Epidemiological and clinical features of pediatric-onset multiple sclerosis: A population-based study in Isfahan, Iran, between 1997-2020

Background: Pediatric-onset multiple sclerosis (POMS) is an autoimmune demyelinating disorder of the central nervous system (CNS), affecting individuals younger than 18 years of age. We sought to characterize the epidemiological and clinical features of patients with POMS in Isfahan, Iran, from April 1997 to March 2020. Methods: The medical records of patients with POMS in the databases of Isfahan Department of Public Health and Isfahan Multiple Sclerosis Society (IMSS) were retrospectively reviewed. The 2006 and 2016 Isfahan Province population censuses were used as reference values for assessing the temporal trend of POMS. Results: From April 1997 to March 2020, 509 individuals under18 years of age were diagnosed with POMS in Isfahan. 404 of these patients (79.4%) were girls, and 105 patients (20.6%) were boys (a female to male ratio of 3.85:1). Most of the patients (83%) were monosymptomatic at onset, with optic neuritis and brainstem-cerebellar disorders being the most frequent initial presentations. Mean ± standard deviation (SD) of age at disease diagnosis was 15.8 ± 2.5 years (ranging from 3 to 18, mode = 18).From April 2019 to March 2020, the crude prevalence and the crude incidence rate of the POMS were 5.42 per 100000 and 1.86 per 100000, respectively. Poisson regression analysis revealed a 3.4% increase in the incidence rate of POMS from April 1997 to March 2020 [relative rate:1.034, 95% confidence interval (CI): 1.021-1.048]. Conclusion: The female to male ratio in our cohort was significantly higher than any other studies conducted previously. The high female to male ratio and increasing incidence of the disease suggest increasing regionalization of care.

b-value of what? Complex behavior of the magnitude distribution during and within the 2016–2017 central Italy sequence

The Magnitude–Frequency-Distribution (MFD) of earthquakes is typically modeled with the (tapered) Gutenberg–Richter relation. The main parameter of this relation, the b-value, controls the relative rate of small and large earthquakes. Resolving spatiotemporal variations of the b-value is critical to understanding the earthquake occurrence process and improving earthquake forecasting. However, this variation is not well understood. Here we present unexpected MFD variability using a high-resolution earthquake catalog of the 2016–2017 central Italy sequence. Isolation of seismicity clusters reveals that the MFD differs in nearby clusters, varies or remains constant in time depending on the cluster, and features an unexpected b-value increase in the cluster where the largest event will occur. These findings suggest a strong influence of the heterogeneity and complexity of tectonic structures on the MFD. Our findings raise the question of the appropriate spatiotemporal scale for resolving the b-value, which poses a serious obstacle to interpreting and using the MFD in earthquake forecasting.

A small but significantly greater incidence of inflammatory heart disease identified after vaccination for SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2)

Background SARS-CoV-2 vaccines are being administered on an unprecedented scale. Assessing the risks of side effects is needed to aid clinicians in early detection and treatment. This study examined the risk of inflammatory heart disease, including pericarditis and myocarditis, following SARS-CoV-2 vaccination. Methods Intermountain Healthcare patients with inflammatory heart disease from December 15, 2020, to June 15, 2021, and with or without preceding SARS-CoV-2 vaccinations were studied. Relative rates of inflammatory heart disease were examined for vaccinated patients compared to unvaccinated patients. Results Of 67 identified inflammatory heart disease patients, 21 (31.3%) had a SARS-Cov-2 vaccination within the previous 60 days. Overall, 914,611 Intermountain Healthcare patients received a SARS-CoV-2 vaccine, resulting in an inflammatory heart disease rate of 2.30 per 100,000 vaccinated patients. The relative risk of inflammatory heart disease for the vaccinated patients compared to the unvaccinated patients was 2.05 times higher rate within the 30-day window (p=0.01) and had a trend toward increase in the 60-day window (relative rate=1.63; p=0.07). All vaccinated patients with inflammatory heart disease were treated successfully with one death related to a pre-existing condition. Conclusions Though rare, the rate of inflammatory heart disease was greater in a SARS-CoV-2 vaccinated population than the unvaccinated population. This risk is eclipsed by the risk of contracting COVID-19 and its associated, commonly severe outcomes. Nevertheless, clinicians and patients should be informed of this risk to facilitate earlier recognition and treatment.

Why Should I Take My Medicine? A Review Of ED Visits For Seizures.

Study hypothesis The costs of anti-epileptic medication (AED) and poor care coordination result in increased Emergency Department (ED) visits for seizure events and produce both direct and indirect economic burdens on patients with frequent seizures. Methods A retrospective chart review study of ED visits with chief concern of seizure from two hospitals over a two-year period was performed; resulting in 152 visits recorded in this study. Data collected included demographic information, relevant seizure or past medical history (PMH), diagnostics performed in the ED, and the admission status of the patient along with the total charges per encounter. Data was analyzed descriptively and with logistic regression analysis. Results The results yielded by this study were generally in-line with the results of similar studies, indicating a higher relative rate of ED seizure visits for males, people of Black race, and infant and toddler populations. A high proportion of Medicaid/Medicare coverage and indiscernible employment status for most patients were also noted. Observed differences in average cost among patients with and without epilepsy and male versus female patients were not shown to be statistically significant. However, the increased likelihood of admission with increasing age was shown to be significant with an average age difference between admitted and discharged populations of approximately 10 years (p= 0.003). Conclusions The data provided here is not sufficient to examine the complex relationship between seizures, epilepsy, and costs among various other patient factors. Further study is necessary to minimize direct and indirect costs of seizures. Acknowledgments This project was funded, in part, with support from the Indiana Clinical and Translational Sciences Institute funded, in part by UL1TR002529 from the National Institutes of Health. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Kinetic Study of the Atmospheric Oxidation of a Series of Epoxy Compounds by OH Radicals

The kinetics of the gas-phase reactions of hydroxyl radicals with cyclohexene oxide (CHO), 1,2-epoxyhexane (EHX), 1,2-epoxybutane (12EB), trans-2,3-epoxybutane (tEB) and cis-2,3-epoxybutane (cEB) have been investigated using the relative rate technique. The experiments have been performed at (298 ± 3) K and (760 ± 10) Torr total pressure of synthetic air using different reference compounds in a 1080 l Quartz Reactor (QUAREC) and a 480 l Duran glass chamber. The following room temperature rate coefficients (cm3 molecule−1 s−1) were obtained: k1 (OH+CHO) = (5.93 ± 1.78) × 10−12, k2 (OH+EHX) = (5.77 ± 1.29) × 10−12, k3 (OH+12EB) = (1.98 ± 0.39) × 10−12, k4 (OH+cEB) = (1.50 ± 0.26) × 10−12, k5 (OH+tEB) = (1.81 ± 0.42) × 10−12. With the exception of previous studies for 1,2-epoxybutane and cyclohexene oxide, this is to the best of our knowledge the first kinetic study of the reaction of these compounds with OH radicals. Atmospheric lifetimes, reactivity trends and atmospheric implications are discussed considering the epoxy compound rate coefficients obtained in the present study. In addition to a direct comparison with the literature data where possible, the results from the present study are compared with values estimated from the Structure Activity Relationship method.

Relative Rates of Gluten Digestion by Nine Commercial Dietary Digestive Supplements

Endopeptidases containing supplements may digest gluten and reduce the impact on celiac and gluten-sensitive subjects who inadvertently consume gluten. We investigated the relative rate of disappearance of coeliac relevant epitopes in extracts of nine commercial supplements, using two competitive enzyme-linked immunosorbent assays (ELISAs)—Ridascreen (detects QQPFP, QQQFP, LQPFP, and QLPFP) and Gluten-Tec (detects Glia-α20 and PFRPQQPYPQ). All epitopes are destroyed by cleavage after P and Q amino acids. Rates at pH 3.5 and pH 7.0 were measured. These experiments were designed to measure relative rates of epitope digestion not to mimic in vivo digestion. The supplements were: 1 GluteGuard, 2 GlutenBlock, 3 GliadinX, 4 GlutnGo, 5 GlutenRescue, 6 Eat E-Z Gluten+, 7 Glutenease, 8 Glutezyme, and 9 Gluten Digest. The mean initial rate and half-lives of epitope digestion were deduced and extrapolated to rates at the recommended dose of one supplement in a fasting stomach volume. At pH 7, supplement 1 was the fastest acting of the supplements, with Ridascreen ELISA, more than twice as fast as the next fastest supplements, 5, 6, 7, and 8. Supplements 2, 3, and 4 showed little activity at pH 7.0. Supplement 1 was also the fastest acting at pH 7 with Gluten-Tec ELISA, more than three times the rate for supplements 2 and 3, with supplements 4–9 showing minimal activity. At pH 3.5, supplement 1 acted more than five times as fast as the next fastest supplements, 2 and 3, when measured by Ridascreen, but supplements 2 and 3 were over two times faster than supplement 1 when measured by Gluten-Tec. Supplements 4–9 demonstrated minimal activity at pH 3.5 with either ELISA. Supplement 1 most rapidly digested the key immuno-reactive gluten epitopes identified by the R5 antibody in the Codex-approved competitive Ridascreen ELISA method and associated with the pathology of celiac disease.

Study of the pharmacokinetics of various drugs under conditions of antiorthostatic hypokinesia and the pharmacokinetics of acetaminophen under long-term spaceflight conditions

Objectives To study the pharmacokinetics and relative bioavailability of drugs of different chemical structure and pharmacological action under conditions simulating the effects of some factors of spaceflight, as well as the peculiarities of the pharmacokinetics of acetaminophen under long-term spaceflight conditions. Methods The pharmacokinetics of verapamil (n=8), propranolol (n=8), etacizine (n=9), furosemide (n=6), and acetaminophen (n=7) in healthy volunteers after a single oral administration under normal conditions (background) and under antiorthostatic hypokinesia (ANOH), the pharmacokinetics of acetaminophen in spaceflight members under normal ground conditions (background) (n=8) and under prolonged spaceflight conditions (SF) (n=5) were studied. Results The stay of volunteers under antiorthostatic hypokinesia had different effects on the pharmacokinetics and bioavailability of drugs: Compared to background, there was a decreasing trend in Vz for verapamil (−54 Δ%), furosemide (−20 Δ%), propranolol (−8 Δ%), and acetaminophen (−9 Δ%), but a statistically significant increase in Vz was found for etacizine (+39 Δ%); there was an increasing trend in Clt for propranolol (+13 Δ%) and acetaminophen (+16 Δ%), and a decreasing trend in Clt for etacizine, verapamil, and furosemide (−22, −23 and −9 Δ% respectively) in ANOH. The relative bioavailability of etacizine, verapamil, and furosemide in ANOH increased compared to background (+40, +23 and +13 Δ%, respectively), propranolol and acetaminophen decreased (−5 and −12 Δ% accordingly). The relative rate of absorption of etacizine and furosemide in ANOH decreased (−19 and −20 Δ%, respectively) while that of verapamil, propranolol, and acetaminophen increased (+42, +58 and +26 Δ%, respectively). A statistically significant decrease in AUC0-∞ (−57 Δ%), Cmax (−53 Δ%), relative bioavailability of acetaminophen (−52 Δ%) and a sharp increase in Clt (+147 Δ%), Tmax (+131 Δ%) as well as a trend towards a significant decrease in T1/2 (−53 Δ%), MRT (−36 Δ%) and a moderate increase in Vz (+24 Δ%) were found under control compared to background. Unidirectional changes in AUC0-∞, Clt, T1/2, MRT and relative bioavailability of acetaminophen, which are more pronounced in SF and opposite dynamics for Cmax, Tmax, Vz were found in ANOH and SP compared to background studies. Conclusions The data obtained allow recommending the studied drugs for rational pharmacotherapy in the possible development of cardiovascular disease in manned spaceflight.

RR Lyrae Stars in the Newly Discovered Ultra-faint Dwarf Galaxy Centaurus I*

We report the detection of three RR Lyrae (RRL) stars (two RRc and one RRab) in the ultra-faint dwarf (UFD) galaxy Centaurus I (Cen I) and two Milky Way (MW) δ Scuti/SX Phoenicis stars based on multi-epoch giz DECam observations. The two RRc stars are located within two times the half-light radius (r h ) of Cen I, while the RRab star (CenI-V3) is at ∼6 r h . The presence of three distant RRL stars clustered this tightly in space represents a 4.7σ excess relative to the smooth distribution of RRL in the Galactic halo. Using the newly detected RRL stars, we obtain a distance modulus to Cen I of μ 0 = 20.354 ± 0.002 mag (σ = 0.03 mag), a heliocentric distance of D ⊙ = 117.7 ± 0.1 kpc (σ = 1.6 kpc), with systematic errors of 0.07 mag and 4 kpc. The location of the Cen I RRL stars in the Bailey diagram is in agreement with other UFD galaxies (mainly Oosterhoff II). Finally, we study the relative rate of RRc+RRd (RRcd) stars (f cd) in UFD and classical dwarf galaxies. The full sample of MW dwarf galaxies gives a mean of f cd = 0.28. While several UFD galaxies, such as Cen I, present higher RRcd ratios, if we combine the RRL populations of all UFD galaxies, the RRcd ratio is similar to the one obtained for the classical dwarfs (f cd ∼ 0.3). Therefore, there is no evidence for a different fraction of RRcd stars in UFD and classical dwarf galaxies.

Detection of Cryptic Sex in Automictic Populations: Theoretical Expectations and a Case Study in Cataglyphis Desert Ants

Reproductive strategies are diverse and a whole continuum of mixed systems lies between strict sexuality and strict clonality (apomixis), including automixis, a parthenogenetic mode of reproduction involving a meiosis and increasing homozygosity over generations. These various systems impact the genetic structure of populations, which can therefore be used to infer reproductive strategies in natural populations. Here, we first develop a mathematical model, validated by simulations, to predict heterozygosity and inbreeding in mixed sexual-automictic populations. It highlights the predominant role of the rate of heterozygosity loss experienced during automixis (γ), which is locus dependent. When γ is low, mixed populations behave like purely sexual ones until sex becomes rare. In contrast, when γ is high, the erosion of genetic diversity is tightly correlated to the rate of sex, so that the individual inbreeding coefficient can inform on the ratio of sexual/asexual reproduction. In the second part of this study, we used our model to test the presence of cryptic sex in a hybridogenetic Cataglyphis ant where new queens are produced parthenogenetically, leaving males with an apparent null fitness while they are essential to colony development as sperm is required to produce workers. Occasional sexual production of queens could resolve this paradox by providing males some fertile progeny. To determine whether this occurs in natural populations, we simulated genotypic datasets in a population under various regimes of sexual vs. asexual reproduction for queen production and compared the distribution of inbreeding, expected heterozygosity and inter-individual relatedness coefficients with those observed in a natural population of Cataglyphis mauritanica using microsatellites. Our simulations show that the distribution of inter-individual relatedness coefficients was particularly informative to assess the relative rate of sexual/asexual reproduction, and our dataset was compatible with pure parthenogenesis but also with up to 2% sexual reproduction. Our approach, implemented in an R script, should be useful to assess reproductive strategies in other biological models.

Increasing Rates of RSV Hospitalization among Preterm Infants: A Decade of Data

Objective In 2014, the American Academy of Pediatrics (AAP) changed its policy on the use of respiratory syncytial virus immunoprophylaxis (RSV-IP) so that RSV-IP was no longer recommended for use among infants without other medical conditions born >29 weeks gestational age (wGA). This study examines 10-year trends in RSV-IP and RSV hospitalizations among term infants and preterm infants born at 29 to 34 wGA, including the 5 RSV seasons before and 5 RSV seasons after the AAP guidance change. Study Design A retrospective observational cohort study of a convenience sample of infants less than 6 months of age during RSV season (November–March) born between July 1, 2008, and June 30, 2019, who were born at 29 to 34 wGA (preterm) or >37 wGA (term) in the IBM MarketScan Commercial and Multi-State Medicaid databases. We excluded infants with medical conditions that would independently qualify them for RSV-IP. We identified RSV-IP utilization along with RSV and all-cause bronchiolitis hospitalizations during each RSV season. A difference-in-difference model was used to determine if there was a significant change in the relative rate of RSV hospitalizations following the 2014 policy change. Results There were 53,535 commercially insured and 85,099 Medicaid-insured qualifying preterm infants and 1,111,670 commercially insured and 1,492,943 Medicaid-insured qualifying term infants. Following the 2014 policy change, RSV-IP utilization decreased for all infants, while hospitalization rates tended to increase for preterm infants. Rate ratios comparing preterm to term infants also increased. The relative rate for RSV hospitalization for infants born at 29 to 34 wGA increased significantly for both commercially and Medicaid-insured infants (1.95, 95% CI: 1.67–2.27, p <0.001; 1.70, 95% CI: 1.55–1.86, p <0.001, respectively). Findings were similar for all-cause bronchiolitis hospitalizations. Conclusion We found that the previously identified increase in RSV hospitalization rates among infants born at 29 to 34 wGA persisted for at least 5 years following the policy change. Key Points