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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Evidence of an early projectile point technology in North America at the Gault Site, Texas, USA.

American archeology has long been polarized over the issue of a human presence in the Western Hemisphere earlier than Clovis. As evidence of early sites across North and South America continues to emerge, stone tool assemblages appear more geographically and temporally diverse than traditionally assumed. Within this new framework, the prevailing models of Clovis origins and the peopling of the Americas are being reevaluated. This paper presents age estimates from a series of alluvial sedimentary samples from the earliest cultural assemblage at the Gault Site, Central Texas. The optically stimulated luminescence age estimates (~16 to 20 thousand years ago) indicate an early human occupation in North America before at least ~16 thousand years ago. Significantly, this assemblage exhibits a previously unknown, early projectile point technology unrelated to Clovis. Within a wider context, this evidence suggests that Clovis technology spread across an already regionalized, indigenous population.

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.

Cognitive control moderates the association between emotional instability and alcohol dependence symptoms.

Previous research has linked emotional instability with problematic alcohol use. This may be a function of increased "hot" information processing (which is relatively automatic in nature and highly influenced by emotional states) for individuals with more emotional instability. According to dual-process models, cognitive control may attenuate the impact of emotional instability by preventing an overreliance on hot information processing. It was hypothesized that emotional instability would be positively associated with alcohol-related consequences, but that cognitive control would moderate this association. Participants were undergraduate students (n = 80) who endorsed drinking at moderate levels. Participants completed laboratory assessments of emotional instability, alcohol use and its consequences, and cognitive control. An observed variable path model examined the association between emotional instability and alcohol problems. Consistent with hypotheses, emotional instability was positively associated with alcohol consequences, and this relationship was moderated by cognitive control, at least for dependence symptoms. At low levels of cognitive control, there was a positive association between emotional instability and dependence symptoms (ß = 0.514, p < .001), however, this association was attenuated and no longer significant at high levels of cognitive control (ß = 0.095, p = .302). Emotional instability may promote alcohol dependence via an overreliance on hot information processing. Consistent with dual-process theory, this relationship is diminished among individuals with more cognitive control. Interventions focusing on increasing cognitive control may be effective in reducing alcohol pathology associated with emotional instability. (PsycINFO Database Record

Mild chlorodifluoroacylation of indoles via self-activation of sodium chlorodifluoroacetate.

A mild acylation of N-alkylindoles is reported using sodium chlorodifluoroacetate (SCDA) to synthesize useful chlorodifluoroketones. Friedel-Crafts reactivity of carboxylate salts is unusual and is not observed in similar electron-deficient acetate salts such as sodium trifluoroacetate. Mechanistic experiments indicate that the characteristic ability of SCDA to generate difluorocarbene is responsible for the reaction pathway via self-activation to form the active ester.

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.

A mild and selective Pd-mediated methodology for the synthesis of highly fluorescent 2-arylated tryptophans and tryptophan-containing peptides: a catalytic role for Pd(0) nanoparticles?

A Pd-mediated direct C-H bond functionalisation of tryptophan has been developed, both as a single amino acid residue and within peptides. Important mechanistic insight into this process has been gained by characterising a Pd catalytically competent nanoparticle phase which evolves during the early stages of reaction.

Strategies for optimizing military physical readiness and preventing musculoskeletal injuries in the 21st century.

With downsizing of the military services and significant budget cuts, it will be more important than ever to optimize the health and performance of individual service members. Musculoskeletal injuries (MSIs) represent a major threat to the health and fitness of Soldiers and other service members that degrade our nation's ability to project military power. This affects both financial (such as the economic burden from medical, healthcare, and disability costs) and human manpower resources (Soldiers medically unable to optimally perform their duties and to deploy). For example, in 2012, MSIs represented the leading cause of medical care visits across the military services resulting in almost 2,200,000 medical encounters. They also result in more disability discharges than any other health condition. Nonbattle injuries (NBIs) have caused more medical evacuations (34%) from recent theaters of operation than any other cause including combat injuries. Physical training and sports are the main cause of these NBIs. The majority (56%) of these injuries are the direct result of physical training. Higher levels of physical fitness protect against such injuries; however, more physical training to improve fitness also causes higher injury rates. Thus, military physical training programs must balance the need for fitness with the risks of injuries. The Army has launched several initiatives that may potentially improve military physical readiness and reduce injuries. These include the US Army Training and Doctrine Command's Baseline Soldier Physical Readiness Requirements and Gender Neutral Physical Performance Standards studies, as well as the reimplementation of the Master Fitness Trainer program and the Army Medical Command's Soldier Medical Readiness and Performance Triad Campaigns. It is imperative for military leaders to understand that military physical readiness can be enhanced at the same time that MSIs are prevented. A strategic paradigm shift in the military's approach to physical readiness policies is needed to avoid further degradation of warfighting capability in an era of austerity. We believe this can be best accomplished through leveraging scientific, evidence-based best practices by Army senior leadership which supports, prioritizes, and implements innovative, synchronized, and integrated human performance optimization/injury prevention policy changes.

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.

Simple and versatile selective synthesis of neutral and cationic copper(I) N-heterocyclic carbene complexes using an electrochemical procedure.

An electrochemical approach for the preparation of copper(I) N-heterocyclic carbene complexes has been developed to include a diverse range of ligand precursors. Importantly, the method is effective for a ligand precursor that contains several acidic protons and for which traditional methods of carbene formation are not suitable.