Limitations associated with transcranial direct current stimulation for enhancement: considerations of performance tradeoffs in active-duty Soldiers.

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method, popular due to its low cost, ease-of-application, and portability. As such, it has gained traction in examining its potential for cognitive enhancement in a diverse range of populations, including active-duty military. However, current literature presents mixed results regarding its efficacy and limited evaluations of possible undesirable side-effects (such as degradation to cognitive processes). Methods: To further examine its potential for enhancing cognition, a double-blind, randomized, sham-controlled, within-subjects design, was used to evaluate both online active-anodal and -cathodal on several cognitive tasks administered. Potential undesirable side effects related to mood, sleepiness, and cognitive performance, were also assessed. Active tDCS was applied for 30 min, using 2 mA, to the left dorsolateral prefrontal cortex with an extracephalic reference placed on the contralateral arm of 27 (14 males) active-duty Soldiers. Results: We report mixed results. Specifically, we found improvements in sustained attention (active-anodal) for males in reaction time (p = 0.024, ηp 2 = 0.16) and for sensitivity index in females (p = 0.013, ηp 2 = 0.18). In addition, we found faster reaction time (p = 0.034, ηp 2 = 0.15) and increased accuracy (p = 0.029, ηp 2 = 0.16) associated with executive function (active-anodal and -cathodal), and worsened working memory performance (active-cathodal; p = 0.008, ηp 2 = 0.18). Additionally, we found increased risk-taking with active-anodal (p = 0.001, ηp 2 = 0.33). Discussion: tDCS may hold promise as a method for cognitive enhancement, as evidenced by our findings related to sustained attention and executive function. However, we caution that further study is required to better understand additional parameters and limitations that may explain results, as our study only focused on anode vs. cathode stimulation. Risk-taking was examined secondary to our main interests which warrants further experimental investigation isolating potential tradeoffs that may be associated with tDCS simulation.

Physiological Fitness of U.S. Army Aviators Compared to the U.S. General Population.

INTRODUCTION: U.S. Army aviators are required to maintain a level of physiological fitness as part of their qualifying process, which suggests that they are generally physically healthy. However, it has not been statistically proven that they are more "physiologically fit" than the general population.METHODS: This retrospective study compares physiological measurements of U.S. Army aviators from the Aeromedical Electronic Resource Office database to the U.S. general population using the Center for Disease Control's National Health and Nutrition Examination Survey data. To enable an accurate comparison of physiological metrics between U.S. Army aviators and the U.S. general population, aviators were categorized into the same age groups and biological genders used for segmentation of the national population data.RESULTS: On average, pulse rate was 4.85 bpm lower in male aviators and 6.84 bpm lower in female aviators. Fasting glucose levels were, on average, 10.6 mg · dL-1 lower in aviators compared to the general population. Key metrics like pulse rate and fasting glucose were lower in aviators, indicating cardiovascular and metabolic advantages. However, parameters like cholesterol showed less consistent differences.DISCUSSION: While aviation physical demands and administrative policies selecting for elite physiological metrics produce improvements on some dimensions, a nuanced view accounting for the multitude of factors influencing an aviator's physiological fitness is still warranted. Implementing targeted health monitoring and maintenance programs based on assessments conducted more frequently than the current annual flight physical may optimize aviator safety and performance over the course of a career.D'Alessandro M, Mackie R, Wolf S, McGhee JS, Curry I. Physiological fitness of U.S. Army aviators compared to the U.S. general population. Aerosp Med Hum Perform. 2024; 95(4):175-186.

Hot, Humid Air Decontamination of Aircraft Confirmed That High Temperature and High Humidity Are Critical for Inactivation of Infectious, Enveloped Ribonucleic Acid (RNA) Virus.

Aims: To develop infectious (live/dead) enveloped virus test indicators and response surface methodology (RSM) models that evaluate survival of an enveloped ribonucleic acid (RNA) virus on contaminated aircraft materials after exposure to hot, humid air (HHA). Methods and Results: Enveloped RNA bacteriophage Phi6 (Φ6) was dried on wiring insulation, aircraft performance coating (APC), polypropylene, and nylon at ≥ 8 log10 plaque-forming units (PFU) test coupon-1. Only 2.4 log10 inactivation was measured on APC at 70°Celsius (°C), 5% relative humidity (RH) after 24 h. In contrast, HHA RSM models showed a 90% probability of a 7 log10 inactivation at ≥63°C, 90% RH after 1 h, and decontamination kinetics were similar across different materials. HHA decontamination of C-130 and C-17 aircraft showed >7 log10 and ≥5.9 log10 inactivation of enveloped virus on 100 and 110 test indicators, respectively, with a 1-h treatment, excluding ramp-up and ramp-down times. Conclusions: Enveloped RNA virus test indicators were successfully developed, lab tested for HHA decontamination, analyzed for RSM, and field-tested in aircraft demonstrations. Significance and Impact of the Study: The utility of HHA decontamination was demonstrated after inactivating enveloped RNA virus on aircraft with a 1-h HHA treatment within aircraft temperature and RH limits.

Immunopathologic Effects of Prednisolone and Cyclosporine A on Feline Immunodeficiency Virus Replication and Persistence.

Feline immunodeficiency virus (FIV) induces opportunistic disease in chronically infected cats, and both prednisolone and cyclosporine A (CsA) are clinically used to treat complications such as lymphoma and stomatitis. However, the impact of these compounds on FIV infection are still unknown and understanding immunomodulatory effects on FIV replication and persistence is critical to guide safe and effective therapies. To determine the immunologic and virologic effects of prednisolone and CsA during FIV infection, FIV-positive cats were administered immunosuppressive doses of prednisolone (2 mg/kg) or CsA (5 mg/kg). Both prednisolone and CsA induced acute and transient increases in FIV DNA and RNA loads as detected by quantitative PCR. Changes in the proportion of lymphocyte immunophenotypes were also observed between FIV-infected and naïve cats treated with CsA and prednisolone, and both treatments caused acute increases in CD4+ lymphocytes that correlated with increased FIV RNA. CsA and prednisolone also produced alterations in cytokine expression that favored a shift toward a Th2 response. Pre-treatment with CsA slightly enhanced the efficacy of antiretroviral therapy but did not enhance clearance of FIV. Results highlight the potential for drug-induced perturbation of FIV infection and underscore the need for more information regarding immunopathologic consequences of therapeutic agents on concurrent viral infections.

FIV vaccine with receptor epitopes results in neutralizing antibodies but does not confer resistance to challenge.

Feline immunodeficiency virus (FIV) is the feline analogue to human immunodeficiency virus (HIV) and utilizes parallel modes of receptor-mediated entry. The FIV surface glycoprotein (SU) is an important target for induction of neutralizing antibodies, and autoantibodies to the FIV binding receptor (CD134) block infection ex vivo; thus highlighting the potential for immunotherapies which utilize anti-receptor antibodies to block viral infection. To determine whether vaccination with CD134-SU complexes could induce protection against FIV infection, cats (n = 5 per group) were immunized with soluble CD134, recombinant FIV-SU protein, and/or CD134+SU complexes. Two trials were performed with different antigen combinations and vaccination schedules. In vivo generation of anti-CD134 and anti-SU IgG antibodies was measured, and in vitro neutralization assays were conducted. Immunization induced production of anti-CD134 and anti-SU antibodies that significantly inhibited FIV infection in vitro. However, no vaccine combination protected cats from FIV infection, and neat serum from vaccinated cats enhanced FIV growth in vitro. CD134+SU vaccinated cats exhibited increased CD4:CD8 ratio immediately prior to challenge, and antibodies were much more efficiently generated against vaccine by-products versus target antigens. Results suggest vaccination against viral and cryptic receptor epitopes yields neutralizing antibodies that synergistically inhibit FIV infection in vitro. Factors contributing to vaccine failure may include: (1) Heat-labile serum factors that enhance viral replication, (2) changes in circulating target cell populations induced by vaccination, and (3) weak immunogenicity of neutralizing epitopes compared to off-target vaccine components. Results reinforce the need to monitor vaccine preparation components and avoid non-specific immune stimulation during vaccination.

Targeted Enrichment for Pathogen Detection and Characterization in Three Felid Species.

Traditional diagnostic assays often lack sensitivity and can be difficult to multiplex across many pathogens. Next-generation sequencing (NGS) can overcome some of these problems but has limited application in the detection of low-copy-number pathogens in complex samples. Targeted genome capture (TGC) utilizes oligonucleotide probes to enrich specific nucleic acids in heterogeneous extracts and can therefore increase the proportion of NGS reads for low-abundance targets. While earlier studies have demonstrated the utility of this technology for detection of novel pathogens in human clinical samples, the capacity and practicality of TGC-NGS in a veterinary diagnostic setting have not yet been evaluated. Here we report the use of TGC-NGS assays for the detection and characterization of diverse feline pathogen taxa. We detected 31 pathogens comprising nine pathogen taxa in 28 felid samples analyzed. This included 20 pathogens detected via traditional PCR and 11 additional pathogens that had not been previously detected in the same samples. Most of the pathogens detected were sequenced at sufficient breadth and depth to confidently classify them at the species or subspecies level. Target nucleic acids were enriched from a low of 58-fold to 56 million-fold relative to host nucleic acids. Despite the promising performance of these assays, a number of pathogens detected by conventional PCR or serology were not isolated by TGC-NGS, suggesting that further validation is required before this technology can be used in lieu of quality-controlled standard assays. We conclude that TGC-NGS offers great potential as a broad multiplex pathogen characterization assay in veterinary diagnostic and research settings.

Integrating heterogeneous drug sensitivity data from cancer pharmacogenomic studies.

The consistency of in vitro drug sensitivity data is of key importance for cancer pharmacogenomics. Previous attempts to correlate drug sensitivities from the large pharmacogenomics databases, such as the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC), have produced discordant results. We developed a new drug sensitivity metric, the area under the dose response curve adjusted for the range of tested drug concentrations, which allows integration of heterogeneous drug sensitivity data from the CCLE, the GDSC, and the Cancer Therapeutics Response Portal (CTRP). We show that there is moderate to good agreement of drug sensitivity data for many targeted therapies, particularly kinase inhibitors. The results of this largest cancer cell line drug sensitivity data analysis to date are accessible through the online portal, which serves as a platform for high power pharmacogenomics analysis.

A role for attention during wilderness navigation: Comparing effects of BDNF, KIBRA, and CHRNA4.

OBJECTIVE: To better understand what influences interindividual differences in ability to navigate in the wilderness, we hypothesized that better performance would be seen in (a) BDNF (rs6265) Val/Val homozygotes increased use of a spatial strategy, (b) KIBRA rs17070145 T/T homozygotes superior episodic memory, (c) CHRNA4 (rs1044396) T allele carriers better ability to focus visuospatial attention. METHOD: Military cadets (n = 382) genotyped for BDNF, KIBRA, and CHRNA4 SNPs used a map and compass to navigate in unmarked woods. Participants completed a morning course within 3.0 km and an afternoon course within 7.0 km. RESULTS: Success or failure in finding each point was analyzed in a logistic regression model with KIBRA, BDNF, and CHRNA4 genotypes as fixed effects. For the morning course, the adjusted odds ratio for the effect of KIBRA T/T over KIBRA C/C was 2.58 (95% CI of 1.31, 5.06) demonstrating a statistical benefit of the KIBRA T/T genotype over individuals with KIBRA C/C genotype. BDNF did not have an independent association with navigational success. For the afternoon course, the adjusted odds ratio for the effect of CHRNA4 C/T over C/C was 1.67 (95% CI of 1.24, 2.25) demonstrating a statistical benefit of CHRNA4 T allele carriers over the C/C genotype. CONCLUSIONS: Ability to navigate in the wilderness benefits less from sense of direction (BDNF and Santa Barbara Sense of Direction) and more from episodic memory (KIBRA) in the first course and heightened ability to focus attention (CHRNA4) after experience in the 2nd course. (PsycINFO Database Record

Dose-Response Modeling for Inhalational Anthrax in Rabbits Following Single or Multiple Exposures.

There is a need to advance our ability to characterize the risk of inhalational anthrax following a low-dose exposure. The exposure scenario most often considered is a single exposure that occurs during an attack. However, long-term daily low-dose exposures also represent a realistic exposure scenario, such as what may be encountered by people occupying areas for longer periods. Given this, the objective of the current work was to model two rabbit inhalational anthrax dose-response data sets. One data set was from single exposures to aerosolized Bacillus anthracis Ames spores. The second data set exposed rabbits repeatedly to aerosols of B. anthracis Ames spores. For the multiple exposure data the cumulative dose (i.e., the sum of the individual daily doses) was used for the model. Lethality was the response for both. Modeling was performed using Benchmark Dose Software evaluating six models: logprobit, loglogistic, Weibull, exponential, gamma, and dichotomous-Hill. All models produced acceptable fits to either data set. The exponential model was identified as the best fitting model for both data sets. Statistical tests suggested there was no significant difference between the single exposure exponential model results and the multiple exposure exponential model results, which suggests the risk of disease is similar between the two data sets. The dose expected to cause 10% lethality was 15,600 inhaled spores and 18,200 inhaled spores for the single exposure and multiple exposure exponential dose-response model, respectively, and the 95% lower confidence intervals were 9,800 inhaled spores and 9,200 inhaled spores, respectively.

Four core genotypes mouse model: localization of the Sry transgene and bioassay for testicular hormone levels.

BACKGROUND: The "four core genotypes" (FCG) mouse model has emerged as a major model testing if sex differences in phenotypes are caused by sex chromosome complement (XX vs. XY) or gonadal hormones or both. The model involves deletion of the testis-determining gene Sry from the Y chromosome and insertion of an Sry transgene onto an autosome. It produces XX and XY mice with testes, and XX and XY mice with ovaries, so that XX and XY mice with the same type of gonad can be compared to assess phenotypic effects of sex chromosome complement in cells and tissues. FINDINGS: We used PCR to amplify the Sry transgene and adjacent genomic sequences, to resolve the location of the Sry transgene to chromosome 3 and confirmed this location by fluorescence in situ hybridization (FISH) of the Sry construct to metaphase chromosomes. Using quantitative PCR, we estimate that 12-14 copies of the transgene were inserted. The anogenital distance (AGD) of FCG pups at 27-29 days after birth was not different in XX vs. XY males, or XX vs. XY females, suggesting that differences between XX and XY mice with the same type of gonad are not caused by difference in prenatal androgen levels. CONCLUSION: The Sry transgene in FCG mice is present in multiple copies at one locus on chromosome 3, which does not interrupt known genes. XX and XY mice with the same type of gonad do not show evidence of different androgen levels prenatally.