to eight participants per course. Glycaemic control and quality of life were measured at baseline, 6, 12 and 24 months. Secondary outcomes were hypoglycaemia, ketoacidosis, fear of hypoglycaemia and diabetes self-efficacy. RESULTS: Three hundred and ninety-six participants provided baseline data (199 intervention and 197 control). At 6 and 12 months the intervention group showed significantly improved total generic quality of life scores compared with controls (baseline: 80 vs. 82; 6 months: 82 vs. 82; P = 0.04). Across the whole intervention group mean HbA1c levels were not significantly different from controls; baseline HbA1c mean (95% confidence interval), 78 mmol/mol (75-81) vs. 76 mmol/mol (74-79) [9.3% (9-9.6%) vs. 9.1% (8.9-9.4%); 24 months: 77 mmol/mol (74-79) vs. 78 mmol/mol (75-81) (9.2% (8.9-9.4%) vs. 9.3% (9-9.6%)], adjusted mean difference, -2.0 mmol/mol (6.5-2.5) [2.3% (-2.7% to 2.4%)], P = 0.38. CONCLUSIONS: Attending a KICk-OFF course was associated with significantly improved total quality of life scores within 6 months. Glycaemic control, as measured by HbA1c , was no different at 24 months. (Clinical Trial Registry No: ISRCTN3704268).

A case series of anal melanoma including the results of treatment with imatinib in selected patients.

AIM: Anal melanoma is a rare malignancy with a poor prognosis. METHOD: All patients with a diagnosis of anal melanoma treated at a single institution between 2000 and 2012 were identified and their treatment and outcome were evaluated. RESULTS: Sixteen patients had a median survival of 2.9 years. Fourteen had Stage I or II disease with a median survival of 4.0 years and progression-free survival of 1.5 years. When used for disease staging, whole body positron emission tomography/CT identified an additional three sites of metastasis in five patients compared with CT of the chest, abdomen and pelvis. Surgery involved wide local excision or abdominoperineal excision with respective local recurrence rates of 50% and 66%. Eleven patients underwent testing for c-Kit mutations, of whom five were positive. Four of these were treated with the tyrosine kinase inhibitor imatinib, and showed rapid response of metastases outside the central nervous system. CONCLUSION: The outcome of this malignancy remains poor. PET is the modality of choice for disease staging. Testing tumours for c-Kit mutations may allow selected patients to participate in trials of tyrosine kinase inhibitors.

Dependent personality, separation anxiety disorder and other anxiety disorders in OCD.

BACKGROUND: The purpose of this study was to investigate whether dependent personality and/or general personality dimensions might explain the strong relationships between separation anxiety disorder (Sep-AD) and three other anxiety disorders (agoraphobia, panic disorder and social anxiety disorder) in individuals with obsessive compulsive disorder (OCD). METHODS: Using data from 509 adult participants collected during the OCD Collaborative Genetic Study, we used logistic regression models to evaluate the relationships between Sep-AD, dependent personality score, general personality dimensions and three additional anxiety disorders. RESULTS: The dependent personality score was strongly associated with Sep-AD and the other anxiety disorders in models adjusted for age at interview, age at onset of OC symptoms and worst ever OCD severity score. Several general personality dimensions, especially neuroticism, extraversion and conscientiousness, were also related to Sep-AD and the other anxiety disorders. Sep-AD was not independently related to these anxiety disorders, in multivariate models including general personality and dependent personality disorder scores. CONCLUSIONS: The results suggest that Sep-AD in childhood and these other anxiety disorders in adulthood are consequences of dependent personality disorder (for agoraphobia and panic disorder) or introversion (for social phobia). It is unknown whether these results would be similar in a non-OCD sample.

Whole-genome association analysis of treatment response in obsessive-compulsive disorder.

Up to 30% of patients with obsessive-compulsive disorder (OCD) exhibit an inadequate response to serotonin reuptake inhibitors (SRIs). To date, genetic predictors of OCD treatment response have not been systematically investigated using genome-wide association study (GWAS). To identify specific genetic variations potentially influencing SRI response, we conducted a GWAS study in 804 OCD patients with information on SRI response. SRI response was classified as 'response' (n=514) or 'non-response' (n=290), based on self-report. We used the more powerful Quasi-Likelihood Score Test (the MQLS test) to conduct a genome-wide association test correcting for relatedness, and then used an adjusted logistic model to evaluate the effect size of the variants in probands. The top single-nucleotide polymorphism (SNP) was rs17162912 (P=1.76 × 10(-8)), which is near the DISP1 gene on 1q41-q42, a microdeletion region implicated in neurological development. The other six SNPs showing suggestive evidence of association (P<10(-5)) were rs9303380, rs12437601, rs16988159, rs7676822, rs1911877 and rs723815. Among them, two SNPs in strong linkage disequilibrium, rs7676822 and rs1911877, located near the PCDH10 gene, gave P-values of 2.86 × 10(-6) and 8.41 × 10(-6), respectively. The other 35 variations with signals of potential significance (P<10(-4)) involve multiple genes expressed in the brain, including GRIN2B, PCDH10 and GPC6. Our enrichment analysis indicated suggestive roles of genes in the glutamatergic neurotransmission system (false discovery rate (FDR)=0.0097) and the serotonergic system (FDR=0.0213). Although the results presented may provide new insights into genetic mechanisms underlying treatment response in OCD, studies with larger sample sizes and detailed information on drug dosage and treatment duration are needed.

Conversion, shrinkage, water sorption, flexural strength and modulus of re-mineralizing dental composites.

OBJECTIVES: Cure, volumetric changes and mechanical properties were assessed for new dental composites containing chlorhexidine (CHX) and reactive calcium phosphate-containing (CaP) to reduce recurrent caries. METHODS: 20wt.% of light curable urethane dimethacrylate based liquid was mixed with 80wt.% glass filler containing 10wt.% CHX and 0-40wt.% CaP. Conversion versus depth with 20 or 40s light exposure was assessed by FTIR. Solidification depth and polymerization shrinkage were determined using ISO 4049 and 17304, respectively. Subsequent volume expansion and biaxial flexural strength and modulus change upon water immersion were determined over 4 weeks. Hydroxyapatite precipitation in simulated body fluid was assessed at 1 week. RESULTS: Conversion decreased linearly with both depth and CaP content. Average solidification depths were 4.5, 3.9, 3.3, 2.9 and 5.0 with 0, 10, 20, and 40% CaP and a commercial composite, Z250, respectively. Conversions at these depths were 53±2% for experimental materials but with Z250 only 32%. With Z250 more than 50% conversion was achieved only below 1.1mm. Shrinkage was 3% and 2.5% for experimental materials and Z250, respectively. Early water sorption increased linearly, whilst strength and modulus decreased exponentially to final values when plotted versus square root of time. Maximum volumetric expansion increased linearly with CaP rise and balanced shrinkage at 10-20wt.% CaP. Strength and modulus for Z250 decreased from 191 to 158MPa and 3.2 to 2.5GPa. Experimental composites initial strength and modulus decreased linearly from 169 to 139MPa and 5.8 to 3.8GPa with increasing CaP. Extrapolated final values decreased from 156 to 84MPa and 4.1 to 1.7GPa. All materials containing CaP promoted hydroxyapatite precipitation. SIGNIFICANCE: The lower surface of composite restorations should both be solid and have greater than 50% conversion. The results, therefore, suggest the experimental composite may be placed in much thicker layers than Z250 and have reduced unbounded cytotoxic monomer. Experimental materials with 10-20wt.% additionally have volumetric expansion to compensate shrinkage, antibacterial and re-mineralizing components and competitive mechanical properties.