Changes in the fractal dimension on pre- and post-implant panoramic radiographs

Objectives  

The aim of this study was to assess the changes in the fractal dimension before and after implant placement. The study also examined the possibility of using fractal analysis as a prognostic indicator for implant success.     

Non-pharmacological management of abdominal pain-related functional gastrointestinal disorders in children

Background

Abdominal pain-related functional gastrointestinal disorder (AP-FGID) comprises of 4 main conditions: functional dyspepsia, irritable bowel syndrome, abdominal migraine and functional abdominal pain. AP-FGIDs are diagnosed clinically based on the Rome IV criteria for FGIDs of childhood. There is limited evidence for pharmacological therapies.

Data sources

This review article discusses nonpharmacological management of AP-FGID based on the current literature including systematic reviews, randomized controlled trials, cohort and case control studies. We aim to provide a comprehensive overview on the available evidence for the pediatricians and pediatric gastroenterologists involved in managing children with AP-FGID.

Results

Managing AP-FGIDs can be challenging. This should follow a stepwise approach with focused history, identification of “red flag” signs and symptoms, physical examination and investigations done following initial consultation. Family needs explaining that there is nothing seriously wrong with the child’s abdomen. This explanation and reassurance can achieve symptom control in large number of cases. Non-pharmacological interventions are delivered through lifestyle and dietary changes and bio-psychosocial therapies. Dietary interventions vary depending on the type of AP-FGID. Bio-psychosocial therapies such as hypnotherapy, cognitive behavioral therapy and yoga aim at stress reduction.

Conclusion

There is increasing evidence for use of non-pharmacological interventions in children with APFGID.

     

ASXL1 mutations are associated with distinct epigenomic alterations that lead to sensitivity to venetoclax and azacytidine

The BCL2-inhibitor, Venetoclax (VEN), has shown significant anti-leukemic efficacy in combination with the DNMT-inhibitor, Azacytidine (AZA). To explore the mechanisms underlying the selective sensitivity of mutant leukemia cells to VEN and AZA, we used cell-based isogenic models containing a common leukemia-associated mutation in the epigenetic regulator ASXL1. KBM5 cells with CRISPR/Cas9-mediated correction of the ASXL1^G710X mutation showed reduced leukemic growth, increased myeloid differentiation, and decreased HOXA and BCL2 gene expression in vitro compared to uncorrected KBM5 cells. Increased expression of the anti-apoptotic gene, BCL2, was also observed in bone marrow CD34+ cells from ASXL1 mutant MDS patients compared to CD34+ cells from wild-type MDS cases. ATAC-sequencing demonstrated open chromatin at the BCL2 promoter in the ASXL1 mutant KBM5 cells. BH3 profiling demonstrated increased dependence of mutant cells on BCL2. Upon treatment with VEN, mutant cells demonstrated increased growth inhibition. In addition, genome-wide methylome analysis of primary MDS samples and isogenic cell lines demonstrated increased gene-body methylation in ASXL1 mutant cells, with consequently increased sensitivity to AZA. These data mechanistically link the common leukemia-associated mutation ASXL1 to enhanced sensitivity to VEN and AZA via epigenetic upregulation of BCL2 expression and widespread alterations in DNA methylation.Subject terms: Myelodysplastic syndrome, Acute myeloid leukaemia