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1. Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort

   https://doi.org/10.1111/epi.16288  

   Encinas, Alejandra C.; Moore, Ida; Watkins, Joseph C.; Hammer, Michael F. (July 2019, Epilepsia)

   Abstract ObjectiveTo characterize a cohort of patients withSCN8A‐related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills. MethodsWe analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children withSCN8Avariants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the DenverIIitems. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression. ResultsThe 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant inSCN8Aand those with an additional variant reported in a gene other thanSCN8A, as well as between patients with different patterns of regression before and at seizure onset. SignificanceThis is the first study of anSCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children withSCN8A‐related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures forSCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome. 

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2. Beyond Autoantibodies: Biologic Roles of Human Autoreactive B Cells in Rheumatoid Arthritis Revealed by RNA‐Sequencing

   https://doi.org/10.1002/art.40772  

   Mahendra, Ankit; Yang, Xingyu; Abnouf, Shaza; Adolacion, Jay_R_T; Park, Daechan; Soomro, Sanam; Roszik, Jason; Coarfa, Cristian; Romain, Gabrielle; Wanzeck, Keith; et al (February 2019, Arthritis & Rheumatology)

   ObjectiveTo obtain the comprehensive transcriptome profile of human citrulline‐specific B cells from patients with rheumatoid arthritis (RA). MethodsCitrulline‐ and hemagglutinin‐specific B cells were sorted by flow cytometry using peptide–streptavidin conjugates from the peripheral blood ofRApatients and healthy individuals. The transcriptome profile of the sorted cells was obtained byRNA‐sequencing, and expression of key protein molecules was evaluated by aptamer‐basedSOMAscan assay and flow cytometry. The ability of these proteins to effect differentiation of osteoclasts and proliferation and migration of synoviocytes was examined by in vitro functional assays. ResultsCitrulline‐specific B cells, in comparison to citrulline‐negative B cells, from patients withRAdifferentially expressed the interleukin‐15 receptor α (IL‐15Rα) gene as well as genes related to protein citrullination and cyclicAMPsignaling. In analyses of an independent cohort of cyclic citrullinated peptide–seropositiveRApatients, the expression ofIL‐15Rα protein was enriched in citrulline‐specific B cells from the patients’ peripheral blood, and surprisingly, all B cells fromRApatients were capable of producing the epidermal growth factor ligand amphiregulin (AREG). Production ofAREGdirectly led to increased migration and proliferation of fibroblast‐like synoviocytes, and, in combination with anti–citrullinated protein antibodies, led to the increased differentiation of osteoclasts. ConclusionTo the best of our knowledge, this is the first study to document the whole transcriptome profile of autoreactive B cells in any autoimmune disease. These data identify several genes and pathways that may be targeted by repurposing severalUSFood and Drug Administration–approved drugs, and could serve as the foundation for the comparative assessment of B cell profiles in other autoimmune diseases. 

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3. Hypoxia‐enhanced adhesion of red blood cells in microscale flow

   https://doi.org/10.1111/micc.12374  

   Kim, Myeongseop; Alapan, Yunus; Adhikari, Anima; Little, Jane A.; Gurkan, Umut A. (July 2017, Microcirculation)

   Abstract ObjectivesThe advancement of microfluidic technology has facilitated the simulation of physiological conditions of the microcirculation, such as oxygen tension, fluid flow, and shear stress in these devices. Here, we present a micro‐gas exchanger integrated with microfluidics to studyRBCadhesion under hypoxic flow conditions mimicking postcapillary venules. MethodsWe simulated a range of physiological conditions and exploredRBCadhesion to endothelial or subendothelial components (FNorLN). Blood samples were injected into microchannels at normoxic or hypoxic physiological flow conditions. Quantitative evaluation ofRBCadhesion was performed on 35 subjects with homozygousSCD. ResultsSignificant heterogeneity inRBCadherence response to hypoxia was seen amongSCDpatients.RBCs from a HEA population showed a significantly greater increase in adhesion compared toRBCs from a HNA population, for bothFNandLN. ConclusionsThe approach presented here enabled the control of oxygen tension in blood during microscale flow and the quantification ofRBCadhesion in a cost‐efficient and patient‐specific manner. We identified a unique patient population in whichRBCs showed enhanced adhesion in hypoxia in vitro. Clinical correlates suggest a more severe clinical phenotype in this subgroup. 

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4. A new phenological metric for use in pheno‐climatic models: A case study using herbarium specimens of Streptanthus tortuosus

   https://doi.org/10.1002/aps3.11276  

   Love, Natalie_L_Rossington; Park, Isaac_W; Mazer, Susan_J (July 2019, Applications in Plant Sciences)

   PremiseHerbarium specimens have been used to detect climate‐induced shifts in flowering time by using the day of year of collection (DOY) as a proxy for first or peak flowering date. Variation among herbarium sheets in their phenological status, however, undermines the assumption thatDOYaccurately represents any particular phenophase. Ignoring this variation can reduce the explanatory power of pheno‐climatic models (PCMs) designed to predict the effects of climate on flowering date. MethodsHere we present a protocol for the phenological scoring of imaged herbarium specimens using an ImageJ plugin, and we introduce a quantitative metric of a specimen's phenological status, the phenological index (PI), which we use inPCMs to control for phenological variation among specimens ofStreptanthus tortuosus(Brassicaceeae) when testing for the effects of climate onDOY. We demonstrate that includingPIas an independent variable improves model fit. ResultsIncludingPIinPCMs increased the modelR²relative toPCMs that excludedPI; regression coefficients for climatic parameters, however, remained constant. DiscussionOur protocol provides a simple, quantitative phenological metric for any observed plant. IncludingPIinPCMs increasesR²and enables predictions of theDOYof any phenophase under any specified climatic conditions. 

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5. Community interest and feasibility of using a novel smartphone‐based formaldehyde exposure detection technology

   https://doi.org/10.1111/phn.12384  

   Castner, Jessica; Gehrke, Gretchen E.; Shapiro, Nicholas; Dannemiller, Karen C. (January 2018, Public Health Nursing)

   Abstract ObjectiveThis study is the first community engagement phase of a project to develop a residential formaldehyde detection system. The objectives were to conduct a feasibility assessment for device use, and identify factors associated with concerns about environmental exposure and community interest in this device. Design and SampleA cross‐sectional, internet‐based survey employing community‐based participatory research principles was utilized. 147 individuals participated from a focused Waycross, Georgia (58.5%) and broader national sample (41.5%). MeasuresVariables included acceptable cost and number of testing samples, interest in conducting tests, levels of concern over pollutants, health status, housing, and demographics. ResultsThe majority of participants desired a system with fewer than 10 samples at ≤$15.00 per sample. Statistically significant higher levels of concern over air quality, formaldehyde exposure, and interest in testing formaldehyde were observed for those with overall worse health status and living in the Waycross, Georgia geographic region. Significant differences in formaldehyde testing interest were observed by health status (OR = 0.31, 95%CI = 0.12–0.81 for home testing) and geographic location (OR = 3.16, 95%CI = 1.22–8.14 for home andOR = 4.06, 95%CI = 1.48–11.12 for ambient testing) in multivariate models. ConclusionsGeographic location and poorer general health status were associated with concerns over and interest in formaldehyde testing. 

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