Peripheral vestibular loss in noise-exposed firefighters.

Introduction: Occupational workers are increasingly aware of the risk of noise overexposure to the auditory system but lack awareness about potential risks to the vestibular system. The purpose of this study was to investigate changes in vestibular end organ function in a known at-risk noise-exposed population, firefighters compared to age- and sex-matched controls using electrophysiologic measures of cervical vestibular evoked myogenic potentials (cVEMP). Methods: A cross-sectional observational study compared cVEMP response characteristics in 38 noise-exposed firefighters. Firefighters were grouped by years of exposure in the fire service. The cVEMP responses were compared within firefighter groups and between firefighters and age- and sex-matched controls. Dependent variables included the response characteristics of amplitude, latency and threshold. Results: cVEMP response amplitudes were significantly decreased in firefighters compared to their age- and sex-matched controls. Threshold of the cVEMP responses were significantly higher in firefighters compared to controls and firefighters had a higher incidence of absent cVEMP responses compared to controls. Response amplitudes decreased with increasing years in the fire-service at an increased rate compared to their age- and sex-matched controls. Latency of the cVEMP response was not significantly different in firefighters compared to controls. These findings are consistent with both animal and human studies suggesting noise-induced changes in the sacculocollic pathway. Discussion: In the absence of any reported vestibular symptoms or auditory indicators of noise-induced hearing loss, these early effects on the vestibular system point to a potential hidden vestibular loss.

Infection clusters can elevate risk of diagnostic target failure for detection of SARS-CoV-2.

The C29197T mutation is one of 4 point mutations known to cause N-gene target failure (NGTF) in the Xpert Xpress SARS-CoV-2 and Xpert Omni SARS-CoV-2 assays from Cepheid (Sunnyvale, CA). We describe a high local prevalence in January of 8.5% (CI 4.9-14.2%) for the C29197T mutation, which was over 3-fold higher than the prevalence estimated statewide in California during the same time frame, 2.5% (CI 2.1-2.8%). Using phylogenetic analysis, we discovered that this increase in prevalence was due, at least in part, to a disproportionately large infection cluster of unknown origin. This study emphasizes the importance of sequencing at the local jurisdictional level and demonstrates the impact that regional variation can have when assessing risk due to point mutations that impact clinical test performance. It also reinforces the need for diligent reporting of abnormal test results by clinical laboratories, especially during Emergency Use Authorization (EUA) periods, as additional information is gathered about the target organism and the performance of EUA-authorized tests over time.

Safety and immunogenicity of an AS03-adjuvanted SARS-CoV-2 recombinant protein vaccine (CoV2 preS dTM) in healthy adults: interim findings from a phase 2, randomised, dose-finding, multicentre study.

BACKGROUND: We evaluated our SARS-CoV-2 prefusion spike recombinant protein vaccine (CoV2 preS dTM) with different adjuvants, unadjuvanted, and in a one-injection and two-injection dosing schedule in a previous phase 1-2 study. Based on interim results from that study, we selected a two-injection schedule and the AS03 adjuvant for further clinical development. However, lower than expected antibody responses, particularly in older adults, and higher than expected reactogenicity after the second vaccination were observed. In the current study, we evaluated the safety and immunogenicity of an optimised formulation of CoV2 preS dTM adjuvanted with AS03 to inform progression to phase 3 clinical trial. METHODS: This phase 2, randomised, parallel-group, dose-ranging study was done in adults (≥18 years old), including those with pre-existing medical conditions, those who were immunocompromised (except those with recent organ transplant or chemotherapy) and those with a potentially increased risk for severe COVID-19, at 20 clinical research centres in the USA and Honduras. Women who were pregnant or lactating or, for those of childbearing potential, not using an effective method of contraception or abstinence, and those who had received a COVID-19 vaccine, were excluded. Participants were randomly assigned (1:1:1) using an interactive response technology system, with stratification by age (18-59 years and ≥60 years), rapid serodiagnostic test result (positive or negative), and high-risk medical conditions (yes or no), to receive two injections (day 1 and day 22) of 5 7mu;g (low dose), 10 7mu;g (medium dose), or 15 7mu;g (high dose) CoV2 preS dTM antigen with fixed AS03 content. All participants and outcome assessors were masked to group assignment; unmasked study staff involved in vaccine preparation were not involved in safety outcome assessments. All laboratory staff performing the assays were masked to treatment. The primary safety objective was to describe the safety profile in all participants, for each candidate vaccine formulation. Safety endpoints were evaluated for all randomised participants who received at least one dose of the study vaccine (safety analysis set), and are presented here for the interim study period (up to day 43). The primary immunogenicity objective was to describe the neutralising antibody titres to the D614G variant 14 days after the second vaccination (day 36) in participants who were SARS-CoV-2 naive who received both injections, provided samples at day 1 and day 36, did not have protocol deviations, and did not receive an authorised COVID-19 vaccine before day 36. Neutralising antibodies were measured using a pseudovirus neutralisation assay and are presented here up to 14 days after the second dose. As a secondary immunogenicity objective, we assessed neutralising antibodies in non-naive participants. This trial is registered with ClinicalTrials.gov (NCT04762680) and is closed to new participants for the cohort reported here. FINDINGS: Of 722 participants enrolled and randomly assigned between Feb 24, 2021, and March 8, 2021, 721 received at least one injection (low dose=240, medium dose=239, and high dose=242). The proportion of participants reporting at least one solicited adverse reaction (injection site or systemic) in the first 7 days after any vaccination was similar between treatment groups (217 [91%] of 238 in the low-dose group, 213 [90%] of 237 in the medium-dose group, and 218 [91%] of 239 in the high-dose group); these adverse reactions were transient, were mostly mild to moderate in intensity, and occurred at a higher frequency and intensity after the second vaccination. Four participants reported immediate unsolicited adverse events; two (one each in the low-dose group and medium-dose group) were considered by the investigators to be vaccine related and two (one each in the low-dose and high-dose groups) were considered unrelated. Five participants reported seven vaccine-related medically attended adverse events (two in the low-dose group, one in the medium-dose group, and four in the high-dose group). No vaccine-related serious adverse events and no adverse events of special interest were reported. Among participants naive to SARS-CoV-2 at day 36, 158 (98%) of 162 in the low-dose group, 166 (99%) of 168 in the medium-dose group, and 163 (98%) of 166 in the high-dose group had at least a two-fold increase in neutralising antibody titres to the D614G variant from baseline. Neutralising antibody geometric mean titres (GMTs) at day 36 for participants who were naive were 2189 (95% CI 1744-2746) for the low-dose group, 2269 (1792-2873) for the medium-dose group, and 2895 (2294-3654) for the high-dose group. GMT ratios (day 36: day 1) were 107 (95% CI 85-135) in the low-dose group, 110 (87-140) in the medium-dose group, and 141 (111-179) in the high-dose group. Neutralising antibody titres in non-naive adults 21 days after one injection tended to be higher than titres after two injections in adults who were naive, with GMTs 21 days after one injection for participants who were non-naive being 3143 (95% CI 836-11 815) in the low-dose group, 2338 (593-9226) in the medium-dose group, and 7069 (1361-36 725) in the high-dose group. INTERPRETATION: Two injections of CoV2 preS dTM-AS03 showed acceptable safety and reactogenicity, and robust immunogenicity in adults who were SARS-CoV-2 naive and non-naive. These results supported progression to phase 3 evaluation of the 10 7mu;g antigen dose for primary vaccination and a 5 7mu;g antigen dose for booster vaccination. FUNDING: Sanofi Pasteur and Biomedical Advanced Research and Development Authority.

Severe Acute Respiratory Syndrome Coronavirus 2 and Respiratory Virus Sentinel Surveillance, California, USA, May 10, 2020-June 12, 2021.

State and local health departments established the California Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and Respiratory Virus Sentinel Surveillance System to conduct enhanced surveillance for SARS-CoV-2 and other respiratory pathogens at sentinel outpatient testing sites in 10 counties throughout California, USA. We describe results obtained during May 10, 2020‒June 12, 2021, and compare persons with positive and negative SARS-CoV-2 PCR results by using Poisson regression. We detected SARS-CoV-2 in 1,696 (19.6%) of 8,662 specimens. Among 7,851 specimens tested by respiratory panel, rhinovirus/enterovirus was detected in 906 (11.5%) specimens and other respiratory pathogens in 136 (1.7%) specimens. We also detected 23 co-infections with SARS-CoV-2 and another pathogen. SARS-CoV-2 positivity was associated with male participants, an age of 35-49 years, Latino race/ethnicity, obesity, and work in transportation occupations. Sentinel surveillance can provide useful virologic and epidemiologic data to supplement other disease monitoring activities and might become increasingly useful as routine testing decreases.

Knowledge, attitudes, intentions, and behavior related to green infrastructure for flood management: A systematic literature review.

Green infrastructure (GI), which mimics natural hydrological systems, is a promising solution for flood management at the intersection of urban built infrastructure and natural systems. However, it has not yet achieved widespread uptake, due in part to insufficient understanding of human dimensions of the broader socio-ecological-technical system. We therefore conducted a multidisciplinary systematic literature review to synthesize research on people's existing knowledge about flood risk and GI, and how that shapes their attitudes and motivation to adopt new solutions. We systematically screened 21,207 studies on GI for flood management; 85 met our inclusion criteria. We qualitatively analyzed these studies to extract results on knowledge, attitudes, intentions, and behavior relating to GI for flood management. Overall, knowledge of GI was low across the 44 studies in which it was evaluated. Seventy studies assessed attitudes about GI, including the functional, aesthetic, health and safety, recreational, conservation, financial, and cultural value of GI, albeit their measurement was inconsistent. Willingness to implement or pay for GI varied considerably across 55 studies in which it was measured. Twenty studies measured and documented behavior relating to GI use, and these found low rates of adoption. Few studies systematically assessed the role of demographic, socio-economic, or geographic characteristics that could influence individuals' knowledge, attitudes, intentions or behavior, and thereby the success of GI programs. We recommend that researchers should more systematically capture data on human dimensions of GI (i.e. knowledge, attitudes, intentions, and behavior) across diverse settings to improve program design and uptake, especially among vulnerable populations. Greater attention to the social component of the socio-ecological-technical system will help ensure that GI programs are equitable, inclusive, and sustainable.

A systematic review of the human health and social well-being outcomes of green infrastructure for stormwater and flood management.

BACKGROUND: The increase in frequency and intensity of urban flooding is a global challenge. Flooding directly impacts residents of industrialized cities with aging combined sewer systems, as well as cities with less centralized infrastructure to manage stormwater, fecal sludge, and wastewater. Green infrastructure is growing in popularity as a sustainable strategy to mimic nature-based flood management. Although its technical performance has been extensively studied, little is known about the effects of green stormwater infrastructure on human health and social well-being. METHODS: We conducted a multidisciplinary systematic review of peer-reviewed and gray literature on the effects of green infrastructure for stormwater and flood management on individuals', households', and communities' a) physical health; b) mental health; c) economic well-being; and d) flood resilience and social acceptance of green infrastructure. We systematically searched databases such as PubMed, Web of Science, and Scopus; the first 300 results in Google Scholar; and websites of key organizations including the United States Environmental Protection Agency. Study quality and strength of evidence was assessed for included studies, and descriptive data were extracted for a narrative summary. RESULTS: Out of 21,213 initial results, only 18 studies reported health or social well-being outcomes. Seven of these studies used primary data, and none allowed for causal inference. No studies connected green infrastructure for stormwater and flood management to mental or physical health outcomes. Thirteen studies were identified on economic outcomes, largely reporting a positive association between green infrastructure and property values. Five studies assessed changes in perceptions about green infrastructure, but with mixed results. Nearly half of all included studies were from Portland, Oregon. CONCLUSIONS: This global systematic review highlights the minimal evidence on human health and social well-being relating to green infrastructure for stormwater and flood management. To enable scale-up of this type of infrastructure to reduce flooding and improve ecological and human well-being, widespread acceptance of green infrastructure will be essential. Policymakers and planners need evidence on the full range of benefits from different contexts to enable financing and implementation of instfrastructure options, especially in highly urbanized, flood-prone settings around the world. Therefore, experts in social science, public health, and program evaluation must be integrated into interdisciplinary green infrastructure research to better relate infrastructure design to tangible human outcomes.

The Recognition, Incidence, and Management of Spinal Cord Monitoring Alerts in Pediatric Cervical Spine Surgery.

BACKGROUND: Perioperative spinal cord injury and postoperative neurological deficits are the major complications in spinal surgery. Monitoring of spinal cord function is of crucial importance. Somatosensory evoked potentials and transcranial electric motor-evoked potentials are now widely used in cervical spine surgery. Although much has been written on spinal cord monitoring in adult spinal surgery, very little has been published on the incidence and management of monitoring of cervical spine surgery in the pediatric population. The goal of this research was to review the recognition, incidence, and management of spinal cord monitoring in pediatric patients undergoing cervical spine surgery over the course of twenty years in a single institution. We postulate spinal cord monitoring alerts in pediatric cervical spine surgery are underreported. METHODS: An IRB-approved retrospective single institution review of pediatric cervical spine cases from 1997 to 2017 was performed. Both the surgeon's dictated operative note and the neuromonitoring team's dictated note were reviewed for each case, and both were cross referenced and correlated with one another to ensure no alerts were missed. All monitoring changes were assumed to be significant and reported. The incidence of alerts, type of changes, and corrective maneuvers were noted. New postoperative neurological injuries were recorded. RESULTS: From 1997 to 2017 fifty-three patients underwent a total of 69 procedures involving the cervical spine. Fourteen procedures (20%) were not monitored, whereas 55 procedures were 80%. There were 12 procedures (21.8%) complicated by neuromonitoring alerts. CONCLUSIONS: The number of cases complicated by alerts doubles that previously reported, and it is important to note there were no new permanent neurological deficits recorded over the study period. Corrective strategies were implemented once the operating surgeon was notified of the neuromonitoring alert. Aborting the case was then considered if corrective strategies failed to restore baseline neurophysiology. LEVEL OF EVIDENCE: Level IV.

Mini review: New pathogen profiles: Elizabethkingia anophelis.

Within a little more than 5 years since its taxonomic description in 2011, from the midgut of mosquitoes, Elizabethkingia anophelis has emerged as an important causes of sepsis in adults and children and in cases of neonatal meningitis. At least 3 moderate- to large-scale outbreaks of disease have been caused by this bacterium, the largest 2 occurring in the Midwest United States in 2015-2016. Several studies suggest that E. anophelis, and not E. meningoseptica, is the predominant human pathogen of this genus; identification to species is difficult. Little is presently known regarding its epidemiology, modes of transmission, and pathogenicity as it relates to virulence-associated factors.

The Recognition, Incidence, and Management of Spinal Cord Monitoring Alerts in Early-onset Scoliosis Surgery.

BACKGROUND: The objective of the research was to study the relevance of intraoperative neuromonitoring throughout all stages of surgical management in patients with progressive early-onset scoliosis (EOS).The routine monitoring of spinal cord potentials has gradually become standard of practice among spinal surgeons. However, there is not a consensus that the added expense of this technique necessitates monitoring in all stages of surgical management. METHODS: A retrospective review of 180 surgical cases of 30 patients with EOS from July 2003 to July 2012 was performed. All monitoring alerts as judged by the neuromonitoring team were identified. Both somatosensory-evoked potentials and transcranial electric motor-evoked potentials were studied and no limiting thresholds for reporting electrophysiological changes were deemed appropriate. RESULTS: Of 150 monitored cases there were 18 (12%) monitoring alerts. This represented 40% of the patient cohort over the 9-year study period. CONCLUSIONS: Index versus routine lengthening rate of alerts showed no significant difference in incidence of monitoring alerts. Conversely, several patients whose primary implantation surgeries were uneventful had monitoring alerts later in their treatment course. Intraoperative neuromonitoring is warranted throughout all stages of surgical management of EOS. LEVEL OF EVIDENCE: Level IV. This study is a retrospective review of surgical cases of 30 patients with EOS.

Alterations in regulatory T cell subpopulations seen in preterm infants.

Regulatory T cells are a population of CD4+ T cells that play a critical role in peripheral tolerance and control of immune responses to pathogens. The purpose of this study was to measure the percentages of two different regulatory T cells subpopulations, identified by the presence or absence of CD31 (Recent thymic emigrants and peripherally induced naïve regulatory T cells), in term and preterm infant cord blood. We report the association of prenatal factors, intrauterine exposure to lipopolysaccharide and inflammation and the percentages of these regulatory T cell subpopulations in term and preterm infants. Cord blood samples were collected from both term and preterm infants and mononuclear cells isolated over a Ficoll-Hypaque cushion. Cells were then stained with fluorochrome-labeled antibodies to characterize regulatory T cell populations and analyzed with multi-color flow cytometry. Cord blood plasma C-reactive protein, and lipopolysaccharide were also measured. Placental pathology was also examined. We report a gestational age-dependent difference in the percentage of total regulatory T cells, in which preterm infants of lower gestational ages have an increased percentage of regulatory T cells. We report the presence of two populations of regulatory T cells (CD31+ and CD31-) in cord blood of term and preterm infants and their association with different maternal and fetal characteristics. Factors associated with differences in the percentage of CD31- Tregs included the use of prenatal antibiotics, steroids and magnesium sulfate. In addition, the percentage of CD31- Tregs was significantly higher in cord blood of preterm pregnancies associated with inflammation and prenatal lipopolysaccharide exposure. The peripheral Treg pool of preterm infants could be altered by prenatal exposure to inflammation and chorioamnionitis; however, the clinical implications of this finding are not yet understood.

Lipopolysaccharide and soluble CD14 in cord blood plasma are associated with prematurity and chorioamnionitis.

BACKGROUND: Lipopolysaccharide (LPS), an endotoxin of Gram-negative bacteria, causes preterm birth in animals and has been implicated as a factor triggering preterm labor and systemic complications in humans. Little is known regarding LPS in the cord blood (CB) of term and preterm infants and its association with maternal and fetal characteristics. METHODS: CB was obtained from term (n = 15) and preterm infants (n = 76) after delivery. Plasma levels of LPS, C-reactive protein (CRP), and soluble CD14 (sCD14) were measured using commercially available kits (limulus amebocyte lysate and enzyme-linked immunosorbent assay). Four linear regression models were created in order to identify independent variables that predict plasma LPS levels. RESULTS: The analyte levels were significantly higher in preterm vs. term infant CB: LPS (24.48 vs. 1 pg/ml; P = 0.0009), CRP (87.9 vs. 47 ng/ml; P = 0.01), and sCD14 (0.32 vs.0.35 µg/ml; P = 0.013). There was a (significant) positive correlation between CB LPS levels and gestational age, birth weight, CRP levels, sCD14 levels, and association with both clinical and histological chorioamnionitis. CONCLUSION: Our data suggest that LPS is associated with preterm labor and inflammation (CRP elevation and chorioamnionitis). These findings may be relevant to the understanding of the role of LPS in prematurity and its role in preterm morbidities.

Responses of human endothelial cells to pathogenic and non-pathogenic Leptospira species.

Leptospirosis is a widespread zoonotic infection that primarily affects residents of tropical regions, but causes infections in animals and humans in temperate regions as well. The agents of leptospirosis comprise several members of the genus Leptospira, which also includes non-pathogenic, saprophytic species. Leptospirosis can vary in severity from a mild, non-specific illness to severe disease that includes multi-organ failure and widespread endothelial damage and hemorrhage. To begin to investigate how pathogenic leptospires affect endothelial cells, we compared the responses of two endothelial cell lines to infection by pathogenic versus non-pathogenic leptospires. Microarray analyses suggested that pathogenic L. interrogans and non-pathogenic L. biflexa triggered changes in expression of genes whose products are involved in cellular architecture and interactions with the matrix, but that the changes were in opposite directions, with infection by L. biflexa primarily predicted to increase or maintain cell layer integrity, while L. interrogans lead primarily to changes predicted to disrupt cell layer integrity. Neither bacterial strain caused necrosis or apoptosis of the cells even after prolonged incubation. The pathogenic L. interrogans, however, did result in significant disruption of endothelial cell layers as assessed by microscopy and the ability of the bacteria to cross the cell layers. This disruption of endothelial layer integrity was abrogated by addition of the endothelial protective drug lisinopril at physiologically relevant concentrations. These results suggest that, through adhesion of L. interrogans to endothelial cells, the bacteria may disrupt endothelial barrier function, promoting dissemination of the bacteria and contributing to severe disease manifestations. In addition, supplementing antibiotic therapy with lisinopril or derivatives with endothelial protective activities may decrease the severity of leptospirosis.

Infantile kyphosis secondary to lumbar hypoplasia: six cases with excessive upright sleeping as a possible cause.

Abnormal thoracolumbar kyphosis in infants may be due to lumbar hypoplasia that resolves with development of upright posture. The cause of this deformity has not been previously identified. The goal of this study was to find whether excessive time in an upright posture while sleeping and sitting may play a role in the etiology of infantile thoracolumbar kyphosis. We retrospectively reviewed infants with the diagnosis of kyphosis from 2001 to 2005. Inclusion criteria were patients diagnosed prior to age 3 years without syndromic, neuromuscular, or congenital kyphosis and minimum 2-year follow-up. Serial radiographic evaluation was used to assess change in kyphotic deformity. Six infants with an average age of 7 months at the time of diagnosis were identified. All had marked thoracolumbar kyphosis with vertebral wedging and scalloping. Some had pseudosubluxation at the T12-L1 level. The initial average Cobb angle was 30° (normal, 0°-5°). Careful history revealed that all patients slept in an upright posture in addition to sitting while awake. All of the patients were observed following parental instruction in proper sleeping and sitting habits. At last follow-up, all patients had normal sagittal alignment with an average Cobb angle of 1.3°. Proper sleeping and sitting habits with good spine support is recommended for infantile thoracolumbar kyphosis with lumbar hypoplasia. Allowing "tummy time" during waking hours may help the paraspinal muscles gain strength to provide support to the spine. Radiographic evidence of vertebral body height restoration may be delayed for several years.

Mycobacterium smegmatis mc2 155 fbiC and MSMEG_2392 are involved in triphenylmethane dye decolorization and coenzyme F420 biosynthesis.

Mycobacteria can tolerate relatively high concentrations of triphenylmethane dyes such as malachite green and methyl violet. To identify mycobacterial genes involved in the decolorization of malachite green, a transposon mutant library of Mycobacterium smegmatis mc2 155 was screened for mutants unable to decolorize this dye. One of the genes identified was MSMEG_5126, an orthologue of Mycobacterium bovis fbiC encoding a 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) synthase, which is essential for the biosynthesis of the electron carrier coenzyme F420. The other gene identified was MSMEG_2392, encoding an alanine-rich protein with a DUF121 domain. The minimum inhibitory concentrations (MICs) for malachite green and methyl violet of the six fbiC mutants and two MSMEG_2392 mutants were one-third and one-fifth, respectively, of the MIC of the parent strain M. smegmatis mc2 155. Representative fbiC and MSMEG_2392 mutant strains were also sensitive to oxidative stress caused by the redox-cycling agents plumbagin and menadione, and the sensitivity was reversed in the complemented strains. HPLC analysis of representative fbiC and MSMEG_2392 strains revealed that, while the fbiC mutant lacked both coenzyme F420 and FO, the MSMEG_2392 mutant contained FO but not coenzyme F420. These results indicate that MSMEG_2392 is involved in the biosynthesis of coenzyme F420.