Treatment-related complications in childhood acute lymphoblastic leukemia: Results of medical research council UKALL X

Background: Acute lymphoblastic leukemia (ALL) is a heterogeneous group of lymphoid neoplasms resulting from the proliferation of malignant lymphoid cells. The aim of this study was to evaluate treatment-related complications in children with ALL receiving the Medical Research Council (MRC) UKALL X protocol. Methods: In this retrospective cross-sectional study, children with ALL receiving the MRC UKALL X protocol from 2008 to 2015 in Bahrami University Hospital, Iran, were enrolled. The clinical and morphological features were analysed and treatment-related complications were assessed. Results: Out of 67 children with ALL receiving the MRC UKALL X protocol, 44 (65.6 ) were boys and 23 (34.4) were girls. Seven patients (10.7) relapsed in the three years of diagnosis, and 50 children (74.6) had an overall survival of three years. Average age in three-year-survival group and mortality group was 6.92 (SD: 3.96) and 6.35 (SD: 7.47), respectively (P= 0.38). Conclusion: Overall survival and relapse rates in this study confirm that this protocol is an appropriate treatment strategy. © 2020, Shiraz University of Medical Sciences. All rights reserved

Impact of the COVID-19 pandemic on tuberculosis national reference laboratory services in the WHO European Region, March to November 2020.

We assessed the impact of COVID-19 on diagnostic services for tuberculosis (TB) by national reference laboratories in the WHO European Region. Of 35 laboratories, 30 reported declines in TB sample numbers, amounting up to > 50% of the pre-COVID-19 volumes. Sixteen reported reagent or consumable shortages. Nineteen reallocated ressources to SARS-CoV-2 testing, resulting in an overall increase in workload, largely without a concomitant increase in personnel (n = 14). This poses a risk to meeting the 2025 milestones of the End TB Strategy

Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity. To “humanize” this molecular network, we developed a computational method, TransposeNet. This integrates a Steiner prize-collecting approach with homology assignment through sequence, structure, and interaction topology. TransposeNet linked α-syn to multiple parkinsonism genes and druggable targets through perturbed protein trafficking and ER quality control as well as mRNA metabolism and translation. A calcium signaling hub linked these processes to perturbed mitochondrial quality control and function, metal ion transport, transcriptional regulation, and signal transduction. Parkinsonism gene interaction profiles spatially opposed in the network (ATP13A2/PARK9 and VPS35/PARK17) were highly distinct, and network relationships for specific genes (LRRK2/PARK8, ATXN2, and EIF4G1/PARK18) were confirmed in patient induced pluripotent stem cell (iPSC)-derived neurons. This cross-species platform connected diverse neurodegenerative genes to proteinopathy through specific mechanisms and may facilitate patient stratification for targeted therapy. Keywords: alpha-synuclein; iPS cell; Parkinson’s disease; stem cell; mRNA translation; RNA-binding protein; LRRK2; VPS35; vesicle trafficking; yeas

Signal Transmission in the Auditory System

Contains table of contents for Section 3, an introduction, and reports on seven research projects.National Institutes of Health Grant 5 R01 DC00194National Institutes of Health Grant P01 DC00119National Institutes of Health Grant F32 DC00073National Institutes of Health Grant 5 R01 DC00473National Institutes of Health Grant 2 R01 DC00238National Institutes of Health Grant 2 R01 DC00235National Institutes of Health Grant 5 P01 DC00361National Institutes of Health Grant T32 DC00006Whitaker Health Sciences Fun