Educating Dentists about Fissure Sealants: Effects on Knowledge, Attitudes, and Use

This study evaluated the effects of three modes of education on dentists' knowledge, attitudes, and use of pit and fissure sealants. A randomly selected group of dentists was invited to participate in a sealant education initiative. During a 12-month period, a total of 662 dentists either (1) attended continuing education courses, (2) received written materials and videotapes by mail, or (3) received only written materials by mail. A comparison group (n=337) received no materials until after the education phase and evaluation had been completed. Pre-and postintervention surveys were used to measure changes in knowledge, attitudes, and sealant use. Response rates to the two surveys were 62 percent and 76 percent, respectively. Preintervention values for knowledge scores, an attitude scale, and sealant use were similar among the four groups. At followup, the three education groups had significantly higher knowledge scores than the comparison group. Attitude values for all but one group were not significantly different, and sealant use by all groups was identical. The numbers of respondents not using sealants declined slightly between surveys in the three education groups while rising slightly in the No-Education Group. Because program outcomes were similar to those of another sealant initiative, it can probably be concluded that continuing education will increase dentists' knowledge about sealants, but have little effect upon their attitudes or their use of the technique. The changes observed in this investigation maybe due to the particular capacity for cognitive and affective change's of participants, characteristics of the technology being promoted, and external forces in the professional environment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66125/1/j.1752-7325.1991.tb02208.x.pd

Beyond group differences: Exploring the preliminary signals of target engagement of an executive function training for autistic children

DATA AVAILABILITY STATEMENT The data that support the findings for this study are available within the National Database for Autism Research (NDAR) at nda.nih.gov.ACKNOWLEDGMENTS The authors thank the staff and students who assisted with collecting and scoring these measures and who provided coaching. The authors specially thank the children and families who contributed their time to this study and joined in the effort to better understand the executive function of children on the autism spectrum. Additional protocol information is available at ClinicalTrials.gov: NCT02361762. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The research reported in this publication was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award no. R00HD071966. Additional funding to support intervention with the waitlist group was provided by the GoFAR Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.Understanding both for whom and how interventions work is a crucial next step in providing personalized care to children with autism spectrum disorder (ASD). Autistic children present with heterogeneity both within core ASD criteria and with respect to co-occurring mental health challenges, which may affect their ability to benefit from intervention. In a secondary data analysis of a randomized control trial evaluating an executive function (EF) training with 70 7- to 11-year-old autistic children, we explored: (1) whether co-occurring attention-deficit/hyperactivity disorder (ADHD) features or anxiety features at baseline moderated the extent to which children benefited from the EF training. In other words, we asked, “For whom is training effective?” We also explored: (2) the extent to which changes in a brain-based measure of target engagement predicted the clinical outcomes of the EF training. This is a step towards asking, “How is training effective?” We found that EF training improved behavioral inhibition only for children with clinically significant cooccurring ADHD features. Anxiety features, while prevalent, did not moderate EF training efficacy. Finally, for the EF training group only, there was a significant correlation between pre-to-post change in an EEG-based measure of target engagement, N2 incongruent amplitude during a flanker task, and change in repetitive behaviors, a behavioral outcome that was reported in the parent RCT to have improved with training compared to waitlist control. This study provides preliminary evidence that EF training may differentially affect subgroups of autistic children and that changes at the neural level may precede changes in behavior.Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under Award no. R00HD071966GoFAR Foundatio

PDE11A gene polymorphism in testicular cancer: sperm parameters and hormonal profile

Purpose: Testicular germ cell tumours (TGCTs) is the most common malignancy among young adult males. The etiology is multifactorial and both environmental and genetic factors play an important role in the origin and development of TGCT. Genetic susceptibility may result from the interaction of multiple common and low-penetrance genetic variants and one of the main candidate genes is PDE11A. Many PDE11A polymorphisms were found responsible for a reduced PDE activity in TGCT patients, who often also display impaired hormone and sperm profile. The aim of this study was to investigate testicular function and PDE11A sequence in testicular cancer cases. Methods: Semen analysis was performed in 116 patients with unilateral and bilateral sporadic TGCTs and in 120 cancer-free controls. We also investigated hormone profile and PDE11A polymorphisms using peripheral blood samples. Results: Our data revealed that TGCT patients showed lower testosterone levels, higher gonadotropins levels and worse semen quality than controls, although the mean and the medians of sperm parameters are within the reference limits. PDE11A sequencing detected ten polymorphisms not yet associated with TGCTs before. Among these, G223A in homozygosity and A288G in heterozygosity were significantly associated with a lower risk of testicular tumour and they displayed a positive correlation with total sperm number. Conclusions: Our findings highlight the key role of PDE11A in testis and suggest the presence of an underlying complex and fine molecular mechanism which controls testis-specific gene expression and susceptibility to testicular cancer

Suppression of endogenous lipogenesis induces reversion of the malignant phenotype and normalized differentiation in breast cancer

Altres ajuts: We are greatly indebted to Prof. Robert A. Weinberg (Whitehead Institute for Biomedical Research, Cambridge, MA, USA) for providing the HMLERshCntrol and HMLERshEcad cells used in this work. Plan Nacional de I+D+I, Spain and the Departament d'Economia I Coneixement, Catalonia, Spain to Javier A. Menendez. Elisabet Cuyàs is the recipient of a "Sara Borrell" post-doctoral contract (CD15/00033, Ministerio de Sanidad y Consumo, Fondo de Investigación Sanitaria -FIS-, Spain).The correction of specific signaling defects can reverse the oncogenic phenotype of tumor cells by acting in a dominant manner over the cancer genome. Unfortunately, there have been very few successful attempts at identifying the primary cues that could redirect malignant tissues to a normal phenotype. Here we show that suppression of the lipogenic enzyme fatty acid synthase (FASN) leads to stable reversion of the malignant phenotype and normalizes differentiation in a model of breast cancer (BC) progression. FASN knockdown dramatically reduced tumorigenicity of BC cells and restored tissue architecture, which was reminiscent of normal ductal-like structures in the mammary gland. Loss of FASN signaling was sufficient to direct tumors to a reversed phenotype that was near normal when considering the development of polarized growth-arrested acinar-like structure similar to those formed by nonmalignant breast cells in a 3D reconstituted basement membrane in vitro. This process, in vivo, resulted in a low proliferation index, mesenchymal-epithelial transition, and shut-off of the angiogenic switch in FASN-depleted BC cells orthotopically implanted into mammary fat pads. The role of FASN as a negative regulator of correct breast tissue architecture and terminal epithelial cell differentiation was dominant over the malignant phenotype of tumor cells possessing multiple cancer-driving genetic lesions as it remained stable during the course of serial in vivo passage of orthotopic tumor-derived cells. Transient knockdown of FASN suppressed hallmark structural and cytosolic/secretive proteins (vimentin, N-cadherin, fibronectin) in a model of EMT-induced cancer stem cells (CSC). Indirect pharmacological inhibition of FASN promoted a phenotypic switch from basal- to luminal-like tumorsphere architectures with reduced intrasphere heterogeneity. The fact that sole correction of exacerbated lipogenesis can stably reprogram cancer cells back to normal-like tissue architectures might open a new avenue to chronically restrain BC progression by using FASN-based differentiation therapies

Nucleophile-Catalyzed Additions to Activated Triple Bonds. Protection of Lactams, Imides, and Nucleosides with MocVinyl and Related Groups

Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or N-methoxy-N-methylpropynamide in the presence of many potential catalysts were examined. DABCO and, second, DMAP appeared to be the best (highest reaction rates and E/Z ratios), while RuCl3, RuClCp*(PPh3)2, AuCl, AuCl(PPh3), CuI, and Cu2(OTf)2 were incapable of catalyzing such additions. The groups incorporated (for example, the 2-(methoxycarbonyl)ethenyl group that we name MocVinyl) serve as protecting groups for the above-mentioned heterocyclic CONH or CONHCO moieties. Deprotections were accomplished via exchange with good nucleophiles: the 1-dodecanethiolate anion turned out to be the most general and efficient reagent, but in some particular cases other nucleophiles also worked (e.g., MocVinyl-inosines can be cleaved with succinimide anion). Some structural and mechanistic details have been accounted for with the help of DFT and MP2 calculations

Facial Identity Recognition in the Broader Autism Phenotype

Peer reviewedPublisher PD

Visual Scan Paths and Recognition of Facial Identity in Autism Spectrum Disorder and Typical Development

Background: Previous research suggests that many individuals with autism spectrum disorder (ASD) have impaired facial identity recognition, and also exhibit abnormal visual scanning of faces. Here, two hypotheses accounting for an association between these observations were tested: i) better facial identity recognition is associated with increased gaze time on the Eye region; ii) better facial identity recognition is associated with increased eye-movements around the face. Methodology and Principal Findings: Eye-movements of 11 children with ASD and 11 age-matched typically developing (TD) controls were recorded whilst they viewed a series of faces, and then completed a two alternative forced-choice recognition memory test for the faces. Scores on the memory task were standardized according to age. In both groups, there was no evidence of an association between the proportion of time spent looking at the Eye region of faces and age-standardized recognition performance, thus the first hypothesis was rejected. However, the 'Dynamic Scanning Index' - which was incremented each time the participant saccaded into and out of one of the core-feature interest areas - was strongly asso ciated with age-standardized face recognition scores in both groups, even after controlling for various other potential predictors of performance. Conclusions and Significance: In support of the second hypothesis, results suggested that increased saccading between core-features was associated with more accurate face recognition ability, both in typical development and ASD. Causal directions of this relationship remain undetermined.10 page(s

Cancer stem cells (CSCs) : metabolic strategies for their identification and eradication

Phenotypic and functional heterogeneity is one of the most relevant features of cancer cells within different tumor types and is responsible for treatment failure. Cancer stem cells (CSCs) are a population of cells with stem cell-like properties that are considered to be the root cause of tumor heterogeneity, because of their ability to generate the full rep- ertoire of cancer cell types. Moreover, CSCs have been invoked as the main drivers of metastatic dissemination and therapeutic resistance. As such, targeting CSCs may be a useful strategy to improve the effectiveness of classical anticancer therapies. Recently, metabolism has been considered as a relevant player in CSC biology, and indeed, onco- genic alterations trigger the metabolite-driven dissemination of CSCs. More interestingly, the action of metabolic pathways in CSC maintenance might not be merely a conse- quence of genomic alterations. Indeed, certain metabotypic phenotypes may play a causative role in maintaining the stem traits, acting as an orchestrator of stemness. Here, we review the current studies on the metabolic features of CSCs, focusing on the bio- chemical energy pathways involved in CSC maintenance and propagation. We provide a detailed overview of the plastic metabolic behavior of CSCs in response to microenvironment changes, genetic aberrations, and pharmacological stressors. In addition, we describe the potential of comprehensive metabolic approaches to identify and selectively eradicate CSCs, together with the possibility to ‘force’ CSCs within certain metabolic dependences, in order to effectively target such metabolic biochemical inflexibilities. Finally, we focus on targeting mitochondria to halt CSC dissemination and effectively eradicate cancer