Fundamental Biological Features of Spaceflight: Advancing the Field to Enable Deep-Space Exploration.

Research on astronaut health and model organisms have revealed six features of spaceflight biology that guide our current understanding of fundamental molecular changes that occur during space travel. The features include oxidative stress, DNA damage, mitochondrial dysregulation, epigenetic changes (including gene regulation), telomere length alterations, and microbiome shifts. Here we review the known hazards of human spaceflight, how spaceflight affects living systems through these six fundamental features, and the associated health risks of space exploration. We also discuss the essential issues related to the health and safety of astronauts involved in future missions, especially planned long-duration and Martian missions.

Assessment of barrier treatments impacting Aedes albopictus (diptera: culicidae) using lambda-cyhalothrin and pyriproxyfen in a suburban neighborhood in Eastern North Carolina, 2018.

Pyrethroids are commonly used in barrier treatments but less is known about how mosquitoes are affected by the simultaneous application of an insect growth regulator (i.e., pyriproxyfen) used in barrier treatments. This field study, conducted from May 14 - October 16, 2018, evaluated the effect of lambda-cyhalothrin (pyrethroid adulticide) and pyriproxyfen on the reproduction (measured by fecundity and adult emergence) and abundance of Aedes albopictus. Nine properties were treated with Demand®CS 0.06% + Archer® 0.010% (every 60 days) and three control properties received no treatment (N=12 total properties). No significant (P>0.05) differences were observed between abundance of Ae. albopictus in treatment compared to control groups. However, significant differences were observed in abundance of Ae. albopictus adults between weeks at both control (P = 0.003) and treatment (P < 0.0001) properties. Results from our research show that continued studies are needed to determine the efficacy of barrier treatments for this species. .

Occupational exposure to solar ultraviolet radiation in an eastern North Carolina university outdoor setting during the four seasons.

Outdoor workers perform tasks throughout the year that expose them to solar ultraviolet radiation (UVR) and increase their risk of UVR-related adverse health effects. Multiple studies on occupational solar UVR exposures during summer have been published but similar investigations during other seasons are limited. The purpose of this study was to assess solar UVR exposure in an eastern North Carolina university setting during all four seasons (fall, winter, spring, and summer) to assess risk for outdoor workers, particularly groundskeepers, throughout the year. UVR effective irradiance (UVReff) was measured by area monitoring using a digital data-logging radiometer and a weatherproof UVR detector for 164 days from October 2020 to October 2021. Results showed that hourly and daily mean UVReff exceeded the 1-hr and 8-hr ACGIH Threshold Limit Values (TLVs), respectively, in all months and seasons at varying degrees. Winter had the lowest mean UVReff (3.4 × 10-3 ± 1.7 × 10-3 mW/cm2), but 91.1% and 100% of the hourly and daily UVReff measurements, respectively, still exceeded the TLVs. This study demonstrates the risk of overexposure to solar UVR among outdoor workers during cold months and seasons and the importance of implementing UVR protection throughout the year.

Pneumococcal IgG Antibody Responses to 23vPPV in Healthy Controls Using an Automated ELISA.

Measurement of pre- and post-pneumococcal antibody levels after immunization with the 23-valent capsular polysaccharide pneumococcal vaccine (23vPPV) is indicative of a T-independent antibody response. The World Health Organisation ELISA is considered gold standard yet is labor-intensive and technically difficult to perform. Interpretation criteria defining an adequate response to 23vPPV remain controversial. The diagnostic Immunology Laboratory at The Royal Children's Hospital, Melbourne (RCH), performs an in-house multi-serotype automated ELISA. The primary objective of this study was to verify RCH interpretation criteria for the laboratory's automated ELISA. Forty pneumococcal conjugate vaccine (PCV)-naïve healthy adults aged 18 to 25 years and 22 PCV-primed healthy children aged 2 to 5 years were immunized with 23vPPV. A serum sample was collected immediately prior and 28 to 42 (± 7) days post immunization. Samples were analyzed on the Tecan Freedom Evo 200 ELISA with adequate response defined as post-immunization antibody level of 1.3 µg/mL or fourfold rise from baseline in ≥ 10/15 serotypes in adult participants and ≥ 4/8 serotypes in pediatric participants. Thirty-nine (97.5%) adults and 22 (100%) children achieved an adequate response to 23vPPV. In PCV-naïve adults, serotypes contained within the conjugate vaccines were less immunogenic, with 12 (30%) adults not achieving an adequate antibody response when only PCV serotypes were used for interpretation. Our diagnostic laboratory has verified the interpretation criteria used for an automated multi-serotype pneumococcal ELISA method. Clinical Trial Registration: ANZCTR registration number ACTRN12618000822280.

Operational Insights Into Mosquito Control Disaster Response in Coastal North Carolina: Experiences With the Federal Emergency Management Agency After Hurricane Florence.

Preparation for post-hurricane mosquito control is essential for an effective emergency response to protect public health and promote recovery efforts. Effective pre-hurricane planning includes laying the groundwork for a successful reimbursement application to the Federal Emergency Management Agency. The critical and overlapping need to sustain funding for mosquito control programs is highlighted here in the context of both normal and emergency responses. Community support is an integral component of an effective integrated pest management program and is established over time with appropriate communication and engagement. Experienced mosquito control operators who are familiar with treatment areas are an essential component of successful operations. Here, practical advice is provided to plan, prepare, and implement a successful ground- and aerial-based mosquito control response.

Mosquito-infecting virus Espirito Santo virus inhibits replication and spread of dengue virus.

The primary vector of dengue virus (DENV) is Aedes aegypti. The mosquito-infecting virus, Espirito Santo virus (ESV), does not infect Vero (mammalian) cells and grows in mosquito (C6/36) cells without cytopathic effects. Effects of ESV infection on replication of DENV were explored in vitro and in vivo, analyzing protein, RNA genome expression, and plaque formation. ESV and DENV simultaneous coinfection did not block protein synthesis from either virus but did result in inhibition of DENV replication in mosquito cells. Furthermore, ESV superinfected with DENV resulted in inhibition of DENV replication and spread in A. aegypti, thus reducing vector competence. Tissue culture experiments on viral kinetics of ESV and DENV coinfection showed that neither virus significantly affects the replication of the other in Vero, HeLa, or HEK cells. Hence, ESV blocks DENV replication in insect cells, but not the mammalian cells evaluated here. Our study provides new insights into ESV-induced suppression of DENV, a globally important pathogen impacting public health.

Relative Sparing of the Left Upper Zone on Chest Radiography in Severe COVID-19 Pneumonia.

The radiological findings of COVID-19 are well-described, including its evolution. In an earlier report of admission chest radiographs of patients with COVID-19, we anecdotally noted relative sparing of the left upper zone (LUZ). We subsequently aimed to describe the main chest radiograph findings in another cohort, focusing on zonal predominance. The admission chest radiographs of 111 patients with CO-VID-19 pneumonia requiring intensive care admission were reviewed by 2 thoracic radiologists and categorized according to the predominant pattern into either ground-glass opacities (GGOs), alveolar infiltrates and/or consolidation, or reticular and/or nodular infiltrates or an equal combination of both, and the extent of disease involvement of each of the zones using a modified Radiologic Assessment of Lung Edema (RALE) score. Parenchymal changes were detected in all. In total, 106 radiographs showed GGOs, alveolar infiltrates, and/or consolidation, and 5 had a combination of reticular/nodular infiltrates as well as GGOs, alveolar infiltrates, and/or consolidation. The LUZ had a significant lower grading score than the right upper zone: 1 versus 2 (p < 0.001). Likewise, the upper zones had a significant lower score than the mid and lower zones (p < 0.001). Our findings confirmed the relative sparing of the LUZ in severe COVID-19 pneumonia.

Malignant Sex Cord-Stromal Tumor, Not Otherwise Specified, Harboring FOXL2, p53, and TERT Promoter Mutations: Report of a Case.

Rare sex cord-stromal tumors of the ovary cannot be further subclassified and are therefore designated "sex cord-stromal tumor-not otherwise specified." These tumors have highly varied morphology, and the literature describing them is limited. Herein, we report the pathology and clinical course of a 46-yr-old woman diagnosed with sex cord-stromal tumor-not otherwise specified. The tumor was composed predominantly of juvenile granulosa cell tumor histology, with elements of thecoma, adult granulosa, Sertoli, as well as poorly differentiated epithelioid and sarcomatoid components. Next-generation sequencing revealed a FOXL2 C134W mutation, seen most commonly in adult granulosa cell tumors, as well as mutations in TP53 (V172F) and TERT promoter (-124C>T). The patient exhibited an aggressive clinical course involving rapid recurrence with distant metastases that responded to 4 cycles of cisplatin, bleomycin, and etoposide.

Diagnosis and management of severe combined immunodeficiency in Australia and New Zealand.

This consensus document outlines the recommendations from the Australasian Society of Clinical Immunology and Allergy Transplantation and Primary Immunodeficiency group for the diagnosis and management of patients with severe combined immunodeficiency. It also provides a proposed framework for the early investigation, management and supportive care prior to haematopoietic stem cell transplantation.

Vector-borne Diseases and Climate Change: North Carolina's Policy Should Promote Regional Resilience.

Emerging and endemic vector-borne diseases remain significant causes of morbidity and economic burden in North Carolina. Effective policies must promote climate change resilience through public health preparedness at local and regional scales to proactively address the diverse environmental, climatic, and demographic factors amplifying vector-borne disease risk.

Inter-rater reliability in the radiological classification of renal injuries.

INTRODUCTION: Although many radiologists invoke the surgical classification of renal injury proposed by the American Association for Surgery in Trauma (AAST), there has been only limited work on the role of the AAST system as an imaging stratification. The aim was to determine the inter-rater reliability (IRR) amongst radiologists and urologists using the AAST system. METHODS: A 1-year retrospective study of consecutive patients with computed tomography (CT) evidence of renal trauma managed at a Level 1 trauma center. Three radiologists and three urologists independently stratified the presentation CT findings according to the AAST renal trauma classification. Agreement between independent raters and mutually exclusive groups was determined utilizing weighted kappa coefficients. RESULTS: One hundred and one patients were included. Individual inter-observer agreements ranged from 54/101 (53.4%) to 62/101 (61.4%), with corresponding weighted kappa values from 0.61 to 0.69, constituting substantial agreement. Urologists achieved intra-disciplinary agreement in 49 cases (48.5%) and radiologists in 36 cases (35.6%). Six-reader agreement was achieved in 24 cases (23.7%). The AAST grade I injuries had the highest level of agreement, overall. CONCLUSION: The finding of substantial IRR amongst radiologists and urologists utilizing the AAST system supports continued use of the broad parameters of the AAST system, with some modification in specific categories with lower agreement.

Breast Cancer Tissue Markers, Genomic Profiling, and Other Prognostic Factors: A Primer for Radiologists.

An understanding of prognostic factors in breast cancer is imperative for guiding patient care. Increased tumor size and more advanced nodal status are established independent prognostic factors of poor outcomes and are incorporated into the American Joint Committee on Cancer (AJCC) TNM (primary tumor, regional lymph node, distant metastasis) staging system. However, other factors including imaging findings, histologic evaluation results, and molecular findings can have a direct effect on a patient's prognosis, including risk of recurrence and relative survival. Several microarray panels for gene profiling of tumors are approved by the U.S. Food and Drug Administration and endorsed by the American Society of Clinical Oncology. This article highlights prognostic factors currently in use for individualizing and guiding breast cancer therapy and is divided into four sections. The first section addresses patient considerations, in which modifiable and nonmodifiable prognostic factors including age, race and ethnicity, and lifestyle factors are discussed. The second part is focused on imaging considerations such as multicentric and/or multifocal disease, an extensive intraductal component, and skin or chest wall involvement and their effect on treatment and prognosis. The third section is about histopathologic findings such as the grade and presence of lymphovascular invasion. Last, tumor biomarkers and tumor biology are discussed, namely hormone receptors, proliferative markers, and categorization of tumors into four recognized molecular subtypes including luminal A, luminal B, human epidermal growth factor receptor 2-enriched, and triple-negative tumors. By understanding the clinical effect of these prognostic factors, radiologists, along with a multidisciplinary team, can use these tools to achieve individualized patient care and to improve patient outcomes. ©RSNA, 2018.

Newborn screening for severe combined immunodeficiency: Evaluation of a commercial T-cell receptor excision circle-based method in Victorian dried blood spots.

AIM: Severe combined immunodeficiency (SCID) is the most severe form of primary immunodeficiency and is fatal in infancy if untreated. As early diagnosis is associated with improved outcomes, SCID is an ideal condition to consider for inclusion in a newborn screening (NBS) programme in Australia. In this feasibility study, we evaluated the EnLite Neonatal TREC kit for detection of T-cell receptor excision circles (TRECs) from NBS dried blood spots for the identification of known SCID patients in Victoria. METHODS: TREC copies/µL were measured retrospectively in 14 children diagnosed with SCID or complete DiGeorge syndrome (CDGS) from 2005 to 2015 at the Royal Children's Hospital, Melbourne. In addition, TREC copies/µL were measured for 501 prospective de-identified NBS cards. RESULTS: Of 14 known SCID or CDGS samples, 11 were correctly identified as presumptive positive samples with low or undetectable TREC on duplicate testing. The remaining three samples also had low or undetectable TREC on duplicate testing but were considered invalid due to insufficient ß-actin DNA amplification. Of the 501 prospective NBS samples, none were identified as presumptive positive samples on duplicate testing. CONCLUSIONS: The EnLite Neonatal TREC kit correctly identified known SCID or CDGS patients as presumptive positive samples, and initial cut-offs for TREC and ß-actin in the Victorian NBS population were determined. A larger pilot study is required to confirm these proposed cut-offs and to evaluate the cost and implementation of this screening programme in Victoria, Australia. Overall, this study provides preliminary data to support the introduction of this assay to the NBS programme in Victoria.

Residual Effectiveness of Permethrin-Treated Clothing for Prevention of Mosquito Bites Under Simulated Conditions.

Biological hazards such as exposure to ticks and mosquitoes can affect health. Permethrin-treated clothing is available to the public. We don't currently understand, however, the effects of environmental factors such as fabric type, washing, sunlight, and temperature on permethrin content in treated clothing with respect to mosquito knockdown and mortality. We evaluated the extent to which fabric type (100% cotton denim jeans, 100% polyester work shirt, 35% cotton/65% polyester work shirt), light exposure (0 or 100%), temperature (18 °C, 32 °C), and number of washes (0, 3, 12, 36) affected mosquito knockdown 2 hours post-exposure, mosquito mortality 24 hours post-exposure, and permethrin content. All fabrics used in this study were treated with permethrin at a concentration of 125 µg/cm2. Denim fabric having no washes and no light exposure showed the highest amount of permethrin. Washing and light exposure significantly reduced the ability of permethrin-treated fabrics to induce mosquito knockdown and/or mortality under the simulated conditions used for this test. Temperatures tested did not affect permethrin content or mosquito knockdown and mortality. Long-lasting impregnation of uniforms protects against mosquito bites under simulated laboratory conditions. Employers and employees should consider the use of permethrin-impregnated clothing and uniforms in addition to daily repellent sprays.

Effects of Blood Coagulate Removal Method on Aedes albopictus (Diptera: Culicidae) Life Table Characteristics and Vector Competence for Dengue Virus.

Commercially available blood can be used as an alternative to live animals to maintain mosquito colonies and deliver infectious bloodmeals during research studies. We analyzed the extent to which two methods for blood coagulate removal (defibrination or addition of sodium citrate) affected life table characteristics (i.e., fecundity, fertility, hatch rate, and adult survival) and vector competence (infection, dissemination, and transmission) of Aedes albopictus (Skuse) for dengue virus (DENV). Two types of bovine blood were tested at two extrinsic incubation temperatures (27 or 30°C) for DENV-infected and uninfected mosquitoes. Fully engorged mosquitoes were transferred to individual cages containing an oviposition cup and a substrate. Eggs (fecundity) and hatched larvae (fertility) were counted. At 14 and 21 d post feeding on a DENV-infected bloodmeal, 15 mosquitoes were sampled from each group, and vector competence was analyzed (bodies [infection], legs [dissemination], and saliva [transmission]). Differences in life table characteristics and vector competence were analyzed for mosquitoes fed blood processed using different methods for removal of coagulates. The method for removal of coagulates significantly impacted fecundity, fertility, and hatch time in the uninfected group, but not DENV-infected group. Infected mosquitoes showed significantly higher fecundity and faster hatch time than uninfected mosquitoes. We show no significant differences in infection or dissemination rates between groups; however, horizontal transmission rate was significantly higher in mosquitoes fed DENV-infected citrated compared with defibrinated blood. We expect the findings of this study to inform research using artificial blood delivery methods to assess vector competence.

Systems analysis of a RIG-I agonist inducing broad spectrum inhibition of virus infectivity.

The RIG-I like receptor pathway is stimulated during RNA virus infection by interaction between cytosolic RIG-I and viral RNA structures that contain short hairpin dsRNA and 5' triphosphate (5'ppp) terminal structure. In the present study, an RNA agonist of RIG-I was synthesized in vitro and shown to stimulate RIG-I-dependent antiviral responses at concentrations in the picomolar range. In human lung epithelial A549 cells, 5'pppRNA specifically stimulated multiple parameters of the innate antiviral response, including IRF3, IRF7 and STAT1 activation, and induction of inflammatory and interferon stimulated genes - hallmarks of a fully functional antiviral response. Evaluation of the magnitude and duration of gene expression by transcriptional profiling identified a robust, sustained and diversified antiviral and inflammatory response characterized by enhanced pathogen recognition and interferon (IFN) signaling. Bioinformatics analysis further identified a transcriptional signature uniquely induced by 5'pppRNA, and not by IFNα-2b, that included a constellation of IRF7 and NF-kB target genes capable of mobilizing multiple arms of the innate and adaptive immune response. Treatment of primary PBMCs or lung epithelial A549 cells with 5'pppRNA provided significant protection against a spectrum of RNA and DNA viruses. In C57Bl/6 mice, intravenous administration of 5'pppRNA protected animals from a lethal challenge with H1N1 Influenza, reduced virus titers in mouse lungs and protected animals from virus-induced pneumonia. Strikingly, the RIG-I-specific transcriptional response afforded partial protection from influenza challenge, even in the absence of type I interferon signaling. This systems approach provides transcriptional, biochemical, and in vivo analysis of the antiviral efficacy of 5'pppRNA and highlights the therapeutic potential associated with the use of RIG-I agonists as broad spectrum antiviral agents.