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

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

Consequences of cathepsin C inactivation for membrane exposure of proteinase 3, the target antigen in autoimmune vasculitis

Membrane-bound proteinase 3 (PR3m) is the main target antigen of anti-neutrophil cytoplasmic autoantibodies (ANCA) in granulomatosis with polyangiitis, a systemic small-vessel vasculitis. Binding of ANCA to PR3m triggers neutrophil activation with the secretion of enzymatically active PR3 and related neutrophil serine proteases, thereby contributing to vascular damage. PR3 and related proteases are activated from pro-forms by the lysosomal cysteine protease cathepsin C (CatC) during neutrophil maturation. We hypothesized that pharmacological inhibition of CatC provides an effective measure to reduce PR3m and therefore has implications as a novel therapeutic approach in granulomatosis with polyangiitis. We first studied neutrophilic PR3 from 24 patients with Papillon-Lefèvre syndrome (PLS), a genetic form of CatC deficiency. PLS neutrophil lysates showed a largely reduced but still detectable (0.5-4%) PR3 activity when compared with healthy control cells. Despite extremely low levels of cellular PR3, the amount of constitutive PR3m expressed on the surface of quiescent neutrophils and the typical bimodal membrane distribution pattern were similar to what was observed in healthy neutrophils. However, following cell activation, there was no significant increase in the total amount of PR3m on PLS neutrophils, whereas the total amount of PR3m on healthy neutrophils was significantly increased. We then explored the effect of pharmacological CatC inhibition on PR3 stability in normal neutrophils using a potent cell-permeable CatC inhibitor and a CD34+ hematopoietic stem cell model. Human CD34+ hematopoietic stem cells were treated with the inhibitor during neutrophil differentiation over 10 days. Weobserved strong reductions in PR3m, cellular PR3 protein, and proteolytic PR3 activity, whereas neutrophil differentiation was not compromised

Chest X-ray in right heart disease

© Springer International Publishing AG, part of Springer Nature 2018. Right heart pathology receives less attention from clinicians than left-sided heart disease, and knowledge of the importance of right heart, in particular right ventricle in disease development lags behind that of the left ventricle. In recent years, increasing evidence shows that right heart disease has significant impact on morbidity and mortality, thus highlighting the importance of recognizing right heart disease in clinical practice. Although ultrasound and computed tomography are the most commonly used diagnostic image techniques in the diagnosis of right heart disease, chest radiography still remains the first line technique in many applications. Despite non-specific findings in most of the situations, chest X-ray provides useful information for further diagnostic imaging tests of assessing right heart disease. This chapter provides an overview of applications of chest X-ray in the diagnosis of various right heart diseases