Search

Objective: The US Vaccine Adverse Event Reporting System (VAERS) collects spontaneous reports of adverse events following vaccination. Medical officers review the reports and often apply standardized case definitions, such as those developed by the Brighton Collaboration. Our objective was to demonstrate a multi-level text mining approach for automated text classification of VAERS reports that could potentially reduce human workload.Design: We selected 6034 VAERS reports for H1N1 vaccine that were classified by medical officers as potentially positive (N(pos)=237) or negative for anaphylaxis. We created a categorized corpus of text files that included the class label and the symptom text field of each report. A validation set of 1100 labeled text files was also used. Text mining techniques were applied to extract three feature sets for important keywords, low- and high-level patterns. A rule-based classifier processed the high-level feature representation, while several machine learning classifiers were trained for the remaining two feature representations.Measurements: Classifiers' performance was evaluated by macro-averaging recall, precision, and F-measure, and Friedman's test; misclassification error rate analysis was also performed.Results: Rule-based classifier, boosted trees, and weighted support vector machines performed well in terms of macro-recall, however at the expense of a higher mean misclassification error rate. The rule-based classifier performed very well in terms of average sensitivity and specificity (79.05% and 94.80%, respectively).Conclusion: Our validated results showed the possibility of developing effective medical text classifiers for VAERS reports by combining text mining with informative feature selection; this strategy has the potential to reduce reviewer workload considerably. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We investigated vaccine risk perception among reporters of autism to the Vaccine Adverse Event Reporting System (VAERS). METHODS: We conducted structured interviews with 124 parents who reported autism and related disorders to VAERS from 1990 to 2001 and compared results with those of a published survey of parents in the general population. RESULTS: Respondents perceived vaccine-preventable diseases as less serious than did other parents. Only 15% of respondents deemed immunization extremely important for children's health; two thirds had withheld vaccines from their children. CONCLUSIONS: Views of parents who believe vaccines injured their children differ significantly from those of the general population regarding the benefits of immunization. Understanding the factors that shape this perspective can improve communication among vaccine providers, policymakers, and parents/patients. [ABSTRACT FROM AUTHOR]

PURPOSE: The US Food and Drug Administration has approved recombinant human bone morphogenetic protein 2 (rhBMP-2) (Infuse Bone Graft; Medtronic Sofamor Danek, Minneapolis, MN) as an alternative to autogenous bone graft for sinus augmentations and for localized alveolar ridge augmentations for defects associated with extraction sockets. The objective of this analysis was to characterize adverse events reported after the use of rhBMP-2 in oral and maxillofacial procedures. MATERIALS AND METHODS: The US Food and Drug Administration's Manufacturer and User Facility Device Experience database contains reports of adverse events involving medical devices. The publicly available version of the database was searched for reports for the brand name Infuse Bone Graft. Descriptive statistics were used to summarize the procedures and adverse events. RESULTS: As of April 30, 2011, the Manufacturer and User Facility Device Experience database contained 83 reports of adverse events after oral and maxillofacial operations involving rhBMP-2. Of these reports, 55 (66.3%) described off-label uses, such as reconstruction of the mandible after fracture or cancer or alveolar cleft repair. The most commonly reported adverse events included local reactions, graft failure, infections, and other wound complications. Of the reports, 25 (30.1%) stated that the patient required additional surgery to address the reported adverse event. CONCLUSIONS: Serious adverse events, some of which may require a second operation, can occur after the use of rhBMP-2 in oral and maxillofacial procedures. In this analysis graft, failure and pseudarthrosis were more commonly reported after off-label uses of rhBMP-2 than approved uses. [ABSTRACT FROM AUTHOR]

Vasovagal syncope, or fainting, can be triggered by various stimuli, including medical procedures. Syncope after vaccination has been reported, most commonly among adolescents, and can result in injuries. Using the Vaccine Adverse Event Reporting System (VAERS), we reviewed and summarized reports of syncope after live attenuated influenza vaccine, intranasal (LAIV) administered as the sole vaccine (i.e., no concomitant injections). From June 17, 2003 (date of LAIV licensure in the US) through May 31, 2024, VAERS received 50 reports of syncope after LAIV. Nearly half (23; 46 %) pertained to individuals 10-19 years of age. While the vast majority of reports (35; 70 %) did not describe any injuries, 15 people (30 %) were injured, most commonly by falling and hitting their head or face. Twenty-two people (44 %) required evaluation in the emergency department or doctor's office, including an individual who lost consciousness while he was driving home from the vaccination appointment. He did not report any injuries, but the car was severely damaged. Nearly three-quarters of people (37; 74 %) developed syncope within 15 min after vaccination, but fewer than half of reports (24; 48 %) stated that the patient had waited in the observation area for at 15 min. Based on approximately 111.9 million doses of LAIV distributed in the US during the same time period, the reporting rate is approximately 0.4 per million doses, suggesting that syncope following LAIV is rare. The information summarized here may enable clinicians, patients, and caregivers to make a more informed decision regarding preventing injuries that may occur following LAIV-related syncope., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Cas12j, a hypercompact and efficient Cas protein, has potential for use in CRISPR diagnostics, but has not yet been used because the trans-cleavage activity of Cas12j is veiled. Here, the trans-cleavage behavior of Cas12j1, 2, and 3 variants and evaluate their suitability for nucleic acid detection is unveiled. The target preferences and mismatch specificities of the Cas12j variants are precisely investigated and the optimal Cas12j reaction conditions are determined. As a result, the EXP-J assay for miRNA detection by harnessing the robust trans-cleavage activity of Cas12j on short ssDNA is developed. The EXP-J method demonstrates exceptional detection capabilities for miRNAs, proving that Cas12j can be a pivotal component in molecular diagnostics. Furthermore, the translational potential of the EXP-J assay is validated by detecting oncogenic miRNAs in plasma samples from lung cancer patients. This investigation not only elucidates the trans-cleavage characteristics of Cas12j variants, but also advances the Cas12j-based diagnostic toolkit., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Targeting the hydrophobic Phe43 pocket of HIV's envelope glycoprotein gp120 is a critical strategy for antiviral interventions due to its role in interacting with the host cell's CD4. Previous inhibitors, including small molecules and CD4 mimetic peptides based on scyllatoxin, have demonstrated significant binding and neutralization capabilities but were often chemically synthesized or contained non-canonical amino acids. Microbial expression using natural amino acids offers advantages such as cost-effectiveness, scalability, and efficient production of fusion proteins. In this study, we enhanced the previous scyllatoxin-based synthetic peptide by substituting natural amino acids and successfully expressed it in E. coli. The peptide was optimized by mutating the C-terminal amidated valine to valine and glutamine, and by reducing the disulfide bonds from three to two. Circular dichroism confirmed proper secondary structure formation, and fluorescence polarization analysis revealed specific, concentration-dependent binding to HIV gp120, supported by molecular dynamics simulations. These findings indicate the potential for scalable microbial production of effective antiviral peptides, with significant applications in pharmaceutical development for HIV treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Bivalent mRNA coronavirus disease 2019 (COVID-19) vaccines may be simultaneously administered with other recommended vaccines, including seasonal influenza vaccines. However, few studies have evaluated the safety of co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines., Objective: The aim was to describe reports to the Vaccine Adverse Event Reporting System (VAERS) after co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines., Methods: We searched the VAERS database for reports of adverse events (AEs) following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines during the period of September 1, 2022-March 31, 2023. We assessed the characteristics of these reports and described the most frequently reported AEs. Clinicians reviewed available medical records for reports of serious AEs and adverse events of special interest (AESI)., Results: During the period of 1 September 2022 through 31 March 2023, VAERS received 3689 reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines. The median age of vaccinees was 59 years (interquartile range 39, 70 years); 342 reports (9.3%) were classified as serious. The most common AEs among non-serious reports were severe-acute-respiratory-syndrome-related coronavirus (SARS-CoV-2) infection (785, 23.5%), cough (592, 17.7%), and fatigue (568, 17.0%). The most common AEs among serious reports were Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection (88, 25.7%), dyspnea (81, 23.7%), and condition aggravated (55, 16.1%)., Discussion: Reports of AEs following co-administration of bivalent mRNA COVID-19 and seasonal influenza vaccines did not reveal any unusual or unexpected patterns of AEs. Increased reporting of certain events (e.g., COVID-19) was expected due to Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) reporting requirements. CDC and FDA will continue to monitor the safety of co-administration of mRNA COVID-19 and seasonal influenza vaccines., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The forAge program estimates the age-at-death of human pubic symphysis using 3-dimensional scans. It was developed by Dennis E. Slice and Bridget F. B. Algee-Hewitt, and utilizes three distinct scores: the Slice and Algee-Hewitt (SAH) score, bending energy (BE), and ventral curvature (VC). However, these scores and age estimation regression equation were obtained through European American pubic symphysis. Changes in the pubic symphysis surface are evaluated as one of the most reliable indicators for estimating age, but in connection with this, using Korean materials, changes in the pubic symphysis surface and the actual changes are evaluated. There is no bar where the relationship between ages is grasped, and there are cases where a methodology developed for a specific group is applied to a Korean group. Changing the pubic symphysis surface by aging was evaluated as one of the most reliable indicators for estimating age. However, there is no study conducted on the relationship between changes in the pubic symphysis and actual age and applied the age estimation method for a specific population among Korean population. The purpose of this study is to compare the difference between the actual age and the estimated age in Korean to see if the forAge program is applicable to other population of different ancestral origin. One hundred and four modern Korean pubic symphyseal surfaces (47 to 96 years old) were used in this study. Through the pubic symphyseal surface 3-dimensional images, age-at-death was estimated via prediction equation and new regression lines using SAH, VC, and BE scores. Firstly, the estimated age via prediction equation using the first version of SAH score was lower than the actual age according to all pubic symphyseal surfaces for those older than 56. With aging, the difference between the actual age and estimated age became markedly larger. Secondly, the estimated ages via the new regression lines using VC, the second version of SAH score, and BE were shown a similar pattern to the previous prediction equation. The current study explored the applicability of a quantitative method using pubic symphyseal surface for age estimation in a modern Korean population. This study showed the forAge program cannot be applied to a modern Korean population, as they present relatively low correlations with the actual age-at-death.

Pulmonary artery catheterization (PAC) has been used as a clinical standard for cardiac output (CO) measurements on humans. On animals, however, an ultrasonic flow sensor (UFS) placed around the ascending aorta or pulmonary artery can measure CO and stroke volume (SV) more accurately. The objective of this paper is to compare CO and SV measurements using a noninvasive electrical impedance tomography (EIT) device and three invasive devices using UFS, PAC-CCO (continuous CO) and arterial pressure-based CO (APCO). Thirty-two pigs were anesthetized and mechanically ventilated. A UFS was placed around the pulmonary artery through thoracotomy in 11 of them, while the EIT, PAC-CCO and APCO devices were used on all of them. Afterload and contractility were changed pharmacologically, while preload was changed through bleeding and injection of fluid or blood. Twenty-three pigs completed the experiment. Among 23, the UFS was used on 7 pigs around the pulmonary artery. The percentage error (PE) between CO UFS and CO EIT was 26.1%, and the 10-min concordance was 92.5%. Between SV UFS and SV EIT , the PE was 24.8%, and the 10-min concordance was 94.2%. On analyzing the data from all 23 pigs, the PE between time-delay-adjusted CO PAC-CCO and CO EIT was 34.6%, and the 10-min concordance was 81.1%. Our results suggest that the performance of the EIT device in measuring dynamic changes of CO and SV on mechanically-ventilated pigs under different cardiac preload, afterload and contractility conditions is at least comparable to that of the PAC-CCO device. Clinical studies are needed to evaluate the utility of the EIT device as a noninvasive hemodynamic monitoring tool., (© 2024. The Author(s).)

The diterpene glycosyltransferase UGT76G1, derived from Stevia rebaudiana, plays a pivotal role in the biosynthesis of rebaudioside A, a natural sugar substitute. Nevertheless, its potential for industrial application is limited by certain enzymatic characteristics, notably thermostability. To enhance the thermostability and enzymatic activity, we employed a computational design strategy, merging stabilizing mutation scanning with a Rosetta-based protein design protocol. Compared to UGT76G1, the designed variant 76_4 exhibited a 9 °C increase in apparent T m , a 2.55-fold increase rebaudioside A production capacity, and a substantial 11% reduction in the undesirable byproduct rebaudioside I. Variant 76_7 also showed a 1.91-fold enhancement rebaudioside A production capacity, which was maintained up to 55 °C, while the wild-type lost most of its activity. These results underscore the efficacy of structure-based design in introducing multiple mutations simultaneously, which significantly improves the enzymatic properties of UGT76G1. This strategy provides a method for the development of efficient, thermostable enzymes for industrial applications., (© 2023. The Author(s).)

The CRISPR-Cas9 system is a widely used gene-editing tool, offering unprecedented opportunities for treating various diseases. Controlling Cas9/dCas9 activity at specific location and time to avoid undesirable effects is very important. Here, we report a conditionally active CRISPR-Cas9 system that regulates target gene expression upon sensing cellular environmental change. We conjugated the oxygen-sensing transcription activation domain (TAD) of hypoxia-inducing factor (HIF-1α) with the Cas9/dCas9 protein. The Cas9-TAD conjugate significantly increased endogenous target gene cleavage under hypoxic conditions compared with that under normoxic conditions, whereas the dCas9-TAD conjugate upregulated endogenous gene transcription. Furthermore, the conjugate system effectively downregulated the expression of SNAIL, an essential gene in cancer metastasis, and upregulated the expression of the tumour-related genes HNF4 and NEUROD1 under hypoxic conditions. Since hypoxia is closely associated with cancer, the hypoxia-dependent Cas9/dCas9 system is a novel addition to the molecular tool kit that functions in response to cellular signals and has potential application for gene therapeutics., (© 2023. Springer Nature Limited.)

UdgX excises uracil from uracil-containing DNA to concurrently form a covalent bond with the resulting AP-DNA. Structurally, UdgX is highly similar to family-4 UDGs (F4-UDGs). However, UdgX is unique in possessing a flexible R-loop (105KRRIH109). Among the class-defining motifs, while its motif A (51GEQPG55) diverged to possess Q53 in place of A53/G53 in F4-UDGs, motif B [178HPS(S/A)(L/V)(L/V)R184] has remained unchanged. Previously, we proposed an SN1 mechanism resulting in a covalent bond between H109 and AP-DNA. In this study, we investigated several single/double mutants of UdgX. The H109A, H109S, H109G, H109Q, H109C and H109K mutants gain conventional UDG activity to varying levels. The crystal structures of UdgX mutants show topological changes in their active sites, rationalizing their UDG activities. The E52Q, E52N and E52A mutants reveal that E52 forms a catalytic dyad with H109 to enhance its nucleophilicity. The Q53A mutant supports that UdgX specific evolution of Q53 occurred essentially to stabilize the R-loop conformation. The R184A mutation (motif B) supports the role of R184 in substrate-binding. Taken together, the structural, bioinformatics, and mutational studies suggest that UdgX diverged from F4-UDGs, and the emergence of the characteristic R-loop in UdgX is functionally assisted by A53/G53 to Q53 changes in motif A., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: On 2/27/2021, FDA authorized Janssen COVID-19 Vaccine (Ad.26.COV2.S) for use in individuals 18 years of age and older. Vaccine safety was monitored using the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance system, and v-safe, a smartphone-based surveillance system., Methods: VAERS and v-safe data from 2/27/2021 to 2/28/2022 were analyzed. Descriptive analyses included sex, age, race/ethnicity, seriousness, AEs of special interest (AESIs), and cause of death. For prespecified AESIs, reporting rates were calculated using the total number of doses of Ad26.COV2.S administered. For myopericarditis, observed-to-expected (O/E) analysis was performed based on the number verified cases, vaccine administration data, and published background rates. Proportions of v-safe participants reporting local and systemic reactions, as well as health impacts, were calculated., Results: During the analytic period, 17,018,042 doses of Ad26.COV2.S were administered in the United States, and VAERS received 67,995 reports of AEs after Ad26.COV2.S vaccination. Most AEs (59,750; 87.9 %) were non-serious and were similar to those observed during clinical trials. Serious AEs included COVID-19 disease, coagulopathy (including thrombosis with thrombocytopenia syndrome; TTS), myocardial infarction, Bell's Palsy, and Guillain-Barré syndrome (GBS). Among AESIs, reporting rates per million doses of Ad26.COV2.S administered ranged from 0.06 for multisystem inflammatory syndrome in children to 263.43 for COVID-19 disease. O/E analysis revealed elevated reporting rate ratios (RRs) for myopericarditis; among adults ages 18-64 years, the RR was 3.19 (95 % CI 2.00, 4.83) within 7 days and 1.79 (95 % CI 1.26, 2.46) within 21 days of vaccination. Of 416,384 Ad26.COV2.S recipients enrolled into v-safe, 60.9 % reported local symptoms (e.g. injection site pain) and 75.9 % reported systemic symptoms (e.g., fatigue, headache). One-third of participants (141,334; 33.9 %) reported a health impact, but only 1.4 % sought medical care., Conclusion: Our review confirmed previously established safety risks for TTS and GBS and identified a potential safety concern for myocarditis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Brown adipose tissue (BAT) has abundant mitochondria with the unique capability of generating heat via uncoupled respiration. Mitochondrial uncoupling protein 1 (UCP1) is activated in BAT during cold stress and dissipates mitochondrial proton motive force generated by the electron transport chain to generate heat. However, other mitochondrial factors required for brown adipocyte respiration and thermogenesis under cold stress are largely unknown. Here, we show LETM1 domain-containing protein 1 (LETMD1) is a BAT-enriched and cold-induced protein required for cold-stimulated respiration and thermogenesis of BAT. Proximity labeling studies reveal that LETMD1 is a mitochondrial matrix protein. Letmd1 knockout male mice display aberrant BAT mitochondria and fail to carry out adaptive thermogenesis under cold stress. Letmd1 knockout BAT is deficient in oxidative phosphorylation (OXPHOS) complex proteins and has impaired mitochondrial respiration. In addition, BAT-specific Letmd1 deficient mice exhibit phenotypes identical to those observed in Letmd1 knockout mice. Collectively, we demonstrate that the BAT-enriched mitochondrial matrix protein LETMD1 plays a tissue-autonomous role that is essential for BAT mitochondrial function and thermogenesis., (© 2023. The Author(s).)

Periplasmic α-amylase MalS (EC. 3.2.1.1), which belongs to glycoside hydrolase (GH) family 13 subfamily 19, is an integral component of the maltose utilization pathway in Escherichia coli K12 and used among Ecnterobacteriaceae for the effective utilization of maltodextrin. We present the crystal structure of MalS from E. coli and reveal that it has unique structural features of circularly permutated domains and a possible CBM69. The conventional C-domain of amylase consists of amino acids 120-180 (N-terminal) and 646-676 (C-terminal) in MalS, and the whole domain architecture shows the complete circular permutation of C-A-B-A-C in domain order. Regarding substrate interaction, the enzyme has a 6-glucosyl unit pocket binding it to the non-reducing end of the cleavage site. Our study found that residues D385 and F367 play important roles in the preference of MalS for maltohexaose as an initial product. At the active site of MalS, β-CD binds more weakly than the linear substrate, possibly due to the positioning of A402. MalS has two Ca 2+ binding sites that contribute significantly to the thermostability of the enzyme. Intriguingly, the study found that MalS exhibits a high binding affinity for polysaccharides such as glycogen and amylopectin. The N domain, of which the electron density map was not observed, was predicted to be CBM69 by AlphaFold2 and might have a binding site for the polysaccharides. Structural analysis of MalS provides new insight into the structure-evolution relationship in GH13 subfamily 19 enzymes and a molecular basis for understanding the details of catalytic function and substrate binding of MalS.

Trotter and Gleser presented two sets of stature estimation equations for the US White males in their 1952 and 1958 studies. Following Trotter's suggestion favouring the 1952 equations simply due to the smaller standard errors, the 1958 equations have been seldom used and have gone without additional systematic validation tests. This study aims to assess the performance of the Trotter and Gleser 1952, Trotter and Gleser 1958, and FORDISC equations for the White males in a quantitative and systematic way, particularly when applied to the WWII and Korean War casualties. In sum, 27 equations (7 from the 1952 study, 10 from the 1958 study, and 10 from FORDISC) were applied to the osteometric data of 240 accounted-for White male casualties of the WWII and Korean War. Then, the bias, accuracy, and Bayes factor for each set of stature estimates were calculated. The results show that, overall, Trotter and Gleser's 1958 equations outperform the 1952 and FORDISC equations in terms of all three measures. Particularly, the equations with higher Bayes factors produced stature estimates where distributions were closer to that of the reported statures than those with lower Bayes factors. When considering Bayes factors, the best performing equation was the "Radius" equation from the 1958 study (BF = 15.34) followed by the "Humerus+Radius" equation from FORDISC (BF = 14.42) and the "Fibula" equation from the 1958 study (BF = 13.82). The results of this study will provide researchers and practitioners applying the Trotter and Gleser stature estimation method with a practical guide for equation selection., Key Points: The performance of three stature estimation methods was compared quantitatively.Trotter and Gleser's (1952, 1958) and FORDISC White male equations were included.Overall, Trotter and Gleser's 1958 method outperformed the other methods.This study provides a practical guide for stature estimation equation selection., (© The Author(s) 2023. Published by OUP on behalf of the Academy of Forensic Science.)

Conductivity tensor imaging (CTI) using MRI is an advanced method that can non-invasively measure the electrical properties of living tissues. The contrast of CTI is based on underlying hypothesis about the proportionality between the mobility and diffusivity of ions and water molecules inside tissues. The experimental validation of CTI in both in vitro and in vivo settings is required as a reliable tool to assess tissue conditions. The changes in extracellular space can be indicators for disease progression, such as fibrosis, edema, and cell swelling. In this study, we conducted a phantom imaging experiment to test the feasibility of CTI for measuring the extracellular volume fraction in biological tissue. To mimic tissue conditions with different extracellular volume fractions, four chambers of giant vesicle suspension (GVS) with different vesicle densities were included in the phantom. The reconstructed CTI images of the phantom were compared with the separately-measured conductivity spectra of the four chambers using an impedance analyzer. Moreover, the values of the estimated extracellular volume fraction in each chamber were compared with those measured by a spectrophotometer. As the vesicle density increased, we found that the extracellular volume fraction, extracellular diffusion coefficient, and low-frequency conductivity decreased, while the intracellular diffusion coefficient slightly increased. On the other hand, the high-frequency conductivity could not clearly distinguish the four chambers. The extracellular volume fraction measured by the spectrophotometer and CTI method in each chamber were quite comparable, i.e., (1.00, 0.98 ± 0.01), (0.59, 0.63 ± 0.02), (0.40, 0.40 ± 0.05), and (0.16, 0.18 ± 0.02). The prominent factor influencing the low-frequency conductivity at different GVS densities was the extracellular volume fraction. Further studies are needed to validate the CTI method as a tool to measure the extracellular volume fractions in living tissues with different intracellular and extracellular compartments., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Choi, Katoch, Park, Kim, Oh, Kim and Woo.)

Continuous monitoring of both hemodynamic and respiratory parameters would be beneficial to patients, e.g., those in intensive care unit. The objective of this exploratory animal study was to test the feasibility of simultaneous measurements of relative tidal volume (rTV) and relative stroke volume (rSV) using an electrical impedance tomography (EIT) device equipped with a new real-time source separation algorithm implemented as two spatial filters. Five pigs were anesthetized and mechanically ventilated. The supplied tidal volume from a mechanical ventilator was reduced to 70, 50 and 30% from the 100% normal volume to simulate hypoventilation. The respiratory volume signal and cardiac volume signal were generated by applying the spatial filters to the acquired EIT data, from which values of rTV and rSV were extracted. The measured rTV values were compared with the TV values from the mechanical ventilator using the four-quadrant concordance analysis method. For changes in TV, the concordance rate in each animal ranged from 81.8% to 100%, while it was 92.5% when the data from all five animals were pooled together. When the measured rTV values for each animal were scaled to the absolute TV EIT values in mL using the TV Vent data from the mechanical ventilator, the smallest 95% limits of agreement (LoA) were - 6.04 and 7.44 mL for the 70% ventilation level, and the largest 95% LoA were - 18.1 and 19.4 mL for the 50% ventilation level. The percentage error between TV EIT and TV Vent was 10.3%. Although similar statistical analyses on rSV data could not be performed due to limited intra-animal variability, changes in rSV values measured by the EIT device were comparable to those measured by an invasive hemodynamic monitor. In this animal study, we were able to demonstrate the feasibility of an EIT device for noninvasive and simultaneous measurements of rTV and rSV in real time. However, the performance of the real-time source separation method needs to be further validated on animals and human subjects, particularly over a wide range of SV values. Future clinical studies are needed to assess the potential usefulness of the new method in dynamic cardiopulmonary monitoring and explore other clinical applications., (© 2022. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Importance: Because of historical associations between vaccines and Guillain-Barré syndrome (GBS), the condition was a prespecified adverse event of special interest for COVID-19 vaccine monitoring., Objective: To evaluate GBS reports to the Vaccine Adverse Event Reporting System (VAERS) and compare reporting patterns within 21 and 42 days after vaccination with Ad26.COV2.S (Janssen), BNT162b2 (Pfizer-BioNTech), and mRNA-1273 (Moderna) COVID-19 vaccines., Design, Setting, and Participants: This retrospective cohort study was conducted using US VAERS reports submitted during December 2020 to January 2022. GBS case reports verified as meeting the Brighton Collaboration case definition for GBS in US adults after COVID-19 vaccination were included., Exposures: Receipt of the Ad26.COV2.S, BNT162b2, or mRNA-1273 COVID-19 vaccine., Main Outcomes and Measures: Descriptive analyses of GBS case were conducted. GBS reporting rates within 21 and 42 days after Ad26.COV2.S, BNT162b2, or mRNA-1273 vaccination based on doses administered were calculated. Reporting rate ratios (RRRs) after receipt of Ad26.COV2.S vs BNT162b2 or mRNA-1273 within 21- and 42-day postvaccination intervals were calculated. Observed-to-expected (OE) ratios were estimated using published GBS background rates., Results: Among 487 651 785 COVID-19 vaccine doses, 17 944 515 doses (3.7%) were Ad26.COV2.S, 266 859 784 doses (54.7%) were BNT162b2, and 202 847 486 doses (41.6%) were mRNA-1273. Of 295 verified reports of individuals with GBS identified after COVID-19 vaccination (12 Asian [4.1%], 18 Black [6.1%], and 193 White [65.4%]; 17 Hispanic [5.8%]; 169 males [57.3%]; median [IQR] age, 59.0 [46.0-68.0] years), 275 reports (93.2%) documented hospitalization. There were 209 and 253 reports of GBS that occurred within 21 days and 42 days of vaccination, respectively. Within 21 days of vaccination, GBS reporting rates per 1 000 000 doses were 3.29 for Ad26.COV.2, 0.29 for BNT162b2, and 0.35 for mRNA-1273 administered; within 42 days of vaccination, they were 4.07 for Ad26.COV.2, 0.34 for BNT162b2, and 0.44 for mRNA-1273. GBS was more frequently reported within 21 days after Ad26.COV2.S than after BNT162b2 (RRR = 11.40; 95% CI, 8.11-15.99) or mRNA-1273 (RRR = 9.26; 95% CI, 6.57-13.07) vaccination; similar findings were observed within 42 days after vaccination (BNT162b2: RRR = 12.06; 95% CI, 8.86-16.43; mRNA-1273: RRR = 9.27; 95% CI, 6.80-12.63). OE ratios were 3.79 (95% CI, 2.88-4.88) for 21-day and 2.34 (95% CI, 1.83-2.94) for 42-day intervals after Ad26.COV2.S vaccination and less than 1 (not significant) after BNT162b2 and mRNA-1273 vaccination within both postvaccination periods., Conclusions and Relevance: This study found disproportionate reporting and imbalances after Ad26.COV2.S vaccination, suggesting that Ad26.COV2.S vaccination was associated with increased risk for GBS. No associations between mRNA COVID-19 vaccines and risk of GBS were observed.

Purpose: The Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID-19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S., Methods: Reports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data., Results: Through February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post-vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/μl) was documented in 63 records (11.5%) and anti-platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered., Conclusions: Life-threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden., (Published 2022. This article is a U.S. Government work and is in the public domain in the USA.)

The 4-α-glucanotransferase (4-α-GTase or amylomaltase) is an essential enzyme in maltodextrin metabolism. Generally, most bacterial 4-α-GTase is classified into glycoside hydrolase (GH) family 77. However, hyperthermophiles have unique 4-α-GTases belonging to GH family 57. These enzymes are the main amylolytic protein in hyperthermophiles, but their mode of action in maltooligosaccharide utilization is poorly understood. In the present study, we investigated the catalytic properties of 4-α-GTase from the hyperthermophile Pyrococcus sp. ST04 (PSGT) in the presence of maltooligosaccharides of various lengths. Unlike 4-α-GTases in GH family 77, GH family 57 PSGT produced maltotriose in the early stage of reaction and preferred maltose and maltotriose over glucose as the acceptor. The kinetic analysis showed that maltotriose had the lowest KM value, which increased amylose degradation activity by 18.3-fold. Structural models of PSGT based on molecular dynamic simulation revealed two aromatic amino acids interacting with the substrate at the +2 and +3 binding sites, and the mutational study demonstrated they play a critical role in maltotriose binding. These results clarify the mode of action in carbohydrate utilization and explain acceptor binding mechanism of GH57 family 4-α-GTases in hyperthermophilic archaea., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jung, Hong, Jeon, Kim, Seo, Woo, Holden and Park.)

Background: On February 27, 2021, the Food and Drug Administration (FDA) issued an Emergency Use Authorization for Ad.26.COV2.S COVID-19 vaccine. As part of post-authorization safety surveillance, the FDA has identified a potential safety concern for thrombocytopenia following receipt of Ad.26.COV2.S COVID-19 vaccine., Methods: Reports of thrombocytopenia were identified in a passive reporting system (Vaccine Adverse Event Reporting System; VAERS) February-December 2021. Demographics, clinical characteristics, laboratory values, and relevant medical history were reviewed. The reporting rate was analyzed, including calculation of the observed-to-expected ratio based on vaccine administration data and the background rate of thrombocytopenia in the general (unvaccinated) population., Results: As of December 31, 2021, 100 reports of thrombocytopenia were identified in VAERS following vaccination with Ad.26.COV2.S. The median platelet count was 33,000 per µL (interquartile range 8,000-86,000). Fifteen reports (15%) documented a platelet count of 5,000 per µL or lower. The median time to onset of thrombocytopenia was 9 days (interquartile range 3-18.5), with most cases (69; 69%) beginning within 14 days after vaccination. A large majority of cases (84; 84%) were serious, including six deaths. With approximately 16,292,911 doses of Ad.26.COV2.S administered to adults in the US, the crude reporting rate was 0.61 cases of thrombocytopenia per 100,000 doses administered. The overall estimated observed-to-expected rate ratio was 2.43 (95% CI 1.97, 2.95)., Conclusions: These findings suggest an increased risk of thrombocytopenia following receipt of Ad.26.COV2.S., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

This study addresses issues associated with limited access to reference skeletal collections and how it hampers regional methodological development. The study also investigates the effects of three different priors on age-at-death estimations of Koreans and quantifies the accuracy of Bayesian estimation compared to a non-Bayesian approach. CT scan images of pubic symphyses were scored following the Suchey-Brooks standards. We specifically examine Bayesian age-at-death estimations under an optimal scenario where both the likelihood and prior probability are derived from a target population of Korean origin. Three different priors (population, forensic, and uniform priors) are evaluated for their age estimation accuracy levels. The results showed that Korean males and females had discrepancies in skeletal aging rates only in certain phases. A similar trend was observed in the comparison of the original Suchey-Brooks and Korean sample aging rates. However, when final age estimates were computed based on an inadequate choice of a prior, the between-group differences may be minimized or even obscured. The uniform and forensic priors produced the most reasonable and unbiased estimates, while the uniform prior consistently provided open-ended estimates for the last phase. The population prior produced consistently higher estimates due to the high survivorship of Koreans. In addition, the original Suchey-Brooks standards persistently under-estimated ages for Korean males and females. Overall, when Bayesian age estimation is based on an informed prior that best matches the context of the case (forensic deaths in this study), there was increased accuracy of final age estimates compared to age estimates of other priors and the original Suchey-Brooks method., Competing Interests: Conflict of interest Authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: The objectives of this study were to develop a multi-channel trans-impedance leadforming method for beat-to-beat stroke volume (SV) and breath-by-breath tidal volume (TV) measurements and assess its feasibility on an existing in vivo animal dataset., Methods: A deterministic leadforming algorithm was developed to extract a cardiac volume signal (CVS) and a respiratory volume signal (RVS) from 208-channel trans-impedance data acquired every 20 ms by an electrical impedance tomography (EIT) device. SV EIT and TV EIT values were computed as a valley-to-peak value in the CVS and RVS, respectively. The method was applied to the existing dataset from five mechanically-ventilated pigs undergoing ten mini-fluid challenges. An invasive hemodynamic monitor was used in the arterial pressure-based cardiac output (APCO) mode to simultaneously measure SV APCO values while a mechanical ventilator provided TV Vent values., Results: The leadforming method could reliably extract the CVS and RVS from the 208-channel trans-impedance data measured with the EIT device, from which SV EIT and TV EIT were computed. The SV EIT and TV EIT values were comparable to those from the invasive hemodynamic monitor and mechanical ventilator. Using the data from 5 pigs and a simple calibration method to remove bias, the error in SV EIT and TV EIT was 9.5% and 5.4%, respectively., Conclusion: We developed a new leadforming method for the EIT device to robustly extract both SV and TV values in a deterministic fashion. Future animal and clinical studies are needed to validate this leadforming method in various subject populations., Significance: The leadforming method could be an integral component for a new cardiopulmonary monitor in the future to simultaneously measure SV and TV noninvasively, which would be beneficial to patients.

Background: Thrombosis with thrombocytopenia syndrome (TTS) is a potentially life-threatening condition associated with adenoviral-vectored COVID-19 vaccination. It presents similarly to spontaneous heparin-induced thrombocytopenia. Twelve cases of cerebral venous sinus thrombosis after vaccination with the Ad26.COV2.S COVID-19 vaccine (Janssen/Johnson & Johnson) have previously been described., Objective: To describe surveillance data and reporting rates of all reported TTS cases after COVID-19 vaccination in the United States., Design: Case series., Setting: United States., Patients: Case patients receiving a COVID-19 vaccine from 14 December 2020 through 31 August 2021 with thrombocytopenia and thrombosis (excluding isolated ischemic stroke or myocardial infarction) reported to the Vaccine Adverse Event Reporting System. If thrombosis was only in an extremity vein or pulmonary embolism, a positive enzyme-linked immunosorbent assay for antiplatelet factor 4 antibodies or functional heparin-induced thrombocytopenia platelet test result was required., Measurements: Reporting rates (cases per million vaccine doses) and descriptive epidemiology., Results: A total of 57 TTS cases were confirmed after vaccination with Ad26.COV2.S ( n  = 54) or a messenger RNA (mRNA)-based COVID-19 vaccine ( n  = 3). Reporting rates for TTS were 3.83 per million vaccine doses (Ad26.COV2.S) and 0.00855 per million vaccine doses (mRNA-based COVID-19 vaccines). The median age of patients with TTS after Ad26.COV2.S vaccination was 44.5 years (range, 18 to 70 years), and 69% of patients were women. Of the TTS cases after mRNA-based COVID-19 vaccination, 2 occurred in men older than 50 years and 1 in a woman aged 50 to 59 years. All cases after Ad26.COV2.S vaccination involved hospitalization, including 36 (67%) with intensive care unit admission. Outcomes of hospitalizations after Ad26.COV2.S vaccination included death (15%), discharge to postacute care (17%), and discharge home (68%)., Limitations: Underreporting and incomplete case follow-up., Conclusion: Thrombosis with thrombocytopenia syndrome is a rare but serious adverse event associated with Ad26.COV2.S vaccination. The different demographic characteristics of the 3 cases reported after mRNA-based COVID-19 vaccines and the much lower reporting rate suggest that these cases represent a background rate., Primary Funding Source: Centers for Disease Control and Prevention.

The purpose of this study was to analyze the accuracy of intra oral scanner (IOS) to confirm the applicability of IOS for the recording and analysis of tooth morphology in forensics. The less damaged mandible specimen with many teeth remaining was scanned three times using three types of intraoral scanners (CS3600, i500, and Trios3). For quantitative comparisons of the scanned images produced by these intraoral scanners, root mean square (RMS) values were computed using a three-dimensional analysis program and a one-way ANOVA was conducted with Tukey HSD (honestly significant difference) as a post-hoc analysis (α=0.05). The repeatability of the full scan data was highest with the i500 (0.14±0.03 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 outcomes ( P -value=0.003). The repeatability of the partial scan data for the teeth in the mandible was highest with the i500 (0.08±0.02 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 ( P -value=0.016). The precision of the full scan data was highest with the i500 (0.16±0.01 mm) but the differences were not statistically significant ( P -value=0.091). Meanwhile, the precision of the partial scan data for the teeth in the mandible was highest with the Trios3 (0.22±0.02 mm), but the differences were not statistically significant ( P -value=0.762). Considering that the scanning of other areas of the oral cavity in addition to the teeth is important in forensic odontology, the i500 scanner appears to be the most appropriate intraoral scanner for human identification. However, as the scope of oral scanning is generally limited to teeth in the practice of dentistry, additional discussions of how to apply the IOS in forensic odontology are needed. Ultimately, the results here can contribute to the overall discussion of the forensic applicability dental data produced by intraoral scanners.

During September 22, 2021-February 6, 2022, approximately 82.6 million U.S. residents aged ≥18 years received a COVID-19 vaccine booster dose.* The Food and Drug Administration (FDA) has authorized a booster dose of either the same product administered for the primary series (homologous) or a booster dose that differs from the product administered for the primary series (heterologous). These booster authorizations apply to all three COVID-19 vaccines used in the United States (1-3). † The Advisory Committee on Immunization Practices (ACIP) recommended preferential use of an mRNA COVID-19 vaccine (mRNA-1273 [Moderna] or BNT162b2 [Pfizer-BioNTech]) for a booster, even for persons who received the Ad26.COV2.S (Janssen [Johnson & Johnson]) COVID-19 vaccine for their single-dose primary series. § To characterize the safety of COVID-19 vaccine boosters among persons aged ≥18 years during September 22, 2021-February 6, 2022, CDC reviewed adverse events and health impact assessments following receipt of a booster that were reported to v-safe, a voluntary smartphone-based safety surveillance system for adverse events after COVID-19 vaccination, and adverse events reported to the Vaccine Adverse Event Reporting System (VAERS), a passive vaccine safety surveillance system managed by CDC and FDA. Among 721,562 v-safe registrants aged ≥18 years who reported receiving a booster, 88.8% received homologous COVID-19 mRNA vaccination. Among registrants who reported a homologous COVID-19 mRNA booster dose, systemic reactions were less frequent following the booster (58.4% [Pfizer-BioNTech] and 64.4% [Moderna], respectively) than were those following dose 2 (66.7% and 78.4%, respectively). The adjusted odds of reporting a systemic reaction were higher following a Moderna COVID-19 vaccine booster, irrespective of the vaccine received for the primary series. VAERS has received 39,286 reports of adverse events after a COVID-19 mRNA booster vaccination for adults aged ≥18 years, including 36,282 (92.4%) nonserious and 3,004 (7.6%) serious events. Vaccination providers should educate patients that local and systemic reactions are expected following a homologous COVID-19 mRNA vaccine booster; however, these reactions appear less common than those following dose 2 of an mRNA-based vaccine. CDC and FDA will continue to monitor vaccine safety and provide data to guide vaccine recommendations and protect public health., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Philip G. Blanc reports stock ownership in Community Health Systems, Inc. No other potential conflicts of interest were reported.

Several natural substances including protein produce sweet taste. Brazzein, derived from the plant Pentadipladra brazzeana, is one of the sweet proteins that bind to the taste receptor with stronger sweetness than sugar. Mutations of this protein affect its flavour, yielding higher sweetness in D29K and lower sweetness in R43A. To elucidate its sweet mechanism in the taste receptor, we determined the structures of two variants, D29K and R43A, to a resolution of 1.5 Å and 1.3 Å, respectively. Structures of the brazzein exhibit two α-helix and three β-sheets connected by four disulfide bonds with a significantly altered electrostatic distribution on the surface. Using the high-resolution structure data and models of the taste receptors T1R2 and T1R3 in the AlphaFold Protein Structure Database, we performed a docking calculation on the receptors and report that brazzein is bound between the two cysteine rich domains (CRDs) of the heterodimer protein complex. Substitution to lysine in D29K resulted in an increased number of hydrogen bonds in the T1R2 receptor, while substitution to alanine in R43A ablated a polar interaction in the T1R3 receptor. The significantly altered interaction of the variants at the interface is consistent with a change of the sweetness. The high-resolution structure and the docking model in this study may provide a structural basis to understand the flavour mechanism induced by the sweet protein., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

On November 4, 2019, the Food and Drug Administration approved high-dose quadrivalent influenza vaccine (Fluzone High-Dose Quadrivalent; QIV-HD) for active immunization for the prevention of influenza disease in individuals 65 years of age and older. A prelicensure randomized, active-controlled, modified double-blind trial did not reveal any major differences in adverse events following QIV-HD versus Fluzone High-Dose (trivalent). To improve our understanding of the safety profile of QIV-HD, we reviewed and summarized reports of adverse events after QIV-HD to the Vaccine Adverse Event Reporting System (VAERS). From July 30, 2020 through June 30, 2021, VAERS received 2,122 reports after QIV-HD. The vast majority (2,018; 95.1%) were non-serious and included events that had been observed in the prelicensure clinical trial, such as injection site reactions, fever, headache, and nausea. The most common serious events included Guillain-Barré syndrome, cellulitis or other local reactions, constitutional signs/symptoms (e.g., fever), and cardiovascular events. Our review did not reveal any new safety concerns. This information may enable policy makers, health officials, clinicians, and patients to make a more informed decision regarding vaccination strategies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Maltodextrin glucosidase (MalZ) is a key enzyme in the maltose utilization pathway in Escherichia coli that liberates glucose from the reducing end of the short malto-oligosaccharides. Unlike other enzymes in the GH13_21 subfamily, the hydrolytic activity of MalZ is limited to maltodextrin rather than long starch substrates, forming various transglycosylation products in α-1,3, α-1,4 or α-1,6 linkages. The mechanism for the substrate binding and hydrolysis of this enzyme is not well understood yet. Here, we present the dimeric crystal structure of MalZ, with the N-domain generating a unique substrate binding groove. The N-domain bears CBM34 architecture and forms a part of the active site in the catalytic domain of the adjacent molecule. The groove found between the N-domain and catalytic domain from the adjacent molecule, shapes active sites suitable for short malto-oligosaccharides, but hinders long stretches of oligosaccharides. The conserved residue of E44 protrudes at subsite +2, elucidating the hydrolysis pattern of the substrate by the glucose unit from the reducing end. The structural analysis provides a molecular basis for the substrate specificity and the enzymatic property, and has potential industrial application for protein engineering., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The importance of perioperative respiration monitoring is highlighted by high incidences of postoperative respiratory complications unrelated to the original disease. The objectives of this pilot study were to (1) simultaneously acquire respiration rate (RR), tidal volume (TV), minute ventilation (MV), SpO 2 and PETCO 2 from patients in post-anesthesia care unit (PACU) and (2) identify a practical continuous respiration monitoring method by analyzing the acquired data in terms of their ability and reliability in assessing a patient's respiratory status. Thirteen non-intubated patients completed this observational study. A portable electrical impedance tomography (EIT) device was used to acquire RR EIT , TV and MV, while PETCO 2 , RR Cap and SpO 2 were measured by a Capnostream35. Hypoventilation and respiratory events, e.g., apnea and hypopnea, could be detected reliably using RR EIT , TV and MV. PETCO 2 and SpO 2 provided the gas exchange information, but were unable to detect hypoventilation in a timely fashion. Although SpO 2 was stable, the sidestream capnography using the oronasal cannula was often unstable and produced fluctuating PETCO 2 values. The coefficient of determination (R 2 ) value between RR EIT and RR Cap was 0.65 with a percentage error of 52.5%. Based on our results, we identified RR, TV, MV and SpO 2 as a set of respiratory parameters for robust continuous respiration monitoring of non-intubated patients. Such a respiration monitor with both ventilation and gas exchange parameters would be reliable and could be useful not only for respiration monitoring, but in making PACU discharge decisions and adjusting opioid dosage on general hospital floor. Future studies are needed to evaluate the potential clinical utility of such an integrated respiration monitor., (© 2021. The Author(s).)

Purpose: Breath-by-breath tidal volume (TV) and beat-by-beat stroke volume (SV) were continuously measured in patients with OSA undergoing polysomnography (PSG). The objectives were to (1) determine the changes in TV/SV in response to respiratory events and (2) assess the relationship between these changes and the disease severity., Methods: From the PSG data of nine patients with OSA, six different types of respiratory events were identified, i.e., flow limitation (FL), respiratory effort related arousal (RERA), hypopnea with arousal only (Ha), hypopnea with desaturation only (Hd), hypopnea with arousal and desaturation (Had), and apnea. The measured TV and SV values during and after each respiratory event were compared with the pre-event baseline values., Results: The mean TV/SV reductions during all hypopneas and apneas were 38.1%/4.2% and 70.5%/8.8%, respectively. Among three different hypopnea types, the reductions in TV during Hd and Had were significantly greater than those during Ha. The TV reductions during Ha and FL were similar. After RERA, Ha, Had, and apnea, there was an overshoot in TV and SV values, whereas there was no overshoot after FL and Hd. During RERA, there was no reduction in TV/SV., Conclusions: The changes in TV during and after each type of respiratory event were significantly different in most cases. The changes in SV between hypopnea and apnea were different with statistical significance. The AHI does not properly account for the ventilation losses caused by respiratory events. Thus, TV measurements might be useful in the future in assessing the OSA severity in conjunction with the AHI., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Abstract: Cardiac output (CO) is an important parameter in fluid management decisions for treating hemodynamically unstable patients in intensive care unit. The gold standard for CO measurements is the thermodilution method, which is an invasive procedure with intermittent results. Recently, electrical impedance tomography (EIT) has emerged as a new method for noninvasive measurements of stroke volume (SV). The objectives of this paper are to compare EIT with an invasive pulse contour analysis (PCA) method in measuring SV during mini-fluid challenge in animals and determine preload responsiveness with EIT. Five pigs were anesthetized and mechanically ventilated. After removing 25% to 30% of the total blood from each animal, multiple fluid injections were conducted. The EIT device successfully tracked changes in SV beat-to-beat during varying volume states, i.e., from hypovolemia and preload responsiveness to target volume and volume overload. From a total of 50 100-mL fluid injections on five pigs (10 injections per pig), the preload responsiveness value was as large as 32.3% in the preload responsiveness state while in the volume overload state it was as low as -4.9%. The bias of the measured SV data using EIT and PCA was 0 mL, and the limits of agreement were ±3.6 mL in the range of 17.6 mL to 51.0 mL. The results of the animal experiments suggested that EIT is capable of measuring beat-to-beat SV changes during mini-fluid challenge and determine preload responsiveness. Further animal and clinical studies will be needed to demonstrate the feasibility of the EIT method as a new tool for fluid management., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)

Hereditary Spastic Paraplegias (HSP) are a group of rare inherited neurological disorders characterized by progressive loss of corticospinal motor-tract function. Numerous patients with HSP remain undiagnosed despite screening for known genetic causes of HSP. Therefore, identification of novel genetic variations related to HSP is needed. In this study, we identified 88 genetic variants in 54 genes from whole-exome data of 82 clinically well-defined Korean HSP families. Fifty-six percent were known HSP genes, and 44% were composed of putative candidate HSP genes involved in the HSPome and originally reported neuron-related genes, not previously diagnosed in HSP patients. Their inheritance modes were 39, de novo; 33, autosomal dominant; and 10, autosomal recessive. Notably, ALDH18A1 showed the second highest frequency. Fourteen known HSP genes were firstly reported in Koreans, with some of their variants being predictive of HSP-causing protein malfunction. SPAST and REEP1 mutants with unknown function induced neurite abnormality. Further, 54 HSP-related genes were closely linked to the HSP progression-related network. Additionally, the genetic spectrum and variation of known HSP genes differed across ethnic groups. These results expand the genetic spectrum for HSP and may contribute to the accurate diagnosis and treatment for rare HSP., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: As part of postauthorization safety surveillance, the US Food and Drug Administration (FDA) has identified a potential safety concern for Guillain-Barré syndrome (GBS) following receipt of the Ad26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccine., Objective: To assess reports of GBS received in the Vaccine Adverse Event Reporting System (VAERS) following Ad26.COV2.S vaccination., Design, Setting, and Participants: Reports of presumptive GBS were identified in a US passive reporting system (VAERS) February-July 2021 and characterized, including demographics, clinical characteristics, and relevant medical history., Exposures: Receipt of the Ad26.COV2.S vaccine; the comparator was the background rate of GBS in the general (unvaccinated) population that had been estimated and published based on a standardized case definition., Main Outcomes and Measures: Presumptive GBS; the reporting rate was analyzed, including calculation of the observed to expected ratio based on background rates and vaccine administration data. Because of limited availability of medical records, cases were not assessed according to the Brighton Collaboration criteria for GBS., Results: As of July 24, 2021, 130 reports of presumptive GBS were identified in VAERS following Ad26.COV2.S vaccination (median age, 56 years; IQR, 45-62 years; 111 individuals [86.0%] were < 65 years; 77 men [59.7%]). The median time to onset of GBS following vaccination was 13 days (IQR, 10-18 days), with 105 cases (81.4%) beginning within 21 days and 123 (95.3%) within 42 days. One hundred twenty-one reports (93.1%) were serious, including 1 death. With approximately 13 209 858 doses of vaccine administered to adults in the US, the estimated crude reporting rate was 1 case of GBS per 100 000 doses administered. The overall estimated observed to expected rate ratio was 4.18 (95% CI, 3.47-4.98) for the 42-day window, and in the worst-case scenario analysis for adults 18 years or older, corresponded to an estimated absolute rate increase of 6.36 per 100 000 person-years (based on a rate of approximately 8.36 cases per 100 000 person-years [123 cases per 1 472 162 person-years] compared with a background rate of approximately 2 cases per 100 000 person-years). For both risk windows, the observed to expected rate ratio was elevated in all age groups except individuals aged 18 through 29 years., Conclusions and Relevance: These findings suggest a potential small but statistically significant safety concern for Guillain-Barré syndrome following receipt of the Ad26.COV2.S vaccine. However, the findings are subject to the limitations of passive reporting systems and presumptive case definition, and they must be considered preliminary pending analysis of medical records to establish a definitive diagnosis.

In December 2020, the Food and Drug Administration (FDA) issued Emergency Use Authorizations (EUAs) for Pfizer-BioNTech and Moderna COVID-19 vaccines, and in February 2021, FDA issued an EUA for the Janssen (Johnson & Johnson) COVID-19 vaccine. After each EUA, the Advisory Committee on Immunization Practices (ACIP) issued interim recommendations for vaccine use; currently Pfizer-BioNTech is authorized and recommended for persons aged ≥12 years and Moderna and Janssen for persons aged ≥18 years (1-3). Both Pfizer-BioNTech and Moderna vaccines, administered as 2-dose series, are mRNA-based COVID-19 vaccines, whereas the Janssen COVID-19 vaccine, administered as a single dose, is a recombinant replication-incompetent adenovirus-vector vaccine. As of July 22, 2021, 187 million persons in the United States had received at least 1 dose of COVID-19 vaccine (4); close monitoring of safety surveillance has demonstrated that serious adverse events after COVID-19 vaccination are rare (5,6). Three medical conditions have been reported in temporal association with receipt of COVID-19 vaccines. Two of these (thrombosis with thrombocytopenia syndrome [TTS], a rare syndrome characterized by venous or arterial thrombosis and thrombocytopenia, and Guillain-Barré syndrome [GBS], a rare autoimmune neurologic disorder characterized by ascending weakness and paralysis) have been reported after Janssen COVID-19 vaccination. One (myocarditis, cardiac inflammation) has been reported after Pfizer-BioNTech COVID-19 vaccination or Moderna COVID-19 vaccination, particularly after the second dose; these were reviewed together and will hereafter be referred to as mRNA COVID-19 vaccination. ACIP has met three times to review the data associated with these reports of serious adverse events and has comprehensively assessed the benefits and risks associated with receipt of these vaccines. During the most recent meeting in July 2021, ACIP determined that, overall, the benefits of COVID-19 vaccination in preventing COVID-19 morbidity and mortality outweigh the risks for these rare serious adverse events in adults aged ≥18 years; this balance of benefits and risks varied by age and sex. ACIP continues to recommend COVID-19 vaccination in all persons aged ≥12 years. CDC and FDA continue to closely monitor reports of serious adverse events and will present any additional data to ACIP for consideration. Information regarding risks and how they vary by age and sex and type of vaccine should be disseminated to providers, vaccine recipients, and the public., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Nicola P. Klein reports institutional research support from Pfizer, Sanofi Pasteur, Merck, GlaxoSmithKline, and Protein Science (now Sanofi Pasteur). No other potential conflicts of interest were disclosed.

Purpose: To establish high-frequency magnetic resonance electrical properties tomography (MREPT) as a novel contrast mechanism for the assessment of glioblastomas using a rat brain tumor model., Methods: Six F98 intracranial tumor bearing rats were imaged longitudinally 8, 11 and 14 days after tumor cell inoculation. Conductivity and mean diffusivity maps were generated using MREPT and Diffusion Tensor Imaging. These maps were co-registered with T 2 -weighted images and volumes of interests (VOIs) were segmented from the normal brain, ventricles, edema, viable tumor, tumor rim, and tumor core regions. Longitudinal changes in conductivity and mean diffusivity (MD) values were compared in these regions. A correlation analysis was also performed between conductivity and mean diffusivity values., Results: The conductivity of ventricles, edematous area and tumor regions (tumor rim, viable tumor, tumor core) was significantly higher (P < .01) compared to the contralateral cortex. The conductivity of the tumor increased over time while MD from the tumor did not change. A marginal positive correlation was noted between conductivity and MD values for tumor rim and viable tumor, whereas this correlation was negative for the tumor core., Conclusion: We demonstrate a novel contrast mechanism based on ionic concentration and mobility, which may aid in providing complementary information to water diffusion in probing the microenvironment of brain tumors., (© 2021 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)