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To the Editors: Please make 'Botany Corner' a staple in every issue. However, the labels on the upper left of the Cuscuta europaea illustration in the November-December 2019 issue have [...]

Objective: To identify predictors of low hemoglobin A(1c) (HbA(1c)) (<5.0%) and to investigate the association of low HbA(1c) with cause-specific mortality and risk of liver disease hospitalization.Research Design and Methods: Prospective cohort study of 13,288 participants in the Atherosclerosis Risk in Communities Study. Logistic regression was used to identify cross-sectional correlates of low HbA(1c), and Cox proportional hazards models were used to estimate the association of low HbA(1c) with cause-specific mortality.Results: Compared with participants with HbA(1c) in the normal range (5.0 to <5.7%), participants with low HbA(1c) were younger, less likely to smoke, had lower BMI, lower white cell count and fibrinogen levels, and lower prevalence of hypercholesterolemia and history of coronary heart disease. However, this group was more likely to have anemia and had a higher mean corpuscular volume. In adjusted Cox models with HbA(1c) of 5.0 to <5.7% as the reference group, HbA(1c) <5.0% was associated with a significantly increased risk of all-cause mortality (hazard ratio [HR]: 1.32, 95% CI: 1.13-1.55) and of cancer death (1.47, 95% CI: 1.16-1.84). We also noted nonsignificant trends toward increased risk of death from cardiovascular causes (1.27, 95% CI: 0.93-1.75) and respiratory causes (1.42, 95% CI: 0.78-2.56). There was a J-shaped association between HbA(1c) and risk of liver disease hospitalization.Conclusions: No single cause of death appeared to drive the association between low HbA(1c) and total mortality. These results add to evidence that low HbA(1c) values may be a generalized marker of mortality risk in the general population. [ABSTRACT FROM AUTHOR]

The most widely accepted indication for a stat EEG (stEEG) is the suspicion of nonconvulsive status epilepticus (NCSE). NCSE has been reported with surprising frequency in a wide variety of acute structural and metabolic brain injuries and significantly increases the risk of permanent brain damage and death. This risk rises and the effectiveness of treatment decreases with delays in diagnosis and increased duration of NCSE. Recent evidence confirms that more than half of NCSE patients improve with anti-seizure treatment. The emergence of NCSE as a common, dangerous, time-urgent, and treatable problem has positioned it as a target for emergency therapeutic intervention. NCSE can only be diagnosed by EEG testing, and stEEG has demonstrated value in improving NCSE management. As a result, in the near future, EEG laboratories will see increasing demands for stEEG related to NCSE. The two main obstacles to an effective stEEG program are EEG technologist coverage and electroencephalographer availability after work hours. We recommend three simple but fundamental changes in the traditional approach to stEEGs in order to overcome these obstacles: the use of EEG set-up templates by onsite personnel, easy access to EEG instruments after hours, and remote stEEG connectivity for real-time, off-site electroencephalographer interpretation. [ABSTRACT FROM AUTHOR]

Emergency or 'stat' EEGs are ordered on patients who are suspected to have serious acute brain dysfunction (ABD). Often, these patients are comatose or have some altered level of consciousness (ALOC) from stroke, brain hemorrhage, head trauma, encephalopathy, seizures, or status epilepticus--which may be convulsive (SE) or non-convulsive (NCSE). As the number of stat EEGs increases, consider alternatives to traditional methods and tools, keeping overall patient care and outcome in mind. [ABSTRACT FROM AUTHOR]

Acute thrombolysis with recombinant tissue plasminogen activator (tPA) is the only treatment of proven effectiveness in acute ischemic stroke (AIS). Cerebral edema (CE) is the most feared and fatal complication of AIS. For both of these conditions, patient selection for treatment and timing of intervention are crucial but controversial issues. Conventional diagnostic tools for AIS, including the neurological exam, computerized cerebral tomography (CT) Scan, and magnetic resonance imaging (MRI) have not as yet been able to determine which patients are the best risk-benefit candidates for thrombolysis, nor are they sensitive to the early detection of patients at risk for cerebral edema. This article suggests that the use of Emergency EEG (EmEEG) in AIS can reveal a distinctive EEG pattern that adds value to the selection of patients for thrombolytic and cerebral edema treatment. This pattern, called RAWOD (Regional Attenuation WithOut Delta) can identify patients with massive AIS earlier than CT or MRI. Patients with RAWOD are unlikely to benefit from thrombolysis but may be candidates for early surveillance and intervention for cerebral edema. [ABSTRACT FROM AUTHOR]

Based on some experimentation in NUM3D Platform, we integrate the possibilities of additive manufacturing processes and the characteristics of the materials. We extend to the specific property inherent in form and control to define a new tetraptych CPMF (Control/Process/Material/Form). We propose, from this tetraptych, an Oriented Object Modelization suited to Additive Manufacturing. In this paper, we set up a virtual representation specific to industrial manufacturing. The final objective, in fine, will be to use this representation in a decision-support tool.

Abstract Background Mortality exhibits seasonal variations, which to a certain extent can be considered as mid-to long-term influences of meteorological conditions. In addition to atmospheric effects, the seasonal pattern of mortality is shaped by non-atmospheric determinants such as environmental conditions or socioeconomic status. Understanding the influence of season and other factors is essential when seeking to implement effective public health measures. The pressures of climate change make an understanding of the interdependencies between season, climate and health especially important. Methods This study investigated daily death counts collected within the Sample Vital Registration System (VSRS) established by the Bangladesh Bureau of Statistics (BBS). The sample was stratified by location (urban vs. rural), gender and socioeconomic status. Furthermore, seasonality was analyzed for all-cause mortality, and several cause-specific mortalities. Daily deviation from average mortality was calculated and seasonal fluctuations were elaborated using non parametric spline smoothing. A seasonality index for each year of life was calculated in order to assess the age-dependency of seasonal effects. Results We found distinctive seasonal variations of mortality with generally higher levels during the cold season. To some extent, a rudimentary secondary summer maximum could be observed. The degree and shape of seasonality changed with the cause of death as well as with location, gender, and SES and was strongly age-dependent. Urban areas were seen to be facing an increased summer mortality peak, particularly in terms of cardiovascular mortality. Generally, children and the elderly faced stronger seasonal effects than youths and young adults. Conclusion This study clearly demonstrated the complex and dynamic nature of seasonal impacts on mortality. The modifying effect of spatial and population characteristics were highlighted. While tropical regions have been, and still are, associated with a marked excess of mortality in summer, only a weakly pronounced secondary summer peak could be observed for Bangladesh, possibly due to the reduced incidence of diarrhoea-related fatalities. These findings suggest that Bangladesh is undergoing an epidemiological transition from summer to winter excess mortality, as a consequence of changes in socioeconomic conditions and health care provision.

Abstract Background and Objective Exposure to ambient particles has been shown to be responsible for cardiovascular effects, especially in elderly with cardiovascular disease. The study assessed the association between deceleration capacity (DC) as well as heart rate variability (HRV) and ambient particulate matter (PM) in patients with coronary artery disease (CAD). Methods A prospective study with up to 12 repeated measurements was conducted in Erfurt, Germany, between October 2000 and April 2001 in 56 patients with physician-diagnosed ischemic heart disease, stable angina pectoris or prior myocardial infarction at an age of at least 50 years. Twenty-minute ECG recordings were obtained every two weeks and 24-hour ECG recordings every four weeks. Exposure to PM (size range from 10 nm to 2.5 μm), and elemental (EC) and organic (OC) carbon was measured. Additive mixed models were used to analyze the association between PM and ECG recordings. Results The short-term recordings showed decrements in the high-frequency component of HRV as well as in RMSSD (root-mean-square of successive differences of NN intervals) in association with increments in EC and OC 0-23 hours prior to the recordings. The long-term recordings revealed decreased RMSSD and pNN50 (% of adjacent NN intervals that differed more than 50 ms) in association with EC and OC 24-47 hours prior to the recordings. In addition, highly significant effects were found for DC which decreased in association with PM2.5, EC and OC concurrent with the ECG recordings as well as with a lag of up to 47 hours. Conclusions The analysis showed significant effects of ambient particulate air pollution on DC and HRV parameters reflecting parasympathetic modulation of the heart in patients with CAD. An air pollution-related decrease in parasympathetic tone as well as impaired heart rate deceleration capacity may contribute to an increased risk for cardiac morbidity and sudden cardiac death in vulnerable populations.

Abstract Background The present study aimed at developing a standardized heat wave definition to estimate and compare the impact on mortality by gender, age and death causes in Europe during summers 1990-2004 and 2003, separately, accounting for heat wave duration and intensity. Methods Heat waves were defined considering both maximum apparent temperature and minimum temperature and classified by intensity, duration and timing during summer. The effect was estimated as percent increase in daily mortality during heat wave days compared to non heat wave days in people over 65 years. City specific and pooled estimates by gender, age and cause of death were calculated. Results The effect of heat waves showed great geographical heterogeneity among cities. Considering all years, except 2003, the increase in mortality during heat wave days ranged from + 7.6% in Munich to + 33.6% in Milan. The increase was up to 3-times greater during episodes of long duration and high intensity. Pooled results showed a greater impact in Mediterranean (+ 21.8% for total mortality) than in North Continental (+ 12.4%) cities. The highest effect was observed for respiratory diseases and among women aged 75-84 years. In 2003 the highest impact was observed in cities where heat wave episode was characterized by unusual meteorological conditions. Conclusions Climate change scenarios indicate that extreme events are expected to increase in the future even in regions where heat waves are not frequent. Considering our results prevention programs should specifically target the elderly, women and those suffering from chronic respiratory disorders, thus reducing the impact on mortality.

Abstract Background and Objective Exposure to fine airborne particles (PM2.5) has been shown to be responsible for cardiovascular and hematological effects, especially in older people with cardiovascular disease. Some epidemiological studies suggest that individuals with diabetes may be a particularly susceptible population. This study examined effects of short-term exposures to ambient PM2.5 on markers of systemic inflammation, coagulation, autonomic control of heart rate, and repolarization in 22 adults (mean age: 61 years) with type 2 diabetes. Methods Each individual was studied for four consecutive days with daily assessments of plasma levels of blood markers. Cardiac rhythm and electrocardiographic parameters were examined at rest and with 24-hour ambulatory ECG monitors. PM2.5 and meteorological data were measured daily on the rooftop of the patient exam site. Data were analyzed with models adjusting for season, weekday, meteorology, and a random intercept. To identify susceptible subgroups, effect modification was analyzed by clinical characteristics associated with insulin resistance as well as with oxidative stress and by medication intake. Results Interleukin (IL)-6 and tumor necrosis factor alpha showed a significant increase with a lag of two days (percent change of mean level: 20.2% with 95%-confidence interval [6.4; 34.1] and 13.1% [1.9; 24.4], respectively) in association with an increase of 10 μg/m3 in PM2.5. Obese participants as well as individuals with elevated glycosylated hemoglobin, lower adiponectin, higher ferritin or with glutathione S-transferase M1 null genotype showed higher IL-6 effects. Changes in repolarization were found immediately as well as up to four days after exposure in individuals without treatment with a beta-adrenergic receptor blocker. Conclusions Exposure to elevated levels of PM2.5 alters ventricular repolarization and thus may increase myocardial vulnerability to arrhythmias. Exposure to PM2.5 also increases systemic inflammation. Characteristics associated with insulin resistance or with oxidative stress were shown to enhance the association.

Abstract Background Growing evidence indicates that ambient air pollution is associated with exacerbation of chronic diseases like chronic pulmonary disease. A prospective panel study was conducted to investigate short-term changes of blood markers of inflammation and coagulation in response to daily changes in air pollution in Erfurt, Germany. 12 clinical visits were scheduled and blood parameters were measured in 38 male patients with chronic pulmonary disease during winter 2001/2002. Additive mixed models with random patient intercept were applied, adjusting for trend, weekday, and meteorological parameters. Hourly data on ultrafine particles (UFP, 0.01-0.1 μm), accumulation mode particles (ACP, 0.1-1.0 μm), PM10 (particulate matter 2], carbon monoxide [CO], and sulphur dioxide [SO2]) were collected at a central monitoring site and meteorological data were received from an official network. For each person and visit the individual 24-hour average of pollutants immediately preceding the blood withdrawal (lag 0) up to day 5 (lag1-4) and 5-day running means were calculated. Results Increased levels of fibrinogen were observed for an increase in one interquartile range of UFP, PM10, EC, OC, CO, and NO revealing the strongest effect for lag 3. E-selectin increased in association with ACP and PM10 with a delay of one day. The ACP effect was also seen with the 5-day-mean. The pattern found for D-dimer was inconsistent. Prothrombin fragment 1+2 decreased with lag 4 consistently for all particulate pollutants. Von Willebrand factor antigen (vWF) showed a consistent decrease in association with almost all air pollutants with all lags except for lag 0. No associations were found for C-reactive protein, soluble intercellular adhesion molecule 1, serum amyloid A and factor VII. Conclusion These results suggest that elevated concentrations of air pollution are associated with changes in some blood markers of inflammation and coagulation in patients with chronic pulmonary disease. The clinical implications of these findings need further investigation.

Abstract Background Advances in translational research have led to the need for well characterized biospecimens for research. The National Mesothelioma Virtual Bank is an initiative which collects annotated datasets relevant to human mesothelioma to develop an enterprising biospecimen resource to fulfill researchers' need. Methods The National Mesothelioma Virtual Bank architecture is based on three major components: (a) common data elements (based on College of American Pathologists protocol and National North American Association of Central Cancer Registries standards), (b) clinical and epidemiologic data annotation, and (c) data query tools. These tools work interoperably to standardize the entire process of annotation. The National Mesothelioma Virtual Bank tool is based upon the caTISSUE Clinical Annotation Engine, developed by the University of Pittsburgh in cooperation with the Cancer Biomedical Informatics Grid™ (caBIG™, see http://cabig.nci.nih.gov). This application provides a web-based system for annotating, importing and searching mesothelioma cases. The underlying information model is constructed utilizing Unified Modeling Language class diagrams, hierarchical relationships and Enterprise Architect software. Result The database provides researchers real-time access to richly annotated specimens and integral information related to mesothelioma. The data disclosed is tightly regulated depending upon users' authorization and depending on the participating institute that is amenable to the local Institutional Review Board and regulation committee reviews. Conclusion The National Mesothelioma Virtual Bank currently has over 600 annotated cases available for researchers that include paraffin embedded tissues, tissue microarrays, serum and genomic DNA. The National Mesothelioma Virtual Bank is a virtual biospecimen registry with robust translational biomedical informatics support to facilitate basic science, clinical, and translational research. Furthermore, it protects patient privacy by disclosing only de-identified datasets to assure that biospecimens can be made accessible to researchers.

Abstract Background Epidemiological studies on health effects of air pollution have consistently shown adverse cardiovascular effects. Toxicological studies have provided evidence for thrombogenic effects of particles. A prospective panel study in a susceptible population was conducted in Erfurt, Germany, to study the effects of daily changes in ambient particles on various blood cells and soluble CD40ligand (sCD40L, also known as CD154), a marker for platelet activation that can cause increased coagulation and inflammation. Blood cells and plasma sCD40L levels were repeatedly measured in 57 male patients with coronary heart disease (CHD) during winter 2000/2001. Fixed effects linear regression models were applied, adjusting for trend, weekday and meteorological parameters. Hourly data on ultrafine particles (UFP, number concentration of particles from 0.01 to 0.1 μm), mass concentration of particles less than 10 and 2.5 μm in diameter (PM10, PM2.5), accumulation mode particle counts (AP, 0.1–1.0 μm), elemental and organic carbon, gaseous pollutants and meteorological data were collected at central monitoring sites. Results An immediate increase in plasma sCD40L was found in association with UFP and AP (% change from geometric mean: 7.1; CI: [0.1, 14.5] and 6.9; CI: [0.5, 13.8], respectively). Platelet counts decreased in association with UFP showing an immediate, a three days delayed (lag 3) and a 5-day average response (% change from the mean: -1.8; CI: [-3.4,-0.2]; -2.4; CI: [-4.5,-0.3] and -2.2; CI: [-4.0,-0.3] respectively). Conclusion The increased plasma sCD40L levels support the hypothesis that higher levels of ambient air pollution lead to an inflammatory response in patients with CHD thus providing a possible explanation for the observed association between air pollution and cardiovascular morbidity and mortality in susceptible parts of the population.

Abstract Background Mock oral board exams, fashioned after the live patient hour of the American Board of Psychiatry and Neurology exam, are commonly part of resident assessment during residency training. Exams using real patients selected from clinics or hospitals are not standardized and do not allow comparisons of resident performance across the residency program. We sought to create a standardized patient mock oral board exam that would allow comparison of residents' clinical performance. Methods Three cases were created and then used for this mock oral boards exercise utilizing trained standardized patients. Residents from the University of Cincinnati and Indiana University participated in the exam. Residents were scored by attending physician examiners who directly observed the encounter with the standardized patient. The standardized patient also assessed each resident. A post-test survey was administered to ascertain participant's satisfaction with the examination process. Results Resident scores were grouped within one standard deviation of the mean, with the exception of one resident who was also subjectively felt to "fail" the exam. In exams with two faculty "evaluators", scores were highly correlated. The survey showed satisfaction with the examination process in general. Conclusion Standardized patients can be used for mock oral boards in the live patient format. Our initial experience with this examination process was positive. Further testing is needed to determine if this examination format is more reliable and valid than traditional methods of assessing resident competency.

Introduction: Women veterans are at elevated risk for suicide and experience a high prevalence of suicidal ideation (SI) and suicide attempt (SA) history. Knowledge regarding SI/SA correlates among women veterans who use reproductive health care services is limited, inhibiting development of evidence-based, gender-sensitive suicide prevention programming tailored to meet women veterans' needs and preferences. This study aimed to 1) describe the prevalence and characteristics of SI and SA among women veterans using Veterans Health Administration (VHA) reproductive health care services and 2) provide an initial exploration of associations between fertility-, pregnancy-, and parenting-related factors with SI and SA to guide future research., Methods: Post-9/11 women veterans (n = 352) who used VHA reproductive health care in fiscal year 2018 completed a cross-sectional survey on reproductive health, mental health, and parenting., Results: Approximately 30% and 12% experienced SI and SA(s), respectively, after military service; 10% reported past-month SI. Infertility, pregnancy loss, age at first pregnancy, and parental status were not significantly associated with SI or SA history, although notable effect sizes were observed for infertility and age at first pregnancy; further research is warranted. Among parents, parental functioning was not associated with SI/SA, but lower parental satisfaction was significantly associated with past-month SI (prevalence ratio, 3.36; 95% confidence interval, 1.19-9.46; adjusting for demographics, military characteristics, mental health symptoms)., Conclusions: Postmilitary SI and SA(s) are common among women veterans accessing VHA reproductive health care services. Those with low parental satisfaction may be at particularly high risk. Findings can guide future research and inform clinical care to facilitate suicide prevention., (Published by Elsevier Inc.)

Sequence-based genetic testing identifies causative variants in ~ 50% of individuals with developmental and epileptic encephalopathies (DEEs). Aberrant changes in DNA methylation are implicated in various neurodevelopmental disorders but remain unstudied in DEEs. We interrogate the diagnostic utility of genome-wide DNA methylation array analysis on peripheral blood samples from 582 individuals with genetically unsolved DEEs. We identify rare differentially methylated regions (DMRs) and explanatory episignatures to uncover causative and candidate genetic etiologies in 12 individuals. Using long-read sequencing, we identify DNA variants underlying rare DMRs, including one balanced translocation, three CG-rich repeat expansions, and four copy number variants. We also identify pathogenic variants associated with episignatures. Finally, we refine the CHD2 episignature using an 850 K methylation array and bisulfite sequencing to investigate potential insights into CHD2 pathophysiology. Our study demonstrates the diagnostic yield of genome-wide DNA methylation analysis to identify causal and candidate variants as 2% (12/582) for unsolved DEE cases., (© 2024. The Author(s).)

Objective: To understand the etiological landscape and phenotypic differences between 2 developmental and epileptic encephalopathy (DEE) syndromes: DEE with spike-wave activation in sleep (DEE-SWAS) and epileptic encephalopathy with spike-wave activation in sleep (EE-SWAS)., Methods: All patients fulfilled International League Against Epilepsy (ILAE) DEE-SWAS or EE-SWAS criteria with a Core cohort (n = 91) drawn from our Epilepsy Genetics research program, together with 10 etiologically solved patients referred by collaborators in the Expanded cohort (n = 101). Detailed phenotyping and analysis of molecular genetic results were performed. We compared the phenotypic features of individuals with DEE-SWAS and EE-SWAS. Brain-specific gene co-expression analysis was performed for D/EE-SWAS genes., Results: We identified the etiology in 42/91 (46%) patients in our Core cohort, including 29/44 (66%) with DEE-SWAS and 13/47 (28%) with EE-SWAS. A genetic etiology was identified in 31/91 (34%). D/EE-SWAS genes were highly co-expressed in brain, highlighting the importance of channelopathies and transcriptional regulators. Structural etiologies were found in 12/91 (13%) individuals. We identified 10 novel D/EE-SWAS genes with a range of functions: ATP1A2, CACNA1A, FOXP1, GRIN1, KCNMA1, KCNQ3, PPFIA3, PUF60, SETD1B, and ZBTB18, and 2 novel copy number variants, 17p11.2 duplication and 5q22 deletion. Although developmental regression patterns were similar in both syndromes, DEE-SWAS was associated with a longer duration of epilepsy and poorer intellectual outcome than EE-SWAS., Interpretation: DEE-SWAS and EE-SWAS have highly heterogeneous genetic and structural etiologies. Phenotypic analysis highlights valuable clinical differences between DEE-SWAS and EE-SWAS which inform clinical care and prognostic counseling. Our etiological findings pave the way for the development of precision therapies. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To identify distinct subgroups of veterans with mild traumatic brain injury (mTBI) based on configurations of postconcussive symptom (PCS) endorsement, and to examine predictors of subgroup membership., Setting: Outpatient Veterans Health Administration (VHA)., Participants: Veterans with clinician-confirmed mTBI who completed the Neurobehavioral Symptom Inventory (NSI), determined using the Comprehensive Traumatic Brain Injury Evaluation database. Individuals who tended to overreport symptoms were excluded via an embedded symptom validity scale., Design: Retrospective cohort study leveraging national VHA clinical data from 2012 to 2020. Latent class analysis (LCA) with a split-sample cross-validation procedure was used to identify subgroups of veterans. Multinomial logistic regression was used to examine predictors of subgroup membership., Main Measures: Latent classes identified using NSI items., Results: The study included 72 252 eligible veterans, who were primarily White (73%) and male (94%). The LCA supported 7 distinct subgroups of veterans with mTBI, characterized by diverging patterns of risk for specific PCS across vestibular (eg, dizziness), somatosensory (eg, headache), cognitive (eg, forgetfulness), and mood domains (eg, anxiety). The most prevalent subgroup was Global (20.7%), followed by Cognitive-Mood (16.3%), Headache-Cognitive-Mood (H-C-M; 16.3%), Headache-Mood (14.2%), Anxiety (13.8%), Headache-Sleep (10.3%), and Minimal (8.5%). The Global class was used as the reference class for multinomial logistic regression because it was distinguished from others based on elevated risk for PCS across all domains. Female (vs male), Black (vs White), and Hispanic veterans (vs non-Hispanic) were less likely to be members of most subgroups characterized by lesser PCS endorsement relative to the Global class (excluding Headache-Mood)., Conclusion: The 7 distinct groups identified in this study distill heterogenous patterns of PCS endorsement into clinically actionable phenotypes that can be used to tailor clinical management of veterans with mTBI. Findings reveal empirical support for potential racial, ethnic, and sex-based disparities in PCS among veterans, informing efforts aimed at promoting equitable recovery from mTBI in this population., Competing Interests: The authors declare no conflicts of interest.

Background: Traumatic brain injury (TBI) is an acute injury that is understudied in civilian cohorts, especially among women, as TBI has historically been considered to be largely a condition of athletes and military service people. Both the Centres for Disease Control and Prevention (CDC) and Department of Defense (DOD)/Veterans Affairs (VA) have developed case definitions to identify patients with TBI from medical records; however, their definitions differ. We sought to re-examine these definitions to construct an expansive and more inclusive definition among a cohort of women with TBI., Methods: In this study, we use electronic health records (EHR) from a single healthcare system to study the impact of using different case definitions to identify patients with TBI. Specifically, we identified adult female patients with TBI using the CDC definition, DOD/VA definition and a combined and expanded definition herein called the Penn definition., Results: We identified 4446 adult-female TBI patients meeting the CDC definition, 3619 meeting the DOD/VA definition, and together, 6432 meeting our expanded Penn definition that includes the CDC ad DOD/VA definitions., Conclusions: Using the expanded definition identified almost two times as many patients, enabling investigations to more fully characterise these patients and related outcomes. Our expanded TBI case definition is available to other researchers interested in employing EHRs to investigate TBI., Competing Interests: Competing interests: ALCS is an Associate Editor at Neurology. DJW provides consulting services on the topic of concussion/TBI epidemiology to the NCAA., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Type 2 (T2) inflammation plays a pathogenic role in chronic rhinosinusitis (CRS). The effects of endoscopic sinus surgery (ESS) on T2 inflammation are unknown., Objective: The aim of this study was to compare T2 inflammatory biomarkers from middle meatal (MM) mucus for distinguishing patients with CRS from CRS-free patients, identifying major phenotypes (CRS without nasal polyps [CRSsNP] and CRS with nasal polyps [CRSwNP]), assessing endotypic change, and establishing cross-sectional and longitudinal outcomes in patients undergoing ESS., Methods: MM mucus samples were collected from patients with CRSsNP and patients with CRSwNP before and 6 to 12 months after ESS and compared with samples from CRS-free control patients. T2 biomarkers were evaluated both continuously and using threshold-based definitions of T2 endotype to identify relationships with patient-reported (based on the 22-Item Sinonasal Outcomes Test and Chronic Rhinosinusitis Patient-Reported Outcomes Measure) and clinician-reported (radiographic and endoscopic) severity. Linear mixed models were developed to analyze clinical variables associated with T2 biomarker levels., Results: A total of 154 patients with CRS (89 with CRSsNP and 65 with CRSwNP) were enrolled, with a mean interval of 9 months between ESS and follow-up. An analysis of pre-ESS MM mucus samples revealed elevated levels of T2 mediators in patients with CRSwNP versus in patients with CRSsNP and CRS-free controls. Temporally stable correlations between levels of IL-13 and IL-5, levels of periostin and complement 5a, and levels of eosinophil cationic protein (ECP) and eotaxin-3 were observed. On this basis and on the basis of pathologic significance, levels of IL-13, periostin and ECP were further analyzed. After ESS, levels of IL-13 and periostin decreased significantly, whereas ECP levels remained unchanged. Across pre- and post-ESS evaluation, the T2 endotype was associated with radiographic severity but did not predict outcomes. CRSwNP status and African American race were associated with higher levels of IL-13 and periostin, whereas ECP level was higher in patients undergoing extensive surgery., Conclusion: ESS decreased levels of IL-13 and periostin in the middle meatus. T2 inflammation after ESS was correlated with patient- and clinician-reported severity across phenotypes. Pre-ESS T2 inflammation did not predict post-ESS outcomes., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Objective: SCN1A variants are associated with epilepsy syndromes ranging from mild genetic epilepsy with febrile seizures plus (GEFS+) to severe Dravet syndrome (DS). Many variants are de novo, making early phenotype prediction difficult, and genotype-phenotype associations remain poorly understood., Methods: We assessed data from a retrospective cohort of 1018 individuals with SCN1A-related epilepsies. We explored relationships between variant characteristics (position, in silico prediction scores: Combined Annotation Dependent Depletion (CADD), Rare Exome Variant Ensemble Learner (REVEL), SCN1A genetic score), seizure characteristics, and epilepsy phenotype., Results: DS had earlier seizure onset than other GEFS+ phenotypes (5.3 vs. 12.0 months, p < .001). In silico variant scores were higher in DS versus GEFS+ (p < .001). Patients with missense variants in functionally important regions (conserved N-terminus, S4-S6) exhibited earlier seizure onset (6.0 vs. 7.0 months, p = .003) and were more likely to have DS (280/340); those with missense variants in nonconserved regions had later onset (10.0 vs. 7.0 months, p = .036) and were more likely to have GEFS+ (15/29, χ 2  = 19.16, p < .001). A minority of protein-truncating variants were associated with GEFS+ (10/393) and more likely to be located in the proximal first and last exon coding regions than elsewhere in the gene (9.7% vs. 1.0%, p < .001). Carriers of the same missense variant exhibited less variability in age at seizure onset compared with carriers of different missense variants for both DS (1.9 vs. 2.9 months, p = .001) and GEFS+ (8.0 vs. 11.0 months, p = .043). Status epilepticus as presenting seizure type is a highly specific (95.2%) but nonsensitive (32.7%) feature of DS., Significance: Understanding genotype-phenotype associations in SCN1A-related epilepsies is critical for early diagnosis and management. We demonstrate an earlier disease onset in patients with missense variants in important functional regions, the occurrence of GEFS+ truncating variants, and the value of in silico prediction scores. Status epilepticus as initial seizure type is a highly specific, but not sensitive, early feature of DS., (© 2024 The Authors. Epilepsia published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

We herein introduce voyAGEr, an online graphical interface to explore age-related gene expression alterations in 49 human tissues. voyAGEr offers a visualisation and statistical toolkit for the finding and functional exploration of sex- and tissue-specific transcriptomic changes with age. In its conception, we developed a novel bioinformatics pipeline leveraging RNA sequencing data, from the GTEx project, encompassing more than 900 individuals. voyAGEr reveals transcriptomic signatures of the known asynchronous ageing between tissues, allowing the observation of tissue-specific age periods of major transcriptional changes, associated with alterations in different biological pathways, cellular composition, and disease conditions. Notably, voyAGEr was created to assist researchers with no expertise in bioinformatics, providing a supportive framework for elaborating, testing and refining their hypotheses on the molecular nature of human ageing and its association with pathologies, thereby also aiding in the discovery of novel therapeutic targets. voyAGEr is freely available at https://compbio.imm.medicina.ulisboa.pt/app/voyAGEr., Competing Interests: AS, RM, AK, NS, NB No competing interests declared, (© 2023, Schneider, Martins-Silva, Kaizeler et al.)

Animal and human bites are a common reason for emergency consultation, especially in children. The most common complication of bite wounds is local infection. Systemic infections are much rarer. The key in reducing the risk of infection after a mammalian bite is local wound management with either primary or delayed closure. The benefit of administering prophylactic antibiotics is controversial.In this review, we provide a summary of the current evidence for the management of mammalian bites in children, including recommendations for appropriate investigations, wound management, administration of prophylactic and therapeutic antibiotics and the prevention of systemic infections., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)