Similar antiseizure medication refill characteristics in Hispanic and White pediatric patients.

AIM: Previous work has shown that children of Hispanic ethnicity have reduced likelihood to achieve seizure remission, but it was unknown why. The purpose of this study was to evaluate antiseizure medicine (ASM) refill characteristics, comparing Hispanic and non-Hispanic White pediatric patients. METHODS: This was a retrospective population-based study in children between ages 6 months and 15 years. Epilepsy outcome was categorized as seizure free, treatment failure, or undetermined. ASM refill characteristics were determined from an insurance provider. RESULTS: 247 patients were identified: 52 (21 %) were treatment failure; 181 (73 %) were seizure free; and 14 (5.7 %) were undetermined. ASM refill rates were similar in Hispanic and White patients (38.2, 32.1, respectively). Hispanic and White patients had similar numbers of different ASMs prescribed (2.1 and 2.4). There was not a significant difference in proportion of days covered between Hispanic and White patients (0.99 and 0.95). INTERPRETATION: We found no differences between pediatric Hispanic and White epilepsy patients, for number of ASM refills, the number of ASMs prescribed, the choice of ASMs, the proportion of days covered, or the lateness of refills. Our findings suggest that the observation of reduced likelihood to achieve seizure remission in pediatric Hispanic patients is not associated with ASM refill patterns.

Long-Term Health Outcomes of Infantile Spasms Following Prednisolone vs. Adrenocorticotropic Hormone Treatment Characterized Using Phenome-Wide Association Study.

Objective: To determine differences in long-term health and neurological outcomes following infantile spasms (IS) in patients treated with adrenocorticotropic hormone (ACTH) vs. prednisolone/prednisone (PRED). Methods: A retrospective, case-control study of patients with an International Classification of Diseases, Ninth Revision, Clinical Modifications (ICD-9) diagnosis of IS, identified over a 10-year period from a national administrative database, was conducted. IS patients treated with ACTH or PRED were determined and cohorts established by propensity score matching. Outcomes, defined by hospital discharge ICD codes, were followed for each patient for 5 years. Related ICD codes were analyzed jointly as phenotype codes (phecodes). Analysis of phecodes between cohorts was performed including phenome-wide association analysis. Results: A total of 5,955 IS patients were identified, and analyses were subsequently performed for 493 propensity score matched patients, each in the ACTH and PRED cohorts. Following Bonferroni correction, no phecode was more common in either cohort (p < 0.001). However, assuming an a priori difference, one phecode, abnormal findings on study of brain or nervous system (a category of abnormal neurodiagnostic tests), was more common in the PRED cohort (p <0.05), and was robust to sensitivity analysis. Variability in outcomes was noted between hospitals. Significance: We found that long-term outcomes for IS patients following ACTH or PRED treatment were very similar, including for both neurological and non-neurological outcomes. In the PRED-treated cohort there was a higher incidence of abnormal neurodiagnostic tests, assuming an a priori statistical model. Future studies can evaluate whether variability in outcomes between hospitals may be affected by post-treatment differences in care models.

Large-Scale Identification of Clonal Hematopoiesis and Mutations Recurrent in Blood Cancers.

Clonal hematopoiesis of indeterminate potential (CHIP) is characterized by detectable hematopoietic-associated gene mutations in a person without evidence of hematologic malignancy. We sought to identify additional cancer-presenting mutations useable for CHIP detection by performing a data mining analysis of 48 somatic mutation studies reporting mutations at diagnoses of 7,430 adult and pediatric patients with hematologic malignancies. Following extraction of 20,141 protein-altering mutations, we identified 434 significantly recurrent mutation hotspots, 364 of which occurred at loci confidently assessable for CHIP. We then performed an additional large-scale analysis of whole exome sequencing data from 4,538 persons belonging to three non-cancer cohorts for clonal mutations. We found the combined cohort prevalence of CHIP with mutations identical to those reported at blood cancer mutation hotspots to be 1.8%, and that some of these CHIP mutations occurred in children. Our findings may help to improve CHIP detection and pre-cancer surveillance for both children and adults.

Australian Bogong moths Agrotis infusa (Lepidoptera: Noctuidae), 1951-2020: decline and crash.

The Bogong moth Agrotis infusa is well known for its remarkable long-distance migration - a return journey from the plains of southeast Australia to the Australian Alps - as well as for its cultural significance for Indigenous Australians. Each spring, as many as four billion moths are estimated to arrive in the Australian Alps to aestivate in cool mountain caves and in boulder fields, bringing with them a massive annual influx of energy and nutrients critical for the health of the alpine ecosystem. However, a massive decline in moths present at their aestivation sites has occurred over the past 3 years, with only a few individuals present where hundreds of thousands could earlier be found. In order to understand the possible sources of decline, we analysed historical records of Bogong moth numbers at aestivation sites in the Australian Alps, including observations on Mt. Gingera (NSW) in the early 1950s, observations from 1980 onwards in the Snowy Mountains (NSW) and an almost-unbroken series of observations each summer over the past 53 years in three caves at different elevations on Mt. Buffalo (Victoria). This analysis shows that moth numbers were probably steady from 1951 until about 1980, fluctuated and slowly fell from then until 2016 and dramatically crashed in 2017. In the Murray-Darling Basin, the main winter breeding ground of Bogong moths, changes in farming practices, such as increasing land clearing for crops (which has removed around a quarter of a billion moths annually from the mountains compared to pre-European levels), has probably driven some of the decline in Bogong moth numbers observed from 1980 to 2016. The impact of insecticide remains unclear and is in urgent need of further study. Even though we found little evidence that increasing global temperatures per se are responsible for the Bogong moth decline, the Australian climate has nonetheless become drier and warmer over past decades, possibly hampering the survival of immature stages in the breeding areas and confining adult aestivation to gradually higher elevations. The crash in moth numbers from 2017 is most likely due to the recent severe drought in the moth's breeding grounds.

Identification of genetic targets in acute myeloid leukaemia for designing targeted therapy.

Few effective therapies exist for acute myeloid leukaemia (AML), in part due to the molecular heterogeneity of this disease. We sought to identify genes crucial to deregulated AML signal transduction pathways which, if inhibited, could effectively eradicate leukaemia stem cells. Due to difficulties in screening primary cells, most previous studies have performed next-generation sequencing (NGS) library knockdown screens in cell lines. Using carefully considered methods including evaluation at multiple timepoints to ensure equitable gene knockdown, we employed a large NGS short hairpin RNA (shRNA) knockdown screen of nearly 5 000 genes in primary AML cells from six patients to identify genes that are crucial for leukaemic survival. Across various levels of stringency, genome-wide bioinformatic analysis identified a gene in the NOX family, NOX1, to have the most consistent knockdown effectiveness in primary cells (P = 5∙39 × 10-5 , Bonferroni-adjusted), impacting leukaemia cell survival as the top-ranked gene for two of the six AML patients and also showing high effectiveness in three of the other four patients. Further investigation of this pathway highlighted NOX2 as the member of the NOX family with clear knockdown efficacy. We conclude that genes in the NOX family are enticing candidates for therapeutic development in AML.

Association of Some Polymorphisms in the VDR Gene, CYP17 Gene and SRD5A2 Gene and Prostate Cancer among Lebanese Men

Aims: The goal of the study was to investigate possible association of some single nucleotide polymorphisms (SNPs) in the VDR gene (the FokI, BsmI, ApaI and TaqαI loci), and the CYP17 gene (the MspA1I locus), and 0 or 9 TA repeats in the SRD5A2 gene, and prostate cancer (PCa) among Lebanese men. Materials and Methods: Blood DNA of 69 subjects with confirmed PCa and 69 controls, all about 50 years of age or older, was subjected to PCR or PCR-restriction fragment-length polymorphism (PCR-RFLP) analyses, and the risk-bearing and the protective alleles were identified. The odds ratio (OR) of having a genotype and the relative risk (RR) of developing PCa were calculated. In addition, the distributions of homozygosis and heterozygosis in the risk-bearing alleles and the protective alleles among the control and the PCa groups were compared. Results: The f allele of the VDR FokI locus and the (TA) 9 repeat allele of the SRD5A2 gene were found to be associated with increased risks of PCa (p = 0.006 and 0.050, respectively). Homozygosis in the risk-bearing alleles was rare both in the control and the PCa groups. A higher fraction of the controls compared to the PCa group was double-homozygous in the two protective alleles (52.2% for controls, 24.6% for PCa group, p = <0.001). Conclusions: To the best of our knowledge, this is the first genetic study demonstrating the association of certain polymorphisms of the VDR gene and the SDR5A2 gene and increased risk of PCa among Lebanese men. Our study also indicates that the overall polymorphism profile of all genes involved in the prostate physiology is likely to be a better indicator for PCa risk than the polymorphisms in the individual genes.