Efficacy of cold piecemeal EMR of medium to large adenomas compared with sessile serrated lesions.

BACKGROUND AND AIMS: There is growing evidence for the role of cold piecemeal EMR (C-EMR) in the treatment of colorectal lesions ≥10 mm. However, it is unclear if C-EMR is equally efficacious for all histologic subtypes and sizes. This retrospective study compares the efficacy and safety of C-EMR in the resection of medium (10-19 mm) and large (≥20 mm) serrated and adenomatous lesions. METHODS: A retrospective analysis was performed of Paris IIa colonic lesions resected by using a C-EMR technique over a 3.5-year period at our center. RESULTS: C-EMR was performed for 242 lesions in 151 patients. Lesion size ranged between 10 and 50 mm, with a median size of 20 mm. Ninety-five polyps were adenomatous, with 147 sessile serrated lesions (SSLs). At 6-month surveillance colonoscopy, the combined recurrence rate was 6.2%. Adenomas ≥20 mm showed a higher rate of recurrence (16.1%) compared with large SSLs (4.1%), medium adenomas (3.0%), and medium SSLs (1.4%). There were no adverse events reported after C-EMR. CONCLUSIONS: C-EMR seems to be less effective for the resection of large adenomas compared with medium adenomas or large SSLs. C-EMR is equally safe for all lesion sizes and histology.

Preinjection With Ligation-Assisted Endoscopic Mucosal Resection for Barrett's Dysplasia and Early Esophageal Adenocarcinoma: Characteristic Histological Features of the Depth of Resection.

BACKGROUND AND AIM: Endoscopic mucosal resection (EMR) is an established technique for the diagnosis and treatment of high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) in Barrett's esophagus. Submucosal preinjection is not universally used or generally recommended when performing routine ligation-assisted EMR. Prior studies, however, have demonstrated evidence of at least superficial muscle injury on ligation-assisted EMR without submucosal injection. There are limited published data supporting any potential benefit of submucosal preinjection. Our aim was to review this technique and determine the rate of any degree of muscle injury in patients with Barrett's HGD and EAC treated with submucosal preinjection before ligation-assisted EMR. METHODS: Patients undergoing submucosal preinjection before ligation-assisted EMR for Barrett's esophagus at a single institution between 2012 and 2016 were identified. Data were collected regarding patient demographics and medical history, endoscopy and histopathology findings, adverse events, and subsequent outcomes. All EMR specimens were reviewed by an expert gastrointestinal pathologist. RESULTS: One hundred fifty consecutive EMR procedures were performed on 70 patients. Of 70 patients, 85.7% of patients were men, with a median age of 68 years. EAC was identified in 75 specimens (50%) and HGD in 44 specimens (29.3%). Deep resection margins were clear of adenocarcinoma in all specimens. Muscularis propria was not identified in any of the 150 specimens. There were no cases of post-EMR perforation. CONCLUSIONS: Preinjection before ligation-assisted EMR achieved complete excision with histologically clear margins, without histological evidence of any inadvertent muscularis propria.

The Subjective Habitability & Acceptability Questionnaire (SHAQ): Development and Validation.

OBJECTIVE: Describe the development and validation of the Subjective Habitability & Acceptability Questionnaire (SHAQ). BACKGROUND: Habitat area size, layout, and design may impact individual and team behavioral health and performance (BHP) outcomes in operational environments. However, there are no standardized measures of these relationships. METHOD: SHAQ is a modular survey consisting of two 6-item scales: BHP Outcomes (Performance of Individual Activities, Performance of Group Activities, Mood, Psychological Stress, Sleep, and Social Interactions) and Habitability Moderators (Privacy, Social Density, Efficiency, Control, Comfort, and Convenience). We collected SHAQ data from NASA's Human Exploration Research Analog (HERA) crews (n = 19) in reference to multiple habitat areas (Sleep/Bedroom, Hygiene/Bathroom, Work/Office/Workshop, and Food Preparation/Kitchen/Galley) in the HERA operational environment, private hotel rooms, and individual home habitats. RESULTS: SHAQ has high construct validity (single factor solutions, mean item factor loading = 0.760, mean % variance = 60.37), internal consistency and reliability (item mean α = 0.880, mean ω=0.894, mean ICC = 0.430), concurrent validity (mean item r with System Usability Scale = 0.42), and discriminant validity (e.g., significantly higher facilitation of group activities in HERA Work/Office/Workshop and Food Preparation/Kitchen/Galley areas vs. Hygiene/Bathroom and Sleep/Bedroom areas; significantly higher ratings of privacy, comfort, and convenience in hotel vs. HERA). CONCLUSION: SHAQ is a reliable, valid, and sensitive measure of BHP impacts of habitat size and layout. APPLICATION: SHAQ can be used to inform evidence-based recommendations and thresholds for habitat area size, layout, and design options to support individual and team BHP in operational environments.

Challenges to the central nervous system during human spaceflight missions to Mars.

Space travel presents a number of environmental challenges to the central nervous system, including changes in gravitational acceleration that alter the terrestrial synergies between perception and action, galactic cosmic radiation that can damage sensitive neurons and structures, and multiple factors (isolation, confinement, altered atmosphere, and mission parameters, including distance from Earth) that can affect cognition and behavior. Travelers to Mars will be exposed to these environmental challenges for up to 3 years, and space-faring nations continue to direct vigorous research investments to help elucidate and mitigate the consequences of these long-duration exposures. This article reviews the findings of more than 50 years of space-related neuroscience research on humans and animals exposed to spaceflight or analogs of spaceflight environments, and projects the implications and the forward work necessary to ensure successful Mars missions. It also reviews fundamental neurophysiology responses that will help us understand and maintain human health and performance on Earth.

Unified mild reaction conditions for C2-selective Pd-catalysed tryptophan arylation, including tryptophan-containing peptides.

Pd-mediated C-H bond functionalisation protocols have been designed and developed on tryptophan derivatives and tryptophan-containing peptides. The examination of different arylation reactions (three sets of different conditions A-C), all of which are notable for their low temperatures (≤40 °C), allowed identification of unified and complementary synthetic approaches toward a series of functionalised tryptophan-containing products. Tryptophan-containing peptides demonstrated to be susceptible to aromatic oxidation were successfully and selectively modified through the application of diaryliodonium salts in good yields.

Alcohol use and alcohol-related consequences: associations with emotion regulation difficulties.

BACKGROUND: Understanding factors associated with alcohol-related consequences is an important area of research. Emotional functioning has been associated with alcohol-related consequences but there is less research examining a comprehensive underlying model of emotional regulation. The Difficulties in Emotion Regulation Scale (DERS) is a recent measure developed to assess six facets of emotion regulation difficulties that contribute to overall emotional functioning. OBJECTIVES: The current study examines associations between these six facets of emotion regulation difficulties and problematic alcohol use. METHODS: Participants (n = 1758 college students) were recruited as part of a larger study and were asked to complete online questionnaires assessing demographics, alcohol use and problems, and emotion regulation difficulties. RESULTS: Negative binomial hurdle models for alcohol use and alcohol-related consequences were estimated. Impulse control difficulties were positively related to the number of drinks consumed during the week among active drinkers. Non-acceptance of emotional responses, impulse control difficulties, lack of emotional clarity, and difficulties engaging in goal-directed behavior were all positively associated with number of consequences endorsed. Difficulty engaging in goal-directed behavior was also positively associated with the likelihood of experiencing any alcohol-related consequences. CONCLUSIONS: The findings support previous research indicating that emotion-regulation difficulties are broadly associated with alcohol-related consequences. Results suggest exposure and/or mindfulness based prevention/interventions with emotion focused psychoeducation may offer one path to reducing alcohol-related consequences among college students.

Cost-effectiveness of taurolidine-citrate in a cohort of patients with intestinal failure receiving home parenteral nutrition.

BACKGROUND: Catheter-related bloodstream infections (CRBSIs) in patients receiving home parenteral nutrition (HPN) for chronic intestinal failure (CIF) are associated with significant morbidity and financial costs. Taurolidine is associated with a reduction in bloodstream infections, with limited information on the cost-effectiveness as the primary prevention. This study aimed to determine the cost-effectiveness of using taurolidine-citrate for the primary prevention of CRBSIs within a quaternary hospital. METHODS: All patients with CIF receiving HPN were identified between January 2015 and November 2022. Data were retrospectively collected regarding patient demographics, HPN use, CRBSI diagnosis, and use of taurolidine-citrate. The direct costs associated with CRBSI-associated admissions and taurolidine-citrate use were obtained from the coding department using a bottom-up approach. An incremental cost-effective analysis was performed, with a time horizon of 4 years, to compare the costs associated with primary and secondary prevention against the outcome of cost per infection avoided. RESULTS: Forty-four patients received HPN within this period. The CRBSI rates were 3.25 infections per 1000 catheter days before the use of taurolidine-citrate and 0.35 infections per 1000 catheter days after taurolidine-citrate use. The incremental cost-effectiveness ratio indicates primary prevention is the weakly dominant intervention, with the base case value of $27.04 per CRBSI avoided. This held with one-way sensitivity analysis. CONCLUSION: Taurolidine-citrate in the primary prevention of CRBSIs in patients with CIF receiving HPN is associated with reduced hospital costs and infection rates.

Ocean warming and acidification adjust inter- and intra-specific variability in the functional trait expression of polar invertebrates.

Climate change is known to affect the distribution and composition of species, but concomitant alterations to functionally important aspects of behaviour and species-environment relations are poorly constrained. Here, we examine the ecosystem ramifications of changes in sediment-dwelling invertebrate bioturbation behaviour-a key process mediating nutrient cycling-associated with near-future environmental conditions (+ 1.5 °C, 550 ppm [pCO2]) for species from polar regions experiencing rapid rates of climate change. We find that responses to warming and acidification vary between species and lead to a reduction in intra-specific variability in behavioural trait expression that adjusts the magnitude and direction of nutrient concentrations. Our analyses also indicate that species behaviour is not predetermined, but can be dependent on local variations in environmental history that set population capacities for phenotypic plasticity. We provide evidence that certain, but subtle, aspects of inter- and intra-specific variation in behavioural trait expression, rather than the presence or proportional representation of species per se, is an important and under-appreciated determinant of benthic biogeochemical responses to climate change. Such changes in species behaviour may act as an early warning for impending ecological transitions associated with progressive climate forcing.

Dilute concentrations of maritime fuel can modify sediment reworking activity of high-latitude marine invertebrates.

Multiple expressions of climate change, in particular warming-induced reductions in the type, extent and thickness of sea ice, are opening access and providing new viable development opportunities in high-latitude regions. Coastal margins are facing these challenges, but the vulnerability of species and ecosystems to the effects of fuel contamination associated with increased maritime traffic is largely unknown. Here, we show that low concentrations of the water-accommodated fraction of marine fuel oil, representative of a dilute fuel oil spill, can alter functionally important aspects of the behaviour of sediment-dwelling invertebrates. We find that the response to contamination is species specific, but that the range in response among individuals is modified by increasing fuel concentrations. Our study provides evidence that species responses to novel and/or unprecedented levels of anthropogenic activity associated with the opening up of high-latitude regions can have substantive ecological effects, even when human impacts are at, or below, commonly accepted safe thresholds. These secondary responses are often overlooked in broad-scale environmental assessments and marine planning yet, critically, they may act as an early warning signal for impending and more pronounced ecological transitions.

Three-dimensional reconstruction of high latitude bamboo coral via X-ray microfocus Computed Tomography.

The skeletons of long-lived bamboo coral (Family Keratoisididae) are promising archives for deep-water palaeoceanographic reconstructions as they can record environmental variation at sub-decadal resolution in locations where in-situ measurements lack temporal coverage. Yet, detailed three dimensional (3D) characterisations of bamboo coral skeletal architecture are not routinely available and non-destructive investigations into microscale variations in calcification are rare. Here, we provide high-resolution micro-focus computed tomography (µCT) data of skeletal density for two species of bamboo coral (Acanella arbuscula: 5 specimens, voxel size, 15 µm (central branch scans) and 50 µm (complete structure scan); Keratoisis sp.: 4 specimens, voxel size, 15 µm) collected from the Labrador Sea and Baffin Bay deep-water basins, Eastern Canadian Arctic. These data provide reference models useful for developing methods to assess structural integrity and other fine-scale complexities in many biological, geological, and industrial systems. This will be of wider value to those investigating structural composition, arrangement and/or composition of complex architecture within the fields and subdisciplines of biology, ecology, medicine, environmental geology, and structural engineering.

The elusive structure of Pd2(dba)3. Examination by isotopic labeling, NMR spectroscopy, and X-ray diffraction analysis: synthesis and characterization of Pd2(dba-Z)3 complexes.

Pd(0)2(dba)3 (dba = E,E-dibenzylidene acetone) is the most widely used Pd(0) source in Pd-mediated transformations. Pd(0)2(dba-Z)3 (Z = dba aryl substituents) complexes exhibit remarkable and differential catalytic performance in an eclectic array of cross-coupling reactions. The precise structure of these types of complexes has been confounding, since early studies in 1970s to the present day. In this study the solution and solid-state structures of Pd(0)2(dba)3 and Pd(0)2(dba-Z)3 have been determined. Isotopic labeling ((2)H and (13)C) has allowed the solution structures of the freely exchanging major and minor isomers of Pd(0)2(dba)3 to be determined at high field (700 MHz). DFT calculations support the experimentally determined major and minor isomeric structures, which show that the major isomer of Pd(0)2(dba)3 possesses bridging dba ligands found exclusively in a s-cis,s-trans conformation. For the minor isomer one of the dba ligands is found exclusively in a s-trans,s-trans conformation. Single crystal X-ray diffraction analysis of Pd(0)2(dba)3·CHCl3 (high-quality data) shows that all three dba ligands are found over two positions. NMR spectroscopic analysis of Pd(0)2(dba-Z)3 reveals that the aryl substituent has a profound effect on the rate of Pd-olefin exchange and the global stability of the complexes in solution. Complexes containing the aryl substituents, 4-CF3, 4-F, 4-t-Bu, 4-hexoxy, 4-OMe, exhibit well-resolved (1)H NMR spectra at 298 K, whereas those containing 3,5-OMe and 3,4,5-OMe exhibit broad spectra. The solid-state structures of three Pd(0)2(dba-Z)3 complexes (4-F, 4-OMe, 3,5-OMe) have been determined by single crystal X-ray diffraction methods, which have been compared with Goodson's X-ray structure of Pd(0)2(dba-4-OH)3.

Intracranial Hemorrhage as a Marker for Mycotic Aneurysm in Patients With Infective Endocarditis.

Background and Objective: Mycotic aneurysms are a significant complication of IE that can lead to intracranial hemorrhage (ICH) and occasionally require intervention before valve surgery. Digital subtraction angiography (DSA) remains the gold standard for the detection of mycotic aneurysms but is an invasive procedure with contrasted dye exposure. Our objective was to determine predictive factors for the presence of mycotic aneurysms in patients with known infective endocarditis (IE). Methods: IRB exemption was obtained from the University of Pittsburgh Medical Center. Patients with left-sided or right-sided endocarditis with patent foramen ovale (PFO) were identified. Records were retrospectively reviewed by an independent investigator. Patients were stratified by demographic information, diagnostic imaging, and clinical outcomes. Standard descriptive statistics were used for characterization. The χ2 analysis and Fisher exact test were used for categorical comparisons. The Student t test was used for group comparisons. Results: 36 cases of left-sided or right-sided endocarditis with PFO undergoing evaluation for valve surgery were identified. Twenty-seven patients underwent CNS imaging, and 24 underwent DSA. Six patients were found to have ICH on CNS imaging. Mycotic aneurysms were identified by DSA in 5 patients (13.9%), and of these patients, 4 (80%) presented with ICH and 1 with ischemic stroke. Notably, the patient who presented with ischemic stroke then developed ICH on follow-up CT imaging. The negative predictive value of the absence of ICH on initial CNS imaging for the presence of mycotic aneurysm was 97.4%. Discussion: Patients with left-sided and right-sided endocarditis with PFO and ICH on CNS imaging were more likely to have mycotic aneurysms detected through DSA than similar patients without ICH. Routine DSA screening for mycotic aneurysms may not be required in patients with endocarditis undergoing evaluation for valve surgery who present without ICH on CNS imaging.

Circuits and Biomarkers of the Central Nervous System Relating to Astronaut Performance: Summary Report for a NASA-Sponsored Technical Interchange Meeting.

Biomarkers, ranging from molecules to behavior, can be used to identify thresholds beyond which performance of mission tasks may be compromised and could potentially trigger the activation of countermeasures. Identification of homologous brain regions and/or neural circuits related to operational performance may allow for translational studies between species. Three discussion groups were directed to use operationally relevant performance tasks as a driver when identifying biomarkers and brain regions or circuits for selected constructs. Here we summarize small-group discussions in tables of circuits and biomarkers categorized by (a) sensorimotor, (b) behavioral medicine and (c) integrated approaches (e.g., physiological responses). In total, hundreds of biomarkers have been identified and are summarized herein by the respective group leads. We hope the meeting proceedings become a rich resource for NASA's Human Research Program (HRP) and the community of researchers.

Fungal-Induced Programmed Cell Death.

Fungal infections are a cause of morbidity in humans, and despite the availability of a range of antifungal treatments, the mortality rate remains unacceptably high. Although our knowledge of the interactions between pathogenic fungi and the host continues to grow, further research is still required to fully understand the mechanism underpinning fungal pathogenicity, which may provide new insights for the treatment of fungal disease. There is great interest regarding how microbes induce programmed cell death and what this means in terms of the immune response and resolution of infection as well as microbe-specific mechanisms that influence cell death pathways to aid in their survival and continued infection. Here, we discuss how programmed cell death is induced by fungi that commonly cause opportunistic infections, including Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, the role of programmed cell death in fungal immunity, and how fungi manipulate these pathways.

The role of nutrition in space exploration: Implications for sensorimotor, cognition, behavior and the cerebral changes due to the exposure to radiation, altered gravity, and isolation/confinement hazards of spaceflight.

Multi-year crewed space exploration missions are now on the horizon; therefore, it is important that we understand and mitigate the physiological effects of spaceflight. The spaceflight hazards-radiation, isolation, confinement, and altered gravity-have the potential to contribute to neuroinflammation and produce long-term cognitive and behavioral effects-while the fifth hazard, distance from earth, limits capabilities to mitigate these risks. Accumulated evidence suggests that nutrition has an important role in optimizing cognition and reducing the risk of neurodegenerative diseases caused by neuroinflammation. Here we review the nutritional perspective of how these spaceflight hazards affect the astronaut's brain, behavior, performance, and sensorimotor function. We also assess potential nutrient/nutritional countermeasures that could prevent or mitigate spaceflight risks and ensure that crewmembers remain healthy and perform well during their missions. Just as history has taught us the importance of nutrition in terrestrial exploration, we must understand the role of nutrition in the development and mitigation of spaceflight risks before humans can successfully explore beyond low-Earth orbit.

Synthesis of ultra-high molecular weight poly(ethylene)-co-(1-hexene) copolymers through high-throughput catalyst screening.

A family of permethylindenyl titanium constrained geometry complexes, Me2SB(R'N,3-RI*)TiX2 ((3-R-η5-C9Me5)Me2Si(R'TiX2)), supported on solid polymethylaluminoxane (sMAO) are investigated as slurry-phase catalysts for ethylene/H2 homopolymerisation and ethylene/1-hexene copolymerisation by high-throughput catalyst screening. Me2SB( tBuN,I*)TiCl2 supported on sMAO [sMAO-Me2SB( tBuN,I*)TiCl2] is responsive to small quantities of H2 (<1.6%), maintaining high polymerisation activities (up to 4900 kgPE molTi -1 h-1 bar-1) and yielding polyethylenes with significantly decreased molecular weight (M w) (from 2700 to 41 kDa with 1.6% H2). In slurry-phase ethylene/1-hexene copolymerisation studies, a decrease in polymerisation activity and polymer molecular weights compared to ethylene homopolymerisation is observed. Compared to many solid supported system, these complexes all display high 1-hexene incorporation levels up to a maximum incorporation of 14.2 mol% for sMAO-Me2SB(iPrN,I*)TiCl2). We observe a proportionate increase in 1-hexene incorporation with concentration, highlighting the ability of these catalysts to controllably tune the amount of 1-hexene incorporated into the polymer chain to produce linear low-density polyethylene (LLDPE) materials.

Assessment of Spaceflight Medical Conditions' and Treatments' Potential Impacts on Behavioral Health and Performance.

Long-duration space exploration missions will pose significant risks to the physical and behavioral health and performance of the crew. We documented the presence and frequency of (1) behavioral health and performance (BHP)-relevant symptoms for each condition in NASA's Exploration Medical Conditions List (EMCL), (2) the BHP-relevant effects of applicable medical treatments in the current International Space Station (ISS) On-Orbit Medication List, (3) the breadth of potential BHP impacts of spaceflight medical treatments, and (4) the likelihood of adverse BHP effects of treating spaceflight medical conditions. BHP symptoms and effects were categorized by the six neurobehavioral domains of the National Institute of Mental Health's Research Domain Criteria (RDoC) framework. Including the cognitive effects of acute and chronic pain (e.g., attention, memory), 94% of spaceflight medical conditions include symptoms relevant to Cognitive Systems (e.g., attention deficits, confusion, psychosis), 36% include symptoms relevant to Negative Valence Systems (e.g., anxiety), 32% include symptoms relevant to Arousal and Regulatory Systems (e.g., sleep disturbances), 22% include symptoms relevant to Sensorimotor Systems (e.g., dizziness), 19% include symptoms relevant to Positive Valence Systems (e.g., mania), and 11% include symptoms relevant to Social Processes (e.g., social withdrawal). Only 2% of spaceflight medical conditions have no documented BHP symptoms. Of the spaceflight medical treatments, 63% affect Arousal and Regulatory Systems, 60% affect Sensorimotor Systems, 59% affect Cognitive Systems, 53% affect Negative Valence Systems, 38% affect Positive Valence Systems, and 31% affect Social Processes. The breadth of potential BHP impacts was bimodal, in that 27% of spaceflight medical treatments had no documented BHP effects; however, 27% of treatments may produce adverse effects across all six neurobehavioral domains. Historical prevalence data on medical conditions, symptoms, and complaints from 14 years of International Space Station operations coupled with documented BHP effects of recommended treatments indicates the potential for up to 481 adverse BHP effects of spaceflight medical treatments per person-year. Assessing the potential BHP impacts of spaceflight medical conditions and their treatments highlights the interactive nature of operational risks, and can provide an enhanced evidence base to support integrated research and countermeasure development strategies for long-duration exploration missions.

Performance comparison of 4 portable oxygen concentrators.

BACKGROUND: Several portable oxygen concentrators (POCs) have become available in the United States. Technical trade-offs are made in designing POCs, so their performance is expected to differ. METHODS: We tested 4 POC models (Invacare XPO(2), Respironics EverGo, AirSep FreeStyle, and Inogen One) for oxygen delivery as a function of respiratory rate. We measured oxygen volume per pulse, pulse duration, trigger sensitivity, oxygen concentration in the gas delivered by the POC (measured with a ceramic-based oxygen sensor), and relative fraction of inspired oxygen (relative F(IO(2))), measured with a setup that included an adult nasal cannula, a model nares, and a lung simulator that has a built-in oxygen sensor. We studied respiratory rates of 15, 20, 25, 30, and 35 breaths/min, at a tidal volume of 500 mL. RESULTS: The XPO(2) had the highest pulse flow, and FreeStyle had the lowest, which corresponded to the highest and lowest pulse volumes (40.8 mL and 18.2 mL respectively) at POC setting 2, at 15 breaths/min. The range of oxygen purity was 91.9-94.4% (P = .36). The Inogen had the shortest pulse-delivery time, and the XPO(2) had the longest (132 ms vs 281 ms, P < .001). The FreeStyle had the highest trigger sensitivity, and the Inogen the lowest (0.15 cm H(2)O vs 0.21 cm H(2)O, P < .001). At the maximum settings, with all 4 POCs, relative F(IO(2)) decreased as respiratory rate increased (relative F(IO(2)) range 28.6-31.4% at 15 breaths/min, 23.0-25.3% at 30 breaths/min). CONCLUSIONS: These 4 POC models have markedly different performance, which emphasizes the need to adjust the POC setting to meet the specific patient's needs at rest and with activity.

Immunotherapeutic approaches for fungal infections.

Despite the availability of antifungal treatments, fungal infections are still causing morbidity all around the globe with unacceptably high mortality rates. A major driver for the rising incidence of serious fungal infections is due to a substantial increase in immunocompromised individuals with autoimmune diseases, cancers and transplants. Because of growing resistance in fungus to frontline triazole antifungals and the association of fungal disease with the immunocompromised host, adjunctive host-directed therapy is seen as a promising choice to improve patient outcomes. Immunotherapeutic treatments being explored as adjunct therapies to existing antifungal treatments include cytokine therapy, monoclonal antibodies and cellular immunotherapy. In this review, we give a brief overview of potential immunotherapies and recent developments in the field, which are needed to tackle the growing problem of fungal diseases.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.