Natural History of Abortive Medication Withdrawal in the Management of Pediatric Medication Overuse Headache

OBJECTIVE: The objective of this study is to document pain scores during withdrawal of abortive medication in patients diagnosed with medication overuse headache. DESIGN: Cross-sectional study. SETTING: Children\u27s National Hospital\u27s Headache Program. SUBJECTS: Patients 6-18 years old who presented to the Headache Clinic at Children\u27s National Hospital with presumed medication overuse headache between March 2017 and March 2019 were consented for participation. METHODS: Patients were instructed to abruptly discontinue overused medications and record their headache characteristics daily in a diary for eight weeks. RESULTS: Fourteen diaries were returned and analyzed at a four-week follow-up visit. 93% of patients were females, with a median age of 14.9 years (SD = 2.0). The average headache intensity upon study entry was 4.7 of 10 (SD = 2.5) and was 3.1 (SD = 2.5) upon study completion. 57% had daily headaches upon study entry. 71% of patients had improved pain intensity from the first to last diary entry. 57% had complete headache resolution at an average of 7.6 days from medication discontinuation (SD = 5.1). Ibuprofen was the most overused medication (71%). CONCLUSIONS: Our findings suggest that medication overuse headache will improve in the majority of pediatric patients who abruptly stop the offending medication(s) in an average of eight days from withdrawal. Average pain intensity was reduced by more than one point among all patients who stopped taking abortive medications. Further larger scale studies on medication withdrawal in pediatric patients with medication overuse headache could help better understand if this management strategy is effective

Probing the O-glycoproteome of Gastric Cancer Cell Lines for Biomarker Discovery

Circulating O-glycoproteins shed from cancer cells represent important serum biomarkers for diagnostic and prognostic purposes. We have recently shown that selective detection of cancer-associated aberrant glycoforms of circulating O-glycoprotein biomarkers can increase specificity of cancer biomarker assays. However, the current knowledge of secreted and circulating O-glycoproteins is limited. Here, we used the COSMC KO “SimpleCell” (SC) strategy to characterize the O-glycoproteome of two gastric cancer SimpleCell lines (AGS, MKN45) as well as a gastric cell line (KATO III) which naturally expresses at least partially truncated O-glycans. Overall, we identified 499 O-glycoproteins and 1236 O-glycosites in gastric cancer SimpleCells, and a total 47 O-glycoproteins and 73 O-glycosites in the KATO III cell line. We next modified the glycoproteomic strategy to apply it to pools of sera from gastric cancer and healthy individuals to identify circulating O-glycoproteins with the STn glycoform. We identified 37 O-glycoproteins in the pool of cancer sera, and only nine of these were also found in sera from healthy individuals. Two identified candidate O-glycoprotein biomarkers (CD44 and GalNAc-T5) circulating with the STn glycoform were further validated as being expressed in gastric cancer tissue. A proximity ligation assay was used to show that CD44 was expressed with the STn glycoform in gastric cancer tissues. The study provides a discovery strategy for aberrantly glycosylated O-glycoproteins and a set of O-glycoprotein candidates with biomarker potential in gastric cancer

Ataxia with vitamin E deficiency: refinement of genetic localization and analysis of linkage disequilibrium by using new markers in 14 families.

Ataxia with vitamin E deficiency (AVED) is an autosomal recessive disease characterized clinically by neurological symptoms with often striking resemblance to those of Friedreich ataxia. This disorder has been reported previously as familial isolated vitamin E deficiency. We have mapped recently the AVED locus to a 5-cM confidence interval on chromosome 8q by homozygosity mapping in six Mediterranean families. We have now analyzed six new and two previously described families and demonstrate genetic homogeneity despite important clinical variability and wide geographic origins. Analysis of nine new tightly linked microsatellite markers, including four characterized in this study, revealed a predominant but not unique mutation in northern African populations, where this condition is more frequent. Haplotype analysis but also classical recombinations allowed us to refine the AVED position to a 1-cM interval. A YAC contig over this interval was constructed from marker STSs and YAC fingerprint data, in order to facilitate the search of the AVED gene.Journal ArticleResearch Support, Non-U.S. Gov'tResearch Support, U.S. Gov't, P.H.S.info:eu-repo/semantics/publishe

Cygnus X-1 contains a 21-solar mass black hole -- implications for massive star winds

The evolution of massive stars is influenced by the mass lost to stellar winds over their lifetimes. These winds limit the masses of the stellar remnants (such as black holes) that the stars ultimately produce. We use radio astrometry to refine the distance to the black hole X-ray binary Cygnus X-1, which we find to be $2.22^{+0.18}_{-0.17}$ kiloparsecs. When combined with previous optical data, this implies a black hole mass of $21.2\pm2.2$ solar masses, higher than previous measurements. The formation of such a high-mass black hole in a high-metallicity system constrains wind mass loss from massive stars.Comment: Published online in Science on 2021 February 18; Main (3 figures; 1 Table) + Supplementary (11 figures; 3 Tables

Inborn Errors of RNA Lariat Metabolism in Humans with Brainstem Viral Infection

Viruses that are typically benign sometimes invade the brainstem in otherwise healthy children. We report bi-allelic DBR1 mutations in unrelated patients from different ethnicities, each of whom had brainstem infection due to herpes simplex virus 1 (HSV1), influenza virus, or norovirus. DBR1 encodes the only known RNA lariat debranching enzyme. We show that DBR1 expression is ubiquitous, but strongest in the spinal cord and brainstem. We also show that all DBR1 mutant alleles are severely hypomorphic, in terms of expression and function. The fibroblasts of DBR1-mutated patients contain higher RNA lariat levels than control cells, this difference becoming even more marked during HSV1 infection. Finally, we show that the patients\ue2\u80\u99 fibroblasts are highly susceptible to HSV1. RNA lariat accumulation and viral susceptibility are rescued by wild-type DBR1. Autosomal recessive, partial DBR1 deficiency underlies viral infection of the brainstem in humans through the disruption of tissue-specific and cell-intrinsic immunity to viruses. Autosomal recessive DBR1 deficiency underlies a cellular accumulation of RNA lariats, resulting in patient susceptibility to severe viral infections of the brainstem