Regeneration of Intrabony Defects with Nano Hydroxyapatite Graft, Derived from Eggshell along with Periosteum as Barrier Membrane under Magnification—An Interventional Study

Intrabony defects can be treated by various approaches. Use of GTR along with bone grafts is said to enhance the outcome. The periosteum has been claimed to increase the regeneration. The egg-shell-derived nano hydroxyapatite (EnHA) has shown a scope as alloplastic graft. Thus, the following study was undertaken to combine the periosteal pedicle along with EnHA for the treatment of intrabony defects under magnification to achieve optimal bone regeneration. A total of 21 patients, having intrabony defects with ≥6 mm probing depth (PD) and two or three wall defects as detected on CBCT, satisfying inclusion criteria were enrolled. The sites were randomly allocated as Group A, B and C (n = 7). The following parameters, defect density and defect fill in CBCT (at baseline and 6 months), PPD, RAL, Plaque index (PI), Gingival index (GI) and Gingival Bleeding Index (GBI) were recorded at baseline, 1, 3 and 6 months. p < 0.05 is considered as statistically significant. Bone density and bone fill values were found to be much higher in pedicle with EnHA and EnHA alone group and the values showed statistically significant results. The current clinical research showed that periosteal pedicle along with EnHA and EnHA as stand-alone therapy gave superior results compared to OFD alone, which is an innovative and feasible treatment option

Prevalence and correlates of autism spectrum disorder in Qatar: a national study

Background Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level. Methods This cross‐sectional survey was conducted from 2015 to 2018 in Qatar school‐age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen‐positive and screen‐negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase. Results One thousand three hundred and ninety‐three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen‐negative children and 163 screen‐positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89–1.46) among 6‐ to 11‐year‐olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042–0.080)/11.8% (95% CI: 0.095–0.146) families. First‐degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression. Conclusions ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast‐growing population.The study was supported by the Qatar National Research Fund. The sponsor had no role in the design and conduct of the study, or the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript, and in the decision to submit the manuscript for publication. The authors thank all the independent and private schools that have participated in the SCQ screening phase. The authors thank the Ministry of Public Health and the Ministry of Education for providing their team with the data required throughout the study. The authors would like to express our gratitude to the psychological services team at the Shafallah Center for Children with Disabilities, as well as Dr. Irshad Shafeullah and Dr. Zakariah Al-Sayed for their support in patient recruitment. The authors also thank our colleagues from QBRI: Dr. Hatem Al-Shanti for his assistance in patient phenotyping, and Mr. Yasser Al-Sarraj and Ms. Hamda AlMutawwa for their support with patient recruitment. The authors thank Dr. Hanaa Massoud for assisting with patient recruitment through the clinic at the Child Development Center in Rumailah Hospital. The authors would also like to express their appreciation to the QBRI administration team for their assistance with planning and logistics pertaining to research-related training sessions and research collaborator visits. Additionally, the authors would like to thank all of the special needs centers and clinics which collaborated with us to provide data needed for the high probability cases; Shafallah Center for Children with Disabilities, Hamad Medical Corporation, Child Development Center ? Rumailah Hospital, Child Development Center-Private, Renad Academy, Al-Tamakun school, Step by Step Center, Qatar Institute for Speech and Hearing, and Hope Center. The authors also thank the HBKU Sponsored Research Office for the support provided throughout the research funding period.?K.R. and the OHSU Biostatistics & Design Program was partially supported by the Oregon Clinical and Translational Research Institute (OCTRI) through OHSU Clinical & Translational Science Awards (CTSA UL1TR0002369) National Consortium. The authors are immensely grateful to the families and their children for their time and participation in any of the phases of the research. F.A. and E.F. designed the research plan. F.A., M.A., and E.F. applied for funding. F.A., H.A., S.E., I.G., M.T., M.A., M.K., N.A.A., M.A., A.H.S., and L.D. organized the data collection. F.A., H.A., S.E., and I.G. completed data entry and cleaning, and performed initial data analyses with M.A. E.F. performed data and statistical analyses. K.R. provided biostatistical advice. E.F., F.A., and I.G. wrote the manuscript. All authors reviewed and approved the manuscript. The authors have declared that they have no competing or potential conflicts of interest.Scopu

Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells

BACKGROUND: With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression. METHODS: To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed. RESULTS: NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary. CONCLUSION: In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo

Joint Binding of OTX2 and MYC in Promotor Regions Is Associated with High Gene Expression in Medulloblastoma

Both OTX2 and MYC are important oncogenes in medulloblastoma, the most common malignant brain tumor in childhood. Much is known about MYC binding to promoter regions, but OTX2 binding is hardly investigated. We used ChIP-on-chip data to analyze the binding patterns of both transcription factors in D425 medulloblastoma cells. When combining the data for all promoter regions in the genome, OTX2 binding showed a remarkable bi-modal distribution pattern with peaks around −250 bp upstream and +650 bp downstream of the transcription start sites (TSSs). Indeed, 40.2% of all OTX2-bound TSSs had more than one significant OTX2-binding peak. This OTX2-binding pattern was very different from the TSS-centered single peak binding pattern observed for MYC and other known transcription factors. However, in individual promoter regions, OTX2 and MYC have a strong tendency to bind in proximity of each other. OTX2-binding sequences are depleted near TSSs in the genome, providing an explanation for the observed bi-modal distribution of OTX2 binding. This contrasts to the enrichment of E-box sequences at TSSs. Both OTX2 and MYC binding independently correlated with higher gene expression. Interestingly, genes of promoter regions with multiple OTX2 binding as well as MYC binding showed the highest expression levels in D425 cells and in primary medulloblastomas. Genes within this class of promoter regions were enriched for medulloblastoma and stem cell specific genes. Our data suggest an important functional interaction between OTX2 and MYC in regulating gene expression in medulloblastoma

Myc proteins in brain tumor development and maintenance

Myc proteins are often deregulated in human brain tumors, especially in embryonal tumors that affect children. Many observations have shown how alterations of these pleiotropic Myc transcription factors provide initiation, maintenance, or progression of tumors. This review will focus on the role of Myc family members (particularly c-myc and Mycn) in tumors like medulloblastoma and glioma and will further discuss how to target stabilization of these proteins for future brain tumor therapies

Integrated Genomics Identifies Five Medulloblastoma Subtypes with Distinct Genetic Profiles, Pathway Signatures and Clinicopathological Features

BACKGROUND: Medulloblastoma is the most common malignant brain tumor in children. Despite recent improvements in cure rates, prediction of disease outcome remains a major challenge and survivors suffer from serious therapy-related side-effects. Recent data showed that patients with WNT-activated tumors have a favorable prognosis, suggesting that these patients could be treated less intensively, thereby reducing the side-effects. This illustrates the potential benefits of a robust classification of medulloblastoma patients and a detailed knowledge of associated biological mechanisms. METHODS AND FINDINGS: To get a better insight into the molecular biology of medulloblastoma we established mRNA expression profiles of 62 medulloblastomas and analyzed 52 of them also by comparative genomic hybridization (CGH) arrays. Five molecular subtypes were identified, characterized by WNT signaling (A; 9 cases), SHH signaling (B; 15 cases), expression of neuronal differentiation genes (C and D; 16 and 11 cases, respectively) or photoreceptor genes (D and E; both 11 cases). Mutations in beta-catenin were identified in all 9 type A tumors, but not in any other tumor. PTCH1 mutations were exclusively identified in type B tumors. CGH analysis identified several fully or partly subtype-specific chromosomal aberrations. Monosomy of chromosome 6 occurred only in type A tumors, loss of 9q mostly occurred in type B tumors, whereas chromosome 17 aberrations, most common in medulloblastoma, were strongly associated with type C or D tumors. Loss of the inactivated X-chromosome was highly specific for female cases of type C, D and E tumors. Gene expression levels faithfully reflected the chromosomal copy number changes. Clinicopathological features significantly different between the 5 subtypes included metastatic disease and age at diagnosis and histology. Metastatic disease at diagnosis was significantly associated with subtypes C and D and most strongly with subtype E. Patients below 3 yrs of age had type B, D, or E tumors. Type B included most desmoplastic cases. We validated and confirmed the molecular subtypes and their associated clinicopathological features with expression data from a second independent series of 46 medulloblastomas. CONCLUSIONS: The new medulloblastoma classification presented in this study will greatly enhance the understanding of this heterogeneous disease. It will enable a better selection and evaluation of patients in clinical trials, and it will support the development of new molecular targeted therapies. Ultimately, our results may lead to more individualized therapies with improved cure rates and a better quality of life

Cytogenetic Prognostication Within Medulloblastoma Subgroups

PURPOSE: Medulloblastoma comprises four distinct molecular subgroups: WNT, SHH, Group 3, and Group 4. Current medulloblastoma protocols stratify patients based on clinical features: patient age, metastatic stage, extent of resection, and histologic variant. Stark prognostic and genetic differences among the four subgroups suggest that subgroup-specific molecular biomarkers could improve patient prognostication. PATIENTS AND METHODS: Molecular biomarkers were identified from a discovery set of 673 medulloblastomas from 43 cities around the world. Combined risk stratification models were designed based on clinical and cytogenetic biomarkers identified by multivariable Cox proportional hazards analyses. Identified biomarkers were tested using fluorescent in situ hybridization (FISH) on a nonoverlapping medulloblastoma tissue microarray (n = 453), with subsequent validation of the risk stratification models. RESULTS: Subgroup information improves the predictive accuracy of a multivariable survival model compared with clinical biomarkers alone. Most previously published cytogenetic biomarkers are only prognostic within a single medulloblastoma subgroup. Profiling six FISH biomarkers (GLI2, MYC, chromosome 11 [chr11], chr14, 17p, and 17q) on formalin-fixed paraffin-embedded tissues, we can reliably and reproducibly identify very low-risk and very high-risk patients within SHH, Group 3, and Group 4 medulloblastomas. CONCLUSION: Combining subgroup and cytogenetic biomarkers with established clinical biomarkers substantially improves patient prognostication, even in the context of heterogeneous clinical therapies. The prognostic significance of most molecular biomarkers is restricted to a specific subgroup. We have identified a small panel of cytogenetic biomarkers that reliably identifies very high-risk and very low-risk groups of patients, making it an excellent tool for selecting patients for therapy intensification and therapy de-escalation in future clinical trials

Lipid Nanoparticles as Delivery Systems for RNA-Based Vaccines

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Lipid nanoparticles (LNPs) have been extensively studied as non-viral vectors for the delivery of mRNA to target cells because of their relatively easy and scalable manufacturing processes. This review highlights key advances in the development of LNPs and reviews the application of mRNA-based vaccines formulated in LNPs for use against infectious diseases and cancer

Learners' use of first language (Arabic) in pair work in an EFL class

One of the concerns foreign language teachers may have about using small group (and pair) work is that students will use their shared first language (L1) instead of the target language. This study investigated the effect of learner proficiency pairing and task type on the amount of L1 used by learners of English as a foreign language (EFL) in pair work and the functions that the L1 served. Learners in this study ( n = 15 pairs) formed three proficiency groupings based on the teacher’s assessment of their second language proficiency: high—high (H—H), high—low (H—L), and low—low (L—L). All pairs completed three tasks — jigsaw, composition and text-editing — and their talk was audio-recorded. The transcribed pair talk was analysed for the quantity of L1 used (L1 words and L1 turns), and the functions the L1 served. The study found that overall, there was a modest use of L1 in pair work activity and that task type had a greater impact on the amount of L1 used than proficiency pairing. L1 was mainly used for the purpose of task management and to facilitate deliberations over vocabulary. When used for task management, L1 tended to reflect the kind of relationship the learners formed. When used for vocabulary deliberations, L1 was used not only to provide explanations to peers but also for private speech.35